Local expressions for one-loop calculations

International Nuclear Information System (INIS)

Wasson, D.A.; Koonin, S.E.

1991-01-01

We develop local expressions for the contributions of the short-wavelength vacuum modes to the one-loop vacuum energy. These expressions significantly improve the convergence properties of various ''brute-force'' calculational methods. They also provide a continuous series of approximations that interpolate between the brute-force calculations and the derivative expansion

Preserved local but disrupted contextual figure-ground influences in an individual with abnormal function of intermediate visual areas

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Brooks, Joseph L.; Gilaie-Dotan, Sharon; Rees, Geraint; Bentin, Shlomo; Driver, Jon

2012-01-01

Visual perception depends not only on local stimulus features but also on their relationship to the surrounding stimulus context, as evident in both local and contextual influences on figure-ground segmentation. Intermediate visual areas may play a role in such contextual influences, as we tested here by examining LG, a rare case of developmental visual agnosia. LG has no evident abnormality of brain structure and functional neuroimaging showed relatively normal V1 function, but his intermediate visual areas (V2/V3) function abnormally. We found that contextual influences on figure-ground organization were selectively disrupted in LG, while local sources of figure-ground influences were preserved. Effects of object knowledge and familiarity on figure-ground organization were also significantly diminished. Our results suggest that the mechanisms mediating contextual and familiarity influences on figure-ground organization are dissociable from those mediating local influences on figure-ground assignment. The disruption of contextual processing in intermediate visual areas may play a role in the substantial object recognition difficulties experienced by LG. PMID:22947116

Expression of human PQBP-1 in Drosophila impairs long-term memory and induces abnormal courtship.

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Yoshimura, Natsue; Horiuchi, Daisuke; Shibata, Masao; Saitoe, Minoru; Qi, Mei-Ling; Okazawa, Hitoshi

2006-04-17

Frame shift mutations of the polyglutamine binding protein-1 (PQBP1) gene lead to total or partial truncation of the C-terminal domain (CTD) and cause mental retardation in human patients. Interestingly, normal Drosophila homologue of PQBP-1 lacks CTD. As a model to analyze the molecular network of PQBP-1 affecting intelligence, we generated transgenic flies expressing human PQBP-1 with CTD. Pavlovian olfactory conditioning revealed that the transgenic flies showed disturbance of long-term memory. In addition, they showed abnormal courtship that male flies follow male flies. Abnormal functions of PQBP-1 or its binding partner might be linked to these symptoms.

Abnormal expression of Nrf2 may play an important role in the pathogenesis and development of adenomyosis.

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Ning Chen

Full Text Available To explore the expression level of Nrf2 in adenomyosis and study the mechanism of abnormal expression of Nrf2 in the pathogenesis of adenomyosis.Western blot, immunohistochemistry(IHC and real time PCR were used to measure Nrf2 expression levels in tissue and cell samples. Knockdown and overexpression of Nrf2 were used to investigate the variation of migration ability of endometrial glandular cells as well as the regulatory mechanism.Nrf2 protein levels were significantly higher in the eutopic and ectopic endometrial glands when compared with control cases using IHC and western blot methods. (p< 0.05. However, there was no statistical difference in Nrf2 mRNA expression levels between the adenomyosis and control groups. Using an agonist and Nrf2 siRNA, we regulated the Nrf2 protein levels of primary cultured endometrial glandular cells. With increased expression of Nrf2, cell scratch assay showed that the agonist-treated group migrated significantly faster than the control group, with MMP9 protein level markedly elevated. In contrast, Nrf2 siRNA-treated group migrated slower than the control group, with decreased expression of MMP9 protein. All of the scratching healing spaces and protein levels between the treated and control groups were statistically significant (p< 0.05.Abnormal expression of Nrf2 may play an important role in the pathogenesis and development of adenomyosis. Specified reduction of Nrf2 expression could prove to be a new therapeutic target in the clinical treatment of adenomyosis.

Expression profile of doublesex/male abnormal-3-related transcription factor-1 during gonadal sex change in the protogynous wrasse, Halichoeres trimaculatus.

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Nozu, Ryo; Horiguchi, Ryo; Kobayashi, Yasuhisa; Nakamura, Masaru

2015-11-01

Sex change in fish involves a dramatic transformation of gonadal tissue and a switch in gametogenesis. Doublesex/male abnormal-3-related transcription factor-1 (DMRT1), encoded by the DMRT1 gene, is involved in testicular differentiation in a wide range of vertebrates as well as in sexual differentiation and gonadal sex change. In the present study, we investigated changes in the expression of dmrt1 during artificial gonadal sex change in the three-spot wrasse, Halichoeres trimaculatus, by real-time quantitative PCR and immunolocalization, using an anti-wrasse-Dmrt1 antibody that we prepared. We found that dmrt1 expression was predominantly observed in the testes, and that Dmrt1 was expressed in Sertoli cells of testes and a few granulosa cells surrounding vitellogenic oocytes of the ovary. Additionally, the upregulation of dmrt1 expression was consistent with an increase in spermatogenic cyst quantity rather than proliferation of presumptive spermatogonia, suggesting that dmrt1 is involved in the progression of spermatogenesis during sex change. Changes in the localization of Dmrt1 during gonadal sex change further implied that Sertoli cells originate from somatic cells adjacent to gonial germ cells during testicular formation in the three-spot wrasse. © 2015 Wiley Periodicals, Inc.

Differential gene expression profile associated with the abnormality of bone marrow mesenchymal stem cells in aplastic anemia.

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Jianping Li

Full Text Available Aplastic anemia (AA is generally considered as an immune-mediated bone marrow failure syndrome with defective hematopoietic stem cells (HSCs and marrow microenvironment. Previous studies have demonstrated the defective HSCs and aberrant T cellular-immunity in AA using a microarray approach. However, little is known about the overall specialty of bone marrow mesenchymal stem cells (BM-MSCs. In the present study, we comprehensively compared the biological features and gene expression profile of BM-MSCs between AA patients and healthy volunteers. In comparison with healthy controls, BM-MSCs from AA patients showed aberrant morphology, decreased proliferation and clonogenic potential and increased apoptosis. BM-MSCs from AA patients were susceptible to be induced to differentiate into adipocytes but more difficult to differentiate into osteoblasts. Consistent with abnormal biological features, a large number of genes implicated in cell cycle, cell division, proliferation, chemotaxis and hematopoietic cell lineage showed markedly decreased expression in BM-MSCs from AA patients. Conversely, more related genes with apoptosis, adipogenesis and immune response showed increased expression in BM-MSCs from AA patients. The gene expression profile of BM-MSCs further confirmed the abnormal biological properties and provided significant evidence for the possible mechanism of the destruction of the bone marrow microenvironment in AA.

CAFE: an R package for the detection of gross chromosomal abnormalities from gene expression microarray data.

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Bollen, Sander; Leddin, Mathias; Andrade-Navarro, Miguel A; Mah, Nancy

2014-05-15

The current methods available to detect chromosomal abnormalities from DNA microarray expression data are cumbersome and inflexible. CAFE has been developed to alleviate these issues. It is implemented as an R package that analyzes Affymetrix *.CEL files and comes with flexible plotting functions, easing visualization of chromosomal abnormalities. CAFE is available from https://bitbucket.org/cob87icW6z/cafe/ as both source and compiled packages for Linux and Windows. It is released under the GPL version 3 license. CAFE will also be freely available from Bioconductor. sander.h.bollen@gmail.com or nancy.mah@mdc-berlin.de Supplementary data are available at Bioinformatics online.

Global gene expression profiling related to temperature-sensitive growth abnormalities in interspecific crosses between tetraploid wheat and Aegilops tauschii.

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Ryusuke Matsuda

Full Text Available Triploid wheat hybrids between tetraploid wheat and Aegilops tauschii sometimes show abnormal growth phenotypes, and the growth abnormalities inhibit generation of wheat synthetic hexaploids. In type II necrosis, one of the growth abnormalities, necrotic cell death accompanied by marked growth repression occurs only under low temperature conditions. At normal temperature, the type II necrosis lines show grass-clump dwarfism with no necrotic symptoms, excess tillers, severe dwarfism and delayed flowering. Here, we report comparative expression analyses to elucidate the molecular mechanisms of the temperature-dependent phenotypic plasticity in the triploid wheat hybrids. We compared gene and small RNA expression profiles in crown tissues to characterize the temperature-dependent phenotypic plasticity. No up-regulation of defense-related genes was observed under the normal temperature, and down-regulation of wheat APETALA1-like MADS-box genes, considered to act as flowering promoters, was found in the grass-clump dwarf lines. Some microRNAs, including miR156, were up-regulated, whereas the levels of transcripts of the miR156 target genes SPLs, known to inhibit tiller and branch number, were reduced in crown tissues of the grass-clump dwarf lines at the normal temperature. Unusual expression of the miR156/SPLs module could explain the grass-clump dwarf phenotype. Dramatic alteration of gene expression profiles, including miRNA levels, in crown tissues is associated with the temperature-dependent phenotypic plasticity in type II necrosis/grass-clump dwarf wheat hybrids.

FXYD-3 expression in relation to local recurrence of rectal cancer

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Loftas, Per; Arbman, Gunnar; Sun, Xiao Feng; Hallbook, Olof [Dept. of Clinical and Experimental Medicine, Linkoping University, Norrkoping (Sweden); Edler, David [Dept. of Surgery, Karolinska Institute, Stockholm (Sweden); Syk, Erik [Dept. of Surgery, Ersta Hospital, Stockholm (Sweden)

2016-03-15

In a previous study, the transmembrane protein FXYD-3 was suggested as a biomarker for a lower survival rate and reduced radiosensitivity in rectal cancer patients receiving preoperative radiotherapy. The purpose of preoperative irradiation in rectal cancer is to reduce local recurrence. The aim of this study was to investigate the potential role of FXYD-3 as a biomarker for increased risk for local recurrence of rectal cancer. FXYD-3 expression was immunohistochemically examined in surgical specimens from a cohort of patients with rectal cancer who developed local recurrence (n = 48). The cohort was compared to a matched control group without recurrence (n = 81). Weak FXYD-3 expression was found in 106/129 (82%) of the rectal tumors and strong expression in 23/129 (18%). There was no difference in the expression of FXYD-3 between the patients with local recurrence and the control group. Furthermore there was no difference in FXYD-3 expression and time to diagnosis of local recurrence between patients who received preoperative radiotherapy and those without. Previous findings indicated that FXYD-3 expression may be used as a marker of decreased sensitivity to radiotherapy or even overall survival. We were unable to confirm this in a cohort of rectal cancer patients who developed local recurrence.

FXYD-3 expression in relation to local recurrence of rectal cancer

International Nuclear Information System (INIS)

Loftas, Per; Arbman, Gunnar; Sun, Xiao Feng; Hallbook, Olof; Edler, David; Syk, Erik

2016-01-01

In a previous study, the transmembrane protein FXYD-3 was suggested as a biomarker for a lower survival rate and reduced radiosensitivity in rectal cancer patients receiving preoperative radiotherapy. The purpose of preoperative irradiation in rectal cancer is to reduce local recurrence. The aim of this study was to investigate the potential role of FXYD-3 as a biomarker for increased risk for local recurrence of rectal cancer. FXYD-3 expression was immunohistochemically examined in surgical specimens from a cohort of patients with rectal cancer who developed local recurrence (n = 48). The cohort was compared to a matched control group without recurrence (n = 81). Weak FXYD-3 expression was found in 106/129 (82%) of the rectal tumors and strong expression in 23/129 (18%). There was no difference in the expression of FXYD-3 between the patients with local recurrence and the control group. Furthermore there was no difference in FXYD-3 expression and time to diagnosis of local recurrence between patients who received preoperative radiotherapy and those without. Previous findings indicated that FXYD-3 expression may be used as a marker of decreased sensitivity to radiotherapy or even overall survival. We were unable to confirm this in a cohort of rectal cancer patients who developed local recurrence

Impaired coupling of local and global functional feedbacks underlies abnormal synchronization and negative symptoms of schizophrenia.

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Noh, Kyungchul; Shin, Kyung Soon; Shin, Dongkwan; Hwang, Jae Yeon; Kim, June Sic; Jang, Joon Hwan; Chung, Chun Kee; Kwon, Jun Soo; Cho, Kwang-Hyun

2013-04-10

Abnormal synchronization of brain oscillations is found to be associated with various core symptoms of schizophrenia. However, the underlying mechanism of this association remains yet to be elucidated. In this study, we found that coupled local and global feedback (CLGF) circuits in the cortical functional network are related to the abnormal synchronization and also correlated to the negative symptom of schizophrenia. Analysis of the magnetoencephalography data obtained from patients with chronic schizophrenia during rest revealed an increase in beta band synchronization and a reduction in gamma band power compared to healthy controls. Using a feedback identification method based on non-causal impulse responses, we constructed functional feedback networks and found that CLGF circuits were significantly reduced in schizophrenia. From computational analysis on the basis of the Wilson-Cowan model, we unraveled that the CLGF circuits are critically involved in the abnormal synchronization and the dynamical switching between beta and gamma bands power in schizophrenia. Moreover, we found that the abundance of CLGF circuits was negatively correlated with the development of negative symptoms of schizophrenia, suggesting that the negative symptom is closely related to the impairment of this circuit. Our study implicates that patients with schizophrenia might have the impaired coupling of inter- and intra-regional functional feedbacks and that the CLGF circuit might serve as a critical bridge between abnormal synchronization and the negative symptoms of schizophrenia.

Expression and Localization of Peroxisome Proliferator-Activated Receptors and Nuclear Factor κB in Normal and Lesional Psoriatic Skin

DEFF Research Database (Denmark)

Westergaard, Majken; Henningsen, Jeanette; Johansen, Claus

2003-01-01

Abnormal epidermal proliferation and differentiation characterize the inflammatory skin disease psoriasis. Here we demonstrate that expression of PPARdelta mRNA and protein is markedly upregulated in psoriatic lesions and that lipoxygenase products accumulating in psoriatic lesions are potent...... activators of PPARdelta. The expression levels of NF-kappaB p50 and p65 were not significantly altered in lesional compared with nonlesional psoriatic skin. In the basal layer of normal epidermis both p50 and p65 were sequestered in the cytoplasm, whereas p50, but not p65, localized to nuclei...... in the suprabasal layers, and this distribution was maintained in lesional psoriatic skin. In normal human keratinocytes PPAR agonists neither impaired IL-1beta-induced translocation of p65 nor IL-1beta-induced NF-kappaB DNA binding. We show that PPARdelta physically interacts with the N-terminal Rel homology...

Abnormal Uterine Bleeding Is Associated With Increased BMP7 Expression in Human Endometrium.

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Richards, Elliott G; El-Nashar, Sherif A; Schoolmeester, John K; Keeney, Gary L; Mariani, Andrea; Hopkins, Matthew R; Dowdy, Sean C; Daftary, Gaurang S; Famuyide, Abimbola O

2017-05-01

Abnormal uterine bleeding (AUB), a common health concern of women, is a heterogeneous clinical entity that is traditionally categorized into organic and nonorganic causes. Despite varied pharmacologic treatments, few offer sustained efficacy, as most are empiric, unfocused, and do not directly address underlying dysregulated molecular mechanisms. Characterization of such molecular derangements affords the opportunity to develop and use novel, more successful treatments for AUB. Given its implication in other organ systems, we hypothesized that bone morphogenetic protein (BMP) expression is altered in patients with AUB and hence comprehensively investigated dysregulation of BMP signaling pathways by systematically screening 489 samples from 365 patients for differences in the expression of BMP2, 4, 6, and 7 ligands, BMPR1A and B receptors, and downstream SMAD4, 6, and 7 proteins. Expression analysis was correlated clinically with data abstracted from medical records, including bleeding history, age at procedure, ethnicity, body mass index, hormone treatment, and histological diagnosis of fibroids, polyps, adenomyosis, hyperplasia, and cancer. Expression of BMP7 ligand was significantly increased in patients with AUB (H-score: 18.0 vs 26.7; P bleeding (menorrhagia) as their specific AUB pattern demonstrated significantly higher BMP7 expression. Significantly, no differences in the expression of any other BMP ligands, receptors, or SMAD proteins were observed in this large patient cohort. However, expression of BMPR1A, BMPR1B, and SMAD4 was significantly decreased in cancer compared to benign samples. Our study demonstrates that BMP7 is a promising target for future investigation and pharmacologic treatment of AUB.

Dopaminergic neuronal loss, reduced neurite complexity and autophagic abnormalities in transgenic mice expressing G2019S mutant LRRK2.

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David Ramonet

2011-04-01

Full Text Available Mutations in the leucine-rich repeat kinase 2 (LRRK2 gene cause late-onset, autosomal dominant familial Parkinson's disease (PD and also contribute to idiopathic PD. LRRK2 mutations represent the most common cause of PD with clinical and neurochemical features that are largely indistinguishable from idiopathic disease. Currently, transgenic mice expressing wild-type or disease-causing mutants of LRRK2 have failed to produce overt neurodegeneration, although abnormalities in nigrostriatal dopaminergic neurotransmission have been observed. Here, we describe the development and characterization of transgenic mice expressing human LRRK2 bearing the familial PD mutations, R1441C and G2019S. Our study demonstrates that expression of G2019S mutant LRRK2 induces the degeneration of nigrostriatal pathway dopaminergic neurons in an age-dependent manner. In addition, we observe autophagic and mitochondrial abnormalities in the brains of aged G2019S LRRK2 mice and markedly reduced neurite complexity of cultured dopaminergic neurons. These new LRRK2 transgenic mice will provide important tools for understanding the mechanism(s through which familial mutations precipitate neuronal degeneration and PD.

Abnormal condition detector for a local power range monitor

International Nuclear Information System (INIS)

Akiyama, Takao.

1976-01-01

Object: to permit determination of abnormal condition by a number of local power range monitors (LPRM) to be quickly made through precise estimation of the ratio between the true rate of change in neutron flux and true change in the neutron flux by making use of the fact that the status of the neutron distribution does not widely change with a change in the core flow rate for a short period of time. Structure: While carrying out power control according to the core flow rate, detection values from LPRM which are disposed in a three-dimensional fashion within the reactor core are indicated on an indicator. The average value of rates of change in the indicated values for a group of LPRM under substantially the same fluid dynamic condition as that for each LPRM is determined while measuring time-wise change rate in the indicated value of each of the LPRM. The average value is successively divided by the rate of change in the indicated value for each LPRM and the amplifier gain thereof to obtain the reference value. When the difference between the average value and reference value obtained in this way exceeds a prescribed value, the corresponding LPRM is determined to be defective. (Moriyama, K.)

Expression of matrix metalloproteinase enzymes in endometrium of women with abnormal uterine bleeding.

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Grzechocinska, Barbara; Dabrowski, Filip A; Chlebus, Marcin; Gondek, Agata; Czarzasta, Katarzyna; Michalowski, Lukasz; Cudnoch-Jedrzejewska, Agnieszka; Wielgos, Miroslaw

2018-02-01

Abnormal uterine bleeding (AUB) is caused by derangement of physiological processes of tissue growth, shedding and regeneration. It is known that interplay between metalloproteinases (MMP's) and tissue inhibitors of metalloproteinases (TIMP's) may play a crucial role in its occurrence. To define if expression of proMMP-2, MMP-2 and TIMP-1 in endometrium of women with AUB is dependent on steroid sex hormone concentration and histopathological picture. Endometrial scraps were taken from 21 women with AUB and 19 controls. Samples were evaluated in light microscopy by a certified pathologist. Activity of proMMP-2 and MMP-2 proteins levels were evaluated by gelatin zymography and TIMP-1 by reversed zymography. The results has been correlated with serum estradiol and progesterone concentrations in linear regression model. Expression: of proMMP-2 in endometrium of women with AUB is correlated with estradiol concentration and inversely correlated with progesterone levels. It was significantly higher in women with dysfunctional endometrium (pbleeding (pbleeding.

Introduction of a normal human chromosome 8 corrects abnormal phenotypes of Werner syndrome cells immortalized by expressing an hTERT gene

International Nuclear Information System (INIS)

Ariyoshi, Kentaro; Kodama, Seiji; Suzuki, Keiji; Goto, Makoto; Oshimura, Mitsuo; Ishizaki, Kanji; Watanabe, Masami

2009-01-01

Werner syndrome (WS) is an autosomal recessive disease characterized by premature aging and caused by mutations of the WRN gene mapped at 8p12. To examine functional complementation of WS phenotypes, we introduced a normal human chromosome 8 into a strain of WS fibroblasts (WS3RGB) immortalized by expressing a human telomerase reverse transcriptase subunit (hTERT) gene. Here, we demonstrate that the abnormal WS phenotypes including cellular sensitivities to 4-nitroquinoline-1-oxide (4NQO) and hydroxy urea (HU), and chromosomal radiosensitivity at G 2 phase are corrected by expression of the WRN gene mediated by introducing a chromosome 8. This indicates that those multiple abnormal WS phenotypes are derived from a primary, but not secondary, defect in the WRN gene. (author)

Expression and Localization of microRNAs in Perinatal Rat Pancreas

DEFF Research Database (Denmark)

Larsen, Louise; Rosenstierne, Maiken Worsøe; Gaarn, Louise Winkel

2011-01-01

OBJECTIVE: To investigate the expression of pancreatic microRNAs (miRNAs) during the period of perinatal beta-cell expansion and maturation in rats, determine the localization of these miRNAs and perform a pathway analysis with predicted target mRNAs expressed in perinatal pancreas. RESEARCH DESIGN...... AND METHODS: RNA was extracted from whole pancreas at embryonic day 20 (E20), on the day of birth (P0) and two days after birth (P2) and hybridized to miRNA microarrays. Differentially expressed miRNAs were verified by northern blotting and their pancreatic localization determined by in situ hybridization...

Porphyromonas gingivalis infection induced reproductive abnormalities in mice

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Ke-min WEI

2016-09-01

Full Text Available Objective 　To establish a pregnant mouse model infected with Porphyromonas gingivalis (P.g, and investigate the relationship of P.g infection to prematurity and associated birth abnormalities. Methods 　Fifty two female mice were randomly divided into P.g infection group (n=26 and control group (n=26. Mice in P.g infection group were anesthetized, the pulp cavity of the first molar was opened and directly injected with W83 strain P.g, and the tooth was then filled. Six weeks after infection, the mice were mated with males and the formation of vagina plug was recorded as 0d. The P.g extracted from the granulation tissue in tooth root was cultivated. The pregnant days and the connatal body weight of infant mouse were recorded, the serum and placental tissue were collected to assess the systemic and local conditions during pregnancy. Results 　After periodontal P.g infection, the TNF-α, IL-17, IL -6 and IL -1βlevels in peripheral blood sera increased significantly. The average gestation was shorter in P.g infection group (18.25d than in control group (20.45d, P<0.01, and the connatal body weight of infant mouse was also less in the former than in the latter (P<0.01. Immunohistochemistry and PCR revealed the existence of P.g in placenta tissue. P.g infection caused premature rupture of membranes, placental abruption, degeneration and necrosis of trophoblastic and endothelial cells; significantly increased the number of neutrophils and macrophages in placenta tissues, and increased the expression of local TNF-αand COX-2 inflammatory factors at the same time. In P.g infection group, the expressions of CD-31 in endothelial cells of placenta tissues and the apoptotic factor caspase-3 decreased, and the DNA oxidative damage index 8-OHdG increased. Conclusions 　P.g infection in female mice may cause premature birth and lower connatal body weight of infant mouse, and increase the expression of serous and local inflammatory factors in the placenta

Synovial joint formation requires local Ext1 expression and heparan sulfate production in developing mouse embryo limbs and spine.

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Mundy, Christina; Yasuda, Tadashi; Kinumatsu, Takashi; Yamaguchi, Yu; Iwamoto, Masahiro; Enomoto-Iwamoto, Motomi; Koyama, Eiki; Pacifici, Maurizio

2011-03-01

Heparan sulfate proteoglycans (HSPGs) regulate a number of major developmental processes, but their roles in synovial joint formation remain unknown. Here we created conditional mouse embryo mutants lacking Ext1 in developing joints by mating Ext1(f/f) and Gdf5-Cre mice. Ext1 encodes a subunit of the Ext1/Ext2 Golgi-associated protein complex responsible for heparan sulfate (HS) synthesis. The proximal limb joints did form in the Gdf5-Cre;Ext1(f/f) mutants, but contained an uneven articulating superficial zone that expressed very low lubricin levels. The underlying cartilaginous epiphysis was deranged as well and displayed random patterns of cell proliferation and matrillin-1 and collagen IIA expression, indicative of an aberrant phenotypic definition of the epiphysis itself. Digit joints were even more affected, lacked a distinct mesenchymal interzone and were often fused likely as a result of local abnormal BMP and hedgehog activity and signaling. Interestingly, overall growth and lengthening of long bones were also delayed in the mutants. To test whether Ext1 function is needed for joint formation at other sites, we examined the spine. Indeed, entire intervertebral discs, normally composed by nucleus pulposus surrounded by the annulus fibrosus, were often missing in Gdf5-Cre;Ext1(f/f) mice. When disc remnants were present, they displayed aberrant organization and defective joint marker expression. Similar intervertebral joint defects and fusions occurred in Col2-Cre;β-catenin(f/f) mutants. The study provides novel evidence that local Ext1 expression and HS production are needed to maintain the phenotype and function of joint-forming cells and coordinate local signaling by BMP, hedgehog and Wnt/β-catenin pathways. The data indicate also that defects in joint formation reverberate on, and delay, overall long bone growth. Copyright © 2011 Elsevier Inc. All rights reserved.

Abnormal functional global and local brain connectivity in female patients with anorexia nervosa

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Geisler, Daniel; Borchardt, Viola; Lord, Anton R.; Boehm, Ilka; Ritschel, Franziska; Zwipp, Johannes; Clas, Sabine; King, Joseph A.; Wolff-Stephan, Silvia; Roessner, Veit; Walter, Martin; Ehrlich, Stefan

2016-01-01

Background Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact. Methods To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities. Results Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus. Limitations The present results may be limited to the methods applied during preprocessing and network construction. Conclusion We demonstrated anorexia nervosa–related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger. PMID:26252451

Bcl-2 and bax expression and prostate cancer outcome in men treated with radiotherapy in Radiation Therapy Oncology Group protocol 86-10

International Nuclear Information System (INIS)

Khor, L.-Y.; De Silvio, Michelle; Li, Rile; McDonnell, Timothy J.; Hammond, M. Elizabeth H.; Sause, William T.; Pilepich, Miljenko V.; Okunieff, Paul; Sandler, Howard M.; Pollack, Alan

2006-01-01

Purpose: Bcl-2 and bax are proteins with opposing roles in apoptosis regulation; yet abnormal expression of either has been associated with failure after radiotherapy (RT). In this study we examined bcl-2 and bax expression as predictive markers in men treated with radiotherapy ± androgen deprivation on Radiation Therapy Oncology Group (RTOG) protocol 86-10. Experimental Design: Suitable archival diagnostic tissue was obtained from 119 (26%) patients for bcl-2 analysis and 104 (23%) patients for bax analysis. Cox proportional hazards multivariate analysis was used to determine the relationship of abnormal bcl-2 and bax expression to the end points of local failure, distant metastasis, cause-specific mortality, and overall mortality. Bcl-2 overexpression was classified as any tumor cell cytoplasmic staining and altered bax expression was classified as greater or lesser cytoplasmic staining intensity of tumor cells as compared with adjacent normal prostate epithelium. Results: The study cohort exhibited bcl-2 overexpression in 26% (n = 30) of cases and abnormal bax expression in 47% (n = 49) of cases. A borderline significant relationship was observed between abnormal bax expression and higher Gleason score (p = 0.08). In univariate and multivariate analyses, there was no statistically significant relationship seen between abnormal bcl-2 or bax expression and outcome. Conclusions: Abnormal bcl-2 and bax expression were not related to any of the end points tested. The cohort examined was comprised of patients with locally advanced disease and it is possible that these markers may be of greater value in men with earlier-stage prostate cancer

The clinical significances of the abnormal expressions of Piwil1 and Piwil2 in colonic adenoma and adenocarcinoma

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Wang HL

2015-05-01

Full Text Available Hai-Ling Wang,1 Bei-Bei Chen,1 Xin-Guang Cao,1 Jin Wang,2 Xiu-Feng Hu,1 Xiao-Qian Mu,1 Xiao-Bing Chen1 1The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, People’s Republic of China; 2The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China Objective: The objective of the present investigation was to study the clinical significances of the abnormal expressions of Piwil1 and Piwil2 protein in colonic adenoma and adenocarcinoma.Methods: This study had applied immunohistochemical method to detect 45 cases of tissues adjacent to carcinoma (distance to cancerous tissue was above 5 cm, 41 cases of colonic adenoma and 92 cases of colon cancer tissues, and their Piwil1 and Piwil2 protein expression levels.Analysis: The correlation of both expression and its relationship with clinicopathological features of colon cancer was analyzed.Results: Positive expression rates of Piwil1 in tissues adjacent to carcinoma, colonic adenoma, and colon cancer were 11.1% (5/45, 53.7% (22/41, and 80.4% (74/92, respectively; the expression rates increased, and the comparisons between each two groups were statistically significant (P<0.05. In each group, the positive expression rates of Piwil2 were 24.4% (11/45 cases, 75.6% (31/41 cases, and 92.4% (85/92 cases; expression rates increased, and the comparisons between each two groups were statistically significant (P<0.05. Piwil1 expression and the correlation of the degree of differentiation, TNM stage, and lymph node metastasis were statistically significant (P<0.05. Piwil2 expression and the correlation of the degree of differentiation, tumor node metastasis (TNM stage, and lymph node metastasis had no statistical significance (P>0.05. In colon cancer tissue, Piwil1 and Piwil2 expressions were positively correlated (r=0.262, P<0.05.Conclusion: The results showed that the abnormal expression of Piwil1 and Piwil2 might play an important role in

Phenotype abnormality: 31 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 31 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u537i abnormal for trait of behavior...al quality during process named localization of cell ... abnormal ... behavioral quality

Imaging findings of sternal abnormalities

International Nuclear Information System (INIS)

Franquet, T.; Gimenez, A.; Alegret, X.; Sanchis, E.; Rivas, A.

1997-01-01

Radiographic findings in the sternal abnormalities are often nonspecific, showing appearances from a localized benign lesion to an aggressive lesion as seen with infections and malignant neoplasms. A specific diagnosis of sternal abnormalities can be suggested on the basis of CT and MR characteristics. Familiarity with the presentation and variable appearance of sternal abnormalities may aid the radiologist is suggesting a specific diagnosis. We present among others characteristic radiographic findings of hemangioma, chondrosarcoma, hydatid disease, and SAPHO syndrome. In those cases in which findings are not specific, cross-sectional imaging modalities may help the clinician in their management. (orig.)

Expression of recombinant Streptokinase from local Egyptian ...

African Journals Online (AJOL)

We reported for the first time the expression of a recombinant SK from a local Streptococcus strain. When produced on industrial scale this r-SK may substantially contribute to reducing the costs of thrombolytic therapy in developing countries. In this study, a highly purified r-SK from Streptococcus sp. isolated from Egyptian ...

Expression and subcellular localization of antiporter regulating ...

African Journals Online (AJOL)

We examined the expression and subcellular localization of antiporter regulating protein OsARP in a submergence tolerant rice (Oryza sativa L.) cultivar FR13A. In the public databases, this protein was designated as putative Os02g0465900 protein. The cDNA containing the full-length sequence of OsARP gene was ...

Unusual interleukin-1 and -6 expression in fetal cartilage is associated with placental abnormalities.

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Robert Klepacz

2010-06-01

Full Text Available Unusual expression of interleukin-1alpha, -1beta and -6 was previously found in the epiphyseal cartilage of rat fetuses prenatally exposed to various non-steroidal anti-inflammatory drugs (NSAID, i.e., ibuprofen, piroxicam, tolmetin and selective cyclooxygenase-2 inhibitor (DFU. The aim of the present study was to evaluate the role of placenta in such phenomenon. Morphology of the organ, thickness of basal and labyrinth layer, immunoexpression of COX isoenzymes were examined, and confronted with maternal biochemical data and fetal developmental parameters. Higher maternal urea level, as well as lower placental weight and labyrinth thickness were found in the group of fetuses who revealed expression of genes coded the selected interleukins, when compared with the xenobiotic-exposed pups without the selected genes expression and untreated control. A significant correlation between placental weight and maternal total protein or urea level was revealed. Histological changes like inflammatory infiltration and calcification were observed sporadically. Location and intensity of COX-1 staining was similar in all cases. However, more intense COX-2 staining for majority of cells of the basal zone and in dispersed giant cells of the labyrinth was found in inflamed organs. It could be concluded that abnormal expression of the selected interleukins is associated with low placental weight and decrease of its thickness, especially labyrinth zone, as well as with high maternal urea level.

Spatial characteristics of white matter abnormalities in schizophrenia

NARCIS (Netherlands)

T.J.H. White (Tonya); S.M. Ehrlich (Stefan); B.C. Ho (Beng ); D.S. Manoach (Dara); A. Caprihan (Arvind); S.C. Schulz (S. Charles); N.C. Andreasen; R.L. Gollub (Randy); V.D. Calhoun (Vince); V. Magnotta

2013-01-01

textabstractThere is considerable evidence implicating brain white matter (WM) abnormalities in the pathophysiology of schizophrenia; however, the spatial localization of WM abnormalities reported in the existing studies is heterogeneous. Thus, the goal of this study was to quantify the spatial

Meta-analysis of the prognostic value of abnormally expressed lncRNAs in hepatocellular carcinoma.

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Qu, Zhen; Yuan, Chun-Hui; Yin, Chang-Qing; Guan, Qing; Chen, Hao; Wang, Fu-Bing

2016-01-01

Many long noncoding RNAs (lncRNAs) have been reported to be abnormally expressed in hepatocellular carcinoma (HCC), and may have the potential to serve as prognostic markers. In this study, a meta-analysis was conducted to systematically evaluate the prognostic value of various lncRNAs in HCC. Eligible literatures were systematically collected from PubMed, Embase, Web of Science, and Cochrane Library (up to December 30, 2015). The main outcomes including overall survival, relapse-free survival, and disease-free survival were analyzed. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using random- or fixed-effects models. A total of 2,991 patients with HCC in People's Republic of China from 27 studies were included in the analysis. The level of lncRNAs showed a significant association with clinical outcomes. Abnormally elevated lncRNA transcription level predicted poor overall survival (HR: 1.68, 95% CI: 1.20-2.34, P=0.002; I (2)=75.5%, P=0.000) and relapse-free survival (HR: 2.08, 95% CI: 1.65-2.61, Panalysis further showed that lncRNA transcription level was significantly associated with tumor size (relative risk [RR]: 1.19, 95% CI: 1.01-1.39, P=0.035), microvascular invasion (RR: 1.44, 95% CI: 1.10-1.89, P=0.009), and portal vein tumor thrombus (RR: 1.50, 95% CI: 1.03-2.20, P=0.036). Publication bias and sensitivity analysis further confirmed the stability of our results. Our present meta-analysis indicates that abnormal lncRNA transcription level may serve as a promising indicator for prognostic evaluation of patients with HCC in People's Republic of China.

Partial rescue of postnatal growth plate abnormalities in Ihh mutants by expression of a constitutively active PTH/PTHrP receptor.

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Maeda, Yukiko; Schipani, Ernestina; Densmore, Michael J; Lanske, Beate

2010-02-01

Indian hedgehog (Ihh) is essential for chondrocyte proliferation/differentiation and osteoblast differentiation during prenatal endochondral bone formation. Ihh expression in postnatal chondrocytes has a non-redundant role in maintaining a growth plate and sustaining trabecular bone after birth. Loss of Ihh in postnatal chondrocytes results in fusion of the growth plate and a decrease in trabecular bone. In order to normalize this abnormal chondrocyte phenotype and to investigate whether a putative rescue of the growth plate anomalies is sufficient to correct the severe alterations in the bone, we expressed a constitutively active PTH/PTHrP receptor (an Ihh downstream target) in the chondrocytes of Col2 alpha 1-Cre ER; Ihh(dld) mice by mating Col2 alpha 1-Cre ER; Ihh(fl/fl) mice with Col2 alpha 1-constitutively active PTH/PTHrP receptor transgenic mice (Jansen, J). Col2 alpha 1-Cre ER; Ihh(f/f); J mice were then injected with tamoxifen at P0 to generate Col2 alpha 1-Cre ER; Ihh(d/d); J mice. In contrast with the previously reported growth plate phenotype of Col2 alpha 1-Cre ER; Ihh(d/d) mice that displayed ectopic chondrocyte hypertrophy at P7, growth plates of Col2 alpha 1-Cre ER; Ihh(d/d); J double mutants were well organized, and exhibited a gene expression pattern similar to the one of control mice. However, expression of osteoblast markers and Dkk1, a Wnt signaling target, remains decreased in the bone collar of Col2 alpha 1-Cre ER; Ihh(d/d); J mice when compared to control mice despite the rescue of abnormal chondrocyte differentiation. Moreover, proliferation of chondrocytes was still significantly impaired in Col2 alpha 1-Cre ER; Ihh(d/d); J mice, and this eventually led to the fusion of the growth plate at P14. In summary, we have demonstrated that expression of a Jansen receptor in chondrocytes was able to rescue abnormal chondrocyte differentiation but not impaired chondrocyte proliferation and the bone anomalies in mice lacking the Ihh gene in

CT of pleural abnormalities

International Nuclear Information System (INIS)

Webb, W.R.

1995-01-01

Briefly discussed were CT diagnosis of pleural thickening, CT technique for examining the pleura or pleuro-pulmonary disease, diagnosis of pleural collections, diagnosis of pleural fluid abnormalities in patients with pneumonia, pleural neoplasms, malignant (diffuse) mesothelioma, metastases, local fibrous tumor of the pleura (benign mesothelioma) (21 refs.)

CT of pleural abnormalities

Energy Technology Data Exchange (ETDEWEB)

Webb, W R [California Univ., San Francisco, CA (United States). Dept. of Radiology

1996-12-31

Briefly discussed were CT diagnosis of pleural thickening, CT technique for examining the pleura or pleuro-pulmonary disease, diagnosis of pleural collections, diagnosis of pleural fluid abnormalities in patients with pneumonia, pleural neoplasms, malignant (diffuse) mesothelioma, metastases, local fibrous tumor of the pleura (benign mesothelioma) (21 refs.).

Proteins associated with critical sperm functions and sperm head shape are differentially expressed in morphologically abnormal bovine sperm induced by scrotal insulation

NARCIS (Netherlands)

Saadi, H.A.S.; Riemsdijk, van E.L.C.; Dance, A.L.; Rajamanickam, G.D.; Kastelic, J.P.; Thundathil, J.C.

2013-01-01

The objective was to investigate expression patterns of proteins in pyriform sperm, a common morphological abnormality in bull sperm. Ejaculates were collected from sexually mature Holstein bulls (n = 3) twice weekly for 10 weeks (pre-thermal insult samples). Testicular temperature was elevated in

Nuclear localization of SNARK; its impact on gene expression

International Nuclear Information System (INIS)

Kuga, Wataru; Tsuchihara, Katsuya; Ogura, Tsutomu; Kanehara, Sakyo; Saito, Marie; Suzuki, Atsushi; Esumi, Hiroyasu

2008-01-01

SNARK, a member of the AMPK-related kinases, has been involved in the cellular stress responses but its precise mechanisms remain unclear. Subcellular localization of SNARK protein was identified. Unlike cytoplasmic localizing AMPKα, SNARK was predominantly localized in the nucleus. SNARK was constitutively distributed in the nucleus even when SNARK was activated by metabolic stimuli such as AICAR and glucose-deprivation. Conserved nuclear localization signal (NLS) was identified at the N-terminal portion ( 68 KKAR 71 ). Deletion and point mutation of this part resulted in the cytoplasmic translocation of mutant proteins. Furthermore, GFP fused with the SNARK fragment containing 68 KKAR 71 translocated to the nucleus. A microarray analysis revealed that the nuclear localizing SNARK altered transcriptome profiles and a considerable part of these alterations were canceled by the mutation of NLS, suggesting the ability of SNARK to modulate gene expression dependent on its nuclear localization.

CELLULAR LOCALIZATION AND EXPRESSION OF pygo DURING DROSOPHILA DEVELOPMENT

Institute of Scientific and Technical Information of China (English)

LINXin-da; LINXin-hua; CHENGJia-an

2003-01-01

Wg/Wnt signaling is a key signaling pathway in Drosophila. Many genes involved in Wingless(wg) signal transduction pathway downstream of Wg, or it'' s vertebrate Wg homologue Wnt, have been identified.Transduction of the Wg signal downstream of Wg is mediated by nuclear TCF/LEF-1, through association with Ar-madillo (Arm)/β-catenin. Pygopus (pygo) is a new identified component in this pathway . Cellular localization experiment showed that pygo was expressed specifically in the nucleus. The expression profile of pygo in embryos was examined using in situ hybridization. Although pygo expressed ubiquitously in the embryos, it expressed at relatively high level in pre-blastoderm embryos which indicate a high degree of maternally provided message, fol-lowed by a low level of ubiquitous zygotic expression. This continues into larval tissues (including wing disc, eye disc and leg disc), where pygo appears to be expressed at low level. Comparison of pygo expression levels, in the wing disc, eye disc and leg disc, showed pygo expression level in the wing disc pouch and leg disc were rela-tive higher.

A note on the post-Newtonian limit of quasi-local energy expressions

International Nuclear Information System (INIS)

Frauendiener, Jörg; Szabados, László B

2011-01-01

An 'effective' quasi-local energy expression, motivated by the (relativistically corrected) Newtonian theory, is introduced in exact general relativity as the volume integral of all the source terms in the field equation for the Newtonian potential in static spacetimes. In particular, we exhibit a new post-Newtonian correction in the source term in the field equation for the Newtonian gravitational potential. In asymptotically flat spacetimes, this expression tends to the Arnowitt-Deser-Misner energy at spatial infinity as a monotonically decreasing set function. We prove its positivity in spherically symmetric spacetimes under certain energy conditions, and that its vanishing characterizes flatness. We argue that any physically acceptable quasi-local energy expression should behave qualitatively like this 'effective' energy expression in this limit. (paper)

Thaumatin-like proteins are differentially expressed and localized in phloem tissues of hybrid poplar

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Dafoe Nicole J

2010-08-01

Full Text Available Abstract Background Two thaumatin-like proteins (TLPs were previously identified in phloem exudate of hybrid poplar (Populus trichocarpa × P. deltoides using proteomics methods, and their sieve element localization confirmed by immunofluorescence. In the current study, we analyzed different tissues to further understand TLP expression and localization in poplar, and used immunogold labelling to determine intracellular localization. Results Immunofluorescence using a TLP antiserum confirmed the presence of TLP in punctate, organelle-like structures within sieve elements. On western blots, the antiserum labeled two constitutively expressed proteins with distinct expression patterns. Immunogold labelling suggested that TLPs are associated with starch granules and starch-containing plastids in sieve elements and phloem parenchyma cells. In addition, the antiserum recognized TLPs in the inner cell wall and sieve plate region of sieve elements. Conclusions TLP localization in poplar cells and tissues is complex. TLP1 is expressed predominantly in tissues with a prominent vascular system such as midveins, petioles and stems, whereas the second TLP is primarily expressed in starch-storing plastids found in young leaves and the shoot apex.

Detection of radiation-induced genetic damage using sperm abnormality assays

International Nuclear Information System (INIS)

Kitazume, Masayuki; Okamoto, Masanori; Nakai, Sayaka

1985-01-01

A quantitative experiment on radiation-induced sperm abnormalities was made with mice, golden hamsters, and crab-eating monkeys. Sperm sites showing morphological abnormalities following irradiation were divided into head, neck, head plus neck, and others (including middle piece and tail). Local x-ray irradiation (200 KVp at a rate of 30 rad min) to the testes was undertaken in mice and golden hamsters, and local gamma-ray irradiation ( 137 Cs at a rate of 30 rad min) to the testes were undertaken in crab-eating monkeys. The head and neck were sensitive to radiation, showing morphological abnormalities. The number of abnormal sperms reached the peak at 5 - 6 wk after irradiation in mice and golden hamsters; at 6 wk with 300 rad and at 8 wk with 100 and 200 rad in crab-eating monkeys. Doubling doses for sperm abnormalities were 30 rad in mice and approximately 50 rad in golden hamsters. The dose-response curves on sperm abnormalities in crab-eating monkeys approximated to those in golden hamsters. (Namekawa, K.)

Dual localized mitochondrial and nuclear proteins as gene expression regulators in plants?

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Philippe eGiegé

2012-09-01

Full Text Available Mitochondria heavily depend on the coordinated expression of both mitochondrial and nuclear genomes because some of their most significant activities are held by multi-subunit complexes composed of both mitochondrial and nuclear encoded proteins. Thus, precise communication and signaling pathways are believed to exist between the two compartments. Proteins dual localized to both mitochondria and the nucleus make excellent candidates for a potential involvement in the envisaged communication. Here, we review the identified instances of dual localized nucleo-mitochondrial proteins with an emphasis on plant proteins and discuss their functions, which are seemingly mostly related to gene expression regulation. We discuss whether dual localization could be achieved by dual targeting and / or by re-localization and try to apprehend the signals required for the respective processes. Finally, we propose that in some instances, dual localized mitochondrial and nuclear proteins might act as retrograde signaling molecules for mitochondrial biogenesis.

Insulation resistance abnormal condition detector for a local power range monitor

International Nuclear Information System (INIS)

Akiyama, Takao; Mizuno, Katsuhiro; Kai, Takaaki.

1976-01-01

Object: To permit determination of abnormal condition by a number of local power range monitors (LPRM ) to be quickly made through estimation of the leakage current value by precisely estimating the ratio between the true rate of change in neutron flux and true change in the neutron flux by making use of the fact that the status of the neutron distribution does not widely change with a change of the core flow rate for a short period of time. Structure: While carrying out power control according to the core flow rate, detection values from LPRM which are disposed in a three-dimensional fashion within the reactor core are indicated on an indicator. The average value of rates of change in the indicated values for a group of LPRM under substantially the same fluid dynamic condition as that for each LPRM is determined by measuring the ratio before and after the alteration of the power of the indicated value. Further, the estimation of leakage current is determined by using the ratio of the indicated value, average value thereof and amplifier gain of each LPRM. When the estimation leakage current exceeds a prescribed value, the corresponding LPRM is determined to be defective. (Moriyama, K.)

Transient Expression and Cellular Localization of Recombinant Proteins in Cultured Insect Cells.

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Fabrick, Jeffrey A; Hull, J Joe

2017-04-20

Heterologous protein expression systems are used for the production of recombinant proteins, the interpretation of cellular trafficking/localization, and the determination of the biochemical function of proteins at the sub-organismal level. Although baculovirus expression systems are increasingly used for protein production in numerous biotechnological, pharmaceutical, and industrial applications, nonlytic systems that do not involve viral infection have clear benefits but are often overlooked and underutilized. Here, we describe a method for generating nonlytic expression vectors and transient recombinant protein expression. This protocol allows for the efficient cellular localization of recombinant proteins and can be used to rapidly discern protein trafficking within the cell. We show the expression of four recombinant proteins in a commercially available insect cell line, including two aquaporin proteins from the insect Bemisia tabaci, as well as subcellular marker proteins specific for the cell plasma membrane and for intracellular lysosomes. All recombinant proteins were produced as chimeras with fluorescent protein markers at their carboxyl termini, which allows for the direct detection of the recombinant proteins. The double transfection of cells with plasmids harboring constructs for the genes of interest and a known subcellular marker allows for live cell imaging and improved validation of cellular protein localization.

Analysis of the influence of subcellular localization of the HIV Rev protein on Rev-dependent gene expression by multi-fluorescence live-cell imaging

International Nuclear Information System (INIS)

Wolff, Horst; Hadian, Kamyar; Ziegler, Manja; Weierich, Claudia; Kramer-Hammerle, Susanne; Kleinschmidt, Andrea; Erfle, Volker; Brack-Werner, Ruth

2006-01-01

The human immunodeficiency virus Rev protein is a post-transcriptional activator of HIV gene expression. Rev is a nucleocytoplasmic shuttle protein that displays characteristic nuclear/nucleolar subcellular localization in various cell lines. Cytoplasmic localization of Rev occurs under various conditions disrupting Rev function. The goal of this study was to investigate the relationship between localization of Rev and its functional activity in living cells. A triple-fluorescent imaging assay, called AQ-FIND, was established for automatic quantitative evaluation of nucleocytoplasmic distribution of fluorescently tagged proteins. This assay was used to screen 500 rev genes generated by error-prone PCR for Rev mutants with different localization phenotypes. Activities of the Rev mutants were determined with a second quantitative, dual-fluorescent reporter assay. In HeLa cells, the majority of nuclear Rev mutants had activities similar to wild-type Rev. The activities of Rev mutants with abnormal cytoplasmic localization ranged from moderately impaired to nonfunctional. There was no linear correlation between subcellular distribution and levels of Rev activity. In astrocytes, nuclear Rev mutants showed similar impaired activities as the cytoplasmic wild-type Rev. Our data suggest that steady-state subcellular localization is not a primary regulator of Rev activity but may change as a secondary consequence of altered Rev function. The methodologies described here have potential for studying the significance of subcellular localization for functions of other regulatory factors

Expression Levels and Localizations of DVL3 and sFRP3 in Glioblastoma

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Anja Kafka

2017-01-01

Full Text Available The expression patterns of critical molecular components of Wnt signaling, sFRP3 and DVL3, were investigated in glioblastoma, the most aggressive form of primary brain tumors, with the aim to offer potential biomarkers. The protein expression levels and localizations in tumor tissue were revealed by immunohistochemistry and evaluated by the semiquantitative method and immunoreactivity score. Majority of glioblastomas had moderate expression levels for both DVL3 (52.4% and sFRP3 (52.3%. Strong expression levels were observed in 23.1% and 36.0% of samples, respectively. DVL3 was localized in cytoplasm in 97% of glioblastomas, of which 44% coexpressed the protein in the nucleus. sFRP3 subcellular distribution showed that it was localized in the cytoplasm in 94% of cases. Colocalization in the cytoplasm and nucleus was observed in 50% of samples. Wilcox test indicated that the domination of the strong signal is in connection with simultaneous localization of DVL3 protein in the cytoplasm and the nucleus. Patients with strong expression of DVL3 will significantly more often have the protein in the nucleus (P=6.33×10−5. No significant correlation between the two proteins was established, nor were their signal strengths correlated with epidemiological parameters. Our study contributes to better understanding of glioblastoma molecular profile.

Age- and Gene-Dosage–Dependent Cre-Induced Abnormalities in the Retinal Pigment Epithelium

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He, Lizhi; Marioutina, Mariya; Dunaief, Joshua L.; Marneros, Alexander G.

2015-01-01

To conditionally inactivate genes in the retinal pigment epithelium (RPE) transgenic mouse strains have been developed, in which Cre recombinase (Cre) expression is driven by an RPE-specific gene promoter. The RPE is a quiescent epithelium, and continuous expression of Cre could affect its function. Here, we tested the hypothesis that continuous postnatal Cre expression in the RPE may lead to cellular abnormalities, which may depend on both age and Cre gene dosage. We therefore examined the eyes of homozygous and heterozygous VMD2-Cre mice at various ages. In VMD2-Cre heterozygous mice variable progressive age-dependent RPE abnormalities were noticed, including attenuation of phalloidin and cytoplasmic active β-catenin staining, reduced cell size, and loss of the typical honeycomb pattern of RPE morphology in those RPE cells that stained for Cre. These morphological RPE abnormalities were not noticed in Cre-negative RPE cells in VMD2-Cre or age-matched control mice. In addition, an abnormal number and morphology of cell nuclei were noticed in a subset of Cre-expressing RPE cells in aged heterozygous VMD2-Cre mice, whereas more severe nuclear abnormalities were observed already in young homozygous VMD2-Cre mice. Thus, continuous postnatal expression of Cre causes abnormalities in the RPE in an age- and Cre gene dosage-dependent manner, which needs to be considered in the interpretation of gene targeting studies in the RPE. PMID:24854863

Left globus pallidus abnormality in never-medicated patients with schizophrenia

International Nuclear Information System (INIS)

Early, T.S.; Reiman, E.M.; Raichle, M.E.; Spitznagel, E.L.

1987-01-01

Schizophrenia is a severe psychiatric disorder characterized by onset in young adulthood, the occurrence of hallucinations and delusions, and the development of enduring psychosocial disability. The pathophysiology of this disorder remains unknown. Studies of cerebral blood flow and metabolism designed to identify brain abnormalities in schizophrenia have been limited by inadequate methods of anatomical localization and the possibility of persistent medication effects. The authors have now used positron emission tomography and a validated method of anatomical localization in an attempt to identify abnormalities of regional cerebral blood flow in newly diagnosed never-medicated patients with schizophrenia. An exploratory study of 5 patients and 10 normal control subjects identified abnormally high blood flow in the left globus pallidus of patients with schizophrenia. A replication study of 5 additional patients and 10 additional control subjects confirmed this finding. No other abnormalities were found

ECG abnormalities in patients with chronic kidney disease

International Nuclear Information System (INIS)

Shafi, S.; Saleem, M.; Anjum, R.; Abdullah, W.; Shafi, T.

2017-01-01

Chronic kidney disease (CKD) is associated with increased risk of cardiovascular disease. Electrocardiographic (ECG) abnormalities are common in CKD patients. However, there is variation in literature regarding frequency of ECG abnormalities in CKD patients and limited information in local population. Methods: The study design was cross-sectional in nature. All patients between ages of 20-80 years with CKD not previously on renal replacement therapy who were admitted to nephrology ward at a tertiary care facility over a 6-month period were included. All patients underwent 12 lead electrocardiograms (ECG). ECG abnormalities were defined based on accepted standard criteria. Results: Total number of patients included in the study was 124. Mean age of all patients was 49.9+-13.8 years, 106 (84.8%) had hypertension, 84 (70%) had diabetes mellitus, and 35 (29.9%) had known cardiovascular disease. Mean serum creatinine was 7.2+-3.4 mg/dl, mean eGFR was 10.6+-9.2 ml/min/1.73 m/sup 2/. Overall 78.4% of all CKD patients have one or more ECG abnormality. Left ventricular hypertrophy (40%), Q waves (27.2%), ST segment elevation or depression (23.4%), prolonged QRS duration (19.2%), tachycardia (17.6%) and left and right atrial enlargement (17.6%) were the most common abnormalities. Conclusion: ECG abnormalities are common in hospitalized CKD patients in local population. All hospitalized CKD patients should undergo ECG to screen for cardiovascular disease. (author)

Facial expression recognition based on weber local descriptor and sparse representation

Science.gov (United States)

Ouyang, Yan

2018-03-01

Automatic facial expression recognition has been one of the research hotspots in the area of computer vision for nearly ten years. During the decade, many state-of-the-art methods have been proposed which perform very high accurate rate based on the face images without any interference. Nowadays, many researchers begin to challenge the task of classifying the facial expression images with corruptions and occlusions and the Sparse Representation based Classification framework has been wildly used because it can robust to the corruptions and occlusions. Therefore, this paper proposed a novel facial expression recognition method based on Weber local descriptor (WLD) and Sparse representation. The method includes three parts: firstly the face images are divided into many local patches, and then the WLD histograms of each patch are extracted, finally all the WLD histograms features are composed into a vector and combined with SRC to classify the facial expressions. The experiment results on the Cohn-Kanade database show that the proposed method is robust to occlusions and corruptions.

Subcellular localization of human neutral ceramidase expressed in HEK293 cells

International Nuclear Information System (INIS)

Hwang, Young-ha; Tani, Motohiro; Nakagawa, Tetsuto; Okino, Nozomu; Ito, Makoto

2005-01-01

We previously reported that rat and mouse neutral ceramidases were mainly localized to plasma membranes as a type II integral membrane protein and partly detached from the cells via processing of the N-terminal/anchor sequence when expressed in HEK293 cells [M. Tani, H. Iida, M. Ito, O-glycosylation of mucin-like domain retains the neutral ceramidase on the plasma membranes as a type II integral membrane protein, J. Biol. Chem. 278 (2003) 10523-10530]. In contrast, the human homologue was exclusively detected in mitochondria when expressed in HEK293 and MCF7 cells as a fusion protein with green fluorescent protein at the N-terminal of the enzyme [S.E. Bawab, P. Roddy, T. Quian, A. Bielawska, J.J. Lemasters, Y.A. Hannun, Molecular cloning and characterization of a human mitochondrial ceramidase, J. Biol. Chem. 275 (2000) 21508-21513]. Given this discrepancy, we decided to clone the neutral ceramidase from human kidney cDNA and re-examine the intracellular localization of the enzyme when expressed in HEK293 cells. The putative amino acid sequence of the newly cloned enzyme was identical to that reported for human neutral ceramidase except at the N-terminal; the new protein was 19 amino acids longer at the N-terminal. We found that the putative full-length human neutral ceramidase was transported to plasma membranes, but not to mitochondria, possibly via a classical ER/Golgi pathway and localized mainly in plasma membranes when expressed in HEK293 cells. The N-terminal-truncated mutant, previously reported as a human mitochondrial ceramidase, was also weakly expressed in HEK293 cells but mainly released into the medium possibly due to the insufficient signal/anchor sequence

In Vivo Imaging of Local Gene Expression Induced by Magnetic Hyperthermia

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Olivier Sandre

2017-02-01

Full Text Available The present work aims to demonstrate that colloidal dispersions of magnetic iron oxide nanoparticles stabilized with dextran macromolecules placed in an alternating magnetic field can not only produce heat, but also that these particles could be used in vivo for local and noninvasive deposition of a thermal dose sufficient to trigger thermo-induced gene expression. Iron oxide nanoparticles were first characterized in vitro on a bio-inspired setup, and then they were assayed in vivo using a transgenic mouse strain expressing the luciferase reporter gene under transcriptional control of a thermosensitive promoter. Iron oxide nanoparticles dispersions were applied topically on the mouse skin or injected subcutaneously with Matrigel™ to generate so-called pseudotumors. Temperature was monitored continuously with a feedback loop to control the power of the magnetic field generator and to avoid overheating. Thermo-induced luciferase expression was followed by bioluminescence imaging 6 h after heating. We showed that dextran-coated magnetic iron oxide nanoparticle dispersions were able to induce in vivo mild hyperthermia compatible with thermo-induced gene expression in surrounding tissues and without impairing cell viability. These data open new therapeutic perspectives for using mild magnetic hyperthermia as noninvasive modulation of tumor microenvironment by local thermo-induced gene expression or drug release.

Prenatal exposure to phencyclidine produces abnormal behaviour and NMDA receptor expression in postpubertal mice.

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Lu, Lingling; Mamiya, Takayoshi; Lu, Ping; Toriumi, Kazuya; Mouri, Akihiro; Hiramatsu, Masayuki; Kim, Hyoung-Chun; Zou, Li-Bo; Nagai, Taku; Nabeshima, Toshitaka

2010-08-01

Several studies have shown the disruptive effects of non-competitive N-methyl-d-aspartate (NMDA) receptor antagonists on neurobehavioural development. Based on the neurodevelopment hypothesis of schizophrenia, there is growing interest in animal models treated with NMDA antagonists at developing stages to investigate the pathogenesis of psychological disturbances in humans. Previous studies have reported that perinatal treatment with phencyclidine (PCP) impairs the development of neuronal systems and induces schizophrenia-like behaviour. However, the adverse effects of prenatal exposure to PCP on behaviour and the function of NMDA receptors are not well understood. This study investigated the long-term effects of prenatal exposure to PCP in mice. The prenatal PCP-treated mice showed hypersensitivity to a low dose of PCP in locomotor activity and impairment of recognition memory in the novel object recognition test at age 7 wk. Meanwhile, the prenatal exposure reduced the phosphorylation of NR1, although it increased the expression of NR1 itself. Furthermore, these behavioural changes were attenuated by atypical antipsychotic treatment. Taken together, prenatal exposure to PCP produced long-lasting behavioural deficits, accompanied by the abnormal expression and dysfunction of NMDA receptors in postpubertal mice. It is worth investigating the influences of disrupted NMDA receptors during the prenatal period on behaviour in later life.

Somatosensory abnormalities in knee OA.

Science.gov (United States)

Wylde, Vikki; Palmer, Shea; Learmonth, Ian D; Dieppe, Paul

2012-03-01

The aim of this study was to use quantitative sensory testing (QST) to explore the range and prevalence of somatosensory abnormalities demonstrated by patients with advanced knee OA. One hundred and seven knee OA patients and 50 age- and sex-matched healthy participants attended a 1-h QST session. Testing was performed on the medial side of the knee and the pain-free forearm. Light-touch thresholds were assessed using von Frey filaments, pressure pain thresholds using a digital pressure algometer, and thermal sensation and pain thresholds using a Thermotest MSA. Significant differences in median threshold values from knee OA patients and healthy participants were identified using Mann-Whitney U-tests. The z-score transformations were used to determine the prevalence of the different somatosensory abnormalities in knee OA patients. Testing identified 70% of knee OA patients as having at least one somatosensory abnormality. Comparison of median threshold values between knee OA patients and healthy participants revealed that patients had localized thermal and tactile hypoaesthesia and pressure hyperalgesia at the osteoarthritic knee. Tactile hypoaesthesia and pressure hyperalgesia were also present at the pain-free forearm. The most prevalent somatosensory abnormalities were tactile hypoaesthesia and pressure hyperalgesia, evident in between 20 and 34% of patients. This study found that OA patients demonstrate an array of somatosensory abnormalities, of which the most prevalent were tactile hypoaesthesia and pressure hyperalgesia. Further research is now needed to establish the clinical implications of these somatosensory abnormalities.

Specific gene expression profiles and chromosomal abnormalities are associated with infant disseminated neuroblastoma

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Kushner Brian

2009-02-01

Full Text Available Abstract Background Neuroblastoma (NB tumours have the highest incidence of spontaneous remission, especially among the stage 4s NB subgroup affecting infants. Clinical distinction of stage 4s from lethal stage 4 can be difficult, but critical for therapeutic decisions. The aim of this study was to investigate chromosomal alterations and differential gene expression amongst infant disseminated NB subgroups. Methods Thirty-five NB tumours from patients diagnosed at Results All stage 4s patients underwent spontaneous remission, only 48% stage 4 patients survived despite combined modality therapy. Stage 4 tumours were 90% near-diploid/tetraploid, 44% MYCN amplified, 77% had 1p LOH (50% 1p36, 23% 11q and/or 14q LOH (27% and 47% had 17q gain. Stage 4s were 90% near-triploid, none MYCN amplified and LOH was restricted to 11q. Initial comparison analyses between stage 4s and 4 P P = 0.0054, 91% with higher expression in stage 4. Less definite expression profiles were observed between stage 4s and 4 P P = 0.005 was maintained. Distinct gene expression profiles but no significant association with specific chromosomal region localization was observed between stage 4s and stage 4 Conclusion Specific chromosomal aberrations are associated with distinct gene expression profiles which characterize spontaneously regressing or aggressive infant NB, providing the biological basis for the distinct clinical behaviour.

Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain

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Minchenko Dimitri

2010-04-01

Full Text Available Abstract Background The Rett Syndrome (RTT brain displays regional histopathology and volumetric reduction, with frontal cortex showing such abnormalities, whereas the occipital cortex is relatively less affected. Results Using microarrays and quantitative PCR, the mRNA expression profiles of these two neuroanatomical regions were compared in postmortem brain tissue from RTT patients and normal controls. A subset of genes was differentially expressed in the frontal cortex of RTT brains, some of which are known to be associated with neurological disorders (clusterin and cytochrome c oxidase subunit 1 or are involved in synaptic vesicle cycling (dynamin 1. RNAi-mediated knockdown of MeCP2 in vitro, followed by further expression analysis demonstrated that the same direction of abnormal expression was recapitulated with MeCP2 knockdown, which for cytochrome c oxidase subunit 1 was associated with a functional respiratory chain defect. Chromatin immunoprecipitation (ChIP analysis showed that MeCP2 associated with the promoter regions of some of these genes suggesting that loss of MeCP2 function may be responsible for their overexpression. Conclusions This study has shed more light on the subset of aberrantly expressed genes that result from MECP2 mutations. The mitochondrion has long been implicated in the pathogenesis of RTT, however it has not been at the forefront of RTT research interest since the discovery of MECP2 mutations. The functional consequence of the underexpression of cytochrome c oxidase subunit 1 indicates that this is an area that should be revisited.

[Abnormal floral meristem development in transgenic tomato plants do not depend on the expression of genes encoding defense-related PR-proteins and antimicrobial peptides].

Science.gov (United States)

Khaliluev, M R; Chaban, I A; Kononenko, N V; Baranova, E N; Dolgov, S V; Kharchenko, P N; Poliakov, V Iu

2014-01-01

In this study, the morphological and cytoembryological analyses of the tomato plants transformed with the genes encoding chitin-binding proteins (ac and RS-intron-Shir) from Amaranthus caudatus L. andA. retroflexus L., respectively, as well as the gene amp2 encoding hevein-like antimicrobial peptides from Stellaria media L., have been performed. The transgenic lines were adapted to soil and grown the greenhouse. The analysis of putative transgenic tomato plants revealed several lines that did not differ phenotypically from the wild type plants and three lines with disruption in differentiation of the inflorescence shoot and the flower, as well as the fruit formation (modified plants of each line were transformed with a single gene as noted before). Abnormalities in the development of the generative organs were maintained for at least six vegetative generations. These transgenic plants were shown to be defective in the mail gametophyte formation, fertilization, and, consequently, led to parthenocarpic fruits. The detailed analysis of growing ovules in the abnormal transgenic plants showed that the replacement tissue was formed and proliferated instead of unfertilized embryo sac. The structure of the replacement tissue differed from both embryonic and endosperm tissue of the normal ovule. The formation of the replacement tissue occurred due to continuing proliferation of the endothelial cells that lost their ability for differentiation. The final step in the development of the replacement tissue was its death, which resulted in the cell lysis. The expression of the genes used was confirmed by RT-PCR in all three lines with abnormal phenotype, as well as in several lines that did not phenotypically differ from the untransformed control. This suggests that abnormalities in the organs of the generative sphere in the transgenic plants do not depend on the expression of the foreign genes that were introduced in the tomato genome. Here, we argue that agrobacterial

Synovial DKK1 expression is regulated by local glucocorticoid metabolism in inflammatory arthritis.

Science.gov (United States)

Hardy, Rowan; Juarez, Maria; Naylor, Amy; Tu, Jinwen; Rabbitt, Elizabeth H; Filer, Andrew; Stewart, Paul M; Buckley, Christopher D; Raza, Karim; Cooper, Mark S

2012-10-18

Inflammatory arthritis is associated with increased bone resorption and suppressed bone formation. The Wnt antagonist dickkopf-1 (DKK1) is secreted by synovial fibroblasts in response to inflammation and this protein has been proposed to be a master regulator of bone remodelling in inflammatory arthritis. Local glucocorticoid production is also significantly increased during joint inflammation. Therefore, we investigated how locally derived glucocorticoids and inflammatory cytokines regulate DKK1 synthesis in synovial fibroblasts during inflammatory arthritis. We examined expression and regulation of DKK1 in primary cultures of human synovial fibroblasts isolated from patients with inflammatory arthritis. The effect of TNFα, IL-1β and glucocorticoids on DKK1 mRNA and protein expression was examined by real-time PCR and ELISA. The ability of inflammatory cytokine-induced expression of the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) to sensitise fibroblasts to endogenous glucocorticoids was explored. Global expression of Wnt signalling and target genes in response to TNFα and glucocorticoids was assessed using a custom array. DKK1 expression in human synovial fibroblasts was directly regulated by glucocorticoids but not proinflammatory cytokines. Glucocorticoids, but not TNFα, regulated expression of multiple Wnt agonists and antagonists in favour of inhibition of Wnt signalling. However, TNFα and IL-1β indirectly stimulated DKK1 production through increased expression of 11β-HSD1. These results demonstrate that in rheumatoid arthritis synovial fibroblasts, DKK1 expression is directly regulated by glucocorticoids rather than TNFα. Consequently, the links between synovial inflammation, altered Wnt signalling and bone remodelling are not direct but are dependent on local activation of endogenous glucocorticoids.

Expression and localization of claudins-3 and -12 in transformed human brain endothelium

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Schrade Anja

2012-02-01

Full Text Available Abstract Background The aim of this study was to characterize the hCMEC/D3 cell line, an in vitro model of the human Blood Brain Barrier (BBB for the expression of brain endothelial specific claudins-3 and -12. Findings hCMEC/D3 cells express claudins-3 and -12. Claudin-3 is distinctly localized to the TJ whereas claudin -12 is observed in the perinuclear region and completely absent from TJs. We show that the expression of both proteins is lost in cell passage numbers where the BBB properties are no longer fully conserved. Expression and localization of claudin-3 is not modulated by simvastatin shown to improve barrier function in vitro and also recommended for routine hCMEC/D3 culture. Conclusions These results support conservation of claudin-3 and -12 expression in the hCMEC/D3 cell line and make claudin-3 a potential marker for BBB characteristics in vitro.

Fusion of local and global features for classification of abnormality in ...

Indian Academy of Sciences (India)

Anuradha C Phadke

cancer death all over the world. In India, breast .... and efficient. Oliver et al [16] proposed a knowledge-based ... microcalcifications morphology is obtained by using bank of filters. ..... fication for management of abnormal mammograms. J. Am.

USP2 Regulates the Intracellular Localization of PER1 and Circadian Gene Expression

DEFF Research Database (Denmark)

Yang, Yaoming; Duguay, David; Fahrenkrug, Jan

2014-01-01

. Although Per1 mRNA expression rhythm remained intact in the Usp2 KO MEFs, the expression profiles of other core clock genes were altered. This was also true for the expression of clock-controlled genes (e.g., Dbp, Tef, Hlf, E4bp4). A similar phase advance of PER1 nuclear localization rhythm and alteration...

Global similarity and local divergence in human and mouse gene co-expression networks

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Koonin Eugene V

2006-09-01

Full Text Available Abstract Background A genome-wide comparative analysis of human and mouse gene expression patterns was performed in order to evaluate the evolutionary divergence of mammalian gene expression. Tissue-specific expression profiles were analyzed for 9,105 human-mouse orthologous gene pairs across 28 tissues. Expression profiles were resolved into species-specific coexpression networks, and the topological properties of the networks were compared between species. Results At the global level, the topological properties of the human and mouse gene coexpression networks are, essentially, identical. For instance, both networks have topologies with small-world and scale-free properties as well as closely similar average node degrees, clustering coefficients, and path lengths. However, the human and mouse coexpression networks are highly divergent at the local level: only a small fraction ( Conclusion The dissonance between global versus local network divergence suggests that the interspecies similarity of the global network properties is of limited biological significance, at best, and that the biologically relevant aspects of the architectures of gene coexpression are specific and particular, rather than universal. Nevertheless, there is substantial evolutionary conservation of the local network structure which is compatible with the notion that gene coexpression networks are subject to purifying selection.

High Smac/DIABLO expression is associated with early local recurrence of cervical cancer

International Nuclear Information System (INIS)

Arellano-Llamas, Abril; Garcia, Francisco J; Perez, Delia; Cantu, David; Espinosa, Magali; De la Garza, Jaime G; Maldonado, Vilma; Melendez-Zajgla, Jorge

2006-01-01

In a recent pilot report, we showed that Smac/DIABLO mRNA is expressed de novo in a subset of cervical cancer patients. We have now expanded this study and analyzed Smac/DIABLO expression in the primary lesions in 109 cervical cancer patients. We used immunohistochemistry of formalin-fixed, paraffin-embedded tissue sections to analyze Smac/DIABLO expression in the 109 primary lesions. Seventy-eight samples corresponded to epidermoid cervical cancer and 31 to cervical adenocarcinoma. The median follow up was 46.86 months (range 10–186). Smac/DIABLO was expressed in more adenocarcinoma samples than squamous tumours (71% vs 50%; p = 0.037). Among the pathological variables, a positive correlation was found between Smac/DIABLO immunoreactivity and microvascular density, a marker for angiogenesis (p = 0.04). Most importantly, Smac/DIABLO immunoreactivity was associated with a higher rate of local recurrence in squamous cell carcinoma (p = 0.002, log rank test). No association was found between Smac/DIABLO and survival rates. Smac/DIABLO expression is a potential marker for local recurrence in cervical squamous cell carcinoma patients

Cytomegalovirus induces abnormal chondrogenesis and osteogenesis during embryonic mandibular development

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Bringas Pablo

2008-03-01

Full Text Available Abstract Background Human clinical studies and mouse models clearly demonstrate that cytomegalovirus (CMV disrupts normal organ and tissue development. Although CMV is one of the most common causes of major birth defects in humans, little is presently known about the mechanism(s underlying CMV-induced congenital malformations. Our prior studies have demonstrated that CMV infection of first branchial arch derivatives (salivary glands and teeth induced severely abnormal phenotypes and that CMV has a particular tropism for neural crest-derived mesenchyme (NCM. Since early embryos are barely susceptible to CMV infection, and the extant evidence suggests that the differentiation program needs to be well underway for embryonic tissues to be susceptible to viral infection and viral-induced pathology, the aim of this study was to determine if first branchial arch NCM cells are susceptible to mCMV infection prior to differentiation of NCM derivatives. Results E11 mouse mandibular processes (MANs were infected with mouse CMV (mCMV for up to 16 days in vitro. mCMV infection of undifferentiated embryonic mouse MANs induced micrognathia consequent to decreased Meckel's cartilage chondrogenesis and mandibular osteogenesis. Specifically, mCMV infection resulted in aberrant stromal cellularity, a smaller, misshapen Meckel's cartilage, and mandibular bone and condylar dysmorphogenesis. Analysis of viral distribution indicates that mCMV primarily infects NCM cells and derivatives. Initial localization studies indicate that mCMV infection changed the cell-specific expression of FN, NF-κB2, RelA, RelB, and Shh and Smad7 proteins. Conclusion Our results indicate that mCMV dysregulation of key signaling pathways in primarily NCM cells and their derivatives severely disrupts mandibular morphogenesis and skeletogenesis. The pathogenesis appears to be centered around the canonical and noncanonical NF-κB pathways, and there is unusual juxtaposition of abnormal stromal

Morphological Abnormalities of Thalamic Subnuclei in Migraine

DEFF Research Database (Denmark)

Magon, Stefano; May, Arne; Stankewitz, Anne

2015-01-01

UNLABELLED: The thalamus contains third-order relay neurons of the trigeminal system, and animal models as well as preliminary imaging studies in small cohorts of migraine patients have suggested a role of the thalamus in headache pathophysiology. However, larger studies using advanced imaging te...... is a disorder of the CNS in which not only is brain function abnormal, but also brain structure is undergoing significant remodeling....... a fully automated multiatlas approach. Deformation-based shape analysis was performed to localize surface abnormalities. Differences between patients with migraine and healthy subjects were assessed using an ANCOVA model. After correction for multiple comparisons, performed using the false discovery rate.......9) was observed in patients. This large-scale study indicates structural thalamic abnormalities in patients with migraine. The thalamic nuclei with abnormal volumes are densely connected to the limbic system. The data hence lend support to the view that higher-order integration systems are altered in migraine...

Expression and Localization of Cathepsins B, D, and G in Dupuytren’s Disease

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Kirin Tan, MB ChB

2018-02-01

Conclusions:. Cathepsins B, D, and G were expressed in the DD tissues, with cathepsins B and D localized to the primitive population in the endothelium of the microvessels, whereas cathepsin G was localized to phenotypic mast cells, suggesting the presence of bypass loops for the RAS.

Leptospira interrogans induces uterine inflammatory responses and abnormal expression of extracellular matrix proteins in dogs.

Science.gov (United States)

Wang, Wei; Gao, Xuejiao; Guo, Mengyao; Zhang, Wenlong; Song, Xiaojing; Wang, Tiancheng; Zhang, Zecai; Jiang, Haichao; Cao, Yongguo; Zhang, Naisheng

2014-10-01

Leptospira interrogans (L. interrogans), a worldwide zoonosis, infect humans and animals. In dogs, four syndromes caused by leptospirosis have been identified: icteric, hemorrhagic, uremic (Stuttgart disease) and reproductive (abortion and premature or weak pups), and also it caused inflammation. Extracellular matrix (ECM) is a complex mixture of matrix molecules that is crucial to the reproduction. Both inflammatory response and ECM are closed relative to reproductive. The aim of this study was to clarify how L. interrogans affected the uterus of dogs, by focusing on the inflammatory responses, and ECM expression in dogs uterine tissue infected by L. interrogans. In the present study, 27 dogs were divided into 3 groups, intrauterine infusion with L. interrogans, to make uterine infection, sterile EMJH, and normal saline as a control, respectively. The uteruses were removed by surgical operation in 10, 20, and 30 days, respectively. The methods of histopathological analysis, ELISA, Western blot and qPCR were used. The results showed that L. interrogans induced significantly inflammatory responses, which were characterized by inflammatory cellular infiltration and high expression levels of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in uterine tissue of these dogs. Furthermore, L. interrogans strongly down-regulated the expression of ECM (collagens (CL) IV, fibronectins (FN) and laminins (LN)) in mRNA and protein levels. These data indicated that strongly inflammatory responses, and abnormal regulation of ECM might contribute to the proliferation of dogs infected by L. interrogans. Copyright © 2014 Elsevier Ltd. All rights reserved.

Expression, localization and possible functions of aquaporins 3 and 8 in rat digestive system.

Science.gov (United States)

Zhao, G X; Dong, P P; Peng, R; Li, J; Zhang, D Y; Wang, J Y; Shen, X Z; Dong, L; Sun, J Y

2016-01-01

Although aquaporins (AQPs) play important roles in transcellular water movement, their precise quantification and localization remains controversial. We investigated expression levels and localizations of AQP3 and AQP8 and their possible functions in the rat digestive system using real-time polymerase chain reactions, western blot analysis and immunohistochemistry. We investigated the expression levels and localizations of AQP3 and AQP8 in esophagus, forestomach, glandular stomach, duodenum, jejunum, ileum, proximal and distal colon, and liver. AQP3 was expressed in the basolateral membranes of stratified epithelia (esophagus and forestomach) and simple columnar epithelia (glandular stomach, ileum, and proximal and distal colon). Expression was particularly abundant in the esophagus, and proximal and distal colon. AQP8 was found in the subapical compartment of columnar epithelial cells of the jejunum, ileum, proximal colon and liver; the most intense staining occurred in the jejunum. Our results suggest that AQP3 and AQP8 play significant roles in intestinal function and/or fluid homeostasis and may be an important subject for future investigation of disorders that involve disruption of intestinal fluid homeostasis, such as inflammatory bowel disease and irritable bowel syndrome.

Hair Shaft Abnormality in Children: a Narrative Review

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Ghasem Rahmatpour Rokni

2017-08-01

Full Text Available Background Hair is an ectodermal structure, and its formation is regulated by master genes important in embryology. Hair shaft consists of three major regions: the medulla, cortex and cuticle. Hair shaft abnormality will divide structural hair abnormalities into two broad categories - those associated with increased hair fragility and those not associated with increased hair fragility. We conducted a review study to assess hair shaft abnormality in children. Materials and Methods We conducted a review of all papers published on hair shaft abnormalities. A literature search was performed using PubMed, Scopus and Google Scholar on papers publish from 1990 to 2016. The search terms were: hair shaft abnormality, Hair loss, Hair fragility. All abstracts and full text English-language articles were studied. Results While common developmental and structural features are shared in hair follicles and hair shafts. Anomalies of the hair shaft are separated into those with and those without increased hair fragility. Conclusion Although hair has no vital function, it may serve as an indicator for human health. Clinical and morphological hair abnormalities can be clues to specific complex disorders. Hair shaft abnormalities can be inherited or acquired, can reflect a local problem or a systemic disease.

ATM localization and gene expression in the adult mouse eye.

Science.gov (United States)

Leemput, Julia; Masson, Christel; Bigot, Karine; Errachid, Abdelmounaim; Dansault, Anouk; Provost, Alexandra; Gadin, Stéphanie; Aoufouchi, Said; Menasche, Maurice; Abitbol, Marc

2009-01-01

High levels of metabolism and oxygen consumption in most adult murine ocular compartments, combined with exposure to light and ultraviolet (UV) radiation, are major sources of oxidative stress, causing DNA damage in ocular cells. Of all mammalian body cells, photoreceptor cells consume the largest amount of oxygen and generate the highest levels of oxidative damage. The accumulation of such damage throughout life is a major factor of aging tissues. Several multiprotein complexes have recently been identified as the major sensors and mediators involved in the maintenance of DNA integrity. The activity of these complexes initially seemed to be restricted to dividing cells, given their ultimate role in major cell cycle checkpoints. However, it was later established that they are also active in post-mitotic cells. Recent findings demonstrate that the DNA damage response (DDR) is essential for the development, maintenance, and normal functioning of the adult central nervous system. One major molecular factor in the DDR is the protein, ataxia telangiectasia mutated (ATM). It is required for the rapid induction of cellular responses to DNA double-strand breaks. These cytotoxic DNA lesions may be caused by oxidative damage. To understand how ATM prevents oxidative stress and participates in the maintenance of genomic integrity and cell viability of the adult retina, we determined the ATM expression patterns and studied its localization in the adult mouse eye. Atm gene expression was analyzed by RT-PCR experiments and its localization by in situ hybridization on adult mouse ocular and cerebellar tissue sections. ATM protein expression was determined by western blot analysis of proteins homogenates extracted from several mouse tissues and its localization by immunohistochemistry experiments performed on adult mouse ocular and cerebellar tissue sections. In addition, subcellular localization was realized by confocal microscopy imaging of ocular tissue sections, with a special

Abnormal expression of 11 beta-hydroxysteroid dehydrogenase type 2 in human pituitary adenomas: a prereceptor determinant of pituitary cell proliferation.

Science.gov (United States)

Rabbitt, E H; Ayuk, J; Boelaert, K; Sheppard, M C; Hewison, M; Stewart, P M; Gittoes, N J L

2003-03-20

The physiological effects of glucocorticoids (GCs) are, at least in part, mediated by inhibition of cell proliferation. Two isozymes of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) interconvert cortisol (F) and inactive cortisone (E), and are thus able to modulate GC action at an autocrine level. Previously, we have demonstrated absent expression of 11 beta-HSD2 in normal pituitaries; however, in a small number of pituitary tumors analysed, 11 beta-HSD2 was readily demonstrable. Here we have used real-time RT-PCR to quantify expression of mRNA for 11 beta-HSD1 and 2 in 105 human pituitary tumors and have performed enzyme expression and activity studies in primary pituitary cultures. Overall, pituitary tumors expressed lower levels of 11 beta-HSDl mRNA compared with normals (0.2-fold, Pprotein (mean+/-s.d.)) but no detectable 11 beta-HSDl activity. Proliferation assays showed that addition of glycyrrhetinic acid (an 11 beta-HSD2 inhibitor) resulted in a 30.3+/-7.7% inhibition of cell proliferation. In summary, we describe a switch in expression from 11 beta-HSDl to 11 beta-HSD2 in neoplastic pituitary tissue. We propose that abnormal expression of 11 beta-HSD2 acts as a proproliferative prereceptor determinant of pituitary cell growth, and may provide a novel target for future tumor therapy.

Cellular endocytic compartment localization of expressed canine CD1 molecules

DEFF Research Database (Denmark)

Schjærff, Mette; Keller, Stefan M.; Affolter, Verena K.

2016-01-01

CD1 molecules are glycoproteins present primarily on dendritic cells (DCs), which recognize and presenta variety of foreign- and self-lipid antigens to T-cells. Humans have five different CD1 isoforms that sur-vey distinct cellular compartments allowing for recognition of a large repertoire...... onlya diminished GFP expression. In conclusion, canine CD1 transfectants show distinct localization patternsthat are similar to human CD1 proteins with the exception of the canine CD1d isoform, which most likelyis non-functional. These findings imply that canine CD1 localization overall resembles human...... CD1 traf-ficking patterns. This knowledge is important for the understanding of lipid antigen-receptor immunityin the dog....

[Prokaryotic expression and histological localization of the Taenia solium CDC37 gene].

Science.gov (United States)

Huang, Jiang; Li, Bo; Dai, Jia-Lin; Zhang, Ai-Hua

2013-02-01

To express Taenia solium gene encoding cell division cycle 37 protein (TsCDC37) and investigate its antigenicity and localization in adults of Taenia solium. The complete coding sequence of TsCDC37 was amplified by PCR based on the recombinant plasmid clone from the cDNA library of adult Taenia solium. The PCR product was cloned into a prokaryotic expression vector pET-28a (+). The recombinant expression plasmid was identified by PCR, double endonuclease digestion and sequencing. The recombinant plasmid was transformed into E. coli BL21/DE3 and followed by expression of the protein induced by IPTG. The mice were immunized subcutaneously with purified recombinant TsCDC37 formulated in Freund's adjuvant. The antigenicity of the recombinant protein was examined by Western blotting. The localization of TsCDC37 in adult worms was demonstrated by immunofluorescent technique. The recombinant expression vector was constructed successfully. The recombinant protein was about M(r) 52 000, it was then purified and specifically recognized by immuno sera of SD rats and sera from patients infected with Taenia solium, Taenia saginata or Taenia asiatica. The immunofluorescence assay revealed that TsCDC37 located at the tegument of T. solium adult and the eggs. TsCDC37 gene has been expressed with immunoreactivity. The recombinant protein is mainly expressed in tegument and egg, and is a common antigen of the three human taenia cestodes.

Partial Tmem106b reduction does not correct abnormalities due to progranulin haploinsufficiency.

Science.gov (United States)

Arrant, Andrew E; Nicholson, Alexandra M; Zhou, Xiaolai; Rademakers, Rosa; Roberson, Erik D

2018-06-22

Loss of function mutations in progranulin (GRN) are a major cause of frontotemporal dementia (FTD). Progranulin is a secreted glycoprotein that localizes to lysosomes and is critical for proper lysosomal function. Heterozygous GRN mutation carriers develop FTD with TDP-43 pathology and exhibit signs of lysosomal dysfunction in the brain, with increased levels of lysosomal proteins and lipofuscin accumulation. Homozygous GRN mutation carriers develop neuronal ceroid lipofuscinosis (NCL), an earlier-onset lysosomal storage disorder caused by severe lysosomal dysfunction. Multiple genome-wide association studies have shown that risk of FTD in GRN mutation carriers is modified by polymorphisms in TMEM106B, which encodes a lysosomal membrane protein. Risk alleles of TMEM106B may increase TMEM106B levels through a variety of mechanisms. Brains from FTD patients with GRN mutations exhibit increased TMEM106B expression, and protective TMEM106B polymorphisms are associated with decreased TMEM106B expression. Together, these data raise the possibility that reduction of TMEM106B levels may protect against the pathogenic effects of progranulin haploinsufficiency. We crossed Tmem106b +/- mice with Grn +/- mice, which model the progranulin haploinsufficiency of GRN mutation carriers and develop age-dependent social deficits and lysosomal abnormalities in the brain. We tested whether partial Tmem106b reduction could normalize the social deficits and lysosomal abnormalities of Grn +/- mice. Partial reduction of Tmem106b levels did not correct the social deficits of Grn +/- mice. Tmem106b reduction also failed to normalize most lysosomal abnormalities of Grn +/- mice, except for β-glucuronidase activity, which was suppressed by Tmem106b reduction and increased by progranulin insufficiency. These data do not support the hypothesis that Tmem106b reduction protects against the pathogenic effects of progranulin haploinsufficiency, but do show that Tmem106b reduction normalizes some

Facial expression recognition based on improved local ternary pattern and stacked auto-encoder

Science.gov (United States)

Wu, Yao; Qiu, Weigen

2017-08-01

In order to enhance the robustness of facial expression recognition, we propose a method of facial expression recognition based on improved Local Ternary Pattern (LTP) combined with Stacked Auto-Encoder (SAE). This method uses the improved LTP extraction feature, and then uses the improved depth belief network as the detector and classifier to extract the LTP feature. The combination of LTP and improved deep belief network is realized in facial expression recognition. The recognition rate on CK+ databases has improved significantly.

Population-based prevalence of abnormal cervical cytology findings and local risk factors in Ibadan, Nigeria: implications for cervical cancer control programs and human papilloma virus immunization.

Science.gov (United States)

Thomas, J O; Ojemakinde, K O; Ajayi, I O; Omigbodun, A O; Fawole, O I; Oladepo, O

2012-01-01

To investigate the prevalence of abnormal cervical cytological findings and local risk factors in Ibadan, Nigeria. All women aged ≥15 years in each household in Idikan, Ibadan, were invited to participate in a population-based study. Structured questionnaires were administered to all consenting women. Conventional cervical Papanicolaou smears obtained from sexually active women were classified using the 2001 Bethesda system. The diagnoses were correlated with sociodemographic data and risk factors. Of 2,870 women aged ≥15 years estimated to live in Idikan, 1,204 sexually active women consented to pelvic examination and cervical smears. Results were available for 1,104 women (mean age: 39.8 years). Mean ages at menarche, first sexual intercourse and first pregnancy were 16.1, 20.3 and 20.7 years, respectively. Cytological results were categorized into atypical squamous cells of undetermined significance and atypical glandular cells 22 (1.99%); low-grade 43 (3.89%) and high-grade squamous intraepithelial lesions (HSIL) 17 (1.54%); invasive cancer 2 (0.18%) and normal 593 (53.8%) and reactive changes 427 (38.7%). The prevalence of epithelial abnormalities is 7.6%. Significant host-related factors in those with HSIL and invasive cancer included older age (mean 56.2 years), high parity and gravidity, lack of formal education and being divorced (p prevalence data and local risk factors for abnormal cervical cytology in a Nigerian population, which will be useful for planning future cervical cancer control programs. Copyright © 2012 S. Karger AG, Basel.

Attenuated expression of HRH4 in colorectal carcinomas: a potential influence on tumor growth and progression

International Nuclear Information System (INIS)

Fang, Zhengyu; Wan, Jun; Yao, Wantong; Xiong, Yi; Li, Jiana; Liu, Li; Shi, Lei; Zhang, Wei; Zhang, Chao; Nie, Liping

2011-01-01

Earlier studies have reported the production of histamine in colorectal cancers (CRCs). The effect of histamine is largely determined locally by the histamine receptor expression pattern. Recent evidence suggests that the expression level of histamine receptor H4 (HRH4) is abnormal in colorectal cancer tissues. However, the role of HRH4 in CRC progression and its clinical relevance is not well understood. The aim of this study is to evaluate the clinical and molecular phenotypes of colorectal tumors with abnormal HRH4 expression. Immunoblotting, real-time PCR, immunofluorescence and immunohistochemistry assays were adopted to examine HRH4 expression in case-matched CRC samples (n = 107) and adjacent normal tissues (ANTs). To assess the functions of HRH4 in CRC cells, we established stable HRH4-transfected colorectal cells and examined cell proliferation, colony formation, cell cycle and apoptosis in these cells. The protein levels of HRH4 were reduced in most of the human CRC samples regardless of grade or Dukes classification. mRNA levels of HRH4 were also reduced in both early-stage and advanced CRC samples. In vitro studies showed that HRH4 over-expression caused growth arrest and induced expression of cell cycle proteins in CRC cells upon exposure to histamine through a cAMP -dependent pathway. Furthermore, HRH4 stimulation promoted the 5-Fu-induced cell apoptosis in HRH4-positive colorectal cells. The results from the current study supported previous findings of HRH4 abnormalities in CRCs. Expression levels of HRH4 could influence the histamine-mediated growth regulation in CRC cells. These findings suggested a potential role of abnormal HRH4 expression in the progression of CRCs and provided some new clues for the application of HRH4-specific agonist or antagonist in the molecular therapy of CRCs

Attenuated expression of HRH4 in colorectal carcinomas: a potential influence on tumor growth and progression

Directory of Open Access Journals (Sweden)

Zhang Wei

2011-05-01

Full Text Available Abstract Background Earlier studies have reported the production of histamine in colorectal cancers (CRCs. The effect of histamine is largely determined locally by the histamine receptor expression pattern. Recent evidence suggests that the expression level of histamine receptor H4 (HRH4 is abnormal in colorectal cancer tissues. However, the role of HRH4 in CRC progression and its clinical relevance is not well understood. The aim of this study is to evaluate the clinical and molecular phenotypes of colorectal tumors with abnormal HRH4 expression. Methods Immunoblotting, real-time PCR, immunofluorescence and immunohistochemistry assays were adopted to examine HRH4 expression in case-matched CRC samples (n = 107 and adjacent normal tissues (ANTs. To assess the functions of HRH4 in CRC cells, we established stable HRH4-transfected colorectal cells and examined cell proliferation, colony formation, cell cycle and apoptosis in these cells. Results The protein levels of HRH4 were reduced in most of the human CRC samples regardless of grade or Dukes classification. mRNA levels of HRH4 were also reduced in both early-stage and advanced CRC samples. In vitro studies showed that HRH4 over-expression caused growth arrest and induced expression of cell cycle proteins in CRC cells upon exposure to histamine through a cAMP -dependent pathway. Furthermore, HRH4 stimulation promoted the 5-Fu-induced cell apoptosis in HRH4-positive colorectal cells. Conclusion The results from the current study supported previous findings of HRH4 abnormalities in CRCs. Expression levels of HRH4 could influence the histamine-mediated growth regulation in CRC cells. These findings suggested a potential role of abnormal HRH4 expression in the progression of CRCs and provided some new clues for the application of HRH4-specific agonist or antagonist in the molecular therapy of CRCs.

MRI of a family with focal abnormalities of gyration

International Nuclear Information System (INIS)

Muntaner, L.; Perez-Ferron, J.J.; Herrera, M.; Rosell, J.; Taboada, D.; Climent, S.

1997-01-01

Focal abnormalities of gyration (FAG) are developmental disorders that may occur in isolated patients or, as in the case being reported, as part of a familial disorder. Analysis of individuals in a family spanning three generations was carried out using MRI. Abnormalities, present in all members of generations II and III, included focal cortical dysplasia (three patients), focal cortical infolding (two patients) and schizencephaly (one patient); associated minor anomalies, such as white matter abnormalities, were seen in the remaining three members of generations II and III. MRI recognition of FAG in the family being reported proved useful in defining their phenotypical expression and providing proper counselling for individual family members. (orig.). With 6 figs

Heterologous expression of a ketohexokinase in potato plants leads to inhibited rates of photosynthesis, severe growth retardation and abnormal leaf development

DEFF Research Database (Denmark)

Geigenberger, P.; Regierer, B.; Lytovchenko, A.

2004-01-01

of ketohexokinase but did not accumulate fructose 1-phosphate. They were, however, characterised by a severe growth retardation and abnormal leaf development. Studies of (14)CO(2) assimilation and metabolism, and of the levels of photosynthetic pigments, revealed that these lines exhibited restricted photosynthesis......In the present paper we investigated the effect of heterologous expression of a rat liver ketohexokinase in potato (Solanum tuberosum L.) plants with the aim of investigating the role of fructose 1-phosphate in plant metabolism. Plants were generated that contained appreciable activity...

The diversity of abnormal hormone receptors in adrenal Cushing's syndrome allows novel pharmacological therapies

Directory of Open Access Journals (Sweden)

Lacroix A.

2000-01-01

Full Text Available Recent studies from several groups have indicated that abnormal or ectopic expression and function of adrenal receptors for various hormones may regulate cortisol production in ACTH-independent hypercortisolism. Gastric inhibitory polypeptide (GIP-dependent Cushing's syndrome has been described in patients with either unilateral adenoma or bilateral macronodular adrenal hyperplasia; this syndrome results from the large adrenal overexpression of the GIP receptor without any activating mutation. We have conducted a systematic in vivo evaluation of patients with adrenal Cushing's syndrome in order to identify the presence of abnormal hormone receptors. In macronodular adrenal hyperplasia, we have identified, in addition to GIP-dependent Cushing's syndrome, other patients in whom cortisol production was regulated abnormally by vasopressin, ß-adrenergic receptor agonists, hCG/LH, or serotonin 5HT-4 receptor agonists. In patients with unilateral adrenal adenoma, the abnormal expression or function of GIP or vasopressin receptor has been found, but the presence of ectopic or abnormal hormone receptors appears to be less prevalent than in macronodular adrenal hyperplasia. The identification of the presence of an abnormal adrenal receptor offers the possibility of a new pharmacological approach to control hypercortisolism by suppressing the endogenous ligands or by using specific antagonists for the abnormal receptors.

Abnormal interhemispheric connectivity in male psychopathic offenders.

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Hoppenbrouwers, Sylco S; De Jesus, Danilo R; Sun, Yinming; Stirpe, Tania; Hofman, Dennis; McMaster, Jeff; Hughes, Ginny; Daskalakis, Zafiris J; Schutter, Dennis J L G

2014-01-01

Psychopathic offenders inevitably violate interpersonal norms and frequently resort to aggressive and criminal behaviour. The affective and cognitive deficits underlying these behaviours have been linked to abnormalities in functional interhemispheric connectivity. However, direct neurophysiological evidence for dysfunctional connectivity in psychopathic offenders is lacking. We used transcranial magnetic stimulation combined with electroencephalography to examine interhemispheric connectivity in the dorsolateral and motor cortex in a sample of psychopathic offenders and healthy controls. We also measured intracortical inhibition and facilitation over the left and right motor cortex to investigate the effects of local cortical processes on interhemispheric connectivity. We enrolled 17 psychopathic offenders and 14 controls in our study. Global abnormalities in right to left functional connectivity were observed in psychopathic offenders compared with controls. Furthermore, in contrast to controls, psychopathic offenders showed increased intracortical inhibition in the right, but not the left, hemisphere. The relatively small sample size limited the sensitivity to show that the abnormalities in interhemispheric connectivity were specifically related to the dorsolateral prefrontal cortex in psychopathic offenders. To our knowledge, this study provides the first neurophysiological evidence for abnormal interhemispheric connectivity in psychopathic offenders and may further our understanding of the disruptive antisocial behaviour of these offenders.

LILRB4 Decrease on uDCs Exacerbate Abnormal Pregnancy Outcomes Following Toxoplasma gondii Infection

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Shaowei Zhan

2018-03-01

Full Text Available Toxoplasma gondii (T. gondii infection in early pregnancy can result in miscarriage, dead fetus, and other abnormalities. The LILRB4 is a central inhibitory receptor in uterine dendritic cells (uDCs that plays essential immune-regulatory roles at the maternal–fetal interface. In this study, T. gondii-infected human primary uDCs and T. gondii-infected LILRB4-/- pregnant mice were utilized. The immune mechanisms underlying the role of LILRB4 on uDCs were explored in the development of abnormal pregnancy outcomes following T. gondii infection in vitro and in vivo. Our results showed that the expression levels of LILRB4 on uDCs from normal pregnant mice were obviously higher than non-pregnant mice, and peaked in mid-gestation. The LILRB4 expression on uDC subsets, especially tolerogenic subsets, from mid-gestation was obviously down-regulated after T. gondii infection and LILRB4 decrease could further regulate the expression of functional molecules (CD80, CD86, and HLA-DR or MHC II on uDCs, contributing to abnormal pregnancy outcomes. Our results will shed light on the molecular immune mechanisms of uDCs in abnormal pregnancy outcomes by T. gondii infection.

Determination of Six Transmembrane Protein of Prostate 2 Gene Expression and Intracellular Localization in Prostate Cancer

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Bora İrer

2017-12-01

Full Text Available Objective: In this study, we aimed to determine the relationship between the RNA and protein expression profile of six transmembrane protein of prostate 2 (STAMP2 gene and androgen and the intracellular localization of STAMP2. Materials and Methods: RNA and protein were obtained from androgen treated lymph node carcinoma of the prostate (LNCaP cells, untreated LNCaP cells, DU145 cells with no androgen receptor, and STAMP2 transfected COS-7 cells. The expression profile of STAMP2 gene and the effect of androgenes on the expression was shown in RNA and protein levels by using Northern and Western blotting methods. In addition, intracellular localization of the naturally synthesized STAMP2 protein and the transfected STAMP2 protein in COS-7 cells after androgen administration in both LNCaP cells was determined by immunofluorescence microscopy. Results: We found that the RNA and protein expression of STAMP2 gene in LNCaP cells are regulated by androgenes, the power of expression is increased with the duration of androgen treatment and there is no STAMP2 expression in DU145 cells which has no androgen receptor. As a result of the immunofluorescence microscopy study we observed that STAMP2 protein was localized at golgi complex and cell membrane. Conclusion: In conclusion, we have demonstrated that STAMP2 may play an important role in the pathogenesis of the prostate cancer and in the androgen-dependent androgen-independent staging of prostate cancer. In addition, STAMP2 protein, which is localized in the intracellular golgi complex and cell membrane, may be a new target molecule for prostate cancer diagnosis and treatment.

Abnormal histopathology, fat percent and hepatic apolipoprotein A I and apolipoprotein B100 mRNA expression in fatty liver hemorrhagic syndrome and their improvement by soybean lecithin.

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Song, Yalu; Ruan, Jiming; Luo, Junrong; Wang, Tiancheng; Yang, Fei; Cao, Huabin; Huang, Jianzhen; Hu, Guoliang

2017-10-01

To investigate the etiopathogenesis of fatty liver hemorrhagic syndrome (FLHS) and the protective effects of soybean lecithin against FLHS in laying hens, 135 healthy 300-day-old Hyline laying hens were randomly divided into groups: control (group 1), diseased (group 2), and protected (group 3). Each group contained 45 layers with 3 replicates. The birds in these 3 groups were fed a control diet, a high-energy/low-protein (HELP) diet or the HELP diet supplemented with 3% soybean lecithin instead of maize. The fat percent in the liver was calculated. Histopathological changes in the liver were determined by staining, and the mRNA expression levels of apolipoproteinA I (apoA I) and apolipoprotein B100 (apoB100) in the liver were determined by RT-PCR. The results showed that the fat percent in the liver of group 2 was much higher (P steatosis in the liver cell on d 30 and 60. The mRNA expression levels of apoA I and apoB100 in the livers were variable throughout the experiment. The expression level of apoA I in group 2 significantly decreased on d 60 (P < 0.05); the expression level of apoB100 slightly increased on d 30 in group 2, while it sharply decreased on d 60. Compared to group 1, the expression level of apoB100 showed no significant difference in group 3 (P < 0.05). This study indicated that FLHS induced pathological changes and abnormal expression of apoA I and apoB100 in the livers of laying hens and that soybean lecithin alleviated these abnormal changes. © 2017 Poultry Science Association Inc.

Anatomical abnormalities in gray and white matter of the cortical surface in persons with schizophrenia.

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Tiziano Colibazzi

Full Text Available Although schizophrenia has been associated with abnormalities in brain anatomy, imaging studies have not fully determined the nature and relative contributions of gray matter (GM and white matter (WM disturbances underlying these findings. We sought to determine the pattern and distribution of these GM and WM abnormalities. Furthermore, we aimed to clarify the contribution of abnormalities in cortical thickness and cortical surface area to the reduced GM volumes reported in schizophrenia.We recruited 76 persons with schizophrenia and 57 healthy controls from the community and obtained measures of cortical and WM surface areas, of local volumes along the brain and WM surfaces, and of cortical thickness.We detected reduced local volumes in patients along corresponding locations of the brain and WM surfaces in addition to bilateral greater thickness of perisylvian cortices and thinner cortex in the superior frontal and cingulate gyri. Total cortical and WM surface areas were reduced. Patients with worse performance on the serial-position task, a measure of working memory, had a higher burden of WM abnormalities.Reduced local volumes along the surface of the brain mirrored the locations of abnormalities along the surface of the underlying WM, rather than of abnormalities of cortical thickness. Moreover, anatomical features of white matter, but not cortical thickness, correlated with measures of working memory. We propose that reductions in WM and smaller total cortical surface area could be central anatomical abnormalities in schizophrenia, driving, at least partially, the reduced regional GM volumes often observed in this illness.

[Cloning, subcellular localization, and heterologous expression of ApNAC1 gene from Andrographis paniculata].

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Wang, Jian; Qi, Meng-Die; Guo, Juan; Shen, Ye; Lin, Hui-Xin; Huang, Lu-Qi

2017-03-01

Andrographis paniculata is widely used as medicinal herb in China for a long time and andrographolide is its main medicinal constituent. To investigate the underlying andrographolide biosynthesis mechanisms, RNA-seq for A. paniculata leaves with MeJA treatment was performed. In A. paniculata transcriptomic data, the expression pattern of one member of NAC transcription factor family (ApNAC1) matched with andrographolide accumulation. The coding sequence of ApNAC1 was cloned by RT-PCR, and GenBank accession number was KY196416. The analysis of bioinformatics showed that the gene encodes a peptide of 323 amino acids, with a predicted relative molecular weight of 35.9 kDa and isoelectric point of 6.14. To confirm the subcellular localization, ApNAC1-GFP was transiently expressed in A. paniculata protoplast. The results indicated that ApNAC1 is a nucleus-localized protein. The analysis of real-time quantitative PCR revealed that ApNAC1 gene predominantly expresses in leaves. Compared with control sample, its expression abundance sharply increased with methyl jasmonate treatment. Based on its expression pattern, ApNAC1 gene might involve in andrographolide biosynthesis. ApNAC1 was heterologously expressed in Escherichia coli and recombinant protein was purified by Ni-NTA agarose. Further study will help us to understand the function of ApNAC1 in andrographolide biosynthesis. Copyright© by the Chinese Pharmaceutical Association.

Expression and localization of heterogeneous nuclear ribonucleoprotein K in mouse ovaries and preimplantation embryos

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Zhang, Ping; Wang, Ningling; Lin, Xianhua; Jin, Li; Xu, Hong; Li, Rong; Huang, Hefeng

2016-01-01

Heterogeneous nuclear ribonucleoprotein K (hnRNP K), an evolutionarily conserved protein, is involved in several important cellular processes that are relevant to cell proliferation, differentiation, apoptosis, and cancer development. However, details of hnRNP K expression during mammalian oogenesis and preimplantation embryo development are lacking. The present study investigates the expression and cellular localization of K protein in the mouse ovaries and preimplantation embryos using immunostaining. We demonstrate, for the first time, that hnRNP K is abundantly expressed in the nuclei of mouse oocytes in primordial, primary and secondary follicles. In germ vesicle (GV)-stage oocytes, hnRNP K accumulates in the germinal vesicle in a spot distribution manner. After germinal vesicle breakdown, speckled hnRNP K is diffusely distributed in the cytoplasm. However, after fertilization, the K protein relocates into the female and male pronucleus and persists in the blastomere nuclei. Localization of K protein in the human ovary and ovarian granulosa cell tumor (GCT) was also investigated. Overall, this study provides important morphological evidence to better understand the possible roles of hnRNP K in mammalian oogenesis and early embryo development. - Highlights: • HnRNP K localizes in the nucleus of GV-stage oocyte in a punctate distribution. • HnRNP K strongly accumulates in zygotic pronuclei as condensed spots. • The localization of hnRNP K during oogenesis and embryogenesis is characteristic. • HnRNP K might have an important role in oogenesis and embryonic development.

Expression and localization of heterogeneous nuclear ribonucleoprotein K in mouse ovaries and preimplantation embryos

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Zhang, Ping [The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (China); Wang, Ningling [Department of Assisted Reproduction, Shanghai Ninth People' s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (China); Lin, Xianhua; Jin, Li [The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (China); Xu, Hong, E-mail: xuhong1168@126.com [The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (China); Li, Rong [The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (China); Huang, Hefeng, E-mail: huanghefg@hotmail.com [The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (China)

2016-02-26

Heterogeneous nuclear ribonucleoprotein K (hnRNP K), an evolutionarily conserved protein, is involved in several important cellular processes that are relevant to cell proliferation, differentiation, apoptosis, and cancer development. However, details of hnRNP K expression during mammalian oogenesis and preimplantation embryo development are lacking. The present study investigates the expression and cellular localization of K protein in the mouse ovaries and preimplantation embryos using immunostaining. We demonstrate, for the first time, that hnRNP K is abundantly expressed in the nuclei of mouse oocytes in primordial, primary and secondary follicles. In germ vesicle (GV)-stage oocytes, hnRNP K accumulates in the germinal vesicle in a spot distribution manner. After germinal vesicle breakdown, speckled hnRNP K is diffusely distributed in the cytoplasm. However, after fertilization, the K protein relocates into the female and male pronucleus and persists in the blastomere nuclei. Localization of K protein in the human ovary and ovarian granulosa cell tumor (GCT) was also investigated. Overall, this study provides important morphological evidence to better understand the possible roles of hnRNP K in mammalian oogenesis and early embryo development. - Highlights: • HnRNP K localizes in the nucleus of GV-stage oocyte in a punctate distribution. • HnRNP K strongly accumulates in zygotic pronuclei as condensed spots. • The localization of hnRNP K during oogenesis and embryogenesis is characteristic. • HnRNP K might have an important role in oogenesis and embryonic development.

Local IGFBP-3 mRNA expression, apoptosis and risk of colorectal adenomas

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Omofoye Oluwaseun

2008-05-01

Full Text Available Abstract Background IGF binding protein-3 (IGFBP-3 regulates the bioavailability of insulin-like growth factors I and II, and has both anti-proliferative and pro-apoptotic properties. Elevated plasma IGFBP-3 has been associated with reduced risk of colorectal cancer (CRC, but the role of tissue IGFBP-3 is not well defined. We evaluated the association between tissue or plasma IGFBP-3 and risk of colorectal adenomas or low apoptosis. Methods Subjects were consenting patients who underwent a clinically indicated colonoscopy at UNC Hospitals and provided information on diet and lifestyle. IGFBP-3 mRNA in normal colon was assessed by real time RT-PCR. Plasma IGFBP-3 was measured by ELISA and apoptosis was determined by morphology on H & E slides. Logistic regression was used to compute odds ratio (OR and 95% confidence intervals. Results We observed a modest correlation between plasma IGFBP-3 and tissue IGFBP-3 expression (p = 0.007. There was no significant association between plasma IGFBP-3 and adenomas or apoptosis. Tissue IGFBP-3 mRNA expression was significantly lower in cases than controls. Subjects in the lowest three quartiles of tissue IGFBP-3 gene expression were more likely to have adenomas. Consistent with previous reports, low apoptosis was significantly associated with increased risk of adenomas (p = 0.003. Surprisingly, local IGFBP-3 mRNA expression was inversely associated with apoptosis. Conclusion Low expression of IGFBP-3 mRNA in normal colonic mucosa predicts increased risk of adenomas. Our findings suggest that local IGFBP-3 in the colon may directly increase adenoma risk but IGFBP-3 may act through a pathway other than apoptosis to influence adenoma risk.

Local IGFBP-3 mRNA expression, apoptosis and risk of colorectal adenomas

International Nuclear Information System (INIS)

Keku, Temitope O; Sandler, Robert S; Simmons, James G; Galanko, Joseph; Woosley, John T; Proffitt, Michelle; Omofoye, Oluwaseun; McDoom, Maya; Lund, Pauline K

2008-01-01

IGF binding protein-3 (IGFBP-3) regulates the bioavailability of insulin-like growth factors I and II, and has both anti-proliferative and pro-apoptotic properties. Elevated plasma IGFBP-3 has been associated with reduced risk of colorectal cancer (CRC), but the role of tissue IGFBP-3 is not well defined. We evaluated the association between tissue or plasma IGFBP-3 and risk of colorectal adenomas or low apoptosis. Subjects were consenting patients who underwent a clinically indicated colonoscopy at UNC Hospitals and provided information on diet and lifestyle. IGFBP-3 mRNA in normal colon was assessed by real time RT-PCR. Plasma IGFBP-3 was measured by ELISA and apoptosis was determined by morphology on H & E slides. Logistic regression was used to compute odds ratio (OR) and 95% confidence intervals. We observed a modest correlation between plasma IGFBP-3 and tissue IGFBP-3 expression (p = 0.007). There was no significant association between plasma IGFBP-3 and adenomas or apoptosis. Tissue IGFBP-3 mRNA expression was significantly lower in cases than controls. Subjects in the lowest three quartiles of tissue IGFBP-3 gene expression were more likely to have adenomas. Consistent with previous reports, low apoptosis was significantly associated with increased risk of adenomas (p = 0.003). Surprisingly, local IGFBP-3 mRNA expression was inversely associated with apoptosis. Low expression of IGFBP-3 mRNA in normal colonic mucosa predicts increased risk of adenomas. Our findings suggest that local IGFBP-3 in the colon may directly increase adenoma risk but IGFBP-3 may act through a pathway other than apoptosis to influence adenoma risk

Study on the relationship of abnormal transcription factors OCT4, HBP1 and Snail expression with progression of osteosarcoma

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Li Li

2016-09-01

Full Text Available Objective: To study the relationship of abnormal transcription factors OCT4, HBP1 and Snail expression with progression of osteosarcoma. Methods: Surgical removed osteosarcoma tissue specimens were selected as pathology group, surgically removed osteoid osteoma specimens were selected as control group, and the expression levels of gene transcription factors OCT4, HBP1 and Snail, proliferation genes, epithelial-mesenchymal transition marker molecules in tissue specimens were determined. Results: Oct4 and Snail protein levels of pathology group were significantly higher than those of control group and HBP1 protein level was significantly lower than that of control group; C-myc and cyclinD1 protein levels of pathology group were significantly higher than those of control group, positively correlated with OCT4 and negatively correlated with HBP1; p16 and p53 protein levels were significantly lower than those of control group, negatively correlated with OCT4 and positively correlated with HBP1; N-cadherin and Vimentin protein levels of pathology group were significantly higher than those of control group and positively correlated with Snail while E-cadherin and Occludin protein levels were significantly lower than those of control group and negatively correlated with Snail. Conclusion: Oct4 and Snail are highly expressed and HBP1 is lowly expressed in osteosarcoma tissue, Oct4 and Snail can participate in the regulation of cell proliferation, and HBP1 can participate in the regulation of epithelial-mesenchymal transition of cells.

Effect of Strain Restored Energy on Abnormal Grain Growth in Mg Alloy Simulated by Phase Field Methods

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Wu, Yan; Huang, Yuan-yuan

2018-03-01

Abnormal grain growth of single phase AZ31 Mg alloy in the spatio-temporal process has been simulated by phase field models, and the influencing factors of abnormal grain growth are studied in order to find the ways to control secondary recrystallization in the microstructure. The study aims to find out the mechanisms for abnormal grain growth in real alloys. It is shown from the simulated results that the abnormal grain growth can be controlled by the strain restored energy. Secondary recrystallization after an annealing treatment can be induced if there are grains of a certain orientation in the microstructure with local high restored energy. However, if the value of the local restored energy at a certain grain orientation is not greater than 1.1E 0, there may be no abnormal grain growth in the microstructure.

Adaptive weighted local textural features for illumination, expression, and occlusion invariant face recognition

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Cui, Chen; Asari, Vijayan K.

2014-03-01

Biometric features such as fingerprints, iris patterns, and face features help to identify people and restrict access to secure areas by performing advanced pattern analysis and matching. Face recognition is one of the most promising biometric methodologies for human identification in a non-cooperative security environment. However, the recognition results obtained by face recognition systems are a affected by several variations that may happen to the patterns in an unrestricted environment. As a result, several algorithms have been developed for extracting different facial features for face recognition. Due to the various possible challenges of data captured at different lighting conditions, viewing angles, facial expressions, and partial occlusions in natural environmental conditions, automatic facial recognition still remains as a difficult issue that needs to be resolved. In this paper, we propose a novel approach to tackling some of these issues by analyzing the local textural descriptions for facial feature representation. The textural information is extracted by an enhanced local binary pattern (ELBP) description of all the local regions of the face. The relationship of each pixel with respect to its neighborhood is extracted and employed to calculate the new representation. ELBP reconstructs a much better textural feature extraction vector from an original gray level image in different lighting conditions. The dimensionality of the texture image is reduced by principal component analysis performed on each local face region. Each low dimensional vector representing a local region is now weighted based on the significance of the sub-region. The weight of each sub-region is determined by employing the local variance estimate of the respective region, which represents the significance of the region. The final facial textural feature vector is obtained by concatenating the reduced dimensional weight sets of all the modules (sub-regions) of the face image

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

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

2012-01-01

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

Facial expression recognition under partial occlusion based on fusion of global and local features

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Wang, Xiaohua; Xia, Chen; Hu, Min; Ren, Fuji

2018-04-01

Facial expression recognition under partial occlusion is a challenging research. This paper proposes a novel framework for facial expression recognition under occlusion by fusing the global and local features. In global aspect, first, information entropy are employed to locate the occluded region. Second, principal Component Analysis (PCA) method is adopted to reconstruct the occlusion region of image. After that, a replace strategy is applied to reconstruct image by replacing the occluded region with the corresponding region of the best matched image in training set, Pyramid Weber Local Descriptor (PWLD) feature is then extracted. At last, the outputs of SVM are fitted to the probabilities of the target class by using sigmoid function. For the local aspect, an overlapping block-based method is adopted to extract WLD features, and each block is weighted adaptively by information entropy, Chi-square distance and similar block summation methods are then applied to obtain the probabilities which emotion belongs to. Finally, fusion at the decision level is employed for the data fusion of the global and local features based on Dempster-Shafer theory of evidence. Experimental results on the Cohn-Kanade and JAFFE databases demonstrate the effectiveness and fault tolerance of this method.

Gray matter abnormalities in patients with narcissistic personality disorder.

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Schulze, Lars; Dziobek, Isabel; Vater, Aline; Heekeren, Hauke R; Bajbouj, Malek; Renneberg, Babette; Heuser, Isabella; Roepke, Stefan

2013-10-01

Despite the relevance of narcissistic personality disorder (NPD) in clinical settings, there is currently no empirical data available regarding the neurobiological correlates of NPD. In the present study, we performed a voxel-based morphometric analysis to provide initial insight into local abnormalities of gray matter (GM) volume. Structural brain images were obtained from patients with NPD (n = 17) and a sample of healthy controls (n = 17) matched regarding age, gender, handedness, and intelligence. Groups were compared with regard to global brain tissue volumes and local abnormalities of GM volume. Regions-of-interest analyses were calculated for the anterior insula. Relative to the control group, NPD patients had smaller GM volume in the left anterior insula. Independent of group, GM volume in the left anterior insula was positively related to self-reported emotional empathy. Complementary whole-brain analyses yielded smaller GM volume in fronto-paralimbic brain regions comprising the rostral and median cingulate cortex as well as dorsolateral and medial parts of the prefrontal cortex. Here we provide the first empirical evidence for structural abnormalities in fronto-paralimbic brain regions of patients with NPD. The results are discussed in the context of NPD patients' restricted ability for emotional empathy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Striatal abnormalities in trichotillomania: A multi-site MRI analysis

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Masanori Isobe

2018-01-01

Full Text Available Trichotillomania (hair-pulling disorder is characterized by the repetitive pulling out of one's own hair, and is classified as an Obsessive-Compulsive Related Disorder. Abnormalities of the ventral and dorsal striatum have been implicated in disease models of trichotillomania, based on translational research, but direct evidence is lacking. The aim of this study was to elucidate subcortical morphometric abnormalities, including localized curvature changes, in trichotillomania. De-identified MRI scans were pooled by contacting authors of previous peer-reviewed studies that examined brain structure in adult patients with trichotillomania, following an extensive literature search. Group differences on subcortical volumes of interest were explored (t-tests and localized differences in subcortical structure morphology were quantified using permutation testing. The pooled sample comprised N = 68 individuals with trichotillomania and N = 41 healthy controls. Groups were well-matched in terms of age, gender, and educational levels. Significant volumetric reductions were found in trichotillomania patients versus controls in right amygdala and left putamen. Localized shape deformities were found in bilateral nucleus accumbens, bilateral amygdala, right caudate and right putamen. Structural abnormalities of subcortical regions involved in affect regulation, inhibitory control, and habit generation, play a key role in the pathophysiology of trichotillomania. Trichotillomania may constitute a useful model through which to better understand other compulsive symptoms. These findings may account for why certain medications appear effective for trichotillomania, namely those modulating subcortical dopamine and glutamatergic function. Future work should study the state versus trait nature of these changes, and the impact of treatment.

Abnormal metabolic network activity in REM sleep behavior disorder.

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Holtbernd, Florian; Gagnon, Jean-François; Postuma, Ron B; Ma, Yilong; Tang, Chris C; Feigin, Andrew; Dhawan, Vijay; Vendette, Mélanie; Soucy, Jean-Paul; Eidelberg, David; Montplaisir, Jacques

2014-02-18

To determine whether the Parkinson disease-related covariance pattern (PDRP) expression is abnormally increased in idiopathic REM sleep behavior disorder (RBD) and whether increased baseline activity is associated with greater individual risk of subsequent phenoconversion. For this cohort study, we recruited 2 groups of RBD and control subjects. Cohort 1 comprised 10 subjects with RBD (63.5 ± 9.4 years old) and 10 healthy volunteers (62.7 ± 8.6 years old) who underwent resting-state metabolic brain imaging with (18)F-fluorodeoxyglucose PET. Cohort 2 comprised 17 subjects with RBD (68.9 ± 4.8 years old) and 17 healthy volunteers (66.6 ± 6.0 years old) who underwent resting brain perfusion imaging with ethylcysteinate dimer SPECT. The latter group was followed clinically for 4.6 ± 2.5 years by investigators blinded to the imaging results. PDRP expression was measured in both RBD groups and compared with corresponding control values. PDRP expression was elevated in both groups of subjects with RBD (cohort 1: p abnormalities in subjects with idiopathic RBD are associated with a greater likelihood of subsequent phenoconversion to a progressive neurodegenerative syndrome.

Expression and Localization of TRK-Fused Gene Products in the Rat Brain and Retina

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Maebayashi, Hisae; Takeuchi, Shigako; Masuda, Chiaki; Makino, Satoshi; Fukui, Kenji; Kimura, Hiroshi; Tooyama, Ikuo

2012-01-01

The TRK-fused gene (TFG in human, Tfg in rat) was originally identified in human papillary thyroid cancer as a chimeric form of the NTRK1 gene. It has been reported that the gene product (TFG) plays a role in regulating phosphotyrosine-specific phosphatase-1 activity. However, no information regarding the localization of Tfg in rat tissues is available. In this study, we investigated the expression of Tfg mRNA in normal rat tissues using reverse transcription-polymerase chain reaction (RT-PCR). We also produced an antibody against Tfg gene products and examined the localization of TFG in the rat brain and retina. The RT-PCR experiments demonstrated that two types of Tfg mRNA were expressed in rat tissues: the conventional form of Tfg (cTfg) and a novel variant form, retinal Tfg (rTfg). RT-PCR analyses demonstrated that cTfg was ubiquitously expressed in rat tissues, while rTfg was predominantly expressed in the brain and retina. Western blot analysis demonstrated two bands with molecular weights of about 30 kDa and 50 kDa in the rat brain. Immunohistochemistry indicated that TFG proteins were predominantly expressed by neurons in the brain. In the rat retina, intense TFG-immunoreactivity was detected in the layer of rods and cones and the outer plexiform layer

Osmotic stress changes the expression and subcellular localization of the Batten disease protein CLN3.

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Amanda Getty

Full Text Available Juvenile CLN3 disease (formerly known as juvenile neuronal ceroid lipofuscinosis is a fatal childhood neurodegenerative disorder caused by mutations in the CLN3 gene. CLN3 encodes a putative lysosomal transmembrane protein with unknown function. Previous cell culture studies using CLN3-overexpressing vectors and/or anti-CLN3 antibodies with questionable specificity have also localized CLN3 in cellular structures other than lysosomes. Osmoregulation of the mouse Cln3 mRNA level in kidney cells was recently reported. To clarify the subcellular localization of the CLN3 protein and to investigate if human CLN3 expression and localization is affected by osmotic changes we generated a stably transfected BHK (baby hamster kidney cell line that expresses a moderate level of myc-tagged human CLN3 under the control of the human ubiquitin C promoter. Hyperosmolarity (800 mOsm, achieved by either NaCl/urea or sucrose, dramatically increased the mRNA and protein levels of CLN3 as determined by quantitative real-time PCR and Western blotting. Under isotonic conditions (300 mOsm, human CLN3 was found in a punctate vesicular pattern surrounding the nucleus with prominent Golgi and lysosomal localizations. CLN3-positive early endosomes, late endosomes and cholesterol/sphingolipid-enriched plasma membrane microdomain caveolae were also observed. Increasing the osmolarity of the culture medium to 800 mOsm extended CLN3 distribution away from the perinuclear region and enhanced the lysosomal localization of CLN3. Our results reveal that CLN3 has multiple subcellular localizations within the cell, which, together with its expression, prominently change following osmotic stress. These data suggest that CLN3 is involved in the response and adaptation to cellular stress.

Localization and Developmental Expression Patterns of CSPG in the RCS Rat Retina

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Li-Feng Chen

2011-05-01

Full Text Available Purpose: Investigate changes in chondroitin sulfate proteoglycan (CSPG distribution in Royal College of Surgeons (RCS rat retinae. Could CSPGs distribution act as a physical barrier to transplanted cell migration in degenerating retinae? Methods: CSPG expression was examined in RCS and Long-Evans rat retinae from birth to postnatal day 150 (PND150 using immunofluorescence and western-blots. Results: Both groups showed a rapid rise in CSPG expression on PND14, which peaked on PND21 before declining to lower levels by PND35. CSPG expression had risen again by PND90 and remained elevated for the duration of the study (PND150. However, from PND21, CSPG expression was significantly higher (p ≤ 0.05, n = 5 in Long-Evans rat retinae. CSPG-positive cells were localized in the ganglion cell layer (GCL and the photoreceptor outer segment debris zone (DZ; CSPG expression in the DZ was the main contributor to the higher expression in older animals for both groups. Conclusions: Increased expression of CSPGs in the DZ may act as a physical barrier following retinal cellular transplantation. CSPGs in the GCL is probably related to dendritic changes. CSPG accumulation in the older retinae suggests that aging influences the microenvironment in the retina, which may affect the efficacy of cell transplantation.

Genetic modification of neurons to express bevacizumab for local anti-angiogenesis treatment of glioblastoma.

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Hicks, Martin J; Funato, Kosuke; Wang, Lan; Aronowitz, Eric; Dyke, Jonathan P; Ballon, Douglas J; Havlicek, David F; Frenk, Esther Z; De, Bishnu P; Chiuchiolo, Maria J; Sondhi, Dolan; Hackett, Neil R; Kaminsky, Stephen M; Tabar, Viviane; Crystal, Ronald G

2015-01-01

The median survival of glioblastoma multiforme (GBM) is approximately 1 year. Following surgical removal, systemic therapies are limited by the blood-brain barrier. To circumvent this, we developed a method to modify neurons with the genetic sequence for therapeutic monoclonal antibodies using adeno-associated virus (AAV) gene transfer vectors, directing persistent, local expression in the tumor milieu. The human U87MG GBM cell line or patient-derived early passage GBM cells were administered to the striatum of NOD/SCID immunodeficient mice. AAVrh.10BevMab, an AAVrh.10-based vector coding for bevacizumab (Avastin), an anti-human vascular endothelial growth factor (VEGF) monoclonal antibody, was delivered to the area of the GBM xenograft. Localized expression of bevacizumab was demonstrated by quantitative PCR, ELISA and western blotting. Immunohistochemistry showed that bevacizumab was expressed in neurons. Concurrent administration of AAVrh.10BevMab with the U87MG tumor reduced tumor blood vessel density and tumor volume, and increased survival. Administration of AAVrh.10BevMab 1 week after U87MG xenograft reduced growth and increased survival. Studies with patient-derived early passage GBM primary cells showed a reduction in primary tumor burden with an increased survival. These data support the strategy of AAV-mediated central nervous system gene therapy to treat GBM, overcoming the blood-brain barrier through local, persistent delivery of an anti-angiogenesis monoclonal antibody.

Characterization of aquaporin 4 protein expression and localization in tissues of the dogfish (Squalus acanthias.

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Christopher P Cutler

2012-02-01

Full Text Available The role of aquaporin water channels in Elasmobanchs such as the dogfish Squalus acanthias is completely unknown. This investigation determines the expression and cellular and sub-cellular localization of AQP4 protein in dogfish tissues. Two polyclonal antibodies were generated (AQP4/1 and AQP4/2. Western blots using the AQP4/1 antibody showed two bands (35.5kDa and 49.5kDa in most tissues similar to mammals. Liver and rectal gland showed further bands. However, unlike in mammals, AQP4 protein was expressed in all tissues including respiratory tract and liver. The AQP4/2 antibody appeared much less specific in blots. Both antibodies were used in immunohistochemistry and showed similar cellular localizations, although the AQP4/2 antibody had a more restricted sub-cellular distribution compared to AQP4/1 and therefore appeared to be more specific. In kidney a sub-set of tubules were stained which may represent intermediate tubule segments. AQP4/1 and AQP4/2 antibodies localized to the same tubules segments in serial sections although the intensity and sub-cellular distribution were different. AQP4/2 showed a basal or basolateral membrane distribution whereas AQP4/1 was often distributed throughout the cell including the nucleus. In rectal gland and cardiac stomach AQP4 was localized to secretary tubules but again AQP/1 and AQP/2 showed different sub-cellular distributions. In gill, both antibodies stained large cells in the primary filament and secondary lamellae. Again AQP4/1 antibody stained most or all the cell including the nucleus, whereas AQP4/2 had a plasma membrane and sometimes cytoplasmic distribution. Two types of large mitochondria-rich cells are known to exist in elasmobranches, that express either Na,K ATPase or V-type ATPase. Using Na,K-ATPase and V-type ATPase antibodies, AQP4 was colocalized with these proteins using the AQP4/1 antibody. Results show AQP4 is expressed in both (and all branchial Na,K ATPase and V-type ATPase

Abnormal proliferation of CD4- CD8+ gammadelta+ T cells with chromosome 6 anomaly: role of Fas ligand expression in spontaneous regression of the cells.

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Ichikawa, N; Kitano, K; Ito, T; Nakazawa, T; Shimodaira, S; Ishida, F; Kiyosawa, K

1999-04-01

We report a case of granular lymphocyte proliferative disorder accompanied with hemolytic anemia and neutropenia. Phenotypes of the cells were T cell receptor gammadelta+ CD3+ CD4- CD8+ CD16+ CD56- CD57-. Southern blot analysis of T cell receptor beta and gamma chains demonstrated rearranged bands in both. Chromosomal analysis after IL-2 stimulation showed deletion of chromosome 6. Sorted gammadelta+ T cells showed an increase in Fas ligand expression compared with the levels in sorted alphabeta+ T cells. The expression of Fas ligand on these gammadelta+ T cells increased after IL-2 stimulation. The patient's anemia improved along with a decrease in granular lymphocyte count and disappearance of the abnormal karyotype without treatment. The expression of Fas ligand may be involved in spontaneous regression of granular lymphocyte proliferation with hemolytic anemia.

Localization and expression of clarin-1, the Clrn1 gene product, in auditory hair cells and photoreceptors

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Zallocchi, Marisa; Meehan, Daniel T.; Delimont, Duane; Askew, Charles; Garrige, Suneetha; Gratton, Michael Anne; Rothermund-Franklin, Christie A.; Cosgrove, Dominic

2009-01-01

The Usher syndrome 3A (CLRN1) gene encodes clarin-1, which is a member of the tetraspanin family of transmembrane proteins. Although identified more than 6 years ago, little is known about its localization or function in the eye and ear. We developed a polyclonal antibody that react with all clarin-1 isoforms and used it to characterize protein expression in cochlea and retina. In the cochlea, we observe clarin-1expression in the stereocilia of P0 mice, and in synaptic terminals present at the base of the auditory hair cells from E18 to P6. In the retina, clarin-1 localizes to the connecting cilia, inner segment of photoreceptors and to the ribbon synapses. RT-PCR from P0 cochlea and P28 retina show mRNAs encoding only isoforms 2 and 3. Western-blots show that only isoform 2 is present in protein extracts from these same tissues. We examined clarin-1 expression in the immortomouse-derived hair cell line UB/OC-1. Only isoform 2 is expressed in UB/OC-1 at both mRNA and protein levels, suggesting this isoform is biologically relevant to hair cell function. The protein co-localizes with microtubules and post-transgolgi vesicles. The sub-cellular localization of clarin-1 in hair cells and photoreceptors suggests it functions at both the basal and apical poles of neurosensoriepithelia. PMID:19539019

Methods for simultaneously identifying coherent local clusters with smooth global patterns in gene expression profiles

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Lee Yun-Shien

2008-03-01

Full Text Available Abstract Background The hierarchical clustering tree (HCT with a dendrogram 1 and the singular value decomposition (SVD with a dimension-reduced representative map 2 are popular methods for two-way sorting the gene-by-array matrix map employed in gene expression profiling. While HCT dendrograms tend to optimize local coherent clustering patterns, SVD leading eigenvectors usually identify better global grouping and transitional structures. Results This study proposes a flipping mechanism for a conventional agglomerative HCT using a rank-two ellipse (R2E, an improved SVD algorithm for sorting purpose seriation by Chen 3 as an external reference. While HCTs always produce permutations with good local behaviour, the rank-two ellipse seriation gives the best global grouping patterns and smooth transitional trends. The resulting algorithm automatically integrates the desirable properties of each method so that users have access to a clustering and visualization environment for gene expression profiles that preserves coherent local clusters and identifies global grouping trends. Conclusion We demonstrate, through four examples, that the proposed method not only possesses better numerical and statistical properties, it also provides more meaningful biomedical insights than other sorting algorithms. We suggest that sorted proximity matrices for genes and arrays, in addition to the gene-by-array expression matrix, can greatly aid in the search for comprehensive understanding of gene expression structures. Software for the proposed methods can be obtained at http://gap.stat.sinica.edu.tw/Software/GAP.

Clinical significance of abnormal nonosseous soft tissue uptake of bone tracer

International Nuclear Information System (INIS)

Zhu Bao; Shang Yukun; Li Jiannan; Bai Jing; Cai Liang

2006-01-01

Objective: To evaluate the clinical significance of abnormal soft tissue uptake of bone tracer. Methods: Thirty patients with abnormal soft tissue uptake of bone tracer on 99 Tc m -methylene diphosphonic acid (MDP) skeletal imaging were analyzed. Radioactivity of soft tissue accumulated equal to or greater than the ribs were considered as abnormal. The result was compared with pathology, MRI, CT, X-ray, ultrasound, findings for evaluating its clinical significance. Results: In 7 patients with diffuse liver uptake of 99 Tc m -MDP, 6 were massive and 1 nodular liver cancer. In 2 patients with local liver uptake, one was metastatic and the other primary liver cancer. In 5 local lung uptake cases 4 were primary lung cancer and one metastatic. In 5 cases with colonic uptake 1 was schistosomiasis while the other 4 unexplainable. Subcutaneous tissue uptake was observed in 4 patients, symmetrical uptake in 2 patients with metastatic calcification microfoci in multiple myeloma, unsymmetrical uptake in 2 patients with hemangioma and abscess. Pleural uptake in 3 patients all was metastatic cancer. Abdominal uptake in 3 patients was omentum, paravertebral soft tissue metastasis and unknown cause. Breast uptake in one patient was due to breast cancer. Conclusions: There are many causes resulting in abnormal nonosseous soft tissue uptake of 99 Tc m -MDP. The final diagnosis should correlate with clinical data and other examinations. (authors)

Local gene expression changes after UV-irradiation of human skin.

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Benjamin Weinkauf

Full Text Available UV-irradiation is a well-known translational pain model inducing local inflammation and primary hyperalgesia. The mediators and receptor proteins specifically contributing to mechanical or heat hyperalgesia are still unclear. Therefore, we irradiated buttock skin of humans (n = 16 with 5-fold MED of UV-C and assessed the time course of hyperalgesia and axon reflex erythema. In parallel, we took skin biopsies at 3, 6 and 24 h after UVC irradiation and assessed gene expression levels (RT-PCR of neurotrophins (e.g. NGF, BDNF, GDNF, ion channels (e.g. NaV1.7, TRPV1, inflammatory mediators (e.g. CCL-2, CCL-3 and enzymes (e.g. PGES, COX2. Hyperalgesia to mechanical impact (12 m/s and heat (48 °C stimuli was significant at 6 h (p<0.05 and p<0.01 and 24 h (p<0.005 and p<0.01 after irradiation. Axon reflex erythema upon mechanical and thermal stimuli was significantly increased 3 h after irradiation and particularly strong at 6 h. A significant modulation of 9 genes was found post UV-C irradiation, including NGF (3, 6, 24 h, TrkA (6, 24 h, artemin, bradykinin-1 receptor, COX-2, CCL-2 and CCL-3 (3 and 6 h each. A significant down-regulation was observed for TRPV1 and iNOS (6, 24 h. Individual one-to-one correlation analysis of hyperalgesia and gene expression revealed that changes of Nav1.7 (SCN9A mRNA levels at 6 and 24 h correlated to the intensity of mechanical hyperalgesia recorded at 24 h post UV-irradiation (Pearson r: 0.57, p<0.04 and r: 0.82, p<0.001. Expression of COX-2 and mPGES at 6 h correlated to the intensity of heat-induced erythema 24 h post UV (r: 0.57, p<0.05 for COX-2 and r: 0.83, p<0.001 for PGES. The individual correlation analyses of functional readouts (erythema and pain response with local expression changes provided evidence for a potential role of Nav1.7 in mechanical hyperalgesia.

Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

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Fernald, Charles D.

1980-01-01

Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

A mutation in Ccdc39 causes neonatal hydrocephalus with abnormal motile cilia development in mice.

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Abdelhamed, Zakia; Vuong, Shawn M; Hill, Lauren; Shula, Crystal; Timms, Andrew; Beier, David; Campbell, Kenneth; Mangano, Francesco T; Stottmann, Rolf W; Goto, June

2018-01-09

Pediatric hydrocephalus is characterized by an abnormal accumulation of cerebrospinal fluid (CSF) and is one of the most common congenital brain abnormalities. However, little is known about the molecular and cellular mechanisms regulating CSF flow in the developing brain. Through whole-genome sequencing analysis, we report that a homozygous splice site mutation in coiled-coil domain containing 39 ( Ccdc39 ) is responsible for early postnatal hydrocephalus in the progressive hydrocephal us ( prh ) mouse mutant. Ccdc39 is selectively expressed in embryonic choroid plexus and ependymal cells on the medial wall of the forebrain ventricle, and the protein is localized to the axoneme of motile cilia. The Ccdc39 prh/prh ependymal cells develop shorter cilia with disorganized microtubules lacking the axonemal inner arm dynein. Using high-speed video microscopy, we show that an orchestrated ependymal ciliary beating pattern controls unidirectional CSF flow on the ventricular surface, which generates bulk CSF flow in the developing brain. Collectively, our data provide the first evidence for involvement of Ccdc39 in hydrocephalus and suggest that the proper development of medial wall ependymal cilia is crucial for normal mouse brain development. © 2018. Published by The Company of Biologists Ltd.

Astrocyte-neuron crosstalk regulates the expression and subcellular localization of carbohydrate metabolism enzymes.

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Mamczur, Piotr; Borsuk, Borys; Paszko, Jadwiga; Sas, Zuzanna; Mozrzymas, Jerzy; Wiśniewski, Jacek R; Gizak, Agnieszka; Rakus, Dariusz

2015-02-01

Astrocytes releasing glucose- and/or glycogen-derived lactate and glutamine play a crucial role in shaping neuronal function and plasticity. Little is known, however, how metabolic functions of astrocytes, e.g., their ability to degrade glucosyl units, are affected by the presence of neurons. To address this issue we carried out experiments which demonstrated that co-culturing of rat hippocampal astrocytes with neurons significantly elevates the level of mRNA and protein for crucial enzymes of glycolysis (phosphofructokinase, aldolase, and pyruvate kinase), glycogen metabolism (glycogen synthase and glycogen phosphorylase), and glutamine synthetase in astrocytes. Simultaneously, the decrease of the capability of neurons to metabolize glucose and glutamine is observed. We provide evidence that neurons alter the expression of astrocytic enzymes by secretion of as yet unknown molecule(s) into the extracellular fluid. Moreover, our data demonstrate that almost all studied enzymes may localize in astrocytic nuclei and this localization is affected by the co-culturing with neurons which also reduces proliferative activity of astrocytes. Our results provide the first experimental evidence that the astrocyte-neuron crosstalk substantially affects the expression of basal metabolic enzymes in the both types of cells and influences their subcellular localization in astrocytes. © 2014 Wiley Periodicals, Inc.

How does structured sparsity work in abnormal event detection?

DEFF Research Database (Denmark)

Ren, Huamin; Pan, Hong; Olsen, Søren Ingvor

the training, which is the due to the fact that abnormal videos are limited or even unavailable in advance in most video surveillance applications. As a result, there could be only one label in the training data which hampers supervised learning; 2) Even though there are multiple types of normal behaviors, how...... many normal patterns lie in the whole surveillance data is still unknown. This is because there is huge amount of video surveillance data and only a small proportion is used in algorithm learning, consequently, the normal patterns in the training data could be incomplete. As a result, any sparse...... structure learned from the training data could have a high bias and ruin the precision of abnormal event detection. Therefore, we in the paper propose an algorithm to solve the abnormality detection problem by sparse representation, in which local structured sparsity is preserved in coefficients. To better...

Expression of nociceptive ligands in canine osteosarcoma.

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Shor, S; Fadl-Alla, B A; Pondenis, H C; Zhang, X; Wycislo, K L; Lezmi, S; Fan, T M

2015-01-01

Canine osteosarcoma (OS) is associated with localized pain as a result of tissue injury from tumor infiltration and peritumoral inflammation. Malignant bone pain is caused by stimulation of peripheral pain receptors, termed nociceptors, which reside in the localized tumor microenvironment, including the periosteal and intramedullary bone cavities. Several nociceptive ligands have been determined to participate directly or indirectly in generating bone pain associated with diverse skeletal abnormalities. Canine OS cells actively produce nociceptive ligands with the capacity to directly or indirectly activate peripheral pain receptors residing in the bone tumor microenvironment. Ten dogs with appendicular OS. Expression of nerve growth factor, endothelin-1, and microsomal prostaglandin E synthase-1 was characterized in OS cell lines and naturally occurring OS samples. In 10 dogs with OS, circulating concentrations of nociceptive ligands were quantified and correlated with subjective pain scores and tumor volume in patients treated with standardized palliative therapies. Canine OS cells express and secrete nerve growth factor, endothelin-1, and prostaglandin E2. Naturally occurring OS samples uniformly express nociceptive ligands. In a subset of OS-bearing dogs, circulating nociceptive ligand concentrations were detectable but failed to correlate with pain status. Localized foci of nerve terminal proliferation were identified in a minority of primary bone tumor samples. Canine OS cells express nociceptive ligands, potentially permitting active participation of OS cells in the generation of malignant bone pain. Specific inhibitors of nociceptive ligand signaling pathways might improve pain control in dogs with OS. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

Steroid hormone regulation of EMP2 expression and localization in the endometrium

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Williams Carmen J

2008-04-01

Full Text Available Abstract Background The tetraspan protein epithelial membrane protein-2 (EMP2, which mediates surface display of diverse proteins, is required for endometrial competence in blastocyst implantation, and is uniquely correlated with poor survival from endometrial adenocarcinoma tumors. Because EMP2 is differentially expressed in the various stages of the murine and human estrous cycle, we tested the hypothesis that the steroid hormones progesterone and estrogen influence EMP2 expression and localization. Methods Frozen human proliferative and secretory endometrium were collected and analyzed for EMP2 expression using SDS-PAGE/Western blot analysis. The response of EMP2 to progesterone and estradiol was determined using a combination of real-time PCR, SDS-PAGE/Western blot analysis, and confocal immunofluorescence in the human endometrial carcinoma cell line RL95-2. To confirm the in vitro results, ovariectomized mice were treated with progesterone or estradiol, and EMP2 expression was analyzed using immunohistochemistry. Results Within normal human endometrium, EMP2 expression is upregulated in the secretory phase relative to the proliferative phase. To understand the role of steroid hormones on EMP2 expression, we utilized RL95-2 cells, which express both estrogen and progesterone receptors. In RL95-2 cells, both estradiol and progesterone induced EMP2 mRNA expression, but only progesterone induced EMP2 protein expression. To compare steroid hormone regulation of EMP2 between humans and mice, we analyzed EMP2 expression in ovarectomized mice. Similar to results observed in humans, progesterone upregulated endometrial EMP2 expression and induced EMP2 translocation to the plasma membrane. Estradiol did not promote translocation to the cell surface, but moderately induced EMP2 expression in cytoplasmic compartments in vivo. Conclusion These findings suggest that targeting of EMP2 to specific locations under the influence of these steroid hormones may

Correlation of plasma nitrite/nitrate levels and inducible nitric oxide gene expression among women with cervical abnormalities and cancer.

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Sowjanya, A Pavani; Rao, Meera; Vedantham, Haripriya; Kalpana, Basany; Poli, Usha Rani; Marks, Morgan A; Sujatha, M

2016-01-30

Cervical cancer is caused by infection with high risk human papillomavirus (HR-HPV). Inducible nitric oxide synthase (iNOS), a soluble factor involved in chronic inflammation, may modulate cervical cancer risk among HPV infected women. The aim of the study was to measure and correlate plasma nitrite/nitrate levels with tissue specific expression of iNOS mRNA among women with different grades of cervical lesions and cervical cancer. Tissue biopsy and plasma specimens were collected from 120 women with cervical neoplasia or cancer (ASCUS, LSIL, HSIL and invasive cancer) and 35 women without cervical abnormalities. Inducible nitric oxide synthase (iNOS) mRNA from biopsy and plasma nitrite/nitrate levels of the same study subjects were measured. Single nucleotide polymorphism (SNP) analysis was performed on the promoter region and Ser608Leu (rs2297518) in exon 16 of the iNOS gene. Differences in iNOS gene expression and plasma nitrite/nitrate levels were compared across disease stage using linear and logistic regression analysis. Compared to normal controls, women diagnosed with HSIL or invasive cancer had a significantly higher concentration of plasma nitrite/nitrate and a higher median fold-change in iNOS mRNA gene expression. Genotyping of the promoter region showed three different variations: A pentanucleotide repeat (CCTTT) n, -1026T > G (rs2779249) and a novel variant -1153T > A. These variants were associated with increased levels of plasma nitrite/nitrate across all disease stages. The higher expression of iNOS mRNA and plasma nitrite/nitrate among women with pre-cancerous lesions suggests a role for nitric oxide in the natural history of cervical cancer. Copyright © 2015. Published by Elsevier Inc.

Local binary pattern variants-based adaptive texture features analysis for posed and nonposed facial expression recognition

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Sultana, Maryam; Bhatti, Naeem; Javed, Sajid; Jung, Soon Ki

2017-09-01

Facial expression recognition (FER) is an important task for various computer vision applications. The task becomes challenging when it requires the detection and encoding of macro- and micropatterns of facial expressions. We present a two-stage texture feature extraction framework based on the local binary pattern (LBP) variants and evaluate its significance in recognizing posed and nonposed facial expressions. We focus on the parametric limitations of the LBP variants and investigate their effects for optimal FER. The size of the local neighborhood is an important parameter of the LBP technique for its extraction in images. To make the LBP adaptive, we exploit the granulometric information of the facial images to find the local neighborhood size for the extraction of center-symmetric LBP (CS-LBP) features. Our two-stage texture representations consist of an LBP variant and the adaptive CS-LBP features. Among the presented two-stage texture feature extractions, the binarized statistical image features and adaptive CS-LBP features were found showing high FER rates. Evaluation of the adaptive texture features shows competitive and higher performance than the nonadaptive features and other state-of-the-art approaches, respectively.

The effect of local sustained delivery of sirolimus on the vascular PAI-1 and t-PA expression after angioplasty

International Nuclear Information System (INIS)

E Yajun; He Nengshu; Fan Hailun

2011-01-01

Objective: To investigate the effect of local sustained delivery of sirolimus on the vascular inhibitor of plasminogen activator-1 (PAI-1) and tissue type plasminogen activator (t-PA) expression after angioplasty. Methods: Experimental common carotid artery injury model was established in the rats. A total of 30 male Wistar rats were divided into experimental group (n=20) and control group (n=10). Adventitial administration of drug was applied. Pluronic F-127 gel containing sirolimus was administered to the exposed adventitial surface of injured carotid artery. The experimental group was divided into high concentration (600 μg/100 μl) sub-group and low concentration (300 μg/100μl) sub-group according to the concentration of sirolimus delivered. The effect of local sustained delivery sirolimus on vascular PAI-1 and t-PA expression after percutaneous angioplasty was evaluated by immunohistochemistry. Results: Compared to control group, 15 and 30 days after injury local sustained delivery of sirolimus in both high concentration and low concentration sub-groups the expression of the PAI-1 in neointima was significantly enhanced (P 0.05). At 15 and 30 days after injury, the expression of t-PA in neointima was decreased in both high and low concentration sub-groups (P<0.05), and the expression of t-PA in media was significantly decreased in high concentration sub-group (P<0.05) while on significant difference could be detected in low concentration sub-group. Conclusion: Local sustained delivery of sirolimus can induce the high expression of PAI-1 and low expression of t-PA in neointima although it inhibits the proliferation of neointima in the same time, and the imbalanced expression of t-PA and PAI-1 may probably play an important role in the late formation of thrombosis after the placement of drug-eluting stent. (authors)

Abnormal islet sphingolipid metabolism in type 1 diabetes.

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Holm, Laurits J; Krogvold, Lars; Hasselby, Jane P; Kaur, Simranjeet; Claessens, Laura A; Russell, Mark A; Mathews, Clayton E; Hanssen, Kristian F; Morgan, Noel G; Koeleman, Bobby P C; Roep, Bart O; Gerling, Ivan C; Pociot, Flemming; Dahl-Jørgensen, Knut; Buschard, Karsten

2018-04-18

Sphingolipids play important roles in beta cell physiology, by regulating proinsulin folding and insulin secretion and in controlling apoptosis, as studied in animal models and cell cultures. Here we investigate whether sphingolipid metabolism may contribute to the pathogenesis of human type 1 diabetes and whether increasing the levels of the sphingolipid sulfatide would prevent models of diabetes in NOD mice. We examined the amount and distribution of sulfatide in human pancreatic islets by immunohistochemistry, immunofluorescence and electron microscopy. Transcriptional analysis was used to evaluate expression of sphingolipid-related genes in isolated human islets. Genome-wide association studies (GWAS) and a T cell proliferation assay were used to identify type 1 diabetes related polymorphisms and test how these affect cellular islet autoimmunity. Finally, we treated NOD mice with fenofibrate, a known activator of sulfatide biosynthesis, to evaluate the effect on experimental autoimmune diabetes development. We found reduced amounts of sulfatide, 23% of the levels in control participants, in pancreatic islets of individuals with newly diagnosed type 1 diabetes, which were associated with reduced expression of enzymes involved in sphingolipid metabolism. Next, we discovered eight gene polymorphisms (ORMDL3, SPHK2, B4GALNT1, SLC1A5, GALC, PPARD, PPARG and B4GALT1) involved in sphingolipid metabolism that contribute to the genetic predisposition to type 1 diabetes. These gene polymorphisms correlated with the degree of cellular islet autoimmunity in a cohort of individuals with type 1 diabetes. Finally, using fenofibrate, which activates sulfatide biosynthesis, we completely prevented diabetes in NOD mice and even reversed the disease in half of otherwise diabetic animals. These results indicate that islet sphingolipid metabolism is abnormal in type 1 diabetes and suggest that modulation may represent a novel therapeutic approach. The RNA expression data is

Protein Kinases C-Mediated Regulations of Drug Transporter Activity, Localization and Expression

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Abdullah Mayati

2017-04-01

Full Text Available Drug transporters are now recognized as major actors in pharmacokinetics, involved notably in drug–drug interactions and drug adverse effects. Factors that govern their activity, localization and expression are therefore important to consider. In the present review, the implications of protein kinases C (PKCs in transporter regulations are summarized and discussed. Both solute carrier (SLC and ATP-binding cassette (ABC drug transporters can be regulated by PKCs-related signaling pathways. PKCs thus target activity, membrane localization and/or expression level of major influx and efflux drug transporters, in various normal and pathological types of cells and tissues, often in a PKC isoform-specific manner. PKCs are notably implicated in membrane insertion of bile acid transporters in liver and, in this way, are thought to contribute to cholestatic or choleretic effects of endogenous compounds or drugs. The exact clinical relevance of PKCs-related regulation of drug transporters in terms of drug resistance, pharmacokinetics, drug–drug interactions and drug toxicity remains however to be precisely determined. This issue is likely important to consider in the context of the development of new drugs targeting PKCs-mediated signaling pathways, for treating notably cancers, diabetes or psychiatric disorders.

Prognostic implications of the nuclear localization of Y-box-binding protein-1 and CXCR4 expression in ovarian cancer: their correlation with activated Akt, LRP/MVP and P-glycoprotein expression.

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Oda, Yoshinao; Ohishi, Yoshihiro; Basaki, Yuji; Kobayashi, Hiroaki; Hirakawa, Toshio; Wake, Norio; Ono, Mayumi; Nishio, Kazuto; Kuwano, Michihiko; Tsuneyoshi, Masazumi

2007-07-01

The nuclear localization of Y-box-binding protein-1 (YB-1) is known to be a poor prognostic factor in several human malignancies, including ovarian carcinoma. Following on from our basic study dealing with microarray analyses of YB-1-associated gene expression in ovarian cancer cells, we examined whether nuclear localization of YB-1 is associated with the expression of CXCR4, a vault protein named lung resistance-related vault protein (LRP/MVP), phosphorylated Akt (p-Akt) or P-glycoprotein (P-gp) in human ovarian carcinoma. Fifty-three surgically resected ovarian carcinomas treated with paclitaxel and carboplatin were examined immunohistochemically for nuclear YB-1 expression and intrinsic expression of p-Akt, P-gp, LRP/MVP and CXCR4. Nuclear expression of YB-1 demonstrated significant correlation with p-Akt, P-gp and LRP expression, but no relationship with CXCR4 expression. By multivariate analysis, only YB-1 nuclear expression and CXCR4 expression were independent prognostic factors with regard to overall survival. These results indicate that YB-1 nuclear expression and CXCR4 expression are important prognostic factors in ovarian carcinoma.

Effect of abnormal notochord delamination on hindgut development in the Adriamycin mouse model.

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Sato, Hideaki; Hajduk, Piotr; Furuta, Shigeyuki; Wakisaka, Munechika; Murphy, Paula; Puri, Prem; Kitagawa, Hiroaki

2013-11-01

Adriamycin mouse model (AMM) is a model of VACTERL anomalies. Sonic hedgehog (Shh) pathway, sourced by the notochord, is implicated of anorectal malformations. We hypothesized hindgut anomalies observed in the AMM are the result of abnormal effect of the notochord. Time-mated CBA/Ca mice received two intraperitoneal injections of Adriamycin (6 mg/kg) or saline as control on embryonic day (E) 7 and 8. Fetuses were harvested from E9 to E11, stained following whole mount in situ hybridization with labeled RNA probes to detect Shh and Fork head box F1(Foxf1) transcripts. Immunolocalization with endoderm marker Hnf3β was used to visualize morphology. Embryos were scanned by OPT to obtain 3D representations of expressions. In AMM, the notochord was abnormally displaced ventrally with attachment to the hindgut endoderm in 71 % of the specimens. In 32 % of the treated embryos abnormal hindgut ended blindly in a cystic structure, and both of types were remarked in 29 % of treated embryos. Endodermal Shh and mesenchymal Foxf1 genes expression were preserved around the hindgut cystic malformation. The delamination of the developing notochord in the AMM is disrupted, which may influence signaling mechanisms from the notochord to the hindgut resulting in abnormal patterning of the hindgut.

Neurological abnormalities in localized scleroderma of the face and head: a case series study for evaluation of imaging findings and clinical course.

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Lis-Święty, Anna; Brzezińska-Wcisło, Ligia; Arasiewicz, Hubert

2017-09-01

Localized scleroderma (LoS) of the face and head is often associated with neurological manifestations and/or imaging abnormalities in the central nervous system (CNS). We present an analysis of 20 cases of LoS affecting the face and head. The CNS symptoms and/or abnormalities in high-resolution computed tomography (HRCT) and/or magnetic resonance imaging (MRI) were observed in 12 patients (60%). In addition to the mild and unspecific disorders (e.g. headaches), serious neurological complications probably in the course of vasculitis were revealed: epilepsy (in two patients), epilepsy and pyramidal sings (in one patient). Neurological disorders and LoS occurred at the same time (in three patients) or at the course of the disease (nine patients) and no later than 29 years since the onset of the disease. No link between neurological disorders and the LoS clinical morphology, immunological and other laboratory parameters has been established. CNS involvement is not correlated with the clinical course of the facial and head LoS and may occur years after the disease initial symptomatology. Imaging follow-up is not required if there is not any emerging neurological symptom. In some cases, however, both HRCT and MRI are useful for monitoring disease evolution and addressing therapeutic choices.

Arginase Inhibition Ameliorates Hepatic Metabolic Abnormalities in Obese Mice

Science.gov (United States)

Moon, Jiyoung; Do, Hyun Ju; Cho, Yoonsu; Shin, Min-Jeong

2014-01-01

Objectives We examined whether arginase inhibition influences hepatic metabolic pathways and whole body adiposity in diet-induced obesity. Methods and Results After obesity induction by a high fat diet (HFD), mice were fed either the HFD or the HFD with an arginase inhibitor, Nω-hydroxy-nor-L-arginine (nor-NOHA). Nor-NOHA significantly prevented HFD-induced increases in body, liver, and visceral fat tissue weight, and ameliorated abnormal lipid profiles. Furthermore, nor-NOHA treatment reduced lipid accumulation in oleic acid-induced hepatic steatosis in vitro. Arginase inhibition increased hepatic nitric oxide (NO) in HFD-fed mice and HepG2 cells, and reversed the elevated mRNA expression of hepatic genes in lipid metabolism. Expression of phosphorylated 5′ AMPK-activated protein kinase α was increased by arginase inhibition in the mouse livers and HepG2 cells. Conclusions Arginase inhibition ameliorated obesity-induced hepatic lipid abnormalities and whole body adiposity, possibly as a result of increased hepatic NO production and subsequent activation of metabolic pathways involved in hepatic triglyceride metabolism and mitochondrial function. PMID:25057910

Effects of competition and life history stage on the expression of local adaptation in two native bunchgrasses

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Rice Kevin J.; Knapp Eric E.

2008-01-01

Concerns about the use of genetically appropriate material in restoration often focus on questions of local adaptation. Many reciprocal transplant studies have demonstrated local adaptation in native plant species, but very few have examined how interspecific competition affects the expression of adaptive variation. Our study examined...

microRNA-7 down-regulation mediates excessive collagen expression in localized scleroderma.

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Etoh, Mitsuhiko; Jinnin, Masatoshi; Makino, Katsunari; Yamane, Keitaro; Nakayama, Wakana; Aoi, Jun; Honda, Noritoshi; Kajihara, Ikko; Makino, Takamitsu; Fukushima, Satoshi; Ihn, Hironobu

2013-01-01

Localized scleroderma (LSc), a connective tissue disorder restricted to the skin and subcutaneous tissue, is characterized by skin fibrosis due to an excessive deposition of types I collagen. The mechanism of such fibrosis is still unknown, but epigenetics may play some roles in the excessive collagen expression. In the present study, we investigated the mechanism of fibrosis seen in LSc, focusing on microRNA (miRNA). miRNA expression was determined by PCR array, real-time PCR, and in situ hybridization. The function of miRNA was evaluated using specific inhibitor. Immunoblotting was performed to detect α2(I) collagen protein. PCR array analysis using tissue miRNA demonstrated miR-7 level was significantly decreased in LSc skin as well as keloid tissue compared to normal skin in vivo. In situ hybridization also showed miR-7 expression in dermal fibroblasts was decreased in LSc dermis. The transfection of specific inhibitor for miR-7 into cultured normal dermal fibroblasts resulted in the up-regulation of α2(I) collagen protein in vitro. Also, the serum levels of miR-7 were significantly decreased in LSc patients compared with healthy controls, but serum miR-29a levels not. Systemic or local down-regulation of miR-7 may contribute to the pathogenesis of LSc via the overexpression of α2(I) collagen, and serum miR-7 may be useful as a disease marker. Investigation of the regulatory mechanisms of LSc by miRNA may lead to new treatments by the transfection into the lesional skin of this disease.

Who Buys Oddly Shaped Food and Why? Impacts of Food Shape Abnormality and Organic Labeling on Purchase Intentions

DEFF Research Database (Denmark)

Loebnitz, Natascha; Schuitema, Geertje; Grunert, Klaus G

2015-01-01

influence consumers’ purchase intentions, but only if the food deviates extremely from the norm; no differences in purchase intentions emerge for moderately abnormal food. Awareness of food waste issues and proenvironmental self-identities also drive purchase intentions, such that participants with high...... experimentally. A representative sample of 964 Danish consumers indicated their purchase intentions for two fruits and two vegetables with varying levels of food shape abnormality (normal, moderately abnormal, and extremely abnormal) and organic labels (organic label, no label). Food shape abnormalities...... levels of these traits express significantly higher purchase intentions for abnormally shaped food. Thus, increasing awareness of food waste issues, particularly among those with strong proenvironmental self-identities, might encourage more consumers to purchase abnormally shaped fruits and vegetables....

Molecular and phenotypic abnormalities in individuals with germline heterozygous PTEN mutations and autism.

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Frazier, T W; Embacher, R; Tilot, A K; Koenig, K; Mester, J; Eng, C

2015-09-01

PTEN is a tumor suppressor associated with an inherited cancer syndrome and an important regulator of ongoing neural connectivity and plasticity. The present study examined molecular and phenotypic characteristics of individuals with germline heterozygous PTEN mutations and autism spectrum disorder (ASD) (PTEN-ASD), with the aim of identifying pathophysiologic markers that specifically associate with PTEN-ASD and that may serve as targets for future treatment trials. PTEN-ASD patients (n=17) were compared with idiopathic (non-PTEN) ASD patients with (macro-ASD, n=16) and without macrocephaly (normo-ASD, n=38) and healthy controls (n=14). Group differences were evaluated for PTEN pathway protein expression levels, global and regional structural brain volumes and cortical thickness measures, neurocognition and adaptive behavior. RNA expression patterns and brain characteristics of a murine model of Pten mislocalization were used to further evaluate abnormalities observed in human PTEN-ASD patients. PTEN-ASD had a high proportion of missense mutations and showed reduced PTEN protein levels. Compared with the other groups, prominent white-matter and cognitive abnormalities were specifically associated with PTEN-ASD patients, with strong reductions in processing speed and working memory. White-matter abnormalities mediated the relationship between PTEN protein reductions and reduced cognitive ability. The Pten(m3m4) murine model had differential expression of genes related to myelination and increased corpus callosum. Processing speed and working memory deficits and white-matter abnormalities may serve as useful features that signal clinicians that PTEN is etiologic and prompting referral to genetic professionals for gene testing, genetic counseling and cancer risk management; and could reveal treatment targets in trials of treatments for PTEN-ASD.

Esophageal abnormalities in juvenile localized scleroderma: is it associated with other extracutaneous manifestations?

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Clarissa C.M. Valões

Full Text Available Abstract Objective: To assess esophageal involvement (EI in juvenile localized scleroderma (JLS population and the possible association between this gastrointestinal manifestation and demographic data, clinical features, laboratory exams, treatments and outcomes. Methods: For a period of 30 years, 5881 patients with rheumatic diseases were followed in our Pediatric Rheumatology Division. EI was defined by the presence of symptoms (solid/liquid dysphagia, heartburn, esophageal regurgitation, nausea/vomiting and epigastralgia and confirmed by at least one EI exam abnormality: barium contrast radiography, upper gastrointestinal endoscopy and 24-hour esophageal pH-monitoring. Results: JLS was observed in 56/5881 patients (0.9%, mainly linear morphea subtype. EI was observed in 23/56(41% of JLS patients. Eight(35% of 23 EI patients with JLS were symptomatic and presented heartburn(5/8, solid and liquid dysphagia(3/8, nausea and epigastralgia(1/8. The frequency of any cumulative extracutaneous manifestations (calcinosis, arthritis/arthralgia, central nervous system, interstitial pneumonitis, mesangial nephritis and/or arrhythmia was significantly higher in JLS patients with EI compared to those without this complication (56% vs. 24%, p = 0.024. No differences were evidenced in demographic data, JLS subtypes and in each extracutaneous manifestation in both groups (p > 0.05. The frequency of methotrexate use was significantly higher in JLS patients with EI compared to those without (52% vs. 12%, p = 0.002. Autoantibody profile (antinuclear antibodies, anti-SCL-70, rheumatoid factor, anticentromere, anti-cardiolipin, anti-Ro/SSA and anti-La/SSB was similar in both groups (p > 0.05. Conclusions: Our study demonstrated that EI was frequently observed in JLS patients, mainly in asymptomatic patients with linear subtype. EI occurred in JLS patients with other extracutaneous manifestations and required methotrexate therapy.

Esophageal abnormalities in juvenile localized scleroderma: is it associated with other extracutaneous manifestations?

Science.gov (United States)

Valões, Clarissa C M; Novak, Glaucia V; Brunelli, Juliana B; Kozu, Katia T; Toma, Ricardo K; Silva, Clovis A

To assess esophageal involvement (EI) in juvenile localized scleroderma (JLS) population and the possible association between this gastrointestinal manifestation and demographic data, clinical features, laboratory exams, treatments and outcomes. For a period of 30 years, 5881 patients with rheumatic diseases were followed in our Pediatric Rheumatology Division. EI was defined by the presence of symptoms (solid/liquid dysphagia, heartburn, esophageal regurgitation, nausea/vomiting and epigastralgia) and confirmed by at least one EI exam abnormality: barium contrast radiography, upper gastrointestinal endoscopy and 24-hour esophageal pH-monitoring. JLS was observed in 56/5881 patients (0.9%), mainly linear morphea subtype. EI was observed in 23/56(41%) of JLS patients. Eight(35%) of 23 EI patients with JLS were symptomatic and presented heartburn(5/8), solid and liquid dysphagia(3/8), nausea and epigastralgia(1/8). The frequency of any cumulative extracutaneous manifestations (calcinosis, arthritis/arthralgia, central nervous system, interstitial pneumonitis, mesangial nephritis and/or arrhythmia) was significantly higher in JLS patients with EI compared to those without this complication (56% vs. 24%, p=0.024). No differences were evidenced in demographic data, JLS subtypes and in each extracutaneous manifestation in both groups (p>0.05). The frequency of methotrexate use was significantly higher in JLS patients with EI compared to those without (52% vs. 12%, p=0.002). Autoantibody profile (antinuclear antibodies, anti-SCL-70, rheumatoid factor, anticentromere, anti-cardiolipin, anti-Ro/SSA and anti-La/SSB) was similar in both groups (p>0.05). Our study demonstrated that EI was frequently observed in JLS patients, mainly in asymptomatic patients with linear subtype. EI occurred in JLS patients with other extracutaneous manifestations and required methotrexate therapy. Copyright © 2016. Published by Elsevier Editora Ltda.

Mastitis therapy and control - Automatic on-line detection of abnormal milk.

NARCIS (Netherlands)

Hogeveen, H.

2011-01-01

Automated online detection of mastitis and abnormal milk is an important subject in the dairy industry, especially because of the introduction of automatic milking systems and the growing farm sizes with consequently less labor available per cow. Demands for performance, which is expressed as

Characterization of Aquaporin 4 Protein Expression and Localization in Tissues of the Dogfish (Squalus acanthias).

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Cutler, Christopher P; Harmon, Sheena; Walsh, Jonathon; Burch, Kia

2012-01-01

The role of aquaporin water channels such as aquaporin 4 (Aqp4) in elasmobranchs such as the dogfish Squalus acanthias is completely unknown. This investigation set out to determine the expression and cellular and sub-cellular localization of Aqp4 protein in dogfish tissues. Two polyclonal antibodies were generated (AQP4/1 and AQP4/2) and these showed somewhat different characteristics in Western blotting and immunohistochemistry. Western blots using the AQP4/1 antibody showed two bands (35.5 and 49.5 kDa) in most tissues in a similar fashion to mammals. Liver had an additional band of 57 kDa and rectal gland two further faint bands of 37.5 and 38.5 kDa. However, unlike in mammals, Aqp4 protein was ubiquitously expressed in all tissues including gill and liver. The AQP4/2 antibody appeared much less specific in Western blots. Both antibodies were used in immunohistochemistry and showed similar cellular localizations, although the AQP4/2 antibody had a more restricted sub-cellular distribution compared to AQP4/1 and therefore appeared to be more specific for Aqp4. In kidney a sub-set of tubules were stained which may represent intermediate tubule segments (In-III-In-VI). AQP4/1 and AQP4/2 antibodies localized to the same tubules segments in serial sections although the intensity and sub-cellular distribution were different. AQP4/2 showed a basal or basolateral membrane distribution whereas AQP4/1 was often distributed throughout the whole cell including the nuclear region. In rectal gland and cardiac stomach Aqp4 was localized to secretory tubules but again AQP/1 and AQP/2 exhibited different sub-cellular distributions. In gill, both antibodies stained large cells in the primary filament and secondary lamellae. Again AQP4/1 antibody stained most or all the cell including the nucleus, whereas AQP4/2 had a plasma membrane or plasma membrane and cytoplasmic distribution. Two types of large mitochondrial rich transport cells are known to exist in elasmobranchs

Rab11 family expression in the human placenta: Localization at the maternal-fetal interface

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Artemiuk, Patrycja A.; Hanscom, Sara R.; Lindsay, Andrew J.; Wuebbolt, Danielle; Breathnach, Fionnuala M.; Tully, Elizabeth C.; Khan, Amir R.; McCaffrey, Mary W.

2017-01-01

Rab proteins are a family of small GTPases involved in a variety of cellular processes. The Rab11 subfamily in particular directs key steps of intracellular functions involving vesicle trafficking of the endosomal recycling pathway. This Rab subfamily works through a series of effector proteins including the Rab11-FIPs (Rab11 Family-Interacting Proteins). While the Rab11 subfamily has been well characterized at the cellular level, its function within human organ systems is still being explored. In an effort to further study these proteins, we conducted a preliminary investigation of a subgroup of endosomal Rab proteins in a range of human cell lines by Western blotting. The results from this analysis indicated that Rab11a, Rab11c(Rab25) and Rab14 were expressed in a wide range of cell lines, including the human placental trophoblastic BeWo cell line. These findings encouraged us to further analyse the localization of these Rabs and their common effector protein, the Rab Coupling Protein (RCP), by immunofluorescence microscopy and to extend this work to normal human placental tissue. The placenta is a highly active exchange interface, facilitating transfer between mother and fetus during pregnancy. As Rab11 proteins are closely involved in transcytosis we hypothesized that the placenta would be an interesting human tissue model system for Rab investigation. By immunofluorescence microscopy, Rab11a, Rab11c(Rab25), Rab14 as well as their common FIP effector RCP showed prominent expression in the placental cell lines. We also identified the expression of these proteins in human placental lysates by Western blot analysis. Further, via fluorescent immunohistochemistry, we noted abundant localization of these proteins within key functional areas of primary human placental tissues, namely the outer syncytial layer of placental villous tissue and the endothelia of fetal blood vessels. Overall these findings highlight the expression of the Rab11 family within the human

Expression Pattern and Localization Dynamics of Guanine Nucleotide Exchange Factor RIC8 during Mouse Oogenesis.

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Merly Saare

Full Text Available Targeting of G proteins to the cell cortex and their activation is one of the triggers of both asymmetric and symmetric cell division. Resistance to inhibitors of cholinesterase 8 (RIC8, a guanine nucleotide exchange factor, activates a certain subgroup of G protein α-subunits in a receptor independent manner. RIC8 controls the asymmetric cell division in Caenorhabditis elegans and Drosophila melanogaster, and symmetric cell division in cultured mammalian cells, where it regulates the mitotic spindle orientation. Although intensely studied in mitosis, the function of RIC8 in mammalian meiosis has remained unknown. Here we demonstrate that the expression and subcellular localization of RIC8 changes profoundly during mouse oogenesis. Immunofluorescence studies revealed that RIC8 expression is dependent on oocyte growth and cell cycle phase. During oocyte growth, RIC8 is abundantly present in cytoplasm of oocytes at primordial, primary and secondary preantral follicle stages. Later, upon oocyte maturation RIC8 also populates the germinal vesicle, its localization becomes cell cycle dependent, and it associates with chromatin and the meiotic spindle. After fertilization, RIC8 protein converges to the pronuclei and is also detectable at high levels in the nucleolus precursor bodies of both maternal and paternal pronucleus. During first cleavage of zygote RIC8 localizes in the mitotic spindle and cell cortex of forming blastomeres. In addition, we demonstrate that RIC8 co-localizes with its interaction partners Gαi1/2:GDP and LGN in meiotic/mitotic spindle, cell cortex and polar bodies of maturing oocytes and zygotes. Downregulation of Ric8 by siRNA leads to interferred translocation of Gαi1/2 to cortical region of maturing oocytes and reduction of its levels. RIC8 is also expressed at high level in female reproductive organs e.g. oviduct. Therefore we suggest a regulatory function for RIC8 in mammalian gametogenesis and fertility.

Sequencing Chromosomal Abnormalities Reveals Neurodevelopmental Loci that Confer Risk across Diagnostic Boundaries

DEFF Research Database (Denmark)

Talkowski, Michael E.; Rosenfeld, Jill A.; Blumenthal, Ian

2012-01-01

Sequencing of balanced chromosomal abnormalities, combined with convergent genomic studies of gene expression, copy-number variation, and genome-wide association, identifies 22 new loci that contribute to autism and related neurodevelopmental disorders. These data support a polygenic risk model...

Transient MRI abnormalities associated with partial status epilepticus: a case report

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Amato, Carmelo; Elia, Maurizio; Musumeci, Sebastiano A; Bisceglie, Pierluigi; Moschini, Massimo

2001-04-01

We report the case of an 18-year-old woman who presented a long-lasting cluster of partial seizures, and MRI cortical abnormalities localized in the left parietal lobe. The MRI changes correlated with the site of the epileptogenic focus, and disappeared within 2 weeks. The recognition of these reversible MRI abnormalities, which are presumably due to a temporary alteration of blood-brain barrier in the epileptogenic zone with subsequent edema, and are not associated with any underlying organic conditions, is extremely useful in the medical management of the patient and allows to avoid other invasive diagnostic procedures.

Transient MRI abnormalities associated with partial status epilepticus: a case report

International Nuclear Information System (INIS)

Amato, Carmelo; Elia, Maurizio; Musumeci, Sebastiano A.; Bisceglie, Pierluigi; Moschini, Massimo

2001-01-01

We report the case of an 18-year-old woman who presented a long-lasting cluster of partial seizures, and MRI cortical abnormalities localized in the left parietal lobe. The MRI changes correlated with the site of the epileptogenic focus, and disappeared within 2 weeks. The recognition of these reversible MRI abnormalities, which are presumably due to a temporary alteration of blood-brain barrier in the epileptogenic zone with subsequent edema, and are not associated with any underlying organic conditions, is extremely useful in the medical management of the patient and allows to avoid other invasive diagnostic procedures

Oral lichen planus may enhance the expression of Th17-associated cytokines in local lesions of chronic periodontitis.

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Wang, Hui; Han, Qi; Luo, Zhenhua; Xu, Caixia; Liu, Jiajia; Dan, Hongxia; Xu, Yi; Zeng, Xin; Chen, Qianming

2014-07-01

This study aims to compare the expression levels of interleukin (IL)-17 and IL-23 in local periodontal tissues from patients with both chronic periodontitis and oral lichen planus (CP-OLP), patients with chronic periodontitis (CP) only, patients with oral lichen planus (OLP) only, and healthy controls (HC). The periodontal tissues were collected from 15 CP-OLP patients, 15 CP patients, 15 OLP patients, and 10 healthy controls. Immunohistochemistry (IHC) and real-time quantitative PCR (qPCR) was performed to investigate the protein and mRNA expression level of IL-17 and IL-23 in periodontal lesions from these four groups. IHC statistical analysis showed that the expression level of IL-17- and IL-23p19-positive cells significantly increased in CP-OLP group compared with that in CP (P periodontal tissues from periodontitis patients with oral lichen planus, which might aggravate the inflammatory response in local lesions. Oral lichen planus and chronic periodontitis may have interaction in disease pathogenesis, while IL-17 detection in local lesions may be helpful in identifying the disease severity in periodontitis patients with oral lichen planus.

Lack of tryptophan hydroxylase-1 in mice results in gait abnormalities.

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Suidan, Georgette L; Duerschmied, Daniel; Dillon, Gregory M; Vanderhorst, Veronique; Hampton, Thomas G; Wong, Siu Ling; Voorhees, Jaymie R; Wagner, Denisa D

2013-01-01

The role of peripheral serotonin in nervous system development is poorly understood. Tryptophan hydroxylase-1 (TPH1) is expressed by non-neuronal cells including enterochromaffin cells of the gut, mast cells and the pineal gland and is the rate-limiting enzyme involved in the biosynthesis of peripheral serotonin. Serotonin released into circulation is taken up by platelets via the serotonin transporter and stored in dense granules. It has been previously reported that mouse embryos removed from Tph1-deficient mothers present abnormal nervous system morphology. The goal of this study was to assess whether Tph1-deficiency results in behavioral abnormalities. We did not find any differences between Tph1-deficient and wild-type mice in general motor behavior as tested by rotarod, grip-strength test, open field and beam walk. However, here we report that Tph1 (-/-) mice display altered gait dynamics and deficits in rearing behavior compared to wild-type (WT) suggesting that tryptophan hydroxylase-1 expression has an impact on the nervous system.

Gamma-tubulin-containing abnormal centrioles are induced by insufficient Plk4 in human HCT116 colorectal cancer cells.

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Kuriyama, Ryoko; Bettencourt-Dias, Monica; Hoffmann, Ingrid; Arnold, Marc; Sandvig, Lisa

2009-06-15

Cancer cells frequently induce aberrant centrosomes, which have been implicated in cancer initiation and progression. Human colorectal cancer cells, HCT116, contain aberrant centrioles composed of disorganized cylindrical microtubules and displaced appendages. These cells also express unique centrosome-related structures associated with a subset of centrosomal components, including gamma-tubulin, centrin and PCM1. During hydroxyurea treatment, these abnormal structures become more abundant and undergo a change in shape from small dots to elongated fibers. Although gamma-tubulin seems to exist as a ring complex, the abnormal structures do not support microtubule nucleation. Several lines of evidence suggest that the fibers correspond to a disorganized form of centriolar microtubules. Plk4, a mammalian homolog of ZYG-1 essential for initiation of centriole biogenesis, is not associated with the gamma-tubulin-specific abnormal centrosomes. The amount of Plk4 at each centrosome was less in cells with abnormal centrosomes than cells without gamma-tubulin-specific abnormal centrosomes. In addition, the formation of abnormal structures was abolished by expression of exogenous Plk4, but not SAS6 and Cep135/Bld10p, which are downstream regulators required for the organization of nine-triplet microtubules. These results suggest that HCT116 cells fail to organize the ninefold symmetry of centrioles due to insufficient Plk4.

Low Iodine in the Follicular Lumen Caused by Cytoplasm Mis-localization of Sodium Iodide Symporter may Induce Nodular Goiter.

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Huang, Huibin; Shi, Yaxiong; Liang, Bo; Cai, Huiyao; Cai, Qingyan

2017-10-01

Iodine is a key ingredient in the synthesis of thyroid hormones and also a major factor in the regulation of thyroid function. A local reduction of iodine content in follicular lumen leads to overexpression of local thyroid-stimulating hormone receptor (TSHr), which in turn excessively stimulates the regional thyroid tissue, and result in the formation of nodular goiter. In this study, we investigated the relationship between iodine content and sodium iodide symporter (NIS) expression by using the clinical specimens from patients with nodular goiter and explored the pathogenesis triggered by iodine deficiency in nodular goiter. In total, 28 patients were clinically histopathologically confirmed to have nodular goiter and the corresponding adjacent normal thyroid specimens were harvested simultaneously. Western blot and immunohistochemistry were performed to assay NIS expression and localization in thyrocytes of both nodular goiter and adjacent normal thyroid tissues. NIS expression mediated by iodine in follicular lumen was confirmed by follicular model in vitro. Meanwhile, radioscan with iodine-131were conducted on both nodular goiter and adjacent normal thyroid. Our data showed that NIS expression in nodular goiter was significantly higher than that in adjacent normal tissues, which was associated with low iodine in the follicular lumen. Abnormal localization of NIS and lower amount of radioactive iodine-131 were also found in nodular goiter. Our data implied that low iodine in the follicular lumen caused by cytoplasm mis-localization of NIS may induce nodular goiter.

SPINK1 Overexpression in Localized Prostate Cancer: a Rare Event Inversely Associated with ERG Expression and Exclusive of Homozygous PTEN Deletion.

Science.gov (United States)

Huang, Kuo-Cheng; Evans, Andrew; Donnelly, Bryan; Bismar, Tarek A

2017-04-01

SPINK1 is proposed as potential prognostic marker in prostate cancer (PCA). However, its relation to PTEN and ERG in localized PCA remains unclear. The study population consisted of two independent cohorts of men treated by radical prostatectomy for localized PCA (discovery n = 218 and validation n = 129). Patterns of association between SPINK1 and each of ERG and PTEN were evaluated by immunohistochemistry and fluorescence in situ hybridization. Associations between SPINK1 expression and various pathologic parameters and clinical outcome were also investigated. SPINK1 was expressed in 15.3 % and 10.9 % of cases in the discovery and validation cohort, respectively. SPINK expression was observed in 5.56 % of high-grade prostatic intraepithelial neoplasia and 1.1 % of adjacent morphologically benign prostatic glands. SPINK1 and ERG expression were almost exclusive, with only 1.0 % of the cases co-expressing both in the same core sample. SPINK1 interfocal and within-core heterogeneity was noted in 29.2 % and 64.6 % of cases, respectively. SPINK1 expression was not significantly associated with PTEN deletion in the two cohorts (p = 0.871 for discovery cohort and p = 0.293 for validation cohort). While SPINK1 expression did occur with hemizygous PTEN deletion, there was a complete absence of SPINK1 expression in PCA showing homozygous PTEN deletion, which was confirmed in the validation cohort (p = 0.02). Despite SPINK1's association with higher Gleason score (>7) (p = 0.02), it was not associated with other pathological parameters or biochemical recurrence post-radical prostatectomy. We documented absolute exclusivity between SPINK1 overexpression and homozygous PTEN deletion in localized PCA. SPINK1 and ERG expressions are exclusive events in PCA. SPINK1 is not of added prognostic value in localized PCA.

Carriers with functional null mutations in LAMA3 have localized enamel abnormalities due to haploinsufficiency

NARCIS (Netherlands)

Gostynska, Katarzyna B.; Yuen, Wing Yan; Pasmooij, Anna Maria Gerdina; Stellingsma, Cornelius; Pas, Hendri H.; Lemmink, Henny; Jonkman, Marcel F.

2017-01-01

The hereditary blistering disease junctional epidermolysis bullosa (JEB) is always accompanied by structural enamel abnormalities of primary and secondary dentition, characterized as amelogenesis imperfecta. Autosomal recessive mutations in LAMA3, LAMB3 and LAMC2 encoding the heterotrimer laminin

Interleukin 20 regulates dendritic cell migration and expression of co-stimulatory molecules

DEFF Research Database (Denmark)

Bech, Rikke; Jalilian, Babak; Agger, Ralf

2016-01-01

BACKGROUND: Psoriasis is an inflammatory disease characterized by leukocyte skin infiltration. Interestingly, recent works suggest that the migration of dendritic cells (DCs) is abnormal in psoriatic skin. DCs have significant role in regulating the function of T lymphocytes, at least in part...... influenced by the local environment of cytokines. In psoriatic skin lesions the expression of IL-20 is highly up-regulated. It is unclear if this cytokine has any influence on DCs. METHODS: Here, we investigated the influence of IL-20 in monocyte-derived dendritic cell (MDDCs) in vitro. This work addressed...

Latent and Abnormal Functional Connectivity Circuits in Autism Spectrum Disorder.

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Chen, Shuo; Xing, Yishi; Kang, Jian

2017-01-01

Autism spectrum disorder (ASD) is associated with disrupted brain networks. Neuroimaging techniques provide noninvasive methods of investigating abnormal connectivity patterns in ASD. In the present study, we compare functional connectivity networks in people with ASD with those in typical controls, using neuroimaging data from the Autism Brain Imaging Data Exchange (ABIDE) project. Specifically, we focus on the characteristics of intrinsic functional connectivity based on data collected by resting-state functional magnetic resonance imaging (rs-fMRI). Our aim was to identify disrupted brain connectivity patterns across all networks, instead of in individual edges, by using advanced statistical methods. Unlike many brain connectome studies, in which networks are prespecified before the edge connectivity in each network is compared between clinical groups, we detected the latent differentially expressed networks automatically. Our network-level analysis identified abnormal connectome networks that (i) included a high proportion of edges that were differentially expressed between people with ASD and typical controls; and (ii) showed highly-organized graph topology. These findings provide new insight into the study of the underlying neuropsychiatric mechanism of ASD.

Canine placental prostaglandin E2 synthase: expression, localization, and biological functions in providing substrates for prepartum PGF2alpha synthesis.

Science.gov (United States)

Gram, Aykut; Fox, Barbara; Büchler, Urs; Boos, Alois; Hoffmann, Bernd; Kowalewski, Mariusz P

2014-12-01

The prepartum output of PGF2alpha in the bitch is associated with increased placental PGE2-synthase (PTGES) mRNA levels. Contrasting with this is a decreased expression of PGF2alpha-synthase (PGFS/AKR1C3) in uteroplacental compartments during prepartum luteolysis, suggesting an involvement of alternative synthetic pathways in PGF2alpha synthesis, for example, conversion of PGE2 to PGF2alpha. However, because the expression and possible functions of the respective PTGES proteins remained unknown, no further conclusion could be drawn. Therefore, a canine-specific PTGES antibody was generated and used to investigate the expression, cellular localization, and biochemical activities of canine uteroplacental PTGES throughout pregnancy and at prepartum luteolysis. Additionally, the biochemical activities of these tissues involved in the conversion of PGE2 to PGF2alpha were investigated. The endometrial PTGES was localized in the uterine surface epithelium at preimplantation and in superficial and deep uterine glands, endothelial cells, and myometrium throughout pregnancy and at parturition. Placental signals were mostly in the trophoblast. The biochemical properties of recombinant PTGES protein were confirmed. Additionally, expression of two PGE2-receptors, PTGER2/EP2 and PTGER4/EP4, revealed their decreasing expression during luteolysis. In contrast, the uteroplacental expression of prostaglandin transporter (PGT) was strongly elevated prior to parturition. These localization patterns resembled that of PTGES. The increased expression of PTGES and PGT at parturition, together with the accompanying decreased levels of PGE2-receptors and the capability of canine uterine and placental homogenates to take part in the conversion of PGE2 to PGF2alpha, as found in this study, suggest that PGE2 could be used locally as a substrate for prepartum PGF2alpha synthesis in the dog. © 2014 by the Society for the Study of Reproduction, Inc.

Basic abnormalities in visual processing affect face processing at an early age in autism spectrum disorder.

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Vlamings, Petra Hendrika Johanna Maria; Jonkman, Lisa Marthe; van Daalen, Emma; van der Gaag, Rutger Jan; Kemner, Chantal

2010-12-15

A detailed visual processing style has been noted in autism spectrum disorder (ASD); this contributes to problems in face processing and has been directly related to abnormal processing of spatial frequencies (SFs). Little is known about the early development of face processing in ASD and the relation with abnormal SF processing. We investigated whether young ASD children show abnormalities in low spatial frequency (LSF, global) and high spatial frequency (HSF, detailed) processing and explored whether these are crucially involved in the early development of face processing. Three- to 4-year-old children with ASD (n = 22) were compared with developmentally delayed children without ASD (n = 17). Spatial frequency processing was studied by recording visual evoked potentials from visual brain areas while children passively viewed gratings (HSF/LSF). In addition, children watched face stimuli with different expressions, filtered to include only HSF or LSF. Enhanced activity in visual brain areas was found in response to HSF versus LSF information in children with ASD, in contrast to control subjects. Furthermore, facial-expression processing was also primarily driven by detail in ASD. Enhanced visual processing of detailed (HSF) information is present early in ASD and occurs for neutral (gratings), as well as for socially relevant stimuli (facial expressions). These data indicate that there is a general abnormality in visual SF processing in early ASD and are in agreement with suggestions that a fast LSF subcortical face processing route might be affected in ASD. This could suggest that abnormal visual processing is causative in the development of social problems in ASD. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Abnormal uterine bleeding

Science.gov (United States)

Anovulatory bleeding; Abnormal uterine bleeding - hormonal; Polymenorrhea - dysfunctional uterine bleeding ... ACOG committee opinion no. 557: Management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women. Reaffirmed 2015. www. ...

The Objective Identification and Quantification of Interstitial Lung Abnormalities in Smokers.

Science.gov (United States)

Ash, Samuel Y; Harmouche, Rola; Ross, James C; Diaz, Alejandro A; Hunninghake, Gary M; Putman, Rachel K; Onieva, Jorge; Martinez, Fernando J; Choi, Augustine M; Lynch, David A; Hatabu, Hiroto; Rosas, Ivan O; Estepar, Raul San Jose; Washko, George R

2017-08-01

Previous investigation suggests that visually detected interstitial changes in the lung parenchyma of smokers are highly clinically relevant and predict outcomes, including death. Visual subjective analysis to detect these changes is time-consuming, insensitive to subtle changes, and requires training to enhance reproducibility. Objective detection of such changes could provide a method of disease identification without these limitations. The goal of this study was to develop and test a fully automated image processing tool to objectively identify radiographic features associated with interstitial abnormalities in the computed tomography scans of a large cohort of smokers. An automated tool that uses local histogram analysis combined with distance from the pleural surface was used to detect radiographic features consistent with interstitial lung abnormalities in computed tomography scans from 2257 individuals from the Genetic Epidemiology of COPD study, a longitudinal observational study of smokers. The sensitivity and specificity of this tool was determined based on its ability to detect the visually identified presence of these abnormalities. The tool had a sensitivity of 87.8% and a specificity of 57.5% for the detection of interstitial lung abnormalities, with a c-statistic of 0.82, and was 100% sensitive and 56.7% specific for the detection of the visual subtype of interstitial abnormalities called fibrotic parenchymal abnormalities, with a c-statistic of 0.89. In smokers, a fully automated image processing tool is able to identify those individuals who have interstitial lung abnormalities with moderate sensitivity and specificity. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Expression of β-catenin protein in hepatocellular carcinoma and its relationship with alpha-fetoprotein.

Science.gov (United States)

Ren, Ya-Jun; Huang, Tao; Yu, Hong-Lu; Zhang, Li; He, Qian-Jin; Xiong, Zhi-Fan; Peng, Hua

2016-12-01

This study aimed to investigate the expression of β-catenin in hepatocellular carcinoma (HCC) tissues and its relationship with α-fetoprotein (AFP) in HCC. Immunohistochemistry was used to determine the expression of β-catenin in normal liver tissues (n=10), liver cirrhosis tissues (n=20), and primary HCC tissues (n=60). The relationship between β-catenin expression and clinical parameters of HCC was investigated. Real-time PCR and Western blotting were used to detect the mRNA and protein expression levels of β-catenin in the liver cancer cell line SMMC-7721 transfected with a plasmid encoding AFP, and also the mRNA and protein expression levels of β-catenin were measured in the liver cancer cell line Huh7 before and after the transfection with AFP shRNA plasmids. The results showed that β-catenin was only expressed on the cell membrane in normal liver tissues. Its localization to the cytoplasm and nucleus of cells was observed in a small proportion of cirrhotic tissues or adjacent HCC tissues, and such ectopic expression of β-catenin was predominant in HCC tissues. The abnormal expression of β-catenin was correlated with serum AFP levels, cancer cell differentiation and vascular invasion (P<0.05). Additionally, the increased expression of AFP resulted in the upregulation of β-catenin mRNA and protein levels, while knockdown of AFP with AFP shRNA led to significantly decreased β-catenin mRNA and protein levels (P<0.05). It was suggested that the abnormal expression of β-catenin is implicated in hepatic carcinogenesis and development. AFP can lead to increased expression of β-catenin, which may account for the poor prognosis of AFP-associated HCC patients.

Urine - abnormal color

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... medlineplus.gov/ency/article/003139.htm Urine - abnormal color To use the sharing features on this page, please enable JavaScript. The usual color of urine is straw-yellow. Abnormally colored urine ...

Tooth - abnormal colors

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... medlineplus.gov/ency/article/003065.htm Tooth - abnormal colors To use the sharing features on this page, please enable JavaScript. Abnormal tooth color is any color other than white to yellowish- ...

Dysglycemia induces abnormal circadian blood pressure variability

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Kumarasamy Sivarajan

2011-11-01

Full Text Available Abstract Background Prediabetes (PreDM in asymptomatic adults is associated with abnormal circadian blood pressure variability (abnormal CBPV. Hypothesis Systemic inflammation and glycemia influence circadian blood pressure variability. Methods Dahl salt-sensitive (S rats (n = 19 after weaning were fed either an American (AD or a standard (SD diet. The AD (high-glycemic-index, high-fat simulated customary human diet, provided daily overabundant calories which over time lead to body weight gain. The SD (low-glycemic-index, low-fat mirrored desirable balanced human diet for maintaining body weight. Body weight and serum concentrations for fasting glucose (FG, adipokines (leptin and adiponectin, and proinflammatory cytokines [monocyte chemoattractant protein-1 (MCP-1 and tumor necrosis factor-α (TNF-α] were measured. Rats were surgically implanted with C40 transmitters and blood pressure (BP-both systolic; SBP and diastolic; DBP and heart rate (HR were recorded by telemetry every 5 minutes during both sleep (day and active (night periods. Pulse pressure (PP was calculated (PP = SBP-DBP. Results [mean(SEM]: The AD fed group displayed significant increase in body weight (after 90 days; p Conclusion These data validate our stated hypothesis that systemic inflammation and glycemia influence circadian blood pressure variability. This study, for the first time, demonstrates a cause and effect relationship between caloric excess, enhanced systemic inflammation, dysglycemia, loss of blood pressure control and abnormal CBPV. Our results provide the fundamental basis for examining the relationship between dysglycemia and perturbation of the underlying mechanisms (adipose tissue dysfunction induced local and systemic inflammation, insulin resistance and alteration of adipose tissue precursors for the renin-aldosterone-angiotensin system which generate abnormal CBPV.

Localized scleroderma: imaging features

International Nuclear Information System (INIS)

Liu, P.; Uziel, Y.; Chuang, S.; Silverman, E.; Krafchik, B.; Laxer, R.

1994-01-01

Localized scleroderma is distinct from the diffuse form of scleroderma and does not show Raynaud's phenomenon and visceral involvement. The imaging features in 23 patients ranging from 2 to 17 years of age (mean 11.1 years) were reviewed. Leg length discrepancy and muscle atrophy were the most common findings (five patients), with two patients also showing modelling deformity of the fibula. One patient with lower extremity involvement showed abnormal bone marrow signals on MR. Disabling joint contracture requiring orthopedic intervention was noted in one patient. In two patients with ''en coup de sabre'' facial deformity, CT and MR scans revealed intracranial calcifications and white matter abnormality in the ipsilateral frontal lobes, with one also showing migrational abnormality. In a third patient, CT revealed white matter abnormality in the ipsilateral parietal lobe. In one patient with progressive facial hemiatrophy, CT and MR scans showed the underlying hypoplastic left maxillary antrum and cheek. Imaging studies of areas of clinical concern revealed positive findings in half our patients. (orig.)

Pneumothorax detection in chest radiographs using local and global texture signatures

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Geva, Ofer; Zimmerman-Moreno, Gali; Lieberman, Sivan; Konen, Eli; Greenspan, Hayit

2015-03-01

A novel framework for automatic detection of pneumothorax abnormality in chest radiographs is presented. The suggested method is based on a texture analysis approach combined with supervised learning techniques. The proposed framework consists of two main steps: at first, a texture analysis process is performed for detection of local abnormalities. Labeled image patches are extracted in the texture analysis procedure following which local analysis values are incorporated into a novel global image representation. The global representation is used for training and detection of the abnormality at the image level. The presented global representation is designed based on the distinctive shape of the lung, taking into account the characteristics of typical pneumothorax abnormalities. A supervised learning process was performed on both the local and global data, leading to trained detection system. The system was tested on a dataset of 108 upright chest radiographs. Several state of the art texture feature sets were experimented with (Local Binary Patterns, Maximum Response filters). The optimal configuration yielded sensitivity of 81% with specificity of 87%. The results of the evaluation are promising, establishing the current framework as a basis for additional improvements and extensions.

Systemic distribution, subcellular localization and differential expression of sphingosine-1-phosphate receptors in benign and malignant human tissues.

Science.gov (United States)

Wang, Chunyi; Mao, Jinghe; Redfield, Samantha; Mo, Yinyuan; Lage, Janice M; Zhou, Xinchun

2014-10-01

Five sphingosine-1-phosphate receptors (S1PR): S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5 (S1PR1-5) have been shown to be involved in the proliferation and progression of various cancers. However, none of the S1PRs have been systemically investigated. In this study, we performed immunohistochemistry (IHC) for S1PR1-S1PR5 on different tissues, in order to simultaneously determine the systemic distribution, subcellular localization and expression level of all five S1PRs. We constructed tissue microarrays (TMAs) from 384 formalin-fixed paraffin-embedded (FFPE) blocks containing 183 benign and 201 malignant tissues from 34 human organs/systems. Then we performed IHC for all five S1PRs simultaneously on these TMA slides. The distribution, subcellular localization and expression of each S1PR were determined for each tissue. The data in benign and malignant tissues from the same organ/tissue were then compared using the Student's t-test. In order to reconfirm the subcellular localization of each S1PR as determined by IHC, immunocytochemistry (ICC) was performed on several malignant cell lines. We found that all five S1PRs are widely distributed in multiple human organs/systems. All S1PRs are expressed in both the cytoplasm and nucleus, except S1PR3, whose IHC signals are only seen in the nucleus. Interestingly, the S1PRs are rarely expressed on cellular membranes. Each S1PR is unique in its organ distribution, subcellular localization and expression level in benign and malignant tissues. Among the five S1PRs, S1PR5 has the highest expression level (in either the nucleus or cytoplasm), with S1PR1, 3, 2 and 4 following in descending order. Strong nuclear expression was seen for S1PR1, S1PR3 and S1PR5, whereas S1PR2 and S1PR4 show only weak staining. Four organs/tissues (adrenal gland, liver, brain and colon) show significant differences in IHC scores for the multiple S1PRs (nuclear and/or cytoplasmic), nine (stomach, lymphoid tissues, lung, ovary, cervix, pancreas, skin, soft

Plant abnormality inspection device

International Nuclear Information System (INIS)

Takenaka, Toshio.

1990-01-01

The present invention concerns a plant abnormality inspection device for conducting remote or automatic patrolling inspection in a plant and, more particularly, relates to such a device as capable of detecting abnormal odors. That is, the device comprises a moving device for moving to a predetermined position in the plant, a plurality of gas sensors for different kind of gases to be inspected mounted thereon, a comparator for comparing the concentration of a gas detected by the gas sensor with the normal gas concentration at the predetermined position and a judging means for judging the absence or presence of abnormality depending on the combination of the result of the comparison and deliverying a signal if the state is abnormal. As a result, a slight amount of gas responsible to odors released upon abnormality of the plant can be detected by a plurality of gas sensors for different kinds gases to rapidly and easily find abnormal portions in the plant. (I.S.)

Radioguided occult lesion localization versus wire-guided localization for non-palpable breast lesions: randomized controlled trial

International Nuclear Information System (INIS)

Ocal, Koray; Dag, Ahmet; Turkmenoglu, Ozgur; Yucel, Erdem; Gunay, Emel Ceylan; Duce, Meltem Nass

2011-01-01

Aim: this prospective randomized clinical study was conducted to compare radioguided occult lesion localization (ROLL) with wire-guided localization to evaluate optimum localization techniques for non-palpable breast lesions. Methods: a total of 108 patients who were undergoing an excisional biopsy for non-palpable breast lesions requiring pathologic diagnosis were randomly assigned to the ROLL group (n 56) and wire-guided localization group (n 52). In the study, patients' characteristics, radiological abnormalities, radiological technique of localization, localization time, operation time, weight of the excised specimen, clearance margins, pathological diagnosis and perioperative complications were assessed. Results: there were no differences between the two groups in terms of age, radiological abnormalities and localization technique (p = non-significant for all). ROLL techniques resulted in 100% retrieval of the lesions; for the wire-guided localization technique, 98%. Both localization time and operation time were significantly reduced with the ROLL technique (p = significant for all). The weight of the specimen was significantly lower in the ROLL group than in the wire-guided localization group (p = significant). The overall complication rate and pathological diagnosis were similar for both groups (p = non-significant for all). Clear margins were achieved in 91% of ROLL patients and in 53% of wire-guided localization patients, and the difference was significant. Conclusions: the present study indicated that the ROLL technique is as effective as wire-guided localization for the excision of non-palpable breast lesions. In addition, ROLL improved the outcomes by reducing localization and operation time, preventing healthy tissue excision and achieving clearer margins. (author)

Radioguided occult lesion localization versus wire-guided localization for non-palpable breast lesions: randomized controlled trial

Energy Technology Data Exchange (ETDEWEB)

Ocal, Koray; Dag, Ahmet; Turkmenoglu, Ozgur; Yucel, Erdem [Mersin University (Turkey). Medical Faculty. Dept. of General Surgery; Gunay, Emel Ceylan [Mersin University (Turkey). Medical Faculty. Dept. of Nuclear Medicine; Duce, Meltem Nass [Mersin University (Turkey). Medical Faculty. Dept. of Radiology

2011-07-01

Aim: this prospective randomized clinical study was conducted to compare radioguided occult lesion localization (ROLL) with wire-guided localization to evaluate optimum localization techniques for non-palpable breast lesions. Methods: a total of 108 patients who were undergoing an excisional biopsy for non-palpable breast lesions requiring pathologic diagnosis were randomly assigned to the ROLL group (n 56) and wire-guided localization group (n 52). In the study, patients' characteristics, radiological abnormalities, radiological technique of localization, localization time, operation time, weight of the excised specimen, clearance margins, pathological diagnosis and perioperative complications were assessed. Results: there were no differences between the two groups in terms of age, radiological abnormalities and localization technique (p = non-significant for all). ROLL techniques resulted in 100% retrieval of the lesions; for the wire-guided localization technique, 98%. Both localization time and operation time were significantly reduced with the ROLL technique (p = significant for all). The weight of the specimen was significantly lower in the ROLL group than in the wire-guided localization group (p = significant). The overall complication rate and pathological diagnosis were similar for both groups (p = non-significant for all). Clear margins were achieved in 91% of ROLL patients and in 53% of wire-guided localization patients, and the difference was significant. Conclusions: the present study indicated that the ROLL technique is as effective as wire-guided localization for the excision of non-palpable breast lesions. In addition, ROLL improved the outcomes by reducing localization and operation time, preventing healthy tissue excision and achieving clearer margins. (author)

STUDY OF POSTURAL ABNORMALITIES OF MALE STUDENTS OF SAHAND UNIVERSITY OF TECHNOLOGY

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Hefzollesan Mehrdad

2013-04-01

Full Text Available The present study has been accomplished in order to examine the prevalence of postural abnormalities of male students. The statistical community was the whole male students in the university. From this community 300 students within the ages range of 18 - 22 were selected randomly as the investigation subjects. Data were obtained by a questionnaire, podoscope, a digital camera (taking photos of the subjects from Anterior, Posterior and lateral views and the software for corrective exercises provided by Iran ministry of education. After that the investigation was finished the abundance percentage was used to express the postural abnormalities percentage of the research subjects. The results show that cervical lordosis and flat foot are the most prevalent abnormalities with18.66 and 17.66 percent respectively, and torticollis and knee hyperextension have less prevalence in investigation subjects. The results show that among all of the participants in the investigation, 140 students (46.66 % have no abnormalities, 160 students (53.34 % have at least one, and 70 students (23.33 % have more than one. From this study it is obvious that the prevalence of the postural abnormalities among the statistical subjects is high. Therefore the need to a serious program concerning the abnormalities, especially ordering corrective exercises and also preparing the way for students to have physical activities seems to be inevitable.

Expression and localization of Smad4 protein in mouse testis after whole-body X-ray irradiation

International Nuclear Information System (INIS)

Zhu Huaping; Zhang Yuanqiang; Zhao Jie; Zhao Yong; Ma Jing; Hou Wugang; Qi Yuhong

2005-01-01

The work is to determine whether and where Transforming growth factor-betas downstream Signaling molecule Smad4 is expressed in the testes after whole-body X-ray irradiation and shed light on the mechanisms of Transforming growth factor-betas/Smad signal pathway mediates cell fate decisions following X-ray exposure. Five groups of adult BALB/c mice, with ten mice in each group, received whole-body of X-ray at dose levels of 0.1 Gy, 0.5 Gy, 1.0 Gy, 1.5 Gy and 2.0 Gy. They were sacrificed at 16 hour, 1 week, 2 weeks, 3 weeks and 4 weeks after the irradiation. Cellular localization and expression changes were examined by immunohistochemical ABC method. Quantitative analysis of the immunostaining was made by an image analysis system. In the seminiferous tubules, the expression of Smad4 was modulated by irradiation. The immunostaining showed that 16 hour post-irradiation, there was a significant decline in the Leydig cell, and it was dose and time depended. In addition, the immunolocalization showed that Smad4 was not exclusively localized in the cytoplasm of Leydig cells, but also localized in various Stages of spermatogenesis after the exposure, especially in premeiotic spermatogonia and primary spermatocytes. There was just a little expression in the 2.0 Gy group 16 h after the irradiation and the 1.0 Gy and 1.5 Gy groups at 2 weeks after the irradiation. Therefore in the 0.1 Gy to 2.0 Gy groups at 3 weeks after the irradiation, the immunostaining positive cells were significantly increased in spermatogonia and primary spermatocytes. There was no significant change in sertoli cells with different doses and different times after the exposure. The different expression patterns and change by dose and time of Smad4, suggest that TGF-β/Smad signal pathway may affect aspect after X-ray impairment and Smad4 may play an important role during these periods. (authors)

Cranial and dental abnormalities of the endangered red wolf Canis rufus

Science.gov (United States)

Federoff, Nicholas E.; Nowak, Ronald M.

1998-01-01

Three skulls of captive-raised female endangered red wolves (Canis rufus) exhibited severe malocclusion of the jaws. Cranial and dental abnormalities (including crowding of upper toothrows, and an extra tooth behind the lower left M3 in one of the three mandibles) were also evident. Ratios of alveolar length of maxillary toothrow to maximum width across the outer sides of crowns of P4 were significantly different (p=0.008) compared to unaffected skulls. Significant differences were also evident when ratios of maximum width across inner edges of alveoli of P1 to alveolar length of maxillary toothrow and maximum width across outer sides of crowns of P4 were compared between the two groups. Although the three skulls all exhibited malocclusion, the abnormality expressed itself differently in relation to the effects to each skull. Captive inbreeding may increase the probability and frequency of expressing these anomalies, although inbreeding coefficients calculated for the wolves expressing malocclusion were not considered high (0.0313-0.0508). A wild female red wolf specimen captured in 1921 in Arkansas also exhibited the malocclusion, although not as severely as in the captive females. This demonstrates that this trait was present in wild populations prior to, and not a result of, the captive breeding program.

Abnormal levels of expression of plasma microRNA-33 in patients with psoriasis.

Science.gov (United States)

García-Rodríguez, S; Arias-Santiago, S; Orgaz-Molina, J; Magro-Checa, C; Valenzuela, I; Navarro, P; Naranjo-Sintes, R; Sancho, J; Zubiaur, M

2014-06-01

Circulating microRNAs (miRNA) are involved in the posttranscriptional regulation of genes associated with lipid metabolism (miRNA-33) and vascular function and angiogenesis (miRNA-126). The objective of this exploratory study was to measure plasma levels of miRNA-33 and miRNA-126 in patients with plaque psoriasis and evaluate their association with clinical parameters. We studied 11 patients with plaque psoriasis. The median Psoriasis Area Severity Index (PASI) was 13 (interquartile range [IQR], 9-14) and body surface area involvement was 12 (IQR, 11-15). Eleven healthy controls matched for age and sex were also included. We analyzed cardiovascular risk factors and subclinical carotid atheromatosis. Plasma miRNAs were evaluated using quantitative real-time polymerase chain reaction. Carotid intima-media thickness was greater in patients (0.57mm; IQR, 0.54-0.61; n=11) than in controls (0.50mm; IQR, 0.48-0.54; data available for 9 controls) (P=.0055, Mann-Whitney). Expression of miRNA-33 in patients (5.34; IQR, 3.12-7.96; n=11) was significantly higher than in controls (2.33; IQR, 1.71-2.84; only detected in 7 of 11 controls) (P=.0049, Wilcoxon signed rank). No differences in miRNA-126 levels were observed between patients and controls. In patients (n=11), we observed a positive correlation between miRNA-33 and insulin levels (r=0.7289, P=.0109) and a negative correlation between miRNA-126 and carotid intima-media thickness (r=-0.6181, P=.0426). In psoriasis patients plasma levels of lipid and glucose metabolism-related miRNA-33 are increased and correlated with insulin. The study of circulating miRNA-33 in psoriasis may provide new insights about the associated systemic inflammatory abnormalities. Copyright © 2013 Elsevier España, S.L. and AEDV. All rights reserved.

Inhibition of Endothelial p53 Improves Metabolic Abnormalities Related to Dietary Obesity

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Masataka Yokoyama

2014-06-01

Full Text Available Accumulating evidence has suggested a role for p53 activation in various age-associated conditions. Here, we identified a crucial role of endothelial p53 activation in the regulation of glucose homeostasis. Endothelial expression of p53 was markedly upregulated when mice were fed a high-calorie diet. Disruption of endothelial p53 activation improved dietary inactivation of endothelial nitric oxide synthase that upregulated the expression of peroxisome proliferator-activated receptor-γ coactivator-1α in skeletal muscle, thereby increasing mitochondrial biogenesis and oxygen consumption. Mice with endothelial cell-specific p53 deficiency fed a high-calorie diet showed improvement of insulin sensitivity and less fat accumulation, compared with control littermates. Conversely, upregulation of endothelial p53 caused metabolic abnormalities. These results indicate that inhibition of endothelial p53 could be a novel therapeutic target to block the vicious cycle of cardiovascular and metabolic abnormalities associated with obesity.

Abnormal pressures as hydrodynamic phenomena

Science.gov (United States)

Neuzil, C.E.

1995-01-01

So-called abnormal pressures, subsurface fluid pressures significantly higher or lower than hydrostatic, have excited speculation about their origin since subsurface exploration first encountered them. Two distinct conceptual models for abnormal pressures have gained currency among earth scientists. The static model sees abnormal pressures generally as relict features preserved by a virtual absence of fluid flow over geologic time. The hydrodynamic model instead envisions abnormal pressures as phenomena in which flow usually plays an important role. This paper develops the theoretical framework for abnormal pressures as hydrodynamic phenomena, shows that it explains the manifold occurrences of abnormal pressures, and examines the implications of this approach. -from Author

Transcriptome Analysis for Abnormal Spike Development of the Wheat Mutant dms.

Science.gov (United States)

Zhu, Xin-Xin; Li, Qiao-Yun; Shen, Chun-Cai; Duan, Zong-Biao; Yu, Dong-Yan; Niu, Ji-Shan; Ni, Yong-Jing; Jiang, Yu-Mei

2016-01-01

Wheat (Triticum aestivum L.) spike development is the foundation for grain yield. We obtained a novel wheat mutant, dms, characterized as dwarf, multi-pistil and sterility. Although the genetic changes are not clear, the heredity of traits suggests that a recessive gene locus controls the two traits of multi-pistil and sterility in self-pollinating populations of the medium plants (M), such that the dwarf genotype (D) and tall genotype (T) in the progeny of the mutant are ideal lines for studies regarding wheat spike development. The objective of this study was to explore the molecular basis for spike abnormalities of dwarf genotype. Four unigene libraries were assembled by sequencing the mRNAs of the super-bulked differentiating spikes and stem tips of the D and T plants. Using integrative analysis, we identified 419 genes highly expressed in spikes, including nine typical homeotic genes of the MADS-box family and the genes TaAP2, TaFL and TaDL. We also identified 143 genes that were significantly different between young spikes of T and D, and 26 genes that were putatively involved in spike differentiation. The result showed that the expression levels of TaAP1-2, TaAP2, and other genes involved in the majority of biological processes such as transcription, translation, cell division, photosynthesis, carbohydrate transport and metabolism, and energy production and conversion were significantly lower in D than in T. We identified a set of genes related to wheat floral organ differentiation, including typical homeotic genes. Our results showed that the major causal factors resulting in the spike abnormalities of dms were the lower expression homeotic genes, hormonal imbalance, repressed biological processes, and deficiency of construction materials and energy. We performed a series of studies on the homeotic genes, however the other three causal factors for spike abnormal phenotype of dms need further study.

Indium 111 WBC scan in local and systemic fungal infections

International Nuclear Information System (INIS)

Haseman, M.K.; Blake, K.; McDougall, I.R.

1984-01-01

We describe two patients-one with a systemic fungal infection and one with a localized form-who had strikingly abnormal indium 111 leukocyte (WBC) scans. The patient with systemic disease had an abnormal WBC scan before lesions became clinically apparent

Structural brain abnormalities in Cushing's syndrome.

Science.gov (United States)

Bauduin, Stephanie E E C; van der Wee, Nic J A; van der Werff, Steven J A

2018-05-08

Alongside various physical symptoms, patients with Cushing's disease and Cushing's syndrome display a wide variety of neuropsychiatric and cognitive symptoms, which are indicative of involvement of the central nervous system. The aim of this review is to provide an overview of the structural brain abnormalities that are associated with Cushing's disease and Cushing's syndrome and their relation to behavioral and cognitive symptomatology. In this review, we discuss the gray matter structural abnormalities found in patients with active Cushing's disease and Cushing's syndrome, the reversibility and persistence of these changes and the white matter structural changes related to Cushing's syndrome. Recent findings are of particular interest because they provide more detailed information on localization of the structural changes as well as possible insights into the underlying biological processes. Active Cushing's disease and Cushing's syndrome is related to volume reductions of the hippocampus and in a prefrontal region involving the anterior cingulate cortex (ACC) and medial frontal gyrus (MFG). Whilst there are indications that the reductions in hippocampal volume are partially reversible, the changes in the ACC and MFG appear to be more persistent. In contrast to the volumetric findings, changes in white matter connectivity are typically widespread involving multiple tracts.

Tissue specific haemoglobin gene expression suggests adaptation to local marine conditions in North Sea flounder (Platichthys flesus L.)

DEFF Research Database (Denmark)

Larsen, P.F.; Eg Nielsen, Einar; Hansen, M.M.

2013-01-01

Recent genetic analyses of candidate genes and gene expression in marine fishes have provided evidence of local adaptation in response to environmental differences, despite the lack of strong signals of population structure from conventional neutral genetic markers. In this study expression...... in flounder. In gill tissue a plastic response to salinity treatments was observed with general up-regulation of these genes concomitant with higher salinity. For liver tissue a population specific expression differences was observed with lower expression at simulated non-native compared to native salinities...... in high gene flow marine fishes. © 2013 The Genetics Society of Korea...

Reversible skeletal abnormalities in gamma-glutamyl transpeptidase-deficient mice

Science.gov (United States)

Levasseur, Regis; Barrios, Roberto; Elefteriou, Florent; Glass, Donald A 2nd; Lieberman, Michael W.; Karsenty, Gerard

2003-01-01

Gamma-glutamyl transpeptidase (GGT) is a widely distributed ectopeptidase responsible for the degradation of glutathione in the gamma-glutamyl cycle. This cycle is implicated in the metabolism of cysteine, and absence of GGT causes a severe intracellular decrease in this amino acid. GGT-deficient (GGT-/-) mice have multiple metabolic abnormalities and are dwarf. We show here that this latter phenotype is due to a decreased of the growth plate cartilage total height resulting from a proliferative defect of chondrocytes. In addition, analysis of vertebrae and tibiae of GGT-/- mice revealed a severe osteopenia. Histomorphometric studies showed that this low bone mass phenotype results from an increased osteoclast number and activity as well as from a marked decrease in osteoblast activity. Interestingly, neither osteoblasts, osteoclasts, nor chondrocytes express GGT, suggesting that the observed defects are secondary to other abnormalities. N-acetylcysteine supplementation has been shown to reverse the metabolic abnormalities of the GGT-/- mice and in particular to restore the level of IGF-1 and sex steroids in these mice. Consistent with these previous observations, N-acetylcysteine treatment of GGT-/- mice ameliorates their skeletal abnormalities by normalizing chondrocytes proliferation and osteoblastic function. In contrast, resorbtion parameters are only partially normalized in GGT-/- N-acetylcysteine-treated mice, suggesting that GGT regulates osteoclast biology at least partly independently of these hormones. These results establish the importance of cysteine metabolism for the regulation of bone remodeling and longitudinal growth.

Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

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Ashton Kevin J

2011-05-01

Full Text Available Abstract Background Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME is characterised by severe prolonged fatigue, and decreases in cognition and other physiological functions, resulting in severe loss of quality of life, difficult clinical management and high costs to the health care system. To date there is no proven pathomechanism to satisfactorily explain this disorder. Studies have identified abnormalities in immune function but these data are inconsistent. We investigated the profile of markers of immune function (including novel markers in CFS/ME patients. Methods We included 95 CFS/ME patients and 50 healthy controls. All participants were assessed on natural killer (NK and CD8+T cell cytotoxic activities, Th1 and Th2 cytokine profile of CD4+T cells, expression of vasoactive intestinal peptide receptor 2 (VPACR2, levels of NK phenotypes (CD56bright and CD56dim and regulatory T cells expressing FoxP3 transcription factor. Results Compared to healthy individuals, CFS/ME patients displayed significant increases in IL-10, IFN-γ, TNF-α, CD4+CD25+ T cells, FoxP3 and VPACR2 expression. Cytotoxic activity of NK and CD8+T cells and NK phenotypes, in particular the CD56bright NK cells were significantly decreased in CFS/ME patients. Additionally granzyme A and granzyme K expression were reduced while expression levels of perforin were significantly increased in the CFS/ME population relative to the control population. These data suggest significant dysregulation of the immune system in CFS/ME patients. Conclusions Our study found immunological abnormalities which may serve as biomarkers in CFS/ME patients with potential for an application as a diagnostic tool.

Novel causative mutations in patients with Nance-Horan syndrome and altered localization of the mutant NHS-A protein isoform

OpenAIRE

Sharma, Shiwani; Burdon, Kathryn P.; Dave, Alpana; Jamieson, Robyn V.; Yaron, Yuval; Billson, Frank; Van Maldergem, Lionel; Lorenz, Birgit; Gécz, Jozef; Craig, Jamie E.

2008-01-01

Purpose Nance-Horan syndrome is typically characterized by severe bilateral congenital cataracts and dental abnormalities. Truncating mutations in the Nance-Horan syndrome (NHS) gene cause this X-linked genetic disorder. NHS encodes two isoforms, NHS-A and NHS-1A. The ocular lens expresses NHS-A, the epithelial and neuronal cell specific isoform. The NHS-A protein localizes in the lens epithelium at the cellular periphery. The data to date suggest a role for this isoform at cell-cell junction...

Expression and Localization of Cathepsins B, D, and G in Two Cancer Stem Cell Subpopulations in Moderately Differentiated Oral Tongue Squamous Cell Carcinoma

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Therese Featherston

2017-07-01

Full Text Available AimWe have previously demonstrated the putative presence of two cancer stem cell (CSC subpopulations within moderately differentiated oral tongue squamous cell carcinoma (MDOTSCC, which express components of the renin–angiotensin system (RAS. In this study, we investigated the expression and localization of cathepsins B, D, and G in relation to these CSC subpopulations within MDOTSCC.Methods3,3-Diaminobenzidine (DAB and immunofluorescent (IF immunohistochemical (IHC staining was performed on MDOTSCC samples to determine the expression and localization of cathepsins B, D, and G in relation to the CSC subpopulations. NanoString mRNA analysis and colorimetric in situ hybridization (CISH were used to study their transcripts expression. Enzyme activity assays were performed to determine the activity of these cathepsins in MDOTSCC.ResultsIHC staining demonstrated expression of cathepsins B, D, and G in MDOTSCC. Cathepsins B and D were localized to CSCs within the tumor nests, while cathepsin B was localized to the CSCs within the peri-tumoral stroma, and cathepsin G was localized to the tryptase+ phenotypic mast cells within the peri-tumoral stroma. NanoString and CISH mRNA analyses confirmed transcription activation of cathepsins B, D, and G. Enzyme activity assays confirmed active cathepsins B and D, but not cathepsin G.ConclusionThe presence of cathepsins B and D on the CSCs and cathspsin G on the phenotypic mast cells suggest the presence of bypass loops for the RAS which may be a potential novel therapeutic target for MDOTSCC.

Abnormal sound detection device

International Nuclear Information System (INIS)

Yamada, Izumi; Matsui, Yuji.

1995-01-01

Only components synchronized with rotation of pumps are sampled from detected acoustic sounds, to judge the presence or absence of abnormality based on the magnitude of the synchronized components. A synchronized component sampling means can remove resonance sounds and other acoustic sounds generated at a synchronously with the rotation based on the knowledge that generated acoustic components in a normal state are a sort of resonance sounds and are not precisely synchronized with the number of rotation. On the other hand, abnormal sounds of a rotating body are often caused by compulsory force accompanying the rotation as a generation source, and the abnormal sounds can be detected by extracting only the rotation-synchronized components. Since components of normal acoustic sounds generated at present are discriminated from the detected sounds, reduction of the abnormal sounds due to a signal processing can be avoided and, as a result, abnormal sound detection sensitivity can be improved. Further, since it is adapted to discriminate the occurrence of the abnormal sound from the actually detected sounds, the other frequency components which are forecast but not generated actually are not removed, so that it is further effective for the improvement of detection sensitivity. (N.H.)

Heterogeneity of miRNA expression in localized prostate cancer with clinicopathological correlations.

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Ahmed Hussein Zedan

Full Text Available In the last decade microRNAs (miRNAs have been widely investigated in prostate cancer (PCa and have shown to be promising biomarkers in diagnostic, prognostic and predictive settings. However, tumor heterogeneity may influence miRNA expression. The aims of this study were to assess the impact of tumor heterogeneity, as demonstrated by a panel of selected miRNAs in PCa, and to correlate miRNA expression with risk profile and patient outcome.Prostatectomy specimens and matched, preoperative needle biopsies from a retrospective cohort of 49 patients, who underwent curatively intended surgery for localized PCa, were investigated with a panel of 6 miRNAs (miRNA-21, miRNA-34a, miRNA-125b, miRNA-126, miRNA-143, and miRNA-145 using tissue micro-array (TMA and in situ hybridization (ISH. Inter- and intra-patient variation was assessed using intra-class correlation (ICC.Four miRNAs (miRNA-21, miRNA-34a, miRNA-125, and miRNA-126 were significantly upregulated in PCa compared to benign prostatic hyperplasia (BPH, and except for miRNA-21 these miRNAs documented a positive correlation between the expression level in PCa cores and their matched BPH cores, (r > 0.72. The ICC varied from 0.451 to 0.764, with miRNA-34a showing an intra-tumoral heterogeneity accounting for less than 50% of the total variation. Regarding clinicopathological outcomes, only miRNA-143 showed potential as a prognostic marker with a higher expression correlating with longer relapse-free survival (p = 0.016.The present study documents significant upregulation of the expression of miRNA-21, miRNA-34a, miRNA-125, and miRNA-126 in PCa compared to BPH and suggests a possible prognostic value associated with the expression of miRNA-143. The results, however, document intra-tumoral heterogeneity in the expression of various miRNAs calling for caution when using these tumor tissue biomarkers in prognostic and predictive settings.

Correlation between dopamine receptor D2 expression and presence of abnormal involuntary movements in Wistar rats with hemiparkinsonism and dyskinesia.

Science.gov (United States)

Caro Aponte, P A; Otálora, C A; Guzmán, J C; Turner, L F; Alcázar, J P; Mayorga, E L

2018-03-07

Parkinson's disease (PD) is characterised by motor alterations, which are commonly treated with L-DOPA. However, long-term L-DOPA use may cause dyskinesia. Although the pathogenic mechanism of L-DOPA-induced dyskinesia is unclear, the condition has been associated with alterations in dopamine receptors, among which D2 receptors (D2R) have received little attention. This study aims to: (i)develop and standardise an experimental model of L-DOPA-induced dyskinesia in rats with hemiparkinsonism; and (ii)evaluate the correlation between D2R expression and presence of abnormal involuntary movements (AIM). We allocated 21 male Wistar rats into 3 groups: intact controls, lesioned rats (with neurotoxin 6-OHDA), and dyskinetic rats (injected with L-DOPA for 19 days). Sensorimotor impairment was assessed with behavioural tests. Dyskinetic rats gradually developed AIMs during the treatment period; front leg AIMs were more severe and locomotor AIMs less severe (Pde Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

On A Quasi-local Mass

OpenAIRE

Zhang, Xiao

2009-01-01

We modify previous quasi-local mass definition. The new definition provides expressions of the quasi-local energy, the quasi-local linear momentum and the quasi-local mass. And they are equal to the ADM expressions at spatial infinity. Moreover, the new quasi-local energy has the positivity property.

DNA methylation abnormalities in congenital heart disease.

Science.gov (United States)

Serra-Juhé, Clara; Cuscó, Ivon; Homs, Aïda; Flores, Raquel; Torán, Núria; Pérez-Jurado, Luis A

2015-01-01

Congenital heart defects represent the most common malformation at birth, occurring also in ∼50% of individuals with Down syndrome. Congenital heart defects are thought to have multifactorial etiology, but the main causes are largely unknown. We have explored the global methylation profile of fetal heart DNA in comparison to blood DNA from control subjects: an absolute correlation with the type of tissue was detected. Pathway analysis revealed a significant enrichment of differential methylation at genes related to muscle contraction and cardiomyopathies in the developing heart DNA. We have also searched for abnormal methylation profiles on developing heart-tissue DNA of syndromic and non-syndromic congenital heart defects. On average, 3 regions with aberrant methylation were detected per sample and 18 regions were found differentially methylated between groups. Several epimutations were detected in candidate genes involved in growth regulation, apoptosis and folate pathway. A likely pathogenic hypermethylation of several intragenic sites at the MSX1 gene, involved in outflow tract morphogenesis, was found in a fetus with isolated heart malformation. In addition, hypermethylation of the GATA4 gene was present in fetuses with Down syndrome with or without congenital heart defects, as well as in fetuses with isolated heart malformations. Expression deregulation of the abnormally methylated genes was detected. Our data indicate that epigenetic alterations of relevant genes are present in developing heart DNA in fetuses with both isolated and syndromic heart malformations. These epimutations likely contribute to the pathogenesis of the malformation by cis-acting effects on gene expression.

Localized scleroderma: imaging features

Energy Technology Data Exchange (ETDEWEB)

Liu, P. (Dept. of Diagnostic Imaging, Hospital for Sick Children, Toronto, ON (Canada)); Uziel, Y. (Div. of Rheumatology, Hospital for Sick Children, Toronto, ON (Canada)); Chuang, S. (Dept. of Diagnostic Imaging, Hospital for Sick Children, Toronto, ON (Canada)); Silverman, E. (Div. of Rheumatology, Hospital for Sick Children, Toronto, ON (Canada)); Krafchik, B. (Div. of Dermatology, Dept. of Pediatrics, Hospital for Sick Children, Toronto, ON (Canada)); Laxer, R. (Div. of Rheumatology, Hospital for Sick Children, Toronto, ON (Canada))

1994-06-01

Localized scleroderma is distinct from the diffuse form of scleroderma and does not show Raynaud's phenomenon and visceral involvement. The imaging features in 23 patients ranging from 2 to 17 years of age (mean 11.1 years) were reviewed. Leg length discrepancy and muscle atrophy were the most common findings (five patients), with two patients also showing modelling deformity of the fibula. One patient with lower extremity involvement showed abnormal bone marrow signals on MR. Disabling joint contracture requiring orthopedic intervention was noted in one patient. In two patients with ''en coup de sabre'' facial deformity, CT and MR scans revealed intracranial calcifications and white matter abnormality in the ipsilateral frontal lobes, with one also showing migrational abnormality. In a third patient, CT revealed white matter abnormality in the ipsilateral parietal lobe. In one patient with progressive facial hemiatrophy, CT and MR scans showed the underlying hypoplastic left maxillary antrum and cheek. Imaging studies of areas of clinical concern revealed positive findings in half our patients. (orig.)

Abnormal megakaryocyte development and platelet function in Nbeal2(-/-) mice.

Science.gov (United States)

Kahr, Walter H A; Lo, Richard W; Li, Ling; Pluthero, Fred G; Christensen, Hilary; Ni, Ran; Vaezzadeh, Nima; Hawkins, Cynthia E; Weyrich, Andrew S; Di Paola, Jorge; Landolt-Marticorena, Carolina; Gross, Peter L

2013-11-07

Gray platelet syndrome (GPS) is an inherited bleeding disorder associated with macrothrombocytopenia and α-granule-deficient platelets. GPS has been linked to loss of function mutations in NEABL2 (neurobeachin-like 2), and we describe here a murine GPS model, the Nbeal2(-/-) mouse. As in GPS, Nbeal2(-/-) mice exhibit splenomegaly, macrothrombocytopenia, and a deficiency of platelet α-granules and their cargo, including von Willebrand factor (VWF), thrombospondin-1, and platelet factor 4. The platelet α-granule membrane protein P-selectin is expressed at 48% of wild-type levels and externalized upon platelet activation. The presence of P-selectin and normal levels of VPS33B and VPS16B in Nbeal2(-/-) platelets suggests that NBEAL2 acts independently of VPS33B/VPS16B at a later stage of α-granule biogenesis. Impaired Nbeal2(-/-) platelet function was shown by flow cytometry, platelet aggregometry, bleeding assays, and intravital imaging of laser-induced arterial thrombus formation. Microscopic analysis detected marked abnormalities in Nbeal2(-/-) bone marrow megakaryocytes, which when cultured showed delayed maturation, decreased survival, decreased ploidy, and developmental abnormalities, including abnormal extracellular distribution of VWF. Our results confirm that α-granule secretion plays a significant role in platelet function, and they also indicate that abnormal α-granule formation in Nbeal2(-/-) mice has deleterious effects on megakaryocyte survival, development, and platelet production.

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.

Are premorbid abnormal personality traits associated with behavioural and psychological symptoms in dementia?

Science.gov (United States)

Prior, Jack; Abraham, Rajesh; Nicholas, Helen; Chan, Tom; Vanvlymen, Jeremy; Lovestone, Simon; Boothby, Harry

2016-09-01

The study aims to investigate associations between behavioural and psychological symptoms of dementia (BPSD) and abnormal premorbid personality traits. Data were obtained from 217 patients with a diagnosis of probable Alzheimer's disease. Behavioural and psychological symptoms of late-onset dementia were assessed with the Neuropsychiatric Inventory. Premorbid personality traits were assessed using the Standardised Assessment of Personality. Abnormal premorbid personality traits were categorised with Diagnostic and Statistical Manual of Mental Disorders fourth edition and International Statistical Classification of Diseases and Related Health Problems-10 diagnostic criteria for personality disorders. Abnormal premorbid personality traits were associated with increased behavioural and psychological symptoms in dementia. Cluster A (solitary/paranoid) premorbid personality traits were associated with anxiety, depression and hallucinations. Cluster C (anxious/dependent) traits were associated with a syndrome of depression. The presence of Clusters A (solitary/paranoid) and C (anxious/dependent) abnormal premorbid personality traits seems to affect the expression of certain behavioural and psychological symptoms in dementia, depression in particular. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Electrocardiographic abnormalities in opiate addicts.

Science.gov (United States)

Wallner, Christina; Stöllberger, Claudia; Hlavin, Anton; Finsterer, Josef; Hager, Isabella; Hermann, Peter

2008-12-01

To determine in a cross-sectional study the prevalence of electrocardiographic (ECG) abnormalities in opiate addicts who were therapy-seeking and its association with demographic, clinical and drug-specific parameters. In consecutive therapy-seeking opiate addicts, a 12-lead ECG was registered within 24 hours after admission and evaluated according to a pre-set protocol between October 2004 and August 2006. Additionally, demographic, clinical and drug-specific parameters were recorded. Included were 511 opiate-addicts, 25% female, with a mean age of 29 years (range 17-59 years). One or more ECG abnormalities were found in 314 patients (61%). In the 511 patients we found most commonly ST abnormalities (19%), QTc prolongation (13%), tall R- and/or S-waves (11%) and missing R progression (10%). ECG abnormalities were more common in males than in females (64 versus 54%, P seizures less often (16 versus 27%, P opiate addicts. The most frequent ECG abnormalities are ST abnormalities, QTc prolongation and tall R- and/or S-waves. ST abnormalities are associated with cannabis, and QTc prolongation with methadone and benzodiazepines.

Local NSAID infusion does not affect protein synthesis and gene expression in human muscle after eccentric exercise

DEFF Research Database (Denmark)

Mikkelsen, U R; Schjerling, P; Helmark, Ida Carøe

2010-01-01

models, and inhibit the exercise-induced satellite cell proliferation and protein synthesis in humans. However, the cellular mechanisms eliciting these responses remain unknown. Eight healthy male volunteers performed 200 maximal eccentric contractions with each leg. To block prostaglandin synthesis...... locally in the skeletal muscle, indomethacin (NSAID) was infused for 7.5 h via microdialysis catheters into m. vastus lateralis of one leg. Protein synthesis was determined by the incorporation of 1,2-(13)C(2) leucine into muscle protein from 24 to 28 h post-exercise. Furthermore, mRNA expression...... of selected genes was measured in muscle biopsies (5 h and 8 days post-exercise) by real-time reverse transcriptase PCR. Myofibrillar and collagen protein synthesis were unaffected by the local NSAID infusion. Five hours post-exercise, the mRNA expression of cyclooxygenase-2 (COX2) was sixfold higher...

CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization

Science.gov (United States)

Tormin, Ariane; Li, Ou; Brune, Jan Claas; Walsh, Stuart; Schütz, Birgit; Ehinger, Mats; Ditzel, Nicholas; Kassem, Moustapha

2011-01-01

Nonhematopoietic bone marrow mesenchymal stem cells (BM-MSCs) are of central importance for bone marrow stroma and the hematopoietic environment. However, the exact phenotype and anatomical distribution of specified MSC populations in the marrow are unknown. We characterized the phenotype of primary human BM-MSCs and found that all assayable colony-forming units-fibroblast (CFU-Fs) were highly and exclusively enriched not only in the lin−/CD271+/CD45−/CD146+ stem-cell fraction, but also in lin−/CD271+/CD45−/CD146−/low cells. Both populations, regardless of CD146 expression, shared a similar phenotype and genotype, gave rise to typical cultured stromal cells, and formed bone and hematopoietic stroma in vivo. Interestingly, CD146 was up-regulated in normoxia and down-regulated in hypoxia. This was correlated with in situ localization differences, with CD146 coexpressing reticular cells located in perivascular regions, whereas bone-lining MSCs expressed CD271 alone. In both regions, CD34+ hematopoietic stem/progenitor cells were located in close proximity to MSCs. These novel findings show that the expression of CD146 differentiates between perivascular versus endosteal localization of non-hematopoietic BM-MSC populations, which may be useful for the study of the hematopoietic environment. PMID:21415267

Roentgenologic abnormalities in Down's syndrome

Energy Technology Data Exchange (ETDEWEB)

Higuchi, Takehiko; Russell, W J; Komatsuda, Michio; Neriishi, Shotaro

1968-07-25

Roentgenograms of 28 patients with Down's syndrome were reviewed with emphasis on all previously reported abnormalities and any possible additional ones. Most of the abnormalities occurred with the same frequency as previously reported, but some less frequently reported findings were also seen. One abnormal vertebral measurement found in this series may be an additional stigma of Down's syndrome. All of the 27 cases studied cytogenetically had chromosomal abnormalities consistent with this disease. This study emphasizes the need for roentgenologic norms for the Japanese, and the desirability of combining chromosome studies with roentgenological abnormalities and clinical observations in diagnosing Down's syndrome. 19 references, 2 figures, 5 tables.

Erythrocyte abnormalities induced by chemotherapy and radiotherapy: Induction of preleukaemic states

International Nuclear Information System (INIS)

Renoux, M.; Bernard, J.-F.; Boivin, P.; Schlegel, N.; Amar, M.; Torres, M.; Lopez, M.

1978-01-01

Increased incidence of acute leukaemia (AL) following exposure to ionizing radiation is well documented. AL has also been reported with increased frequency after chemotherapy for nonmalignant diseases. The effect of chemotherapy and/or radiotherapy on the following erythrocyte parameters: pyruvate-kinase (PK) activity, phospho-fructo-kinase (PFK) activity, HbF level, red cell antigens production and bone marrow sideroblasts, has been studied in 31 patients with myelomatosis and in 33 patients with nonhaematological malignancies. We have demonstrated the apperance after chemotherapy or radiotherapy of some abnormalities usually associated with leukaemia or preleukaemic states. In patients treated for myelomatosis, a PK deficiency has been detected in 58 % of the cases, an increased HbF level in 47 %, a modification of blood groups antigens in 68 % and abnormal sideroblasts in 30 %. No PFK deficiency was found. In patients treated for solid tumors, a PK deficiency in 50 % of the cases, a PFK deficiency in 20 %, an increased HbF level in 10 %, a modification of blood group antigens in 40 % has been detected. Chemotherapy administered over a period of 3 months has been shown to induce these abnormalities. Localized radiotherapy may have a similar effect. The combination of these two factors seems to cause an increase in the frequency and intensity of these abnormalities. (author)

A comparative antibody analysis of Pannexin1 expression in four rat brain regions reveals varying subcellular localizations

Directory of Open Access Journals (Sweden)

Angela C Cone

2013-02-01

Full Text Available Pannexin1 (Panx1 channels release cytosolic ATP in response to signaling pathways. Panx1 is highly expressed in the central nervous system. We used four antibodies with different Panx1 anti-peptide epitopes to analyze four regions of rat brain. These antibodies labeled the same bands in Western blots and had highly similar patterns of immunofluorescence in tissue culture cells expressing Panx1, but Western blots of brain lysates from Panx1 knockout and control mice showed different banding patterns. Localizations of Panx1 in brain slices were generated using automated wide-field mosaic confocal microscopy for imaging large regions of interest while retaining maximum resolution for examining cell populations and compartments. We compared Panx1 expression over the cerebellum, hippocampus with adjacent cortex, thalamus and olfactory bulb. While Panx1 localizes to the same neuronal cell types, subcellular localizations differ. Two antibodies with epitopes against the intracellular loop and one against the carboxy terminus preferentially labeled cell bodies, while an antibody raised against an N-terminal peptide highlighted neuronal processes more than cell bodies. These labeling patterns may be a reflection of different cellular and subcellular localizations of full-length and/or modified Panx1 channels where each antibody is highlighting unique or differentially accessible Panx1 populations. However, we cannot rule out that one or more of these antibodies have specificity issues. All data associated with experiments from these four antibodies are presented in a manner that allows them to be compared and our claims thoroughly evaluated, rather than eliminating results that were questionable. Each antibody is given a unique identifier through the NIF Antibody Registry that can be used to track usage of individual antibodies across papers and all image and metadata are made available in the public repository, the Cell Centered Database, for on

Gamma band oscillations: a key to understanding schizophrenia symptoms and neural circuit abnormalities.

Science.gov (United States)

McNally, James M; McCarley, Robert W

2016-05-01

We review our current understanding of abnormal γ band oscillations in schizophrenia, their association with symptoms and the underlying cortical circuit abnormality, with a particular focus on the role of fast-spiking parvalbumin gamma-aminobutyric acid (GABA) neurons in the disease state. Clinical electrophysiological studies of schizophrenia patients and pharmacological models of the disorder show an increase in spontaneous γ band activity (not stimulus-evoked) measures. These findings provide a crucial link between preclinical and clinical work examining the role of γ band activity in schizophrenia. MRI-based experiments measuring cortical GABA provides evidence supporting impaired GABAergic neurotransmission in schizophrenia patients, which is correlated with γ band activity level. Several studies suggest that stimulation of the cortical circuitry, directly or via subcortical structures, has the potential to modulate cortical γ activity, and improve cognitive function. Abnormal γ band activity is observed in patients with schizophrenia and disease models in animals, and is suggested to underlie the psychosis and cognitive/perceptual deficits. Convergent evidence from both clinical and preclinical studies suggest the central factor in γ band abnormalities is impaired GABAergic neurotransmission, particularly in a subclass of neurons which express parvalbumin. Rescue of γ band abnormalities presents an intriguing option for therapeutic intervention.

Abnormal grain growth in Eurofer-97 steel in the ferrite phase field

Energy Technology Data Exchange (ETDEWEB)

Oliveira, V.B. [Lorena School of Engineering, University of Sao Paulo, Lorena, SP, 12602-810 (Brazil); Sandim, H.R.Z., E-mail: hsandim@demar.eel.usp.br [Lorena School of Engineering, University of Sao Paulo, Lorena, SP, 12602-810 (Brazil); Raabe, D. [Max-Planck-Institut für Eisenforschung, Düsseldorf, D-40237 (Germany)

2017-03-15

Reduced-activation ferritic-martensitic (RAFM) Eurofer-97 steel is a candidate material for structural applications in future fusion reactors. Depending on the amount of prior cold rolling strain and annealing temperature, important solid-state softening reactions such as recovery, recrystallization, and grain growth occur. Eurofer-97 steel was cold rolled up to 70, 80 and 90% reductions in thickness and annealed in the ferrite phase field (below ≈ 800 °C). Changes in microstructure, micro-, and mesotexture were followed by orientation mappings provided by electron backscatter diffraction (EBSD). Eurofer-97 steel undergoes abnormal grain growth above 650 °C and this solid-state reaction seems to be closely related to the high mobility of a few special grain boundaries that overcome pinning effects caused by fine particles. This solid-state reaction promotes important changes in the microstructure and microtexture of this steel. Abnormal grain growth kinetics for each condition was determined by means of quantitative metallography. - Highlights: • Abnormal grain growth (AGG) occurs in Eurofer-97 steel deformed to several strains. • Kinetics of abnormal grain growth has been determined at 750 and 800 °C. • Significant changes in crystallographic texture take place during AGG. • Grain boundaries with misorientations above 45° may explain abnormal grain growth. • Local microstructural instabilities (coarsening of M23C6 carbides) also explain AGG.

Analysis of APC allelic imbalance/loss of heterozygosity and APC protein expression in cutaneous squamous cell carcinomas.

LENUS (Irish Health Repository)

Gray, Sarah E

2012-02-01

BACKGROUND: The adenomatous polyposis coli (APC) gene is a tumor suppressor gene which is mutated in the hereditary disease, familial adenomatous polyposis (FAP). Somatic mutations of the APC gene have also been identified in the majority of sporadic colorectal carcinomas, and mutation of the APC gene appears to be an early step in the initiation of colon cancer. Loss of heterozygosity (LOH) of APC has been described in a variety of other cancer types, including renal cell carcinoma, gastric cancer, non-small cell lung cancer, endometrial cancer and oral squamous cell carcinomas (SCC). AIM: To determine the role played by APC gene in the genesis of cutaneous SCC. MATERIALS AND METHODS: Allelic imbalance\\/loss of heterozygosity (AI\\/LOH) was examined in twenty-two histologically confirmed cutaneous squamous cell carcinomas (SCC) using microsatellite markers, proximal to the APC gene. Immunohistochemical analysis of APC protein expression was also examined in the cutaneous SCC. RESULTS: AI\\/LOH was detected in 60% of the SCC samples using D5S346 marker (proximal to the APC gene). Ninty-five percent of the SCC samples showed positive reduced APC expression, however the localization of the APC protein was abnormal. CONCLUSION: The abnormal expression of APC suggests that APC gene may play a role in cutaneous SCC development.

Subcutaneous administration of polymerized type I collagen downregulates interleukin (IL)-17A, IL-22 and transforming growth factor-β1 expression, and increases Foxp3-expressing cells in localized scleroderma.

Science.gov (United States)

Furuzawa-Carballeda, J; Ortíz-Ávalos, M; Lima, G; Jurado-Santa Cruz, F; Llorente, L

2012-08-01

Localized scleroderma (LS) is a disfiguring inflammatory autoimmune disease of the skin and underlying tissue. As in systemic sclerosis, a key feature is the presence of T cells in inflammatory lesions. To evaluate the effect of polymerized type I collagen vs. methylprednisolone (MP) in LS, and to determine the influence of this polymerized collagen (PC) on CD4+ peripheral T cells expressing interleukin (IL)-4, IL-17A, interferon-γ and Forkhead box protein (Foxp)3, and on cells expressing transforming growth factor (TGF)-β1, IL-17A, IL-22 and Foxp3 in the skin. In total, 16 patients with LS were treated for 3 months with monthly subcutaneous intralesional injections of 0.1 mL MP (giving a total dose of 20 mg/mL each month) and 15 patients were treated, with weekly subcutaneous intralesional injections of PC, ranging from 0.2 mL (equivalent to 1.66 mg collagen) for a lesion of 50 mm in size, up to a maximum of 1.0 mL (8.3 mg collagen) for a lesion > 100 mm in size, and followed up for a further 6 months. Skin biopsies were obtained from lesions at baseline (before treatment) and 9 months later (6 months after treatment end). Tissue sections were evaluated by histology and immunohistochemistry (IL-17A, IL-22, TGF-β1 and Foxp3). CD4+ T-cell subsets were determined in peripheral blood by flow cytometry. Abnormal tissue architecture was seen in the biopsies taken from patients treated with MP, whereas the PC treatment restored normal skin architecture. PC downregulated pro-inflammatory/profibrotic cytokine expression in peripheral cells, and upregulated the number of regulatory T cells (Tregs) in skin. PC was safe and well tolerated. PC is not only an antifibrotic/fibrolytic agent but also an immunomodulator biodrug that restores the balance between T helper (Th)1, Th2, Th17 and Tregs, downregulates production of pro-inflammatory or profibrogenic cytokines (IL-17A, IL-22 and TGF-β1), and renews skin architecture, without adverse effects. © The Author(s). CED �

Abnormality diagnosis device for nuclear reactor

Energy Technology Data Exchange (ETDEWEB)

Utsunomiya, Kazuhiro; Oyama, Shinmi; Sakaba, Hideo

1989-02-21

According to the present invention, abnormality such as abnormal increase of temperature in a nuclear reactor is detected to send a signal to control rod drives, etc. thereby stopping the operation of the nuclear reactor. Receiving/transmission device transmits a signal for conducting normal operation of an abnormality information section, as well as receives an echo signal from the abnormality information section to transmit an abnormal signal to a reactor protection system. The abnormality information section is disposed to fuel assemblies, receives a signal from the receiving/transmission device for conducting the normal operation to transmit a normal echo signal, as well as changes the echo signal when detecting the nuclear reactor abnormality. By the foregoing method, since the abnormality information section is disposed to the fuel assemblies, various effects can be attained such as: (1) there is no response delay from the occurrence of abnormality to emergency counter measure after detection, (2) high burnup degree for fuels can thus be possible to improve the economical property, (3) the abnormality information section can be taken out from the reactor container together with fuel assemablies by an existent take-out mechanism and (4) since wireless transmission and reception are established between the receiving/transmission device and the abnormality information section, cables are not required in the container. (K.M.).

Urokinase receptor-associated protein (uPARAP) is expressed in connection with malignant as well as benign lesions of the human breast and occurs in specific populations of stromal cells

DEFF Research Database (Denmark)

Schnack Nielsen, Boye; Rank, Fritz; Engelholm, Lars H

2002-01-01

recognized uPARAP in Western blotting and gave a strong signal in immunohistochemistry. The immunohistochemic localization pattern was found to be identical to that of uPARAP mRNA as determined in parallel by in situ hybridization. uPARAP expression was then studied in both benign and malignant breast...... conclude that expression of uPARAP is associated with the abnormal breast and that expression appears in myofibroblasts, macrophages and myoepithelium. We suggest that uPARAP is involved in the clearance of the uPA:uPAR complex as well as other possible ligands during benign and malignant tissue remodeling....

Abnormal uterine bleeding: advantages of formal classification to patients, clinicians and researchers.

Science.gov (United States)

Madhra, Mayank; Fraser, Ian S; Munro, Malcolm G; Critchley, Hilary O D

2014-07-01

To highlight the advantages of formal classification of causes of abnormal uterine bleeding from a clinical and scientific perspective. Review and recommendations for local implementation. In the past, research in the field of menstrual disorders has not been funded adequately with respect to the impact of symptoms on individuals, healthcare systems and society. This was confounded by a diverse terminology, which lead to confusion between clinical and scientific groups, ultimately harming the underlying evidence base. To address this, a formal classification system (PALM-COEIN) for the causes of abnormal uterine bleeding has been published for worldwide use by FIGO (International Federation of Gynecology and Obstetrics). This commentary explains problems created by the prior absence of such a system, the potential advantages stemming from its use, and practical suggestions for local implementation. The PALM-COEIN classification is applicable globally and, as momentum gathers, will ameliorate recurrence of historic problems, and harmonise reporting of clinical and scientific research to facilitate future progress in women's health. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Decreased expression of Sprouty2 in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder: a correlation with BDNF expression.

Directory of Open Access Journals (Sweden)

Anilkumar Pillai

Full Text Available BACKGROUND: Current theories on the pathophysiology of schizophrenia suggest altered brain plasticity such as decreased neural proliferation and migration, delayed myelination, and abnormal synaptic modeling, in the brain of subjects with schizophrenia. Though functional alterations in BDNF, which plays important role in neuroplasticity, are implicated in many abnormalities found in schizophrenia, the regulatory mechanism(s involved in the abnormal signaling of BDNF in schizophrenia is not clear. The present study investigated whether Sprouty2, a regulator of growth factor signaling, is abnormally expressed in schizophrenia, and is associated with the changes in BDNF mRNA in this disorder. The potential effect of antipsychotic drugs on Sprouty2 expression was tested in adult rats. METHODS AND FINDINGS: Sprouty2 and BDNF gene expression were analyzed in dorsolateral prefrontal cortex samples from the Stanley Array Collection. Quantitative real-time PCR analysis of RNA in 100 individuals (35 with schizophrenia, 31 with bipolar disorder, and 34 psychiatrically normal controls showed significantly decreased expression of Sprouty2 and BDNF in both schizophrenia and bipolar disorder. Moreover, a significant correlation between these two genes existed in control, schizophrenia and bipolar subjects. Long-term treatment with antipsychotic drugs, haloperidol and olanzapine, showed differential effects on both Sprouty2 and BDNF mRNA and protein levels in the frontal cortex of rats. CONCLUSION: These findings demonstrating decreased expression of Sprouty2 associated with changes in BDNF, suggest the possibility that these decreases are secondary to treatment rather than to factors that are significant in the disease process of either schizophrenia and/or bipolar disorder. Further exploration of Sprouty2-related signal transduction pathways may be helpful to design novel treatment strategies for these disorders.

Expression and localization of tubulin cofactors TBCD and TBCE in human gametes.

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Jiménez-Moreno, Victoria; Agirregoitia, Ekaitz

2017-06-01

The tubulin cofactors TBCD and TBCE play an essential role in regulation of the microtubule dynamics in a wide variety of somatic cells, but little information is known about the expression of these cofactors in human sperm and oocytes. In this study, we focused on the investigation of the presence of, and the differential distribution of, the tubulin cofactors TBCD and TBCE in human sperm and during human oocyte maturation. We performed expression assays for TBCD and TBCE by reverse transcription-polymerase chain reaction (RT-PCR), western blot and immunofluorescence and verified the presence of both cofactors in human gametes. TBCD and TBCE were located mainly in the middle region and in the tail of the sperm while in the oocyte the localization was cytosolic. The mRNA of both tubulin cofactors were present in the human oocytes but not in sperm cells. This finding gives a first insight into where TBCD and TBCE could carry out their function in the continuous changes that the cytoskeleton experiences during gametogenesis and also prior to fertilization.

Prognostic and Predictive Value of Baseline and Posttreatment Molecular Marker Expression in Locally Advanced Rectal Cancer Treated With Neoadjuvant Chemoradiotherapy

International Nuclear Information System (INIS)

Bertolini, Federica; Bengala, Carmelo; Losi, Luisa; Pagano, Maria; Iachetta, Francesco; Dealis, Cristina; Jovic, Gordana; Depenni, Roberta; Zironi, Sandra; Falchi, Anna Maria; Luppi, Gabriele; Conte, Pier Franco

2007-01-01

Purpose: To evaluate expression of a panel of molecular markers, including p53, p21, MLH1, MSH2, MIB-1, thymidylate synthase, epidermal growth factor receptor (EGFR), and tissue vascular endothelial growth factor (VEGF), before and after treatment in patients treated with neoadjuvant chemoradiotherapy for locally advanced rectal cancer, to correlate the constitutive profile and dynamics of expression with pathologic response and outcome. Methods and Materials: Expression of biomarkers was evaluated by immunohistochemistry in tumor samples from 91 patients with clinical Stage II and III rectal cancer treated with preoperative pelvic radiotherapy (50 Gy) plus concurrent 5-fluorouracil by continuous intravenous infusion. Results: A pathologic complete remission was observed in 14 patients (15.4%). Patients with MLH1-positive tumors had a higher pathologic complete response rate (24.3% vs. 9.4%; p = 0.055). Low expression of constitutive p21, absence of EGFR expression after chemoradiotherapy, and high Dworak's tumor regression grade (TRG) were significantly associated with improved disease-free survival and overall survival. A high MIB-1 value after chemoradiotherapy was significantly associated with worse overall survival. Multivariate analysis confirmed the prognostic value of constitutive p21 expression as well as EGFR expression and MIB-1 value after chemoradiotherapy among patients not achieving TRG 3-4. Conclusions: In our study, we observed the independent prognostic value of EGFR expression after chemoradiotherapy on disease-free survival. Moreover, our study suggests that a constitutive high p21 expression and a high MIB-1 value after neoadjuvant chemoradiotherapy treatment could predict worse outcome in locally advanced rectal cancer

Differential expression and localization of lipid transporters in the bovine mammary gland during the pregnancy-lactation cycle

DEFF Research Database (Denmark)

Mani, O; Sørensen, M T; Sejrsen, K

2009-01-01

biopsies and blood samples were taken from 10 animals at 7 stages of the pregnancy-lactation cycle. Expression levels of the specific mRNAs were determined by quantitative reverse transcription-PCR, whereas ABCA1 was localized by immunohistochemistry. Blood serum metabolites were determined by common...

Abnormal wiring of the connectome in adults with high-functioning autism spectrum disorder

OpenAIRE

Roine, Ulrika; Roine, Timo; Salmi, Juha; Nieminen-von Wendt, Taina; Tani, Pekka; Lepp?m?ki, Sami; Rintahaka, Pertti; Caeyenberghs, Karen; Leemans, Alexander; Sams, Mikko

2015-01-01

Abstract Background Recent brain imaging findings suggest that there are widely distributed abnormalities affecting the brain connectivity in individuals with autism spectrum disorder (ASD). Using graph theoretical analysis, it is possible to investigate both global and local properties of brain’s wiring diagram, i.e., the connectome. Methods We acquired diffusion-...

Decreased B and T lymphocyte attenuator in Behcet's disease may trigger abnormal Th17 and Th1 immune responses.

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Ye, Zi; Deng, Bolin; Wang, Chaokui; Zhang, Dike; Kijlstra, Aize; Yang, Peizeng

2016-02-04

Behcet's disease (BD) is a chronic, systemic and recurrent inflammatory disease associated with hyperactive Th17 and Th1 immune responses. Recent studies have shown that B and T lymphocyte attenuator (BTLA) negatively regulates the immune response. In this study, we investigated whether BTLA activation could be exploited to inhibit the development of abnormal immune responses in BD patients. BTLA expression in PBMCs and CD4(+) T cells was significantly decreased in active BD patients. Decreased BTLA level was associated with increased Th17 and Th1 responses. Activation of BTLA inhibited the abnormal Th17 and Th1 responses and IL-22 expression in both patients and controls. Addition of an agonistic anti-BTLA antibody remarkably inhibited DC-induced Th17 and Th1 cell responses, resulted in decreased production of the Th17 and Th1-related cytokines IL-1beta, IL-6, IL-23 and IL-12p70 and reduced CD40 expression in DCs. In conclusion, decreased BTLA expression in ocular BD may lead to inappropriate control of the Th17 and Th1 immune responses and DC functions. Therefore, BTLA may be involved in the development and recurrence of this disease. Agonistic agents of BTLA may represent a potential therapeutic approach for the treatment of BD and other inflammatory diseases mediated by abnormal Th17 and Th1 immune responses.

LDLR expression and localization are altered in mouse and human cell culture models of Alzheimer's disease.

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Jose F Abisambra

Full Text Available BACKGROUND: Alzheimer's disease (AD is a chronic neurodegenerative disorder and the most common form of dementia. The major molecular risk factor for late-onset AD is expression of the epsilon-4 allele of apolipoprotein E (apoE, the major cholesterol transporter in the brain. The low-density lipoprotein receptor (LDLR has the highest affinity for apoE and plays an important role in brain cholesterol metabolism. METHODOLOGY/PRINCIPAL FINDINGS: Using RT-PCR and western blotting techniques we found that over-expression of APP caused increases in both LDLR mRNA and protein levels in APP transfected H4 neuroglioma cells compared to H4 controls. Furthermore, immunohistochemical experiments showed aberrant localization of LDLR in H4-APP neuroglioma cells, Abeta-treated primary neurons, and in the PSAPP transgenic mouse model of AD. Finally, immunofluorescent staining of LDLR and of gamma- and alpha-tubulin showed a change in LDLR localization preferentially away from the plasma membrane that was paralleled by and likely the result of a disruption of the microtubule-organizing center and associated microtubule network. CONCLUSIONS/SIGNIFICANCE: These data suggest that increased APP expression and Abeta exposure alters microtubule function, leading to reduced transport of LDLR to the plasma membrane. Consequent deleterious effects on apoE uptake and function will have implications for AD pathogenesis and/or progression.

High RAB25 expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma

International Nuclear Information System (INIS)

Téllez-Gabriel, Marta; Arroyo-Solera, Irene; León, Xavier; Gallardo, Alberto; López, Montserrat; Céspedes, Maria V; Casanova, Isolda; López-Pousa, Antonio; Quer, Miquel; Mangues, Maria A; Barnadas, Agustí; Mangues, Ramón; Pavón, Miguel A

2013-01-01

Currently there are no molecular markers able to predict clinical outcome in locally advanced head and neck squamous cell carcinoma (HNSCC). In a previous microarray study, RAB25 was identified as a potential prognostic marker. The aim of this study was to analyze the association between RAB25 expression and clinical outcome in patients with locally advanced HNSCC treated with standard therapy. In a retrospective immunohistochemical study (n = 97), we observed that RAB25-negative tumors had lower survival (log-rank, P = 0.01) than patients bearing positive tumors. In an independent prospective mRNA study (n = 117), low RAB25 mRNA expression was associated with poor prognosis. Using classification and regression tree analysis (CART) we established two groups of patients according to their RAB25 mRNA level and their risk of death. Low mRNA level was associated with poor local recurrence-free (log-rank, P = 0.005), progression-free (log-rank, P = 0.002) and cancer-specific (log-rank, P < 0.001) survival. Multivariate Cox model analysis showed that low expression of RAB25 was an independent poor prognostic factor for survival (hazard ratio: 3.84, 95% confidence interval: 1.93–7.62, P < 0.001). Patients whose tumors showed high RAB25 expression had a low probability of death after treatment. We also found lower RAB25 expression in tumors than in normal tissue (Mann–Whitney U, P < 0.001). Moreover, overexpression of RAB25 in the UM-SCC-74B HNSCC cell line increased cisplatin sensitivity, and reduced cell migration and invasion. Our findings support a tumor suppressor role for RAB25 in HNSCC and its potential use to identify locally advanced patients with a high probability of survival after genotoxic treatment

Abnormal splicing switch of DMD's penultimate exon compromises muscle fibre maintenance in myotonic dystrophy.

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Rau, Frédérique; Lainé, Jeanne; Ramanoudjame, Laetitita; Ferry, Arnaud; Arandel, Ludovic; Delalande, Olivier; Jollet, Arnaud; Dingli, Florent; Lee, Kuang-Yung; Peccate, Cécile; Lorain, Stéphanie; Kabashi, Edor; Athanasopoulos, Takis; Koo, Taeyoung; Loew, Damarys; Swanson, Maurice S; Le Rumeur, Elisabeth; Dickson, George; Allamand, Valérie; Marie, Joëlle; Furling, Denis

2015-05-28

Myotonic Dystrophy type 1 (DM1) is a dominant neuromuscular disease caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors resulting in alternative splicing misregulation and muscular dysfunction. Here we show that the abnormal splicing of DMD exon 78 found in dystrophic muscles of DM1 patients is due to the functional loss of MBNL1 and leads to the re-expression of an embryonic dystrophin in place of the adult isoform. Forced expression of embryonic dystrophin in zebrafish using an exon-skipping approach severely impairs the mobility and muscle architecture. Moreover, reproducing Dmd exon 78 missplicing switch in mice induces muscle fibre remodelling and ultrastructural abnormalities including ringed fibres, sarcoplasmic masses or Z-band disorganization, which are characteristic features of dystrophic DM1 skeletal muscles. Thus, we propose that splicing misregulation of DMD exon 78 compromises muscle fibre maintenance and contributes to the progressive dystrophic process in DM1.

Meclozine facilitates proliferation and differentiation of chondrocytes by attenuating abnormally activated FGFR3 signaling in achondroplasia.

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Masaki Matsushita

Full Text Available Achondroplasia (ACH is one of the most common skeletal dysplasias with short stature caused by gain-of-function mutations in FGFR3 encoding the fibroblast growth factor receptor 3. We used the drug repositioning strategy to identify an FDA-approved drug that suppresses abnormally activated FGFR3 signaling in ACH. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, facilitates chondrocyte proliferation and mitigates loss of extracellular matrix in FGF2-treated rat chondrosarcoma (RCS cells. Meclozine also ameliorated abnormally suppressed proliferation of human chondrosarcoma (HCS-2/8 cells that were infected with lentivirus expressing constitutively active mutants of FGFR3-K650E causing thanatophoric dysplasia, FGFR3-K650M causing SADDAN, and FGFR3-G380R causing ACH. Similarly, meclozine alleviated abnormally suppressed differentiation of ATDC5 chondrogenic cells expressing FGFR3-K650E and -G380R in micromass culture. We also confirmed that meclozine alleviates FGF2-mediated longitudinal growth inhibition of embryonic tibia in bone explant culture. Interestingly, meclozine enhanced growth of embryonic tibia in explant culture even in the absence of FGF2 treatment. Analyses of intracellular FGFR3 signaling disclosed that meclozine downregulates phosphorylation of ERK but not of MEK in FGF2-treated RCS cells. Similarly, meclozine enhanced proliferation of RCS cells expressing constitutively active mutants of MEK and RAF but not of ERK, which suggests that meclozine downregulates the FGFR3 signaling by possibly attenuating ERK phosphorylation. We used the C-natriuretic peptide (CNP as a potent inhibitor of the FGFR3 signaling throughout our experiments, and found that meclozine was as efficient as CNP in attenuating the abnormal FGFR3 signaling. We propose that meclozine is a potential therapeutic agent for treating ACH and other FGFR3-related skeletal dysplasias.

Meclozine Facilitates Proliferation and Differentiation of Chondrocytes by Attenuating Abnormally Activated FGFR3 Signaling in Achondroplasia

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Matsushita, Masaki; Kitoh, Hiroshi; Ohkawara, Bisei; Mishima, Kenichi; Kaneko, Hiroshi; Ito, Mikako; Masuda, Akio; Ishiguro, Naoki; Ohno, Kinji

2013-01-01

Achondroplasia (ACH) is one of the most common skeletal dysplasias with short stature caused by gain-of-function mutations in FGFR3 encoding the fibroblast growth factor receptor 3. We used the drug repositioning strategy to identify an FDA-approved drug that suppresses abnormally activated FGFR3 signaling in ACH. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, facilitates chondrocyte proliferation and mitigates loss of extracellular matrix in FGF2-treated rat chondrosarcoma (RCS) cells. Meclozine also ameliorated abnormally suppressed proliferation of human chondrosarcoma (HCS-2/8) cells that were infected with lentivirus expressing constitutively active mutants of FGFR3-K650E causing thanatophoric dysplasia, FGFR3-K650M causing SADDAN, and FGFR3-G380R causing ACH. Similarly, meclozine alleviated abnormally suppressed differentiation of ATDC5 chondrogenic cells expressing FGFR3-K650E and -G380R in micromass culture. We also confirmed that meclozine alleviates FGF2-mediated longitudinal growth inhibition of embryonic tibia in bone explant culture. Interestingly, meclozine enhanced growth of embryonic tibia in explant culture even in the absence of FGF2 treatment. Analyses of intracellular FGFR3 signaling disclosed that meclozine downregulates phosphorylation of ERK but not of MEK in FGF2-treated RCS cells. Similarly, meclozine enhanced proliferation of RCS cells expressing constitutively active mutants of MEK and RAF but not of ERK, which suggests that meclozine downregulates the FGFR3 signaling by possibly attenuating ERK phosphorylation. We used the C-natriuretic peptide (CNP) as a potent inhibitor of the FGFR3 signaling throughout our experiments, and found that meclozine was as efficient as CNP in attenuating the abnormal FGFR3 signaling. We propose that meclozine is a potential therapeutic agent for treating ACH and other FGFR3-related skeletal dysplasias. PMID:24324705

Normal and abnormal growth plate

International Nuclear Information System (INIS)

Kumar, R.; Madewell, J.E.; Swischuk, L.E.

1987-01-01

Skeletal growth is a dynamic process. A knowledge of the structure and function of the normal growth plate is essential in order to understand the pathophysiology of abnormal skeletal growth in various diseases. In this well-illustrated article, the authors provide a radiographic classification of abnormal growth plates and discuss mechanisms that lead to growth plate abnormalities

GFI1B mutation causes a bleeding disorder with abnormal platelet function.

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Stevenson, W S; Morel-Kopp, M-C; Chen, Q; Liang, H P; Bromhead, C J; Wright, S; Turakulov, R; Ng, A P; Roberts, A W; Bahlo, M; Ward, C M

2013-11-01

GFI1B is a transcription factor important for erythropoiesis and megakaryocyte development but previously unknown to be associated with human disease. A family with a novel bleeding disorder was identified and characterized. Genetic linkage analysis and massively parallel sequencing were used to localize the mutation causing the disease phenotype on chromosome 9. Functional studies were then performed in megakaryocytic cell lines to determine the biological effects of the mutant transcript. We have identified a family with an autosomal dominant bleeding disorder associated with macrothrombocytopenia, red cell anisopoikilocytosis, and platelet dysfunction. The severity of bleeding is variable with some affected individuals experiencing spontaneous bleeding while other family members exhibit only abnormal bleeding with surgery. A single nucleotide insertion was identified in GFI1B that predicts a frameshift mutation in the fifth zinc finger DNA-binding domain. This mutation alters the transcriptional activity of the protein, resulting in a reduction in platelet α-granule content and aberrant expression of key platelet proteins. GFI1B mutation represents a novel human bleeding disorder, and the described phenotype identifies GFI1B as a critical regulator of platelet shape, number, and function. © 2013 International Society on Thrombosis and Haemostasis.

Photoreactivation of developmental abnormality in sea urchin embryos induced by UV-irradiated sperm

International Nuclear Information System (INIS)

Ejima, Yosuke; Shiroya, Tuguo.

1980-01-01

The effects of UV-irradiation of sperm on the embryonic development of sea urchins (H. pulcherrimus, Anthocidaris crassispina, Pseudocentrotus depressus, and C. japonicus) were studied. Eggs inseminated with UV-irradiated sperm developed almost normally into blastulae without arrest of cleavage or hatching, even though they showed some division delay. Morphogenesis was disturbed in and after the gastrula stage, and the formation of normal pluteus larvae was inhibited depending on the UV dose (5 - 30 J/m 2 ) given to the sperm. Morphological abnormalities observed were as follows: inhibition of gastrulation; abnormal delamination and random arrangement of primary mesenchymal cells onto the ectodermal wall; abnormal localization or an excess number of spicules; malformed skeletons. These developmental abnormalities were photoreactivated with high efficiency. Inhibition of pluteus formation to less than 5% by the UV-irradiation with 20 J/m 2 completely recovered under fluorescent light illumination with 10 klux. By treating the eggs with brief illumination at various times after insemination, a stage-dependent change of the photoreactivation (PR) efficiency was found. PR treatment after the insemination up to the onset of the first DNA synthesizing phase was highly effective for the recovery, while the PR efficiency began to decrease during the S phase, becoming zero on and after the end of the phase. In eggs fertilized with UV-irradiated sperm, mitoses were abnormal and shromosomal bridges were formed at the anaphase of the first mitosis. Their frequency increased depending on the UV dose. The mitotic abnormality was also photoreactivated with visible light treatment after fertilization. The change in PR efficiency of the illumination was very similar to that of morphological abnormality. (Author)

Abnormal neuronal migration: radiologic-clinic study

International Nuclear Information System (INIS)

Martinez Fernandez, M.; Menor Serrano, F.; Bordon Ferre, F.; Garcia Tena, J.; Esteban Hernandez, E.; Sanguesa Nebot, C.; Marti Bonnati, L.

1994-01-01

We present our experience in 18 pediatric patients with abnormal neuronal migration. Seven cases of heterotopia of the gray matter, 7 agyria-pachygyria complexes, 1 case of polymicrogyria, 2 cases of schizencephaly and 1 case of hemimegalencephaly were diagnosed by means of ultrasonography, computed tomography and magnetic resonance. The clinical picture was reviewed in each case, with special attention to the occurrence of convulsions, psycho motor development and visual changes. In general, the greater the morphological change, the greater the neurological involvement in these patients. However, the two cases of schizencephaly presented mild clinical expression. Magnetic resonance increases the diagnostic yield in neuronal migration disorders. Nevertheless, either ultrasonography or, especially, computed tomography is useful as a first diagnostic approach in these malformative disorders. (Author)

Aquaporin-11 (AQP11 Expression in the Mouse Brain

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Shin Koike

2016-06-01

Full Text Available Aquaporin-11 (AQP11 is an intracellular aquaporin expressed in various tissues, including brain tissues in mammals. While AQP11-deficient mice have developed fatal polycystic kidneys at one month old, the role of AQP11 in the brain was not well appreciated. In this study, we examined the AQP11 expression in the mouse brain and the brain phenotype of AQP11-deficient mice. AQP11 messenger ribonucleic acid (mRNA and protein were expressed in the brain, but much less than in the thymus and kidney. Immunostaining showed that AQP11 was localized at the epithelium of the choroid plexus and at the endothelium of the brain capillary, suggesting that AQP11 may be involved in water transport at the choroid plexus and blood-brain barrier (BBB in the brain. The expression of AQP4, another brain AQP expressed at the BBB, was decreased by half in AQP11-deficient mice, thereby suggesting the presence of the interaction between AQP11 and AQP4. The brain of AQP11-deficient mice, however, did not show any morphological abnormalities and the function of the BBB was intact. Our findings provide a novel insight into a water transport mechanism mediated by AQPs in the brain, which may lead to a new therapy for brain edema.

Expression and localization of p-glycoprotein, multidrug resistance protein 4, and breast cancer resistance protein in the female lower genital tract of human and pigtailed macaque.

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Zhou, Tian; Hu, Minlu; Pearlman, Andrew; Patton, Dorothy; Rohan, Lisa

2014-11-01

Antiretroviral drug absorption and disposition in cervicovaginal tissue is important for the effectiveness of vaginally or orally administered drug products in preexposure prophylaxis (PrEP) of HIV-1 sexual transmission to women. Therefore, it is imperative to understand critical determinants of cervicovaginal tissue pharmacokinetics. This study aimed to examine the mRNA expression and protein localization of three efflux transporters, P-glycoprotein (P-gp), multidrug resistance-associated protein 4 (MRP4), and breast cancer resistance protein (BCRP), in the lower genital tract of premenopausal women and pigtailed macaques. Along the human lower genital tract, the three transporters were moderately to highly expressed compared to colorectal tissue and liver, as revealed by real-time reverse transcriptase polymerase chain reaction (RT-PCR). In a given genital tract segment, the transporter with the highest expression level was either BCRP or P-gp, while MRP4 was always expressed at the lowest level among the three transporters tested. The immunohistochemical staining showed that P-gp and MRP4 were localized in multiple cell types including epithelial cells and vascular endothelial cells. BCRP was predominantly localized in the vascular endothelial cells. Differences in transporter mRNA level and localization were observed among endocervix, ectocervix, and vagina. Compared to human tissues, the macaque cervicovaginal tissues displayed comparable expression and localization patterns of the three transporters, although subtle differences were observed between the two species. The role of these cervicovaginal transporters in drug absorption and disposition warrants further studies. The resemblance between human and pigtailed macaque in transporter expression and localization suggests the utility of the macaque model in the studies of human cervicovaginal transporters.

Molecular cloning, expression analysis and transcript localization of testicular orphan nuclear receptor 2 in the male catfish, Clarias batrachus.

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Murugananthkumar, R; Akhila, M V; Rajakumar, A; Mamta, S K; Sudhakumari, C C; Senthilkumaran, B

2016-12-01

Testicular receptor 2 (TR2; also known as Nr2c1) is one of the first orphan nuclear receptors identified and known to regulate various physiological process with or without any ligand. In this study, we report the cloning of full length nr2c1 and its expression analysis during gonadal development, seasonal testicular cycle and after human chorionic gonadotropin (hCG) induction. In addition, in situ hybridization (ISH) was performed to localize nr2c1 transcripts in adult testis and whole catfish (1day post hatch). Tissue distribution and gonadal ontogeny studies revealed high expression of nr2c1 in developing and adult testis. Early embryonic stage-wise expression of nr2c1 seems to emphasize its importance in cellular differentiation and development. Substantial expression of nr2c1 during pre-spawning phase and localization of nr2c1 transcripts in sperm/spermatids were observed. Significant upregulation after hCG induction indicate that nr2c1 is under the regulation of gonadotropins. Whole mount ISH analysis displayed nr2c1 expression in notochord indicating its role in normal vertebrate development. Taken together, our findings suggest that nr2c1 may have a plausible role in the testicular and embryonic development of catfish. Copyright © 2015. Published by Elsevier Inc.

The murine ufo receptor: molecular cloning, chromosomal localization and in situ expression analysis.

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Faust, M; Ebensperger, C; Schulz, A S; Schleithoff, L; Hameister, H; Bartram, C R; Janssen, J W

1992-07-01

We have cloned the mouse homologue of the ufo oncogene. It encodes a novel tyrosine kinase receptor characterized by a unique extracellular domain containing two immunoglobulin-like and two fibronectin type III repeats. Comparison of the predicted ufo amino acid sequences of mouse and man revealed an overall identity of 87.6%. The ufo locus maps to mouse chromosome 7A3-B1 and thereby extends the known conserved linkage group between mouse chromosome 7 and human chromosome 19. RNA in situ hybridization analysis established the onset of specific ufo expression in the late embryogenesis at day 12.5 post coitum (p.c.) and localized ufo transcription to distinct substructures of a broad spectrum of developing tissues (e.g. subepidermal cells of the skin, mesenchymal cells of the periosteum). In adult animals ufo is expressed in cells forming organ capsules as well as in connective tissue structures. ufo may function as a signal transducer between specific cell types of mesodermal origin.

Expression and Localization of Brain-Derived Neurotrophic Factor (BDNF) mRNA and Protein in Human Submandibular Gland

International Nuclear Information System (INIS)

Saruta, Juri; Fujino, Kazuhiro; To, Masahiro; Tsukinoki, Keiichi

2012-01-01

Brain-derived neurotrophic factor (BDNF) promotes cell survival and differentiation in the central and peripheral nervous systems. Previously, we reported that BDNF is produced by salivary glands under acute immobilization stress in rats. However, expression of BDNF is poorly understood in humans, although salivary gland localization of BDNF in rodents has been demonstrated. In the present study, we investigated the expression and localization of BDNF in the human submandibular gland (HSG) using reverse transcription-polymerase chain reaction, western blot analysis, in situ hybridization (ISH), immunohistochemistry (IHC), and ELISA. BDNF was consistently localized in HSG serous and ductal cells, as detected by ISH and IHC, with reactivity being stronger in serous cells. In addition, immunoreactivity for BDNF was observed in the saliva matrix of ductal cavities. Western blotting detected one significant immunoreactive 14 kDa band in the HSG and saliva. Immunoreactivities for salivary BDNF measured by ELISA in humans were 40.76±4.83 pg/mL and 52.64±8.42 pg/mL, in men and women, respectively. Although salivary BDNF concentrations in females tended to be higher than in males, the concentrations were not significantly different. In conclusion, human salivary BDNF may originate from salivary glands, as the HSG appears to produce BDNF

Cloning, localization and expression analysis of vacuolar sugar transporters in the CAM plant Ananas comosus (pineapple).

Science.gov (United States)

Antony, Edna; Taybi, Tahar; Courbot, Mikaël; Mugford, Sam T; Smith, J Andrew C; Borland, Anne M

2008-01-01

In photosynthetic tissues of the CAM plant pineapple (Ananas comosus), storage of soluble sugars in the central vacuole during the daytime and their remobilization at night is required to provide carbon skeletons for nocturnal CO(2) fixation. However, soluble sugars produced photosynthetically must also be exported to support growth processes in heterotrophic tissues. To begin to address how vacuolar sugar storage and assimilate partitioning are regulated in A. comosus, degenerate PCR and cDNA library screening were used to clone three candidate sugar transporters from the leaves of this species. Subcellular localization of the three transporters was investigated via expression of YFP-fusion proteins in tobacco epidermal cells and their co-localization with subcellular markers by confocal microscopy. Using this strategy, a putative hexose transporter (AcMST1) and a putative inositol transporter (AcINT1) were identified that both localized to the tonoplast, whereas a putative sucrose transporter (AcSUT1) was found to localize to prevacuolar compartments. A cDNA (AcMST2) with high similarity to a recently characterized tonoplast hexose transporter in Arabidopsis was also identified from an A. comosus fruit EST database. Analyses of transcript abundance indicated that AcMST1 was more highly expressed in fruits compared to leaves of A. comosus, whilst transcripts of AcINT1, AcSUT1, and AcMST2 were more abundant in leaves. Transcript abundance of AcINT1, the putative inositol transporter, showed day-night changes comparable to those of other CAM-related transcripts described in Mesembryanthemum crystallinum. The results are discussed in terms of the role of vacuolar sugar transporters in regulating carbon flow during the diel cycle in CAM plants.

Thrombin impairs human endometrial endothelial angiogenesis; implications for progestin-only contraceptive-induced abnormal uterine bleeding.

Science.gov (United States)

Shapiro, John P; Guzeloglu-Kayisli, Ozlem; Kayisli, Umit A; Semerci, Nihan; Huang, S Joseph; Arlier, Sefa; Larsen, Kellie; Fadda, Paolo; Schatz, Frederick; Lockwood, Charles J

2017-06-01

Progestin-only contraceptives induce abnormal uterine bleeding, accompanied by prothrombin leakage from dilated endometrial microvessels and increased thrombin generation by human endometrial stromal cell (HESC)-expressed tissue factor. Initial studies of the thrombin-treated HESC secretome identified elevated levels of cleaved chondroitin sulfate proteoglycan 4 (CSPG4), impairing pericyte-endothelial interactions. Thus, we investigated direct and CSPG4-mediated effects of thrombin in eliciting abnormal uterine bleeding by disrupting endometrial angiogenesis. Liquid chromatography/tandem mass spectrometry, enzyme-linked immunosorbent assay (ELISA) and quantitative real-time-polymerase chain reaction (PCR) evaluated conditioned medium supernatant and cell lysates from control versus thrombin-treated HESCs. Pre- and post-Depo medroxyprogesterone acetate (DMPA)-administered endometria were immunostained for CSPG4. Proliferation, apoptosis and tube formation were assessed in human endometrial endothelial cells (HEECs) incubated with recombinant human (rh)-CSPG4 or thrombin or both. Thrombin induced CSPG4 protein expression in cultured HESCs as detected by mass spectrometry and ELISA (pabnormal uterine bleeding in DMPA users. Mass spectrometry analysis identified several HESC-secreted proteins regulated by thrombin. Therapeutic agents blocking angiogenic effects of thrombin in HESCs can prevent or minimize progestin-only contraceptive-induced abnormal uterine bleeding. Copyright © 2017. Published by Elsevier Inc.

Progestins Upregulate FKBP51 Expression in Human Endometrial Stromal Cells to Induce Functional Progesterone and Glucocorticoid Withdrawal: Implications for Contraceptive- Associated Abnormal Uterine Bleeding.

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Ozlem Guzeloglu Kayisli

Full Text Available Use of long-acting progestin only contraceptives (LAPCs offers a discrete and highly effective family planning method. Abnormal uterine bleeding (AUB is the major side effect of, and cause for, discontinuation of LAPCs. The endometria of LAPC-treated women display abnormally enlarged, fragile blood vessels, decreased endometrial blood flow and oxidative stress. To understanding to mechanisms underlying AUB, we propose to identify LAPC-modulated unique gene cluster(s in human endometrial stromal cells (HESCs. Protein and RNA isolated from cultured HESCs treated 7 days with estradiol (E2 or E2+ medroxyprogesterone acetate (MPA or E2+ etonogestrel (ETO or E2+ progesterone (P4 were analyzed by quantitative Real-time (q-PCR and immunoblotting. HSCORES were determined for immunostained-paired endometria of pre-and 3 months post-Depot MPA (DMPA treated women and ovariectomized guinea pigs (GPs treated with placebo or E2 or MPA or E2+MPA for 21 days. In HESCs, whole genome analysis identified a 67 gene group regulated by all three progestins, whereas a 235 gene group was regulated by E2+ETO and E2+MPA, but not E2+P4. Ingenuity pathway analysis identified glucocorticoid receptor (GR activation as one of upstream regulators of the 235 MPA and ETO-specific genes. Among these, microarray results demonstrated significant enhancement of FKBP51, a repressor of PR/GR transcriptional activity, by both MPA and ETO. q-PCR and immunoblot analysis confirmed the microarray results. In endometria of post-DMPA versus pre-DMPA administered women, FKBP51 expression was significantly increased in endometrial stromal and glandular cells. In GPs, E2+MPA or MPA significantly increased FKBP51 immunoreactivity in endometrial stromal and glandular cells versus placebo- and E2-administered groups. MPA or ETO administration activates GR signaling and increases endometrial FKBP51 expression, which could be one of the mechanisms causing AUB by inhibiting PR and GR

Progestins Upregulate FKBP51 Expression in Human Endometrial Stromal Cells to Induce Functional Progesterone and Glucocorticoid Withdrawal: Implications for Contraceptive- Associated Abnormal Uterine Bleeding.

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Guzeloglu Kayisli, Ozlem; Kayisli, Umit A; Basar, Murat; Semerci, Nihan; Schatz, Frederick; Lockwood, Charles J

2015-01-01

Use of long-acting progestin only contraceptives (LAPCs) offers a discrete and highly effective family planning method. Abnormal uterine bleeding (AUB) is the major side effect of, and cause for, discontinuation of LAPCs. The endometria of LAPC-treated women display abnormally enlarged, fragile blood vessels, decreased endometrial blood flow and oxidative stress. To understanding to mechanisms underlying AUB, we propose to identify LAPC-modulated unique gene cluster(s) in human endometrial stromal cells (HESCs). Protein and RNA isolated from cultured HESCs treated 7 days with estradiol (E2) or E2+ medroxyprogesterone acetate (MPA) or E2+ etonogestrel (ETO) or E2+ progesterone (P4) were analyzed by quantitative Real-time (q)-PCR and immunoblotting. HSCORES were determined for immunostained-paired endometria of pre-and 3 months post-Depot MPA (DMPA) treated women and ovariectomized guinea pigs (GPs) treated with placebo or E2 or MPA or E2+MPA for 21 days. In HESCs, whole genome analysis identified a 67 gene group regulated by all three progestins, whereas a 235 gene group was regulated by E2+ETO and E2+MPA, but not E2+P4. Ingenuity pathway analysis identified glucocorticoid receptor (GR) activation as one of upstream regulators of the 235 MPA and ETO-specific genes. Among these, microarray results demonstrated significant enhancement of FKBP51, a repressor of PR/GR transcriptional activity, by both MPA and ETO. q-PCR and immunoblot analysis confirmed the microarray results. In endometria of post-DMPA versus pre-DMPA administered women, FKBP51 expression was significantly increased in endometrial stromal and glandular cells. In GPs, E2+MPA or MPA significantly increased FKBP51 immunoreactivity in endometrial stromal and glandular cells versus placebo- and E2-administered groups. MPA or ETO administration activates GR signaling and increases endometrial FKBP51 expression, which could be one of the mechanisms causing AUB by inhibiting PR and GR-mediated transcription

Periostin in Mature Stage Localized Scleroderma.

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Kim, Min-Woo; Park, Jung Tae; Kim, Jung Ho; Koh, Seong-Joon; Yoon, Hyun-Sun; Cho, Soyun; Park, Hyun-Sun

2017-06-01

Periostin is a novel matricellular protein expressed in many tissues, including bone, periodontal ligament, and skin. Although its expression is prominent in various fibrotic conditions, studies of periostin in localized scleroderma are rare. To investigate the expression of periostin and other molecules in localized scleroderma. A retrospective study of 14 patients with confirmed mature stage localized scleroderma was undertaken. Fourteen age-matched and biopsy site-matched subjects with normal skin were included as controls. Collagen fiber deposition, periostin, procollagen, transforming growth factor-β, and matrix metalloproteinase (MMP)-1 expression were assessed and compared between the two groups. Co-localization of α-smooth muscle actin and periostin was evaluated using confocal microscopy. Periostin was predominantly expressed along the dermo-epidermal junction in the controls. Conversely, patients with localized scleroderma demonstrated increased collagen fiber deposition and periostin expression that was more widely distributed along the entire dermis. MMP-1 staining showed increased expression in the epidermis and dermis of patients compared to scanty expression in the controls. A semi-quantitative evaluation showed a higher proportion of excessive collagen bundle deposition (57.1% vs. 7.1%, p =0.013), diffuse periostin positivity (42.9% vs. 0%, p =0.016), and moderate MMP-1 positivity (71.4% vs. 7.1%, p =0.001) in patients than in the controls. Compared to the controls, patients with localized scleroderma had enhanced periostin expression corresponding to increased collagen fiber deposition and unexpected overexpression of MMP-1. The results of this human in vivo study may implicate the pathogenesis of localized scleroderma.

Abnormal labyrinthine zone in the Hectd1-null placenta.

Science.gov (United States)

Sarkar, Anjali A; Sabatino, Julia A; Sugrue, Kelsey F; Zohn, Irene E

2016-02-01

The labyrinthine zone of the placenta is where exchange of nutrients and waste occurs between maternal and fetal circulations. Proper development of the placental labyrinth is essential for successful growth of the developing fetus and abnormalities in placental development are associated with intrauterine growth restriction (IUGR), preeclampsia and fetal demise. Our previous studies demonstrate that Hectd1 is essential for development of the junctional and labyrinthine zones of the placenta. Here we further characterize labyrinthine zone defects in the Hectd1 mutant placenta. The structure of the mutant placenta was compared to wildtype littermates using histological methods. The expression of cell type specific markers was examined by immunohistochemistry and in situ hybridization. Hectd1 is expressed in the labyrinthine zone throughout development and the protein is enriched in syncytiotrophoblast layer type I cells (SynT-I) and Sinusoidal Trophoblast Giant cells (S-TGCs) in the mature placenta. Mutation of Hectd1 results in pale placentas with frequent hemorrhages along with gross abnormalities in the structure of the labyrinthine zone including a smaller overall volume and a poorly elaborated fetal vasculature that contain fewer fetal blood cells. Examination of molecular markers of labyrinthine trophoblast cell types reveals increased Dlx3 positive cells and Syna positive SynT-I cells, along with decreased Hand1 and Ctsq positive sinusoidal trophoblast giant cells (S-TGCs). Together these defects indicate that Hectd1 is required for development of the labyrinthine zonethe mouse placenta. Copyright © 2015 Elsevier Ltd. All rights reserved.

Abnormal nuclear envelopes in the striatum and motor deficits in DYT11 myoclonus-dystonia mouse models.

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Yokoi, Fumiaki; Dang, Mai T; Zhou, Tong; Li, Yuqing

2012-02-15

DYT11 myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonic symptoms and caused by mutations in paternally expressed SGCE, which codes for ε-sarcoglycan. Paternally inherited Sgce heterozygous knock-out (KO) mice exhibit motor deficits and spontaneous myoclonus. Abnormal nuclear envelopes have been reported in cellular and mouse models of early-onset DYT1 generalized torsion dystonia; however, the relationship between the abnormal nuclear envelopes and motor symptoms are not clear. Furthermore, it is not known whether abnormal nuclear envelope exists in non-DYT1 dystonia. In the present study, abnormal nuclear envelopes in the striatal medium spiny neurons (MSNs) were found in Sgce KO mice. To analyze whether the loss of ε-sarcoglycan in the striatum alone causes abnormal nuclear envelopes, motor deficits or myoclonus, we produced paternally inherited striatum-specific Sgce conditional KO (Sgce sKO) mice and analyzed their phenotypes. Sgce sKO mice exhibited motor deficits in both beam-walking and accelerated rotarod tests, while they did not exhibit abnormal nuclear envelopes, alteration in locomotion, or myoclonus. The results suggest that the loss of ε-sarcoglycan in the striatum contributes to motor deficits, while it alone does not produce abnormal nuclear envelopes or myoclonus. Development of therapies targeting the striatum to compensate for the loss of ε-sarcoglycan function may rescue the motor deficits in DYT11 M-D patients.

Defining Abnormally Low Tenders

DEFF Research Database (Denmark)

Ølykke, Grith Skovgaard; Nyström, Johan

2017-01-01

The concept of an abnormally low tender is not defined in EU public procurement law. This article takes an interdisciplinary law and economics approach to examine a dataset consisting of Swedish and Danish judgments and verdicts concerning the concept of an abnormally low tender. The purpose...

Expression and localization of nerve growth factor (NGF in the testis of alpaca (llama pacos

Directory of Open Access Journals (Sweden)

Haidong Wang

2011-04-01

Full Text Available During alpaca testis development and spermatogenesis, nerve growth factor (NGF may play an importantrole. The main aim of this study was to determine the expression and localization of NGF in the alpacatestis, and to discuss the important role of NGF in alpaca reproductive characteristics. Immunohistochemicalstaining technique and real-time PCR were used. The expression of NGF in the same cells one-month old(newborn alpacas 12-month, and 24-month old alpacas showed significant differences (p 0.05; NGF at different cell stages showed nosignificant differences (p > 0.05. It suggests that NGF may be involved in the regulation of spermatogenesis,which provides direct evidence for NGF action in the alpaca testis during postnatal development and spermatogenesis.

Biological activity evaluation of cloned and expressed caprine growth hormone from local Pakistani goat breed beetal

International Nuclear Information System (INIS)

Butt, H.I.; Shahzad, M.I.; Bashir, Q.

2011-01-01

Growth hormone cDNA of local goat breed-beetal was amplified by RT PCR and gene including leader sequence was cloned in pTZR57 cloning vector. The cGH-pTZR57 clone was confirmed by restriction digestion and sequence analyses before finally sub-cloning the gene in pND- a mammalian expression vector. The clones were again confirmed by restriction digestion and PCR analyses. Highly purified, supercoiled cGH-pND construct was used to transfect Vero cell lines for expression studies. The in vitro expression of cGH was checked by dot-ELISA technique. After confirming its in vitro cell line based expression, the construct was injected to 4 weeks old balb/c mice intramuscularly. Two animals were euthanized per week till four weeks to monitor the in vivo biological activity by evaluating the tibia epiphyseal width and body weight gain assays. Significant increase in tibia epiphyseal width and gain in body weight was observed from vaccinated animals. The study supports the concept that DNA based therapeutics are an efficient and cost effective method for gene delivery and in vivo transgene expressions. (author)

Acquired Localized Cutis Laxa due to Increased Elastin Turnover

DEFF Research Database (Denmark)

Nygaard, Rie Harboe; Maynard, Scott; Schjerling, Peter

2016-01-01

Cutis laxa is a rare disease characterized by abnormal skin wrinkling and laxity, due to decreased elastin synthesis or structural extracellular matrix defects. We have explored elastin metabolism in a case of adult onset cutis laxa localized to the upper body of a woman. For this purpose, we...... obtained skin biopsies from affected and unaffected skin areas of the patient and analyzed these with microscopy, polymerase chain reaction, western blotting and cell culture experiments. Skin from the affected area lacked elastin fibers in electron microscopy but had higher mRNA expression of elastin...... and total RNA. Levels of an apparent tropoelastin degradation product were higher in the affected area. Fibroblast cultures from the affected area were able to produce elastin and showed higher proliferation and survival after oxidative and UVB stress compared to fibroblasts from the unaffected area...

MR imaging of abnormal synovial processes

International Nuclear Information System (INIS)

Quinn, S.F.; Sanchez, R.; Murray, W.T.; Silbiger, M.L.; Ogden, J.; Cochran, C.

1987-01-01

MR imaging can directly image abnormal synovium. The authors reviewed over 50 cases with abnormal synovial processes. The abnormalities include Baker cysts, semimembranous bursitis, chronic shoulder bursitis, peroneal tendon ganglion cyst, periarticular abscesses, thickened synovium from rheumatoid and septic arthritis, and synovial hypertrophy secondary to Legg-Calve-Perthes disease. MR imaging has proved invaluable in identifying abnormal synovium, defining the extent and, to a limited degree, characterizing its makeup

Significance of localization of nonpalpable breast lesions

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Oh, Ki Keun; Choi, Hyun Ju [Yongdong Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

1990-12-15

As mammography has become more popular for the evaluation of breast symptoms and for the screening of asymptomatic women, the smaller lesions are being detected before they become palpable, therefore preoperative localization became necessary. This has led to the development of several methods for preoperative localization of nonpalpable lesions. Authors analyzed 50 cases with preoperative localization in 45 patients which had abnormal findings on film mammogram or ultrasonomammogram since October 1985 through March 1990 at Yongdong Severance Hospital, College of Medicine, Yonsei University. The results were as follows: 1. Techniques of localization were spot method in 8 cases, conventional needle localization method in 38 cases and Kopan's needle localization method in 4 cases. 2. The most common mammographic indication for localization was focal calcifications in 29 cases(58%), which was followed by a newly developed mass in 25 cases(50%). 3. Outcome of pathologically confirmed diagnosis put into benign lesions in 37 cases(74%) and malignant lesions in 13 cases(26%). 4. Among the cases with localization of lesions which has suggested as benign lesions in film and ultrasonomammogram,all cases(100%) were confirmed in benign lesions pathologically. Among the cases with localization of lesions which has suggested as malignant lesions in film and ultrasonomammogram, pathologic malignant has been proved of 44% and possible histopathologic precursor of malignant was resulted in 25% such as atypical hyperplasia and adenosis. Conclusively, authors consider that the abnormal areas should be removed in their entirety with the sacrifice of minimum volume of contiguous normal breast tissue through the preoperative localization, hence our preoperative localization has contributed favorable prognosis based on material lesions in early stage breast cancer.

Significance of localization of nonpalpable breast lesions

International Nuclear Information System (INIS)

Oh, Ki Keun; Choi, Hyun Ju

1990-01-01

As mammography has become more popular for the evaluation of breast symptoms and for the screening of asymptomatic women, the smaller lesions are being detected before they become palpable, therefore preoperative localization became necessary. This has led to the development of several methods for preoperative localization of nonpalpable lesions. Authors analyzed 50 cases with preoperative localization in 45 patients which had abnormal findings on film mammogram or ultrasonomammogram since October 1985 through March 1990 at Yongdong Severance Hospital, College of Medicine, Yonsei University. The results were as follows: 1. Techniques of localization were spot method in 8 cases, conventional needle localization method in 38 cases and Kopan's needle localization method in 4 cases. 2. The most common mammographic indication for localization was focal calcifications in 29 cases(58%), which was followed by a newly developed mass in 25 cases(50%). 3. Outcome of pathologically confirmed diagnosis put into benign lesions in 37 cases(74%) and malignant lesions in 13 cases(26%). 4. Among the cases with localization of lesions which has suggested as benign lesions in film and ultrasonomammogram,all cases(100%) were confirmed in benign lesions pathologically. Among the cases with localization of lesions which has suggested as malignant lesions in film and ultrasonomammogram, pathologic malignant has been proved of 44% and possible histopathologic precursor of malignant was resulted in 25% such as atypical hyperplasia and adenosis. Conclusively, authors consider that the abnormal areas should be removed in their entirety with the sacrifice of minimum volume of contiguous normal breast tissue through the preoperative localization, hence our preoperative localization has contributed favorable prognosis based on material lesions in early stage breast cancer

Characterization of a baculovirus nuclear localization signal domain in the late expression factor 3 protein

International Nuclear Information System (INIS)

Au, Victoria; Yu Mei; Carstens, Eric B.

2009-01-01

The baculovirus Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) single-stranded DNA binding protein LEF-3 is a multi-functional protein that is required to transport the helicase protein P143 into the nucleus of infected cells where they function to replicate viral DNA. The N-terminal 56 amino acid region of LEF-3 is required for nuclear transport. In this report, we analyzed the effect of site-specific mutagenesis of LEF-3 on its intracellular distribution. Fluorescence microscopy of expression plasmid-transfected cells demonstrated that the residues 28 to 32 formed the core nuclear localization signal, but other adjacent positively-charged residues augmented these sequences. Comparison with other group I Alphabaculoviruses suggested that this core region functionally duplicated residues including 18 and 19. This was demonstrated by the loss of nuclear localization when the equivalent residues (18 to 20) in Choristoneura fumiferana nucleopolyhedrovirus (CfMNPV) LEF-3 were mutated. The AcMNPV LEF-3 nuclear localization domain was also shown to drive nuclear transport in mammalian cells indicating that the protein nuclear import systems in insect and mammalian cells are conserved. We also demonstrated by mutagenesis that two conserved cysteine residues located at 82 and 106 were not essential for nuclear localization or for interaction with P143. However, by using a modified construct of P143 that localized on its own to the nucleus, we demonstrated that a functional nuclear localization domain on LEF-3 was required for interaction between LEF-3 and P143

Xcat, a novel mouse model for Nance-Horan syndrome inhibits expression of the cytoplasmic-targeted Nhs1 isoform.

Science.gov (United States)

Huang, Kristen M; Wu, Junhua; Duncan, Melinda K; Moy, Chris; Dutra, Amalia; Favor, Jack; Da, Tong; Stambolian, Dwight

2006-01-15

Nance-Horan syndrome (NHS) is an X-linked disorder characterized by congenital cataracts, dental anomalies, dysmorphic features and mental retardation. A recent report suggests that the novel gene NHS1 is involved in this disorder due to the presence of point mutations in NHS patients. A possible mouse model for NHS, Xcat, was mapped to a 2.11 Mb interval on the X-chromosome. Sequence and FISH analysis of the X-chromosome region containing the Xcat mutation reveal a large insertion between exons 1 and 2 of the mouse Nhs1 gene. The insertion inhibits the expression of the Nhs1 isoform containing exon 1 and results in exclusive expression of the alternative isoform containing exon 1A. Quantitative RT-PCR of Xcat cDNA shows reduced levels of Nhs1 transcripts. The Nhs1 protein is strongly expressed within the cytoplasm of elongating lens fiber cells from wild-type neonate lens, but is significantly reduced within the Xcat lens. Transient transfection studies of CHO cells with Nhs1-GFP fusion proteins were done to determine whether the amino acids encoded by exon 1 were critical for protein localization. We found the presence of Nhs1 exon 1 critical for localization of the fusion protein to the cytoplasm, whereas fusion proteins lacking Nhs1 exon 1 are predominantly nuclear. These results indicate that the first exon of Nhs1 contains crucial information required for the proper expression and localization of Nhs1 protein. Inhibition of expression of the exon 1 containing isoform results in the abnormal phenotype of Xcat.

Clinical and imaging characteristics of localized megalencephaly: a retrospective comparison of diffuse hemimegalencephaly and multilobar cortical dysplasia

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Nakahashi, Masumi; Tsushima, Yoshito; Amanuma, Makoto; Endo, Keigo [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Sato, Noriko; Ota, Miho [National Center Hospital of Neurology and Psychiatry, Department of Radiology, Kodaira, Tokyo (Japan); Yagishita, Akira [Tokyo Metropolitan Neurological Hospital, Department of Neuroradiology, Kokubunji, Tokyo (Japan); Saito, Yoshiaki; Sugai, Kenji; Sasaki, Masayuki [National Center Hospital of Neurology and Psychiatry, Department of Child Neurology, Kodaira, Tokyo (Japan); Natsume, Jun [Nagoya University Graduate School of Medicine, Department of Pediatrics, Nagoya, Aichi (Japan)

2009-12-15

Hemimegalencephaly is a well-known congenital malformation. However, localized megalencephaly, which may be one of the subtypes of hemimegalencephaly, has not been separately investigated. In the present study, we attempted to characterize the clinical and magnetic resonance (MR) imaging features of localized megalencephaly in comparison with ordinary diffuse hemimegalencephaly and multilobar cortical dysplasia. MR findings for 43 patients with hemimegalencephaly and ten with multilobar cortical dysplasia, which is the differential diagnosis of localized megalencephaly, were retrospectively reviewed. Clinical findings such as the onset and severity of seizures and imaging findings including the affected area of the brain, structures outside of the hemisphere, and interval morphological changes were examined. Of the 43 patients, 11 showed signs of localized megalencephaly (25.6%). Localized megalencephaly was predominantly seen on the left side (72.7%) and had a tendency toward severe-grade seizures compared to multilobar cortical dysplasia. The frequencies of the extracerebral abnormalities in the diffuse hemimegalencephaly, localized megalencephaly, and multilobar cortical dysplasia groups were 84.4%, 36.4%, and 0.0%, respectively. There were three localized megalencephaly patients whose affected areas shrank and whose images were similar to those of multilobar cortical dysplasia. Localized megalencephaly accounts for one quarter of all hemimegalencephaly cases in this study. The incidence of extracerebral abnormalities in patients with localized hemimegalencephaly was almost half that of patients with diffuse hemimegalencephaly. Extracerebral abnormalities were absent in patients with multilobar cortical dysplasia. Associated extracerebral abnormalities may be a clue to differentiating localized megalencephaly from multilobar cortical dysplasia. (orig.)

Phenotype abnormality - Arabidopsis Phenome Database | LSDB Archive [Life Science Database Archive metadata

Lifescience Database Archive (English)

Full Text Available ion of ontology terms and properties. Phenotypes for morphology are standardized using Plant Ontology... (PO) or Trait Ontology (TO), with Phenotype Ontology (PATO). PATO is the vocabulary cov... tolerance can be expressed using Gene Ontology (GO), ChEBI etc. Some phenotypes are observed under some spe...h URL http://togodb.biosciencedbc.jp/togodb/view/cpp_abnormality#en Data acquisition method Plant Ontology, Phenotype Ontology

P-cadherin expression and survival rate in oral squamous cell carcinoma:an immunohistochemical study

Directory of Open Access Journals (Sweden)

Laino Gregorio

2005-06-01

Full Text Available Abstract Background P-cadherin (P-cad is a transmembrane molecule involved in the cell-cell adhesion and similar to E-cadherin (E-cad, but less investigated in oncology, especially in in vivo studies. Aims of the present study were to assess the prevalence of P-cad expression in oral squamous cell carcinoma (OSCC and to verify whether P-cad can be considered a marker of prognosis in patients with OSCC. Methods In a retrospective study, a cohort of 67 OSCC patients was investigated for P-cad expression and its cellular localization by immunohistochemistry; some respective healthy margins of resection were similarly investigated as standard controls. After grouping for P-cad expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G, TNM, Staging, and overall survival rate. Univariate and multivariate analyses were performed. Results 37 cases (55.2% of OSCC showed membranous/cytoplasmic positivity for P-cad, whereas 30 (44.8 % were negative. Although with some differences in membranous vs cytoplasmic localization of P-cad in OSCC with different G, no statistical association was found between P-cad expression and any variables considered at baseline. In terms of prognostic significance, P-cad non expression was found to have an independent association with poorer overall survival rate than P-cad expressing group (P = 0.056; moreover, among P-cad +ve patients the best prognosis was for those OSCC with membranous (P Conclusion On the basis of these results, it is possible to suggest P-cad as an early marker of poor prognosis. The abnormal or lack of P-cad expression could constitute an hallmark of aggressive biological behavior in OSCC

Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms

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Huang, Hegui; He, Zheng; Zhu, Chunyan; Liu, Lian; Kou, Hao; Shen, Lang [Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071 (China)

2015-10-01

Fetal adrenal developmental status is the major determinant of fetal tissue maturation and offspring growth. We have previously proposed that prenatal ethanol exposure (PEE) suppresses fetal adrenal corticosterone (CORT) synthesis. Here, we focused on PEE-induced adrenal developmental abnormalities of male offspring rats before and after birth, and aimed to explore its intrauterine programming mechanisms. A rat model of intrauterine growth retardation (IUGR) was established by PEE (4 g/kg·d). In PEE fetus, increased serum CORT concentration and decreased insulin-like growth factor 1 (IGF1) concentration, with lower bodyweight and structural abnormalities as well as a decreased Ki67 expression (proliferative marker), were observed in the male fetal adrenal cortex. Adrenal glucocorticoid (GC)-metabolic activation system was enhanced while gene expression of IGF1 signaling pathway with steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) was decreased. Furthermore, in the male adult offspring of PEE, serum CORT level was decreased but IGF1 was increased with partial catch-up growth, and Ki67 expression demonstrated no obvious change. Adrenal GC-metabolic activation system was inhibited, while IGF1 signaling pathway and 3β-HSD was enhanced with the steroidogenic factor 1 (SF1), and StAR was down-regulated in the adult adrenal. Based on these findings, we propose a “two-programming” mechanism for PEE-induced adrenal developmental toxicity: “the first programming” is a lower functional programming of adrenal steroidogenesis, and “the second programming” is GC-metabolic activation system-related GC-IGF1 axis programming. - Highlights: • Prenatal ethanol exposure induces adrenal developmental abnormality in offspring rats. • Prenatal ethanol exposure induces intrauterine programming of adrenal steroidogenesis. • Intrauterine GC-IGF1 axis programming might mediate adrenal developmental abnormality.

Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms

International Nuclear Information System (INIS)

Huang, Hegui; He, Zheng; Zhu, Chunyan; Liu, Lian; Kou, Hao; Shen, Lang; Wang, Hui

2015-01-01

Fetal adrenal developmental status is the major determinant of fetal tissue maturation and offspring growth. We have previously proposed that prenatal ethanol exposure (PEE) suppresses fetal adrenal corticosterone (CORT) synthesis. Here, we focused on PEE-induced adrenal developmental abnormalities of male offspring rats before and after birth, and aimed to explore its intrauterine programming mechanisms. A rat model of intrauterine growth retardation (IUGR) was established by PEE (4 g/kg·d). In PEE fetus, increased serum CORT concentration and decreased insulin-like growth factor 1 (IGF1) concentration, with lower bodyweight and structural abnormalities as well as a decreased Ki67 expression (proliferative marker), were observed in the male fetal adrenal cortex. Adrenal glucocorticoid (GC)-metabolic activation system was enhanced while gene expression of IGF1 signaling pathway with steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) was decreased. Furthermore, in the male adult offspring of PEE, serum CORT level was decreased but IGF1 was increased with partial catch-up growth, and Ki67 expression demonstrated no obvious change. Adrenal GC-metabolic activation system was inhibited, while IGF1 signaling pathway and 3β-HSD was enhanced with the steroidogenic factor 1 (SF1), and StAR was down-regulated in the adult adrenal. Based on these findings, we propose a “two-programming” mechanism for PEE-induced adrenal developmental toxicity: “the first programming” is a lower functional programming of adrenal steroidogenesis, and “the second programming” is GC-metabolic activation system-related GC-IGF1 axis programming. - Highlights: • Prenatal ethanol exposure induces adrenal developmental abnormality in offspring rats. • Prenatal ethanol exposure induces intrauterine programming of adrenal steroidogenesis. • Intrauterine GC-IGF1 axis programming might mediate adrenal developmental abnormality.

Study on localization diagnosis with SPECT rCBF image in childhood epilepsy: in comparison with EEG and MRI findings

International Nuclear Information System (INIS)

Wu Meiqian; Tang Jihong; Wu Jinchang; Shi Yizhen

1999-01-01

Objective: To evaluate the diagnostic value of SPECT rCBF imaging in localization of childhood epileptic foci. Methods: rCBF imaging was performed in 74 epileptic patients not in seizure and 10 epileptic patients right in seizure. EEG was performed in 84, MRI in 67 of the subjects mentioned above. All the results of three modalities were compared with each other. Results: The highest positive rate (82.14%) was found in SPECT rCBF imaging, the positive rate in EEG or MRI was 71.43 or 47.76%. The epileptic foci localized by EEG (60 abnormalities) and by MRI (32 abnormalities) were 70.59% or 58.82% in concordance with those by SPECT, respectively. Conclusions: SPECT rCBF imaging is a sensitive and effective method for epileptic foci localization. It may have some advantages over EEG and MRI in detecting and localizing epileptic foci. However, abnormal SPECT areas may cover some abnormalities which do not belong to epileptic category. A combination of these three methods (SPECT, EEG and MRI) will improve the positive rate and accuracy for localizing

Alterative Expression and Localization of Profilin 1/VASPpS157 and Cofilin 1/VASPpS239 Regulates Metastatic Growth and is Modified by DHA Supplementation

Science.gov (United States)

Ali, Mehboob; Heyob, Kathryn; Jacob, Naduparambil K.; Rogers, Lynette K.

2016-01-01

Profilin 1, cofilin 1, and vasodialator stimulated phosphoprotein (VASP) are actin binding proteins (ABP) which regulate actin remodelling and facilitate cancer cell metastases. MiR~17–92 is highly expressed in metastatic tumors and profilin1 and cofilin1 are predicted targets. Docosahexaenoic acid (DHA) inhibits cancer cell proliferation and adhesion. These studies tested the hypothesis that the metastatic phenotype is driven by changes in ABPs including alternative phosphorylation and/or changes in subcellular localization. Additionally, we tested the efficacy of DHA supplementation to attenuate or inhibit these changes. Human lung cancer tissue sections were analyzed for F-actin content and expression and cellular localization of profilin1, cofilin1 and VASP (S157 or S239 phosphorylation). The metastatic phenotype was investigated in A549 and MLE12 cells lines using 8 Br-cAMP as a metastasis inducer and DHA as a therapeutic agent. Migration was assessed by wound assay and expression measured by western blot and confocal analysis. MiR~17–92 expression was measured by qRT-PCR. Results indicated increased expression and altered cellular distribution of profilin1/VASPpS157 but no changes in cofilin1/VASPpS239 in the human malignant tissues compared to normal tissues. In A549 and MLE12 cells, the expression patterns of profilin1/VASPpS157 or cofilin1/VASPpS239 suggested an interaction in regulation of actin dynamics. Furthermore, DHA inhibited cancer cell migration and viability, ABP expression and cellular localization, and modulated expression of miR~17–92 in A549 cells with minimal effects in MLE12 cells. Further investigations are warranted to understand ABP interactions, changes in cellular localization, regulation by miR~17–92, and DHA as a novel therapeutic. PMID:27496138

Colonic epithelium is diffusely abnormal in ulcerative colitis and colorectal cancer.

OpenAIRE

Gibson, P; Rosella, O; Nov, R; Young, G

1995-01-01

The hypothesis that the colonic epithelium is diffusely abnormal in ulcerative colitis was examined by comparing disease related responses in expression of markers of differentiation by colonic crypt cells to culture with and without butyrate. Cells were isolated from patients with normal colon (15), cancer (24), ulcerative colitis (19), or Crohn's disease (16). Alkaline phosphatase activities were measured in cell homogenates and the rate of glycoprotein synthesis assessed at the end of 24 h...

Abnormality of thyroid function tests in geriatric population undergoing chronic dialysis

Directory of Open Access Journals (Sweden)

Mustafa Altay

2014-06-01

Conclusions: Elderly dialysis patients had higher thyroid function test abnormalities than controls. They had lower fT3 levels than controls such as young and middle age chronic dialysis patients. However, what does it mean for clinical process and how its clinical expression is not clearly known, especially in an elderly patients. Large, prospective, randomized and controlled trials are necessary for this topic. [J Contemp Med 2014; 4(2.000: 54-58

1α,25 dihydroxi-vitamin D3 modulates CDK4 and CDK6 expression and localization

International Nuclear Information System (INIS)

Irazoqui, Ana P.; Heim, Nadia B.; Boland, Ricardo L.; Buitrago, Claudia G.

2015-01-01

We recently reported that the vitamin D receptor (VDR) and p38 MAPK participate in pro-differentiation events triggered by 1α,25(OH) 2 -vitamin D 3 [1,25D] in skeletal muscle cells. Specifically, our studies demonstrated that 1,25D promotes G0/G1 arrest of cells inducing cyclin D3 and cyclin dependent kinases inhibitors (CKIs) p21 Waf1/Cip1 and p27 Kip1 expression in a VDR and p38 MAPK dependent manner. In this work we present data indicating that cyclin-dependent kinases (CDKs) 4 and 6 also play a role in the mechanism by which 1,25D stimulates myogenesis. To investigate VDR involvement in hormone regulation of CDKs 4 and 6, we significantly reduced its expression by the use of a shRNA against mouse VDR, generating the skeletal muscle cell line C2C12-VDR. Investigation of changes in cellular cycle regulating proteins by immunoblotting showed that the VDR is involved in the 1,25D –induced CDKs 4 and 6 protein levels at 6 h of hormone treatment. CDK4 levels remains high during S phase peak and G0/G1 arrest while CDK6 expression decreases at 12 h and increases again al 24 h. The up-regulation of CDKs 4 and 6 by 1,25D (6 h) was abolished in C2C12 cells pre-treated with the ERK1/2 inhibitor, UO126. Moreover, CDKs 4 and 6 expression induced by the hormone nor was detected when α and β isoforms of p38 MAPK were inhibited by compound SB203580. Confocal images show that there is not co-localization between VDR and CDKs at 6 h of hormone treatment, however CDK4 and VDR co-localizates in nucleus after 12 h of 1,25D exposure. Of relevance, at this time 1,25D promotes CDK6 localization in a peri-nuclear ring. Our data demonstrate that the VDR, ERK1/2 and p38 MAPK are involved in the control of CDKs 4 and 6 by 1,25D in skeletal muscle cells sustaining the operation of a VDR and MAPKs –dependent mechanism in hormone modulation of myogenesis. - Highlights: • 1,25D modulates CDKs 4 and 6 expression in skeletal muscle cells. • CDK4 co-localizates with VDR after 1

Special report on abnormal climate in 2010

International Nuclear Information System (INIS)

2010-12-01

This reports on abnormal climate in 2010 with impact on the each field. It is comprised of four chapters, which deal with Introduction with purpose of publish and background, current situation and cause of abnormal climate in 2010 on abnormal climate around the world and Korea, Action and impact against abnormal climate in 2010 to agriculture, industry and energy, prevention of disasters, forest, fishery products, environment and health, Evaluation and policy proposal. It also has an appendix about occurrence and damage on abnormal climate of the world in 2010 and media reports on abnormal climate in Korea in 2010.

ABNORMAL UTERINE BLEEDING IN ADOLESCENTS — ENDOCRINE PROFILE CONDITION

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E. V. Sibirskaya

2014-01-01

Full Text Available Aim: The purpose of the study was to evaluate the endocrine profile condition in adolescent girls with abnormal uterine bleeding. Patients and methods: The participants of the study were 110 adolescent girls in the age between 11 and 15 years taken to hospital by emergency indication in the period between 2010–2013 years with dysfunctional uterine bleeding for the term from 3 to 48 days. In the first day of hospitalization before starting the hormonal therapy all patients underwent the physical examination, ultrasonic examination of pelvic organs and endocrine profile assessment. Concentration of follicle-stimulating hormone (FSH and luteinizing hormone (LH and the levels of mammotropic hormone, thyrotropic hormone, estradiol, progesterone and testosterone in their blood were determined. Besides that physicians assessed the complete blood count indices: hemoglobin concentration, erythrocyte number and hematocrits. Results: It was determined that the predisposing causes of abnormal uterine bleeding development in adolescents: high somatic pathology frequency, abnormalities of neuroendocrinal system and menstrual cycle. Gynecological pathology in adolescents is represented by significant disorders of menstrual function establishment expressed in the later beginning of menstruation, its intensity and duration. The authors also note the higher frequency of inflammatory diseases such as adnexitis, edeitis, vulvovaginitis and coleitis in comparison with the control group (37.3 and 30%, respectively. Another tendency was observed while studying the endocrine profile: in patients with hyperestrogenism the normal or increased content of FSH at the normal or lowered LH concentration is observed. At the same time, in patients with hypestrogenism FSH concentration at the lower limits of the age group is lowered, while LH concentration is lowered or normal. Conclusion: Abnormal uterine bleeding in adolescents in the most cases is developing in the setting

Dopamine in the Auditory Brainstem and Midbrain: Co-localization with Amino Acid Neurotransmitters and Gene Expression following Cochlear Trauma

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Avril Genene eHolt

2015-07-01

Full Text Available Dopamine (DA modulates the effects of amino acid neurotransmitters, including GABA and glutamate, in motor, visual, olfactory and reward systems (Hnasko et al., 2010; Stuber et al., 2010; Hnasko and Edwards, 2012. The results suggest that DA may play a similar modulatory role in the auditory pathways. Previous studies have shown that deafness results in decreased GABA release, changes in excitatory neurotransmitter levels, and increased spontaneous neuronal activity within brainstem regions related to auditory function. Modulation of the expression and localization of tyrosine hydroxylase (TH; the rate limiting enzyme in the production of DA in the IC following cochlear trauma has been previously reported (Tong et al., 2005. In the current study the possibility of co-localization of TH with amino acid neurotransmitters (AANs was examined. Changes in the gene expression of TH were compared with changes in the gene expression of markers for AANs in the cochlear nucleus (CN and IC to determine whether those deafness related changes occur concurrently. The results indicate that bilateral cochlear ablation significantly reduced TH gene expression in the CN after two months while in the IC the reduction in TH was observed at both three days and two months following ablation. Furthermore, in the CN, glycine transporter 2 (GlyT2 and the GABA transporter (GABAtp were also significantly reduced only after two months. However, in the IC, DA receptor 1 (DRDA1, vesicular glutamate transporters 2 and 3 (vGluT2, vGluT3, GABAtp and GAD67 were reduced in expression both at the three day and two month time points. A close relationship between the distribution of TH and several of the AANs was determined in both the CN and the IC. In addition, GlyT2 and vGluT3 each co-localized with TH within IC somata and dendrites. Therefore, the results of the current study suggest that DA is spatially well positioned to influence the effects of AANs on auditory neurons.

Abnormal I-123 HIPDM images in various disease entities

International Nuclear Information System (INIS)

Shih, W.J.; Magoun, S.; Coupal, J.J.; Clark, D.B.; Dekosky, S.T.; Kung, H.F.; Beihn, R.; Ryo, U.Y.

1987-01-01

Eighty patients who were referred from neurology service for evaluation of stroke, Alzheimer disease (AD), and/or other neurologic diseases underwent the study. Four views of planar images were obtained following the intravenous injection of 3-5 mCi of I-123 HIPDM. SPECT images were then obtained using a camera interfaced to a PDP-11 computer. Forty of the 80 patients had scintigraphic findings of stroke, which correlated well with head CT/cerebral angiogram. Sixteen patients with AD had good correlation between the degree of temporoparietal abnormality in the images. Severe AD and severe stroke patients almost always had a positive planar image. Normal I-123 HIPDM localization in the brain requires intact cerebral flow and cerebral neuronal function. A focal area of decreased I-123 HIPDM localization may represent either interruption of blood flow or neurochemical dysfunction

Venous anomalies and abnormalities of the posterior fossa

International Nuclear Information System (INIS)

Goulao, A.; Alvarez, H.; Garcia Monaco, R.; Pruvost, P.; Lasjaunias, P.

1990-01-01

The authors report a series of 16 patients with venous anomalies or abnormalities of the posterior fossa studied by angiography, CT and/or MRI. We believe that so-called 'venous angioma' are extreme anatomic variants that drain normal territories, and we prefer to call them developmental venous anomalies (DVA). Posterior fossa DVA, like the supra-tentorial ones are classified according to their drainage into deep and superficial type. They are exclusively located in the cerebellum or tectum. In 4 cases DVA was an incidental finding, in 3 an associated cerebral venous malformation (CVM) was found and felt to be the cause of the symptoms and only in one (Trigeminal pain) was a link between both suspected. Cavernous venous malformation (CVM) were found in frequent association with DVA (27%). 4 cases were single and 2 multiple. 5 CVM were located in the brain stem and 3 in the cerebellum. The clinical and radiological files were reviewed and a direct relationship between symptoms and localization was found in all patients with CVM. In 2 cases venous dysplasia was found: 1 Sturge-Weber and 1 First branchial arch syndrome. Both posterior fossa venous abnormalities were incidental findings. (orig.)

Conditional estimation of local pooled dispersion parameter in small-sample RNA-Seq data improves differential expression test.

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Gim, Jungsoo; Won, Sungho; Park, Taesung

2016-10-01

High throughput sequencing technology in transcriptomics studies contribute to the understanding of gene regulation mechanism and its cellular function, but also increases a need for accurate statistical methods to assess quantitative differences between experiments. Many methods have been developed to account for the specifics of count data: non-normality, a dependence of the variance on the mean, and small sample size. Among them, the small number of samples in typical experiments is still a challenge. Here we present a method for differential analysis of count data, using conditional estimation of local pooled dispersion parameters. A comprehensive evaluation of our proposed method in the aspect of differential gene expression analysis using both simulated and real data sets shows that the proposed method is more powerful than other existing methods while controlling the false discovery rates. By introducing conditional estimation of local pooled dispersion parameters, we successfully overcome the limitation of small power and enable a powerful quantitative analysis focused on differential expression test with the small number of samples.

Refined localization of the Prieto-syndrome locus

Energy Technology Data Exchange (ETDEWEB)

Martinez, F.; Prieto, F. [Unidad de Genetica, Valencia (Spain); Gal, A. [Universitaets-Krankenhaus Eppendorf, Hamburg (Germany)

1996-07-12

PRS designates the locus for a syndromal form of X-linked mental retardation (Prieto syndrome) characterized by minor facial anomalies, ear malformation, abnormal growth of teeth, clinodactyly, sacral dimple, patellar luxation, malformation of lower limbs, abnormalities of the fundus of the eye, and subcortical cerebral atrophy. Linkage analysis localized the disease locus between DXS84 (Xp21.1) and DXS255. Here we present additional linkage data that provide further support and refinement of this localization. Individual III-18 gave birth to a male, currently aged 2 7/12 years, who clearly shows delayed psychomotor development. He began to walk at 23 months and his speech is delayed. In addition, he shows the characteristic facial anomalies, {open_quotes}dysplastic{close_quotes} ears, sacral dimple, and clinodactyly, as do all other affected males in this family. 7 refs., 1 tab.

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.

Abnormal nuclear envelopes in the striatum and motor deficits in DYT11 myoclonus-dystonia mouse models

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Yokoi, Fumiaki; Dang, Mai T.; Zhou, Tong; Li, Yuqing

2012-01-01

DYT11 myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonic symptoms and caused by mutations in paternally expressed SGCE, which codes for ɛ-sarcoglycan. Paternally inherited Sgce heterozygous knock-out (KO) mice exhibit motor deficits and spontaneous myoclonus. Abnormal nuclear envelopes have been reported in cellular and mouse models of early-onset DYT1 generalized torsion dystonia; however, the relationship between the abnormal nuclear envelopes and motor symptoms are not clear. Furthermore, it is not known whether abnormal nuclear envelope exists in non-DYT1 dystonia. In the present study, abnormal nuclear envelopes in the striatal medium spiny neurons (MSNs) were found in Sgce KO mice. To analyze whether the loss of ɛ-sarcoglycan in the striatum alone causes abnormal nuclear envelopes, motor deficits or myoclonus, we produced paternally inherited striatum-specific Sgce conditional KO (Sgce sKO) mice and analyzed their phenotypes. Sgce sKO mice exhibited motor deficits in both beam-walking and accelerated rotarod tests, while they did not exhibit abnormal nuclear envelopes, alteration in locomotion, or myoclonus. The results suggest that the loss of ɛ-sarcoglycan in the striatum contributes to motor deficits, while it alone does not produce abnormal nuclear envelopes or myoclonus. Development of therapies targeting the striatum to compensate for the loss of ɛ-sarcoglycan function may rescue the motor deficits in DYT11 M-D patients. PMID:22080833

Expression, purification, characterization and subcellular localization of the goose parvovirus rep1 protein.

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Chen, Zongyan; Li, Chuanfeng; Peng, Gaojing; Liu, Guangqing

2013-07-01

The goose parvovirus (GPV) Rep1 protein is both essential for viral replication and a potential target for GPV diagnosis, but its protein characterization and intracellular localization is not clear. We constructed a recombinant plasmid, pET28a/GPV-Rep1, and expressed the Rep1 gene in BL21 (DE3) Escherichia coli. A protein approximately 75 kDa in size was obtained from lysates of E. coli cells expressing the recombinant plasmid. SDS-PAGE analysis showed that after induction with 0.6 mM isopropyl β-D-thiogalactosidase (IPTG) at 30°C for 5 h, the Rep1 protein was highly overexpressed. Two methods used to purify proteins, a salinity-gradient elution and Ni-NTA affinity chromatography, were performed. The amount of Rep1 protein obtained by Ni-NTA affinity chromatography was 41.23 mg, while 119.9 mg of Rep1 protein was obtained by a salinity-gradient elution from a 1 L E. coli BL21 (DE3) culture. An immunogenicity analysis showed that the protein could significantly elicit a specific antibody response in immunized goslings compared to control groups. Antibody titers peaked to 1:5120 (optical density (OD) 450 = 3.9) on day 28 after immunization but had mean titers of 1:10,240 (OD450 = 4.2) in gosling groups immunized with a commercially available GPV-attenuated vaccine strain. Experiments examining subcellular localization showed that the Rep1 protein appeared to associate predominantly with the nuclear membrane, especially during later times of infection. This work provides a basis for biochemical and structural studies on the GPV Rep1 protein.

Nuclear Medicine Methods for Evaluation of Abnormal Parathyroid Glands in Patients with Primary and Secondary Hyperparathyroidism

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Botushanova Albena D.

2017-12-01

Full Text Available Considered rare disease in the past, primary hyperparathyroidism (PHPT has dramatically increased in incidence over the past thirty years with the introduction of routine calcium measurements; it is now approximately 42 per 100 000 persons. By far, the most common lesion found in patients with PHPT is the solitary parathyroid adenoma, occurring in 85%-90% of patients, while in the rest 10%- 15% primary hyperplasia of the parathyroid glands is present. Currently, the most widely used surgical approach is minimally invasive parathyroidectomy which is associated with less post-surgery complications and shorter operation time. To be successful this procedure needs to rely on a precise preoperative localization of the abnormal parathyroid glands, hence preoperative parathyroid imaging gained so large importance. The rationale for locating abnormal parathyroid tissue prior to surgery is that the glands can be notoriously unpredictable in their location. There is a general consensus that the best imaging procedure identifying abnormal parathyroid glands is the preoperative scintigraphy with 99mTc-sestamibi or 99mTc-tetrofosmin. It is characterized with high sensitivity and specificity exceeding those of ultrasound, CT or MRI. Combining scintigraphy with the other imaging techniques increases the precision for topic localization.

Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition

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Zhu Zhu

2016-01-01

Full Text Available Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice by altering exposure to light. C57 BL/6J mice (C57 mice and ApoE-KO mice (ApoE-KO mice exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1 levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

Reduced caveolin-1 promotes hyper-inflammation due to abnormal heme oxygenase-1 localizationin LPS challenged macrophages with dysfunctional CFTR

Science.gov (United States)

Zhang, Ping-Xia; Murray, Thomas S.; Villella, Valeria Rachela; Ferrari, Eleonora; Esposito, Speranza; D'Souza, Anthony; Raia, Valeria; Maiuri, Luigi; Krause, Diane S.; Egan, Marie E.; Bruscia, Emanuela M.

2013-01-01

We have previously reported that TLR4 signaling is increased in lipopolysaccharide (LPS) -stimulated Cystic Fibrosis (CF) macrophages (MΦs), contributing to the robust production of pro-inflammatory cytokines. The heme oxygenase (HO-1)/carbon monoxide (CO) pathway modulates cellular redox status, inflammatory responses, and cell survival. The HO-1 enzyme, together with the scaffold protein caveolin 1 (CAV-1), also acts as a negative regulator of TLR4 signaling in MΦs. Here, we demonstrate that in LPS-challenged CF MΦs, HO-1 does not compartmentalize normally to the cell surface and instead accumulates intracellularly. The abnormal HO-1 localization in CF MΦs in response to LPS is due to decreased CAV-1 expression, which is controlled by the cellular oxidative state, and is required for HO-1 delivery to the cell surface. Overexpression of HO-1 or stimulating the pathway with CO-releasing molecules (CORM2)enhancesCAV-1 expression in CF MΦs, suggesting a positive-feed forward loop between HO-1/CO induction and CAV-1 expression. These manipulations reestablished HO-1 and CAV-1 cell surface localization in CF MΦ's. Consistent with restoration of HO-1/CAV-1 negative regulation of TLR4 signaling, genetic or pharmacological (CORM2)-induced enhancement of this pathway decreased the inflammatory response of CF MΦs and CF mice treated with LPS. In conclusion, our results demonstrate that the counter-regulatory HO-1/CO pathway, which is critical in balancing and limiting the inflammatory response, is defective in CF MΦs through a CAV-1-dependent mechanism, exacerbating the CF MΦ's response to LPS. This pathway could be a potential target for therapeutic intervention for CF lung disease. PMID:23606537

An artificial vector model for generating abnormal electrocardiographic rhythms

International Nuclear Information System (INIS)

Clifford, Gari D; Nemati, Shamim; Sameni, Reza

2010-01-01

We present generalizations of our previously published artificial models for generating multi-channel ECG to provide simulations of abnormal cardiac rhythms. Using a three-dimensional vectorcardiogram (VCG) formulation, we generate the normal cardiac dipole for a patient using a sum of Gaussian kernels, fitted to real VCG recordings. Abnormal beats are specified either as perturbations to the normal dipole or as new dipole trajectories. Switching between normal and abnormal beat types is achieved using a first-order Markov chain. Probability transitions can be learned from real data or modeled by coupling to heart rate and sympathovagal balance. Natural morphology changes from beat-to-beat are incorporated by varying the angular frequency of the dipole as a function of the inter-beat (RR) interval. The RR interval time series is generated using our previously described model whereby time- and frequency-domain heart rate (HR) and heart rate variability characteristics can be specified. QT-HR hysteresis is simulated by coupling the Gaussian kernels associated with the T-wave in the model with a nonlinear factor related to the local HR (determined from the last n RR intervals). Morphology changes due to respiration are simulated by introducing a rotation matrix couple to the respiratory frequency. We demonstrate an example of the use of this model by simulating HR-dependent T-wave alternans (TWA) with and without phase-switching due to ectopy. Application of our model also reveals previously unreported effects of common TWA estimation methods

Report on abnormal climate in 2011

International Nuclear Information System (INIS)

2011-12-01

This paper reports of impact on abnormal climate in 2011. It has Introduction with purpose and background of publish and summary of this report. The cause and current state on abnormal climate of the world and Korea in 2011, Measurement and impact against abnormal climate in 2011 to agriculture, land and maritime, industry and energy, prevention of disasters, environment and health, assessment and advice on the policy. It lists the appendix about occurrence and damage on abnormal climate of the world and Korea in 2011 and media report data.

Pregnancy Complications: Umbilical Cord Abnormalities

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... Umbilical cord abnormalities Umbilical cord abnormalities Now playing: E-mail to a friend Please fill in all fields. ... blood supply) to the baby. The two arteries transport waste from the baby to the placenta (where ...

Spectrum of endocrine abnormalities associated with acanthosis nigricans.

Science.gov (United States)

Matsuoka, L Y; Wortsman, J; Gavin, J R; Goldman, J

1987-10-01

Acanthosis nigricans is a marker for disorders of insulin action, endocrine abnormalities, and cancer of internal organs. To evaluate the clinical significance of this marker the systemic alterations and clinical features of 26 patients with acanthosis nigricans seen at two institutions were reviewed. Most subjects affected by acanthosis nigricans were female (20 patients), Caucasian (22 patients), in the third decade of life (13 patients), and overweight (24 patients greater than 120 percent ideal body weight). Gonadal disease, present in 17 patients, was expressed as polycystic ovary syndrome (11 cases), disorders of prolactin secretion (two cases, one with polycystic ovary syndrome), streak gonads (one case), and hypogonadism of the male (four cases). Thyroid disease and tinea versicolor were present in four patients each. Three patients were receiving insulin therapy for diabetes mellitus, and in two additional patients diabetes mellitus was detected during the diagnostic workup. All patients had elevated fasting insulin levels; most of them also had an exaggerated insulin response to a glucose load. Two of 18 patients tested had antibodies against the insulin receptor in the circulation. Skin biopsy of acanthosis nigricans lesions from all 26 patients showed a typical pattern of hyperkeratosis, acanthosis, and epidermal papillomatosis. Colloidal iron staining showed glycosaminoglycan infiltration of the papillary dermis (21 of 21 cases), consisting mainly of hyaluronic acid. It is concluded that: (1) hyperinsulinenemia and local dermal glycosaminoglycan deposition are regular features in acanthosis nigricans and (2) patients with acanthosis nigricans should be screened for diabetes mellitus, gonadal disease, and hypothyroidism.

Environmental obesogen tributyltin chloride leads to abnormal hypothalamic-pituitary-gonadal axis function by disruption in kisspeptin/leptin signaling in female rats.

Science.gov (United States)

Sena, Gabriela C; Freitas-Lima, Leandro C; Merlo, Eduardo; Podratz, Priscila L; de Araújo, Julia F P; Brandão, Poliane A A; Carneiro, Maria T W D; Zicker, Marina C; Ferreira, Adaliene V M; Takiya, Christina M; de Lemos Barbosa, Carolina M; Morales, Marcelo M; Santos-Silva, Ana Paula; Miranda-Alves, Leandro; Silva, Ian V; Graceli, Jones B

2017-03-15

Tributyltin chloride (TBT) is a xenobiotic used as a biocide in antifouling paints that has been demonstrated to induce endocrine-disrupting effects, such as obesity and reproductive abnormalities. An integrative metabolic control in the hypothalamus-pituitary-gonadal (HPG) axis was exerted by leptin. However, studies that have investigated the obesogenic TBT effects on the HPG axis are especially rare. We investigated whether metabolic disorders as a result of TBT are correlated with abnormal hypothalamus-pituitary-gonadal (HPG) axis function, as well as kisspeptin (Kiss) action. Female Wistar rats were administered vehicle and TBT (100ng/kg/day) for 15days via gavage. We analyzed their effects on the tin serum and ovary accumulation (as biomarker of TBT exposure), estrous cyclicity, surge LH levels, GnRH expression, Kiss action, fertility, testosterone levels, ovarian apoptosis, uterine inflammation, fibrosis, estrogen negative feedback, body weight gain, insulin, leptin, adiponectin levels, as well as the glucose tolerance (GTT) and insulin sensitivity tests (IST). TBT led to increased serum and ovary tin levels, irregular estrous cyclicity, and decreased surge LH levels, GnRH expression and Kiss responsiveness. A strong negative correlation between the serum and ovary tin levels with lower Kiss responsiveness and GnRH mRNA expression was observed in TBT rats. An increase in the testosterone levels, ovarian and uterine fibrosis, ovarian apoptosis, and uterine inflammation and a decrease in fertility and estrogen negative feedback were demonstrated in the TBT rats. We also identified an increase in the body weight gain and abnormal GTT and IST tests, which were associated with hyperinsulinemia, hyperleptinemia and hypoadiponectinemia, in the TBT rats. TBT disrupted proper functioning of the HPG axis as a result of abnormal Kiss action. The metabolic dysfunctions co-occur with the HPG axis abnormalities. Hyperleptinemia as a result of obesity induced by TBT may be

Esophagogastric junction outflow obstruction is often associated with coexistent abnormal esophageal body motility and abnormal bolus transit.

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Zheng, E; Gideon, R M; Sloan, J; Katz, P O

2017-10-01

Currently, the diagnosis of esophageal motility disorders is in part based upon a hierarchical algorithm in which abnormalities of the esophagogastric junction (EGJ) is prioritized. An important metric in evaluating the EGJ is the integrated relaxation pressure (IRP). Patients who do not have achalasia but are found to have an elevated IRP are diagnosed with EGJ outflow obstruction. It has been our observation that a subset of these patients also has a second named motility disorder and may also have abnormal bolus transit. The aim of this study is to determine the frequency of abnormal body motility and or abnormal bolus movement in patients with EGJ outflow obstruction. Further, in an effort to evaluate the potential clinical value in measuring bolus transit as a complement to esophageal manometry, specifically in patients with EGJ outflow obstruction, we analyzed the presenting symptoms of these patients. A total of 807 patients with a mean age of 53 years completed esophageal function testing with impedance monitoring and high-resolution manometry between January 2012 and October 2016. There were 74 patients with achalasia who were excluded from the study. Of the remaining 733 patients, 138 (19%) had an elevated IRP and were given a diagnosis of EGJ outflow obstruction. Among these patients, 56 (40%) were diagnosed with an abnormal motility pattern to liquids (ineffective esophageal motility = 28, distal esophageal spasm = 19, Jackhammer = 6), of which 44 (76%) had abnormal bolus transit to liquids, viscous, or both. In contrast, there were 82 patients with EGJ outflow obstruction and normal esophageal motility, of which 33 (40%) had abnormal bolus transit. Patients with preserved esophageal motility and EGJ outflow obstruction were then evaluated. Of the 733 patients, 299 (40%) had intact esophageal motility. Of the 299 patients with normal esophageal motility, 56 patients had an elevated IRP, of which 16 (28%) had abnormal bolus transit. There were 243 (33

Abnormal neural precursor cell regulation in the early postnatal Fragile X mouse hippocampus.

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Sourial, Mary; Doering, Laurie C

2017-07-01

The regulation of neural precursor cells (NPCs) is indispensable for a properly functioning brain. Abnormalities in NPC proliferation, differentiation, survival, or integration have been linked to various neurological diseases including Fragile X syndrome. Yet, no studies have examined NPCs from the early postnatal Fragile X mouse hippocampus despite the importance of this developmental time point, which marks the highest expression level of FMRP, the protein missing in Fragile X, in the rodent hippocampus and is when hippocampal NPCs have migrated to the dentate gyrus (DG) to give rise to lifelong neurogenesis. In this study, we examined NPCs from the early postnatal hippocampus and DG of Fragile X mice (Fmr1-KO). Immunocytochemistry on neurospheres showed increased Nestin expression and decreased Ki67 expression, which collectively indicated aberrant NPC biology. Intriguingly, flow cytometric analysis of the expression of the antigens CD15, CD24, CD133, GLAST, and PSA-NCAM showed a decreased proportion of neural stem cells (GLAST + CD15 + CD133 + ) and an increased proportion of neuroblasts (PSA-NCAM + CD15 + ) in the DG of P7 Fmr1-KO mice. This was mirrored by lower expression levels of Nestin and the mitotic marker phospho-histone H3 in vivo in the P9 hippocampus, as well as a decreased proportion of cells in the G 2 /M phases of the P7 DG. Thus, the absence of FMRP leads to fewer actively cycling NPCs, coinciding with a decrease in neural stem cells and an increase in neuroblasts. Together, these results show the importance of FMRP in the developing hippocampal formation and suggest abnormalities in cell cycle regulation in Fragile X. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Exercises to Improve Gait Abnormalities

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... Articles Directories Videos Resources Contact Exercises to Improve Gait Abnormalities Home » Article Categories » Exercise and Fitness Font Size: A A A A Exercises to Improve Gait Abnormalities Next Page The manner of how a ...

Report to Congress on abnormal occurrences

International Nuclear Information System (INIS)

1993-06-01

Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health and safety and requires a quarterly report of such events to be made to Congress. This report covers the period January through March 1993. There is one abnormal occurrence at a nuclear power plant disposed in this report that involved a steam generator tube rupture at Palo Verde Unit 2, and none for fuel cycle facilities. Three abnormal occurrences involving medical misadminstrations (two therapeutic and one diagnostic) at NRC-licensed facilities are also discussed in this report. No abnormal occurrences were reported by NRC's Agreement States. The report also contains information updating previously reported abnormal occurrences

Changes in Expression of Connexin 32, Bile Canaliculus-Like Structures, and Localization of Alkaline Phosphatase in Primary Cultures of Fetal Rat Hepatocytes

International Nuclear Information System (INIS)

Fukazawa, Shoko; Chida, Kohsuke; Taguchi, Meiko; Takeuchi, Akihiro; Ikeda, Noriaki

2013-01-01

We devised an experimental design in primary cultures of fetal rat hepatocytes for studying hepatocyte differentiation over a short period. In the present study, hepatocytes were first cultured for 3 days in dexamethasone-supplemented medium and then for an additional 3 days in dexamethasone- or epidermal growth factor-supplemented medium. In hepatocytes cultured continuously in dexamethasone-supplemented medium, the expression of connexin 32 increased and bile canaliculus-like structures and localization of alkaline phosphatase in the plasma membrane around bile canaliculus-like structures were maintained. Few cells incorporated bromodeoxyuridine. On the other hand, in most of the hepatocytes cultured in epidermal growth factor-supplemented medium, the expression of connexin 32 was minimally recognized, bile canaliculus-like structures were shortened or eliminated, and alkaline phosphatase was localized as numerous fine spots throughout the cytoplasm. More than 20% of all hepatocytes incorporated bromodeoxyuridine. The present study suggests that in hepatocytes, there is a close relationship among connexin 32 expression, the maintenance of bile canaliculus-like structures, and the localization of alkaline phosphatase to the plasma membrane around the bile canaliculus-like structures, and this indicates that the present experimental model is useful for studying hepatocyte differentiation over a short period

Search for Local Variations of Atmospheric H2O and CO on Mars with PFS/Mars Express

Science.gov (United States)

Lellouch, E.; Encrenaz, T.; Fouchet, T.; Billebaud, F.; Formisano, V.; Atreya, S.; Ignatiev, N.; Moroz, V.; Maturilli, A.; Grassi, D.; Pfs Team

Spectra recorded by the PFS instrument onboard Mars Express include clear spectral signatures due to CO at 4.7 and 2.3 micron, and H2O at 1.38, 2.6 and 30-50 micron. These features can be used to determine the horizontal distribution of these species on global and local scales and to monitor it with time. Here we investigate the local variations of H2O and CO, focussing on the regions of high-altitude volcanoes. Preliminary results suggest a significant decrease of the CO mixing ratio in these regions, as was found from ISM/Phobos observations (Rosenqvist et al. Icarus 98, 254, 1992).

Memetics clarification of abnormal behavior

Institute of Scientific and Technical Information of China (English)

无

2007-01-01

AIM: Biological medicine is hard to fully and scientifically explain the etiological factor and pathogenesis of abnormal behaviors; while, researches on philosophy and psychology (including memetics) are beneficial to better understand and explain etiological factor and pathogenesis of abnormal behaviors. At present, the theory of philosophy and psychology is to investigate the entity of abnormal behavior based on the views of memetics.METHODS: Abnormal behavior was researched in this study based on three aspects, including instinctive behavior disorder, poorly social-adapted behavior disorder and mental or body disease associated behavior disorder. Most main viewpoints of memetics were derived from "The Meme Machine", which was written by Susan Blackmore. When questions about abnormal behaviors induced by mental and psychological diseases and conduct disorder of teenagers were discussed, some researching achievements which were summarized by authors previously were added in this study, such as aggressive behaviors, pathologically aggressive behaviors, etc.RESULTS: The abnormal behaviors mainly referred to a part of people's substandard behaviors which were not according with the realistic social environment, culture background and the pathologic behaviors resulted from people's various psychological diseases. According to the theory of "meme", it demonstrated that the relevant behavioral obstacles of various psychological diseases, for example, the unusual behavior of schizophrenia, were caused, because the old meme was destroyed thoroughly but the new meme was unable to establish; psychoneurosis and personality disorder were resulted in hard establishment of meme; the behavioral obstacles which were ill-adapted to society, for example, various additional and homosexual behaviors, were because of the selfish replications and imitations of "additional meme" and "homosexual meme"; various instinct behavioral and congenital intelligent obstacles were not significance

Eye Movement Abnormalities in Multiple Sclerosis: Pathogenesis, Modeling, and Treatment

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Alessandro Serra

2018-02-01

Full Text Available Multiple sclerosis (MS commonly causes eye movement abnormalities that may have a significant impact on patients’ disability. Inflammatory demyelinating lesions, especially occurring in the posterior fossa, result in a wide range of disorders, spanning from acquired pendular nystagmus (APN to internuclear ophthalmoplegia (INO, among the most common. As the control of eye movements is well understood in terms of anatomical substrate and underlying physiological network, studying ocular motor abnormalities in MS provides a unique opportunity to gain insights into mechanisms of disease. Quantitative measurement and modeling of eye movement disorders, such as INO, may lead to a better understanding of common symptoms encountered in MS, such as Uhthoff’s phenomenon and fatigue. In turn, the pathophysiology of a range of eye movement abnormalities, such as APN, has been clarified based on correlation of experimental model with lesion localization by neuroimaging in MS. Eye movement disorders have the potential of being utilized as structural and functional biomarkers of early cognitive deficit, and possibly help in assessing disease status and progression, and to serve as platform and functional outcome to test novel therapeutic agents for MS. Knowledge of neuropharmacology applied to eye movement dysfunction has guided testing and use of a number of pharmacological agents to treat some eye movement disorders found in MS, such as APN and other forms of central nystagmus.

Transvaginal sonography in abnormal uterine bleeding and correlation to hysteroscopy

International Nuclear Information System (INIS)

Saeed, S.; Shah, S.; Ali, H.; Khan, S.; Ehsan, N.; Ahmed, S.Z.

2017-01-01

To correlate results of Transvaginal sonography with those of hysteroscopy and biopsy in abnormal uterine bleeding to estimate the accuracy and analytical values of non-invasive transvaginal sonography in abnormal uterine bleeding. Methodology: This cross-sectional Study was carried out at BMCH, Quetta, Balochistan, Pakistan from March 2013 to February 2014 and included 200 patients of abnormal uterine bleeding. Exclusion criteria were pregnancy, virginity, local bleeding of perineal or vaginal origin. Hysteroscopy and biopsy and Transvaginal Ultrasound (TVS) were performed in all. Result: The most common type of bleeding was found to be menorrhagia in 39% while the least common type was postmenopausal bleeding in 9%. Mean endometrial thickness was 11.64 mm and it was noted that at less than 14mm thickness no serious pathology was found. Sensitivity of TVS for endometrial hyperplasia was found to be 66.66% while specificity was 100%. Positive analytical value was 100% while negative value was 100%. Overall sensitivity calculated for TVS was 94.44%, specificity 98.55%, PPV was 81.93% and NPV 98.55%. Conclusion: Sensitivity and specificity of TVS were lower than hysteroscopy and biopsy but the difference was not significant. TVS can be used as first line investigation while hysteroscopy and biopsy may be left for cases of high risk or in those cases where some positive findings could be found on TVS. (author)

Neurologic abnormalities in murderers.

Science.gov (United States)

Blake, P Y; Pincus, J H; Buckner, C

1995-09-01

Thirty-one individuals awaiting trial or sentencing for murder or undergoing an appeal process requested a neurologic examination through legal counsel. We attempted in each instance to obtain EEG, MRI or CT, and neuropsychological testing. Neurologic examination revealed evidence of "frontal" dysfunction in 20 (64.5%). There were symptoms or some other evidence of temporal lobe abnormality in nine (29%). We made a specific neurologic diagnosis in 20 individuals (64.5%), including borderline or full mental retardation (9) and cerebral palsy (2), among others. Neuropsychological testing revealed abnormalities in all subjects tested. There were EEG abnormalities in eight of the 20 subjects tested, consisting mainly of bilateral sharp waves with slowing. There were MRI or CT abnormalities in nine of the 19 subjects tested, consisting primarily of atrophy and white matter changes. Psychiatric diagnoses included paranoid schizophrenia (8), dissociative disorder (4), and depression (9). Virtually all subjects had paranoid ideas and misunderstood social situations. There was a documented history of profound, protracted physical abuse in 26 (83.8%) and of sexual abuse in 10 (32.3%). It is likely that prolonged, severe physical abuse, paranoia, and neurologic brain dysfunction interact to form the matrix of violent behavior.

TOLL-LIKE RECEPTORS (TLR 2 AND 4 EXPRESSION OF KERATINOCYTES FROM PATIENTS WITH LOCALIZED AND DISSEMINATED DERMATOPHYTOSIS

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Cristiane Beatriz de Oliveira

2015-02-01

Full Text Available There are few studies on the role of innate immune response in dermatophytosis. An investigation was conducted to define the involvement of Toll-Like Receptors (TLRs 2 and 4 in localized (LD and disseminated (DD dermatophytosis due to T. rubrum. Fifteen newly diagnosed patients, eight patients with LD and seven with DD, defined by involvement of at least three body segments were used in this study. Controls comprised twenty skin samples from healthy individuals undergoing plastic surgery. TLR2 and TLR4 were quantified in skin lesions by immunohistochemistry. A reduced expression of TLR4 in the lower and upper epidermis of both LD and DD patients was found compared to controls; TLR2 expression was preserved in the upper and lower epidermis of all three groups. As TLR4 signaling induces the production of inflammatory cytokines and neutrophils recruitment, its reduced expression likely contributed to the lack of resolution of the infection and the consequent chronic nature of the dermatophytosis. As TLR2 expression acts to limit the inflammatory process and preserves the epidermal structure, its preserved expression may also contribute to the persistent infection and limited inflammation that are characteristic of dermatophytic infections.

Modeling pulmonary fibrosis by abnormal expression of telomerase/apoptosis/collagen V in experimental usual interstitial pneumonia

International Nuclear Information System (INIS)

Parra, E.R.; Pincelli, M.S.; Teodoro, W.R.; Velosa, A.P.P.; Martins, V.; Rangel, M.P.; Barbas-Filho, J.V.; Capelozzi, V.L.

2014-01-01

Limitations on tissue proliferation capacity determined by telomerase/apoptosis balance have been implicated in pathogenesis of idiopathic pulmonary fibrosis. In addition, collagen V shows promise as an inductor of apoptosis. We evaluated the quantitative relationship between the telomerase/apoptosis index, collagen V synthesis, and epithelial/fibroblast replication in mice exposed to butylated hydroxytoluene (BHT) at high oxygen concentration. Two groups of mice were analyzed: 20 mice received BHT, and 10 control mice received corn oil. Telomerase expression, apoptosis, collagen I, III, and V fibers, and hydroxyproline were evaluated by immunohistochemistry, in situ detection of apoptosis, electron microscopy, immunofluorescence, and histomorphometry. Electron microscopy confirmed the presence of increased alveolar epithelial cells type 1 (AEC1) in apoptosis. Immunostaining showed increased nuclear expression of telomerase in AEC type 2 (AEC2) between normal and chronic scarring areas of usual interstitial pneumonia (UIP). Control lungs and normal areas from UIP lungs showed weak green birefringence of type I and III collagens in the alveolar wall and type V collagen in the basement membrane of alveolar capillaries. The increase in collagen V was greater than collagens I and III in scarring areas of UIP. A significant direct association was found between collagen V and AEC2 apoptosis. We concluded that telomerase, collagen V fiber density, and apoptosis evaluation in experimental UIP offers the potential to control reepithelization of alveolar septa and fibroblast proliferation. Strategies aimed at preventing high rates of collagen V synthesis, or local responses to high rates of cell apoptosis, may have a significant impact in pulmonary fibrosis

Modeling pulmonary fibrosis by abnormal expression of telomerase/apoptosis/collagen V in experimental usual interstitial pneumonia

Energy Technology Data Exchange (ETDEWEB)

Parra, E.R.; Pincelli, M.S. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Teodoro, W.R.; Velosa, A.P.P. [Disciplina de Reumatologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Martins, V.; Rangel, M.P.; Barbas-Filho, J.V.; Capelozzi, V.L. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

2014-06-04

Limitations on tissue proliferation capacity determined by telomerase/apoptosis balance have been implicated in pathogenesis of idiopathic pulmonary fibrosis. In addition, collagen V shows promise as an inductor of apoptosis. We evaluated the quantitative relationship between the telomerase/apoptosis index, collagen V synthesis, and epithelial/fibroblast replication in mice exposed to butylated hydroxytoluene (BHT) at high oxygen concentration. Two groups of mice were analyzed: 20 mice received BHT, and 10 control mice received corn oil. Telomerase expression, apoptosis, collagen I, III, and V fibers, and hydroxyproline were evaluated by immunohistochemistry, in situ detection of apoptosis, electron microscopy, immunofluorescence, and histomorphometry. Electron microscopy confirmed the presence of increased alveolar epithelial cells type 1 (AEC1) in apoptosis. Immunostaining showed increased nuclear expression of telomerase in AEC type 2 (AEC2) between normal and chronic scarring areas of usual interstitial pneumonia (UIP). Control lungs and normal areas from UIP lungs showed weak green birefringence of type I and III collagens in the alveolar wall and type V collagen in the basement membrane of alveolar capillaries. The increase in collagen V was greater than collagens I and III in scarring areas of UIP. A significant direct association was found between collagen V and AEC2 apoptosis. We concluded that telomerase, collagen V fiber density, and apoptosis evaluation in experimental UIP offers the potential to control reepithelization of alveolar septa and fibroblast proliferation. Strategies aimed at preventing high rates of collagen V synthesis, or local responses to high rates of cell apoptosis, may have a significant impact in pulmonary fibrosis.

A case of viral encephalitis localized in the occipital lobe

International Nuclear Information System (INIS)

Izawa, Masahiro; Okino, Teruhiko; Kagawa, Mizuo; Kitamura, Koichi.

1987-01-01

A case is reported of a 63-year-old female admitted to our hospital in Oct., 1986, with complaints of headache and visual field disturbance. A plain CT scan showed no abnormal low-density focal area. A contrast-enhancement CT scan, however, showed a localized linear abnormal enhancement in the right occipital lobe, without any mass-effect. A dynamic CT scan demonstrated a hyperemic perfusion pattern of the right occipital lobe. A visual-field examination showed left homonymous hemianopsia with concentric narrowing. These abnormal findings on CT, EEG, and ophthalmological examination disappeared within 3 weeks. (author)

Environmental obesogen tributyltin chloride leads to abnormal hypothalamic-pituitary-gonadal axis function by disruption in kisspeptin/leptin signaling in female rats

Energy Technology Data Exchange (ETDEWEB)

Sena, Gabriela C.; Freitas-Lima, Leandro C.; Merlo, Eduardo; Podratz, Priscila L.; Araújo, Julia F.P. de [Department of Morphology, Federal University of Espírito Santo (Brazil); Brandão, Poliane A.A.; Carneiro, Maria T.W.D. [Department of Chemistry, Federal University of Espírito Santo (Brazil); Zicker, Marina C. [Department of Food Science, Faculty of Pharmacy, Federal University of Minas Gerais (Brazil); Ferreira, Adaliene V.M. [Department of Basic Nursing, Nursing School, Federal University of Minas Gerais (Brazil); Takiya, Christina M.; Lemos Barbosa, Carolina M. de; Morales, Marcelo M. [Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (Brazil); Santos-Silva, Ana Paula [Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (Brazil); Experimental Endocrinology Research, Development and Innovation Group, Institute of Biomedical Sciences, Federal University of Rio de Janeiro (Brazil); Postgraduate Program in Endocrinology, School of Medicine, Federal University of Rio de Janeiro (Brazil); Miranda-Alves, Leandro [Experimental Endocrinology Research, Development and Innovation Group, Institute of Biomedical Sciences, Federal University of Rio de Janeiro (Brazil); Postgraduate Program in Endocrinology, School of Medicine, Federal University of Rio de Janeiro (Brazil); Silva, Ian V. [Department of Morphology, Federal University of Espírito Santo (Brazil); Graceli, Jones B., E-mail: jbgraceli@gmail.com [Department of Morphology, Federal University of Espírito Santo (Brazil)

2017-03-15

Tributyltin chloride (TBT) is a xenobiotic used as a biocide in antifouling paints that has been demonstrated to induce endocrine-disrupting effects, such as obesity and reproductive abnormalities. An integrative metabolic control in the hypothalamus-pituitary-gonadal (HPG) axis was exerted by leptin. However, studies that have investigated the obesogenic TBT effects on the HPG axis are especially rare. We investigated whether metabolic disorders as a result of TBT are correlated with abnormal hypothalamus-pituitary-gonadal (HPG) axis function, as well as kisspeptin (Kiss) action. Female Wistar rats were administered vehicle and TBT (100 ng/kg/day) for 15 days via gavage. We analyzed their effects on the tin serum and ovary accumulation (as biomarker of TBT exposure), estrous cyclicity, surge LH levels, GnRH expression, Kiss action, fertility, testosterone levels, ovarian apoptosis, uterine inflammation, fibrosis, estrogen negative feedback, body weight gain, insulin, leptin, adiponectin levels, as well as the glucose tolerance (GTT) and insulin sensitivity tests (IST). TBT led to increased serum and ovary tin levels, irregular estrous cyclicity, and decreased surge LH levels, GnRH expression and Kiss responsiveness. A strong negative correlation between the serum and ovary tin levels with lower Kiss responsiveness and GnRH mRNA expression was observed in TBT rats. An increase in the testosterone levels, ovarian and uterine fibrosis, ovarian apoptosis, and uterine inflammation and a decrease in fertility and estrogen negative feedback were demonstrated in the TBT rats. We also identified an increase in the body weight gain and abnormal GTT and IST tests, which were associated with hyperinsulinemia, hyperleptinemia and hypoadiponectinemia, in the TBT rats. TBT disrupted proper functioning of the HPG axis as a result of abnormal Kiss action. The metabolic dysfunctions co-occur with the HPG axis abnormalities. Hyperleptinemia as a result of obesity induced by TBT may

Environmental obesogen tributyltin chloride leads to abnormal hypothalamic-pituitary-gonadal axis function by disruption in kisspeptin/leptin signaling in female rats

International Nuclear Information System (INIS)

Sena, Gabriela C.; Freitas-Lima, Leandro C.; Merlo, Eduardo; Podratz, Priscila L.; Araújo, Julia F.P. de; Brandão, Poliane A.A.; Carneiro, Maria T.W.D.; Zicker, Marina C.; Ferreira, Adaliene V.M.; Takiya, Christina M.; Lemos Barbosa, Carolina M. de; Morales, Marcelo M.; Santos-Silva, Ana Paula; Miranda-Alves, Leandro; Silva, Ian V.; Graceli, Jones B.

2017-01-01

Tributyltin chloride (TBT) is a xenobiotic used as a biocide in antifouling paints that has been demonstrated to induce endocrine-disrupting effects, such as obesity and reproductive abnormalities. An integrative metabolic control in the hypothalamus-pituitary-gonadal (HPG) axis was exerted by leptin. However, studies that have investigated the obesogenic TBT effects on the HPG axis are especially rare. We investigated whether metabolic disorders as a result of TBT are correlated with abnormal hypothalamus-pituitary-gonadal (HPG) axis function, as well as kisspeptin (Kiss) action. Female Wistar rats were administered vehicle and TBT (100 ng/kg/day) for 15 days via gavage. We analyzed their effects on the tin serum and ovary accumulation (as biomarker of TBT exposure), estrous cyclicity, surge LH levels, GnRH expression, Kiss action, fertility, testosterone levels, ovarian apoptosis, uterine inflammation, fibrosis, estrogen negative feedback, body weight gain, insulin, leptin, adiponectin levels, as well as the glucose tolerance (GTT) and insulin sensitivity tests (IST). TBT led to increased serum and ovary tin levels, irregular estrous cyclicity, and decreased surge LH levels, GnRH expression and Kiss responsiveness. A strong negative correlation between the serum and ovary tin levels with lower Kiss responsiveness and GnRH mRNA expression was observed in TBT rats. An increase in the testosterone levels, ovarian and uterine fibrosis, ovarian apoptosis, and uterine inflammation and a decrease in fertility and estrogen negative feedback were demonstrated in the TBT rats. We also identified an increase in the body weight gain and abnormal GTT and IST tests, which were associated with hyperinsulinemia, hyperleptinemia and hypoadiponectinemia, in the TBT rats. TBT disrupted proper functioning of the HPG axis as a result of abnormal Kiss action. The metabolic dysfunctions co-occur with the HPG axis abnormalities. Hyperleptinemia as a result of obesity induced by TBT may

Omnivores Going Astray: A Review and New Synthesis of Abnormal Behavior in Pigs and Laying Hens

Science.gov (United States)

Brunberg, Emma I.; Rodenburg, T. Bas; Rydhmer, Lotta; Kjaer, Joergen B.; Jensen, Per; Keeling, Linda J.

2016-01-01

Pigs and poultry are by far the most omnivorous of the domesticated farm animals and it is in their nature to be highly explorative. In the barren production environments, this motivation to explore can be expressed as abnormal oral manipulation directed toward pen mates. Tail biting (TB) in pigs and feather pecking (FP) in laying hens are examples of unwanted behaviors that are detrimental to the welfare of the animals. The aim of this review is to draw these two seemingly similar abnormalities together in a common framework, in order to seek underlying mechanisms and principles. Both TB and FP are affected by the physical and social environment, but not all individuals in a group express these behaviors and individual genetic and neurobiological characteristics play an important role. By synthesizing what is known about environmental and individual influences, we suggest a novel possible mechanism, common for pigs and poultry, involving the brain–gut–microbiota axis. PMID:27500137

Expression and subcellular localization of ORC1 in Leishmania major

International Nuclear Information System (INIS)

Kumar, Diwakar; Mukherji, Agnideep; Saha, Swati

2008-01-01

The mechanism of DNA replication is highly conserved in eukaryotes, with the process being preceded by the ordered assembly of pre-replication complexes (pre-RCs). Pre-RC formation is triggered by the association of the origin replication complex (ORC) with chromatin. Leishmania major appears to have only one ORC ortholog, ORC1. ORC1 in other eukaryotes is the largest of the ORC subunits and is believed to play a significant role in modulating replication initiation. Here we report for the first time, the cloning of ORC1 from L. major, and the analysis of its expression in L. major promastigotes. In human cells ORC1 levels have been found to be upregulated in G1 and subsequently degraded, thus playing a role in controlling replication initiation. We examine the subcellular localization of L. major ORC1 in relation to the different stages of the cell cycle. Our results show that, unlike what is widely believed to be the case with ORC1 in human cells, ORC1 in L. major is nuclear at all stages of the cell cycle

Expression of Bcl-2, p53, and MDM2 in Localized Prostate Cancer With Respect to the Outcome of Radical Radiotherapy Dose Escalation

International Nuclear Information System (INIS)

Vergis, Roy; Corbishley, Catherine M.; Thomas, Karen

2010-01-01

Purpose: Established prognostic factors in localized prostate cancer explain only a moderate proportion of variation in outcome. We analyzed tumor expression of apoptotic markers with respect to outcome in men with localized prostate cancer in two randomized controlled trials of radiotherapy dose escalation. Methods and Materials: Between 1995 and 2001, 308 patients with localized prostate cancer received neoadjuvant androgen deprivation and radical radiotherapy at our institution in one of two dose-escalation trials. The biopsy specimens in 201 cases were used to make a biopsy tissue microarray. We evaluated tumor expression of Bcl-2, p53, and MDM2 by immunohistochemistry with respect to outcome. Results: Median follow-up was 7 years, and 5-year freedom from biochemical failure (FFBF) was 70.4% (95% CI, 63.5-76.3%). On univariate analysis, expression of Bcl-2 (p < 0.001) and p53 (p = 0.017), but not MDM2 (p = 0.224), was significantly associated with FFBF. Expression of Bcl-2 remained significantly associated with FFBF (p = 0.001) on multivariate analysis, independently of T stage, Gleason score, initial prostate-specific antigen level, and radiotherapy dose. Seven-year biochemical control was 61% vs. 41% (p = 0.0122) for 74 Gy vs. 64 Gy, respectively, among patients with Bcl-2-positive tumors and 87% vs. 81% (p = 0.423) for 74 Gy vs. 64 Gy, respectively, among patients with Bcl-2-negative tumors. There was no statistically significant interaction between dose and Bcl-2 expression. Conclusions: Bcl-2 expression was a significant, independent determinant of biochemical control after neoadjuvant androgen deprivation and radical radiotherapy for prostate cancer. These data generate the hypothesis that Bcl-2 expression could be used to inform the choice of radiotherapy dose in individual patients.

Abnormal placental development and early embryonic lethality in EpCAM-null mice.

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Keisuke Nagao

Full Text Available BACKGROUND: EpCAM (CD326 is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. METHODOLOGY/PRINCIPAL FINDINGS: To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts, eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. CONCLUSION: EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.

Abnormal placental development and early embryonic lethality in EpCAM-null mice.

Science.gov (United States)

Nagao, Keisuke; Zhu, Jianjian; Heneghan, Mallorie B; Hanson, Jeffrey C; Morasso, Maria I; Tessarollo, Lino; Mackem, Susan; Udey, Mark C

2009-12-31

EpCAM (CD326) is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts), eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.

Abnormal Sensory Protein Expression and Urothelial Dysfunction in Ketamine-Related Cystitis in Humans

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Yao Chou Tsai

2016-09-01

Full Text Available Purpose The aim of this study was to analyze patterns of sensory protein expression and urothelial dysfunction in ketamine-related cystitis (KC in humans. Methods Biopsies of bladder mucosa were performed in 29 KC patients during cystoscopy. Then specimens were analyzed for tryptase, zonula occludens-1 (ZO-1, E-cadherin, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL with immunofluorescence staining and quantification. In addition, 10 healthy control bladder specimens were analyzed and compared with the KC specimens. Another 16 whole bladder specimens obtained from partial cystectomy were also analyzed for the muscarinic receptors M2 and M3, endothelial nitric oxide synthase (eNOS, inducible nitric oxide synthase (iNOS, β-3 adrenergic receptors (β3-ARs, and the P2X3 receptor by western blotting. In addition, 3 normal control bladder specimens were analyzed and compared with the KC specimens. Results The KC bladder mucosa revealed significantly less expression of ZO-1 and E-cadherin, and greater expression of TUNEL and tryptase activity than the control samples. The expression of M3 and β3-AR in the KC specimens was significantly greater than in the controls. The expression of iNOS, eNOS, M2, and P2X3 was not significantly different between the KC and control specimens. Conclusions The bladder tissue of KC patients revealed significant urothelial dysfunction, which was associated with mast-cell mediated inflammation, increased urothelial cell apoptosis, and increased expression of the M3 and β3-AR.

Expression-robust 3D face recognition via weighted sparse representation of multi-scale and multi-component local normal patterns

KAUST Repository

Li, Huibin

2014-06-01

In the theory of differential geometry, surface normal, as a first order surface differential quantity, determines the orientation of a surface at each point and contains informative local surface shape information. To fully exploit this kind of information for 3D face recognition (FR), this paper proposes a novel highly discriminative facial shape descriptor, namely multi-scale and multi-component local normal patterns (MSMC-LNP). Given a normalized facial range image, three components of normal vectors are first estimated, leading to three normal component images. Then, each normal component image is encoded locally to local normal patterns (LNP) on different scales. To utilize spatial information of facial shape, each normal component image is divided into several patches, and their LNP histograms are computed and concatenated according to the facial configuration. Finally, each original facial surface is represented by a set of LNP histograms including both global and local cues. Moreover, to make the proposed solution robust to the variations of facial expressions, we propose to learn the weight of each local patch on a given encoding scale and normal component image. Based on the learned weights and the weighted LNP histograms, we formulate a weighted sparse representation-based classifier (W-SRC). In contrast to the overwhelming majority of 3D FR approaches which were only benchmarked on the FRGC v2.0 database, we carried out extensive experiments on the FRGC v2.0, Bosphorus, BU-3DFE and 3D-TEC databases, thus including 3D face data captured in different scenarios through various sensors and depicting in particular different challenges with respect to facial expressions. The experimental results show that the proposed approach consistently achieves competitive rank-one recognition rates on these databases despite their heterogeneous nature, and thereby demonstrates its effectiveness and its generalizability. © 2014 Elsevier B.V.

Abnormal megakaryocyte development and platelet function in Nbeal2−/− mice

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Lo, Richard W.; Li, Ling; Pluthero, Fred G.; Christensen, Hilary; Ni, Ran; Vaezzadeh, Nima; Hawkins, Cynthia E.; Weyrich, Andrew S.; Di Paola, Jorge; Landolt-Marticorena, Carolina; Gross, Peter L.

2013-01-01

Gray platelet syndrome (GPS) is an inherited bleeding disorder associated with macrothrombocytopenia and α-granule-deficient platelets. GPS has been linked to loss of function mutations in NEABL2 (neurobeachin-like 2), and we describe here a murine GPS model, the Nbeal2−/− mouse. As in GPS, Nbeal2−/− mice exhibit splenomegaly, macrothrombocytopenia, and a deficiency of platelet α-granules and their cargo, including von Willebrand factor (VWF), thrombospondin-1, and platelet factor 4. The platelet α-granule membrane protein P-selectin is expressed at 48% of wild-type levels and externalized upon platelet activation. The presence of P-selectin and normal levels of VPS33B and VPS16B in Nbeal2−/− platelets suggests that NBEAL2 acts independently of VPS33B/VPS16B at a later stage of α-granule biogenesis. Impaired Nbeal2−/− platelet function was shown by flow cytometry, platelet aggregometry, bleeding assays, and intravital imaging of laser-induced arterial thrombus formation. Microscopic analysis detected marked abnormalities in Nbeal2−/− bone marrow megakaryocytes, which when cultured showed delayed maturation, decreased survival, decreased ploidy, and developmental abnormalities, including abnormal extracellular distribution of VWF. Our results confirm that α-granule secretion plays a significant role in platelet function, and they also indicate that abnormal α-granule formation in Nbeal2−/− mice has deleterious effects on megakaryocyte survival, development, and platelet production. PMID:23861251

Localization and expression of Orexin A and its receptor in mouse testis during different stages of postnatal development.

Science.gov (United States)

Joshi, Deepanshu; Singh, Shio Kumar

2017-01-15

Orexin A (OXA), a hypothalamic neuropeptide, is involved in regulation of various biological functions and its actions are mediated through G-protein-coupled receptor, OX1R. This neuropeptide has emerged as a central neuroendocrine modulator of reproductive functions. Both OXA and OX1R have been shown to be expressed in peripheral organs such as gastrointestinal and genital tracts. In the present study, localization and expression of OXA and OX1R in mouse testis during different stages of postnatal development have been investigated. Immunohistochemical results demonstrated localization of OXA and OX1R in both the interstitial and the tubular compartments of the testis throughout the period of postnatal development. In testicular sections on 0day postpartum (dpp), gonocytes, Sertoli cells and foetal Leydig cells showed OXA and OX1R-immunopositive signals. At 10dpp, Sertoli cells, spermatogonia, early spermatocytes and Leydig cells showed immunopositive signals for both, the ligand and the receptor. On 30 and 90dpp, the spermatogonia, Sertoli cells, spermatocytes, spermatids and Leydig cells showed the OXA and OX1R-immunopositive signals. At 90dpp, strong OXA-positive signals were seen in Leydig cells, primary spermatocytes and spermatogonia, while OX1R-immunopositive intense signals were observed in Leydig cells and elongated spermatids. Further, semiquantitative RT-PCR and immunoblot analyses showed that OXA and OX1R were expressed in the testis both at transcript and protein levels during different stages of postnatal development. The expression of OXA and OX1R increased progressively from day of birth (0dpp) until adulthood (90dpp), with maximal expression at 90 dpp. The results suggest that OXA and OX1R are expressed in the testis and that they may help in proliferation and development of germ cells, Leydig cells and Sertoli cells, and in the spermatogenic process and steroidogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Amplitude of low frequency fluctuation abnormalities in adolescents with online gaming addiction.

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Yuan, Kai; Jin, Chenwang; Cheng, Ping; Yang, Xuejuan; Dong, Tao; Bi, Yanzhi; Xing, Lihong; von Deneen, Karen M; Yu, Dahua; Liu, Junyu; Liang, Jun; Cheng, Tingting; Qin, Wei; Tian, Jie

2013-01-01

The majority of previous neuroimaging studies have demonstrated both structural and task-related functional abnormalities in adolescents with online gaming addiction (OGA). However, few functional magnetic resonance imaging (fMRI) studies focused on the regional intensity of spontaneous fluctuations in blood oxygen level-dependent (BOLD) during the resting state and fewer studies investigated the relationship between the abnormal resting-state properties and the impaired cognitive control ability. In the present study, we employed the amplitude of low frequency fluctuation (ALFF) method to explore the local features of spontaneous brain activity in adolescents with OGA and healthy controls during resting-state. Eighteen adolescents with OGA and 18 age-, education- and gender-matched healthy volunteers participated in this study. Compared with healthy controls, adolescents with OGA showed a significant increase in ALFF values in the left medial orbitofrontal cortex (OFC), the left precuneus, the left supplementary motor area (SMA), the right parahippocampal gyrus (PHG) and the bilateral middle cingulate cortex (MCC). The abnormalities of these regions were also detected in previous addiction studies. More importantly, we found that ALFF values of the left medial OFC and left precuneus were positively correlated with the duration of OGA in adolescents with OGA. The ALFF values of the left medial OFC were also correlated with the color-word Stroop test performance. Our results suggested that the abnormal spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology of OGA.

Amplitude of low frequency fluctuation abnormalities in adolescents with online gaming addiction.

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Kai Yuan

Full Text Available The majority of previous neuroimaging studies have demonstrated both structural and task-related functional abnormalities in adolescents with online gaming addiction (OGA. However, few functional magnetic resonance imaging (fMRI studies focused on the regional intensity of spontaneous fluctuations in blood oxygen level-dependent (BOLD during the resting state and fewer studies investigated the relationship between the abnormal resting-state properties and the impaired cognitive control ability. In the present study, we employed the amplitude of low frequency fluctuation (ALFF method to explore the local features of spontaneous brain activity in adolescents with OGA and healthy controls during resting-state. Eighteen adolescents with OGA and 18 age-, education- and gender-matched healthy volunteers participated in this study. Compared with healthy controls, adolescents with OGA showed a significant increase in ALFF values in the left medial orbitofrontal cortex (OFC, the left precuneus, the left supplementary motor area (SMA, the right parahippocampal gyrus (PHG and the bilateral middle cingulate cortex (MCC. The abnormalities of these regions were also detected in previous addiction studies. More importantly, we found that ALFF values of the left medial OFC and left precuneus were positively correlated with the duration of OGA in adolescents with OGA. The ALFF values of the left medial OFC were also correlated with the color-word Stroop test performance. Our results suggested that the abnormal spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology of OGA.

1α,25 dihydroxi-vitamin D{sub 3} modulates CDK4 and CDK6 expression and localization

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Irazoqui, Ana P.; Heim, Nadia B.; Boland, Ricardo L.; Buitrago, Claudia G., E-mail: cbuitrag@criba.edu.ar

2015-03-27

We recently reported that the vitamin D receptor (VDR) and p38 MAPK participate in pro-differentiation events triggered by 1α,25(OH){sub 2}-vitamin D{sub 3} [1,25D] in skeletal muscle cells. Specifically, our studies demonstrated that 1,25D promotes G0/G1 arrest of cells inducing cyclin D3 and cyclin dependent kinases inhibitors (CKIs) p21{sup Waf1/Cip1} and p27{sup Kip1} expression in a VDR and p38 MAPK dependent manner. In this work we present data indicating that cyclin-dependent kinases (CDKs) 4 and 6 also play a role in the mechanism by which 1,25D stimulates myogenesis. To investigate VDR involvement in hormone regulation of CDKs 4 and 6, we significantly reduced its expression by the use of a shRNA against mouse VDR, generating the skeletal muscle cell line C2C12-VDR. Investigation of changes in cellular cycle regulating proteins by immunoblotting showed that the VDR is involved in the 1,25D –induced CDKs 4 and 6 protein levels at 6 h of hormone treatment. CDK4 levels remains high during S phase peak and G0/G1 arrest while CDK6 expression decreases at 12 h and increases again al 24 h. The up-regulation of CDKs 4 and 6 by 1,25D (6 h) was abolished in C2C12 cells pre-treated with the ERK1/2 inhibitor, UO126. Moreover, CDKs 4 and 6 expression induced by the hormone nor was detected when α and β isoforms of p38 MAPK were inhibited by compound SB203580. Confocal images show that there is not co-localization between VDR and CDKs at 6 h of hormone treatment, however CDK4 and VDR co-localizates in nucleus after 12 h of 1,25D exposure. Of relevance, at this time 1,25D promotes CDK6 localization in a peri-nuclear ring. Our data demonstrate that the VDR, ERK1/2 and p38 MAPK are involved in the control of CDKs 4 and 6 by 1,25D in skeletal muscle cells sustaining the operation of a VDR and MAPKs –dependent mechanism in hormone modulation of myogenesis. - Highlights: • 1,25D modulates CDKs 4 and 6 expression in skeletal muscle cells. • CDK4 co

A rice chloroplast transit peptide sequence does not alter the cytoplasmic localization of sheep serotonin N-acetyltransferase expressed in transgenic rice plants.

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Byeon, Yeong; Lee, Hyoung Yool; Lee, Kyungjin; Back, Kyoungwhan

2014-09-01

Ectopic overexpression of melatonin biosynthetic genes of animal origin has been used to generate melatonin-rich transgenic plants to examine the functional roles of melatonin in plants. However, the subcellular localization of these proteins expressed in the transgenic plants remains unknown. We studied the localization of sheep (Ovis aries) serotonin N-acetyltransferase (OaSNAT) and a translational fusion of a rice SNAT transit peptide to OaSNAT (TS:OaSNAT) in plants. Laser confocal microscopy analysis revealed that both OaSNAT and TS:OaSNAT proteins were localized to the cytoplasm even with the addition of the transit sequence to OaSNAT. Transgenic rice plants overexpressing the TS:OaSNAT fusion transgene exhibited high SNAT enzyme activity relative to untransformed wild-type plants, but lower activity than transgenic rice plants expressing the wild-type OaSNAT gene. Melatonin levels in both types of transgenic rice plant corresponded well with SNAT enzyme activity levels. The TS:OaSNAT transgenic lines exhibited increased seminal root growth relative to wild-type plants, but less than in the OaSNAT transgenic lines, confirming that melatonin promotes root growth. Seed-specific OaSNAT expression under the control of a rice prolamin promoter did not confer high levels of melatonin production in transgenic rice seeds compared with seeds from transgenic plants expressing OaSNAT under the control of the constitutive maize ubiquitin promoter. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Expression, Localization of SUMO-1, and Analyses of Potential SUMOylated Proteins in Bubalus bubalis Spermatozoa.

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Brohi, Rahim Dad; Wang, Li; Hassine, Najla Ben; Cao, Jing; Talpur, Hira Sajjad; Wu, Di; Huang, Chun-Jie; Rehman, Zia-Ur; Bhattarai, Dinesh; Huo, Li-Jun

2017-01-01

Mature spermatozoa have highly condensed DNA that is essentially silent both transcriptionally and translationally. Therefore, post translational modifications are very important for regulating sperm motility, morphology, and for male fertility in general. Protein sumoylation was recently demonstrated in human and rodent spermatozoa, with potential consequences for sperm motility and DNA integrity. We examined the expression and localization of small ubiquitin-related modifier-1 (SUMO-1) in the sperm of water buffalo ( Bubalus bubalis ) using immunofluorescence analysis. We confirmed the expression of SUMO-1 in the acrosome. We further found that SUMO-1 was lost if the acrosome reaction was induced by calcium ionophore A23187. Proteins modified or conjugated by SUMO-1 in water buffalo sperm were pulled down and analyzed by mass spectrometry. Sixty proteins were identified, including proteins important for sperm morphology and motility, such as relaxin receptors and cytoskeletal proteins, including tubulin chains, actins, and dyneins. Forty-six proteins were predicted as potential sumoylation targets. The expression of SUMO-1 in the acrosome region of water buffalo sperm and the identification of potentially SUMOylated proteins important for sperm function implicates sumoylation as a crucial PTM related to sperm function.

Expression, Localization of SUMO-1, and Analyses of Potential SUMOylated Proteins in Bubalus bubalis Spermatozoa

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Rahim Dad Brohi

2017-06-01

Full Text Available Mature spermatozoa have highly condensed DNA that is essentially silent both transcriptionally and translationally. Therefore, post translational modifications are very important for regulating sperm motility, morphology, and for male fertility in general. Protein sumoylation was recently demonstrated in human and rodent spermatozoa, with potential consequences for sperm motility and DNA integrity. We examined the expression and localization of small ubiquitin-related modifier-1 (SUMO-1 in the sperm of water buffalo (Bubalus bubalis using immunofluorescence analysis. We confirmed the expression of SUMO-1 in the acrosome. We further found that SUMO-1 was lost if the acrosome reaction was induced by calcium ionophore A23187. Proteins modified or conjugated by SUMO-1 in water buffalo sperm were pulled down and analyzed by mass spectrometry. Sixty proteins were identified, including proteins important for sperm morphology and motility, such as relaxin receptors and cytoskeletal proteins, including tubulin chains, actins, and dyneins. Forty-six proteins were predicted as potential sumoylation targets. The expression of SUMO-1 in the acrosome region of water buffalo sperm and the identification of potentially SUMOylated proteins important for sperm function implicates sumoylation as a crucial PTM related to sperm function.

Facial Expression Recognition from Video Sequences Based on Spatial-Temporal Motion Local Binary Pattern and Gabor Multiorientation Fusion Histogram

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Lei Zhao

2017-01-01

Full Text Available This paper proposes novel framework for facial expressions analysis using dynamic and static information in video sequences. First, based on incremental formulation, discriminative deformable face alignment method is adapted to locate facial points to correct in-plane head rotation and break up facial region from background. Then, spatial-temporal motion local binary pattern (LBP feature is extracted and integrated with Gabor multiorientation fusion histogram to give descriptors, which reflect static and dynamic texture information of facial expressions. Finally, a one-versus-one strategy based multiclass support vector machine (SVM classifier is applied to classify facial expressions. Experiments on Cohn-Kanade (CK + facial expression dataset illustrate that integrated framework outperforms methods using single descriptors. Compared with other state-of-the-art methods on CK+, MMI, and Oulu-CASIA VIS datasets, our proposed framework performs better.

Expression and significance of GRHL2 in esophageal cancer

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Shao CC

2017-04-01

Full Text Available Chengcheng Shao,1 Chushu Ji,1 Xiaoqiu Wang,2 Bing Hu1 1Department of Medical Oncology, 2Department of Pathology, Anhui Provincial Hospital, Anhui Medical University, Hefei, People’s Republic of China Abstract: Esophageal cancer (EC is one of the most common causes of cancer-related mortality in the world. Although much effort has been made to improve the 5-year survival rate of patients with EC, it still remains low due to diagnosis at an advanced stage, aggressive local invasion, early metastasis, and resistance to chemotherapy. Although grainyhead-like 2 (GRHL2 has attracted interest since it has been recently identified as a novel suppressor of the epithelial–mesenchymal transition, clinical values of GRHL2 and its relationship with the metastasis-related factors, such as hypoxia-inducible factor 1α (HIF-1α and vascular endothelial growth factor (VEGF, remain unclear. In order to investigate the expression of GRHL2, HIF-1α, and VEGF, and their correlation with angiogenesis in EC, 63 patients with EC were examined. The expression of GRHL2, HIF-1α, and VEGF in tumor tissues was higher than that in adjacent tissues and was associated with tumor differentiation. GRHL2 expression was significantly correlated with lymph node metastasis and invasion depth, whereas VEGF expression was associated with tumor (TNM stage. A significant correlation was found between the expression of GRHL2 and HIF-1α. The patients expressing low GRHL2 and high HIF-1α showed significant reduction in both overall survival rate and disease-free survival rate. The results demonstrated that abnormal expression of GRHL2 is common in EC, and low expression of GRHL2 accompanied by a high expression of HIF-1α indicates poor prognosis. Keywords: esophageal neoplasms, GRHL2, HIF-1α, VEGF, MVD

Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer.

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Gianni, Luca; Zambetti, Milvia; Clark, Kim; Baker, Joffre; Cronin, Maureen; Wu, Jenny; Mariani, Gabriella; Rodriguez, Jaime; Carcangiu, Marialuisa; Watson, Drew; Valagussa, Pinuccia; Rouzier, Roman; Symmans, W Fraser; Ross, Jeffrey S; Hortobagyi, Gabriel N; Pusztai, Lajos; Shak, Steven

2005-10-10

We sought to identify gene expression markers that predict the likelihood of chemotherapy response. We also tested whether chemotherapy response is correlated with the 21-gene Recurrence Score assay that quantifies recurrence risk. Patients with locally advanced breast cancer received neoadjuvant paclitaxel and doxorubicin. RNA was extracted from the pretreatment formalin-fixed paraffin-embedded core biopsies. The expression of 384 genes was quantified using reverse transcriptase polymerase chain reaction and correlated with pathologic complete response (pCR). The performance of genes predicting for pCR was tested in patients from an independent neoadjuvant study where gene expression was obtained using DNA microarrays. Of 89 assessable patients (mean age, 49.9 years; mean tumor size, 6.4 cm), 11 (12%) had a pCR. Eighty-six genes correlated with pCR (unadjusted P < .05); pCR was more likely with higher expression of proliferation-related genes and immune-related genes, and with lower expression of estrogen receptor (ER) -related genes. In 82 independent patients treated with neoadjuvant paclitaxel and doxorubicin, DNA microarray data were available for 79 of the 86 genes. In univariate analysis, 24 genes correlated with pCR with P < .05 (false discovery, four genes) and 32 genes showed correlation with P < .1 (false discovery, eight genes). The Recurrence Score was positively associated with the likelihood of pCR (P = .005), suggesting that the patients who are at greatest recurrence risk are more likely to have chemotherapy benefit. Quantitative expression of ER-related genes, proliferation genes, and immune-related genes are strong predictors of pCR in women with locally advanced breast cancer receiving neoadjuvant anthracyclines and paclitaxel.

Comparison of brain volume abnormalities between ADHD and conduct disorder in adolescence

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Stevens, Michael C.; Haney-Caron, Emily

2012-01-01

associated with numerous frontal lobe structural deficits, a conclusion that is not strongly supported following direct comparison of diagnostically pure groups. The results are important for future etiological studies, particularly those seeking to identify how early expression of specific brain structure abnormalities could potentiate the risk for antisocial behaviour. PMID:22663946

Serotonin Neuron Abnormalities in the BTBR Mouse Model of Autism

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Guo, Yue-Ping; Commons, Kathryn G.

2017-01-01

The inbred mouse strain BTBR T+ Itpr3tf/J (BTBR) i studied as a model of idiopathic autism because they are less social and more resistant to change than other strains. Forebrain serotonin receptors and the response to serotonin drugs are altered in BTBR mice, yet it remains unknown if serotonin neurons themselves are abnormal. In this study, we found that serotonin tissue content and the density of serotonin axons is reduced in the hippocampus of BTBR mice in comparison to C57BL/6J (C57) mice. This was accompanied by possible compensatory changes in serotonin neurons that were most pronounced in regions known to provide innervation to the hippocampus: the caudal dorsal raphe (B6) and the median raphe. These changes included increased numbers of serotonin neurons and hyperactivation of Fos expression. Metrics of serotonin neurons in the rostral 2/3 of the dorsal raphe and serotonin content of the prefrontal cortex were less impacted. Thus, serotonin neurons exhibit region-dependent abnormalities in the BTBR mouse that may contribute to their altered behavioral profile. PMID:27478061

Disk abnormality coexists with any degree of synovial and osseous abnormality in the temporomandibular joints of children with juvenile idiopathic arthritis

International Nuclear Information System (INIS)

Kirkhus, Eva; Smith, Hans-Joergen; Arvidsson, Linda Z.; Larheim, Tore A.; Flatoe, Berit; Hetlevik, Siri O.

2016-01-01

MRI manifestation of temporomandibular joint arthritis is frequently reported in children with juvenile idiopathic arthritis. However, little attention has been paid to temporomandibular joint disk abnormalities. To assess combinations of MRI findings in the symptomatic temporomandibular joint in children with juvenile idiopathic arthritis with focus on disk abnormalities. This was a retrospective study of 46 patients with juvenile idiopathic arthritis, mean age 12 years (range: 5-17 years). Mean disease duration was 70 months (standard deviation: 61 months). MR images of 92 temporomandibular joints were scored for thickness of abnormally enhancing synovium (synovitis), joint effusion, bone marrow oedema, abnormal bone shape, bone erosion and disk abnormalities. The 92 temporomandibular joints were categorized as A: No synovitis and normal bone shape (30/92; 33%), B: Synovitis and normal bone shape (14/92: 15%), C: Synovitis and abnormal bone shape (38/92; 41%) and D: No synovitis but abnormal bone shape (10/92; 11%). Thirty-six of the 46 patients (78%) had synovitis and 33/46 (72%) had abnormal bone shape, most frequently in combination (30/46; 65%). Disk abnormalities (flat disk, fragmented disk, adherent disk and displaced disk) were found in 29/46 patients (63%). Disk abnormalities were found in all categories of juvenile idiopathic arthritis involved temporomandibular joints (B: 8/14 [57%]; C: 25/38 [66%] and D: 7/10 [70%]). Disk displacement was found in half of the joints (7/14) in category B. Synovitis was most pronounced in this category. Disk abnormalities were frequent. Disk displacement also occurred in joints with early temporomandibular joint arthritis, i.e., with normal bone shape. Other disk abnormalities were found in joints with bone abnormalities. Attention should be paid to disk abnormalities both in early and long-standing temporomandibular joint arthritis in children with juvenile idiopathic arthritis. (orig.)

Disk abnormality coexists with any degree of synovial and osseous abnormality in the temporomandibular joints of children with juvenile idiopathic arthritis

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Kirkhus, Eva; Smith, Hans-Joergen [Oslo University Hospital, Rikshospitalet, Department of Radiology and Nuclear Medicine, Oslo (Norway); University of Oslo, Institute of Clinical Medicine, Oslo (Norway); Arvidsson, Linda Z.; Larheim, Tore A. [University of Oslo, Department of Maxillofacial Radiology, Institute of Clinical Dentistry, Oslo (Norway); Flatoe, Berit; Hetlevik, Siri O. [Oslo University Hospital, Rikshospitalet, Department of Rheumatology, Oslo (Norway); University of Oslo, Institute of Clinical Medicine, Oslo (Norway)

2016-03-15

MRI manifestation of temporomandibular joint arthritis is frequently reported in children with juvenile idiopathic arthritis. However, little attention has been paid to temporomandibular joint disk abnormalities. To assess combinations of MRI findings in the symptomatic temporomandibular joint in children with juvenile idiopathic arthritis with focus on disk abnormalities. This was a retrospective study of 46 patients with juvenile idiopathic arthritis, mean age 12 years (range: 5-17 years). Mean disease duration was 70 months (standard deviation: 61 months). MR images of 92 temporomandibular joints were scored for thickness of abnormally enhancing synovium (synovitis), joint effusion, bone marrow oedema, abnormal bone shape, bone erosion and disk abnormalities. The 92 temporomandibular joints were categorized as A: No synovitis and normal bone shape (30/92; 33%), B: Synovitis and normal bone shape (14/92: 15%), C: Synovitis and abnormal bone shape (38/92; 41%) and D: No synovitis but abnormal bone shape (10/92; 11%). Thirty-six of the 46 patients (78%) had synovitis and 33/46 (72%) had abnormal bone shape, most frequently in combination (30/46; 65%). Disk abnormalities (flat disk, fragmented disk, adherent disk and displaced disk) were found in 29/46 patients (63%). Disk abnormalities were found in all categories of juvenile idiopathic arthritis involved temporomandibular joints (B: 8/14 [57%]; C: 25/38 [66%] and D: 7/10 [70%]). Disk displacement was found in half of the joints (7/14) in category B. Synovitis was most pronounced in this category. Disk abnormalities were frequent. Disk displacement also occurred in joints with early temporomandibular joint arthritis, i.e., with normal bone shape. Other disk abnormalities were found in joints with bone abnormalities. Attention should be paid to disk abnormalities both in early and long-standing temporomandibular joint arthritis in children with juvenile idiopathic arthritis. (orig.)

Heterotaxy syndromes and abnormal bowel rotation

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Newman, Beverley [Stanford University, Lucile Packard Children' s Hospital, Department of Radiology, Stanford, CA (United States); Koppolu, Raji; Sylvester, Karl [Lucile Packard Children' s Hospital at Stanford, Department of Surgery, Stanford, CA (United States); Murphy, Daniel [Lucile Packard Children' s Hospital at Stanford, Department of Cardiology, Stanford, CA (United States)

2014-05-15

Bowel rotation abnormalities in heterotaxy are common. As more children survive cardiac surgery, the management of gastrointestinal abnormalities has become controversial. To evaluate imaging of malrotation in heterotaxy with surgical correlation and provide an algorithm for management. Imaging reports of heterotaxic children with upper gastrointestinal (UGI) and/or small bowel follow-through (SBFT) were reviewed. Subsequently, fluoroscopic images were re-reviewed in conjunction with CT/MR studies. The original reports and re-reviewed images were compared and correlated with surgical findings. Nineteen of 34 children with heterotaxy underwent UGI, 13/19 also had SBFT. In 15/19 reports, bowel rotation was called abnormal: 11 malrotation, 4 non-rotation, no cases of volvulus. Re-review, including CT (10/19) and MR (2/19), designated 17/19 (90%) as abnormal, 10 malrotation (abnormal bowel arrangement, narrow or uncertain length of mesentery) and 7 non-rotation (small bowel and colon on opposite sides plus low cecum with probable broad mesentery). The most useful CT/MR findings were absence of retroperitoneal duodenum in most abnormal cases and location of bowel, especially cecum. Abnormal orientation of mesenteric vessels suggested malrotation but was not universal. Nine children had elective bowel surgery; non-rotation was found in 4/9 and malrotation was found in 5/9, with discrepancies (non-rotation at surgery, malrotation on imaging) with 4 original interpretations and 1 re-review. We recommend routine, early UGI and SBFT studies once other, urgent clinical concerns have been stabilized, with elective laparoscopic surgery in abnormal or equivocal cases. Cross-sectional imaging, usually obtained for other reasons, can contribute diagnostically. Attempting to assess mesenteric width is important in differentiating non-rotation from malrotation and more accurately identifies appropriate surgical candidates. (orig.)

Heterotaxy syndromes and abnormal bowel rotation

International Nuclear Information System (INIS)

Newman, Beverley; Koppolu, Raji; Sylvester, Karl; Murphy, Daniel

2014-01-01

Bowel rotation abnormalities in heterotaxy are common. As more children survive cardiac surgery, the management of gastrointestinal abnormalities has become controversial. To evaluate imaging of malrotation in heterotaxy with surgical correlation and provide an algorithm for management. Imaging reports of heterotaxic children with upper gastrointestinal (UGI) and/or small bowel follow-through (SBFT) were reviewed. Subsequently, fluoroscopic images were re-reviewed in conjunction with CT/MR studies. The original reports and re-reviewed images were compared and correlated with surgical findings. Nineteen of 34 children with heterotaxy underwent UGI, 13/19 also had SBFT. In 15/19 reports, bowel rotation was called abnormal: 11 malrotation, 4 non-rotation, no cases of volvulus. Re-review, including CT (10/19) and MR (2/19), designated 17/19 (90%) as abnormal, 10 malrotation (abnormal bowel arrangement, narrow or uncertain length of mesentery) and 7 non-rotation (small bowel and colon on opposite sides plus low cecum with probable broad mesentery). The most useful CT/MR findings were absence of retroperitoneal duodenum in most abnormal cases and location of bowel, especially cecum. Abnormal orientation of mesenteric vessels suggested malrotation but was not universal. Nine children had elective bowel surgery; non-rotation was found in 4/9 and malrotation was found in 5/9, with discrepancies (non-rotation at surgery, malrotation on imaging) with 4 original interpretations and 1 re-review. We recommend routine, early UGI and SBFT studies once other, urgent clinical concerns have been stabilized, with elective laparoscopic surgery in abnormal or equivocal cases. Cross-sectional imaging, usually obtained for other reasons, can contribute diagnostically. Attempting to assess mesenteric width is important in differentiating non-rotation from malrotation and more accurately identifies appropriate surgical candidates. (orig.)

Ventricular shape and relative position abnormalities in preterm neonates

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N. Paquette

2017-01-01

Full Text Available Recent neuroimaging findings have highlighted the impact of premature birth on subcortical development and morphological changes in the deep grey nuclei and ventricular system. To help characterize subcortical microstructural changes in preterm neonates, we recently implemented a multivariate tensor-based method (mTBM. This method allows to precisely measure local surface deformation of brain structures in infants. Here, we investigated ventricular abnormalities and their spatial relationships with surrounding subcortical structures in preterm neonates. We performed regional group comparisons on the surface morphometry and relative position of the lateral ventricles between 19 full-term and 17 preterm born neonates at term-equivalent age. Furthermore, a relative pose analysis was used to detect individual differences in translation, rotation, and scale of a given brain structure with respect to an average. Our mTBM results revealed broad areas of alterations on the frontal horn and body of the left ventricle, and narrower areas of differences on the temporal horn of the right ventricle. A significant shift in the rotation of the left ventricle was also found in preterm neonates. Furthermore, we located significant correlations between morphology and pose parameters of the lateral ventricles and that of the putamen and thalamus. These results show that regional abnormalities on the surface and pose of the ventricles are also associated with alterations on the putamen and thalamus. The complementarity of the information provided by the surface and pose analysis may help to identify abnormal white and grey matter growth, hinting toward a pattern of neural and cellular dysmaturation.

Abnormalities of Object Visual Processing in Body Dysmorphic Disorder

Science.gov (United States)

Feusner, Jamie D.; Hembacher, Emily; Moller, Hayley; Moody, Teena D.

2013-01-01

Background Individuals with body dysmorphic disorder may have perceptual distortions for their appearance. Previous studies suggest imbalances in detailed relative to configural/holistic visual processing when viewing faces. No study has investigated the neural correlates of processing non-symptom-related stimuli. The objective of this study was to determine whether individuals with body dysmorphic disorder have abnormal patterns of brain activation when viewing non-face/non-body object stimuli. Methods Fourteen medication-free participants with DSM-IV body dysmorphic disorder and 14 healthy controls participated. We performed functional magnetic resonance imaging while participants matched photographs of houses that were unaltered, contained only high spatial frequency (high detail) information, or only low spatial frequency (low detail) information. The primary outcome was group differences in blood oxygen level-dependent signal changes. Results The body dysmorphic disorder group showed lesser activity in the parahippocampal gyrus, lingual gyrus, and precuneus for low spatial frequency images. There were greater activations in medial prefrontal regions for high spatial frequency images, although no significant differences when compared to a low-level baseline. Greater symptom severity was associated with lesser activity in dorsal occipital cortex and ventrolateral prefrontal cortex for normal and high spatial frequency images. Conclusions Individuals with body dysmorphic disorder have abnormal brain activation patterns when viewing objects. Hypoactivity in visual association areas for configural and holistic (low detail) elements and abnormal allocation of prefrontal systems for details is consistent with a model of imbalances in global vs. local processing. This may occur not only for appearance but also for general stimuli unrelated to their symptoms. PMID:21557897

Localized 1H-MR spectroscopy in moyamoya disease before and after revascularization surgery

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Lim, Soo Mee; Choi, Hye Young; Suh, Jung Soo [Ewha Womans University Hospital, Seoul (Korea, Republic of); Lee, Jung Hee; Lim, Keun Ho; Suh, Dae Chul; Lee, Ho Kyu; Lim, Tae Hwan; Ra, Young Shin [Ulsan University College of Medicine, Seoul (Korea, Republic of)

2003-06-01

To evaluate, using localized proton magnetic resonance spectroscopy (1H-MRS), the cerebral metabolic change apparent after revascularization surgery in patients with moyamoya disease. Sixteen children with moyamoya disease and eight age-matched normal controls underwent MR imaging, MR angiography, conventional angiography, and {sup 99m}Tc- ECD SPECT. Frontal white matter and the basal ganglia of both hemispheres were subjected to localized {sup 1}H-MRS, and after revascularization surgery, four patients underwent follow-up {sup 1}H-MRS. Decreased NAA/Cr ratios (1.35{+-}0.14 in patients vs. 1.55{+-}0.24 in controls) and Cho/Cr ratios (0.96{+-}0.13 in patients vs. 1.10{+-}0.11 in controls) were observed in frontal white matter. After revascularization surgery, NAA/Cr and Cho/Cr ratios in this region increased. In the basal ganglia, there is no abnormal metabolic ratios. Localized 1H-MRS revealed abnormal metabolic change in both hemispheres of children with moyamoya disease. Because of its non-invasive nature, {sup 1}H-MRS is potentially useful for the preoperative evaluation of metabolic abnormalities and their postoperative monitoring.

Localized 1H-MR spectroscopy in moyamoya disease before and after revascularization surgery

International Nuclear Information System (INIS)

Lim, Soo Mee; Choi, Hye Young; Suh, Jung Soo; Lee, Jung Hee; Lim, Keun Ho; Suh, Dae Chul; Lee, Ho Kyu; Lim, Tae Hwan; Ra, Young Shin

2003-01-01

To evaluate, using localized proton magnetic resonance spectroscopy (1H-MRS), the cerebral metabolic change apparent after revascularization surgery in patients with moyamoya disease. Sixteen children with moyamoya disease and eight age-matched normal controls underwent MR imaging, MR angiography, conventional angiography, and 99m Tc- ECD SPECT. Frontal white matter and the basal ganglia of both hemispheres were subjected to localized 1 H-MRS, and after revascularization surgery, four patients underwent follow-up 1 H-MRS. Decreased NAA/Cr ratios (1.35±0.14 in patients vs. 1.55±0.24 in controls) and Cho/Cr ratios (0.96±0.13 in patients vs. 1.10±0.11 in controls) were observed in frontal white matter. After revascularization surgery, NAA/Cr and Cho/Cr ratios in this region increased. In the basal ganglia, there is no abnormal metabolic ratios. Localized 1H-MRS revealed abnormal metabolic change in both hemispheres of children with moyamoya disease. Because of its non-invasive nature, 1 H-MRS is potentially useful for the preoperative evaluation of metabolic abnormalities and their postoperative monitoring

Normal and abnormal neuronal migration in the developing cerebral cortex.

Science.gov (United States)

Sun, Xue-Zhi; Takahashi, Sentaro; Cui, Chun; Zhang, Rui; Sakata-Haga, Hiromi; Sawada, Kazuhiko; Fukui, Yoshihiro

2002-08-01

Neuronal migration is the critical cellular process which initiates histogenesis of cerebral cortex. Migration involves a series of complex cell interactions and transformation. After completing their final mitosis, neurons migrate from the ventricular zone into the cortical plate, and then establish neuronal lamina and settle onto the outermost layer, forming an "inside-out" gradient of maturation. This process is guided by radial glial fibers, requires proper receptors, ligands, other unknown extracellular factors, and local signaling to stop neuronal migration. This process is also highly sensitive to various physical, chemical and biological agents as well as to genetic mutations. Any disturbance of the normal process may result in neuronal migration disorder. Such neuronal migration disorder is believed as major cause of both gross brain malformation and more special cerebral structural and functional abnormalities in experimental animals and in humans. An increasing number of instructive studies on experimental models and several genetic model systems of neuronal migration disorder have established the foundation of cortex formation and provided deeper insights into the genetic and molecular mechanisms underlying normal and abnormal neuronal migration.

Isolated macrodactyly or extremely localized Proteus syndrome?

NARCIS (Netherlands)

van Bever, Y.; Hennekam, R. C.

1994-01-01

We report on a woman with unilateral macrosyndactyly of the second and third toes, a local plantar soft tissue lump, and radiographically an abnormal shape of the phalanges of the affected toes. This finding may represent either an isolated macrosyndactyly or an extremely localised form of Proteus

Quasi-local mass in the covariant Newtonian spacetime

International Nuclear Information System (INIS)

Wu, Y-H; Wang, C-H

2008-01-01

In general relativity, quasi-local energy-momentum expressions have been constructed from various formulae. However, the Newtonian theory of gravity gives a well-known and a unique quasi-local mass expression (surface integration). Since geometrical formulation of Newtonian gravity has been established in the covariant Newtonian spacetime, it provides a covariant approximation from relativistic to Newtonian theories. By using this approximation, we calculate the Komar integral, the Brown-York quasi-local energy and the Dougan-Mason quasi-local mass in the covariant Newtonian spacetime. It turns out that the Komar integral naturally gives the Newtonian quasi-local mass expression; however, further conditions (spherical symmetry) need to be made for Brown-York and Dougan-Mason expressions

Abnormal Cervical Cancer Screening Test Results

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... AQ FREQUENTLY ASKED QUESTIONS FAQ187 GYNECOLOGIC PROBLEMS Abnormal Cervical Cancer Screening Test Results • What is cervical cancer screening? • What causes abnormal cervical cancer screening test ...

Communication and abnormal behaviour.

Science.gov (United States)

Crown, S

1979-01-01

In this paper the similarities between normal and abnormal behaviour are emphasized and selected aspects of communication, normal and aberrant, between persons are explored. Communication in a social system may be verbal or non-verbal: one person's actions cause a response in another person. This response may be cognitive, behavioural or physiological. Communication may be approached through the individual, the social situation or social interaction. Psychoanalysis approaches the individual in terms of the coded communications of psychoneurotic symptoms or psychotic behaviour; the humanist-existential approach is concerned more with emotional expression. Both approaches emphasize the development of individual identity. The interaction between persons and their social background is stressed. Relevant are sociological concepts such as illness behaviour, stigma, labelling, institutionalization and compliance. Two approaches to social interactions are considered: the gamesplaying metaphor, e.g. back pain as a psychosocial manipulation--the 'pain game'; and the 'spiral of reciprocal perspectives' which emphasizes the interactional complexities of social perceptions. Communicatory aspects of psychological treatments are noted: learning a particular metaphor such as 'resolution' of the problem (psychotherapy), learning more 'rewarding' behaviour (learning theory) or learning authenticity or self-actualization (humanist-existential).

Statistics of Local Extremes

DEFF Research Database (Denmark)

Larsen, Gunner Chr.; Bierbooms, W.; Hansen, Kurt Schaldemose

2003-01-01

. A theoretical expression for the probability density function associated with local extremes of a stochasticprocess is presented. The expression is basically based on the lower four statistical moments and a bandwidth parameter. The theoretical expression is subsequently verified by comparison with simulated...

Ectodomain of plasmodesmata-localized protein 5 in Arabidopsis: expression, purification, crystallization and crystallographic analysis.

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Wang, Xiaocui; Zhu, Peiyan; Qu, Shanshan; Zhao, Jie; Singh, Prashant K; Wang, Wei

2017-09-01

Plasmodesmata-localized protein 5 (PDLP5) is a cysteine-rich receptor-like protein which is localized on the plasmodesmata of Arabidopsis thaliana. Overexpression of PDLP5 can reduce the permeability of the plasmodesmata and further affect the cell-to-cell movement of viruses and macromolecules in plants. The ectodomain of PDLP5 contains two DUF26 domains; however, the function of these domains is still unknown. Here, the ectodomain of PDLP5 from Arabidopsis was cloned and overexpressed using an insect expression system and was then purified and crystallized. X-ray diffraction data were collected to 1.90 Å resolution and were indexed in space group P1, with unit-cell parameters a = 41.9, b = 48.1, c = 62.2 Å, α = 97.3, β = 103.1, γ = 99.7°. Analysis of the crystal content indicated that there are two molecules in the asymmetric unit, with a Matthews coefficient of 2.51 Å 3  Da -1 and a solvent content of 50.97%.

GLP-2 receptor localizes to enteric neurons and endocrine cells expressing vasoactive peptides and mediates increased blood flow

DEFF Research Database (Denmark)

Guan, Xinfu; Karpen, Heidi E; Stephens, John

2006-01-01

. These actions are mediated by the G-protein-coupled receptor, GLP-2R. Cellular localization of the GLP-2R and the nature of its signaling network in the gut, however, are poorly defined. Thus, our aim was to establish cellular localization of GLP-2R and functional connection to vascular action of GLP-2......-dependently stimulated intestinal blood flow and coordinately upregulated the expression of intestinal eNOS mRNA, protein, and phosphorylation (eNOS-Ser1117). CONCLUSIONS: We conclude that the GLP-2-induced stimulation of blood flow is mediated by vasoactive neurotransmitters that are colocalized with GLP-2R in 2...

Low-set ears and pinna abnormalities

Science.gov (United States)

Low-set ears; Microtia; "Lop" ear; Pinna abnormalities; Genetic defect - pinna; Congenital defect - pinna ... conditions: Abnormal folds or location of the pinna Low-set ears No opening to the ear canal ...

Molecular cloning and expression analysis of a zebrafish novel zinc finger protein gene rnf141

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Wenqian Deng

2009-01-01

Full Text Available ZNF230 is a novel zinc finger gene cloned by our laboratory. In order to understand the potential functions of this gene in vertebrate development, we cloned the zebrafish orthologue of human ZNF230, named rnf141. The cDNA fragment of rnf141 was obtained by rapid amplification of cDNA ends (RACE. The open reading frame (ORF encodes a polypeptide of 222 amino acids which shares 75.65% identity with the human ZNF230. RT-PCR analysis in zebrafish embryo and adult tissues revealed that rnf141 transcripts are maternally derived and that rnf141 mRNA has a broad distribution. Zygotic rnf141 message is strongly localized in the central nervous system, as shown by whole-mount in situ hybridization. Knockdown and over expression of rnf141 can induce abnormal phenotypes, including abnormal development of brain, as well as yolk sac and axis extendsion. Marker gene analysis showed that rnf141 may play a role in normal dorsoventral patterning of zebrafish embryos, suggesting that rnf141 may have a broad function during early development of vertebrates.

Congenital abnormalities of the vertebral column in ferrets.

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Proks, Pavel; Stehlik, Ladislav; Paninarova, Michaela; Irova, Katarina; Hauptman, Karel; Jekl, Vladimir

2015-01-01

Vertebral column pathologies requiring surgical intervention have been described in pet ferrets, however little information is available on the normal vertebral formula and congenital variants in this species. The purpose of this retrospective study was to describe vertebral formulas and prevalence of congenital vertebral anomalies in a sample of pet ferrets. Radiographs of 172 pet ferrets (96 males and 76 females) were included in this retrospective study. In 143 ferrets (83.14%), five different formulas of the vertebral column were recorded with normal morphology of vertebrae (rib attachment included) but with a variable number of thoracic (Th), lumbar (L), and sacral (S) vertebrae. The number of cervical (C) vertebrae was constant in all examined animals. Observed vertebral formulas were C7/Th14/L6/S3 (51.74%), C7/Th14/L6/S4 (22.10%), C7/Th14/L7/S3 (6.98%), C7/Th15/L6/S3 (1.74%), and C7/Th15/L6/S4 (0.58%). Formula C7/Th14/L6/S4 was significantly more common in males than in females (P < 0.05). Congenital spinal abnormalities were found in 29 ferrets (16.86%), mostly localized in the thoracolumbar and lumbosacral regions. The cervical region was affected in only one case. Transitional vertebrae represented the most common congenital abnormalities (26 ferrets) in the thoracolumbar (13 ferrets) and lumbosacral regions (10 ferrets) or simultaneously in both regions (three ferrets). Other vertebral anomalies included block (two ferrets) and wedge vertebra (one ferret). Spina bifida was not detected. Findings from the current study indicated that vertebral formulas may vary in ferrets and congenital abnormalities are common. This should be taken into consideration for surgical planning. © 2014 American College of Veterinary Radiology.

Construction of recombinant ZNF230/GFP fused plasmids and their expression and cellular localization

DEFF Research Database (Denmark)

Xu, Wen-Ming; Zhang, Si-Zhong; Qiu, Wei-Min

2004-01-01

To use green fluorescent protein as a marker to study the localization of the fusion protein, the mutant full length cDNAs of human ZNF230 and mouse znf230 with their stop codon TGA changed to TGG were obtained by PCR amplification, and then cloned into pGEM-Teasy vector. After the double enzyme...... cutting, the mutated human and mouse ZNF230(znf230) were inserted into mammalian expression plasmid pEGFP-N1. Thus we constructed the plasmid with fusion gene of ZNF230 and green fluorescent protein(GFP). Then the Cos cell was transfected with the fused gene by liposome. Fluorescence microscopy showed...

Differentially expressed genes in embryonic cardiac tissues of mice lacking Folr1 gene activity

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Schwartz Robert J

2007-11-01

Full Text Available Abstract Background Heart anomalies are the most frequently observed among all human congenital defects. As with the situation for neural tube defects (NTDs, it has been demonstrated that women who use multivitamins containing folic acid peri-conceptionally have a reduced risk for delivering offspring with conotruncal heart defects 123. Cellular folate transport is mediated by a receptor or binding protein and by an anionic transporter protein system. Defective function of the Folr1 (also known as Folbp1; homologue of human FRα gene in mice results in inadequate transport, accumulation, or metabolism of folate during cardiovascular morphogenesis. Results We have observed cardiovascular abnormalities including outflow tract and aortic arch arterial defects in genetically compromised Folr1 knockout mice. In order to investigate the molecular mechanisms underlying the failure to complete development of outflow tract and aortic arch arteries in the Folr1 knockout mouse model, we examined tissue-specific gene expression difference between Folr1 nullizygous embryos and morphologically normal heterozygous embryos during early cardiac development (14-somite stage, heart tube looping (28-somite stage, and outflow track septation (38-somite stage. Microarray analysis was performed as a primary screening, followed by investigation using quantitative real-time PCR assays. Gene ontology analysis highlighted the following ontology groups: cell migration, cell motility and localization of cells, structural constituent of cytoskeleton, cell-cell adhesion, oxidoreductase, protein folding and mRNA processing. This study provided preliminary data and suggested potential candidate genes for further description and investigation. Conclusion The results suggested that Folr1 gene ablation and abnormal folate homeostasis altered gene expression in developing heart and conotruncal tissues. These changes affected normal cytoskeleton structures, cell migration and

Abnormal increase of cosmic ray on August 7th, 1972

International Nuclear Information System (INIS)

Kodama, Masahiro; Murakami, Kazuaki; Wada, Masami

1974-01-01

The abnormal increase of cosmic ray on Aug. 7th particularly the dependence of its starting time on local time was studied. Cosmic ray increased twice before and after the greatest Forbush decrease in history on August 4th and 7th, 1972. This study is a trial to estimate the anisotropic flow of solar cosmic ray from the time difference time at different places. Further, the past instance of 23 ground-level events were statistically restudied, and the relationship between the time of generation of solar cosmic ray and the time of transmission to the earth was investigated. A list is given regarding the solar cosmic ray of more than 10 9 eV which occurred since the observation had started. The list shows definite three groups. Attention is paid to the transmission time of F type which is considered to have the most simplest transmission mechanism. The dispersion of the transmission time is large regarding flare-starting time and peak wave intensity time, but is small regarding solar wave-starting time, but the dependence on the longitude is systematic. After all, cosmic ray is accelerated after 10 minutes since solar electric wave has started, and arrives at the earth most early in the case of a flare occurred at the root of garden force line toward the earth. In conclusion, the method of studying the difference of the starting time of abnormal increase according to local time may be an effective means for examining in the characteristics of anisotropic flow of solar cosmic ray. (Iwakiri, K.)

How can the process of postnatal adaptation be changed by the presence of congenital abnormalities of lip and palate

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Brucknerová Ingrid

2017-12-01

Full Text Available Despite modern approaches in molecular biology and genetics, we are still not able to identify the actual cause in more than 50% of all congenital defects. One-half of the unidentified cases is referred to as “multifactorial”. Detailed prenatal investigation of the fetus can discover the presence of congenital abnormality, which can worsen the process of postnatal adaptation. Retrospective analysis of newborns admitted to the Neonatal Department of Intensive Medicine (NDIM in 2012-2016 with the aim to analyze how the process of postnatal adaptation can be changed by the presence of congenital abnormalities of lip and palate. During a five-year period, 13 newborns were admitted to NDIM (2 premature; 11 term newborns. Chromosomal abnormality was confirmed in one patient (Down syndrome and in one patient suspicion of Patau syndrome was found. Twelve newborns had complete cheilognathopalatoschisis. Two premature newborns and two term newborns had perinatal asphyxia. In this group of patients, 33% had respiratory insufficiency without the presence of congenital heart abnormality, 66% had congenital heart abnormality with respiratory insufficiency, and 2 patients had feeding problems. Only one patient had a positive family history. The diagnosis of complete cheilognathopalatoschisis was confirmed prenatally only in 9 patients. We confirmed that clinical consequences of congenital abnormalities of lip and palate depend on the nature, localization and range of abnormalities, as well as on the genetic background and accompanying congenital abnormalities. Prenatal confirmation of the presence of congenital abnormalities has an important influence on the postnatal management of a patient.

Congenital Abnormalities

Science.gov (United States)

... tube defects. However, there is also a genetic influence to this type of congenital anomaly. Unknown Causes The vast majority of congenital abnormalities have no known cause. This is particularly troubling for parents who plan to have more children, because there is no way to predict if ...

Chromosomal Abnormalities Associated With Omphalocele

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Chih-Ping Chen

2007-03-01

Full Text Available Fetuses with omphalocele have an increased risk for chromosomal abnormalities. The risk varies with maternal age, gestational age at diagnosis, association with umbilical cord cysts, complexity of associated anomalies, and the contents of omphalocele. There is considerable evidence that genetics contributes to the etiology of omphalocele. This article provides an overview of chromosomal abnormalities associated with omphalocele and a comprehensive review of associated full aneuploidy such as trisomy 18, trisomy 13, triploidy, trisomy 21, 45,X, 47,XXY, and 47,XXX, partial aneuploidy such as dup(3q, dup(11p, inv(11, dup(1q, del(1q, dup(4q, dup(5p, dup(6q, del(9p, dup(15q, dup(17q, Pallister-Killian syndrome with mosaic tetrasomy 12p and Miller-Dieker lissencephaly syndrome with deletion of 17p13.3, and uniparental disomy (UPD such as UPD 11 and UPD 14. Omphalocele is a prominent marker for chromosomal abnormalities. Perinatal identification of omphalocele should alert chromosomal abnormalities and familial unbalanced translocations, and prompt thorough cytogenetic investigations and genetic counseling.

Abnormal notochord branching is associated with foregut malformations in the adriamycin treated mouse model.

Science.gov (United States)

Hajduk, Piotr; Sato, Hideaki; Puri, Prem; Murphy, Paula

2011-01-01

Oesophageal atresia (OA) and tracheooesophageal fistula (TOF) are relatively common human congenital malformations of the foregut where the oesophagus does not connect with the stomach and there is an abnormal connection between the stomach and the respiratory tract. They require immediate corrective surgery and have an impact on the future health of the individual. These abnormalities are mimicked by exposure of rat and mouse embryos in utero to the drug adriamycin. The causes of OA/TOF during human development are not known, however a number of mouse mutants where different signalling pathways are directly affected, show similar abnormalities, implicating multiple and complex signalling mechanisms. The similarities in developmental outcome seen in human infants and in the adriamycin treated mouse model underline the potential of this model to unravel the early embryological events and further our understanding of the processes disturbed, leading to such abnormalities. Here we report a systematic study of the foregut and adjacent tissues in embryos treated with adriamycin at E7 and E8 and analysed between E9 and E12, comparing morphology in 3D in 149 specimens. We describe a spectrum of 8 defects, the most common of which is ventral displacement and branching of the notochord (in 94% of embryos at E10) and a close spatial correspondence between the site of notochord branching and defects of the foregut. In addition gene expression analysis shows altered dorso-ventral foregut patterning in the vicinity of notochord branches. This study shows a number of features of the adriamycin mouse model not previously reported, implicates the notochord as a primary site of disturbance in such abnormalities and underlines the importance of the model to further address the mechanistic basis of foregut congenital abnormalities.

Dynein and EFF-1 control dendrite morphology by regulating the localization pattern of SAX-7 in epidermal cells.

Science.gov (United States)

Zhu, Ting; Liang, Xing; Wang, Xiang-Ming; Shen, Kang

2017-12-01

Our previous work showed that the cell adhesion molecule SAX-7 forms an elaborate pattern in Caenorhabditis elegans epidermal cells, which instructs PVD dendrite branching. However, the molecular mechanism forming the SAX-7 pattern in the epidermis is not fully understood. Here, we report that the dynein light intermediate chain DLI-1 and the fusogen EFF-1 are required in epidermal cells to pattern SAX-7. While previous reports suggest that these two molecules act cell-autonomously in the PVD, our results show that the disorganized PVD dendritic arbors in these mutants are due to the abnormal SAX-7 localization patterns in epidermal cells. Three lines of evidence support this notion. First, the epidermal SAX-7 pattern was severely affected in dli-1 and eff-1 mutants. Second, the abnormal SAX-7 pattern was predictive of the ectopic PVD dendrites. Third, expression of DLI-1 or EFF-1 in the epidermis rescued both the SAX-7 pattern and the disorganized PVD dendrite phenotypes, whereas expression of these molecules in the PVD did not. We also show that DLI-1 functions cell-autonomously in the PVD to promote distal branch formation. These results demonstrate the unexpected roles of DLI-1 and EFF-1 in the epidermis in the control of PVD dendrite morphogenesis. © 2017. Published by The Company of Biologists Ltd.

Frequency of metabolic abnormalities in urinary stones patients.

Science.gov (United States)

Ahmad, Iftikhar; Pansota, Mudassar Saeed; Tariq, Muhammad; Tabassum, Shafqat Ali

2013-11-01

To determine the frequency of metabolic abnormalities in the serum and urine of patients with urinary stones disease. Two hundred patients with either multiple or recurrent urolithiasis diagnosed on ultrasonography and intravenous urography were included in this study. 24 hour urine sample were collected from each patient and sent for PH, specific gravity, Creatinine, uric acid, calcium, phosphate, oxalate, citrate and magnesium. In addition, blood sample of each patient was also sent for serum levels of urea, creatinine, uric acid, phosphate and calcium. Mean age of patients was 38 ± 7.75 years with male to female ratio of 2:1. The main presenting complaint was lumber pain and 82.5% patients were found to have calcium oxalate stones on chemical analysis. Metabolic abnormalities were found in 90.5% patients, whereas there were no metabolic abnormalities in 19 (9.5%) patients. Forty patients (21.5%) only had one metabolic abnormality and 157 (78.5%) patients had multiple metabolic abnormalities. Hyperoxaluria was the most commonly observed metabolic abnormality and was found in 64.5% patients. Other significant metabolic abnormalities were hypercalciuria, Hypercalcemia, hypocitraturia and hyperuricemia. This study concludes that frequency of metabolic abnormalities is very high in patients with urolithiasis and hyperoxaluria, hypercalciuria and hypocitraturia are the most important metabolic abnormalities observed in these patients.

Semi-quantitative approach of tracer uptake abnormalities in myocardial SPECT: application to inferior defects

International Nuclear Information System (INIS)

Damien, J.; Bontemps, L.; Gabain, M.; Felecan, R.; Itti, R.

1997-01-01

This study was designed in order to evaluate in a more objective manner than visual inspection, the detection of myocardial inferior wall hypo-fixations in perfusion SPECT. We have studied 90 patients, divided into four groups: GO (7 M, 13 F, 55 ± 21 years) and G1 (9 M, 12 F, 49 ± 26 years) are groups of patients considered as normal; G2 (20 M, 3 F, 60 ± 12 years) corresponds to patients with reversible ischaemia, where the stress examination is abnormal but the resting one is close to normality; G3 (21 H, 5 F, 63 ± 8 years) includes infarcts where both examinations are definitely abnormal. Intra and inter-group statistical comparisons were first done using polar maps (Bull's eye) and an iterative method has then been developed for comparing each image of groups 1, 2 and to the mean normal data (GO). Finally, we have built a ROC (receiver operating characteristic) curves network for determining the best confidence interval and the optimal normality / abnormality criterion (number of pixels located without the confidence interval). The results are expressed in terms of sensitivity and specificity using the most favourable situation derived from the ROC curves. For 2.5 standard deviations, we obtain, for G2 (reversible injury) compared to G1, 78.3 % sensibility and 76.2 % for specificity at rest with at maximum 20 abnormal pixels as normality criterion, and at stress 81 % and 82.6 % for pixels. For G3 (permanent injury) compared to G1, the values are respectively : sensitivity = 88.5 % and specificity = 85.2 % at rest for 40 pixels; sensitivity = 92.3 % and specificity = 85.2 % at stress for 80 pixels. The method developed seems to be applicable on a wider scale, not only limited to inferior area abnormalities. It is able to optimise, for each situation, the confidence interval for an abnormal image definition and the most significant criterion, in terms of number of abnormal pixels, to detect a diseased myocardial area. (authors)

[Longjintonglin Capsules for type IIIA prostatitis accompanied by abnormal semen liquefaction: A clinical observation].

Science.gov (United States)

Cai, Hong-cai; Wan, Chang-chun; Geng, Qiang; Liu, Wei; Zhang, Guo-wei; Shang, Xue-jun; Huang, Yu-feng

2016-01-01

To evaluate the therapeutic effect of Longjintonglin Capsules on type IIIA prostatitis accompanied by abnormal semen liquefaction. We selected 140 patients with type IIIA prostatitis accompanied by abnormal semen liquefaction according to the diagnostic standards of the American Institutes of Health (NIH) and treated them with Longjintonglin Capsules orally 3 capsules once tid for 12 weeks. We obtained the NIH Chronic Prostatitis Symptom Indexes (NIH-CPSI), traditional Chinese medicine (TCM) syndrome scores, leukocyte count in the expressed prostatic secretion (EPS), semen liquefaction time, and the results of semen analysis and compared these indicators before and after the treatment. Of the 140 cases, 132 were included in this study, excluding 8 due to their incomplete case histories. Before and after 4, 8 and 12 weeks of medication, the total NIH-CPSI scores were 24.52 ± 5.43, 21.28 ± 4.85, 18.01 ± 4.28, and 14.49 ± 3.65 (P prostatitis were cured and another 72 well responded, with an overall response rate of 78.0%. Of those with abnormal semen liquefaction, 61 were cured, 39 well responded, and 32 failed to respond, with an overall effectiveness rate of 75.8%. Semen analysis showed significantly increased percentage of progressively motile sperm after 4, 8 and 12 weeks of medication as compared with the baseline (P prostatitis accompanied by abnormal semen liquefaction.

Hepatitis B virus X protein (HBx)-induced abnormalities of nucleic acid metabolism revealed by (1)H-NMR-based metabonomics.

Science.gov (United States)

Dan Yue; Zhang, Yuwei; Cheng, Liuliu; Ma, Jinhu; Xi, Yufeng; Yang, Liping; Su, Chao; Shao, Bin; Huang, Anliang; Xiang, Rong; Cheng, Ping

2016-04-14

Hepatitis B virus X protein (HBx) plays an important role in HBV-related hepatocarcinogenesis; however, mechanisms underlying HBx-mediated carcinogenesis remain unclear. In this study, an NMR-based metabolomics approach was applied to systematically investigate the effects of HBx on cell metabolism. EdU incorporation assay was conducted to examine the effects of HBx on DNA synthesis, an important feature of nucleic acid metabolism. The results revealed that HBx disrupted metabolism of glucose, lipids, and amino acids, especially nucleic acids. To understand the potential mechanism of HBx-induced abnormalities of nucleic acid metabolism, gene expression profiles of HepG2 cells expressing HBx were investigated. The results showed that 29 genes involved in DNA damage and DNA repair were differentially expressed in HBx-expressing HepG2 cells. HBx-induced DNA damage was further demonstrated by karyotyping, comet assay, Western blotting, immunofluorescence and immunohistochemistry analyses. Many studies have previously reported that DNA damage can induce abnormalities of nucleic acid metabolism. Thus, our results implied that HBx initially induces DNA damage, and then disrupts nucleic acid metabolism, which in turn blocks DNA repair and induces the occurrence of hepatocellular carcinoma (HCC). These findings further contribute to our understanding of the occurrence of HCC.

Prevalence of asymptomatic urinary abnormalities among adolescents

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Mohamed Fouad

2016-01-01

Full Text Available To determine the prevalence of asymptomatic urinary abnormalities in adolescents, first morning clean mid-stream urine specimens were obtained from 2500 individuals and examined by dipstick and light microscopy. Adolescents with abnormal screening results were reexamined after two weeks and those who had abnormal results twice were subjected to systemic clinical examination and further clinical and laboratory investigations. Eight hundred and three (32.1% individuals had urinary abnormalities at the first screening, which significantly decreased to 345 (13.8% at the second screening, (P <0.001. Hematuria was the most common urinary abnormalities detected in 245 (9.8% adolescents who had persistent urine abnormalities; 228 (9.1% individuals had non glomerular hematuria. The hematuria was isolated in 150 (6% individuals, combined with leukocyturia in 83 (3.3% individuals, and combined with proteinuria in 12 (0.5% individuals. Leukocyturia was detected in 150 (6% of all studied adolescents; it was isolated in 39 (1.6% individuals and combined with proteinuria in 28 (1.1% of them. Asymp- tomatic bacteriuria was detected in 23 (0.9% of all studied adolescents; all the cases were females. Proteinuria was detected in 65 (2.6% of all the studied adolescents; 45 (1.8% indivi- duals had <0.5 g/day and twenty (0.8% individuals had 0.5-3 g/day. Asymptomatic urinary abnormalities were more common in males than females and adolescents from rural than urban areas (P <0.01 and (P <0.001, respectively. The present study found a high prevalence of asymptomatic urinary abnormalities among adolescents in our population.

Reciprocal Effects of Oxidative Stress on Heme Oxygenase Expression and Activity Contributes to Reno-Vascular Abnormalities in EC-SOD Knockout Mice

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Tomoko Kawakami

2012-01-01

although, HO activity was significantly (P<0.05 attenuated along with attenuation of serum adiponectin and vascular epoxide levels (P<0.05. CoPP, in EC-SOD(−/− mice, enhanced HO activity (P<0.05 and reversed aforementioned pathophysiological abnormalities along with restoration of vascular EET, p-eNOS, p-AKT and serum adiponectin levels in these animals. Taken together our results implicate a causative role of insufficient activation of heme-HO-adiponectin system in pathophysiological abnormalities observed in animal models of chronic oxidative stress such as EC-SOD(−/− mice.

Expression and localization of ionotropic glutamate receptor subunits in the goldfish retina--an in situ hybridization and immunocytochemical study

NARCIS (Netherlands)

Vandenbranden, C. A.; Kamphuis, W.; Nunes Cardozo, B.; Kamermans, M.

2000-01-01

The expression and distribution of AMPA, kainate and NMDA glutamate receptor subunits was studied in the goldfish retina. For the immunocytochemical localization of the AMPA receptor antisera against GluR2, GluR2/3 and GluR4 were used, and for in situ hybridization rat specific probes for GluR1 and

Expression of PD-L1 and presence of CD8-positive T cells in pre-treatment specimens of locally advanced cervical cancer.

Science.gov (United States)

Enwere, Emeka K; Kornaga, Elizabeth N; Dean, Michelle; Koulis, Theodora A; Phan, Tien; Kalantarian, Maria; Köbel, Martin; Ghatage, Prafull; Magliocco, Anthony M; Lees-Miller, Susan P; Doll, Corinne M

2017-04-01

Several of the cancer immunotherapies under investigation or in clinical use target the programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) signaling axis. PD-L1 expression in tumor samples has been used as a predictive marker for response to these therapeutics, and may also have independent prognostic utility when assessed along with immune cell markers. Our objectives were to assess the expression of PD-L1 in tumor specimens from a uniformly treated patient cohort with locally advanced cervical cancer, and to determine its prognostic significance along with the density of tumor-infiltrating T cells. We identified 120 patients with locally advanced cervical cancer treated with radical chemoradiotherapy, and built tissue microarrays from their formalin-fixed, paraffin-embedded pre-treatment biopsies. We used conventional brightfield and fluorescence immunohistochemistry to detect PD-L1, and quantified protein expression using both manual pathologist scoring and automated software analysis. We also evaluated the effect of PD-L1 expression in tumors, along with the presence and density of intra-tumoral CD8 + T cells, on patient survival outcomes. Approximately 96% of the tumor samples expressed PD-L1, as determined using quantitative software analysis. Neither expression of PD-L1 nor density of CD8 + T cells was associated with progression-free or overall survival. However, there was a trend towards worse progression-free survival in patients whose tumors expressed PD-L1 but lacked CD8 + T cells (hazard ratio=0.43 (0.18-1.01), P=0.053). Nevertheless, the high percentage of cervical cancer tumor samples expressing PD-L1 suggests that anti-PD-L1 or anti-PD-1 therapies are potential treatment options for this patient population.

Impairment in local and global processing and set-shifting in body dysmorphic disorder

Science.gov (United States)

Kerwin, Lauren; Hovav, Sarit; Helleman, Gerhard; Feusner, Jamie D.

2014-01-01

Body dysmorphic disorder (BDD) is characterized by distressing and often debilitating preoccupations with misperceived defects in appearance. Research suggests that aberrant visual processing may contribute to these misperceptions. This study used two tasks to probe global and local visual processing as well as set shifting in individuals with BDD. Eighteen unmedicated individuals with BDD and 17 non-clinical controls completed two global-local tasks. The embedded figures task requires participants to determine which of three complex figures contained a simpler figure embedded within it. The Navon task utilizes incongruent stimuli comprised of a large letter (global level) made up of smaller letters (local level). The outcome measures were response time and accuracy rate. On the embedded figures task, BDD individuals were slower and less accurate than controls. On the Navon task, BDD individuals processed both global and local stimuli slower and less accurately than controls, and there was a further decrement in performance when shifting attention between the different levels of stimuli. Worse insight correlated with poorer performance on both tasks. Taken together, these results suggest abnormal global and local processing for non-appearance related stimuli among BDD individuals, in addition to evidence of poor set-shifting abilities. Moreover, these abnormalities appear to relate to the important clinical variable of poor insight. Further research is needed to explore these abnormalities and elucidate their possible role in the development and/or persistence of BDD symptoms. PMID:24972487

Report to Congress on abnormal occurrences

International Nuclear Information System (INIS)

1990-10-01

Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from April 1 through June 30, 1990. The report discusses six abnormal occurrences, none involving a nuclear power plant. There were five abnormal occurrences at NRC licensees: (1) deficiencies in brachytherapy program; (2) a radiation overexposure of a radiographer; (3) a medical diagnostic misadministration; (4) administration of iodine-131 to a lactating female with subsequent uptake by her infant; and (5) a medical therapy misadministration. An Agreement State (Arizona) reported an abnormal occurrence involving a medical diagnostic misadministration. The report also contains information that updates a previously reported occurrence

IGF-I and branchial IGF receptor expression and localization during salinity acclimation in striped bass

DEFF Research Database (Denmark)

Tipsmark, Christian Kølbaek; Luckenbach, John Adam; Madsen, Steffen

2007-01-01

The initial response of the IGF-I system and the expression and cellular localization of IGF type-I receptor (IGF-IR) were studied in the gill of a euryhaline teleost during salinity acclimation. Exposure of striped bass (Morone saxatilis) to hyperosmotic and hypoosmotic challenges induced small...... in either plasma IGF-I, liver, or gill IGF-I mRNA, or gill IGF-IR mRNA levels. In a separate experiment, FW-acclimated fish were injected with saline or IGF-I prior to a 24-h SW challenge. Rapid regain of osmotic balance following SW transfer was hindered by IGF-I. Immunohistochemistry revealed...

Local-global classifier fusion for screening chest radiographs

Science.gov (United States)

Ding, Meng; Antani, Sameer; Jaeger, Stefan; Xue, Zhiyun; Candemir, Sema; Kohli, Marc; Thoma, George

2017-03-01

Tuberculosis (TB) is a severe comorbidity of HIV and chest x-ray (CXR) analysis is a necessary step in screening for the infective disease. Automatic analysis of digital CXR images for detecting pulmonary abnormalities is critical for population screening, especially in medical resource constrained developing regions. In this article, we describe steps that improve previously reported performance of NLM's CXR screening algorithms and help advance the state of the art in the field. We propose a local-global classifier fusion method where two complementary classification systems are combined. The local classifier focuses on subtle and partial presentation of the disease leveraging information in radiology reports that roughly indicates locations of the abnormalities. In addition, the global classifier models the dominant spatial structure in the gestalt image using GIST descriptor for the semantic differentiation. Finally, the two complementary classifiers are combined using linear fusion, where the weight of each decision is calculated by the confidence probabilities from the two classifiers. We evaluated our method on three datasets in terms of the area under the Receiver Operating Characteristic (ROC) curve, sensitivity, specificity and accuracy. The evaluation demonstrates the superiority of our proposed local-global fusion method over any single classifier.

Ergonomics for enhancing detection of machine abnormalities.

Science.gov (United States)

Illankoon, Prasanna; Abeysekera, John; Singh, Sarbjeet

2016-10-17

Detecting abnormal machine conditions is of great importance in an autonomous maintenance environment. Ergonomic aspects can be invaluable when detection of machine abnormalities using human senses is examined. This research outlines the ergonomic issues involved in detecting machine abnormalities and suggests how ergonomics would improve such detections. Cognitive Task Analysis was performed in a plant in Sri Lanka where Total Productive Maintenance is being implemented to identify sensory types that would be used to detect machine abnormalities and relevant Ergonomic characteristics. As the outcome of this research, a methodology comprising of an Ergonomic Gap Analysis Matrix for machine abnormality detection is presented.

Over-expression of β-catenin is associated with high grade of ...

African Journals Online (AJOL)

The aim of this study was to evaluate abnormalities of β-catenin protein expression, subcellular ... Patients and methods: Forty prostate cancer specimens, obtained from patients with different stages ... Conclusions: We concluded that changes in expression and cell distribution of β-catenin correlated ... HOW TO USE AJOL.

Benign chronic neutropenia with abnormalities involving 16q22, affecting mother and daughter.

Science.gov (United States)

Glasser, Lewis; Meloni-Ehrig, Aurelia; Joseph, Plakyil; Mendiola, Jennifer

2006-04-01

We report a case of familial, chronic, benign neutropenia in a 17-year-old female showing (1) the spontaneous expression of a heritable rare fragile site at 16q22 and (2) a deletion at the same region. The del(16)(q22), which most likely originated from the fragile site, was the main clonal abnormality detected in the patient's bone marrow cells, whereas a few cells with either del(16)(q22) or fra(16)(q22) were seen in the patient's peripheral blood. Interestingly, the del(16q) was also detected in the patient's uncultured cells, as demonstrated by FISH, excluding an in vitro origin of the del(16q) during culture. The bone marrow was hypocellular with decreased neutrophils and their precursors. Absolute neutrophil counts ranged from (0.62 to 1.24) x 10(9)/L with a median value of 1.02 x 10(9)/L. The patient had a more severe neutropenia than her mother, which correlated with the presence of more cells with del(16q) in the marrow. The patient's mother, who was also diagnosed with neutropenia, revealed only a few cells with the rare fra(16)(q22) in her peripheral blood cells, whereas her bone marrow showed cells with both fra(16)(q22) and del(16)(q22), although the del(16q) was present in only 2/20 cells. Some possible candidate genes contributing to the pathogenesis of the neutropenia are discussed. Chromosome abnormalities involving the 16q22 breakpoint have been observed in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In this patient, the del(16)(q22) risk factor is unknown for subsequent development of MDS or AML. Another point to consider is the need to determine the origin of a chromosome abnormality, particularly when the clinical picture does not fit the chromosome findings. Although, the observation of a constitutional structural abnormality in a mosaic form is an extremely rare event, it is somewhat different in the case of a fragile site expression, which can, as in this case, be present in some cells and not in others. Copyright 2006

No Tryptophan, Tyrosine and Phenylalanine Abnormalities in Children with Attention-Deficit/Hyperactivity Disorder

OpenAIRE

Bergwerff, C.E.; Luman, M.; Blom, H.J.; Oosterlaan, J.

2016-01-01

Background The aim of the current study was to explore the role of aromatic amino acids (AAAs) in blood in relation to attention-deficit/hyperactivity disorder (ADHD). Given their impact on the synthesis of serotonin and dopamine, decreased concentrations of the AAAs tryptophan, tyrosine and phenylalanine in blood may contribute to the expression of ADHD symptoms. Decreased AAA blood concentrations, in turn, may be related to lowered dietary protein intake or to abnormal AAA catabolism, as ev...

[Hysteroscopic polypectomy, treatment of abnormal uterine bleeding].

Science.gov (United States)

de Los Rios, P José F; López, R Claudia; Cifuentes, P Carolina; Angulo, C Mónica; Palacios-Barahona, Arlex U

2015-07-01

To evaluate the effectiveness of the hysteroscopic polypectomy in terms of the decrease of the abnormal uterine bleeding. A cross-sectional and analytical study was done with patients to whom a hysteroscopic polypectomy was done for treating the abnormal uterine bleeding, between January 2009 and December 2013. The response to the treatment was evaluated via a survey given to the patients about the behavior of the abnormal uterine bleeding after the procedure and about overall satisfaction. The results were obtained after a hysteroscopic polypectomy done to 128 patients and were as follows. The average time from the polypectomy applied until the survey was 30.5 months, with a standard deviation of 18 months. 67.2% of the patients reported decreased abnormal uterine bleeding and the 32.8% reported a persistence of symptoms. On average 82.8% of the. patients were satisfied with the treatment. Bivariate and multivariate analysis showed no association between the variables studied and no improvement of abnormal uterine bleeding after surgery (polypectomy). There were no complications. Hysteroscopic polypectomy is a safe surgical treatment, which decreases on two of three patients the abnormal uterine bleeding in the presence of endometrial polyps, with an acceptable level of satisfaction.

The expression, localization and function of α7 nicotinic acetylcholine receptor in rat corpus cavernosum.

Science.gov (United States)

Faghir-Ghanesefat, Hedyeh; Rahimi, Nastaran; Yarmohammadi, Fatemeh; Mokhtari, Tahmineh; Abdollahi, Ali Reza; Ejtemaei Mehr, Shahram; Dehpour, Ahmad R

2017-12-01

Alpha7 nicotinic acetylcholine receptor (α7-nAChR), an emerging pharmacological target for a variety of medical conditions, is expressed in the most mammalian tissues with different effects. So, this study was designed to investigate the expression, localization and effect of α7-nAChR in rat corpus cavernosum (CC). Reverse transcription polymerase chain reaction (RT-PCR) revealed that α7-nAChR was expressed in rat CC and double immunofluorescence studies demonstrated the presence of α7-nAChR in corporal neurons. The rat CC segments were mounted in organ bath chambers and contracted with phenylephrine (0.1 μm -300 μm) to investigate the relaxation effect of electrical field stimulation (EFS,10 Hz) assessed in the presence of guanethidine (adrenergic blocker, 5 μm) and atropine (muscarinic cholinergic blocker, 1 μm) to obtain non-adrenergic non-cholinergic (NANC) response. Cumulative administration of nicotine significantly potentiated the EFS-induced NANC relaxation (-log EC50 = 7.5 ± 0.057). Whereas, the potentiated NANC relaxation of nicotine was significantly inhibited with different concentrations of methyllycaconitine citrate (α7-nAChR antagonist, P < 0.05) in preincubated strips. L-NAME (non-specific nitric oxide synthase inhibitor, 1 μm) completely blocked the neurogenic relaxation induced by EFS plus nicotine. To conclude α7-nAChR is expressed in rat CC and modulates the neurogenic relaxation response to nicotine. © 2017 Royal Pharmaceutical Society.

LPS challenge regulates gene expression and tissue localization of a Ciona intestinalis gene through an alternative polyadenylation mechanism.

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Aiti Vizzini

Full Text Available A subtractive hybridization strategy for the identification of differentially expressed genes was performed between LPS-challenged and naive Ciona intestinalis. This strategy allowed the characterization of two transcripts (Ci8short and Ci8long generated by the use of two Alternative Polyadenylation sites. The Ci8long transcript contains a protein domain with relevant homology to several components of the Receptor Transporting Protein (RTP family not present in the Ci8short mRNA. By means of Real Time PCR and Northern Blot, the Ci8short and Ci8long transcripts showed a different pattern of gene expression with the Ci8short mRNA being strongly activated after LPS injection in the pharynx. In situ hybridization analysis demonstrated that the activation of the APA site also influenced the tissue localization of the Ci8short transcript. This analysis showed that the Ci8long mRNA was expressed in hemocytes meanwhile the Ci8short mRNA was highly transcribed also in vessel endothelial cells and in the epithelium of pharynx. These findings demonstrated that regulation of gene expression based on different polyadenylation sites is an ancestral powerful strategy influencing both the level of expression and tissue distribution of alternative transcripts.

Equipment abnormality monitoring device

International Nuclear Information System (INIS)

Ando, Yasumasa

1991-01-01

When an operator hears sounds in a plantsite, the operator compares normal sounds of equipment which he previously heard and remembered with sounds he actually hears, to judge if they are normal or abnormal. According to the method, there is a worry that abnormal conditions can not be appropriately judged in a case where the number of objective equipments is increased and in a case that the sounds are changed gradually slightly. Then, the device of the present invention comprises a plurality of monitors for monitoring the operation sound of equipments, a recording/reproducing device for recording and reproducing the signals, a selection device for selecting the reproducing signals among the recorded signals, an acoustic device for converting the signals to sounds, a switching device for switching the signals to be transmitted to the acoustic device between to signals of the monitor and the recording/reproducing signals. The abnormality of the equipments can be determined easily by comparing the sounds representing the operation conditions of equipments for controlling the plant operation and the sounds recorded in their normal conditions. (N.H.)

Normal mammogram detection based on local probability difference transforms and support vector machines

International Nuclear Information System (INIS)

Chiracharit, W.; Kumhom, P.; Chamnongthai, K.; Sun, Y.; Delp, E.J.; Babbs, C.F

2007-01-01

Automatic detection of normal mammograms, as a ''first look'' for breast cancer, is a new approach to computer-aided diagnosis. This approach may be limited, however, by two main causes. The first problem is the presence of poorly separable ''crossed-distributions'' in which the correct classification depends upon the value of each feature. The second problem is overlap of the feature distributions that are extracted from digitized mammograms of normal and abnormal patients. Here we introduce a new Support Vector Machine (SVM) based method utilizing with the proposed uncrossing mapping and Local Probability Difference (LPD). Crossed-distribution feature pairs are identified and mapped into a new features that can be separated by a zero-hyperplane of the new axis. The probability density functions of the features of normal and abnormal mammograms are then sampled and the local probability difference functions are estimated to enhance the features. From 1,000 ground-truth-known mammograms, 250 normal and 250 abnormal cases, including spiculated lesions, circumscribed masses or microcalcifications, are used for training a support vector machine. The classification results tested with another 250 normal and 250 abnormal sets show improved testing performances with 90% sensitivity and 89% specificity. (author)

Proximal patellar tendinosis and abnormalities of patellar tracking

International Nuclear Information System (INIS)

Allen, G.M.; Tauro, P.G.; Ostlere, S.J.

1999-01-01

Objective. To assess whether an association exists between patellar tendinosis and abnormal patellar tracking. Design and patients. The MRI examinations of 630 patients (i.e. 860 knees) referred with anterior knee pain over a 4-year period were assessed in retrospect for the presence of patellar tendinosis and abnormal patellar tracking. The images of the patients with patellar tendinosis were reviewed and the location within the patellar tendon was recorded. Results. There were 44 knees with proximal patellar tendinosis. Twenty-four of these were considered to have normal patellar tracking and 20 to have abnormal patellar tracking. In the group of 816 knees without proximal patellar tendinosis, 581 were considered to have normal patellar tracking and 235 knees to have abnormal patellar tracking. When the two groups were compared there was a statistically significant difference in the ratio of patients with and without abnormal tracking. Conclusion. In patients referred with anterior knee pain or suspected abnormal patellar tracking there is a significant association between proximal patellar tendinosis and abnormal patellar tracking. (orig.)

Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy

Energy Technology Data Exchange (ETDEWEB)

Beggs, A.H.; Neumann, P.E.; Anderson, M.S.; Kunkel, L.M. (Harvard Medical School, Boston, MA (United States)); Arahata, Kiichi; Arikawa, Eri; Nonaka, Ikuya (National Inst. of Neuroscience, Tokyo (Japan))

1992-01-15

Abnormalities of dystrophin, a cytoskeletal protein of muscle and nerve, are generally considered specific for Duchenne and Becker muscular dystrophy. However, several patients have recently been identified with dystrophin deficiency who, before dystrophin testing, were considered to have Fukuyama congenital muscular dystrophy (FCMD) on the basis of clinical findings. Epidemiologic data suggest that only 1/3,500 males with autosomal recessive FCMD should have abnormal dystrophin. To explain the observation of 3/23 FCMD males with abnormal dystrophin, the authors propose that dystrophin and the FCMD gene product interact and that the earlier onset and greater severity of these patients' phenotype (relative to Duchenne muscular dystrophy) are due to their being heterozygous for the FCMD mutation in addition to being hemizygous for Duchenne muscular dystrophy, a genotype that is predicted to occur in 1/175,000 Japanese males. This model may help explain the genetic basis for some of the clinical and pathological variability seen among patients with FCMD, and it has potential implications for understanding the inheritance of other autosomal recessive disorders in general. For example, sex ratios for rare autosomal recessive disorders caused by mutations in proteins that interact with X chromosome-linked gene products may display predictable deviation from 1:1.

Real-time Multiple Abnormality Detection in Video Data

DEFF Research Database (Denmark)

Have, Simon Hartmann; Ren, Huamin; Moeslund, Thomas B.

2013-01-01

Automatic abnormality detection in video sequences has recently gained an increasing attention within the research community. Although progress has been seen, there are still some limitations in current research. While most systems are designed at detecting specific abnormality, others which...... are capable of detecting more than two types of abnormalities rely on heavy computation. Therefore, we provide a framework for detecting abnormalities in video surveillance by using multiple features and cascade classifiers, yet achieve above real-time processing speed. Experimental results on two datasets...... show that the proposed framework can reliably detect abnormalities in the video sequence, outperforming the current state-of-the-art methods....

Clinical Findings Documenting Cellular and Molecular Abnormalities of Glia in Depressive Disorders

Directory of Open Access Journals (Sweden)

Boldizsár Czéh

2018-02-01

Full Text Available Depressive disorders are complex, multifactorial mental disorders with unknown neurobiology. Numerous theories aim to explain the pathophysiology. According to the “gliocentric theory”, glial abnormalities are responsible for the development of the disease. The aim of this review article is to summarize the rapidly growing number of cellular and molecular evidences indicating disturbed glial functioning in depressive disorders. We focus here exclusively on the clinical studies and present the in vivo neuroimaging findings together with the postmortem molecular and histopathological data. Postmortem studies demonstrate glial cell loss while the in vivo imaging data reveal disturbed glial functioning and altered white matter microstructure. Molecular studies report on altered gene expression of glial specific genes. In sum, the clinical findings provide ample evidences on glial pathology and demonstrate that all major glial cell types are affected. However, we still lack convincing theories explaining how the glial abnormalities develop and how exactly contribute to the emotional and cognitive disturbances. Abnormal astrocytic functioning may lead to disturbed metabolism affecting ion homeostasis and glutamate clearance, which in turn, affect synaptic communication. Abnormal oligodendrocyte functioning may disrupt the connectivity of neuronal networks, while microglial activation indicates neuroinflammatory processes. These cellular changes may relate to each other or they may indicate different endophenotypes. A theory has been put forward that the stress-induced inflammation—mediated by microglial activation—triggers a cascade of events leading to damaged astrocytes and oligodendroglia and consequently to their dysfunctions. The clinical data support the “gliocentric” theory, but future research should clarify whether these glial changes are truly the cause or simply the consequences of this devastating disorder.

Monitoring of local CD8 β-expressing cell populations during Eimeria tenella infection of naïve and immune chickens

DEFF Research Database (Denmark)

Wattrang, Eva; Thebo, Per; Lunden, Anna

2016-01-01

The purpose of this study was to monitor abundance and activation of local CD8β-expressing T-cell populations during Eimeria tenella infections of naïve chickens and chickens immune by previous infections. Chickens were infected with E. tenella up to three times. Caecal T-cell receptor (TCR) γ...

Abnormal regional homogeneity in patients with essential tremor revealed by resting-state functional MRI.

Directory of Open Access Journals (Sweden)

Weidong Fang

Full Text Available Essential tremor (ET is one of the most common movement disorders in human adults. It can be characterized as a progressive neurological disorder of which the most recognizable feature is a tremor of the arms or hands that is apparent during voluntary movements such as eating and writing. The pathology of ET remains unclear. Resting-state fMRI (RS-fMRI, as a non-invasive imaging technique, was employed to investigate abnormalities of functional connectivity in ET in the brain. Regional homogeneity (ReHo was used as a metric of RS-fMRI to assess the local functional connectivity abnormality in ET with 20 ET patients and 20 age- and gender-matched healthy controls (HC. The ET group showed decreased ReHo in the anterior and posterior bilateral cerebellar lobes, the bilateral thalamus and the insular lobe, and increased ReHo in the bilateral prefrontal and parietal cortices, the left primary motor cortex and left supplementary motor area. The abnormal ReHo value of ET patients in the bilateral anterior cerebellar lobes and the right posterior cerebellar lobe were negatively correlated with the tremor severity score, while positively correlated with that in the left primary motor cortex. These findings suggest that the abnormality in cerebello-thalamo-cortical motor pathway is involved in tremor generation and propagation, which may be related to motor-related symptoms in ET patients. Meanwhile, the abnormality in the prefrontal and parietal regions may be associated with non-motor symptoms in ET. These findings suggest that the ReHo could be utilized for investigations of functional-pathological mechanism of ET.

Survivin Expression as a Predictive Marker for Local Control in Patients With High-Risk T1 Bladder Cancer Treated With Transurethral Resection and Radiochemotherapy

International Nuclear Information System (INIS)

Weiss, Christian; Roemer, Felix von; Capalbo, Gianni; Ott, Oliver J.; Wittlinger, Michael; Krause, Steffen F.; Sauer, Rolf; Roedel, Claus; Roedel, Franz

2009-01-01

Purpose: The objectives of this study were to investigate the expression of survivin in tumor samples from patients with high-risk T1 bladder cancer and to correlate its expression with clinicopathologic features as well as clinical outcomes after initial transurethral resection (TURBT) followed by radiotherapy (RT) or radiochemotherapy (RCT). Methods and Materials: Survivin protein expression was evaluated by immunohistochemistry on tumor specimen (n = 48) from the initial TURBT, and was correlated with clinical and histopathologic characteristics as well as with 5-year rates of local failure, tumor progression, and death from urothelial cancer after primary bladder sparring treatment with RT/RCT. Results: Survivin was not expressed in normal bladder urothelium but was overexpressed in 67% of T1 tumors. No association between survivin expression and clinicopathologic factors (age, gender, grading, multifocality, associated carcinoma in situ) could be shown. With a median follow-up of 27 months (range, 3-140 months), elevated survivin expression was significantly associated with an increased probability of local failure after TURBT and RCT/RT (p = 0.003). There was also a clear trend toward a higher risk of tumor progression (p = 0.07) and lower disease-specific survival (p = 0.10). Conclusions: High survivin expression is a marker of tumor aggressiveness and may help to identify a subgroup of patients with T1 bladder cancer at a high risk for recurrence when treated with primary organ-sparing approaches such as TURBT and RCT.

Hysterosalpingography: analysis of 473 abnormal examinations

International Nuclear Information System (INIS)

Petta, C.A.; Costa-Paiva, L.H.S. da; Pinto-Neto, A.M.; Martins, R.; Souza, G.A.

1990-01-01

The authors reviewed the reports of 4/3 abnormal hysterosalpingographies from 1,200 medical records of patients at the sterility and infertility out-patient clinic of the School of Medical Sciences of the State University of Campinas (Unicamp), from July, 1974 to December, 1981. The objective was to evaluate the incidence and main alterations diagnosed by hysterosalpingography. The most frequent findings were tuboperitoneal factors in 91% of the examinations, uterine cavity abnormalities in 17.4% and cervical factor in 6.3% of the cases. The examinations showed a great incident of tuboperitoneal abnormalities as cause of sterility from lower social classes. (author) [pt

Numerically abnormal chromosome constitutions in humans

Energy Technology Data Exchange (ETDEWEB)

NONE

1993-12-31

Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

Study on the abnormalities in sperm and gene mutation induced by retention of 147Pm in testis

International Nuclear Information System (INIS)

Zhu Shoupeng; Lun Mingyue; Yang Shuqin

1990-05-01

The purpose of the present study is to ascertain 147 Pm retention in testis and its radiogenotoxicological effects of gene mutation through varying radioactivities of internal exposure. Especially the accumulation of 147 Pm in testis induces the dominant lethal, dominant skeletal mutation and abnormalities in sperm. Studies indicated that the cumulative absorption dose in testis increases as the internal exposure of 147 Pm increases. The internal exposure of 147 Pm can destroy the genetic materials and raise the rates of dominant lethal and dominant mutation of skeletal abnormalities in the offspring. The relationship between the rate of dominant skeletal mutation (B) and accumulated radioactivities of 147 Pm (D) in testis can be described by a linear equation that is B 20.68 + 35.48 D. The relationship between abnormalities of the sperm and the cumulative dose from 147 Pm in testis can be expressed by the following equation: S = 10.8705 D 0.5224 + 3.1768

Abnormal Uterine Bleeding

Science.gov (United States)

... especially the progestin-only pill (also called the “mini-pill”) can actually cause abnormal bleeding for some ... Basics Sports Safety Injury Rehabilitation Emotional Well-Being Mental Health Sex and Birth Control Sex and Sexuality ...

Hemizygous Le-Cre Transgenic Mice Have Severe Eye Abnormalities on Some Genetic Backgrounds in the Absence of LoxP Sites

Science.gov (United States)

Dorà, Natalie J.; Collinson, J. Martin; Hill, Robert E.; West, John D.

2014-01-01

Eye phenotypes were investigated in Le-CreTg/−; Pax6fl/+ mice, which were expected to show tissue-specific reduction of Pax6 in surface ectoderm derivatives. To provide a better comparison with our previous studies of Pax6+/− eye phenotypes, hemizygous Le-CreTg/− and heterozygous Pax6fl/+mice were crossed onto the CBA/Ca genetic background. After the Le-Cre transgene had been backcrossed to CBA/Ca for seven generations, significant eye abnormalities occurred in some hemizygous Le-CreTg/−; Pax6+/+ controls (without a floxed Pax6fl allele) as well as experimental Le-CreTg/−; Pax6fl/+ mice. However, no abnormalities were seen in Le-Cre−/−; Pax6fl/+ or Le-Cre−/−; Pax6+/+ controls (without the Le-Cre transgene). The severity and frequency of the eye abnormalities in Le-CreTg/−; Pax6+/+ control mice diminished after backcrossing Le-CreTg/− mice to the original FVB/N strain for two generations, showing that the effect was reversible. This genetic background effect suggests that the eye abnormalities are a consequence of an interaction between the Le-Cre transgene and alleles of unknown modifier genes present in certain genetic backgrounds. The abnormalities were also ameliorated by introducing additional Pax6 gene copies on a CBA/Ca background, suggesting involvement of Pax6 depletion in Le-CreTg/−; Pax6+/+ mice rather than direct action of Cre recombinase on cryptic pseudo-loxP sites. One possibility is that expression of Cre recombinase from the Pax6-Le regulatory sequences in the Le-Cre transgene depletes cofactors required for endogenous Pax6 gene expression. Our observation that eye abnormalities can occur in hemizygous Le-CreTg/−; Pax6+/+ mice, in the absence of a floxed allele, demonstrates the importance of including all the relevant genetic controls in Cre-loxP experiments. PMID:25272013

Latrunculin A treatment prevents abnormal chromosome segregation for successful development of cloned embryos.

Directory of Open Access Journals (Sweden)

Yukari Terashita

Full Text Available Somatic cell nuclear transfer to an enucleated oocyte is used for reprogramming somatic cells with the aim of achieving totipotency, but most cloned embryos die in the uterus after transfer. While modifying epigenetic states of cloned embryos can improve their development, the production rate of cloned embryos can also be enhanced by changing other factors. It has already been shown that abnormal chromosome segregation (ACS is a major cause of the developmental failure of cloned embryos and that Latrunculin A (LatA, an actin polymerization inhibitor, improves F-actin formation and birth rate of cloned embryos. Since F-actin is important for chromosome congression in embryos, here we examined the relation between ACS and F-actin in cloned embryos. Using LatA treatment, the occurrence of ACS decreased significantly whereas cloned embryo-specific epigenetic abnormalities such as dimethylation of histone H3 at lysine 9 (H3K9me2 could not be corrected. In contrast, when H3K9me2 was normalized using the G9a histone methyltransferase inhibitor BIX-01294, the Magea2 gene-essential for normal development but never before expressed in cloned embryos-was expressed. However, this did not increase the cloning success rate. Thus, non-epigenetic factors also play an important role in determining the efficiency of mouse cloning.

Latrunculin A Treatment Prevents Abnormal Chromosome Segregation for Successful Development of Cloned Embryos

Science.gov (United States)

Terashita, Yukari; Yamagata, Kazuo; Tokoro, Mikiko; Itoi, Fumiaki; Wakayama, Sayaka; Li, Chong; Sato, Eimei; Tanemura, Kentaro; Wakayama, Teruhiko

2013-01-01

Somatic cell nuclear transfer to an enucleated oocyte is used for reprogramming somatic cells with the aim of achieving totipotency, but most cloned embryos die in the uterus after transfer. While modifying epigenetic states of cloned embryos can improve their development, the production rate of cloned embryos can also be enhanced by changing other factors. It has already been shown that abnormal chromosome segregation (ACS) is a major cause of the developmental failure of cloned embryos and that Latrunculin A (LatA), an actin polymerization inhibitor, improves F-actin formation and birth rate of cloned embryos. Since F-actin is important for chromosome congression in embryos, here we examined the relation between ACS and F-actin in cloned embryos. Using LatA treatment, the occurrence of ACS decreased significantly whereas cloned embryo-specific epigenetic abnormalities such as dimethylation of histone H3 at lysine 9 (H3K9me2) could not be corrected. In contrast, when H3K9me2 was normalized using the G9a histone methyltransferase inhibitor BIX-01294, the Magea2 gene—essential for normal development but never before expressed in cloned embryos—was expressed. However, this did not increase the cloning success rate. Thus, non-epigenetic factors also play an important role in determining the efficiency of mouse cloning. PMID:24205216

Tissue specific promoters improve the localization of radiation-inducible gene expression

International Nuclear Information System (INIS)

Hallahan, Dennis; Kataoka, Yasushi; Kuchibhotla, Jaya; Virudachalam, Subbu; Weichselbaum, Ralph

1996-01-01

expression was quantified in vascular endothelial cells from large vessel (HUVEC) and small vessels (HMEC). We found cell-type specificity of radiation-induction. The promoter region from the ELAM gene gave no expression in cells that were not of endothelial cell origin and x-ray-induction of ELAM in the endothelium required the NFkB binding cis-acting element. ELAM induction was achieved at doses as low as 1 Gy, whereas induction of other radiation inducible genes required 5 to 10 Gy. Cells transfected with the minimal promoter (plasmid pTK-CAT) demonstrated no radiation induction. Expression of the CMV-LacZ genetic construct that was used as a negative control in each transfection was not altered by x-irradiation. Moreover, intravenous administration of liposomes containing a reporter gene linked to the ELAM promoter and a transcriptional amplification system were induced specifically at sites of x-irradiation in an animal model. Conclusions: Activation of transcription of the ELAM-1 promoter by ionizing radiation is a means of activating gene therapy within the vascular endothelium and demonstrates the feasibility of treating vascular lesions with noninvasive procedures. Tissue specific promoters (e. g., ELAM-1) combined with radiation inducible gene therapy improves the localization of gene therapy expression. These results have applications in intravascular brachytherapy for the prevention of blood vessel restenosis

G protein abnormalities in pituitary adenomas.

Science.gov (United States)

Spada, A; Lania, A; Ballarè, E

1998-07-25

It has been demonstrated that the majority of secreting and nonsecreting adenomas is monoclonal in origin suggesting that these neoplasia arise from the replication of a single mutated cell, in which growth advantage results from either activation of protooncogenes or inactivation of antioncogenes. Although a large number of genes has been screened for mutations, only few genetic abnormalities have been found in pituitary tumors such as allelic deletion of chromosome 11q13 where the MEN-1 gene has been localised, and mutations in the gene encoding the alpha subunit of the stimulatory Gs and Gi2 protein. These mutations constitutively activate the alpha subunit of the Gs and Gi2 protein by inhibiting their intrinsic GTPase activity. Both Gs alpha and Gi2alpha can be considered products of protooncogenes (gsp and gip2, respectively) since gain of function mutations that activate mitogenic signals have been recognized in human tumors. Gsp oncogene is found in 30-40% of GH-secreting adenomas, in a low percentage of nonfunctioning and ACTH-secreting pituitary adenomas, in toxic thyroid adenomas and differentiated thyroid carcinomas. The same mutations, occurred early in embriogenesis, have been also identified in tissues from patients affected with the McCune Albright syndrome. These mutations result in an increased cAMP production and in the subsequent overactivation of specific pathways involved in both cell growth and specific programmes of cell differentiation. By consequence, the endocrine tumors expressing gsp oncogene retain differentiated functions. The gip2 oncogene has been identified in about 10% of nonfunctioning pituitary adenomas, in tumors of the ovary and the adrenal cortex. However, it remains to be established whether Gi proteins activate mitogenic signals in pituitary cells. Since Gi proteins are involved in mediating the effect of inhibitory neurohormones on intracellular effectors, it has been proposed that in pituitary tumors the low expression of

Increased expression of p62/SQSTM1 in prion diseases and its association with pathogenic prion protein.

Science.gov (United States)

Homma, Takujiro; Ishibashi, Daisuke; Nakagaki, Takehiro; Satoh, Katsuya; Sano, Kazunori; Atarashi, Ryuichiro; Nishida, Noriyuki

2014-03-28

Prion diseases are neurodegenerative disorders characterized by the aggregation of abnormally folded prion protein (PrP(Sc)). In this study, we focused on the mechanism of clearance of PrP(Sc), which remains unclear. p62 is a cytosolic protein known to mediate both the formation and degradation of aggregates of abnormal proteins. The levels of p62 protein increased in prion-infected brains and persistently infected cell cultures. Upon proteasome inhibition, p62 co-localized with PrP(Sc), forming a large aggregate in the perinuclear region, hereafter referred to as PrP(Sc)-aggresome. These aggregates were surrounded with autophagosome marker LC3 and lysosomes in prion-infected cells. Moreover, transient expression of the phosphomimic form of p62, which has enhanced ubiquitin-binding activity, reduced the amount of PrP(Sc) in prion-infected cells, indicating that the activation of p62 could accelerate the clearance of PrP(Sc). Our findings would thus suggest that p62 could be a target for the therapeutic control of prion diseases.

Prevalence of cervical cytology abnormalities among HIV infected ...

African Journals Online (AJOL)

Objectives: To establish the prevalence of cervical cytology abnormalities, determine the correlation between CD4+ cell count and abnormal Pap smear, determine the correlation between WHO-HIV staging and abnormal pap smear among HIV infected women attending HIV clinic at Rwanda Military Hospital. Design: ...

Abnormal resistance switching behaviours of NiO thin films: possible occurrence of both formation and rupturing of conducting channels

Energy Technology Data Exchange (ETDEWEB)

Liu Chunli; Chae, S C; Chang, S H; Lee, S B; Noh, T W [ReCOE and FPRD, Department of Physics and Astronomy, Seoul National University, Seoul 151-747 (Korea, Republic of); Lee, J S; Kahng, B [Department of Physics and Astronomy, Seoul National University, Seoul 151-747 (Korea, Republic of); Kim, D-W [Division of Nano Sciences and Department of Physics, Ewha Womens University, Seoul 120-750 (Korea, Republic of); Jung, C U [Department of Physics, Hankuk University of Foreign Studies, Yongin, Gyeonggi-do 449-791 (Korea, Republic of); Seo, S; Ahn, S-E [Samsung Advanced Institute of Technology, Suwon 440-600 (Korea, Republic of)], E-mail: twnoh@snu.ac.kr

2009-01-07

We report a detailed study on the abnormal resistance switching behaviours observed in NiO thin films which show unipolar resistance switching phenomena. During the RESET process, in which the NiO film changed from a low resistance state to a high resistance state, we sometimes observed that the resistance became smaller than the initial value. We simulated the resistance switching by using a random circuit breaker network model. We found that local conducting channels could be formed as well as ruptured during the RESET process, which result in the occurrence of such abnormal switching behaviours.

Abnormal devitrification behavior and mechanical response of cold-rolled Mg-rich Mg-Cu-Gd metallic glasses

International Nuclear Information System (INIS)

Lee, J.I.; Kim, J.W.; Oh, H.S.; Park, J.S.; Park, E.S.

2016-01-01

Abnormal devitrification behavior and mechanical response of Mg 75 Cu 15 Gd 10 (relatively strong glass former with higher structural stability) and Mg 85 Cu 5 Gd 10 (relatively fragile glass former with lower structural stability) metallic glasses, fabricated by repeated forced cold rolling, have been investigated. When metallic glasses were cold-rolled up to a thickness reduction ratio of ∼33%, the heat of relaxation (ΔH relax. ) below T g of the cold-rolled specimens was reduced, which indicates the formation of local structural ordering via cold rolling due to stress-induced relaxation. The local structural ordering results in abnormal devitrification behavior, such as higher resistance of glass-to-supercooled liquid transition and delayed growth, in the following heat treatment due to increased nuclei density and pinning site. In particular, the fragility index, m, could assist in understanding structural stability and local structural variation by mechanical processing as well as compositional tuning. Indeed, we examine the shear avalanche size to rationalize the variation of the deformation unit size depending on the structural instability before and after cold rolling. The deformation mode in Mg 85 Cu 5 Gd 10 metallic glass might change from self-organized critical state to chaotic state by cold rolling, which results in unique hardening behavior under the condition for coexisting well distributed local structural ordering and numerous thinner shear deformed areas. These results would give us a guideline for atomic scale structural manipulation of metallic glasses, and help develop novel metallic glass matrix composites with optimal properties through effective mechanical processing as well as heat treatment.

Localization studies in patients with persistent or recurrent hyperparathyroidism

International Nuclear Information System (INIS)

Clark, O.H.; Okerlund, M.D.; Moss, A.A.

1985-01-01

Preoperative localization studies are essential for patients who have undergone previous parathyroid operations. This is because the remaining parathyroid glands are more difficult to identify at operation because of increased scarring with loss of normal tissue planes and because the remaining abnormal parathyroid tissue is more likely to be situated in an ectopic position. This investigation concerns the accuracy of preoperative localization studies in 36 consecutive patients. All patients had symptoms and clinical and laboratory data diagnostic of primary (31 patients) or secondary (five patients) hyperparathyroidism. Ultrasonography was performed in all 36 patients; 18 (50%) were positive, 14 (39%) were negative, and four (11%) were false positive examinations. Eight of the negative study results occurred in patients with abnormal parathyroid glands situated in the mediastinum. Computerized tomography (CT) was performed in 25 patients. There was an equal number of positive (11; 44%) and negative (11; 44%) studies with three (12%) false positive test results. CT was helpful in identifying substernal lesions and other abnormal parathyroid glands situated in ectopic positions. Thallium chloride 201-technetium 99m pertechnetate scans were used in 22 patients. There was an equal number of positive (eight; 36%) and negative (eight; 36%) studies. Six patients (27%) had false positive scans. One or more of these noninvasive tests was positive in 27 of the 36 patients (75%). Highly selective venous catheterization for the measurement of immunoreactive parathyroid hormone concentrations localized the elusive parathyroid tumor in 12 of the 16 patients (75%) overall and in six of the nine patients (66%) whose tumors were not identified by other studies

Diagnostic value of saline contrast sonohysterography comparing with hysteroscopy for detecting endometrial abnormalities in women with abnormal uterine bleeding

Directory of Open Access Journals (Sweden)

Farzaneh Goharzad

2011-01-01

Full Text Available Background: Abnormal uterine bleeding is a common presentation of uterine abnormalities among premenopausal and postmenopausal women.Objective: To evaluate and compare the diagnostic accuracy of saline contrast sonohysterography and hysteroscopy for detecting the cause of abnormal uterine bleeding.Materials and Methods: A total of 65 women with abnormal uterine bleeding were enrolled in this study. A prior saline contrast sonohysetrography followed by a hysteroscopy was performed in all cases. Sensitivity, specificity, positive and negative predictive value and test accuracy were calculated.Results: As the most common abnormality, SCSH showed hyperplasia in 19 patients while hysteroscopy diagnosed polyp in 15 cases. A sensitivity of 73.3%, 71.4% and 90.9% were reported for polyp, hyperplasia and submucous myoma respectively whereas the specificity was calculated 96% for polyps, 82.3% for hyperplasia and 90.7% for submucous myoma.Conclusion: Comparing with hysteroscopy, sonohysterography showed a high sensitivity and specificity for detecting submucous myoma but not for endometrial polyp and endometrial hyperplasia

Arthropathy of the abnormal temporo-mandibular joint

Energy Technology Data Exchange (ETDEWEB)

Stampfel, G.; Gausch, K.; Waldhart, E.

1984-05-01

Arthrography provides accurate information concerning abnormal changes and function of the soft tissue components of the T.M.J. It is superior to all other clinical and radiological methods of examination for elucidating functional abnormalities. The increasing incidence of functional T.M.J. abnormalities and improvements in treatment make arthrography of the T.M.J. of increasing importance. The importance of views in the sagittal plane and of video recordings is stressed. 3 figs.

Gene expression and localization of two types of AQP5 in Xenopus tropicalis under hydration and dehydration.

Science.gov (United States)

Shibata, Yuki; Sano, Takahiro; Tsuchiya, Nobuhito; Okada, Reiko; Mochida, Hiroshi; Tanaka, Shigeyasu; Suzuki, Masakazu

2014-07-01

Two types of aquaporin 5 (AQP5) genes (aqp-xt5a and aqp-xt5b) were identified in the genome of Xenopus tropicalis by synteny comparison and molecular phylogenetic analysis. When the frogs were in water, AQP-xt5a mRNA was expressed in the skin and urinary bladder. The expression of AQP-xt5a mRNA was significantly increased in dehydrated frogs. AQP-xt5b mRNA was also detected in the skin and increased in response to dehydration. Additionally, AQP-xt5b mRNA began to be slightly expressed in the lung and stomach after dehydration. For the pelvic skin of hydrated frogs, immunofluorescence staining localized AQP-xt5a and AQP-xt5b to the cytoplasm of secretory cells of the granular glands and the apical plasma membrane of secretory cells of the small granular glands, respectively. After dehydration, the locations of both AQPs in their respective glands did not change, but AQP-xt5a was visualized in the cytoplasm of secretory cells of the small granular glands. For the urinary bladder, AQP-xt5a was observed in the apical plasma membrane and cytoplasm of a number of granular cells under normal hydration. After dehydration, AQP-xt5a was found in the apical membrane and cytoplasm of most granular cells. Injection of vasotocin into hydrated frogs did not induce these changes in the localization of AQP-xt5a in the small granular glands and urinary bladder, however. The results suggest that AQP-xt5a might be involved in water reabsorption from the urinary bladder during dehydration, whereas AQP-xt5b might play a role in water secretion from the small granular gland. Copyright © 2014 the American Physiological Society.

Expression, characterization, and cellular localization of knowpains, papain-like cysteine proteases of the Plasmodium knowlesi malaria parasite.

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Rajesh Prasad

Full Text Available Papain-like cysteine proteases of malaria parasites degrade haemoglobin in an acidic food vacuole to provide amino acids for intraerythrocytic parasites. These proteases are potential drug targets because their inhibitors block parasite development, and efforts are underway to develop chemotherapeutic inhibitors of these proteases as the treatments for malaria. Plasmodium knowlesi has recently been shown to be an important human pathogen in parts of Asia. We report expression and characterization of three P. knowlesi papain-like proteases, termed knowpains (KP2-4. Recombinant knowpains were produced using a bacterial expression system, and tested for various biochemical properties. Antibodies against recombinant knowpains were generated and used to determine their cellular localization in parasites. Inhibitory effects of the cysteine protease inhibitor E64 were assessed on P. knowlesi culture to validate drug target potential of knowpains. All three knowpains were present in the food vacuole, active in acidic pH, and capable of degrading haemoglobin at the food vacuolar pH (≈5.5, suggesting roles in haemoglobin degradation. The proteases showed absolute (KP2 and KP3 to moderate (KP4 preference for peptide substrates containing leucine at the P2 position; KP4 preferred arginine at the P2 position. While the three knowpains appear to have redundant roles in haemoglobin degradation, KP4 may also have a role in degradation of erythrocyte cytoskeleton during merozoite egress, as it displayed broad substrate specificity and was primarily localized at the parasite periphery. Importantly, E64 blocked erythrocytic development of P. knowlesi, with enlargement of food vacuoles, indicating inhibition of haemoglobin hydrolysis and supporting the potential for inhibition of knowpains as a strategy for the treatment of malaria. Functional expression and characterization of knowpains should enable simultaneous screening of available cysteine protease

Sub-cellular mRNA localization modulates the regulation of gene expression by small RNAs in bacteria

Science.gov (United States)

Teimouri, Hamid; Korkmazhan, Elgin; Stavans, Joel; Levine, Erel

2017-10-01

Small non-coding RNAs can exert significant regulatory activity on gene expression in bacteria. In recent years, substantial progress has been made in understanding bacterial gene expression by sRNAs. However, recent findings that demonstrate that families of mRNAs show non-trivial sub-cellular distributions raise the question of how localization may affect the regulatory activity of sRNAs. Here we address this question within a simple mathematical model. We show that the non-uniform spatial distributions of mRNA can alter the threshold-linear response that characterizes sRNAs that act stoichiometrically, and modulate the hierarchy among targets co-regulated by the same sRNA. We also identify conditions where the sub-cellular organization of cofactors in the sRNA pathway can induce spatial heterogeneity on sRNA targets. Our results suggest that under certain conditions, interpretation and modeling of natural and synthetic gene regulatory circuits need to take into account the spatial organization of the transcripts of participating genes.

Abnormal Selective Attention Normalizes P3 Amplitudes in PDD

Science.gov (United States)

Hoeksma, Marco R.; Kemner, Chantal; Kenemans, J. Leon; van Engeland, Herman

2006-01-01

This paper studied whether abnormal P3 amplitudes in PDD are a corollary of abnormalities in ERP components related to selective attention in visual and auditory tasks. Furthermore, this study sought to clarify possible age differences in such abnormalities. Children with PDD showed smaller P3 amplitudes than controls, but no abnormalities in…

EGFR-expression in primary urinary bladder cancer and corresponding metastases and the relation to HER2-expression. On the possibility to target these receptors with radionuclides

International Nuclear Information System (INIS)

Carlsson, Jörgen; Wester, Kenneth; De La Torre, Manuel; Malmström, Per-Uno; Gårdmark, Truls

2015-01-01

There is limited effect of tyrosine kinase inhibitors or “naked” antibodies binding EGFR or HER2 for therapy of metastasized urinary bladder cancer and these methods are therefore not routinely used. Targeting radio-nuclides to the extracellular domain of the receptors is potentially a better possibility. EGFR- and HER2-expression was analyzed for primary tumors and corresponding metastases from 72 patients using immunohistochemistry and the internationally recommended HercepTest. Intracellular mutations were not analyzed since only the receptors were considered as targets and intracellular abnormalities should have minor effect on radiation dose. EGFR was positive in 71% of the primary tumors and 69% of corresponding metastases. Local and distant metastases were EGFR-positive in 75% and 66% of the cases, respectively. The expression frequency of HER2 in related lesions was slightly higher (data from previous study). The EGFR-positive tumors expressed EGFR in metastases in 86% of the cases. The co-expression of EGFR and HER2 was 57% for tumors and 53% for metastases. Only 3% and 10% of the lesions were negative for both receptors in tumors and metastases, respectively. Thus, targeting these receptors with radionuclides might be applied for most patients. At least one of the EGFR- or HER2-receptors was present in most cases and co-expressed in more than half the cases. It is therefore interesting to deliver radionuclides for whole-body receptor-analysis, dosimetry and therapy. This can hopefully compensate for resistance to other therapies and more patients can hopefully be treated with curative instead of palliative intention

Contrast sensitivity abnormalities in deaf individuals

Directory of Open Access Journals (Sweden)

Masoud Khorrami-Nejad

2018-01-01

Conclusion: Hearing impaired boys are at a greater risk for contrast sensitivity abnormalities than boys with normal hearing. The larger frequency of contrast sensitivity abnormalities in high spatial frequencies than in other frequencies may demonstrate greater defects in the central visual system compared with the periphery in individuals with hearing loss.

Effect of vitamin E on preovulatory stage irradiated female mouse expressed as chromosomal abnormalities in generated embryos

International Nuclear Information System (INIS)

Salimi, M.; Mozdarani, H.

2006-01-01

The present study has been carried out to investigate the effects of preovulatory stage gamma-irradiation of female mice in the absence or presence of vitamin E on numerical chromosome abnormalities in 8-cell embryos after mating with non- irradiated males. Materials and Methods: The 8-11 weeks adult female NMRl mice were whole body irradiated at preovulatory stage (post PMSG injection and about 12-18 hours before Injecting HCG) with 4 Gy gamma-rays generated from a cobalt-60 source alone or in combination with 200 IU/kg vitamin E, intraperitoneally administered one hour prior to irradiation. Soon after HCG injection super ovulated irradiated females were mated with non-irradiated males. About 68-h post coitus (p.c), 8-cell embryos were flushed from the oviducts of pregnant mice and were fixed on slides using standard methods in order to screen for metaphase spreads and numerical chromosome abnormalities. Results: In control embryos, 8% of metaphase plates were aneuploidy whereas in preovulatory stage irradiated female mice, about 50% of metaphase plates of embryos showed numerical chromosome aberrations (P nd meiotic division. Reduction of the frequency of chromosome aberrations in the presence of vitamin E is probably due to antioxidant effects of this vitamin, and scavenging free radicals induced by gamma-rays in mice oocytes' environment

Preliminary evidence for association of genetic variants in pri-miR-34b/c and abnormal miR-34c expression with attention deficit and hyperactivity disorder.

Science.gov (United States)

Garcia-Martínez, I; Sánchez-Mora, C; Pagerols, M; Richarte, V; Corrales, M; Fadeuilhe, C; Cormand, B; Casas, M; Ramos-Quiroga, J A; Ribasés, M

2016-08-30

Attention deficit and hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by impairment to sustain attention and inability to control impulses and activity level. The etiology of ADHD is complex, with an estimated heritability of 70-80%. Under the hypothesis that alterations in the processing or target binding of microRNAs (miRNAs) may result in functional alterations predisposing to ADHD, we explored whether common polymorphisms potentially affecting miRNA-mediated regulation are involved in this psychiatric disorder. We performed a comprehensive association study focused on 134 miRNAs in 754 ADHD subjects and 766 controls and found association between the miR-34b/c locus and ADHD. Subsequently, we provided preliminary evidence for overexpression of the miR-34c-3p mature form in peripheral blood mononuclear cells of ADHD subjects. Next, we tested the effect on gene expression of single-nucleotide polymorphisms within the ADHD-associated region and found that rs4938923 in the promoter of the pri-miR-34b/c tags cis expression quantitative trait loci for both miR-34b and miR-34c and has an impact on the expression levels of 681 transcripts in trans, including genes previously associated with ADHD. This gene set was enriched for miR-34b/c binding sites, functional categories related to the central nervous system, such as axon guidance or neuron differentiation, and serotonin biosynthesis and signaling canonical pathways. Our results provide preliminary evidence for the contribution to ADHD of a functional variant in the pri-miR-34b/c promoter, possibly through dysregulation of the expression of mature forms of miR-34b and miR-34c and some target genes. These data highlight the importance of abnormal miRNA function as a potential epigenetic mechanism contributing to ADHD.

The role of leiomyomas in the genesis of abnormal uterine bleeding (AUB).

Science.gov (United States)

Lasmar, Ricardo Bassil; Lasmar, Bernardo Portugal

2017-04-01

Abnormal uterine bleeding (AUB) is the major complaint in approximately one-third of gynecological visits in premenopausal women, and in >70% of appointments of perimenopausal and postmenopausal women. Uterine myoma is one of the main causes of AUB during menacme, especially when it is submucosal. The association of myoma and AUB may be related to several factors, from local alterations of angiogenic and vasoactive substances to changes in uterine contractility. The objective of this paper is to show the different associations of myoma and AUB. Copyright © 2016. Published by Elsevier Ltd.

Frequency and severity of myocardial perfusion abnormalities using Tc-99m MIBI SPECT in cardiac syndrome X

International Nuclear Information System (INIS)

Saghari, Mohsen; Assadi, Majid; Eftekhari, Mohammad; Yaghoubi, Mohammad; Fard-Esfahani, Armaghan; Malekzadeh, Jan-Mohammad; Sichani, Babak Fallhi; Beiki, Davood; Takavar, Abbas

2006-01-01

Cardiac syndrome X is defined by a typical angina pectoris with normal or near normal (stenosis <40%) coronary angiogram with or without electrocardiogram (ECG) change or atypical angina pectoris with normal or near normal coronary angiogram plus a positive none-invasive test (exercise tolerance test or myocardial perfusion scan) with or without ECG change. Studies with myocardial perfusion imaging on this syndrome have indicated some abnormal perfusion scan. We evaluated the role of myocardial perfusion imaging (MPI) and also the severity and extent of perfusion abnormality using Tc-99m MIBI Single Photon Emission Computed Tomography (SPECT) in these patients. The study group consisted of 36 patients with cardiac syndrome X. The semiquantitative perfusion analysis was performed using exercise Tc-99m MIBI SPECT. The MPI results were analyzed by the number, location and severity of perfusion defects. Abnormal perfusion defects were detected in 13 (36.10%) cases, while the remaining 23 (63.90%) had normal cardiac imaging. Five of 13 (38.4%) abnormal studies showed multiple perfusion defects. The defects were localized in the apex in 3, apical segments in 4, midventricular segments in 12 and basal segments in 6 cases. Fourteen (56%) of all abnormal segments revealed mild, 7(28%) moderate and 4 (16%) severe reduction of tracer uptake. No fixed defects were identified. The vessel territories were approximately the same in all subjects. The Exercise treadmill test (ETT) was positive in 25(69%) and negative in 11(30%) patients. There was no consistent pattern as related to the extent of MPI defects or exercise test results. Our study suggests that multiple perfusion abnormalities with different levels of severity are common in cardiac syndrome X, with more than 30 % of these patients having at least one abnormal perfusion segment. Our findings suggest that in these patients microvascular angina is probably more common than is generally believed

Tau regulates the subcellular localization of calmodulin

Energy Technology Data Exchange (ETDEWEB)

Barreda, Elena Gomez de [Centro de Biologia Molecular ' Severo Ochoa' , CSIC/UAM, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain); Avila, Jesus, E-mail: javila@cbm.uam.es [Centro de Biologia Molecular ' Severo Ochoa' , CSIC/UAM, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain); CIBER de Enfermedades Neurodegenerativas, 28031 Madrid (Spain)

2011-05-13

Highlights: {yields} In this work we have tried to explain how a cytoplasmic protein could regulate a cell nuclear function. We have tested the role of a cytoplasmic protein (tau) in regulating the expression of calbindin gene. We found that calmodulin, a tau-binding protein with nuclear and cytoplasmic localization, increases its nuclear localization in the absence of tau. Since nuclear calmodulin regulates calbindin expression, a decrease in nuclear calmodulin, due to the presence of tau that retains it at the cytoplasm, results in a change in calbindin expression. -- Abstract: Lack of tau expression in neuronal cells results in a change in the expression of few genes. However, little is known about how tau regulates gene expression. Here we show that the presence of tau could alter the subcellular localization of calmodulin, a protein that could be located at the cytoplasm or in the nucleus. Nuclear calmodulin binds to co-transcription factors, regulating the expression of genes like calbindin. In this work, we have found that in neurons containing tau, a higher proportion of calmodulin is present in the cytoplasm compared with neurons lacking tau and that an increase in cytoplasmic calmodulin correlates with a higher expression of calbindin.

Tau regulates the subcellular localization of calmodulin

International Nuclear Information System (INIS)

Barreda, Elena Gomez de; Avila, Jesus

2011-01-01

Highlights: → In this work we have tried to explain how a cytoplasmic protein could regulate a cell nuclear function. We have tested the role of a cytoplasmic protein (tau) in regulating the expression of calbindin gene. We found that calmodulin, a tau-binding protein with nuclear and cytoplasmic localization, increases its nuclear localization in the absence of tau. Since nuclear calmodulin regulates calbindin expression, a decrease in nuclear calmodulin, due to the presence of tau that retains it at the cytoplasm, results in a change in calbindin expression. -- Abstract: Lack of tau expression in neuronal cells results in a change in the expression of few genes. However, little is known about how tau regulates gene expression. Here we show that the presence of tau could alter the subcellular localization of calmodulin, a protein that could be located at the cytoplasm or in the nucleus. Nuclear calmodulin binds to co-transcription factors, regulating the expression of genes like calbindin. In this work, we have found that in neurons containing tau, a higher proportion of calmodulin is present in the cytoplasm compared with neurons lacking tau and that an increase in cytoplasmic calmodulin correlates with a higher expression of calbindin.

How facial expressions in a Rett syndrome population are recognised and interpreted by those around them as conveying emotions

DEFF Research Database (Denmark)

Bergström-Isacsson, Märith; Lagerkvist, Bengt; Holck, Ulla

2013-01-01

to investigate if the Facial Action Coding System (FACS) could be used to identify facial expressions, and differentiate between those that expressed emotions and those that were elicited by abnormal brainstem activation in RTT. The sample comprised 29 participants with RTT and 11 children with a normal...... developmental pattern, exposed to six different musical stimuli during non-invasive registration of autonomic brainstem functions. The results indicate that FACS makes it possible both to identify facial expressions and to differentiate between those that stem from emotions and those caused by abnormal...

Comparison of expressed human and mouse sodium/iodide sym-porters reveals differences in transport properties and subcellular localization

Energy Technology Data Exchange (ETDEWEB)

Dayem, M.; Basquin, C.; Navarro, V.; Carrier, P.; Marsault, R.; Lindenthal, S.; Pourcher, T. [Univ Nice Sophia Antipolis, Sch Med, CEA, DSV, iBEB, SBTN, TIRO, F-06107 Nice (France); Chang, P. [CNRS, UPMC Biol Dev, UMR 7009, F-06230 Villefranche Sur Mer (France); Huc, S.; Darrouzet, E. [CEA Valrho, DSV, iBEB, SBTN, F-30207 Bagnols Sur Ceze (France)

2008-07-01

The active transport of iodide from the blood stream into thyroid follicular cells is mediated by the Na{sup +}/I{sup -} sym-porter (NIS). We studied mouse NIS (mNIS) and found that it catalyzes iodide transport into transfected cells more efficiently than human NIS (hNIS). To further characterize this difference,we compared {sup 125}I, uptake in the transiently transfected human embryonic kidney (HEK) 293 cells. We found that the Vmax for mNIS was four times higher than that for hNIS, and that the iodide transport constant (Km) was 2-5-fold lower for hNIS than mNIS. We also performed immuno-cyto-localization studies and observed that the subcellular distribution of the two ortho-logs differed. While the mouse protein was predominantly found at the plasma membrane, its human ortho-log was intracellular in {approx} 40% of the expressing cells. Using cell surface protein-labeling assays, we found that the plasma membrane localization frequency of the mouse protein was only 2-5-fold higher than that of the human protein, and therefore cannot alone account for,x values. We reasoned that the difference in the obtained Vmax the observed difference could also be caused by a higher turnover number for iodide transport in the mouse protein. We then expressed and analyzed chimeric proteins. The data obtained with these constructs suggest that the iodide recognition site could be located in the region extending from the N-terminus to transmembrane domain 8, and that the region between transmembrane domain 5 and the C-terminus could play a role in the subcellular localization of the protein. (authors)

Comparison of expressed human and mouse sodium/iodide sym-porters reveals differences in transport properties and subcellular localization

International Nuclear Information System (INIS)

Dayem, M.; Basquin, C.; Navarro, V.; Carrier, P.; Marsault, R.; Lindenthal, S.; Pourcher, T.; Chang, P.; Huc, S.; Darrouzet, E.

2008-01-01

The active transport of iodide from the blood stream into thyroid follicular cells is mediated by the Na + /I - sym-porter (NIS). We studied mouse NIS (mNIS) and found that it catalyzes iodide transport into transfected cells more efficiently than human NIS (hNIS). To further characterize this difference,we compared 125 I, uptake in the transiently transfected human embryonic kidney (HEK) 293 cells. We found that the Vmax for mNIS was four times higher than that for hNIS, and that the iodide transport constant (Km) was 2-5-fold lower for hNIS than mNIS. We also performed immuno-cyto-localization studies and observed that the subcellular distribution of the two ortho-logs differed. While the mouse protein was predominantly found at the plasma membrane, its human ortho-log was intracellular in ∼ 40% of the expressing cells. Using cell surface protein-labeling assays, we found that the plasma membrane localization frequency of the mouse protein was only 2-5-fold higher than that of the human protein, and therefore cannot alone account for,x values. We reasoned that the difference in the obtained Vmax the observed difference could also be caused by a higher turnover number for iodide transport in the mouse protein. We then expressed and analyzed chimeric proteins. The data obtained with these constructs suggest that the iodide recognition site could be located in the region extending from the N-terminus to transmembrane domain 8, and that the region between transmembrane domain 5 and the C-terminus could play a role in the subcellular localization of the protein. (authors)

Abnormal nuclear envelope in the cerebellar Purkinje cells and impaired motor learning in DYT11 myoclonus-dystonia mouse models.

Science.gov (United States)

Yokoi, Fumiaki; Dang, Mai T; Yang, Guang; Li, Jindong; Doroodchi, Atbin; Zhou, Tong; Li, Yuqing

2012-02-01

Myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonia. DYT11 M-D is caused by mutations in SGCE which codes for ɛ-sarcoglycan. SGCE is maternally imprinted and paternally expressed. Abnormal nuclear envelope has been reported in mouse models of DYT1 generalized torsion dystonia. However, it is not known whether similar alterations occur in DYT11 M-D. We developed a mouse model of DYT11 M-D using paternally inherited Sgce heterozygous knockout (Sgce KO) mice and reported that they had myoclonus and motor coordination and learning deficits in the beam-walking test. However, the specific brain regions that contribute to these phenotypes have not been identified. Since ɛ-sarcoglycan is highly expressed in the cerebellar Purkinje cells, here we examined the nuclear envelope in these cells using a transmission electron microscope and found that they are abnormal in Sgce KO mice. Our results put DYT11 M-D in a growing family of nuclear envelopathies. To analyze the effect of loss of ɛ-sarcoglycan function in the cerebellar Purkinje cells, we produced paternally inherited cerebellar Purkinje cell-specific Sgce conditional knockout (Sgce pKO) mice. Sgce pKO mice showed motor learning deficits, while they did not show abnormal nuclear envelope in the cerebellar Purkinje cells, robust motor deficits, or myoclonus. The results suggest that ɛ-sarcoglycan in the cerebellar Purkinje cells contributes to the motor learning, while loss of ɛ-sarcoglycan in other brain regions may contribute to nuclear envelope abnormality, myoclonus and motor coordination deficits. Copyright © 2011 Elsevier B.V. All rights reserved.

Chromosome abnormalities in atomic bomb survivors

Energy Technology Data Exchange (ETDEWEB)

Tomonaga, Y [Nagasaki Univ. (Japan). School of Medicine

1976-09-01

Chromosome abnormalities in bone marrow cells were recognized in 6 cases which consisted of one case of chronic myelogenous leukemia, two cases of acute myelogenous leukemia, one case of sideroblastic anemia, and two cases of myelodysplasis. Frequency of stable type chromosome abnormalities in bone marrow cells was investigated in 45 atomic bomb survivors without hematologic disorders and 15 controls. It was 1.4% (15 cases) in the group exposed to atomic bomb within 1 km from the hypocenter, which was significantly higher as compared with 0.1% (15 cases) in the group exposed to atomic bomb over 2.5 km from the hypocenter and 0.2% in normal controls. Examination of chromosome was also made on 2 of 3 cases which were the seconds born of female with high chromosome abnormality, who was exposed to within 1 km from the hypocenter, and healthy male exposed 3 km from the hypocenter. These two cases showed chromosome of normal male type, and balanced translocation was not recognized. There was not a significant difference in chromosome abnormalities between the seconds of atomic bomb survivors and controls.

An abnormal carbohydrate tolerance in acromegaly

International Nuclear Information System (INIS)

Qi Jinwu

1988-01-01

An abnormal secretion of plasma human growth hormore (hGH) and insulin in 67 acromegalic patients had been previously treated by external pituitary radiation were studied. All subjects, following an overnight fast, a standard 100 g oral glucose tolerance test, were performed and venous blood samples were taken at 0, 30, 60, 120 and 180 min. They were measured for blood glucose, plasma insulin and hGH. The results of this study have shown that, of the 67 subjects, 23 cases had an abnormal glucose tolerance(34.32%). Diabetes was detected in 17 cases (23.37%) and 6 patients had decreased glucose tolerance(8.69%). In all, hGH levels were consistantly above 5 ng/ml and were not suppressed after an oral glucose load. In these patients, however, about one-third had abnormal glucose tolerance. Low plasma insulin response to glucose and that of the releasing were evident in them than the normal glucose tolerance and a healthy control group. In addition, the mechanism of the abnormal secretion of hGH and insulin were disscussed

Cardiac abnormality prediction using HMLP network

Science.gov (United States)

Adnan, Ja'afar; Ahmad, K. A.; Mat, Muhamad Hadzren; Rizman, Zairi Ismael; Ahmad, Shahril

2018-02-01

Cardiac abnormality often occurs regardless of gender, age and races but depends on the lifestyle. This problem sometimes does not show any symptoms and usually detected once it already critical which lead to a sudden death to the patient. Basically, cardiac abnormality is the irregular electrical signal that generate by the pacemaker of the heart. This paper attempts to develop a program that can detect cardiac abnormality activity through implementation of Hybrid Multilayer Perceptron (HMLP) network. A certain amount of data of the heartbeat signals from the electrocardiogram (ECG) will be used in this project to train the MLP and HMLP network by using Modified Recursive Prediction Error (MRPE) algorithm and to test the network performance.

Study on the abnormalities in sperm and gene mutation induced by retention of {sup 147}Pm in testis

Energy Technology Data Exchange (ETDEWEB)

Shoupeng, Zhu; Mingyue, Lun; Shuqin, Yang [Suzhou Medical Coll., JS (China)

1990-05-01

The purpose of the present study is to ascertain {sup 147}Pm retention in testis and its radiogenotoxicological effects of gene mutation through varying radioactivities of internal exposure. Especially the accumulation of {sup 147}Pm in testis induces the dominant lethal, dominant skeletal mutation and abnormalities in sperm. Studies indicated that the cumulative absorption dose in testis increases as the internal exposure of {sup 147}Pm increases. The internal exposure of {sup 147}Pm can destroy the genetic materials and raise the rates of dominant lethal and dominant mutation of skeletal abnormalities in the offspring. The relationship between the rate of dominant skeletal mutation (B) and accumulated radioactivities of {sup 147}Pm (D) in testis can be described by a linear equation that is B 20.68 + 35.48 D. The relationship between abnormalities of the sperm and the cumulative dose from {sup 147}Pm in testis can be expressed by the following equation: S = 10.8705 D{sup 0.5224} + 3.1768.

Altered fucosyltransferase expression in the superior temporal gyrus of elderly patients with schizophrenia.

Science.gov (United States)

Mueller, Toni M; Yates, Stefani D; Haroutunian, Vahram; Meador-Woodruff, James H

2017-04-01

Glycosylation is a post-translational modification that is an essential element in cell signaling and neurodevelopmental pathway regulation. Glycan attachment can influence the tertiary structure and molecular interactions of glycosylated substrates, adding an additional layer of regulatory complexity to functional mechanisms underlying central cell biological processes. One type of enzyme-mediated glycan attachment, fucosylation, can mediate glycoprotein and glycolipid cell surface expression, trafficking, secretion, and quality control to modulate a variety of inter- and intracellular signaling cascades. Building on prior reports of glycosylation abnormalities and evidence of dysregulated glycosylation enzyme expression in schizophrenia, we examined the protein expression of 5 key fucose-modifying enzymes: GDP-fucose:protein O-fucosyltransferase 1 (POFUT1), GDP-fucose:protein O-fucosyltransferase 2 (POFUT2), fucosyltransferase 8 (FUT8), fucosyltransferase 11 (FUT11), and plasma α-l-fucosidase (FUCA2) in postmortem superior temporal gyrus of schizophrenia (N=16) and comparison (N=14) subjects. We also used the fucose binding protein, Aleuria aurantia lectin (AAL), to assess α-1,6-fucosylated N-glycoprotein abundance in the same subjects. In schizophrenia, we found increased expression of POFUT2, a fucosyltransferase uniquely responsible for O-fucosylation of thrombospondin-like repeat domains that is involved in a non-canonical endoplasmic reticulum quality control pathway. We also found decreased expression of FUT8 in schizophrenia. Given that FUT8 is the only α-1,6-fucosyltransferase expressed in mammals, the concurrent decrease in AAL binding in schizophrenia, particularly evident for N-glycoproteins in the ~52-58kDa and ~60-70kDa molecular mass ranges, likely reflects a consequence of abnormal FUT8 expression in the disorder. Dysregulated FUT8 and POFUT2 expression could potentially explain a variety of molecular abnormalities in schizophrenia. Copyright �

Robust 3D face landmark localization based on local coordinate coding.

Science.gov (United States)

Song, Mingli; Tao, Dacheng; Sun, Shengpeng; Chen, Chun; Maybank, Stephen J

2014-12-01

In the 3D facial animation and synthesis community, input faces are usually required to be labeled by a set of landmarks for parameterization. Because of the variations in pose, expression and resolution, automatic 3D face landmark localization remains a challenge. In this paper, a novel landmark localization approach is presented. The approach is based on local coordinate coding (LCC) and consists of two stages. In the first stage, we perform nose detection, relying on the fact that the nose shape is usually invariant under the variations in the pose, expression, and resolution. Then, we use the iterative closest points algorithm to find a 3D affine transformation that aligns the input face to a reference face. In the second stage, we perform resampling to build correspondences between the input 3D face and the training faces. Then, an LCC-based localization algorithm is proposed to obtain the positions of the landmarks in the input face. Experimental results show that the proposed method is comparable to state of the art methods in terms of its robustness, flexibility, and accuracy.

Co-Expression and Co-Localization of Cartilage Glycoproteins CHI3L1 and Lubricin in Osteoarthritic Cartilage: Morphological, Immunohistochemical and Gene Expression Profiles

Directory of Open Access Journals (Sweden)

Marta Anna Szychlinska

2016-03-01

Full Text Available Osteoarthritis is the most common human arthritis characterized by degeneration of articular cartilage. Several studies reported that levels of human cartilage glycoprotein chitinase 3-like-1 (CHI3L1 are known as a potential marker for the activation of chondrocytes and the progression of Osteoarthritis (OA, whereas lubricin appears to be chondroprotective. The aim of this study was to investigate the co-expression and co-localization of CHI3L1 and lubricin in normal and osteoarthritic rat articular cartilage to correlate their modified expression to a specific grade of OA. Samples of normal and osteoarthritic rat articular cartilage were analyzed by the Kellgren–Lawrence OA severity scores, the Kraus’ modified Mankin score and the Histopathology Osteoarthritis Research Society International (OARSI system for histomorphometric evaluations, and through CHI3L1 and lubricin gene expression, immunohistochemistry and double immuno-staining analysis. The immunoexpression and the mRNA levels of lubricin increased in normal cartilage and decreased in OA cartilage (normal vs. OA, p < 0.01. By contrast, the immunoexpression and the mRNA levels of CHI3L1 increased in OA cartilage and decreased in normal cartilage (normal vs. OA, p < 0.01. Our findings are consistent with reports suggesting that these two glycoproteins are functionally associated with the development of OA and in particular with grade 2/3 of OA, suggesting that in the future they could be helpful to stage the severity and progression of the disease.

GRP78 Protein Expression as Prognostic Values in Neoadjuvant Chemoradiotherapy and Laparoscopic Surgery for Locally Advanced Rectal Cancer.

Science.gov (United States)

Lee, Hee Yeon; Jung, Ji-Han; Cho, Hyun-Min; Kim, Sung Hwan; Lee, Kang-Moon; Kim, Hyung-Jin; Lee, Jong Hoon; Shim, Byoung Yong

2015-10-01

We investigated the relationships between biomarkers related to endoplasmic reticulum stress proteins (glucose-regulated protein of molecular mass 78 [GRP78] and Cripto-1 [teratocarcinoma-derived growth factor 1 protein]), pathologic response, and prognosis in locally advanced rectal cancer. All clinical stage II and III rectal cancer patients received 50.4 Gy over 5.5 weeks, plus 5-fluorouracil (400 mg/m(2)/day) and leucovorin (20 mg/m(2)/day) bolus on days 1 to 5 and 29 to 33, and surgery was performed at 7 to 10 weeks after completion of all therapies. Expression of GRP78 and Cripto-1 proteins was determined by immunohistochemistry and was assessed in 101 patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT). High expression of GRP78 and Cripto-1 proteins was observed in 86 patients (85.1%) and 49 patients (48.5%), respectively. Low expression of GRP78 protein was associated with a significantly high rate of down staging (80.0% vs. 52.3%, respectively; p=0.046) and a significantly low rate of recurrence (0% vs. 33.7%, respectively; p=0.008) compared with high expression of GRP78 protein. Mean recurrence-free survival according to GRP78 expression could not be estimated because the low expression group did not develop recurrence events but showed a significant correlation with time to recurrence, based on the log rank method (p=0.007). GRP78 also showed correlation with overall survival, based on the log rank method (p=0.045). GRP78 expression is a predictive and prognostic factor for down staging, recurrence, and survival in rectal cancer patients treated with 5-fluorouracil and leucovorin neoadjuvant CRT.

Enhanced monitoring of abnormal emergency department demands

KAUST Repository

Harrou, Fouzi; Sun, Ying; Kadri, Farid

2016-01-01

of abnormal situations caused by abnormal patient arrivals to the ED. More specifically, This work proposed the application of autoregressive moving average (ARMA) models combined with the generalized likelihood ratio (GLR) test for anomaly-detection. ARMA

Abstinent Heroin Addicts Tend to Take Risks: ERP and Source Localization

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Qinglin Zhao

2017-12-01

Full Text Available Abnormal decision making is a behavioral characteristic of drug addiction. Indeed, drug addicts prefer immediate rewards at the expense of future interests. Assessing the neurocognitive basis of decision-making related to drug dependence, combining event-related potential (ERP analysis and source localization techniques, may provide new insights into understanding decision-making deficits in drug addicts and further guide withdrawal treatment. In this study, EEG was performed in 20 abstinent heroin addicts (AHAs and 20 age-, education- and gender-matched healthy controls (HCs while they participated in a simple two-choice gambling task (99 vs. 9. Our behavioral results showed that AHAs tend to select higher-risk choices compared with HCs (i.e., more “99” choices than “9”. ERP results showed that right hemisphere preponderance of stimulus-preceding negativity was disrupted in AHAs, but not in HCs. Feedback-related negativity of difference wave was higher in AHAs than HCs, with the P300 amplitude associated with risk magnitude and valence. Using source localization that allows identification of abnormal brain activity in consequential cognitive stages, including the reward expectation and outcome evaluation stages, we found abnormalities in both behavioral and neural responses on gambling in AHAs. Taken together, our findings suggest AHAs have risk-prone tendency and dysfunction in adaptive decision making, since they continue to choose risky options even after accruing considerable negative scores, and fail to shift to a safer strategy to avoid risk. Such abnormal decision-making bias to risk and immediate reward seeking may be accompanied by abnormal reward expectation and evaluation in AHAs, which explains their high risk-seeking and impulsivity.

Prediction of heart abnormality using MLP network

Science.gov (United States)

Hashim, Fakroul Ridzuan; Januar, Yulni; Mat, Muhammad Hadzren; Rizman, Zairi Ismael; Awang, Mat Kamil

2018-02-01

Heart abnormality does not choose gender, age and races when it strikes. With no warning signs or symptoms, it can result to a sudden death of the patient. Generally, heart's irregular electrical activity is defined as heart abnormality. Via implementation of Multilayer Perceptron (MLP) network, this paper tries to develop a program that allows the detection of heart abnormality activity. Utilizing several training algorithms with Purelin activation function, an amount of heartbeat signals received through the electrocardiogram (ECG) will be employed to condition the MLP network.

Expression and localization of nerve growth factor (NGF in the testis of alpaca (llama pacos

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Changsheng Dong

2011-04-01

Full Text Available During alpaca testis development and spermatogenesis, nerve growth factor (NGF may play an important role. The main aim of this study was to determine the expression and localization of NGF in the alpaca testis, and to discuss the important role of NGF in alpaca reproductive characteristics. Immunohistochemical staining technique and real-time PCR were used. The expression of NGF in the same cells one-month old (newborn alpacas 12-month, and 24-month old alpacas showed significant differences (p < 0.05; 12- and 24-month old alpacas showed no significant differences (p > 0.05; NGF at different cell stages showed no significant differences (p > 0.05. It suggests that NGF may be involved in the regulation of spermatogenesis, which provides direct evidence for NGF action in the alpaca testis during postnatal development and spermatogenesis. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 55–61