WorldWideScience

Sample records for normal cytoskeletal function

  1. Cytoskeletal Tropomyosin Tm5NM1 Is Required for Normal Excitation–Contraction Coupling in Skeletal Muscle

    Science.gov (United States)

    Vlahovich, Nicole; Kee, Anthony J.; Van der Poel, Chris; Kettle, Emma; Hernandez-Deviez, Delia; Lucas, Christine; Lynch, Gordon S.; Parton, Robert G.; Gunning, Peter W.

    2009-01-01

    The functional diversity of the actin microfilaments relies in part on the actin binding protein tropomyosin (Tm). The muscle-specific Tms regulate actin-myosin interactions and hence contraction. However, there is less known about the roles of the numerous cytoskeletal isoforms. We have shown previously that a cytoskeletal Tm, Tm5NM1, defines a Z-line adjacent cytoskeleton in skeletal muscle. Recently, we identified a second cytoskeletal Tm in this region, Tm4. Here we show that Tm4 and Tm5NM1 define separate actin filaments; the former associated with the terminal sarcoplasmic reticulum (SR) and other tubulovesicular structures. In skeletal muscles of Tm5NM1 knockout (KO) mice, Tm4 localization was unchanged, demonstrating the specificity of the membrane association. Tm5NM1 KO muscles exhibit potentiation of T-system depolarization and decreased force rundown with repeated T-tubule depolarizations consistent with altered T-tubule function. These results indicate that a Tm5NM1-defined actin cytoskeleton is required for the normal excitation–contraction coupling in skeletal muscle. PMID:19005216

  2. Cytoskeletal tropomyosin Tm5NM1 is required for normal excitation-contraction coupling in skeletal muscle.

    Science.gov (United States)

    Vlahovich, Nicole; Kee, Anthony J; Van der Poel, Chris; Kettle, Emma; Hernandez-Deviez, Delia; Lucas, Christine; Lynch, Gordon S; Parton, Robert G; Gunning, Peter W; Hardeman, Edna C

    2009-01-01

    The functional diversity of the actin microfilaments relies in part on the actin binding protein tropomyosin (Tm). The muscle-specific Tms regulate actin-myosin interactions and hence contraction. However, there is less known about the roles of the numerous cytoskeletal isoforms. We have shown previously that a cytoskeletal Tm, Tm5NM1, defines a Z-line adjacent cytoskeleton in skeletal muscle. Recently, we identified a second cytoskeletal Tm in this region, Tm4. Here we show that Tm4 and Tm5NM1 define separate actin filaments; the former associated with the terminal sarcoplasmic reticulum (SR) and other tubulovesicular structures. In skeletal muscles of Tm5NM1 knockout (KO) mice, Tm4 localization was unchanged, demonstrating the specificity of the membrane association. Tm5NM1 KO muscles exhibit potentiation of T-system depolarization and decreased force rundown with repeated T-tubule depolarizations consistent with altered T-tubule function. These results indicate that a Tm5NM1-defined actin cytoskeleton is required for the normal excitation-contraction coupling in skeletal muscle.

  3. Cytoskeletal proteins in the follicular wall of normal andcystic ovaries of sows

    Directory of Open Access Journals (Sweden)

    Fabiano J.F. de Sant'Ana

    2015-02-01

    Full Text Available The expression of cytoskeletal proteins was evaluated immunohistochemically in 36 normal ovaries sampled from 18 sows and 44 cystic ovaries sampled from of 22 sows, was evaluated. All sows had history of reproductive problems, such as infertility or subfertility. The immunohistochemically stained area (IHCSA was quantified through image analysis to evaluate the expression of these proteins in the follicular wall of secondary, tertiary, and cystic follicles. Cytokeratins (CK immunoreactivity was strong in the granulosa cell layer (GC and mild in the theca interna (TI and externa (TE of the normal follicles. There was severe reduction of the reaction to CK in the GC in the cystic follicles, mainly in the luteinized cysts. The immunoreactivity for vimentin was higher in the GC from normal and cystic follicles in contrast with the other follicular structures. In the luteinized cysts, the IHCSA for vimentin was significantly higher in TI and in both observed cysts, the labeling was more accentuated in TE. Immunohistochemical detection of desmin and α-SMA was restricted to the TE, without differences between the normal and cystic follicles. The results of the current study show that the development of ovarian cysts in sows is associated to changes in the expression of the cytoskeletal proteins CK and vimentin.

  4. Cytoskeletal Tropomyosin Tm5NM1 Is Required for Normal Excitation–Contraction Coupling in Skeletal Muscle

    OpenAIRE

    Vlahovich, Nicole; Kee, Anthony J.; Van der Poel, Chris; Kettle, Emma; Hernandez-Deviez, Delia; Lucas, Christine; Lynch, Gordon S.; Parton, Robert G.; Gunning, Peter W.; Hardeman, Edna C.

    2009-01-01

    The functional diversity of the actin microfilaments relies in part on the actin binding protein tropomyosin (Tm). The muscle-specific Tms regulate actin-myosin interactions and hence contraction. However, there is less known about the roles of the numerous cytoskeletal isoforms. We have shown previously that a cytoskeletal Tm, Tm5NM1, defines a Z-line adjacent cytoskeleton in skeletal muscle. Recently, we identified a second cytoskeletal Tm in this region, Tm4. Here we show that Tm4 and Tm5N...

  5. Normal Functioning Family

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Español Text Size Email Print Share Normal Functioning Family Page Content Article Body Is there any way ...

  6. Cytoskeletal defects in Bmpr2-associated pulmonary arterial hypertension.

    Science.gov (United States)

    Johnson, Jennifer A; Hemnes, Anna R; Perrien, Daniel S; Schuster, Manfred; Robinson, Linda J; Gladson, Santhi; Loibner, Hans; Bai, Susan; Blackwell, Tom R; Tada, Yuji; Harral, Julie W; Talati, Megha; Lane, Kirk B; Fagan, Karen A; West, James

    2012-03-01

    The heritable form of pulmonary arterial hypertension (PAH) is typically caused by a mutation in bone morphogenic protein receptor type 2 (BMPR2), and mice expressing Bmpr2 mutations develop PAH with features similar to human disease. BMPR2 is known to interact with the cytoskeleton, and human array studies in PAH patients confirm alterations in cytoskeletal pathways. The goal of this study was to evaluate cytoskeletal defects in BMPR2-associated PAH. Expression arrays on our Bmpr2 mutant mouse lungs revealed cytoskeletal defects as a prominent molecular consequence of universal expression of a Bmpr2 mutation (Rosa26-Bmpr2(R899X)). Pulmonary microvascular endothelial cells cultured from these mice have histological and functional cytoskeletal defects. Stable transfection of different BMPR2 mutations into pulmonary microvascular endothelial cells revealed that cytoskeletal defects are common to multiple BMPR2 mutations and are associated with activation of the Rho GTPase, Rac1. Rac1 defects are corrected in cell culture and in vivo through administration of exogenous recombinant human angiotensin-converting enzyme 2 (rhACE2). rhACE2 reverses 77% of gene expression changes in Rosa26-Bmpr2(R899X) transgenic mice, in particular, correcting defects in cytoskeletal function. Administration of rhACE2 to Rosa26-Bmpr2(R899X) mice with established PAH normalizes pulmonary pressures. Together, these findings suggest that cytoskeletal function is central to the development of BMPR2-associated PAH and that intervention against cytoskeletal defects may reverse established disease.

  7. Semigroups of data normalization functions

    NARCIS (Netherlands)

    Warrens, Matthijs J.

    2016-01-01

    Variable centering and scaling are functions that are typically used in data normalization. Various properties of centering and scaling functions are presented. It is shown that if we use two centering functions (or scaling functions) successively, the result depends on the order in which the

  8. Cytoskeletal actin genes function downstream of HNF-3beta in ascidian notochord development.

    Science.gov (United States)

    Jeffery, W R; Ewing, N; Machula, J; Olsen, C L; Swalla, B J

    1998-11-01

    We have examined the expression and regulation of cytoskeletal actin genes in ascidians with tailed (Molgula oculata) and tailless larvae (Molgula occulta). Four cDNA clones were isolated representing two pairs of orthologous cytoskeletal actin genes (CA1 and CA2), which encode proteins differing by five amino acids in the tailed and tailless species. The CA1 and CA2 genes are present in one or two copies, although several related genes may also be present in both species. Maternal CA1 and CA2 mRNA is present in small oocytes but transcript levels later decline, suggesting a role in early oogenesis. In the tailed species, embryonic CA1 and CA2 mRNAs first appear in the presumptive mesenchyme and muscle cells during gastrulation, subsequently accumulate in the presumptive notochord cells, and can be detected in these tissues through the tadpole stage. CA1 mRNAs accumulate initially in the same tissues in the tailless species but subsequently disappear, in concert with the arrest of notochord and tail development. In contrast, CA2 mRNAs were not detected in embryos of the tailless species. Fertilization of eggs of the tailless species with sperm of the tailed species, which restores the notochord and the tail, also results in the upregulation of CA1 and CA2 gene expression in hybrid embryos. Antisense oligodeoxynucleotide experiments suggest that CA1 and CA2 expression in the notochord, but not in the muscle cells, is dependent on prior expression of Mocc FHI, an ascidian HNF-3beta-like gene. The expression of the CA1 and CA2 genes in the notochord in the tailed species, downregulation in the tailless species, upregulation in interspecific hybrids, and dependence on HNF-3beta activity is consistent with a role of these genes in development of the ascidian notochord.

  9. Alternative cytoskeletal landscapes: cytoskeletal novelty and evolution in basal excavate protists

    Science.gov (United States)

    Dawson, Scott C.; Paredez, Alexander R.

    2016-01-01

    Microbial eukaryotes encompass the majority of eukaryotic evolutionary and cytoskeletal diversity. The cytoskeletal complexity observed in multicellular organisms appears to be an expansion of components present in genomes of diverse microbial eukaryotes such as the basal lineage of flagellates, the Excavata. Excavate protists have complex and diverse cytoskeletal architectures and life cycles – essentially alternative cytoskeletal “landscapes” – yet still possess conserved microtubule- and actin-associated proteins. Comparative genomic analyses have revealed that a subset of excavates, however, lack many canonical actin-binding proteins central to actin cytoskeleton function in other eukaryotes. Overall, excavates possess numerous uncharacterized and “hypothetical” genes, and may represent an undiscovered reservoir of novel cytoskeletal genes and cytoskeletal mechanisms. The continued development of molecular genetic tools in these complex microbial eukaryotes will undoubtedly contribute to our overall understanding of cytoskeletal diversity and evolution. PMID:23312067

  10. Cdc42 regulates epithelial cell polarity and cytoskeletal function during kidney tubule development

    DEFF Research Database (Denmark)

    Elias, Bertha C; Das, Amrita; Parekh, Diptiben V

    2015-01-01

    The Rho GTPase Cdc42 regulates key signaling pathways required for multiple cell functions, including maintenance of shape, polarity, proliferation, migration, differentiation and morphogenesis. Although previous studies have shown that Cdc42 is required for proper epithelial development and main......The Rho GTPase Cdc42 regulates key signaling pathways required for multiple cell functions, including maintenance of shape, polarity, proliferation, migration, differentiation and morphogenesis. Although previous studies have shown that Cdc42 is required for proper epithelial development...

  11. Cellular automata in cytoskeletal lattices

    Energy Technology Data Exchange (ETDEWEB)

    Smith, S A; Watt, R C; Hameroff, S R

    1984-01-01

    Cellular automata (CA) activities could mediate biological regulation and information processing via nonlinear electrodynamic effects in cytoskeletal lattice arrays. Frohlich coherent oscillations and other nonlinear mechanisms may effect discrete 10/sup -10/ to 10/sup -11/ s interval events which result in dynamic patterns in biolattices such as cylindrical protein polymers: microtubules (MT). Structural geometry and electrostatic forces of MT subunit dipole oscillations suggest neighbor rules among the hexagonally packed protein subunits. Computer simulations using these suggested rules and MT structural geometry demonstrate CA activities including dynamical and stable self-organizing patterns, oscillators, and traveling gliders. CA activities in MT and other cytoskeletal lattices may have important biological regulatory functions. 23 references, 6 figures, 1 table.

  12. Normal Functions As A New Way Of Defining Computable Functions

    Directory of Open Access Journals (Sweden)

    Leszek Dubiel

    2004-01-01

    Full Text Available Report sets new method of defining computable functions. This is formalization of traditional function descriptions, so it allows to define functions in very intuitive way. Discovery of Ackermann function proved that not all functions that can be easily computed can be so easily described with Hilbert’s system of recursive functions. Normal functions lack this disadvantage.

  13. Normal Functions as a New Way of Defining Computable Functions

    Directory of Open Access Journals (Sweden)

    Leszek Dubiel

    2004-01-01

    Full Text Available Report sets new method of defining computable functions. This is formalization of traditional function descriptions, so it allows to define functions in very intuitive way. Discovery of Ackermann function proved that not all functions that can be easily computed can be so easily described with Hilbert's system of recursive functions. Normal functions lack this disadvantage.

  14. Dissociative Functions in the Normal Mourning Process.

    Science.gov (United States)

    Kauffman, Jeffrey

    1994-01-01

    Sees dissociative functions in mourning process as occurring in conjunction with integrative trends. Considers initial shock reaction in mourning as model of normal dissociation in mourning process. Dissociation is understood to be related to traumatic significance of death in human consciousness. Discerns four psychological categories of…

  15. Does partial occlusion promote normal binocular function?

    Science.gov (United States)

    Li, Jingrong; Thompson, Benjamin; Ding, Zhaofeng; Chan, Lily Y L; Chen, Xiang; Yu, Minbin; Deng, Daming; Hess, Robert F

    2012-10-03

    There is growing evidence that abnormal binocular interactions play a key role in the amblyopia syndrome and represent a viable target for treatment interventions. In this context the use of partial occlusion using optical devices such as Bangerter filters as an alternative to complete occlusion is of particular interest. The aims of this study were to understand why Bangerter filters do not result in improved binocular outcomes compared to complete occlusion, and to compare the effects of Bangerter filters, optical blur and neutral density (ND) filters on normal binocular function. The effects of four strengths of Bangerter filters (0.8, 0.6, 0.4, 0.2) on letter and vernier acuity, contrast sensitivity, stereoacuity, and interocular suppression were measured in 21 observers with normal vision. In a subset of 14 observers, the partial occlusion effects of Bangerter filters, ND filters and plus lenses on stereopsis and interocular suppression were compared. Bangerter filters did not have graded effect on vision and induced significant disruption to binocular function. This disruption was greater than that of monocular defocus but weaker than that of ND filters. The effect of the Bangerter filters on stereopsis was more pronounced than their effect on monocular acuity, and the induced monocular acuity deficits did not predict the induced deficits in stereopsis. Bangerter filters appear to be particularly disruptive to binocular function. Other interventions, such as optical defocus and those employing computer generated dichoptic stimulus presentation, may be more appropriate than partial occlusion for targeting binocular function during amblyopia treatment.

  16. VEGF-A, cytoskeletal dynamics, and the pathological vascular phenotype

    International Nuclear Information System (INIS)

    Nagy, Janice A.; Senger, Donald R.

    2006-01-01

    Normal angiogenesis is a complex process involving the organization of proliferating and migrating endothelial cells (ECs) into a well-ordered and highly functional vascular network. In contrast, pathological angiogenesis, which is a conspicuous feature of tumor growth, ischemic diseases, and chronic inflammation, is characterized by vessels with aberrant angioarchitecture and compromised barrier function. Herein we review the subject of pathological angiogenesis, particularly that driven by vascular endothelial growth factor (VEGF-A), from a new perspective. We propose that the serious structural and functional anomalies associated with VEGF-A-elicited neovessels, reflect, at least in part, imbalances in the internal molecular cues that govern the ordered assembly of ECs into three dimensional vascular networks and preserve vessel barrier function. Adopting such a viewpoint widens the focus from solely on specific pro-angiogenic stimuli such as VEGF-A to include a key set of cytoskeletal regulatory molecules, the Rho GTPases, which are known to direct multiple aspects of vascular morphogenesis including EC motility, alignment, multi-cellular organization, as well as intercellular junction integrity. We offer this perspective to draw attention to the importance of endothelial cytoskeletal dynamics for proper neovascularization and to suggest new therapeutic strategies with the potential to improve the pathological vascular phenotype

  17. Normal families and isolated singularities of meromorphic functions

    International Nuclear Information System (INIS)

    Chee, P.S.; Subramaniam, A.

    1985-06-01

    Based on the criterion of Zalcman for normal families, a generalization of a well-known result relating normal families and isolated essential singularities of meromorphic functions is proved, using a theorem of Lehto and Virtanen on normal functions. (author)

  18. Diverse mitotic functions of the cytoskeletal cross-linking protein Shortstop suggest a role in Dynein/Dynactin activity.

    Science.gov (United States)

    Dewey, Evan B; Johnston, Christopher A

    2017-09-15

    Proper assembly and orientation of the bipolar mitotic spindle is critical to the fidelity of cell division. Mitotic precision fundamentally contributes to cell fate specification, tissue development and homeostasis, and chromosome distribution within daughter cells. Defects in these events are thought to contribute to several human diseases. The underlying mechanisms that function in spindle morphogenesis and positioning remain incompletely defined, however. Here we describe diverse roles for the actin-microtubule cross-linker Shortstop (Shot) in mitotic spindle function in Drosophila Shot localizes to mitotic spindle poles, and its knockdown results in an unfocused spindle pole morphology and a disruption of proper spindle orientation. Loss of Shot also leads to chromosome congression defects, cell cycle progression delay, and defective chromosome segregation during anaphase. These mitotic errors trigger apoptosis in Drosophila epithelial tissue, and blocking this apoptotic response results in a marked induction of the epithelial-mesenchymal transition marker MMP-1. The actin-binding domain of Shot directly interacts with Actin-related protein-1 (Arp-1), a key component of the Dynein/Dynactin complex. Knockdown of Arp-1 phenocopies Shot loss universally, whereas chemical disruption of F-actin does so selectively. Our work highlights novel roles for Shot in mitosis and suggests a mechanism involving Dynein/Dynactin activation. © 2017 Dewey and Johnston. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  19. Normal thyroid function values in Ethiopians

    International Nuclear Information System (INIS)

    Wassie, Emnetu; Abdulkadir, Jemal

    1990-01-01

    Thyroid function values were determined in 56 healthy nongoitrous adult Ethiopians. The mean triiodothyronine (T3) values for 20 males and 36 females were 1.42+-0.32 nmol/L and 1.51+-0.25 nmol/L, and thyroxine (T4) values were 119 22 nmol/L and 116+21 nmol/L respectively. The mean thyrotropin (TSH) values for males and females were identical at 1.86+-0.94 mu/L. Radioactive iodine uptake (RAIU) at 2 hours was 8.6+-4.4% in males and 11.3+-4.3% in females, and at 24 hours 31.7+-11.7% and 38.9+-11.1% respectively. The difference between males and females were significant at both 2 and 24 hours (P<0.05). The ranges for the 3 hormones derived from the mean 2SD values are close to these supplied with the kits but the Ethiopian RAIU values are higher than the values currently applicable in developed countries, probably indicative of the lower level of dietary iodine available to the population here. The values obtained in this study are offered to serve as normal reference for the interpretation of thyroid function results in Ethiopian patients. A strategy for the rational utilization of the available in vitro tests is suggested

  20. Normal Function of the Colon and Anorectal Area

    Science.gov (United States)

    ... What is Constipation Introduction: What is Constipation? Normal Function Common Questions & Mistaken Beliefs Signs & Symptoms Symptoms Overview ... What is Constipation Introduction: What is Constipation? Normal Function Common Questions & Mistaken Beliefs Signs & Symptoms Symptoms Overview ...

  1. Dendritic Cytoskeletal Architecture Is Modulated by Combinatorial Transcriptional Regulation in Drosophila melanogaster.

    Science.gov (United States)

    Das, Ravi; Bhattacharjee, Shatabdi; Patel, Atit A; Harris, Jenna M; Bhattacharya, Surajit; Letcher, Jamin M; Clark, Sarah G; Nanda, Sumit; Iyer, Eswar Prasad R; Ascoli, Giorgio A; Cox, Daniel N

    2017-12-01

    Transcription factors (TFs) have emerged as essential cell autonomous mediators of subtype specific dendritogenesis; however, the downstream effectors of these TFs remain largely unknown, as are the cellular events that TFs control to direct morphological change. As dendritic morphology is largely dictated by the organization of the actin and microtubule (MT) cytoskeletons, elucidating TF-mediated cytoskeletal regulatory programs is key to understanding molecular control of diverse dendritic morphologies. Previous studies in Drosophila melanogaster have demonstrated that the conserved TFs Cut and Knot exert combinatorial control over aspects of dendritic cytoskeleton development, promoting actin and MT-based arbor morphology, respectively. To investigate transcriptional targets of Cut and/or Knot regulation, we conducted systematic neurogenomic studies, coupled with in vivo genetic screens utilizing multi-fluor cytoskeletal and membrane marker reporters. These analyses identified a host of putative Cut and/or Knot effector molecules, and a subset of these putative TF targets converge on modulating dendritic cytoskeletal architecture, which are grouped into three major phenotypic categories, based upon neuromorphometric analyses: complexity enhancer, complexity shifter, and complexity suppressor. Complexity enhancer genes normally function to promote higher order dendritic growth and branching with variable effects on MT stabilization and F-actin organization, whereas complexity shifter and complexity suppressor genes normally function in regulating proximal-distal branching distribution or in restricting higher order branching complexity, respectively, with spatially restricted impacts on the dendritic cytoskeleton. Collectively, we implicate novel genes and cellular programs by which TFs distinctly and combinatorially govern dendritogenesis via cytoskeletal modulation. Copyright © 2017 by the Genetics Society of America.

  2. Nucleocytoplasmic Shuttling of Cytoskeletal Proteins: Molecular Mechanism and Biological Significance

    Directory of Open Access Journals (Sweden)

    Masahiro Kumeta

    2012-01-01

    Full Text Available Various nuclear functional complexes contain cytoskeletal proteins as regulatory subunits; for example, nuclear actin participates in transcriptional complexes, and actin-related proteins are integral to chromatin remodeling complexes. Nuclear complexes such as these are involved in both basal and adaptive nuclear functions. In addition to nuclear import via classical nuclear transport pathways or passive diffusion, some large cytoskeletal proteins spontaneously migrate into the nucleus in a karyopherin-independent manner. The balance of nucleocytoplasmic distribution of such proteins can be altered by several factors, such as import versus export, or capture and release by complexes. The resulting accumulation or depletion of the nuclear populations thereby enhances or attenuates their nuclear functions. We propose that such molecular dynamics constitute a form of cytoskeleton-modulated regulation of nuclear functions which is mediated by the translocation of cytoskeletal components in and out of the nucleus.

  3. Normal macrophage function in copper deficient mice

    International Nuclear Information System (INIS)

    Lukasewycz, O.A.; Kolquist, K.L.; Prohaska, J.R.

    1986-01-01

    Copper deficiency (-Cu) was produced in C57 BL and C58 mice by feeding a low copper diet (modified AIN-76A) from birth. Mice given supplemental copper in the drinking water (+Cu) served as controls. Copper status was monitored by assay of ceruloplasmin (CP) activity. Macrophages (M0) were obtained from matched +Cu and -Cu male 7 week-old mice by peritoneal lavage 3 days after thioglycollate stimulation. M0 were assayed in terms of lipopolysaccharide-induced hexose monophosphate shunt activity by monitoring 14 CO 2 production from [1- 14 C]-glucose and by the determination of phagocytic index using fluorescein labelled latex bead ingestion. M0 from -Cu mice were equivalent to those of +Cu mice in both these parameters. However, superoxide dismutase and cytochrome oxidase activities were both significantly lower in -Cu M0, confirming a functional copper deficiency. Previous results from this laboratory have shown that -Cu mice have a decreased antibody response to sheep erythrocyte antigens and a diminished reactivity to B and T cell mitogens. These immunological insufficiencies appear to be proportional to the severity of copper depletion as determined by CP levels. Furthermore, -Cu lymphocytes exhibit depressed mixed lymphocyte reactivity consistent with alterations at the membrane surface. The present results suggest that M0/monocytes are less severely affected than lymphocytes in copper deficiency states

  4. Aggregatibacter actinomycetemcomitans lipopolysaccharide affects human gingival fibroblast cytoskeletal organization.

    Science.gov (United States)

    Gutiérrez-Venegas, Gloria; Contreras-Marmolejo, Luis Arturo; Román-Alvárez, Patricia; Barajas-Torres, Carolina

    2008-04-01

    The cytoskeleton is a dynamic structure that plays a key role in maintaining cell morphology and function. This study investigates the effect of bacterial wall lipopolysaccharide (LPS), a strong inflammatory agent, on the dynamics and organization of actin, tubulin, vimentin, and vinculin proteins in human gingival fibroblasts (HGF). A time-dependent study showed a noticeable change in actin architecture after 1.5 h of incubation with LPS (1 microg/ml) with the formation of orthogonal fibers and further accumulation of actin filament at the cell periphery by 24 h. When 0.01-10 microg/ml of LPS was added to human gingival fibroblast cultures, cells acquired a round, flat shape and gradually developed cytoplasmic ruffling. Lipopolysaccharides extracted from Aggregatibacter actinomycetemcomitans periodontopathogenic bacteria promoted alterations in F-actin stress fibres of human gingival cells. Normally, human gingival cells have F-actin fibres that are organized in linear distribution throughout the cells, extending along the cell's length. LPS-treated cells exhibited changes in cytoskeletal protein organization, and F-actin was reorganized by the formation of bundles underneath and parallel to the cell membrane. We also found the reorganization of the vimentin network into vimentin bundling after 1.5 h of treatment. HGF cells exhibited diffuse and granular gamma-tubulin stain. There was no change in LPS-treated HGF. However, vinculin plaques distributed in the cell body diminished after LPS treatment. We conclude that the dynamic and structured organization of cytoskeletal filaments and actin assembly in human gingival fibroblasts is altered by LPS treatment and is accompanied by a decrease in F-actin pools.

  5. Temperament Affects Sympathetic Nervous Function in a Normal Population

    OpenAIRE

    Kim, Bora; Lee, Jae-Hon; Kang, Eun-Ho; Yu, Bum-Hee

    2012-01-01

    Objective Although specific temperaments have been known to be related to autonomic nervous function in some psychiatric disorders, there are few studies that have examined the relationship between temperaments and autonomic nervous function in a normal population. In this study, we examined the effect of temperament on the sympathetic nervous function in a normal population. Methods Sixty eight healthy subjects participated in the present study. Temperament was assessed using the Korean vers...

  6. Neuronal Function in Male Sprague Dawley Rats During Normal ...

    African Journals Online (AJOL)

    olayemitoyin

    Summary: During normal ageing, there are physiological changes especially in high energy ... science and technology (U.S. Bureau of the Census ... strategies that can be applied to preserve function with ..... Intelligent Technology for an.

  7. Normal central retinal function and structure preserved in retinitis pigmentosa.

    Science.gov (United States)

    Jacobson, Samuel G; Roman, Alejandro J; Aleman, Tomas S; Sumaroka, Alexander; Herrera, Waldo; Windsor, Elizabeth A M; Atkinson, Lori A; Schwartz, Sharon B; Steinberg, Janet D; Cideciyan, Artur V

    2010-02-01

    To determine whether normal function and structure, as recently found in forms of Usher syndrome, also occur in a population of patients with nonsyndromic retinitis pigmentosa (RP). Patients with simplex, multiplex, or autosomal recessive RP (n = 238; ages 9-82 years) were studied with static chromatic perimetry. A subset was evaluated with optical coherence tomography (OCT). Co-localized visual sensitivity and photoreceptor nuclear layer thickness were measured across the central retina to establish the relationship of function and structure. Comparisons were made to patients with Usher syndrome (n = 83, ages 10-69 years). Cross-sectional psychophysical data identified patients with RP who had normal rod- and cone-mediated function in the central retina. There were two other patterns with greater dysfunction, and longitudinal data confirmed that progression can occur from normal rod and cone function to cone-only central islands. The retinal extent of normal laminar architecture by OCT corresponded to the extent of normal visual function in patients with RP. Central retinal preservation of normal function and structure did not show a relationship with age or retained peripheral function. Usher syndrome results were like those in nonsyndromic RP. Regional disease variation is a well-known finding in RP. Unexpected was the observation that patients with presumed recessive RP can have regions with functionally and structurally normal retina. Such patients will require special consideration in future clinical trials of either focal or systemic treatment. Whether there is a common molecular mechanism shared by forms of RP with normal regions of retina warrants further study.

  8. Normalization methods in time series of platelet function assays

    Science.gov (United States)

    Van Poucke, Sven; Zhang, Zhongheng; Roest, Mark; Vukicevic, Milan; Beran, Maud; Lauwereins, Bart; Zheng, Ming-Hua; Henskens, Yvonne; Lancé, Marcus; Marcus, Abraham

    2016-01-01

    Abstract Platelet function can be quantitatively assessed by specific assays such as light-transmission aggregometry, multiple-electrode aggregometry measuring the response to adenosine diphosphate (ADP), arachidonic acid, collagen, and thrombin-receptor activating peptide and viscoelastic tests such as rotational thromboelastometry (ROTEM). The task of extracting meaningful statistical and clinical information from high-dimensional data spaces in temporal multivariate clinical data represented in multivariate time series is complex. Building insightful visualizations for multivariate time series demands adequate usage of normalization techniques. In this article, various methods for data normalization (z-transformation, range transformation, proportion transformation, and interquartile range) are presented and visualized discussing the most suited approach for platelet function data series. Normalization was calculated per assay (test) for all time points and per time point for all tests. Interquartile range, range transformation, and z-transformation demonstrated the correlation as calculated by the Spearman correlation test, when normalized per assay (test) for all time points. When normalizing per time point for all tests, no correlation could be abstracted from the charts as was the case when using all data as 1 dataset for normalization. PMID:27428217

  9. Normal left ventricular function does not protect against propafenone ...

    African Journals Online (AJOL)

    Normal left ventricular function does not protect against propafenone-induced incessant ventricular tachycardia. R. N. Scott Millar, J. B. Lawrenson, D.A. Milne. Abstract. Propafenone is a class Ic anti-arrhythmic agent with mild B-blocking properties which has recently become available in South Africa. We have used the ...

  10. Temperament affects sympathetic nervous function in a normal population.

    Science.gov (United States)

    Kim, Bora; Lee, Jae-Hon; Kang, Eun-Ho; Yu, Bum-Hee

    2012-09-01

    Although specific temperaments have been known to be related to autonomic nervous function in some psychiatric disorders, there are few studies that have examined the relationship between temperaments and autonomic nervous function in a normal population. In this study, we examined the effect of temperament on the sympathetic nervous function in a normal population. Sixty eight healthy subjects participated in the present study. Temperament was assessed using the Korean version of the Cloninger Temperament and Character Inventory (TCI). Autonomic nervous function was determined by measuring skin temperature in a resting state, which was recorded for 5 minutes from the palmar surface of the left 5th digit using a thermistor secured with a Velcro® band. Pearson's correlation analysis and multiple linear regression were used to examine the relationship between temperament and skin temperature. A higher harm avoidance score was correlated with a lower skin temperature (i.e. an increased sympathetic tone; r=-0.343, p=0.004) whereas a higher persistence score was correlated with a higher skin temperature (r=0.433, p=0.001). Hierarchical linear regression analysis revealed that harm avoidance was able to predict the variance of skin temperature independently, with a variance of 7.1% after controlling for sex, blood pressure and state anxiety and persistence was the factor predicting the variance of skin temperature with a variance of 5.0%. These results suggest that high harm avoidance is related to an increased sympathetic nervous function whereas high persistence is related to decreased sympathetic nervous function in a normal population.

  11. Neuronal Function in Male Sprague Dawley Rats During Normal Ageing.

    Science.gov (United States)

    Idowu, A J; Olatunji-Bello, I I; Olagunju, J A

    2017-03-06

    During normal ageing, there are physiological changes especially in high energy demanding tissues including the brain and skeletal muscles. Ageing may disrupt homeostasis and allow tissue vulnerability to disease. To establish an appropriate animal model which is readily available and will be useful to test therapeutic strategies during normal ageing, we applied behavioral approaches to study age-related changes in memory and motor function as a basis for neuronal function in ageing in male Sprague Dawley rats. 3 months, n=5; 6 months, n=5 and 18 months, n=5 male Sprague Dawley Rats were tested using the Novel Object Recognition Task (NORT) and the Elevated plus Maze (EPM) Test. Data was analyzed by ANOVA and the Newman-Keuls post hoc test. The results showed an age-related gradual decline in exploratory behavior and locomotor activity with increasing age in 3 months, 6 months and 18 months old rats, although the values were not statistically significant, but grooming activity significantly increased with increasing age. Importantly, we established a novel finding that the minimum distance from the novel object was statistically significant between 3 months and 18 months old rats and this may be an index for age-related memory impairment in the NORT. Altogether, we conclude that the male Sprague Dawley rat show age-related changes in neuronal function and may be a useful model for carrying out investigations into the mechanisms involved in normal ageing.

  12. Normalization of the collage regions of iterated function systems

    Science.gov (United States)

    Zhang, Zhengbing; Zhang, Wei

    2012-11-01

    Fractal graphics, generated with iterated function systems (IFS), have been applied in broad areas. Since the collage regions of different IFS may be different, it is difficult to respectively show the attractors of iterated function systems in a same region on a computer screen using one program without modifying the display parameters. An algorithm is proposed in this paper to solve this problem. A set of transforms are repeatedly applied to modify the coefficients of the IFS so that the collage region of the resulted IFS changes toward the unit square. Experimental results demonstrate that the collage region of any IFS can be normalized to the unit square with the proposed method.

  13. Sex differences in normal age trajectories of functional brain networks.

    Science.gov (United States)

    Scheinost, Dustin; Finn, Emily S; Tokoglu, Fuyuze; Shen, Xilin; Papademetris, Xenophon; Hampson, Michelle; Constable, R Todd

    2015-04-01

    Resting-state functional magnetic resonance image (rs-fMRI) is increasingly used to study functional brain networks. Nevertheless, variability in these networks due to factors such as sex and aging is not fully understood. This study explored sex differences in normal age trajectories of resting-state networks (RSNs) using a novel voxel-wise measure of functional connectivity, the intrinsic connectivity distribution (ICD). Males and females showed differential patterns of changing connectivity in large-scale RSNs during normal aging from early adulthood to late middle-age. In some networks, such as the default-mode network, males and females both showed decreases in connectivity with age, albeit at different rates. In other networks, such as the fronto-parietal network, males and females showed divergent connectivity trajectories with age. Main effects of sex and age were found in many of the same regions showing sex-related differences in aging. Finally, these sex differences in aging trajectories were robust to choice of preprocessing strategy, such as global signal regression. Our findings resolve some discrepancies in the literature, especially with respect to the trajectory of connectivity in the default mode, which can be explained by our observed interactions between sex and aging. Overall, results indicate that RSNs show different aging trajectories for males and females. Characterizing effects of sex and age on RSNs are critical first steps in understanding the functional organization of the human brain. © 2014 Wiley Periodicals, Inc.

  14. Differential proteomics study of platelets in asymptomatic constitutional macrothrombocytopenia: altered levels of cytoskeletal proteins.

    Science.gov (United States)

    Karmakar, Shilpita; Saha, Sutapa; Banerjee, Debasis; Chakrabarti, Abhijit

    2015-01-01

    Harris platelet syndrome (HPS), also known as asymptomatic constitutional macrothrombocytopenia (ACMT), is an autosomal dominant platelet disorder characterized by mild-to-severe thrombocytopenia and giant platelets with normal platelet aggregation and absence of bleeding symptoms. We have attempted a comparative proteomics study for profiling of platelet proteins in healthy vs. pathological states to discover characteristic protein expression changes in macrothrombocytes and decipher the factors responsible for the functionally active yet morphologically distinct platelets. We have used 2-D gel-based protein separation techniques coupled with MALDI-ToF/ToF-based mass spectrometric identification and characterization of the proteins to investigate the differential proteome profiling of platelet proteins isolated from the peripheral blood samples of patients and normal volunteers. Our study revealed altered levels of actin-binding proteins such as myosin light chain, coactosin-like protein, actin-related protein 2/3 complex, and transgelin2 that hint toward the cytoskeletal changes necessary to maintain the structural and functional integrity of macrothrombocytes. We have also observed over expressed levels of peroxiredoxin2 that signifies the prevailing oxidative stress in these cells. Additionally, altered levels of protein disulfide isomerase and transthyretin provide insights into the measures adapted by the macrothrombocytes to maintain their normal functional activity. This first proteomics study of platelets from ACMT may provide an understanding of the structural stability and normal functioning of these platelets in spite of their large size. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Functional evaluation of transplanted kidneys in normal function and acute rejection using BOLD MR imaging

    International Nuclear Information System (INIS)

    Xiao Wenbo; Xu Jingjing; Wang Qindong; Xu Ying; Zhang Minming

    2012-01-01

    In this study, we evaluated a large number of subjects using BOLD MRI to provide more information about oxygen metabolism in the normal function of transplanted kidneys and to distinguish acute graft rejection from normal function kidneys. This study included 122 subjects (20 volunteers, 72 patients with normal functioning transplants, and 21 patients with acute rejection), and 9 patients had normal function grafts received examination while grafts dysfunction occurred within 6 months during the follow-up. The R2* (1/s) values in the cortex and medulla as well as the R2* ratio of the medulla to cortex (R2* ratio of M/C) were recorded. The R2* values of the medulla were higher than those of the cortex in the normal function group and the volunteers which have a steep R2* ratio of M/C. All the R2* values in the acute rejection group were lower than those in the normal function grafts group (P 1.1) is an important reason for keeping clinical normal function.

  16. Functional relationship between the cerebrum and cerebellum in normal subjects

    International Nuclear Information System (INIS)

    Hanyu, Haruo; Arai, Hisayuki; Hatano, Nobuyoshi; Abe, Shinei; Katsunuma, Hideyo

    1991-01-01

    To determine whether a functional relationship between the cerebrum and cerebellum exists in normal subjects, the correlation between asymmetry in cerebral blood flow and asymmetry in cerebellar blood flow was investigated. Twenty-one healthy right-handed subjects were studied using SPECT with N-isopropyl-p-( 123 I)iodoamphetamine while in a resting state. The asymmetry index (AI) for both the cerebral and cerebellar hemisphere was calculated as follows. AI=right side - left side/right side + left side/200 (%). A negative correlation was found between AI in the cerebellum and AI in the cerebrum. Especially, AI in the cerebellar hemisphere was significantly correlated with AIs in the upper frontal cortex (r=-0.58, p<0.01), middle frontal cortex (r=-0.55, p<0.02), lower frontal cortex (r=-0.49, p<0.05), and mean cerebral hemisphere (r=-0.52, p<0.02). These results suggest the existence of a functional relationship between the cerebral hemisphere and the contralateral cerebellar hemisphere in the resting state of normal subjects. We strongly suspect that the frontal cortex exert an influence on the function in the contralateral cerebellum, probably due to a transneuronal mechanism, mainly through the corticopontocerebellar pathway. (author)

  17. Stress and strain in the contractile and cytoskeletal filaments of airway smooth muscle.

    Science.gov (United States)

    Deng, Linhong; Bosse, Ynuk; Brown, Nathan; Chin, Leslie Y M; Connolly, Sarah C; Fairbank, Nigel J; King, Greg G; Maksym, Geoffrey N; Paré, Peter D; Seow, Chun Y; Stephen, Newman L

    2009-10-01

    Stress and strain are omnipresent in the lung due to constant lung volume fluctuation associated with respiration, and they modulate the phenotype and function of all cells residing in the airways including the airway smooth muscle (ASM) cell. There is ample evidence that the ASM cell is very sensitive to its physical environment, and can alter its structure and/or function accordingly, resulting in either desired or undesired consequences. The forces that are either conferred to the ASM cell due to external stretching or generated inside the cell must be borne and transmitted inside the cytoskeleton (CSK). Thus, maintaining appropriate levels of stress and strain within the CSK is essential for maintaining normal function. Despite the importance, the mechanisms regulating/dysregulating ASM cytoskeletal filaments in response to stress and strain remained poorly understood until only recently. For example, it is now understood that ASM length and force are dynamically regulated, and both can adapt over a wide range of length, rendering ASM one of the most malleable living tissues. The malleability reflects the CSK's dynamic mechanical properties and plasticity, both of which strongly interact with the loading on the CSK, and all together ultimately determines airway narrowing in pathology. Here we review the latest advances in our understanding of stress and strain in ASM cells, including the organization of contractile and cytoskeletal filaments, range and adaptation of functional length, structural and functional changes of the cell in response to mechanical perturbation, ASM tone as a mediator of strain-induced responses, and the novel glassy dynamic behaviors of the CSK in relation to asthma pathophysiology.

  18. Biotechnological aspects of cytoskeletal regulation in plants.

    Science.gov (United States)

    Komis, George; Luptovciak, Ivan; Doskocilova, Anna; Samaj, Jozef

    2015-11-01

    The cytoskeleton is a protein-based intracellular superstructure that evolved early after the appearance of bacterial prokaryotes. Eventually cytoskeletal proteins and their macromolecular assemblies were established in eukaryotes and assumed critical roles in cell movements, intracellular organization, cell division and cell differentiation. In biomedicine the small-molecules targeting cytoskeletal elements are in the frontline of anticancer research with plant-derived cytoskeletal drugs such as Vinca alkaloids and toxoids, being routinely used in the clinical practice. Moreover, plants are also major material, food and energy resources for human activities ranging from agriculture, textile industry, carpentry, energy production and new material development to name some few. Most of these inheritable traits are associated with cell wall synthesis and chemical modification during primary and secondary plant growth and inevitably are associated with the dynamics, organization and interactions of the plant cytoskeleton. Taking into account the vast intracellular spread of microtubules and actin microfilaments the cytoskeleton collectively assumed central roles in plant growth and development, in determining the physical stance of plants against the forces of nature and becoming a battleground between pathogenic invaders and the defense mechanisms of plant cells. This review aims to address the role of the plant cytoskeleton in manageable features of plants including cellulose biosynthesis with implications in wood and fiber properties, in biofuel production and the contribution of plant cytoskeletal elements in plant defense responses against pathogens or detrimental environmental conditions. Ultimately the present work surveys the potential of cytoskeletal proteins as platforms of plant genetic engineering, nominating certain cytoskeletal proteins as vectors of favorable traits in crops and other economically important plants. Copyright © 2015 Elsevier Inc. All

  19. Functional neuroimaging of normal aging: Declining brain, adapting brain.

    Science.gov (United States)

    Sugiura, Motoaki

    2016-09-01

    Early functional neuroimaging research on normal aging brain has been dominated by the interest in cognitive decline. In this framework the age-related compensatory recruitment of prefrontal cortex, in terms of executive system or reduced lateralization, has been established. Further details on these compensatory mechanisms and the findings reflecting cognitive decline, however, remain the matter of intensive investigations. Studies in another framework where age-related neural alteration is considered adaptation to the environmental change are recently burgeoning and appear largely categorized into three domains. The age-related increase in activation of the sensorimotor network may reflect the alteration of the peripheral sensorimotor systems. The increased susceptibility of the network for the mental-state inference to the socioemotional significance may be explained by the age-related motivational shift due to the altered social perception. The age-related change in activation of the self-referential network may be relevant to the focused positive self-concept of elderly driven by a similar motivational shift. Across the domains, the concept of the self and internal model may provide the theoretical bases of this adaptation framework. These two frameworks complement each other to provide a comprehensive view of the normal aging brain. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Occupational (? constrictive bronchiolitis with normal physical, functional and image findings

    Directory of Open Access Journals (Sweden)

    Sandra Figueiredo

    2009-07-01

    Full Text Available Constrictive bronchiolitis is characterized by alterations in the walls of membranous and respiratory bronchioles. These changes lead to concentric narrowing or complete obliteration of the airway lumen. Suspicion of possible bronchiolar disorders may arise from clinical, funcional, and radiologic findings. However, constrictive bronchiolitis may be present even with normal physical, functional and image findings, which turns the diagnosis difficult. A high index of suspicion is necessary to justify invasive tests that lead to pulmonary biopsy. In this report, we describe a patient with cough and dyspnoea, with normal physical, functional and image findings, whose work-up leaded to the diagnosis of constrictive bronchiolitis. Resumo: A bronquiolite constritiva é caracterizada por alterações das paredes dos bronquíolos membranosos e respiratórios. Estas alterações incluem um espectro de alterações que podem variar, desde a inflamação à fibrose concêntrica progressiva, com obstrução completa do lúmen bronquiolar. O diagnóstico pode ser sugerido pela história clínica e por alterações radiológicas e funcionais. No entanto, o exame físico e os exames complementares de diagnóstico podem ser normais, o que dificulta o diagnóstico, sendo necessário um elevado índice de suspeita para se sujeitar o doente a exames invasivos, tal como a biópsia pulmonar cirúrgica. Os autores apresentam um caso clínico de uma doente com quadro arrastado de tosse e dispneia, com exame físico, funcional e imagiológico normais, cujo estudo exaustivo veio a revelar o diagnóstico de bronquiolite constritiva. Key-words: Constrictive bronchiolitis, iron oxide, Palavras-chave: Bronquiolite constritiva, óxido de ferro

  1. Cytoskeletal Linker Protein Dystonin Is Not Critical to Terminal Oligodendrocyte Differentiation or CNS Myelination.

    Directory of Open Access Journals (Sweden)

    Samantha F Kornfeld

    Full Text Available Oligodendrocyte differentiation and central nervous system myelination require massive reorganization of the oligodendrocyte cytoskeleton. Loss of specific actin- and tubulin-organizing factors can lead to impaired morphological and/or molecular differentiation of oligodendrocytes, resulting in a subsequent loss of myelination. Dystonin is a cytoskeletal linker protein with both actin- and tubulin-binding domains. Loss of function of this protein results in a sensory neuropathy called Hereditary Sensory Autonomic Neuropathy VI in humans and dystonia musculorum in mice. This disease presents with severe ataxia, dystonic muscle and is ultimately fatal early in life. While loss of the neuronal isoforms of dystonin primarily leads to sensory neuron degeneration, it has also been shown that peripheral myelination is compromised due to intrinsic Schwann cell differentiation abnormalities. The role of this cytoskeletal linker in oligodendrocytes, however, remains unclear. We sought to determine the effects of the loss of neuronal dystonin on oligodendrocyte differentiation and central myelination. To address this, primary oligodendrocytes were isolated from a severe model of dystonia musculorum, Dstdt-27J, and assessed for morphological and molecular differentiation capacity. No defects could be discerned in the differentiation of Dstdt-27J oligodendrocytes relative to oligodendrocytes from wild-type littermates. Survival was also compared between Dstdt-27J and wild-type oligodendrocytes, revealing no significant difference. Using a recently developed migration assay, we further analysed the ability of primary oligodendrocyte progenitor cell motility, and found that Dstdt-27J oligodendrocyte progenitor cells were able to migrate normally. Finally, in vivo analysis of oligodendrocyte myelination was done in phenotype-stage optic nerve, cerebral cortex and spinal cord. The density of myelinated axons and g-ratios of Dstdt-27J optic nerves was normal, as

  2. Regulation of cytoskeletal organization by syndecan transmembrane proteoglycans

    DEFF Research Database (Denmark)

    Yoneda, Atsuko; Couchman, John R

    2003-01-01

    have recently suggested that signaling through core protein of syndecans can regulate cytoskeletal organization through their clustering, association with cytoskeletal structures, binding to cytoplasmic binding proteins, and intracellular phosphorylation. Here we will review current understanding...... of signaling through syndecans in cytoskeletal organization....

  3. Characterization of cytoskeletal and junctional proteins expressed by cells cultured from human arachnoid granulation tissue

    Directory of Open Access Journals (Sweden)

    Mehta Bhavya C

    2005-10-01

    Full Text Available Abstract Background The arachnoid granulations (AGs are projections of the arachnoid membrane into the dural venous sinuses. They function, along with the extracranial lymphatics, to circulate the cerebrospinal fluid (CSF to the systemic venous circulation. Disruption of normal CSF dynamics may result in increased intracranial pressures causing many problems including headaches and visual loss, as in idiopathic intracranial hypertension and hydrocephalus. To study the role of AGs in CSF egress, we have grown cells from human AG tissue in vitro and have characterized their expression of those cytoskeletal and junctional proteins that may function in the regulation of CSF outflow. Methods Human AG tissue was obtained at autopsy, and explanted to cell culture dishes coated with fibronectin. Typically, cells migrated from the explanted tissue after 7–10 days in vitro. Second or third passage cells were seeded onto fibronectin-coated coverslips at confluent densities and grown to confluency for 7–10 days. Arachnoidal cells were tested using immunocytochemical methods for the expression of several common cytoskeletal and junctional proteins. Second and third passage cultures were also labeled with the common endothelial markers CD-31 or VE-cadherin (CD144 and their expression was quantified using flow cytometry analysis. Results Confluent cultures of arachnoidal cells expressed the intermediate filament protein vimentin. Cytokeratin intermediate filaments were expressed variably in a subpopulation of cells. The cultures also expressed the junctional proteins connexin43, desmoplakin 1 and 2, E-cadherin, and zonula occludens-1. Flow cytometry analysis indicated that second and third passage cultures failed to express the endothelial cell markers CD31 or VE-cadherin in significant quantities, thereby showing that these cultures did not consist of endothelial cells from the venous sinus wall. Conclusion To our knowledge, this is the first report of

  4. Unique expression of cytoskeletal proteins in human soft palate muscles.

    Science.gov (United States)

    Shah, Farhan; Berggren, Diana; Holmlund, Thorbjörn; Levring Jäghagen, Eva; Stål, Per

    2016-03-01

    The human oropharyngeal muscles have a unique anatomy with diverse and intricate functions. To investigate if this specialization is also reflected in the cytoarchitecture of muscle fibers, intermediate filament proteins and the dystrophin-associated protein complex have been analyzed in two human palate muscles, musculus uvula (UV) and musculus palatopharyngeus (PP), with immunohistochenmical and morphological techniques. Human limb muscles were used as reference. The findings show that the soft palate muscle fibers have a cytoskeletal architecture that differs from the limb muscles. While all limb muscles showed immunoreaction for a panel of antibodies directed against different domains of cytoskeletal proteins desmin and dystrophin, a subpopulation of palate muscle fibers lacked or had a faint immunoreaction for desmin (UV 11.7% and PP 9.8%) and the C-terminal of the dystrophin molecule (UV 4.2% and PP 6.4%). The vast majority of these fibers expressed slow contractile protein myosin heavy chain I. Furthermore, an unusual staining pattern was also observed in these fibers for β-dystroglycan, caveolin-3 and neuronal nitric oxide synthase nNOS, which are all membrane-linking proteins associated with the dystrophin C-terminus. While the immunoreaction for nNOS was generally weak or absent, β-dystroglycan and caveolin-3 showed a stronger immunostaining. The absence or a low expression of cytoskeletal proteins otherwise considered ubiquitous and important for integration and contraction of muscle cells indicate a unique cytoarchitecture designed to meet the intricate demands of the upper airway muscles. It can be concluded that a subgroup of muscle fibers in the human soft palate appears to have special biomechanical properties, and their unique cytoarchitecture must be taken into account while assessing function and pathology in oropharyngeal muscles. © 2015 Anatomical Society.

  5. Subclinical atherosclerosis in obese adolescents with normal left ventricular function.

    Science.gov (United States)

    Abdel-Wahab, Amina M; Atwa, Hoda A; El-Eraky, Azza Z; El-Aziz, Mohamed A

    2011-09-01

    To assess the impact of obesity on carotid intima media thickness and left ventricular (LV) mass in obese adolescents. The study included 52 obese adolescents (mean age 14.16+/-2.64 years) and 52 healthy adolescents who served as a control group (mean age 12+/-2.3 years), who were attended the outpatient clinic at Suez Canal University Hospital, Ismailia, Egypt. The study population was submitted for medical history, clinical examination, laboratory investigations (fasting blood sugar and lipid profile), and echocardiographic examination of LV mass and dimensions. Assessment of carotid intima-media thickness was carried out by using carotid duplex. All children had normal LV function. Obese adolescents had a significant increase in total cholesterol, triglyceride, LDL-C, and low HDL-C compared to the control group. Also, there was a significant increase in blood pressure, carotid intima media thickness, LV mass, and LV mass index. There was a significant correlation between BMI and dyslipidemia, blood pressure, carotid intima/media thickness, LV mass, and posterior wall thickness. Carotid intima-media thickness had a significant correlation with increased LDL-C and low HDL-C, blood pressure, LV mass, and posterior wall thickness. Obesity in childhood and adolescents is associated with subclinical atherosclerosis. Although obese children had no LV dysfunction, yet there are LV structure changes.

  6. cAMP/PKA signalling reinforces the LATS–YAP pathway to fully suppress YAP in response to actin cytoskeletal changes

    Science.gov (United States)

    Kim, Minchul; Kim, Miju; Lee, Seunghee; Kuninaka, Shinji; Saya, Hideyuki; Lee, Ho; Lee, Sookyung; Lim, Dae-Sik

    2013-01-01

    Actin cytoskeletal damage induces inactivation of the oncoprotein YAP (Yes-associated protein). It is known that the serine/threonine kinase LATS (large tumour suppressor) inactivates YAP by phosphorylating its Ser127 and Ser381 residues. However, the events downstream of actin cytoskeletal changes that are involved in the regulation of the LATS–YAP pathway and the mechanism by which LATS differentially phosphorylates YAP on Ser127 and Ser381 in vivo have remained elusive. Here, we show that cyclic AMP (cAMP)-dependent protein kinase (PKA) phosphorylates LATS and thereby enhances its activity sufficiently to phosphorylate YAP on Ser381. We also found that PKA activity is involved in all contexts previously reported to trigger the LATS–YAP pathway, including actin cytoskeletal damage, G-protein-coupled receptor activation, and engagement of the Hippo pathway. Inhibition of PKA and overexpression of YAP cooperate to transform normal cells and amplify neural progenitor pools in developing chick embryos. We also implicate neurofibromin 2 as an AKAP (A-kinase-anchoring protein) scaffold protein that facilitates the function of the cAMP/PKA–LATS–YAP pathway. Our study thus incorporates PKA as novel component of the Hippo pathway. PMID:23644383

  7. Characteristic functions of scale mixtures of multivariate skew-normal distributions

    KAUST Repository

    Kim, Hyoung-Moon

    2011-08-01

    We obtain the characteristic function of scale mixtures of skew-normal distributions both in the univariate and multivariate cases. The derivation uses the simple stochastic relationship between skew-normal distributions and scale mixtures of skew-normal distributions. In particular, we describe the characteristic function of skew-normal, skew-t, and other related distributions. © 2011 Elsevier Inc.

  8. Asymptotic normality of kernel estimator of $\\psi$-regression function for functional ergodic data

    OpenAIRE

    Laksaci ALI; Benziadi Fatima; Gheriballak Abdelkader

    2016-01-01

    In this paper we consider the problem of the estimation of the $\\psi$-regression function when the covariates take values in an infinite dimensional space. Our main aim is to establish, under a stationary ergodic process assumption, the asymptotic normality of this estimate.

  9. Adaptive Linear and Normalized Combination of Radial Basis Function Networks for Function Approximation and Regression

    Directory of Open Access Journals (Sweden)

    Yunfeng Wu

    2014-01-01

    Full Text Available This paper presents a novel adaptive linear and normalized combination (ALNC method that can be used to combine the component radial basis function networks (RBFNs to implement better function approximation and regression tasks. The optimization of the fusion weights is obtained by solving a constrained quadratic programming problem. According to the instantaneous errors generated by the component RBFNs, the ALNC is able to perform the selective ensemble of multiple leaners by adaptively adjusting the fusion weights from one instance to another. The results of the experiments on eight synthetic function approximation and six benchmark regression data sets show that the ALNC method can effectively help the ensemble system achieve a higher accuracy (measured in terms of mean-squared error and the better fidelity (characterized by normalized correlation coefficient of approximation, in relation to the popular simple average, weighted average, and the Bagging methods.

  10. Normal forms for characteristic functions on n-ary relations

    NARCIS (Netherlands)

    D.J.N. van Eijck (Jan)

    2004-01-01

    textabstractFunctions of type (n) are characteristic functions on n-ary relations. Keenan established their importance for natural language semantics, by showing that natural language has many examples of irreducible type (n) functions, i.e., functions of type (n) that cannot be represented as

  11. CONSERVED ROLES FOR CYTOSKELETAL COMPONENTS IN DETERMINING LATERALITY

    Science.gov (United States)

    McDowell, Gary S.; Lemire, Joan M.; Paré, Jean-Francois; Cammarata, Garrett; Lowery, Laura Anne; Levin, Michael

    2016-01-01

    SUMMARY Consistently-biased left-right (LR) patterning is required for the proper placement of organs including the heart and viscera. The LR axis is especially fascinating as an example of multi-scale pattern formation, since here chiral events at the subcellular level are integrated and amplified into asymmetric transcriptional cascades and ultimately into the anatomical patterning of the entire body. In contrast to the other two body axes, there is considerable controversy about the earliest mechanisms of embryonic laterality. Many molecular components of asymmetry have not been widely tested among phyla with diverse bodyplans, and it is unknown whether parallel (redundant) pathways may exist that could reverse abnormal asymmetry states at specific checkpoints in development. To address conservation of the early steps of LR patterning, we used the Xenopus laevis (frog) embryo to functionally test a number of protein targets known to direct asymmetry in plants, fruit fly, and rodent. Using the same reagents that randomize asymmetry in Arabidopsis, Drosophila, and mouse embryos, we show that manipulation of the microtubule and actin cytoskeleton immediately post-fertilization, but not later, results in laterality defects in Xenopus embryos. Moreover, we observed organ-specific randomization effects and a striking dissociation of organ situs from effects on the expression of left side control genes, which parallel data from Drosophila and mouse. Remarkably, some early manipulations that disrupt laterality of transcriptional asymmetry determinants can be subsequently “rescued” by the embryo, resulting in normal organ situs. These data reveal the existence of novel corrective mechanisms, demonstrate that asymmetric expression of Nodal is not a definitive marker of laterality, and suggest the existence of amplification pathways that connect early cytoskeletal processes to control of organ situs bypassing Nodal. Counter to alternative models of symmetry breaking

  12. Characteristic functions of scale mixtures of multivariate skew-normal distributions

    KAUST Repository

    Kim, Hyoung-Moon; Genton, Marc G.

    2011-01-01

    We obtain the characteristic function of scale mixtures of skew-normal distributions both in the univariate and multivariate cases. The derivation uses the simple stochastic relationship between skew-normal distributions and scale mixtures of skew

  13. Internodal function in normal and regenerated mammalian axons

    DEFF Research Database (Denmark)

    Moldovan, M; Krarup, C

    2007-01-01

    AIM: Following Wallerian degeneration, peripheral myelinated axons have the ability to regenerate and, given a proper pathway, establish functional connections with targets. In spite of this capacity, the clinical outcome of nerve regeneration remains unsatisfactory. Early studies have found...... that regenerated internodes remain persistently short though this abnormality did not seem to influence recovery in conduction. It remains unclear to which extent abnormalities in axonal function itself may contribute to the poor outcome of nerve regeneration. METHODS: We review experimental evidence indicating...... that internodes play an active role in axonal function. RESULTS: By investigating internodal contribution to axonal excitability we have found evidence that axonal function may be permanently compromised in regenerated nerves. Furthermore, we illustrate that internodal function is also abnormal in regenerated...

  14. Nonischemic changes in right ventricular function on exercise. Do normal volunteers differ from patients with normal coronary arteries

    International Nuclear Information System (INIS)

    Caplin, J.L.; Maltz, M.B.; Flatman, W.D.; Dymond, D.S.

    1988-01-01

    Factors other than ischemia may alter right ventricular function both at rest and on exercise. Normal volunteers differ from cardiac patients with normal coronary arteries with regard to their left ventricular response to exercise. This study examined changes in right ventricular function on exercise in 21 normal volunteers and 13 patients with normal coronary arteries, using first-pass radionuclide angiography. There were large ranges of right ventricular ejection fraction in the two groups, both at rest and on exercise. Resting right ventricular ejection fraction was 40.2 +/- 10.6% (mean +/- SD) in the volunteers and 38.6 +/- 9.7% in the patients, p = not significant, and on exercise rose significantly in both groups to 46.1 +/- 9.9% and 45.8 +/- 9.7%, respectively. The difference between the groups was not significant. In both groups some subjects with high resting values showed large decreases in ejection fraction on exercise, and there were significant negative correlations between resting ejection fraction and the change on exercise, r = -0.59 (p less than 0.01) in volunteers, and r = -0.66 (p less than 0.05) in patients. Older volunteers tended to have lower rest and exercise ejection fractions, but there was no difference between normotensive and hypertensive patients in their rest or exercise values. In conclusion, changes in right ventricular function on exercise are similar in normal volunteers and in patients with normal coronary arteries. Some subjects show decreases in right ventricular ejection fraction on exercise which do not appear to be related to ischemia

  15. Redox biology in normal cells and cancer: restoring function of the redox/Fyn/c-Cbl pathway in cancer cells offers new approaches to cancer treatment.

    Science.gov (United States)

    Noble, Mark; Mayer-Pröschel, Margot; Li, Zaibo; Dong, Tiefei; Cui, Wanchang; Pröschel, Christoph; Ambeskovic, Ibro; Dietrich, Joerg; Han, Ruolan; Yang, Yin Miranda; Folts, Christopher; Stripay, Jennifer; Chen, Hsing-Yu; Stevens, Brett M

    2015-02-01

    This review discusses a unique discovery path starting with novel findings on redox regulation of precursor cell and signaling pathway function and identification of a new mechanism by which relatively small changes in redox status can control entire signaling networks that regulate self-renewal, differentiation, and survival. The pathway central to this work, the redox/Fyn/c-Cbl (RFC) pathway, converts small increases in oxidative status to pan-activation of the c-Cbl ubiquitin ligase, which controls multiple receptors and other proteins of central importance in precursor cell and cancer cell function. Integration of work on the RFC pathway with attempts to understand how treatment with systemic chemotherapy causes neurological problems led to the discovery that glioblastomas (GBMs) and basal-like breast cancers (BLBCs) inhibit c-Cbl function through altered utilization of the cytoskeletal regulators Cool-1/βpix and Cdc42, respectively. Inhibition of these proteins to restore normal c-Cbl function suppresses cancer cell division, increases sensitivity to chemotherapy, disrupts tumor-initiating cell (TIC) activity in GBMs and BLBCs, controls multiple critical TIC regulators, and also allows targeting of non-TICs. Moreover, these manipulations do not increase chemosensitivity or suppress division of nontransformed cells. Restoration of normal c-Cbl function also allows more effective harnessing of estrogen receptor-α (ERα)-independent activities of tamoxifen to activate the RFC pathway and target ERα-negative cancer cells. Our work thus provides a discovery strategy that reveals mechanisms and therapeutic targets that cannot be deduced by standard genetics analyses, which fail to reveal the metabolic information, isoform shifts, protein activation, protein complexes, and protein degradation critical to our discoveries. Copyright © 2015. Published by Elsevier Inc.

  16. An Introduction to Normalization and Calibration Methods in Functional MRI

    Science.gov (United States)

    Liu, Thomas T.; Glover, Gary H.; Mueller, Bryon A.; Greve, Douglas N.; Brown, Gregory G.

    2013-01-01

    In functional magnetic resonance imaging (fMRI), the blood oxygenation level dependent (BOLD) signal is often interpreted as a measure of neural activity. However, because the BOLD signal reflects the complex interplay of neural, vascular, and metabolic processes, such an interpretation is not always valid. There is growing evidence that changes…

  17. Overexpression of neurofilament H disrupts normal cell structure and function

    Science.gov (United States)

    Szebenyi, Gyorgyi; Smith, George M.; Li, Ping; Brady, Scott T.

    2002-01-01

    Studying exogenously expressed tagged proteins in live cells has become a standard technique for evaluating protein distribution and function. Typically, expression levels of experimentally introduced proteins are not regulated, and high levels are often preferred to facilitate detection. However, overexpression of many proteins leads to mislocalization and pathologies. Therefore, for normative studies, moderate levels of expression may be more suitable. To understand better the dynamics of intermediate filament formation, transport, and stability in a healthy, living cell, we inserted neurofilament heavy chain (NFH)-green fluorescent protein (GFP) fusion constructs in adenoviral vectors with tetracycline (tet)-regulated promoters. This system allows for turning on or off the synthesis of NFH-GFP at a selected time, for a defined period, in a dose-dependent manner. We used this inducible system for live cell imaging of changes in filament structure and cell shape, motility, and transport associated with increasing NFH-GFP expression. Cells with low to intermediate levels of NFH-GFP were structurally and functionally similar to neighboring, nonexpressing cells. In contrast, overexpression led to pathological alterations in both filament organization and cell function. Copyright 2002 Wiley-Liss, Inc.

  18. Normal function of immunologic stem cells from aged mice

    International Nuclear Information System (INIS)

    Harrison, D.E.; Doubleday, J.W.

    1975-01-01

    Marrow or spleen grafts from aged donor mice produced antibody-forming cells as effectively as did grafts from younger controls in recipients tested 3 to 10 months after the transplantation. All recipients were lethally irradiated, and the T6 chromosome marker was used to demonstrate that they were populated by donor cell lines. Recipients of aged or younger control grafts gave similar responses when stimulated with varying doses of antigen and when tested at different times after the transplantation except in two cases. Recipients of aged spleen grafts gave significantly lower responses than younger controls for the first few weeks after the transplantation. If recipients had been thymectomized before lethal irradiation, aged cell lines (pooled marrow and spleen cells) gave only 37 percent of the responses of younger controls. Given sufficient time and intact young recipients, immunologic stem cell lines from old donors populated recipients with cells having normal immune responses. These results suggest that age-related immunologic defects are not intrinsically timed in the precursor cell lines that populate the immune system. (U.S.)

  19. Evaluation of the neuronal apoptotic pathways involved in cytoskeletal disruption-induced apoptosis.

    Science.gov (United States)

    Jordà, Elvira G; Verdaguer, Ester; Jimenez, Andrés; Arriba, S Garcia de; Allgaier, Clemens; Pallàs, Mercè; Camins, Antoni

    2005-08-01

    The cytoskeleton is critical to neuronal functioning and survival. Cytoskeletal alterations are involved in several neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. We studied the possible pathways involved in colchicine-induced apoptosis in cerebellar granule neurons (CGNs). Although colchicine evoked an increase in caspase-3, caspase-6 and caspase-9 activation, selective caspase inhibitors did not attenuate apoptosis. Inhibitors of other cysteine proteases such as PD150606 (a calpain-specific inhibitor), Z-Phe-Ala fluoromethyl ketone (a cathepsins-inhibitors) and N(alpha)-p-tosyl-l-lysine chloromethyl ketone (serine-proteases inhibitor) also had no effect on cell death/apoptosis induced by colchicine. However, BAPTA-AM 10 microM (intracellular calcium chelator) prevented apoptosis mediated by cytoskeletal alteration. These data indicate that calcium modulates colchicine-induced apoptosis in CGNs. PARP-1 inhibitors did not prevent apoptosis mediated by colchicine. Finally, colchicine-induced apoptosis in CGNs was attenuated by kenpaullone, a cdk5 inhibitor. Kenpaullone and indirubin also prevented cdk5/p25 activation mediated by colchicine. These findings indicate that cytoskeletal alteration can compromise cdk5 activation, regulating p25 formation and suggest that cdk5 inhibitors attenuate apoptosis mediated by cytoskeletal alteration. The present data indicate the potential therapeutic value of drugs that prevent the formation of p25 for the treatment of neurodegenerative disorders.

  20. Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder.

    Science.gov (United States)

    Koch, Saskia B J; van Zuiden, Mirjam; Nawijn, Laura; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

    2016-07-01

    The neuropeptide oxytocin (OT) has been suggested as a promising pharmacological agent for medication-enhanced psychotherapy in posttraumatic stress disorder (PTSD) because of its anxiolytic and prosocial properties. We therefore investigated the behavioral and neurobiological effects of a single intranasal OT administration (40 IU) in PTSD patients. We conducted a randomized, placebo-controlled, cross-over resting-state fMRI study in male and female police officers with (n=37, 21 males) and without PTSD (n=40, 20 males). We investigated OT administration effects on subjective anxiety and functional connectivity of basolateral (BLA) and centromedial (CeM) amygdala subregions with prefrontal and salience processing areas. In PTSD patients, OT administration resulted in decreased subjective anxiety and nervousness. Under placebo, male PTSD patients showed diminished right CeM to left ventromedial prefrontal cortex (vmPFC) connectivity compared with male trauma-exposed controls, which was reinstated after OT administration. Additionally, female PTSD patients showed enhanced right BLA to bilateral dorsal anterior cingulate cortex (dACC) connectivity compared with female trauma-exposed controls, which was dampened after OT administration. Although caution is warranted, our findings tentatively suggest that OT has the potential to diminish anxiety and fear expression of the amygdala in PTSD, either via increased control of the vmPFC over the CeM (males) or via decreased salience processing of the dACC and BLA (females). Our findings add to accumulating evidence that OT administration could potentially enhance treatment response in PTSD.

  1. Normal values for inspiratory muscle function in children

    International Nuclear Information System (INIS)

    Mellies, Uwe; Stehling, Florian; Dohna-Schwake, Christian

    2014-01-01

    Assessment of inspiratory muscle function (IMF) is limited in children with neuromuscular disorders, because respiratory muscle tests are poorly standardized and valid normative data are unavailable. We investigated maximum inspiratory pressure after exhalation to residual volume (MIP), mouth occlusion pressure (P0.1) and time of inspiration during quiet breathing and derived inspiratory muscle load (P0.1/MIP), and tension time index (TTI) in 301 healthy schoolchildren 6–16 years old. Gender-specific and age-dependent percentile curves for MIP were drawn with the median, 5%, 10%, 25%, 75% and 95% percentile. P0.1 was equal in boys and girls (0.23  ±  0.11 kPa), while MIP was significantly higher in boys (6.8  ±  2.2 versus 5.8  ±  2.4 kPa). Consequently, P0.1/MIP (4.8% ± 3.2% versus 4.0% ± 3.1%) and TTI (0.2  ±  0.14 versus 0.16  ±  0.14) were significantly higher in girls. MIP was 2.90 + 0.36 × age (kPa) and 3.19 + 0.24 × age (kPa) in boys and girls, respectively. The 95% confidence intervals for boys and girls, respectively, were MIP, 6.3–7.3 kPA and 5.4–6.2 kPa; P0.1/MIP, 3.5%–4.5% and 4.3%–5.3%; TTI, 0.14–0.18 and 0.18–0.22; and P0.1, 0.20–0.24 kPa for both. IMF in children has a wide interindividual variability; however percentile curves facilitate a longitudinal assessment of individual patients. Furthermore, narrow confidence intervals allow for comparisons of study populations, making IMF an appropriate endpoint for clinical trials. (paper)

  2. ACL-RSI and KOOS Measures Predict Normal Knee Function after ACL-SPORTS Training

    OpenAIRE

    White, Kathleen; Zeni, Joseph; Snyder-Mackler, Lynn

    2014-01-01

    Objectives: After anterior cruciate ligament reconstruction (ACLR) athletes commonly report increased fear of re-injury and below normal knee function. Implementing a post-operative training protocol (ACL-SPORTS Training) to improve patient perceived knee function, may improve short term outcomes after surgery. Identifying pre-training measures that predict normal knee function after training may allow us to determine who may respond to the treatment intervention. The purpose of this study wa...

  3. Age-related normal structural and functional ventricular values in cardiac function assessed by magnetic resonance

    International Nuclear Information System (INIS)

    Fiechter, Michael; Gaemperli, Oliver; Kaufmann, Philipp A; Fuchs, Tobias A; Gebhard, Catherine; Stehli, Julia; Klaeser, Bernd; Stähli, Barbara E; Manka, Robert; Manes, Costantina; Tanner, Felix C

    2013-01-01

    The heart is subject to structural and functional changes with advancing age. However, the magnitude of cardiac age-dependent transformation has not been conclusively elucidated. This retrospective cardiac magnetic resonance (CMR) study included 183 subjects with normal structural and functional ventricular values. End systolic volume (ESV), end diastolic volume (EDV), and ejection fraction (EF) were obtained from the left and the right ventricle in breath-hold cine CMR. Patients were classified into four age groups (20–29, 30–49, 50–69, and ≥70 years) and cardiac measurements were compared using Pearson’s rank correlation over the four different groups. With advanced age a slight but significant decrease in ESV (r=−0.41 for both ventricles, P<0.001) and EDV (r=−0.39 for left ventricle, r=−0.35 for right ventricle, P<0.001) were observed associated with a significant increase in left (r=0.28, P<0.001) and right (r=0.27, P<0.01) ventricular EF reaching a maximal increase in EF of +8.4% (P<0.001) for the left and +6.1% (P<0.01) for the right ventricle in the oldest compared to the youngest patient group. Left ventricular myocardial mass significantly decreased over the four different age groups (P<0.05). The aging process is associated with significant changes in left and right ventricular EF, ESV and EDV in subjects with no cardiac functional and structural abnormalities. These findings underline the importance of using age adapted values as standard of reference when evaluating CMR studies

  4. Neutron importance and the generalized Green function for the conventionally critical reactor with normalized neutron distribution

    International Nuclear Information System (INIS)

    Khromov, V.V.

    1978-01-01

    The notion of neutron importance when applied to nuclear reactor statics problems described by time-independent homogeneous equations of neutron transport with provision for normalization of neutron distribution is considered. An equation has been obtained for the function of neutron importance in a conditionally critical reactor with respect to an arbitrary nons linear functional determined for the normalized neutron distribution. Relation between this function and the generalized Green function of the selfconjugated operator of the reactor equation is determined and the formula of small perturbations for the functionals of a conditionally critical reactor is deduced

  5. Reinforcement versus fluidization in cytoskeletal mechanoresponsiveness.

    Directory of Open Access Journals (Sweden)

    Ramaswamy Krishnan

    Full Text Available Every adherent eukaryotic cell exerts appreciable traction forces upon its substrate. Moreover, every resident cell within the heart, great vessels, bladder, gut or lung routinely experiences large periodic stretches. As an acute response to such stretches the cytoskeleton can stiffen, increase traction forces and reinforce, as reported by some, or can soften and fluidize, as reported more recently by our laboratory, but in any given circumstance it remains unknown which response might prevail or why. Using a novel nanotechnology, we show here that in loading conditions expected in most physiological circumstances the localized reinforcement response fails to scale up to the level of homogeneous cell stretch; fluidization trumps reinforcement. Whereas the reinforcement response is known to be mediated by upstream mechanosensing and downstream signaling, results presented here show the fluidization response to be altogether novel: it is a direct physical effect of mechanical force acting upon a structural lattice that is soft and fragile. Cytoskeletal softness and fragility, we argue, is consistent with early evolutionary adaptations of the eukaryotic cell to material properties of a soft inert microenvironment.

  6. Role of endothelial function in coronary slow-flow phenomenon with angiographically normal coronaries

    Directory of Open Access Journals (Sweden)

    Srikanth Nathani

    2016-01-01

    Conclusion: Coronary slow flow phenomenon is a marker of atherosclerosis (as documented by carotid intima media thickness and our study has also shown that endothelial function is significantly impaired in patients with coronary slow flow (as documented by impaired endothelial dependent vasodilatation than that of patients with normal epicardial coronaries with normal flow.

  7. Mycoplasma pneumoniae Cytoskeletal Protein HMW2 and the Architecture of the Terminal Organelle▿

    OpenAIRE

    Bose, Stephanie R.; Balish, Mitchell F.; Krause, Duncan C.

    2009-01-01

    The terminal organelle of Mycoplasma pneumoniae mediates cytadherence and gliding motility and functions in cell division. The defining feature of this complex membrane-bound cell extension is an electron-dense core of two segmented rods oriented longitudinally and enlarging to form a bulb at the distal end. While the components of the core have not been comprehensively identified, previous evidence suggested that the cytoskeletal protein HMW2 forms parallel bundles oriented lengthwise to yie...

  8. SYNTHESIS METHODS OF ALGEBRAIC NORMAL FORM OF MANY-VALUED LOGIC FUNCTIONS

    Directory of Open Access Journals (Sweden)

    A. V. Sokolov

    2016-01-01

    Full Text Available The rapid development of methods of error-correcting coding, cryptography, and signal synthesis theory based on the principles of many-valued logic determines the need for a more detailed study of the forms of representation of functions of many-valued logic. In particular the algebraic normal form of Boolean functions, also known as Zhegalkin polynomial, that well describe many of the cryptographic properties of Boolean functions is widely used. In this article, we formalized the notion of algebraic normal form for many-valued logic functions. We developed a fast method of synthesis of algebraic normal form of 3-functions and 5-functions that work similarly to the Reed-Muller transform for Boolean functions: on the basis of recurrently synthesized transform matrices. We propose the hypothesis, which determines the rules of the synthesis of these matrices for the transformation from the truth table to the coefficients of the algebraic normal form and the inverse transform for any given number of variables of 3-functions or 5-functions. The article also introduces the definition of algebraic degree of nonlinearity of the functions of many-valued logic and the S-box, based on the principles of many-valued logic. Thus, the methods of synthesis of algebraic normal form of 3-functions applied to the known construction of recurrent synthesis of S-boxes of length N = 3k, whereby their algebraic degrees of nonlinearity are computed. The results could be the basis for further theoretical research and practical applications such as: the development of new cryptographic primitives, error-correcting codes, algorithms of data compression, signal structures, and algorithms of block and stream encryption, all based on the perspective principles of many-valued logic. In addition, the fast method of synthesis of algebraic normal form of many-valued logic functions is the basis for their software and hardware implementation.

  9. Impact of age and sex on normal left heart structure and function.

    Science.gov (United States)

    Hagström, Linn; Henein, Michael Y; Karp, Kjell; Waldenström, Anders; Lindqvist, Per

    2017-11-01

    Accurate age- and sex-related normal reference values of ventricular structure and function are important to determine the level of dysfunction in patients. The aim of this study therefore was to document normal age range sex-related measurements of LV structural and functional measurements to serve such purpose. We evaluated left ventricular structure and function in 293 healthy subjects between 20 and 90 years with equally distributed gender. Doppler echocardiography was used including measure of both systolic and diastolic functions. Due to systolic LV function, only long axis function correlated with age (r = 0·55, P<0·01) and the correlation was stronger in females. Concerning diastolic function, there was a strong age correlation in all parameters used (r = 0·40-0·74, P<0·001). Due to LV structural changes over age, females showed a larger reduction in end-diastolic volumes, but no or trivial difference in wall thickness after the age of 60 years. Age is associated with significant normal changes in left ventricular structure and function, which should be considered when deciding on normality. These changes are related to systemic arterial changes as well as body stature, thus reflecting overall body ageing process. Furthermore, normal cardiac ageing in females might partly explain the higher prevalence of heart failure with preserved ejection in females. © 2016 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  10. Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

    Science.gov (United States)

    Appert-Rolland, C.; Ebbinghaus, M.; Santen, L.

    2015-09-01

    Cells are the elementary units of living organisms, which are able to carry out many vital functions. These functions rely on active processes on a microscopic scale. Therefore, they are strongly out-of-equilibrium systems, which are driven by continuous energy supply. The tasks that have to be performed in order to maintain the cell alive require transportation of various ingredients, some being small, others being large. Intracellular transport processes are able to induce concentration gradients and to carry objects to specific targets. These processes cannot be carried out only by diffusion, as cells may be crowded, and quite elongated on molecular scales. Therefore active transport has to be organized. The cytoskeleton, which is composed of three types of filaments (microtubules, actin and intermediate filaments), determines the shape of the cell, and plays a role in cell motion. It also serves as a road network for a special kind of vehicles, namely the cytoskeletal motors. These molecules can attach to a cytoskeletal filament, perform directed motion, possibly carrying along some cargo, and then detach. It is a central issue to understand how intracellular transport driven by molecular motors is regulated. The interest for this type of question was enhanced when it was discovered that intracellular transport breakdown is one of the signatures of some neuronal diseases like the Alzheimer. We give a survey of the current knowledge on microtubule based intracellular transport. Our review includes on the one hand an overview of biological facts, obtained from experiments, and on the other hand a presentation of some modeling attempts based on cellular automata. We present some background knowledge on the original and variants of the TASEP (Totally Asymmetric Simple Exclusion Process), before turning to more application oriented models. After addressing microtubule based transport in general, with a focus on in vitro experiments, and on cooperative effects in the

  11. Fragility of foot process morphology in kidney podocytes arises from chaotic spatial propagation of cytoskeletal instability.

    Directory of Open Access Journals (Sweden)

    Cibele V Falkenberg

    2017-03-01

    Full Text Available Kidney podocytes' function depends on fingerlike projections (foot processes that interdigitate with those from neighboring cells to form the glomerular filtration barrier. The integrity of the barrier depends on spatial control of dynamics of actin cytoskeleton in the foot processes. We determined how imbalances in regulation of actin cytoskeletal dynamics could result in pathological morphology. We obtained 3-D electron microscopy images of podocytes and used quantitative features to build dynamical models to investigate how regulation of actin dynamics within foot processes controls local morphology. We find that imbalances in regulation of actin bundling lead to chaotic spatial patterns that could impair the foot process morphology. Simulation results are consistent with experimental observations for cytoskeletal reconfiguration through dysregulated RhoA or Rac1, and they predict compensatory mechanisms for biochemical stability. We conclude that podocyte morphology, optimized for filtration, is intrinsically fragile, whereby local transient biochemical imbalances may lead to permanent morphological changes associated with pathophysiology.

  12. Chronic Lymphocytic Leukemia B-Cell Normal Cellular Counterpart: Clues From a Functional Perspective.

    Science.gov (United States)

    Darwiche, Walaa; Gubler, Brigitte; Marolleau, Jean-Pierre; Ghamlouch, Hussein

    2018-01-01

    Chronic lymphocytic leukemia (CLL) is characterized by the clonal expansion of small mature-looking CD19+ CD23+ CD5+ B-cells that accumulate in the blood, bone marrow, and lymphoid organs. To date, no consensus has been reached concerning the normal cellular counterpart of CLL B-cells and several B-cell types have been proposed. CLL B-cells have remarkable phenotypic and gene expression profile homogeneity. In recent years, the molecular and cellular biology of CLL has been enriched by seminal insights that are leading to a better understanding of the natural history of the disease. Immunophenotypic and molecular approaches (including immunoglobulin heavy-chain variable gene mutational status, transcriptional and epigenetic profiling) comparing the normal B-cell subset and CLL B-cells provide some new insights into the normal cellular counterpart. Functional characteristics (including activation requirements and propensity for plasma cell differentiation) of CLL B-cells have now been investigated for 50 years. B-cell subsets differ substantially in terms of their functional features. Analysis of shared functional characteristics may reveal similarities between normal B-cell subsets and CLL B-cells, allowing speculative assignment of a normal cellular counterpart for CLL B-cells. In this review, we summarize current data regarding peripheral B-cell differentiation and human B-cell subsets and suggest possibilities for a normal cellular counterpart based on the functional characteristics of CLL B-cells. However, a definitive normal cellular counterpart cannot be attributed on the basis of the available data. We discuss the functional characteristics required for a cell to be logically considered to be the normal counterpart of CLL B-cells.

  13. Enhanced disease characterization through multi network functional normalization in fMRI.

    Science.gov (United States)

    Çetin, Mustafa S; Khullar, Siddharth; Damaraju, Eswar; Michael, Andrew M; Baum, Stefi A; Calhoun, Vince D

    2015-01-01

    Conventionally, structural topology is used for spatial normalization during the pre-processing of fMRI. The co-existence of multiple intrinsic networks which can be detected in the resting brain are well-studied. Also, these networks exhibit temporal and spatial modulation during cognitive task vs. rest which shows the existence of common spatial excitation patterns between these identified networks. Previous work (Khullar et al., 2011) has shown that structural and functional data may not have direct one-to-one correspondence and functional activation patterns in a well-defined structural region can vary across subjects even for a well-defined functional task. The results of this study and the existence of the neural activity patterns in multiple networks motivates us to investigate multiple resting-state networks as a single fusion template for functional normalization for multi groups of subjects. We extend the previous approach (Khullar et al., 2011) by co-registering multi group of subjects (healthy control and schizophrenia patients) and by utilizing multiple resting-state networks (instead of just one) as a single fusion template for functional normalization. In this paper we describe the initial steps toward using multiple resting-state networks as a single fusion template for functional normalization. A simple wavelet-based image fusion approach is presented in order to evaluate the feasibility of combining multiple functional networks. Our results showed improvements in both the significance of group statistics (healthy control and schizophrenia patients) and the spatial extent of activation when a multiple resting-state network applied as a single fusion template for functional normalization after the conventional structural normalization. Also, our results provided evidence that the improvement in significance of group statistics lead to better accuracy results for classification of healthy controls and schizophrenia patients.

  14. The normal function of a speciation gene, Odysseus, and its hybrid sterility effect.

    Science.gov (United States)

    Sun, Sha; Ting, Chau-Ti; Wu, Chung-I

    2004-07-02

    To understand how postmating isolation is connected to the normal process of species divergence and why hybrid male sterility is often the first sign of speciation, we analyzed the Odysseus (OdsH) gene of hybrid male sterility in Drosophila. We carried out expression analysis, transgenic study, and gene knockout. The combined evidence suggests that the sterility phenotype represents a novel manifestation of the gene function rather than the reduction or loss of the normal one. The gene knockout experiment identified the normal function of OdsH as a modest enhancement of sperm production in young males. The implication of a weak effect of OdsH on the normal phenotype but a strong influence on hybrid male sterility is discussed in light of Haldane's rule of postmating isolation.

  15. Validation of MCDS by comparison of predicted with experimental velocity distribution functions in rarefied normal shocks

    Science.gov (United States)

    Pham-Van-diep, Gerald C.; Erwin, Daniel A.

    1989-01-01

    Velocity distribution functions in normal shock waves in argon and helium are calculated using Monte Carlo direct simulation. These are compared with experimental results for argon at M = 7.18 and for helium at M = 1.59 and 20. For both argon and helium, the variable-hard-sphere (VHS) model is used for the elastic scattering cross section, with the velocity dependence derived from a viscosity-temperature power-law relationship in the way normally used by Bird (1976).

  16. Renal function maturation in children: is normalization to surface area valid?

    International Nuclear Information System (INIS)

    Rutland, M.D.; Hassan, I.M.; Que, L.

    1999-01-01

    Full text: Gamma camera DTPA renograms were analysed to measure renal function by the rate at which the kidneys took up tracer from the blood. This was expressed either directly as the fractional uptake rate (FUR), which is not related to body size, or it was converted to a camera-based GFR by the formula GFR blood volume x FUR, and this GFR was normalized to a body surface area of 1.73 m2. Most of the patients studied had one completely normal kidney, and one kidney with reflux but normal function and no large scars. The completely normal kidneys contributed, on average, 50% of the total renal function. The results were considered in age bands, to display the effect of age on renal function. The camera-GFR measurements showed the conventional results of poor renal function in early childhood, with a slow rise to near-adult values by the age of 2 years, and somewhat low values throughout childhood. The uptake values showed a different pattern, with renal function rising to adult equivalent values by the age of 4 months, and with children having better renal function than adults throughout most of their childhood. The standard deviations expressed as coefficients of variation (CV) were smaller for the FUR technique than the GFR (Wilcoxon rank test, P < 0.01). These results resemble recent published measurements of absolute DMSA uptake, which are also unrelated to body size and show early renal maturation. The results also suggest that the reason children have lower serum creatinine levels than adults is that they have better renal function. If this were confirmed, it would raise doubts about the usefulness of normalizing renal function to body surface area in children

  17. The Application of Normal Stress Reduction Function in Tilt Tests for Different Block Shapes

    Science.gov (United States)

    Kim, Dong Hyun; Gratchev, Ivan; Hein, Maw; Balasubramaniam, Arumugam

    2016-08-01

    This paper focuses on the influence of the shapes of rock cores, which control the sliding or toppling behaviours in tilt tests for the estimation of rock joint roughness coefficients (JRC). When the JRC values are estimated by performing tilt tests, the values are directly proportional to the basic friction of the rock material and the applied normal stress on the sliding planes. Normal stress obviously varies with the shape of the sliding block, and the basic friction angle is also affected by the sample shapes in tilt tests. In this study, the shapes of core blocks are classified into three representative shapes and those are created using plaster. Using the various shaped artificial cores, a set of tilt tests is carried out to identify the shape influences on the normal stress and the basic friction angle in tilt tests. The test results propose a normal stress reduction function to estimate the normal stress for tilt tests according to the sample shapes based on Barton's empirical equation. The proposed normal stress reduction functions are verified by tilt tests using artificial plaster joints and real rock joint sets. The plaster joint sets are well matched and cast in detailed printed moulds using a 3D printing technique. With the application of the functions, the obtained JRC values from the tilt tests using the plaster samples and the natural rock samples are distributed within a reasonable JRC range when compared with the measured values.

  18. Coronary flow reserve/diastolic function relationship in angina-suffering patients with normal coronary angiography.

    Science.gov (United States)

    Anchisi, Chiara; Marti, Giuliano; Bellacosa, Ilaria; Mary, David; Vacca, Giovanni; Marino, Paolo; Grossini, Elena

    2017-05-01

    Coronary blood flow and diastolic function are well known to interfere with each other through mechanical and metabolic mechanisms. We aimed to assess the relationship between coronary flow reserve (CFR) and diastolic dysfunction in patients suffering from angina but with normal coronary angiography. In 16 patients with chest pain and angiographically normal coronary arteries, CFR was measured using transthoracic echo-Doppler by inducing hyperemia through dipyridamole infusion. Diastolic function (E/A, deceleration time, isovolumetric relaxation time [IVRT], propagation velocity [Vp]) and left ventricular mass were evaluated by means of two-dimensional transthoracic echocardiography. The patients were initially divided into two groups on the grounds of CFR only (ACFR: altered CFR, n = 9; NACFR: unaltered CFR, n = 7). Thereafter they were divided into four groups on the grounds of CFR and diastolic function (NN: normal; AA: altered CFR/diastole; AN: altered CFR/normal diastole; NA: normal CFR/altered diastole). Most of the subjects were scheduled in AA (n = 8) or NA (n = 5) groups, which were taken into consideration for further analysis. Patients were not different regarding various risk factors. ACFR and AA patients were older with normal body weight in comparison with NACFR and NA patients (P relationship between altered CFR and diastole.

  19. Ultrafine particles cause cytoskeletal dysfunctions in macrophages: role of intracellular calcium

    Directory of Open Access Journals (Sweden)

    Brown David M

    2005-10-01

    Full Text Available Abstract Background Particulate air pollution is reported to cause adverse health effects in susceptible individuals. Since most of these particles are derived form combustion processes, the primary composition product is carbon with a very small diameter (ultrafine, less than 100 nm in diameter. Besides the induction of reactive oxygen species and inflammation, ultrafine particles (UFP can cause intracellular calcium transients and suppression of defense mechanisms of alveolar macrophages, such as impaired migration or phagocytosis. Methods In this study the role of intracellular calcium transients caused by UFP was studied on cytoskeleton related functions in J774A.1 macrophages. Different types of fine and ultrafine carbon black particles (CB and ufCB, respectively, such as elemental carbon (EC90, commercial carbon (Printex 90, diesel particulate matter (DEP and urban dust (UD, were investigated. Phagosome transport mechanisms and mechanical cytoskeletal integrity were studied by cytomagnetometry and cell viability was studied by fluorescence microscopy. Macrophages were exposed in vitro with 100 and 320 μg UFP/ml/million cells for 4 hours in serum free medium. Calcium antagonists Verapamil, BAPTA-AM and W-7 were used to block calcium channels in the membrane, to chelate intracellular calcium or to inhibit the calmodulin signaling pathways, respectively. Results Impaired phagosome transport and increased cytoskeletal stiffness occurred at EC90 and P90 concentrations of 100 μg/ml/million cells and above, but not with DEP or UD. Verapamil and W-7, but not BAPTA-AM inhibited the cytoskeletal dysfunctions caused by EC90 or P90. Additionally the presence of 5% serum or 1% bovine serum albumin (BSA suppressed the cytoskeletal dysfunctions. Cell viability showed similar results, where co-culture of ufCB together with Verapamil, W-7, FCS or BSA produced less cell dead compared to the particles only.

  20. Cytoskeletal-assisted dynamics of the mitochondrial reticulum in living cells.

    Science.gov (United States)

    Knowles, Michelle K; Guenza, Marina G; Capaldi, Roderick A; Marcus, Andrew H

    2002-11-12

    Subcellular organelle dynamics are strongly influenced by interactions with cytoskeletal filaments and their associated motor proteins, and lead to complex multiexponential relaxations that occur over a wide range of spatial and temporal scales. Here we report spatio-temporal measurements of the fluctuations of the mitochondrial reticulum in osteosarcoma cells by using Fourier imaging correlation spectroscopy, over time and distance scales of 10(-2) to 10(3) s and 0.5-2.5 microm. We show that the method allows a more complete description of mitochondrial dynamics, through the time- and length-scale-dependent collective diffusion coefficient D(k,tau), than available by other means. Addition of either nocodazole to disrupt microtubules or cytochalasin D to disassemble microfilaments simplifies the intermediate scattering function. When both drugs are used, the reticulum morphology of mitochondria is retained even though the cytoskeletal elements have been de-polymerized. The dynamics of the organelle are then primarily diffusive and can be modeled as a collection of friction points interconnected by elastic springs. This study quantitatively characterizes organelle dynamics in terms of collective cytoskeletal interactions in living cells.

  1. p21-Activated kinase (PAK regulates cytoskeletal reorganization and directional migration in human neutrophils.

    Directory of Open Access Journals (Sweden)

    Asako Itakura

    Full Text Available Neutrophils serve as a first line of defense in innate immunity owing in part to their ability to rapidly migrate towards chemotactic factors derived from invading pathogens. As a migratory function, neutrophil chemotaxis is regulated by the Rho family of small GTPases. However, the mechanisms by which Rho GTPases orchestrate cytoskeletal dynamics in migrating neutrophils remain ill-defined. In this study, we characterized the role of p21-activated kinase (PAK downstream of Rho GTPases in cytoskeletal remodeling and chemotactic processes of human neutrophils. We found that PAK activation occurred upon stimulation of neutrophils with f-Met-Leu-Phe (fMLP, and PAK accumulated at the actin-rich leading edge of stimulated neutrophils, suggesting a role for PAK in Rac-dependent actin remodeling. Treatment with the pharmacological PAK inhibitor, PF3758309, abrogated the integrity of RhoA-mediated actomyosin contractility and surface adhesion. Moreover, inhibition of PAK activity impaired neutrophil morphological polarization and directional migration under a gradient of fMLP, and was associated with dysregulated Ca(2+ signaling. These results suggest that PAK serves as an important effector of Rho-family GTPases in neutrophil cytoskeletal reorganization, and plays a key role in driving efficient directional migration of human neutrophils.

  2. Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging.

    Science.gov (United States)

    Vlassara, Helen; Torreggiani, Massimo; Post, James B; Zheng, Feng; Uribarri, Jaime; Striker, Gary E

    2009-12-01

    Oxidant stress (OS) and inflammation increase in normal aging and in chronic kidney disease (CKD), as observed in human and animal studies. In cross-sectional studies of the US population, these changes are associated with a decrease in renal function, which is exhibited by a significant proportion of the population. However, since many normal adults have intact renal function, and longitudinal studies show that some persons maintain normal renal function with age, the link between OS, inflammation, and renal decline is not clear. In aging mice, greater oxidant intake is associated with increased age-related CKD and mortality, which suggests that interventions that reduce OS and inflammation may be beneficial for older individuals. Both OS and inflammation can be readily lowered in normal subjects and patients with CKD stage 3-4 by a simple dietary modification that lowers intake and results in reduced serum and tissue levels of advanced glycation end products. Diabetic patients, including those with microalbuminuria, have a decreased ability to metabolize and excrete oxidants prior to observable changes in serum creatinine. Thus, OS and inflammation may occur in the diabetic kidney at an early time. We review the evidence that oxidants in the diet directly lead to increased serum levels of OS and inflammatory mediators in normal aging and in CKD. We also discuss a simple dietary intervention that helps reduce OS and inflammation, an important and achievable therapeutic goal for patients with CKD and aging individuals with reduced renal function.

  3. Normal pancreatic exocrine function does not exclude MRI/MRCP chronic pancreatitis findings.

    Science.gov (United States)

    Alkaade, Samer; Cem Balci, Numan; Momtahen, Amir Javad; Burton, Frank

    2008-09-01

    Abnormal pancreatic function tests have been reported to precede the imaging findings of chronic pancreatitis. Magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) is increasingly accepted as the primary imaging modality for the detection of structural changes of early mild chronic pancreatitis. The aim of this study was to evaluate MRI/MRCP findings in patients with symptoms consistent with chronic pancreatitis who have normal Secretin Endoscopic Pancreatic Function test. A retrospective study of 32 patients referred for evaluation of chronic abdominal pain consistent with chronic pancreatitis and reported normal standard abdominal imaging (ultrasound, computed tomography, or MRI). All patients underwent Secretin Endoscopic Pancreatic Function testing and pancreatic MRI/MRCP at our institution. We reviewed the MRI/MRCP images in patients who had normal Secretin Endoscopic Pancreatic Function testing. MRI/MRCP images were assessed for pancreatic duct morphology, gland size, parenchymal signal and morphology, and arterial contrast enhancement. Of the 32 patients, 23 had normal Secretin Endoscopic Pancreatic Function testing, and 8 of them had mild to marked spectrum of abnormal MRI/MRCP findings that were predominantly focal. Frequencies of the findings were as follows: pancreatic duct stricture (n=3), pancreatic duct dilatation (n=3), side branch ectasia (n=4), atrophy (n=5), decreased arterial enhancement (n=5), decreased parenchymal signal (n=1), and cavity formation (n=1). The remaining15 patients had normal pancreatic structure on MRI/MRCP. Normal pancreatic function testing cannot exclude abnormal MRI/MRCP especially focal findings of chronic pancreatitis. Further studies needed to verify significance of these findings and establish MRI/MRCP imaging criteria for the diagnosis of chronic pancreatitis.

  4. Closed-form confidence intervals for functions of the normal mean and standard deviation.

    Science.gov (United States)

    Donner, Allan; Zou, G Y

    2012-08-01

    Confidence interval methods for a normal mean and standard deviation are well known and simple to apply. However, the same cannot be said for important functions of these parameters. These functions include the normal distribution percentiles, the Bland-Altman limits of agreement, the coefficient of variation and Cohen's effect size. We present a simple approach to this problem by using variance estimates recovered from confidence limits computed for the mean and standard deviation separately. All resulting confidence intervals have closed forms. Simulation results demonstrate that this approach performs very well for limits of agreement, coefficients of variation and their differences.

  5. Kidney function and size in normal subjects before and during growth hormone administration for one week

    DEFF Research Database (Denmark)

    Gammelgaard, Jens; Orskov, H; Andersen, A R

    1981-01-01

    Kidney function and size were studied in seven normal male subjects before and after administration of highly purified human growth hormone for 1 week. Glomerular filtration rate, renal plasma flow (steady-state infusion technique with urinary collections using 125I-iothalamate and 131I-hippuran)......Kidney function and size were studied in seven normal male subjects before and after administration of highly purified human growth hormone for 1 week. Glomerular filtration rate, renal plasma flow (steady-state infusion technique with urinary collections using 125I-iothalamate and 131I...

  6. Echocardiographic reference ranges for normal left atrial function parameters: results from the EACVI NORRE study.

    Science.gov (United States)

    Sugimoto, Tadafumi; Robinet, Sébastien; Dulgheru, Raluca; Bernard, Anne; Ilardi, Federica; Contu, Laura; Addetia, Karima; Caballero, Luis; Kacharava, George; Athanassopoulos, George D; Barone, Daniele; Baroni, Monica; Cardim, Nuno; Hagendorff, Andreas; Hristova, Krasimira; Lopez, Teresa; de la Morena, Gonzalo; Popescu, Bogdan A; Penicka, Martin; Ozyigit, Tolga; Rodrigo Carbonero, Jose David; van de Veire, Nico; Von Bardeleben, Ralph Stephan; Vinereanu, Dragos; Zamorano, Jose Luis; Go, Yun Yun; Marchetta, Stella; Nchimi, Alain; Rosca, Monica; Calin, Andreea; Moonen, Marie; Cimino, Sara; Magne, Julien; Cosyns, Bernard; Galli, Elena; Donal, Erwan; Habib, Gilbert; Esposito, Roberta; Galderisi, Maurizio; Badano, Luigi P; Lang, Roberto M; Lancellotti, Patrizio

    2018-02-23

    To obtain the normal ranges for echocardiographic measurements of left atrial (LA) function from a large group of healthy volunteers accounting for age and gender. A total of 371 (median age 45 years) healthy subjects were enrolled at 22 collaborating institutions collaborating in the Normal Reference Ranges for Echocardiography (NORRE) study of the European Association of Cardiovascular Imaging (EACVI). Left atrial data sets were analysed with a vendor-independent software (VIS) package allowing homogeneous measurements irrespective of the echocardiographic equipment used to acquire data sets. The lowest expected values of LA function were 26.1%, 48.7%, and 41.4% for left atrial strain (LAS), 2D left atrial emptying fraction (LAEF), and 3D LAEF (reservoir function); 7.7%, 24.2%, and -0.53/s for LAS-active, LAEF-active, and LA strain rate during LA contraction (SRa) (pump function) and 12.0% and 21.6% for LAS-passive and LAEF-passive (conduit function). Left atrial reservoir and conduit function were decreased with age while pump function was increased. All indices of reservoir function and all LA strains had no difference in both gender and vendor. However, inter-vendor differences were observed in LA SRa despite the use of VIS. The NORRE study provides contemporary, applicable echocardiographic reference ranges for LA function. Our data highlight the importance of age-specific reference values for LA functions.

  7. Comparing Executive Function and Behavioral Inhibition in Schizophrenia, Bipolar Mood Disorder Type I and Normal Groups

    Directory of Open Access Journals (Sweden)

    Marziye Khodaee

    2015-11-01

    Full Text Available Introduction: Cognitive performance in patients with schizophrenia and Bipolar I disorder seems to be different from the normal individuals, that these defects affect their treatment results. Therefore, this study aimed to compare executive function and behavioral inhibition within patients suffering from schizophrenia, bipolar type I as well as a normal group. Methods: In this descriptive-comparative study, out of all patients hospitalized in daily psychiatric clinic in Najafabad in 2014 due to these disorders, 20 schizophrenia and 20 bipolar type I as well as 20 normal individuals were selected via the convinience sampling. All the study participants completed the computerizing tests including Tower of London and Go-No Go. The study data were analyzed utilizing SPSS software (ver 22 via MANOVA. Results: The study findings revealed a significant difference between the two patient groups and the normal group in regard with executive function and behavioral inhibition (p<0.05, whereas no differences were detected between schizophrenics and bipolar patient groups. Furthermore, patients suffering from schizophrenia and bipolar I mood disorder demonstrated significantly poor performance in cognitive function and behavioral inhibition compared to the normal group. Conclusion: The present study results can be significantly applied in pathology and therapy of these disorders, so as recognizing the inability of such patients can be effective in developing cognitive rehabilitation programs in these patients.

  8. Respiratory functions in asthmatic and normal women during different phases of menstrual cycle

    International Nuclear Information System (INIS)

    Arora, D.B.; Sandhu, P.K.; Dhillon, S.; Arora, A.

    2015-01-01

    Menstrual cycle is an integral part of life of women. There is widespread agreement that changes in the levels of oestrogen and progesterone associated with menstrual cycle also affect different systems of the body besides reproductive system. Levels of oestrogen and progesterone are maximum in the secretory phase and minimum just before the menstruation .Bronchial asthma is one of the commonest chronic respiratory diseases. Premenstrual worsening of asthma symptoms has been reported to affect 33-40% of asthmatic women. This exacerbation of asthma symptoms has been correlated with the oestrogen and progesterone levels. The association between menstrual cycle and lung functions in normal females has also been recognised. The pathophysiology of this process is still not proved. The purpose of our study was to confirm the probable effects of the female hormones on lung functions in normal and asthmatic women in different phases of menstrual cycle and to compare them. Methods: The study was done on 40 normal and 40 asthmatic females in the age group of 15-45 years. Pulmonary function tests were done in three phases of menstrual cycle i.e. follicular, secretory and menstrual in all the subjects. Results: The mean value of lung functions, i.e., FVC, FEV, PEFR, FEF25-75%, FEF 200-1200 were significantly lower in asthmatic females than normal ones (p<0.01) in all three phases. The lung functions of both asthmatic and non-asthmatic females in secretory phase were significantly higher than in menstrual phase (p<0.005). The PFTs in menstrual phase were even lower than the follicular phase (p<0.04). Conclusion: Respiratory parameters of both asthmatic and non-asthmatic women in reproductive age group show significant variation in different phases of menstrual cycle. The smooth muscle relaxant effect of progesterone and probably oestrogen might have contributed to it. The lung function parameters in asthmatics were of lower value compared to normal women. (author)

  9. Green's functions for a graphene sheet and quantum dot in a normal magnetic field

    International Nuclear Information System (INIS)

    Horing, Norman J Morgenstern; Liu, S Y

    2009-01-01

    This paper is concerned with the derivation of the retarded Green's function for a two-dimensional graphene layer in a perpendicular magnetic field in two explicit, analytic forms, which we employ in obtaining a closed-form solution for the Green's function of a tightly confined magnetized graphene quantum dot. The dot is represented by a δ (2) (r)-potential well and the system is subject to Landau quantization in the normal magnetic field

  10. Cytoskeletal role in the transition from compensated to decompensated hypertrophy during adult canine left ventricular pressure overloading

    Science.gov (United States)

    Tagawa, H.; Koide, M.; Sato, H.; Zile, M. R.; Carabello, B. A.; Cooper, G. 4th

    1998-01-01

    Increased microtubule density causes cardiocyte contractile dysfunction in right ventricular (RV) pressure-overload hypertrophy, and these linked phenotypic and contractile abnormalities persist and progress during the transition to failure. Although more severe in cells from failing than hypertrophied RVs, the mechanical defects are normalized in each case by microtubule depolymerization. To define the role of increased microtubule density in left ventricular (LV) pressure-overload hypertrophy and failure, in a given LV we examined ventricular mechanics, sarcomere mechanics, and free tubulin and microtubule levels in control dogs and in dogs with aortic stenosis both with LV hypertrophy alone and with initially compensated hypertrophy that had progressed to LV muscle failure. In comparing initial values with those at study 8 weeks later, dogs with hypertrophy alone had a very substantial increase in LV mass but preservation of a normal ejection fraction and mean systolic wall stress. Dogs with hypertrophy and associated failure had a substantial but lesser increase in LV mass and a reduction in ejection fraction, as well as a marked increase in mean systolic wall stress. Cardiocyte contractile function was equivalent, and unaffected by microtubule depolymerization, in cells from control LVs and those with compensated hypertrophy. In contrast, cardiocyte contractile function in cells from failing LVs was quite depressed but was normalized by microtubule depolymerization. Microtubules were increased only in failing LVs. These contractile and cytoskeletal changes, when assayed longitudinally in a given dog by biopsy, appeared in failing ventricles only when wall stress began to increase and function began to decrease. Thus, the microtubule-based cardiocyte contractile dysfunction characteristic of pressure-hypertrophied myocardium, originally described in the RV, obtains equally in the LV but is shown here to have a specific association with increased wall stress.

  11. Psychosocial Functioning of Adult Epileptic and MS Patients and Adult Normal Controls on the WPSI.

    Science.gov (United States)

    Tan, Siang-Yang

    1986-01-01

    Psychosocial functioning of adult epileptic outpatients as assessed by the Washington Psychosocial Seizure Inventory (WPSI) was compared to that of adult multiple sclerosis (MS) outpatients and normal subjects. When only valid WPSI profiles were considered, the only significant finding was that the epilepsy group and the MS group had more…

  12. A study of the up-and-down method for non-normal distribution functions

    DEFF Research Database (Denmark)

    Vibholm, Svend; Thyregod, Poul

    1988-01-01

    The assessment of breakdown probabilities is examined by the up-and-down method. The exact maximum-likelihood estimates for a number of response patterns are calculated for three different distribution functions and are compared with the estimates corresponding to the normal distribution. Estimates...

  13. Connection between Dynamically Derived Initial Mass Function Normalization and Stellar Population Parameters

    NARCIS (Netherlands)

    McDermid, Richard M.; Cappellari, Michele; Alatalo, Katherine; Bayet, Estelle; Blitz, Leo; Bois, Maxime; Bournaud, Frédéric; Bureau, Martin; Crocker, Alison F.; Davies, Roger L.; Davis, Timothy A.; de Zeeuw, P. T.; Duc, Pierre-Alain; Emsellem, Eric; Khochfar, Sadegh; Krajnović, Davor; Kuntschner, Harald; Morganti, Raffaella; Naab, Thorsten; Oosterloo, Tom; Sarzi, Marc; Scott, Nicholas; Serra, Paolo; Weijmans, Anne-Marie; Young, Lisa M.

    We report on empirical trends between the dynamically determined stellar initial mass function (IMF) and stellar population properties for a complete, volume-limited sample of 260 early-type galaxies from the ATLAS3D project. We study trends between our dynamically derived IMF normalization αdyn ≡

  14. Normalization of voltage-sensitive dye signal with functional activity measures.

    Directory of Open Access Journals (Sweden)

    Kentaroh Takagaki

    Full Text Available In general, signal amplitude in optical imaging is normalized using the well-established DeltaF/F method, where functional activity is divided by the total fluorescent light flux. This measure is used both directly, as a measure of population activity, and indirectly, to quantify spatial and spatiotemporal activity patterns. Despite its ubiquitous use, the stability and accuracy of this measure has not been validated for voltage-sensitive dye imaging of mammalian neocortex in vivo. In this report, we find that this normalization can introduce dynamic biases. In particular, the DeltaF/F is influenced by dye staining quality, and the ratio is also unstable over the course of experiments. As methods to record and analyze optical imaging signals become more precise, such biases can have an increasingly pernicious impact on the accuracy of findings, especially in the comparison of cytoarchitechtonic areas, in area-of-activation measurements, and in plasticity or developmental experiments. These dynamic biases of the DeltaF/F method may, to an extent, be mitigated by a novel method of normalization, DeltaF/DeltaF(epileptiform. This normalization uses as a reference the measured activity of epileptiform spikes elicited by global disinhibition with bicuculline methiodide. Since this normalization is based on a functional measure, i.e. the signal amplitude of "hypersynchronized" bursts of activity in the cortical network, it is less influenced by staining of non-functional elements. We demonstrate that such a functional measure can better represent the amplitude of population mass action, and discuss alternative functional normalizations based on the amplitude of synchronized spontaneous sleep-like activity. These findings demonstrate that the traditional DeltaF/F normalization of voltage-sensitive dye signals can introduce pernicious inaccuracies in the quantification of neural population activity. They further suggest that normalization

  15. A phylogenetic analysis of normal modes evolution in enzymes and its relationship to enzyme function.

    Science.gov (United States)

    Lai, Jason; Jin, Jing; Kubelka, Jan; Liberles, David A

    2012-09-21

    Since the dynamic nature of protein structures is essential for enzymatic function, it is expected that functional evolution can be inferred from the changes in protein dynamics. However, dynamics can also diverge neutrally with sequence substitution between enzymes without changes of function. In this study, a phylogenetic approach is implemented to explore the relationship between enzyme dynamics and function through evolutionary history. Protein dynamics are described by normal mode analysis based on a simplified harmonic potential force field applied to the reduced C(α) representation of the protein structure while enzymatic function is described by Enzyme Commission numbers. Similarity of the binding pocket dynamics at each branch of the protein family's phylogeny was analyzed in two ways: (1) explicitly by quantifying the normal mode overlap calculated for the reconstructed ancestral proteins at each end and (2) implicitly using a diffusion model to obtain the reconstructed lineage-specific changes in the normal modes. Both explicit and implicit ancestral reconstruction identified generally faster rates of change in dynamics compared with the expected change from neutral evolution at the branches of potential functional divergences for the α-amylase, D-isomer-specific 2-hydroxyacid dehydrogenase, and copper-containing amine oxidase protein families. Normal mode analysis added additional information over just comparing the RMSD of static structures. However, the branch-specific changes were not statistically significant compared to background function-independent neutral rates of change of dynamic properties and blind application of the analysis would not enable prediction of changes in enzyme specificity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Pore size determination using normalized J-function for different hydraulic flow units

    Directory of Open Access Journals (Sweden)

    Ali Abedini

    2015-06-01

    Full Text Available Pore size determination of hydrocarbon reservoirs is one of the main challenging areas in reservoir studies. Precise estimation of this parameter leads to enhance the reservoir simulation, process evaluation, and further forecasting of reservoir behavior. Hence, it is of great importance to estimate the pore size of reservoir rocks with an appropriate accuracy. In the present study, a modified J-function was developed and applied to determine the pore radius in one of the hydrocarbon reservoir rocks located in the Middle East. The capillary pressure data vs. water saturation (Pc–Sw as well as routine reservoir core analysis include porosity (φ and permeability (k were used to develop the J-function. First, the normalized porosity (φz, the rock quality index (RQI, and the flow zone indicator (FZI concepts were used to categorize all data into discrete hydraulic flow units (HFU containing unique pore geometry and bedding characteristics. Thereafter, the modified J-function was used to normalize all capillary pressure curves corresponding to each of predetermined HFU. The results showed that the reservoir rock was classified into five separate rock types with the definite HFU and reservoir pore geometry. Eventually, the pore radius for each of these HFUs was determined using a developed equation obtained by normalized J-function corresponding to each HFU. The proposed equation is a function of reservoir rock characteristics including φz, FZI, lithology index (J*, and pore size distribution index (ɛ. This methodology used, the reservoir under study was classified into five discrete HFU with unique equations for permeability, normalized J-function and pore size. The proposed technique is able to apply on any reservoir to determine the pore size of the reservoir rock, specially the one with high range of heterogeneity in the reservoir rock properties.

  17. Detection of rheumatoid arthritis by evaluation of normalized variances of fluorescence time correlation functions

    Science.gov (United States)

    Dziekan, Thomas; Weissbach, Carmen; Voigt, Jan; Ebert, Bernd; MacDonald, Rainer; Bahner, Malte L.; Mahler, Marianne; Schirner, Michael; Berliner, Michael; Berliner, Birgitt; Osel, Jens; Osel, Ilka

    2011-07-01

    Fluorescence imaging using the dye indocyanine green as a contrast agent was investigated in a prospective clinical study for the detection of rheumatoid arthritis. Normalized variances of correlated time series of fluorescence intensities describing the bolus kinetics of the contrast agent in certain regions of interest were analyzed to differentiate healthy from inflamed finger joints. These values are determined using a robust, parameter-free algorithm. We found that the normalized variance of correlation functions improves the differentiation between healthy joints of volunteers and joints with rheumatoid arthritis of patients by about 10% compared to, e.g., ratios of areas under the curves of raw data.

  18. Abnormal expression of leiomyoma cytoskeletal proteins involved in cell migration.

    Science.gov (United States)

    Ura, Blendi; Scrimin, Federica; Arrigoni, Giorgio; Athanasakis, Emmanouil; Aloisio, Michelangelo; Monasta, Lorenzo; Ricci, Giuseppe

    2016-05-01

    Uterine leiomyomas are monoclonal tumors. Several factors are involved in the neoplastic transformation of the myometrium. In our study we focused on dysregulated cytoskeletal proteins in the leiomyoma as compared to the myometrium. Paired tissue samples of ten leiomyomas and adjacent myometria were obtained and analyzed by two‑dimensional gel electrophoresis (2-DE). Mass spectrometry was used for protein identification, and western blotting for 2-DE data validation. The values of ten cytoskeletal proteins were found to be significantly different: eight proteins were upregulated in the leiomyoma and two proteins were downregulated. Three of the upregulated proteins (myosin regulatory light polypeptide 9, four and a half LIM domains protein 1 and LIM and SH3 domain protein 1) are involved in cell migration, while downregulated protein transgelin is involved in replicative senescence. Myosin regulatory light polypeptide 9 (MYL9) was further validated by western blotting because it is considered to be a cell migration marker in several cancers and could play a key role in leiomyoma development. Our data demonstrate significant alterations in the expression of cytoskeletal proteins involved in leiomyoma growth. A better understanding of the involvement of cytoskeletal proteins in leiomyoma pathogenesis may contribute to the identification of new therapeutic targets and the development of new pharmacological approaches.

  19. Detection of cytoskeletal proteins in small cell lung carcinoma

    Czech Academy of Sciences Publication Activity Database

    Hložánková, M.; Lukáš, Z.; Viklický, Vladimír

    1999-01-01

    Roč. 18, - (1999), s. 47-49 ISSN 0231-5882 Grant - others:MŠk1(CZ) OE10a/EU1450 Keywords : cytoskeletal proteins * small cell lung carcinoma Subject RIV: EI - Biotechnology ; Bionics Impact factor: 0.400, year: 1999

  20. Novel Approach to Design Ultra Wideband Microwave Amplifiers: Normalized Gain Function Method

    Directory of Open Access Journals (Sweden)

    R. Kopru

    2013-09-01

    Full Text Available In this work, we propose a novel approach called as “Normalized Gain Function (NGF method” to design low/medium power single stage ultra wide band microwave amplifiers based on linear S parameters of the active device. Normalized Gain Function TNGF is defined as the ratio of T and |S21|^2, desired shape or frequency response of the gain function of the amplifier to be designed and the shape of the transistor forward gain function, respectively. Synthesis of input/output matching networks (IMN/OMN of the amplifier requires mathematically generated target gain functions to be tracked in two different nonlinear optimization processes. In this manner, NGF not only facilitates a mathematical base to share the amplifier gain function into such two distinct target gain functions, but also allows their precise computation in terms of TNGF=T/|S21|^2 at the very beginning of the design. The particular amplifier presented as the design example operates over 800-5200 MHz to target GSM, UMTS, Wi-Fi and WiMAX applications. An SRFT (Simplified Real Frequency Technique based design example supported by simulations in MWO (MicroWave Office from AWR Corporation is given using a 1400mW pHEMT transistor, TGF2021-01 from TriQuint Semiconductor.

  1. Cognitive functions in methamphetamine induced psychosis compared to schizophrenia and normal subjects.

    Directory of Open Access Journals (Sweden)

    Zahra Ezzatpanah

    2014-09-01

    Full Text Available The purpose of this research was to study the cognitive functions in patients with methamphetamine-induced psychosis (MIP in comparison with schizophrenia patients and normal subjects.This was a cross-sectional study, 30 patients with MIP, 30 patients with schizophrenia and 30 normal individuals were selected via convenient sampling and were matched on age, sex and education. Wisconsin Cards Sorting, Stroop, Visual Search and Attention and Wechsler Memory Tests were used to assess the subjects.The study showed that patients with MIP and schizophrenia have more deficits in executive functions, selective attention, sustained attention and memory than normal subjects. There were no significant differences in cognitive functions between patients with MIP and schizophrenia except for visual search and attention that showed more impairment in patients with schizophrenia.Although, cognitive dysfunctions of patients with MIP are mostly similar to patients with schizophrenia, some differences seem to exist, especially in those functions that are not primarily dependent on frontal lobe.

  2. Structural and functional perspectives on classification and seriation in psychotic and normal children.

    Science.gov (United States)

    Breslow, L; Cowan, P A

    1984-02-01

    This study describes a strategy for examining cognitive functioning in psychotic and normal children without the usual confounding effects of marked differences in cognitive structure that occur when children of the same age are compared. Participants were 14 psychotic children, 12 males and 2 females, mean age 9-2, matched with normal children at preoperational and concrete operational stage levels on a set of Piagetian classification tasks. The mean age of the normal children was 6-4, replicating the usually found developmental delay in psychotic samples. Participants were then compared on both structural level and functional abilities on a set of tasks involving seriation of sticks; the higher-level children were also administered a seriation drawing task. Analysis of children's processes of seriating and seriation drawings indicated that over and above the structural retardation, psychotic children at all levels showed functional deficits, especially in the use of anticipatory imagery. The implications for general developmental theory are that progress in structural development is not sufficient for imaginal development, and that structural development of logical concepts is relatively independent of the development of imagery. It was suggested that "thought disorder" may not be a disordered structure of thinking or a retardation in psychotic populations but rather a mismatch between higher-level logical structures and lower-level functions.

  3. Normal Forms for Retarded Functional Differential Equations and Applications to Bogdanov-Takens Singularity

    Science.gov (United States)

    Faria, T.; Magalhaes, L. T.

    The paper addresses, for retarded functional differential equations (FDEs), the computation of normal forms associated with the flow on a finite-dimensional invariant manifold tangent to invariant spaces for the infinitesimal generator of the linearized equation at a singularity. A phase space appropriate to the computation of these normal forms is introduced, and adequate nonresonance conditions for the computation of the normal forms are derived. As an application, the general situation of Bogdanov-Takens singularity and its versal unfolding for scalar retarded FDEs with nondegeneracy at second order is considered, both in the general case and in the case of differential-delay equations of the form ẋ( t) = ƒ( x( t), x( t-1)).

  4. Brain Energy and Oxygen Metabolism: Emerging Role in Normal Function and Disease

    Directory of Open Access Journals (Sweden)

    Michelle E. Watts

    2018-06-01

    Full Text Available Dynamic metabolic changes occurring in neurons are critically important in directing brain plasticity and cognitive function. In other tissue types, disruptions to metabolism and the resultant changes in cellular oxidative state, such as increased reactive oxygen species (ROS or induction of hypoxia, are associated with cellular stress. In the brain however, where drastic metabolic shifts occur to support physiological processes, subsequent changes to cellular oxidative state and induction of transcriptional sensors of oxidative stress likely play a significant role in regulating physiological neuronal function. Understanding the role of metabolism and metabolically-regulated genes in neuronal function will be critical in elucidating how cognitive functions are disrupted in pathological conditions where neuronal metabolism is affected. Here, we discuss known mechanisms regulating neuronal metabolism as well as the role of hypoxia and oxidative stress during normal and disrupted neuronal function. We also summarize recent studies implicating a role for metabolism in regulating neuronal plasticity as an emerging neuroscience paradigm.

  5. CT Densitometry of the Lung in Healthy Nonsmokers with Normal Pulmonary Function

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Tack Sun; Chae, Eun Jin; Seo, Joon Beom; Jung, Young Ju; Oh, Yeon Mok; Lee, Sang Do [University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2012-09-15

    To investigate the upper normal limit of low attenuation area in healthy nonsmokers. A total of 36 nonsmokers with normal pulmonary function test underwent a CT scan. Six thresholds (-980 --930 HU) on inspiration CT and two thresholds (-950 and -910 HU) on expiration CT were used for obtaining low attenuation area. The mean lung density was obtained on both inspiration CT and expiration CT. Descriptive statistics of low attenuation area and the mean lung density, evaluation of difference of low attenuation area and the mean lung density in both sex and age groups, analysis of the relationship between demographic information and CT parameters were performed. Upper normal limit for low attenuation area was 12.96% on inspiration CT (-950 HU) and 9.48% on expiration CT (-910 HU). Upper normal limit for the mean lung density was -837.58 HU on inspiration CT and 686.82 HU on expiration CT. Low attenuation area and the mean lung density showed no significant differences in both sex and age groups. Body mass index (BMI) was negatively correlated with low attenuation area on inspiration CT (-950 HU, r = -0.398, p = 0.016) and positively correlated with the mean lung density on inspiration CT (r 0.539, p = 0.001) and expiration CT (r = 0.432, p = 0.009). Age and body surface area were not correlated with low attenuation area or the mean lung density. Low attenuation area on CT densitometry of the lung could be found in healthy nonsmokers with normal pulmonary function, and showed negative association with BMI. Reference values, such as range and upper normal limit for low attenuation area in healthy subjects could be helpful in quantitative analysis and follow up of early emphysema, using CT densitometry of the lung.

  6. The autonomic higher order processing nuclei of the lower brain stem are among the early targets of the Alzheimer's disease-related cytoskeletal pathology.

    Science.gov (United States)

    Rüb, U; Del Tredici, K; Schultz, C; Thal, D R; Braak, E; Braak, H

    2001-06-01

    The nuclei of the pontine parabrachial region (medial parabrachial nucleus, MPB; lateral parabrachial nucleus, LPB; subpeduncular nucleus, SPP) together with the intermediate zone of the medullary reticular formation (IRZ) are pivotal relay stations within central autonomic regulatory feedback systems. This study was undertaken to investigate the evolution of the Alzheimer's disease-related cytoskeletal pathology in these four sites of the lower brain stem. We examined the MPB, LPB, SPP and IRZ in 27 autopsy cases and classified the cortical Alzheimer-related cytoskeletal anomalies according to an established staging system (neurofibrillary tangle/neuropil threads [NFT/NT] stages I-VI). The lesions were visualized either with the antibody AT8, which is immunospecific for the abnormally phosphorylated form of the cytoskeletal protein tau, or with a modified Gallyas silver iodide stain. The MPB, SPB, and IRZ display cytoskeletal pathology in stage I and the LPB in stage II, whereby bothstages correspond to the preclinical phase of Alzheimer's disease (AD). In stages III-IV (incipient AD), the MPB and SPP are severely affected. In all of the stage III-IV cases, the lesions in the LPB and IRZ are well developed. In stages V and VI (clinical phase of AD), the MPB and SPP are filled with the abnormal intraneuronal material. At stages V-VI, the LPB is moderately involved and the IRZ shows severe damage. The pathogenesis of the AD-related cytoskeletal lesions in the nuclei of the pontine parabrachial region and in the IRZ conforms with the cortical NFT/NT staging sequence I-VI. In the event that the cytoskeletal pathology observed in this study impairs the function of the nerve cells involved, it is conceivable that autonomic mechanisms progressively deteriorate with advancing cortical NFT/NT stages. This relationship remains to be established, but it could provide insights into the illusive correlation between the AD-related cytoskeletal pathology and the function of

  7. Left ventricular functional, structural and energetic effects of normal aging: Comparison with hypertension.

    Directory of Open Access Journals (Sweden)

    Jehill D Parikh

    Full Text Available Both aging and hypertension are significant risk factors for heart failure in the elderly. The purpose of this study was to determine how aging, with and without hypertension, affects left ventricular function.Cross-sectional study of magnetic resonance imaging and 31P spectroscopy-based measurements of left ventricular structure, global function, strains, pulse wave velocity, high energy phosphate metabolism in 48 normal subjects and 40 treated hypertensive patients (though no other cardiovascular disease or diabetes stratified into 3 age deciles from 50-79 years.Normal aging was associated with significant increases in systolic blood pressure, vascular stiffness, torsion, and impaired diastolic function (all P<0.05. Age-matched hypertension exacerbated the effects of aging on systolic pressure, and diastolic function. Hypertension alone, and not aging, was associated with increased left ventricular mass index, reduced energetic reserve, reduced longitudinal shortening and increased endocardial circumferential shortening (all P<0.05. Multiple linear regression analysis showed that these unique hypertensive features were significantly related to systolic blood pressure (P<0.05.1 Hypertension adds to the age-related changes in systolic blood pressure and diastolic function; 2 hypertension is uniquely associated with changes in several aspects of left ventricular structure, function, systolic strains, and energetics; and 3 these uniquely hypertensive-associated parameters are related to the level of systolic blood pressure and so are potentially modifiable.

  8. Normal Parathyroid Function with Decreased Bone Mineral Density in Treated Celiac Disease

    Directory of Open Access Journals (Sweden)

    Bernard Lemieux

    2001-01-01

    Full Text Available Decreased bone mineral density (BMD has been reported in patients with celiac disease in association with secondary hyperparathyroidism. The present study investigated whether basal parathyroid hormone (PTH remained elevated and whether abnormalities of parathyroid function were still present in celiac disease patients treated with a gluten-free diet. Basal seric measurements of calcium and phosphate homeostasis and BMD were obtained in 17 biopsy-proven patients under treatment for a mean period of 5.7±3.7 years (range 1.1 to 15.9. In addition, parathyroid function was studied with calcium chloride and sodium citrate infusions in seven patients. Basal measurements of patients were compared with those of 26 normal individuals, while parathyroid function results were compared with those of seven sex- and age-matched controls. Basal results were similar in patients and controls except for intact PTH (I-PTH (3.77±0.88 pmol/L versus 2.28±0.63 pmol/L, P<0.001, which was higher in the former group but still within normal limits. Mean 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D values were normal in patients. Parathyroid function results were also found to be similar in both groups. Compared with a reference population of the same age (Z score, patients had significantly lower BMDs of the hip (-0.60±0.96 SDs, P<0.05 and lumbar spine (-0.76±1.15 SDs, P<0.05. T scores were also decreased for the hip (-1.3±0.9 SDs, P<0.0001 and lumbar spine (-1.4±1.35 SDs, P<0.0001, with two to three patients being osteoporotic (T score less than -2.5 SDs and seven to eight osteopenic (T score less than -1 SDs but greater than or equal to -2.5 SDs in at least one site. Height and weight were the only important determinants of BMD values by multivariate or logistical regression analysis in these patients. The results show higher basal I-PTH values with normal parathyroid function in treated celiac disease. Height and weight values are, but I-PTH values are not

  9. Prevalence of normal TSH value among patients with autonomously functioning thyroid nodule.

    Science.gov (United States)

    Treglia, Giorgio; Trimboli, Pierpaolo; Verburg, Frederik A; Luster, Markus; Giovanella, Luca

    2015-07-01

    International guidelines significantly diverge on the effectiveness of thyroid scintigraphy (TS) in the initial work-up of thyroid nodules. In particular, the role of TS to detect or exclude the presence of autonomously functioning thyroid nodules (AFTN) in patients with normal serum thyrotropin (TSH) is still a matter to debate. Here, we aimed to review the literature on the prevalence of normal TSH value among patients with AFTN and meta-analyse data of the retrieved eligible papers. A comprehensive literature search of studies published from January 2000 to December 2014 on AFTN detected by TS was performed. Records reporting serum TSH values in AFTN were selected. Pooled prevalence of AFTN with normal TSH values was calculated on a per-patient analysis including 95% confidence intervals (95% CI). Eight records including 2761 AFTN were selected for the meta-analysis. Pooled prevalence of AFTN with normal TSH detected by TS was 50% (95% CI: 32-68%). Selection bias in the included studies and heterogeneity among studies were potential limitations of the meta-analysis. Present meta-analysis shows that about one in two patients with AFTN demonstrated by TS has a TSH value within normal references. As a consequence, TSH measurement may not be considered as effective as a single tool to detect or exclude AFTN, and TS remains mandatory. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

  10. Microtubule depolymerization normalizes in vivo myocardial contractile function in dogs with pressure-overload left ventricular hypertrophy

    Science.gov (United States)

    Koide, M.; Hamawaki, M.; Narishige, T.; Sato, H.; Nemoto, S.; DeFreyte, G.; Zile, M. R.; Cooper G, I. V.; Carabello, B. A.

    2000-01-01

    BACKGROUND: Because initially compensatory myocardial hypertrophy in response to pressure overloading may eventually decompensate to myocardial failure, mechanisms responsible for this transition have long been sought. One such mechanism established in vitro is densification of the cellular microtubule network, which imposes a viscous load that inhibits cardiocyte contraction. METHODS AND RESULTS: In the present study, we extended this in vitro finding to the in vivo level and tested the hypothesis that this cytoskeletal abnormality is important in the in vivo contractile dysfunction that occurs in experimental aortic stenosis in the adult dog. In 8 dogs in which gradual stenosis of the ascending aorta had caused severe left ventricular (LV) pressure overloading (gradient, 152+/-16 mm Hg) with contractile dysfunction, LV function was measured at baseline and 1 hour after the intravenous administration of colchicine. Cardiocytes obtained by biopsy before and after in vivo colchicine administration were examined in tandem. Microtubule depolymerization restored LV contractile function both in vivo and in vitro. CONCLUSIONS: These and additional corroborative data show that increased cardiocyte microtubule network density is an important mechanism for the ventricular contractile dysfunction that develops in large mammals with adult-onset pressure-overload-induced cardiac hypertrophy.

  11. Periodontal disease characterization in dogs with normal renal function or chronic renal failure

    OpenAIRE

    Barbudo-Selmi,Glenda Ramalho; Carvalho,Marileda Bonafim; Selmi,André Luis; Martins,Silvio Emílio Cuevas

    2004-01-01

    The purpose of this study was to evaluate periodontal disease (PD) in dogs with chronic renal failure (CRF) and to compare it to PD in dogs with normal renal function (NRF). Twelve dogs with CRF and 24 dogs with NRF, all presenting dental pocket formation, were compared. In all dogs, serum creatinine, blood urea nitrogen, urine specific gravity and total red and white blood cells were determined. A complete oral examination was also performed including evaluation of bacterial plaque, gingivit...

  12. Age and Gender Effects on Wideband Absorbance in Adults with Normal Outer and Middle Ear Function

    Science.gov (United States)

    Mazlan, Rafidah; Kei, Joseph; Ya, Cheng Li; Yusof, Wan Nur Hanim Mohd; Saim, Lokman; Zhao, Fei

    2015-01-01

    Purpose: This study examined the effects of age and gender on wideband energy absorbance in adults with normal middle ear function. Method: Forty young adults (14 men, 26 women, aged 20-38 years), 31 middle-aged adults (16 men, 15 women, aged 42-64 years), and 30 older adults (20 men, 10 women, aged 65-82 years) were assessed. Energy absorbance…

  13. Disrupted functional and structural networks in cognitively normal elderly subjects with the APOE ɛ4 allele.

    Science.gov (United States)

    Chen, Yaojing; Chen, Kewei; Zhang, Junying; Li, Xin; Shu, Ni; Wang, Jun; Zhang, Zhanjun; Reiman, Eric M

    2015-03-13

    As the Apolipoprotein E (APOE) ɛ4 allele is a major genetic risk factor for sporadic Alzheimer's disease (AD), which has been suggested as a disconnection syndrome manifested by the disruption of white matter (WM) integrity and functional connectivity (FC), elucidating the subtle brain structural and functional network changes in cognitively normal ɛ4 carriers is essential for identifying sensitive neuroimaging based biomarkers and understanding the preclinical AD-related abnormality development. We first constructed functional network on the basis of resting-state functional magnetic resonance imaging and a structural network on the basis of diffusion tensor image. Using global, local and nodal efficiencies of these two networks, we then examined (i) the differences of functional and WM structural network between cognitively normal ɛ4 carriers and non-carriers simultaneously, (ii) the sensitivity of these indices as biomarkers, and (iii) their relationship to behavior measurements, as well as to cholesterol level. For ɛ4 carriers, we found reduced global efficiency significantly in WM and marginally in FC, regional FC dysfunctions mainly in medial temporal areas, and more widespread for WM network. Importantly, the right parahippocampal gyrus (PHG.R) was the only region with simultaneous functional and structural damage, and the nodal efficiency of PHG.R in WM network mediates the APOE ɛ4 effect on memory function. Finally, the cholesterol level correlated with WM network differently than with the functional network in ɛ4 carriers. Our results demonstrated ɛ4-specific abnormal structural and functional patterns, which may potentially serve as biomarkers for early detection before the onset of the disease.

  14. Anionic lipids and the cytoskeletal proteins MreB and RodZ define the spatio-temporal distribution and function of membrane stress controller PspA in Escherichia coli.

    Science.gov (United States)

    Jovanovic, Goran; Mehta, Parul; Ying, Liming; Buck, Martin

    2014-11-01

    All cell types must maintain the integrity of their membranes. The conserved bacterial membrane-associated protein PspA is a major effector acting upon extracytoplasmic stress and is implicated in protection of the inner membrane of pathogens, formation of biofilms and multi-drug-resistant persister cells. PspA and its homologues in Gram-positive bacteria and archaea protect the cell envelope whilst also supporting thylakoid biogenesis in cyanobacteria and higher plants. In enterobacteria, PspA is a dual function protein negatively regulating the Psp system in the absence of stress and acting as an effector of membrane integrity upon stress. We show that in Escherichia coli the low-order oligomeric PspA regulatory complex associates with cardiolipin-rich, curved polar inner membrane regions. There, cardiolipin and the flotillin 1 homologue YqiK support the PspBC sensors in transducing a membrane stress signal to the PspA-PspF inhibitory complex. After stress perception, PspA high-order oligomeric effector complexes initially assemble in polar membrane regions. Subsequently, the discrete spatial distribution and dynamics of PspA effector(s) in lateral membrane regions depend on the actin homologue MreB and the peptidoglycan machinery protein RodZ. The consequences of loss of cytoplasmic membrane anionic lipids, MreB, RodZ and/or YqiK suggest that the mode of action of the PspA effector is closely associated with cell envelope organization. © 2014 The Authors.

  15. A f-MRI study on memory function in normal subjects and patients with partial epilepsies

    International Nuclear Information System (INIS)

    Kamoda, Sachiko

    2004-01-01

    To investigate cerebral regions concerning a memory function and presence of memory lateralization, activated areas and the difference between the right and left hemisphere in functional magnetic resonance imaging (f-MRI) during verbal and visual memory tasks were examined in normal subjects and, as its clinical application, in patients with partial epilepsies. Subjects were 39 normal adult subjects and 10 adult patients. Of the 39 normal subjects, 30 were right-handed and 9 were left-handed. Further, of the 10 patients, 9 were right-handed and one was left-handed, and 7, 2 and 1 had temporal lobe, frontal lobe and undetermined partial epilepsies, respectively. Following the three type of memory task were designed; verbal memory tasks consisting of covert and overt recall tests of 10 words given auditory and visual memory task of covert recall tasks of 6 figures given visually. Activated cerebral areas were imaged with f-MRI using 1.5 tesla Magnetom Vision taken repeatedly during these tasks and neutral condition. Most of the 30 right-handed normal subjects showed activated areas over the left hemisphere specifically on the anterior cingulate, superior, middle and inferior frontal gyri during the verbal memory tasks of covert recall tests. Left hemisphere dominant activated areas in the precentral gyri were added during the verbal memory tasks of overt recall tests. On the other hand, 4 of the 9 left-handed normal subjects showed the left side-dominantly activated areas in the above-mentioned regions during the verbal memory tasks of covert and overt tests, in common with the right-handed subjects. However, 3 of the 9 left-handed normal subjects had right hemisphere dominant activation during the verbal memory tasks, while none of the 30 right-handed normal subjects showed such right side-dominancy. Further, the bilateral occipital lobes were activated during visual memory tasks. The reproducibility in this activation during these verbal and visual memory tasks

  16. Pivotal advance: CTLA-4+ T cells exhibit normal antiviral functions during acute viral infection.

    Science.gov (United States)

    Raué, Hans-Peter; Slifka, Mark K

    2007-05-01

    Previous studies have shown that T cells, which are genetically deficient in CTLA-4/CD152 expression, will proliferate uncontrollably, resulting in lethal autoimmune disease. This and other evidence indicate that CTLA-4 plays a critical role in the negative regulation of effector T cell function. In contrast to expectations, BrdU incorporation experiments demonstrated that CTLA-4 expression was associated with normal or even enhanced in vivo proliferation of virus-specific CD4+ and CD8+ T cells following acute lymphocytic choriomeningitis virus or vaccinia virus infection. When compared with CTLA-4- T cells directly ex vivo, CTLA-4+ T cells also exhibited normal antiviral effector functions following stimulation with peptide-coated cells, virus-infected cells, plate-bound anti-CD3/anti-CTLA-4, or the cytokines IL-12 and IL-18. Together, this indicates that CTLA-4 does not directly inhibit antiviral T cell expansion or T cell effector functions, at least not under the normal physiological conditions associated with either of these two acute viral infections.

  17. Reversible changes in brain glucose metabolism following thyroid function normalization in hyperthyroidism.

    Science.gov (United States)

    Miao, Q; Zhang, S; Guan, Y H; Ye, H Y; Zhang, Z Y; Zhang, Q Y; Xue, R D; Zeng, M F; Zuo, C T; Li, Y M

    2011-01-01

    Patients with hyperthyroidism frequently present with regional cerebral metabolic changes, but the consequences of endocrine-induced brain changes after thyroid function normalization are unclear. We hypothesized that the changes of regional cerebral glucose metabolism are related to thyroid hormone levels in patients with hyperthyroid, and some of these changes can be reversed with antithyroid therapy. Relative regional cerebral glucose metabolism was compared between 10 new-onset untreated patients with hyperthyroidism and 20 healthy control participants by using brain FDG-PET scans. Levels of emotional distress were evaluated by using the SAS and SDS. Patients were treated with methimazole. A follow-up PET scan was performed to assess metabolic changes of the brain when thyroid functions normalized. Compared with controls, patients exhibited lower activity in the limbic system, frontal lobes, and temporal lobes before antithyroid treatment. There were positive correlations between scores of depression and regional metabolism in the cingulate and paracentral lobule. The severity of depression and anxiety covaried negatively with pretreatment activity in the inferior temporal and inferior parietal gyri respectively. Compared with the hyperthyroid status, patients with normalized thyroid functions showed an increased metabolism in the left parahippocampal, fusiform, and right superior frontal gyri. The decrease in both FT3 and FT4 was associated with increased activity in the left parahippocampal and right superior frontal gyri. The changes of regional cerebral glucose metabolism are related to thyroid hormone levels in patients with hyperthyroidism, and some cerebral hypometabolism can be improved after antithyroid therapy.

  18. Functional pulmonary atresia in newborn with normal intracardiac anatomy: Successful treatment with inhaled nitric oxide and pulmonary vasodilators

    Directory of Open Access Journals (Sweden)

    Gürkan Altun

    2013-01-01

    Full Text Available Functional pulmonary atresia is characterized by a structurally normal pulmonary valve that does not open during right ventricular ejection. It is usually associated with Ebstein′s anomaly, Uhl′s anomaly, neonatal Marfan syndrome and tricuspid valve dysplasia. However, functional pulmonary atresia is rarely reported in newborn with anatomically normal heart. We report a newborn with functional pulmonary atresia who had normal intracardiac anatomy, who responded to treatment with nitric oxide and other vasodilator therapy successfully.

  19. Carcinogenesis: alterations in reciprocal interactions of normal functional structure of biologic systems.

    Science.gov (United States)

    Davydyan, Garri

    2015-12-01

    The evolution of biologic systems (BS) includes functional mechanisms that in some conditions may lead to the development of cancer. Using mathematical group theory and matrix analysis, previously, it was shown that normally functioning BS are steady functional structures regulated by three basis regulatory components: reciprocal links (RL), negative feedback (NFB) and positive feedback (PFB). Together, they form an integrative unit maintaining system's autonomy and functional stability. It is proposed that phylogenetic development of different species is implemented by the splitting of "rudimentary" characters into two relatively independent functional parts that become encoded in chromosomes. The functional correlate of splitting mechanisms is RL. Inversion of phylogenetic mechanisms during ontogenetic development leads cell differentiation until cells reach mature states. Deterioration of reciprocal structure in the genome during ontogenesis gives rise of pathological conditions characterized by unsteadiness of the system. Uncontrollable cell proliferation and invasive cell growth are the leading features of the functional outcomes of malfunctioning systems. The regulatory element responsible for these changes is RL. In matrix language, pathological regulation is represented by matrices having positive values of diagonal elements ( TrA  > 0) and also positive values of matrix determinant ( detA  > 0). Regulatory structures of that kind can be obtained if the negative entry of the matrix corresponding to RL is replaced with the positive one. To describe not only normal but also pathological states of BS, a unit matrix should be added to the basis matrices representing RL, NFB and PFB. A mathematical structure corresponding to the set of these four basis functional patterns (matrices) is a split quaternion (coquaternion). The structure and specific role of basis elements comprising four-dimensional linear space of split quaternions help to understand what

  20. Longstanding Hyperthyroidism Is Associated with Normal or Enhanced Intrinsic Cardiomyocyte Function despite Decline in Global Cardiac Function

    Science.gov (United States)

    Redetzke, Rebecca A.; Gerdes, A. Martin

    2012-01-01

    Thyroid hormones (THs) play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV) contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure. To evaluate the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined LV isolated myocyte function, chamber function, and whole tissue remodeling in a hamster model. Three-month-old F1b hamsters were randomized to control or 10 months TH treatment (0.1% grade I desiccated TH). LV chamber remodeling and function was assessed by echocardiography at 1, 2, 4, 6, 8, and 10 months of treatment. After 10 months, terminal cardiac function was assessed by echocardiography and LV hemodynamics. Hyperthyroid hamsters exhibited significant cardiac hypertrophy and deleterious cardiac remodeling characterized by myocyte lengthening, chamber dilatation, decreased relative wall thickness, increased wall stress, and increased LV interstitial fibrotic deposition. Importantly, hyperthyroid hamsters demonstrated significant LV systolic and diastolic dysfunction. Despite the aforementioned remodeling and global cardiac decline, individual isolated cardiac myocytes from chronically hyperthyroid hamsters had enhanced function when compared with myocytes from untreated age-matched controls. Thus, it appears that long-term hyperthyroidism may impair global LV function, at least in part by increasing interstitial ventricular fibrosis, in spite of normal or enhanced intrinsic cardiomyocyte function. PMID:23056390

  1. Longstanding hyperthyroidism is associated with normal or enhanced intrinsic cardiomyocyte function despite decline in global cardiac function.

    Directory of Open Access Journals (Sweden)

    Nathan Y Weltman

    Full Text Available Thyroid hormones (THs play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure. To evaluate the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined LV isolated myocyte function, chamber function, and whole tissue remodeling in a hamster model. Three-month-old F1b hamsters were randomized to control or 10 months TH treatment (0.1% grade I desiccated TH. LV chamber remodeling and function was assessed by echocardiography at 1, 2, 4, 6, 8, and 10 months of treatment. After 10 months, terminal cardiac function was assessed by echocardiography and LV hemodynamics. Hyperthyroid hamsters exhibited significant cardiac hypertrophy and deleterious cardiac remodeling characterized by myocyte lengthening, chamber dilatation, decreased relative wall thickness, increased wall stress, and increased LV interstitial fibrotic deposition. Importantly, hyperthyroid hamsters demonstrated significant LV systolic and diastolic dysfunction. Despite the aforementioned remodeling and global cardiac decline, individual isolated cardiac myocytes from chronically hyperthyroid hamsters had enhanced function when compared with myocytes from untreated age-matched controls. Thus, it appears that long-term hyperthyroidism may impair global LV function, at least in part by increasing interstitial ventricular fibrosis, in spite of normal or enhanced intrinsic cardiomyocyte function.

  2. Cognitive functioning and its influence on sexual behavior in normal aging and dementia.

    Science.gov (United States)

    Hartmans, Carien; Comijs, Hannie; Jonker, Cees

    2014-05-01

    Motivational aspects, emotional factors, and cognition, all of which require intact cognitive functioning may be essential in sexual functioning. However, little is known about the association between cognitive functioning and sexual behavior. The aim of this article is to review the current evidence for the influence of cognitive functioning on sexual behavior in normal aging and dementia. A systematic literature search was conducted in PubMed, Ovid, Cochrane, and PsycINFO databases. The databases were searched for English language papers focusing on human studies published relating cognitive functioning to sexual behavior in the aging population. Keywords included sexual behavior, sexuality, cognitive functioning, healthy elderly, elderly, aging and dementia. Eight studies fulfilled our inclusion criteria. Of these studies, five included dementia patients and/or their partners, whereas only three studies included healthy older persons. Although not consistently, results indicated a trend that older people who are not demented and continue to engage in sexual activity have better overall cognitive functioning. Cognitive decline and dementia seem to be associated with diminished sexual behavior in older persons. The association between cognitive functioning and sexual behavior in the aging population is understudied. The results found are inconclusive. Copyright © 2013 John Wiley & Sons, Ltd.

  3. Percutaneous renal angioplasty and stenting: application of embolic protection device in patients with normal renal function

    International Nuclear Information System (INIS)

    Tong Xiaoqiang; Yang Ming; Wang Jian; Song Li; Wang Chao; Lv Yongxing; Sun Hongliang; Zou Yinghua; Yin Ming

    2007-01-01

    Objective: To investigate the Value of embolic protection device (EPD)in renal artery stenting (RAS)for the patients with normal renal function. Methods: Total 24 patients (26 renal arteries) suffering from renal artery stenosis with normal serum creatinine were divided into two groups: EPD group (n12)and non-EPD group (n=12). Serum creatinine was calculated and analized statistically between the two groups, 1 month and 6months after stenting respectively, and followed by comparisons taking inside of each group and between both groups. Results: Serum creatinine of the EPD and non-EPD groups before, 1 month and 6 month after stenting were(99.18 ± 18.26) μmol/L, (101.73 ± 12.65) μmol/L, (96.82 ± 15.81) μmol/L and (100.18 ± 19.81) μmol/L, (107.36 ± 29.49) μmol/L, (127.64 ± 88.05) μmol/L, respectively; showing no significant difference inside each group individually (P>0.05), and also no statistically significant difference between the two groups (P>0.05). Conclusion: For the patients suffering from renal artery stenosis with normal serum creatinine, application of EPD may have no impact on renal function. Further evaluation is needed. (authors)

  4. Proportional and functional analogical reasoning in normal and language-impaired children.

    Science.gov (United States)

    Nippold, M A; Erskine, B J; Freed, D B

    1988-11-01

    Teachers often use analogies in classroom settings to clarify new concepts for their students. However, analogies may inadvertently confuse the youngster who has difficulty identifying the one-to-one comparisons underlying them. Although analogical reasoning has been studied extensively in normal children, no information was available concerning this construct in children having a specific language impairment. Thus, it was unknown to what extent they might be deficient in analogical reasoning. Therefore, in the present study, 20 children ages 6-8 years (mean age = 7:6) having normal nonverbal intelligence but deficits in language comprehension were administered tasks of verbal and perceptual proportional analogical reasoning and a problem-solving task of functional analogical reasoning. Compared to a normal-language control group matched on the basis of chronological age and sex, the language-impaired group was deficient in all three tasks of analogical reasoning. However, when the factor of nonverbal intelligence was controlled statistically, the differences between the groups on each of the tasks were removed. Additional findings were that verbal proportional analogical reasoning was significantly correlated to perceptual proportional analogical reasoning and to functional analogical reasoning. Implications for assessment and intervention with young school-age language-impaired children are discussed.

  5. Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy.

    Science.gov (United States)

    Chen, Jiahuan; Ganguly, Anutosh; Mucsi, Ashley D; Meng, Junchen; Yan, Jiacong; Detampel, Pascal; Munro, Fay; Zhang, Zongde; Wu, Mei; Hari, Aswin; Stenner, Melanie D; Zheng, Wencheng; Kubes, Paul; Xia, Tie; Amrein, Matthias W; Qi, Hai; Shi, Yan

    2017-02-01

    Dendritic cells are targeted by regulatory T (T reg) cells, in a manner that operates as an indirect mode of T cell suppression. In this study, using a combination of single-cell force spectroscopy and structured illumination microscopy, we analyze individual T reg cell-DC interaction events and show that T reg cells exhibit strong intrinsic adhesiveness to DCs. This increased DC adhesion reduces the ability of contacted DCs to engage other antigen-specific cells. We show that this unusually strong LFA-1-dependent adhesiveness of T reg cells is caused in part by their low calpain activities, which normally release integrin-cytoskeleton linkage, and thereby reduce adhesion. Super resolution imaging reveals that such T reg cell adhesion causes sequestration of Fascin-1, an actin-bundling protein essential for immunological synapse formation, and skews Fascin-1-dependent actin polarization in DCs toward the T reg cell adhesion zone. Although it is reversible upon T reg cell disengagement, this sequestration of essential cytoskeletal components causes a lethargic state of DCs, leading to reduced T cell priming. Our results reveal a dynamic cytoskeletal component underlying T reg cell-mediated DC suppression in a contact-dependent manner. © 2017 Chen et al.

  6. The multifaceted functions of C/EBPα in normal and malignant haematopoiesis.

    Science.gov (United States)

    Ohlsson, E; Schuster, M B; Hasemann, M; Porse, B T

    2016-04-01

    The process of blood formation, haematopoiesis, depends upon a small number of haematopoietic stem cells (HSCs) that reside in the bone marrow. Differentiation of HSCs is characterised by decreased expression of genes associated with self-renewal accompanied by a stepwise activation of genes promoting differentiation. Lineage branching is further directed by groups of cooperating and counteracting genes forming complex networks of lineage-specific transcription factors. Imbalances in such networks can result in blockage of differentiation, lineage reprogramming and malignant transformation. CCAAT/enhancer-binding protein-α (C/EBPα) was originally identified 30 years ago as a transcription factor that binds both promoter and enhancer regions. Most of the early work focused on the role of C/EBPα in regulating transcriptional processes as well as on its functions in key differentiation processes during liver, adipogenic and haematopoietic development. Specifically, C/EBPα was shown to control differentiation by its ability to coordinate transcriptional output with cell cycle progression. Later, its role as an important tumour suppressor, mainly in acute myeloid leukaemia (AML), was recognised and has been the focus of intense studies by a number of investigators. More recent work has revisited the role of C/EBPα in normal haematopoiesis, especially its function in HSCs, and also started to provide more mechanistic insights into its role in normal and malignant haematopoiesis. In particular, the differential actions of C/EBPα isoforms, as well as its importance in chromatin remodelling and cellular reprogramming, are beginning to be elucidated. Finally, recent work has also shed light on the dichotomous function of C/EBPα in AML by demonstrating its ability to act as both a tumour suppressor and promoter. In the present review, we will summarise the current knowledge on the functions of C/EBPα during normal and malignant haematopoiesis with special emphasis on

  7. Kaempferol inhibits Entamoeba histolytica growth by altering cytoskeletal functions.

    Science.gov (United States)

    Bolaños, Verónica; Díaz-Martínez, Alfredo; Soto, Jacqueline; Marchat, Laurence A; Sanchez-Monroy, Virginia; Ramírez-Moreno, Esther

    2015-11-01

    The flavonoid kaempferol obtained from Helianthemum glomeratum, an endemic Mexican medicinal herb used to treat gastrointestinal disorders, has been shown to inhibit growth of Entamoeba histolytica trophozoites in vitro; however, the mechanisms associated with this activity have not been documented. Several works reported that kaempferol affects cytoskeleton in mammalian cells. In order to gain insights into the action mechanisms involved in the anti-amoebic effect of kaempferol, here we evaluated the effect of this compound on the pathogenic events driven by the cytoskeleton during E. histolytica infection. We also carried out a two dimensional gel-based proteomic analysis to evidence modulated proteins that could explain the phenotypical changes observed in trophozoites. Our results showed that kaempferol produces a dose-dependent effect on trophozoites growth and viability with optimal concentration being 27.7 μM. Kaempferol also decreased adhesion, it increased migration and phagocytic activity, but it did not affect erythrocyte binding nor cytolytic capacity of E. histolytica. Congruently, proteomic analysis revealed that the cytoskeleton proteins actin, myosin II heavy chain and cortexillin II were up-regulated in response to kaempferol treatment. In conclusion, kaempferol anti-amoebic effects were associated with deregulation of proteins related with cytoskeleton, which altered invasion mechanisms. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Kynurenic Acid Prevents Cytoskeletal Disorganization Induced by Quinolinic Acid in Mixed Cultures of Rat Striatum.

    Science.gov (United States)

    Pierozan, Paula; Biasibetti-Brendler, Helena; Schmitz, Felipe; Ferreira, Fernanda; Pessoa-Pureur, Regina; Wyse, Angela T S

    2018-06-01

    Kynurenic acid (KYNA) is a neuroactive metabolite of tryptophan known to modulate a number of mechanisms involved in neural dysfunction. Although its activity in the brain has been widely studied, the effect of KYNA counteracting the actions of quinolinic acid (QUIN) remains unknown. The present study aims at describing the ability of 100 μM KYNA preventing cytoskeletal disruption provoked by QUIN in astrocyte/neuron/microglia mixed culture. KYNA totally preserved cytoskeletal organization, cell morphology, and redox imbalance in mixed cultures exposed to QUIN. However, KYNA partially prevented morphological alteration in isolated primary astrocytes and failed to protect the morphological alterations of neurons caused by QUIN exposure. Moreover, KYNA prevented QUIN-induced microglial activation and upregulation of ionized calcium-binding adapter molecule 1 (Iba-1) and partially preserved tumor necrosis factor-α (TNF-α) level in mixed cultures. TNF-α level was also partially preserved in astrocytes. In addition to the mechanisms dependent on redox imbalance and microglial activation, KYNA prevented downregulation of connexin-43 and the loss of functionality of gap junctions (GJs), preserving cell-cell contact, cytoskeletal organization, and cell morphology in QUIN-treated cells. Furthermore, the toxicity of QUIN targeting the cytoskeleton of mixed cultures was not prevented by the N-methyl-D-aspartate (NMDA) antagonist MK-801. We suggest that KYNA protects the integrity of the cytoskeleton of mixed cultures by complex mechanisms including modulating microglial activation preventing oxidative imbalance and misregulated GJs leading to disrupted cytoskeleton in QUIN-treated cells. This study contributed to elucidate the molecular basis of KYNA protection against QUIN toxicity.

  9. Can Functional Cardiac Age be Predicted from ECG in a Normal Healthy Population

    Science.gov (United States)

    Schlegel, Todd; Starc, Vito; Leban, Manja; Sinigoj, Petra; Vrhovec, Milos

    2011-01-01

    In a normal healthy population, we desired to determine the most age-dependent conventional and advanced ECG parameters. We hypothesized that changes in several ECG parameters might correlate with age and together reliably characterize the functional age of the heart. Methods: An initial study population of 313 apparently healthy subjects was ultimately reduced to 148 subjects (74 men, 84 women, in the range from 10 to 75 years of age) after exclusion criteria. In all subjects, ECG recordings (resting 5-minute 12-lead high frequency ECG) were evaluated via custom software programs to calculate up to 85 different conventional and advanced ECG parameters including beat-to-beat QT and RR variability, waveform complexity, and signal-averaged, high-frequency and spatial/spatiotemporal ECG parameters. The prediction of functional age was evaluated by multiple linear regression analysis using the best 5 univariate predictors. Results: Ignoring what were ultimately small differences between males and females, the functional age was found to be predicted (R2= 0.69, P ECGs, functional cardiac age can be estimated by multiple linear regression analysis of mostly advanced ECG results. Because some parameters in the regression formula, such as QTcorr, high frequency QRS amplitude and P-wave width also change with disease in the same direction as with increased age, increased functional age of the heart may reflect subtle age-related pathologies in cardiac electrical function that are usually hidden on conventional ECG.

  10. Decreased IGF-1 concentration during the first trimester of pregnancy in women with normal somatotroph function.

    Science.gov (United States)

    Persechini, Marie-Laure; Gennero, Isabelle; Grunenwald, Solange; Vezzosi, Delphine; Bennet, Antoine; Caron, Philippe

    2015-08-01

    A decrease of insulin-like growth factor-I levels (IGF-I) has been reported during the first trimester of pregnancy in women with acromegaly before the secretion of placental growth hormone (GH) progressively increases IGF-1 concentration. To evaluate variations of concentrations of IGF-1, insulin-like growth factor (IGF)-binding protein-3 (IGF-BP3) and GH during the first trimester of pregnancy in women with normal somatotroph function. Sixteen women (median age 31 years) with as who were followed for benign thyroid disorders (n = 15) or prolactin-secreting microadenoma (n = 1) were evaluated before and in the first trimester of pregnancy. Serum concentrations of GH, IGF-1, IGF-BP3, TSH and estradiol (E2) were measured before and in the first trimester (5.4 ± 2.2 weeks of gestation). Before pregnancy, somatotroph and thyroid functions (median TSH 1.2 mU/L) were normal in all women. At the first trimester IGF-1 levels decreased significantly (before = 210 ng/mL, first trimester = 145 ng/mL, p function, IGF-1 levels decrease in the first trimester of pregnancy without changes in GH or IGF-BP3 levels. These results confirm liver resistance to GH as a consequence of the physiological increase of estrogens during the first trimester.

  11. Interplay between cytoskeletal stresses and cell adaptation under chronic flow.

    Directory of Open Access Journals (Sweden)

    Deepika Verma

    Full Text Available Using stress sensitive FRET sensors we have measured cytoskeletal stresses in α-actinin and the associated reorganization of the actin cytoskeleton in cells subjected to chronic shear stress. We show that long-term shear stress reduces the average actinin stress and this effect is reversible with removal of flow. The flow-induced changes in cytoskeletal stresses are found to be dynamic, involving a transient decrease in stress (phase-I, a short-term increase (3-6 min (Phase-II, followed by a longer-term decrease that reaches a minimum in ~20 min (Phase-III, before saturating. These changes are accompanied by reorganization of the actin cytoskeleton from parallel F-actin bundles to peripheral bundles. Blocking mechanosensitive ion channels (MSCs with Gd(3+ and GsMTx4 (a specific inhibitor eliminated the changes in cytoskeletal stress and the corresponding actin reorganization, indicating that Ca(2+ permeable MSCs participate in the signaling cascades. This study shows that shear stress induced cell adaptation is mediated via MSCs.

  12. Disrupted-in-Schizophrenia-1 is essential for normal hypothalamic-pituitary-interrenal (HPI) axis function.

    Science.gov (United States)

    Eachus, Helen; Bright, Charlotte; Cunliffe, Vincent T; Placzek, Marysia; Wood, Jonathan D; Watt, Penelope J

    2017-06-01

    Psychiatric disorders arise due to an interplay of genetic and environmental factors, including stress. Studies in rodents have shown that mutants for Disrupted-In-Schizophrenia-1 (DISC1), a well-accepted genetic risk factor for mental illness, display abnormal behaviours in response to stress, but the mechanisms through which DISC1 affects stress responses remain poorly understood. Using two lines of zebrafish homozygous mutant for disc1, we investigated behaviour and functioning of the hypothalamic-pituitary-interrenal (HPI) axis, the fish equivalent of the hypothalamic-pituitary-adrenal (HPA) axis. Here, we show that the role of DISC1 in stress responses is evolutionarily conserved and that DISC1 is essential for normal functioning of the HPI axis. Adult zebrafish homozygous mutant for disc1 show aberrant behavioural responses to stress. Our studies reveal that in the embryo, disc1 is expressed in neural progenitor cells of the hypothalamus, a conserved region of the vertebrate brain that centrally controls responses to environmental stressors. In disc1 mutant embryos, proliferating rx3+ hypothalamic progenitors are not maintained normally and neuronal differentiation is compromised: rx3-derived ff1b+ neurons, implicated in anxiety-related behaviours, and corticotrophin releasing hormone (crh) neurons, key regulators of the stress axis, develop abnormally, and rx3-derived pomc+ neurons are disorganised. Abnormal hypothalamic development is associated with dysfunctional behavioural and neuroendocrine stress responses. In contrast to wild type siblings, disc1 mutant larvae show altered crh levels, fail to upregulate cortisol levels when under stress and do not modulate shoal cohesion, indicative of abnormal social behaviour. These data indicate that disc1 is essential for normal development of the hypothalamus and for the correct functioning of the HPA/HPI axis. © The Author 2017. Published by Oxford University Press.

  13. Anxiety and beta-adrenergic receptor function in a normal population.

    Science.gov (United States)

    Kang, Eun-Ho; Yu, Bum-Hee

    2005-06-01

    Many studies have shown a close relationship between anxiety and beta-adrenergic receptor function in patients with anxiety disorders. This study examined the relationship between beta-adrenergic receptor function and anxiety levels in a normal population. Subjects for this study included 36 men and 44 women between the ages of 20 and 40 years whose Body Mass Index (BMI) was between 18 and 26. All of them were healthy subjects who had no previous history of medical or psychiatric illnesses. The authors measured the Spielberger State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and Chronotropic 25 Dose (CD25) of isoproterenol, previously developed to assess in vivo beta-adrenergic receptor sensitivity. We also examined correlations between log normalized CD25 and mood states. The mean of CD25 was 2.64+/-1.37 mug and the mean of CD25 in men was significantly higher (i.e., lower beta-adrenergic receptor sensitivity) than that of women (3.26+/-1.35 vs. 2.14+/-1.17 microg; t = 3.99, p anxiety (r = -0.344, p = 0.002), trait anxiety (r = -0.331, p = 0.003), and BDI (r = -0.283, p = 0.011). CD25 was positively correlated with BMI (r = 0.423, p anxiety, and BMI. The sensitivity of beta-adrenergic receptors increased as anxiety levels became higher in a normal population. Thus, the relationship between anxiety and beta-adrenergic receptor function in healthy subjects may be different from that of patients with anxiety disorders.

  14. Moment generating functions and Normalized implied volatilities: unification and extension via Fukasawa's pricing formula

    OpenAIRE

    De Marco, Stefano; Martini, Claude

    2017-01-01

    We extend the model-free formula of [Fukasawa 2012] for $\\mathbb E[\\Psi(X_T)]$, where $X_T=\\log S_T/F$ is the log-price of an asset, to functions $\\Psi$ of exponential growth. The resulting integral representation is written in terms of normalized implied volatilities. Just as Fukasawa's work provides rigourous ground for Chriss and Morokoff's (1999) model-free formula for the log-contract (related to the Variance swap implied variance), we prove an expression for the moment generating functi...

  15. Classification of Normal Subjects and Pulmonary Function Disease Patients using Tracheal Respiratory Sound Detection System

    Energy Technology Data Exchange (ETDEWEB)

    Im, Jae Joong; Yi, Young Ju; Jeon, Young Ju [Chonbuk National University (Korea)

    2000-04-01

    A new auscultation system for the detection of breath sound from trachea was developed in house. Small size microphone(panasonic pin microphone) was encapsuled in a housing for resonant effect, and hardware for the sound detection was fabricated. Pulmonary function test results were compared with the parameters extracted from frequency spectrum of breath sound obtained from the developed system. Results showed that the peak frequency and relative ratio of integral values between low(80-400Hz) and high(400-800Hz) frequency ranges revealed the significant differences. Developed system could be used for distinguishing normal subject and the patients who have pulmonary disease. (author). 13 refs., 9 figs.

  16. Predicting above normal wildfire activity in southern Europe as a function of meteorological drought

    International Nuclear Information System (INIS)

    Gudmundsson, L; Seneviratne, S I; Rego, F C; Rocha, M

    2014-01-01

    Wildfires are a recurrent feature of ecosystems in southern Europe, regularly causing large ecological and socio-economic damages. For efficient management of this hazard, long lead time forecasts could be valuable tools. Using logistic regression, we show that the probability of above normal summer wildfire activity in the 1985–2010 time period can be forecasted as a function of meteorological drought with significant predictability (p <0.05) several months in advance. The results show that long lead time forecasts of this natural hazard are feasible in southern Europe, which could potentially aid decision-makers in the design of strategies for forest management. (letter)

  17. The effect of short-term glucagon infusion on kidney function in normal man

    DEFF Research Database (Denmark)

    Parving, H H; Noer, J; Kehlet, H

    1977-01-01

    Kidney function was studied in six normal males before and during a 2 h glucagon (10 ng/kg/min) infusion. The following variables were determined during each 20 min clearance period; glomerular filtration rate (GFR), renal plasma-flow (RPF) , filtration fraction (FF), urinary albumin and beta2......-microglobulin-excretion rates. Glucagon infusion resulted in a fourfold increase in plasma glucagon concentration. The infusion induced a significant increase in GFR (+9%), FF (+9%) and urinary beta2-microglobulin excretion rate (+32%), (p less than 0.01). RPF and urinary albumin excretion rates were...

  18. Ultrasonographic assessment of maternal cardiac function and peripheral circulation during normal gestation in dogs.

    Science.gov (United States)

    Blanco, Paula G; Tórtora, Mariana; Rodríguez, Raúl; Arias, Daniel O; Gobello, Cristina

    2011-10-01

    The aim of this study was to describe changes in cardiac morphology, systolic function and some peripheral hemodynamic parameters during normal pregnancy in dogs. Twenty healthy bitches, 10 pregnant (PG) and 10 non-pregnant controls (CG), were evaluated every 10 days using echocardiography from day 0 of the estrus cycle to parturition or to day 65 for the PG and CG groups, respectively. Systolic blood pressure (SBP) and uterine artery resistance index (RI) were also assessed. Throughout the study, the shortening fraction and cardiac output increased up to 30% vs. 5% (Pdogs. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. ATG5 overexpression is neuroprotective and attenuates cytoskeletal and vesicle-trafficking alterations in axotomized motoneurons.

    Science.gov (United States)

    Leiva-Rodríguez, Tatiana; Romeo-Guitart, David; Marmolejo-Martínez-Artesero, Sara; Herrando-Grabulosa, Mireia; Bosch, Assumpció; Forés, Joaquim; Casas, Caty

    2018-05-24

    Injured neurons should engage endogenous mechanisms of self-protection to limit neurodegeneration. Enhancing efficacy of these mechanisms or correcting dysfunctional pathways may be a successful strategy for inducing neuroprotection. Spinal motoneurons retrogradely degenerate after proximal axotomy due to mechanical detachment (avulsion) of the nerve roots, and this limits recovery of nervous system function in patients after this type of trauma. In a previously reported proteomic analysis, we demonstrated that autophagy is a key endogenous mechanism that may allow motoneuron survival and regeneration after distal axotomy and suture of the nerve. Herein, we show that autophagy flux is dysfunctional or blocked in degenerated motoneurons after root avulsion. We also found that there were abnormalities in anterograde/retrograde motor proteins, key secretory pathway factors, and lysosome function. Further, LAMP1 protein was missorted and underglycosylated as well as the proton pump v-ATPase. In vitro modeling revealed how sequential disruptions in these systems likely lead to neurodegeneration. In vivo, we observed that cytoskeletal alterations, induced by a single injection of nocodazole, were sufficient to promote neurodegeneration of avulsed motoneurons. Besides, only pre-treatment with rapamycin, but not post-treatment, neuroprotected after nerve root avulsion. In agreement, overexpressing ATG5 in injured motoneurons led to neuroprotection and attenuation of cytoskeletal and trafficking-related abnormalities. These discoveries serve as proof of concept for autophagy-target therapy to halting the progression of neurodegenerative processes.

  20. CONNECTION BETWEEN DYNAMICALLY DERIVED INITIAL MASS FUNCTION NORMALIZATION AND STELLAR POPULATION PARAMETERS

    International Nuclear Information System (INIS)

    McDermid, Richard M.; Cappellari, Michele; Bayet, Estelle; Bureau, Martin; Davies, Roger L.; Alatalo, Katherine; Blitz, Leo; Bois, Maxime; Bournaud, Frédéric; Duc, Pierre-Alain; Crocker, Alison F.; Davis, Timothy A.; De Zeeuw, P. T.; Emsellem, Eric; Kuntschner, Harald; Khochfar, Sadegh; Krajnović, Davor; Morganti, Raffaella; Oosterloo, Tom; Naab, Thorsten

    2014-01-01

    We report on empirical trends between the dynamically determined stellar initial mass function (IMF) and stellar population properties for a complete, volume-limited sample of 260 early-type galaxies from the ATLAS 3D project. We study trends between our dynamically derived IMF normalization α dyn ≡ (M/L) stars /(M/L) Salp and absorption line strengths, and interpret these via single stellar population-equivalent ages, abundance ratios (measured as [α/Fe]), and total metallicity, [Z/H]. We find that old and alpha-enhanced galaxies tend to have on average heavier (Salpeter-like) mass normalization of the IMF, but stellar population does not appear to be a good predictor of the IMF, with a large range of α dyn at a given population parameter. As a result, we find weak α dyn -[α/Fe] and α dyn –Age correlations and no significant α dyn –[Z/H] correlation. The observed trends appear significantly weaker than those reported in studies that measure the IMF normalization via the low-mass star demographics inferred through stellar spectral analysis

  1. CONNECTION BETWEEN DYNAMICALLY DERIVED INITIAL MASS FUNCTION NORMALIZATION AND STELLAR POPULATION PARAMETERS

    Energy Technology Data Exchange (ETDEWEB)

    McDermid, Richard M. [Department of Physics and Astronomy, Macquarie University, Sydney NSW 2109 (Australia); Cappellari, Michele; Bayet, Estelle; Bureau, Martin; Davies, Roger L. [Sub-Department of Astrophysics, Department of Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Alatalo, Katherine [Infrared Processing and Analysis Center, California Institute of Technology, Pasadena, CA 91125 (United States); Blitz, Leo [Department of Astronomy, Campbell Hall, University of California, Berkeley, CA 94720 (United States); Bois, Maxime [Observatoire de Paris, LERMA and CNRS, 61 Av. de l' Observatoire, F-75014 Paris (France); Bournaud, Frédéric; Duc, Pierre-Alain [Laboratoire AIM Paris-Saclay, CEA/IRFU/SAp- CNRS-Université Paris Diderot, F-91191 Gif-sur-Yvette Cedex (France); Crocker, Alison F. [Ritter Astrophysical Observatory, University of Toledo, Toledo, OH 43606 (United States); Davis, Timothy A.; De Zeeuw, P. T.; Emsellem, Eric; Kuntschner, Harald [European Southern Observatory, Karl-Schwarzschild-Str. 2, D-85748 Garching (Germany); Khochfar, Sadegh [Institute for Astronomy, University of Edinburgh, Royal Observatory, Edinburgh, EH9 3HJ (United Kingdom); Krajnović, Davor [Leibniz-Institut für Astrophysik Potsdam (AIP), An der Sternwarte 16, D-14482 Potsdam (Germany); Morganti, Raffaella; Oosterloo, Tom [Netherlands Institute for Radio Astronomy (ASTRON), Postbus 2, 7990 AA Dwingeloo (Netherlands); Naab, Thorsten, E-mail: richard.mcdermid@mq.edu.au [Max-Planck-Institut für Astrophysik, Karl-Schwarzschild-Str. 1, D-85741 Garching (Germany); and others

    2014-09-10

    We report on empirical trends between the dynamically determined stellar initial mass function (IMF) and stellar population properties for a complete, volume-limited sample of 260 early-type galaxies from the ATLAS{sup 3D} project. We study trends between our dynamically derived IMF normalization α{sub dyn} ≡ (M/L){sub stars}/(M/L){sub Salp} and absorption line strengths, and interpret these via single stellar population-equivalent ages, abundance ratios (measured as [α/Fe]), and total metallicity, [Z/H]. We find that old and alpha-enhanced galaxies tend to have on average heavier (Salpeter-like) mass normalization of the IMF, but stellar population does not appear to be a good predictor of the IMF, with a large range of α{sub dyn} at a given population parameter. As a result, we find weak α{sub dyn}-[α/Fe] and α{sub dyn} –Age correlations and no significant α{sub dyn} –[Z/H] correlation. The observed trends appear significantly weaker than those reported in studies that measure the IMF normalization via the low-mass star demographics inferred through stellar spectral analysis.

  2. Connection between Dynamically Derived Initial Mass Function Normalization and Stellar Population Parameters

    Science.gov (United States)

    McDermid, Richard M.; Cappellari, Michele; Alatalo, Katherine; Bayet, Estelle; Blitz, Leo; Bois, Maxime; Bournaud, Frédéric; Bureau, Martin; Crocker, Alison F.; Davies, Roger L.; Davis, Timothy A.; de Zeeuw, P. T.; Duc, Pierre-Alain; Emsellem, Eric; Khochfar, Sadegh; Krajnović, Davor; Kuntschner, Harald; Morganti, Raffaella; Naab, Thorsten; Oosterloo, Tom; Sarzi, Marc; Scott, Nicholas; Serra, Paolo; Weijmans, Anne-Marie; Young, Lisa M.

    2014-09-01

    We report on empirical trends between the dynamically determined stellar initial mass function (IMF) and stellar population properties for a complete, volume-limited sample of 260 early-type galaxies from the ATLAS3D project. We study trends between our dynamically derived IMF normalization αdyn ≡ (M/L)stars/(M/L)Salp and absorption line strengths, and interpret these via single stellar population-equivalent ages, abundance ratios (measured as [α/Fe]), and total metallicity, [Z/H]. We find that old and alpha-enhanced galaxies tend to have on average heavier (Salpeter-like) mass normalization of the IMF, but stellar population does not appear to be a good predictor of the IMF, with a large range of αdyn at a given population parameter. As a result, we find weak αdyn-[α/Fe] and αdyn -Age correlations and no significant αdyn -[Z/H] correlation. The observed trends appear significantly weaker than those reported in studies that measure the IMF normalization via the low-mass star demographics inferred through stellar spectral analysis.

  3. Pluripotency Genes and Their Functions in the Normal and Aberrant Breast and Brain

    Directory of Open Access Journals (Sweden)

    Tracy Seymour

    2015-11-01

    Full Text Available Pluripotent stem cells (PSCs attracted considerable interest with the successful isolation of embryonic stem cells (ESCs from the inner cell mass of murine, primate and human embryos. Whilst it was initially thought that the only PSCs were ESCs, in more recent years cells with similar properties have been isolated from organs of the adult, including the breast and brain. Adult PSCs in these organs have been suggested to be remnants of embryonic development that facilitate normal tissue homeostasis during repair and regeneration. They share certain characteristics with ESCs, such as an inherent capacity to self-renew and differentiate into cells of the three germ layers, properties that are regulated by master pluripotency transcription factors (TFs OCT4 (octamer-binding transcription factor 4, SOX2 (sex determining region Y-box 2, and homeobox protein NANOG. Aberrant expression of these TFs can be oncogenic resulting in heterogeneous tumours fueled by cancer stem cells (CSC, which are resistant to conventional treatments and are associated with tumour recurrence post-treatment. Further to enriching our understanding of the role of pluripotency TFs in normal tissue function, research now aims to develop optimized isolation and propagation methods for normal adult PSCs and CSCs for the purposes of regenerative medicine, developmental biology, and disease modeling aimed at targeted personalised cancer therapies.

  4. Relating Memory To Functional Performance In Normal Aging to Dementia Using Hierarchical Bayesian Cognitive Processing Models

    Science.gov (United States)

    Shankle, William R.; Pooley, James P.; Steyvers, Mark; Hara, Junko; Mangrola, Tushar; Reisberg, Barry; Lee, Michael D.

    2012-01-01

    Determining how cognition affects functional abilities is important in Alzheimer’s disease and related disorders (ADRD). 280 patients (normal or ADRD) received a total of 1,514 assessments using the Functional Assessment Staging Test (FAST) procedure and the MCI Screen (MCIS). A hierarchical Bayesian cognitive processing (HBCP) model was created by embedding a signal detection theory (SDT) model of the MCIS delayed recognition memory task into a hierarchical Bayesian framework. The SDT model used latent parameters of discriminability (memory process) and response bias (executive function) to predict, simultaneously, recognition memory performance for each patient and each FAST severity group. The observed recognition memory data did not distinguish the six FAST severity stages, but the latent parameters completely separated them. The latent parameters were also used successfully to transform the ordinal FAST measure into a continuous measure reflecting the underlying continuum of functional severity. HBCP models applied to recognition memory data from clinical practice settings accurately translated a latent measure of cognition to a continuous measure of functional severity for both individuals and FAST groups. Such a translation links two levels of brain information processing, and may enable more accurate correlations with other levels, such as those characterized by biomarkers. PMID:22407225

  5. Importance of circulating IGF-1 for normal cardiac morphology, function and post infarction remodeling.

    Science.gov (United States)

    Scharin Täng, M; Redfors, B; Lindbom, M; Svensson, J; Ramunddal, T; Ohlsson, C; Shao, Y; Omerovic, E

    2012-12-01

    IGF-1 plays an important role in cardiovascular homeostasis, and plasma levels of IGF-1 correlate inversely with systolic function in heart failure. It is not known to what extent circulating IGF-1 secreted by the liver and local autocrine/paracrine IGF-1 expressed in the myocardium contribute to these beneficial effects on cardiac function and morphology. In the present study, we used a mouse model of liver-specific inducible deletion of the IGF-1 gene (LI-IGF-1 -/- mouse) in an attempt to evaluate the importance of circulating IGF-I on cardiac morphology and function under normal and pathological conditions, with an emphasis on its regulatory role in myocardial phosphocreatine metabolism. Echocardiography was performed in LI-IGF-1 -/- and control mice at rest and during dobutamine stress, both at baseline and post myocardial infarction (MI). High-energy phosphate metabolites were compared between LI-IGF-1 -/- and control mice at 4 weeks post MI. We found that LI-IGF-1 -/- mice had significantly greater left ventricular dimensions at baseline and showed a greater relative increase in cardiac dimensions, as well as deterioration of cardiac function, post MI. Myocardial creatine content was 17.9% lower in LI-IGF-1 -/- mice, whereas there was no detectable difference in high-energy nucleotides. These findings indicate an important role of circulating IGF-1 in preserving cardiac structure and function both in physiological settings and post MI. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Mood states, sympathetic activity, and in vivo beta-adrenergic receptor function in a normal population.

    Science.gov (United States)

    Yu, Bum-Hee; Kang, Eun-Ho; Ziegler, Michael G; Mills, Paul J; Dimsdale, Joel E

    2008-01-01

    The purpose of this study was to examine the relationship between mood states and beta-adrenergic receptor function in a normal population. We also examined if sympathetic nervous system activity is related to mood states or beta-adrenergic receptor function. Sixty-two participants aged 25-50 years were enrolled in this study. Mood states were assessed using the Profile of Mood States (POMS). Beta-adrenergic receptor function was determined using the chronotropic 25 dose isoproterenol infusion test. Level of sympathetic nervous system activity was estimated from 24-hr urine norepinephrine excretion. Higher tension-anxiety, depression-dejection, and anger-hostility were related to decreased beta-adrenergic receptor sensitivity (i.e., higher chronotropic 25 dose values), but tension-anxiety was the only remaining independent predictor of beta-adrenergic receptor function after controlling for age, gender, ethnicity, and body mass index (BMI). Urinary norepinephrine excretion was unrelated to either mood states or beta-adrenergic receptor function. These findings replicate previous reports that anxiety is related to decreased (i.e., desensitized) beta-adrenergic receptor sensitivity, even after controlling for age, gender, ethnicity, and body mass index.

  7. The regulation of cytoskeletal and liver-specific gene expression during liver regeneration and primary hepatocyte culture

    International Nuclear Information System (INIS)

    Robinson, G.S.

    1989-01-01

    The focus of this dissertation is to determine what role(s) the extracellular matrix and expression of certain cytoskeletal genes play in the regulation of hepatocyte growth and the maintenance of a differential state. The expression of several cytoskeletal and liver-specific genes was examined during liver regeneration and in hepatocyte cultures maintained in a hormonally-defined, serum-free medium and plated on two different matrices: rat tail collagen and the EHS matrix. During liver regeneration and in hepatocytes cultured on rat tail collagen, there was a dramatic increase in tubulin mRNA levels coincident with but not linked to DNA synthesis. The message levels for other cytoskeletal genes similarly increased, while a decrease was observed in the mRNA levels of the liver-specific genes, serum albumin and alpha 1 inhibitor III. Hepatocytes cultured on the EHS matrix resulted in the maintenance of low levels of cytoskeletal gene expression and high levels of liver-specific gene expression, similar to that observed in the normal liver. Results from subcellar fractionation and two-dimensional gel electrophoresis of 35 S-labelled proteins paralleled the results seen at the mRNA level. Preliminary work suggests that microtubule organization may play a role in the expression of the liver-specific genes which encode secreted proteins. These studies, which compare hepatocytes cultured on collagen or the EHS matrix gel, reveal that both cell-cell and cell-matrix interactions play a major role in the maintenance of the differential phenotype in hepatocytes

  8. Normal mitochondrial respiratory function is essential for spatial remote memory in mice

    Directory of Open Access Journals (Sweden)

    Tanaka Daisuke

    2008-12-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA with pathogenic mutations has been found in patients with cognitive disorders. However, little is known about whether pathogenic mtDNA mutations and the resultant mitochondrial respiration deficiencies contribute to the expression of cognitive alterations, such as impairments of learning and memory. To address this point, we used two groups of trans-mitochondrial mice (mito-mice with heteroplasmy for wild-type and pathogenically deleted (Δ mtDNA; the "low" group carried 50% or less ΔmtDNA, and the "high" group carried more than 50% ΔmtDNA. Results Both groups had normal phenotypes for not only spatial learning, but also memory at short retention delays, indicating that ΔmtDNA load did not affect learning and temporal memory. The high group, however, showed severe impairment of memory at long retention delays. In the visual cortex and dentate gyrus of these mice, we observed mitochondrial respiration deficiencies, and reduced Ca2+/calmodulin-dependent kinase II-α (α-CaMKII, a protein important for the establishment of spatial remote memory. Conclusion Our results indicated that normal mitochondrial respiratory function is necessary for retention and consolidation of memory trace; deficiencies in this function due to high loads of pathogenically mutated mtDNA are responsible for the preferential impairment of spatial remote memory.

  9. The effect of irradiation on function in self-renewing normal tissues with differing proliferative organisation

    International Nuclear Information System (INIS)

    Wheldon, T.E.; Michalowski, A.S.

    1982-01-01

    The primary effect of irradiation on self-renewing normal tissues is sterilisation of their proliferative cells, but how this translates into failure of tissue function depends on the mode of organisation of the tissue concerned. It has recently been suggested (Michalowski, 1981) that proliferative normal tissues may be classed as ''hierarchical'' (like haemopoietic tissues) or as ''flexible'' (like liver parenchyma) and that radiation injury to tissue function develops by different pathways in these tissues. Mathematical model studies confirm the different radiation responses of differently organized tissues. Tissues of the ''flexible'' or ''F-type'' category display a variety of novel radiobiological properties, different from those of the more familiar ''hierarchical'' or ''H-type'' tissues. The ''F-type'' responses are strongly influenced by radiation-sterilised (''doomed'') cells, and is is suggested that the role of ''doomed'' cells has been undervalued relative to that of clonogenic survivors. Since ''F-type'' tissues have characteristically low rates of cell renewal, it is possible that these tissues are preferentially responsible for late effects of irradiation in clinical radiotherapy. (author)

  10. HIV Infection Is Associated with Impaired Striatal Function during Inhibition with Normal Cortical Functioning on Functional MRI

    NARCIS (Netherlands)

    du Plessis, Stéfan; Vink, Matthijs; Joska, John A; Koutsilieri, Eleni; Bagadia, Asif; Stein, Dan J; Emsley, Robin

    2015-01-01

    The aim of the present study was to investigate the effect of HIV infection on cortical and subcortical regions of the frontal-striatal system involved in the inhibition of voluntary movement. Functional MRI (fMRI) studies suggest that human immunodeficiency virus (HIV) infection is associated with

  11. Using Force to Probe Single-Molecule Receptor-Cytoskeletal Anchoring Beneath the Surface of a Living Cell

    DEFF Research Database (Denmark)

    Evans, Evan; Kinoshita, Koji

    2007-01-01

    -cytoskeletal unbinding increased exponentially with the level of force, suggesting disruption at a site of single-molecule interaction. Since many important enzymes and signaling molecules are closely associated with a membrane receptor-cytoskeletal linkage, pulling on a receptor could alter interactions among its......The ligation of cell surface receptors often communicates a signal that initiates a cytoplasmic chemical cascade to implement an important cell function. Less well understood is how physical stress applied to a cell surface adhesive bond propagates throughout the cytostructure to catalyze...... or trigger important steps in these chemical processes. Probing the nanoscale impact of pulling on cell surface bonds, we discovered that receptors frequently detach prematurely from the interior cytostructure prior to failure of the exterior adhesive bond [Evans, E., Heinrich, V., Leung, A., and Kinoshita...

  12. Gemfibrozil-induced myositis in a patient with normal renal function.

    Science.gov (United States)

    Hahn, Martin; Sriharan, Kalavally; McFarland, M Shawn

    2010-01-01

    To describe a case of gemfibrozil monotherapy-induced myositis in a patient with normal renal function A 68-year-old white man presented to his primary care clinic complaining of a 6-month history of total body pain. His past medical history was significant for hypertension, diabetes mellitus, hyperlipidemia, gastroesophageal reflux disease, benign prostatic hypertrophy, arthritis, impotence, and pancreatic cancer that required excision of part of his pancreas. His home drug regimen included bupropion 75 mg twice daily, gemfibrozil 600 mg twice daily for the past 8 months, glimiperide 1 mg daily, insulin glargine 5 units at bedtime, insulin aspart 5 units in the evening, lisinopril 10 mg daily, omeprazole 40 mg daily, pregabalin 100 mg daily, and sildenafil 100 mg as needed. Laboratory test results were significant for elevated aspartate aminotransferase (AST) 78 U/L (reference range 15-46 U/L), alanine aminotransferase (ALT) 83 U/L (13-69 U/L), and creatine kinase (CK) 3495 U/L (55-170 U/L). Serum creatinine was normal at 1.19 mg/dL. The physician determined that the elevated CK indicated myositis secondary to gemfibrozil use, and gemfibrozil was subsequently discontinued. The patient returned 1 week later to repeat the laboratory tests. Results were CK 220 U/L, AST 26 U/L, ALT 43 U/L, and serum creatinine 1.28 mg/dL. The patient was asked to return in 3 weeks to repeat the laboratory tests. At that time, CK had continued to decrease to 142 U/L, and the AST and ALT had returned to normal, at 22 and 29 U/L, respectively. The patient reported complete resolution of total body pain 3 weeks after discontinuation of gemfibrozil. Follow-up 5 weeks after discontinuation revealed no change compared to the 3-week follow-up. Myositis most often produces weakness and elevated CK levels more than 10 times the upper limit of normal. The risk of developing myositis, myopathy, or rhabdomyolysis is low (1%) when fibrates such as gemfibrozil are used as monotherapy. Evaluation of

  13. An accurate higher order displacement model with shear and normal deformations effects for functionally graded plates

    International Nuclear Information System (INIS)

    Jha, D.K.; Kant, Tarun; Srinivas, K.; Singh, R.K.

    2013-01-01

    Highlights: • We model through-thickness variation of material properties in functionally graded (FG) plates. • Effect of material grading index on deformations, stresses and natural frequency of FG plates is studied. • Effect of higher order terms in displacement models is studied for plate statics. • The benchmark solutions for the static analysis and free vibration of thick FG plates are presented. -- Abstract: Functionally graded materials (FGMs) are the potential candidates under consideration for designing the first wall of fusion reactors with a view to make best use of potential properties of available materials under severe thermo-mechanical loading conditions. A higher order shear and normal deformations plate theory is employed for stress and free vibration analyses of functionally graded (FG) elastic, rectangular, and simply (diaphragm) supported plates. Although FGMs are highly heterogeneous in nature, they are generally idealized as continua with mechanical properties changing smoothly with respect to spatial coordinates. The material properties of FG plates are assumed here to vary through thickness of plate in a continuous manner. Young's modulii and material densities are considered to be varying continuously in thickness direction according to volume fraction of constituents which are mathematically modeled here as exponential and power law functions. The effects of variation of material properties in terms of material gradation index on deformations, stresses and natural frequency of FG plates are investigated. The accuracy of present numerical solutions has been established with respect to exact three-dimensional (3D) elasticity solutions and the other models’ solutions available in literature

  14. Severe hyposmia and aberrant functional connectivity in cognitively normal Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Noritaka Yoneyama

    Full Text Available Severe hyposmia is a risk factor of dementia in Parkinson's disease (PD, while the underlying functional connectivity (FC and brain volume alterations in PD patients with severe hyposmia (PD-SH are unclear.We examined voxel-based morphometric and resting state functional magnetic resonance imaging findings in 15 cognitively normal PD-SH, 15 cognitively normal patients with PD with no/mild hyposmia (PD-N/MH, and 15 healthy controls (HCs.Decreased gray matter volume (GMV was observed in the bilateral cuneus, right associative visual area, precuneus, and some areas in anterior temporal lobes in PD-SH group compared to HCs. Both the PD-SH and PD-N/MH groups showed increased GMV in the bilateral posterior insula and its surrounding regions. A widespread significant decrease in amygdala FC beyond the decreased GMV areas and olfactory cortices were found in the PD-SH group compared with the HCs. Above all, decreased amygdala FC with the inferior parietal lobule, lingual gyrus, and fusiform gyrus was significantly correlated with both reduction of Addenbrooke's Cognitive Examination-Revised scores and severity of hyposmia in all participants. Canonical resting state networks exhibited decreased FC in the precuneus and left executive control networks but increased FC in the primary and high visual networks of patients with PD compared with HCs. Canonical network FC to other brain regions was enhanced in the executive control, salience, primary visual, and visuospatial networks of the PD-SH.PD-SH showed extensive decreased amygdala FC. Particularly, decreased FC between the amygdala and inferior parietal lobule, lingual gyrus, and fusiform gyrus were associated with the severity of hyposmia and cognitive performance. In contrast, relatively preserved canonical networks in combination with increased FC to brain regions outside of canonical networks may be related to compensatory mechanisms, and preservation of brain function.

  15. Progressive supranuclear palsy: neuronal and glial cytoskeletal pathology in the higher order processing autonomic nuclei of the lower brainstem.

    Science.gov (United States)

    Rüb, U; Del Tredici, K; Schultz, C; de Vos, R A I; Jansen Steur, E N H; Arai, K; Braak, H

    2002-02-01

    The medial and lateral parabrachial nuclei (MPB, LPB), the gigantocellular reticular nucleus (GI), the raphes magnus (RMG) and raphes obscurus nuclei (ROB), as well as the intermediate reticular zone (IRZ) represent pivotal subordinate brainstem centres, all of which control autonomic functions. In this study, we investigated the occurrence and severity of the neuronal and glial cytoskeletal pathology in these six brainstem nuclei from 17 individuals with clinically diagnosed and neuropathologically confirmed progressive supranuclear palsy (PSP). The association between the severity of the pathology and the duration of the disease was investigated by means of correlation analysis. The brainstem nuclei in all of the PSP cases were affected by the neuronal cytoskeletal pathology, with the IRZ and GI regularly showing severe involvement, the MPB, RMG, and ROB marked involvement, and the LPB mild involvement. In the six nuclear greys studied, glial cells undergo alterations of their cytoskeleton on an irregular basis, whereby diseased oligodendrocytes predominantly presented as coiled bodies and affected astrocytes as thorn-shaped astrocytes. In all six nuclei, the severity of the neuronal or glial cytoskeletal pathology showed no correlation with the duration of PSP. In view of their functional role, the neuronal pathology in the nuclei studied offers a possible explanation for the autonomic dysfunctions that eventually develop in the course of PSP.

  16. Fracture transmissivity as a function of normal and shear stress: first results in Opalinus Clay

    International Nuclear Information System (INIS)

    Cuss, R.J.; Milodowski, A.; Noy, D.J.; Harrington, J.F.

    2010-01-01

    Document available in extended abstract form only. Rock-mass failure around openings is usually observed in the form of a highly complex fracture network (EDZ), which is heterogeneous in distribution around a circular tunnel opening because of the heterogeneous stress distribution. The orientation of stress with respect to the fracture network is known to be important. The complex heterogeneous stress trajectory and heterogeneous fracture network results in a broad range of stresses and stress directions acting on the open fracture network. During the open stage of a repository, stress will slowly alter as shear movements occur along the fractures, as well as other time-dependent phenomena. As the repository is back filled, the stress field is further altered as the backfill settles and changes volume because of re-saturation. Therefore, a complex and wide ranging stress regime and stress history will result. In a purely mechanical sense, fracture transmissivity is a function of normal stress, shear stress, and fracture aperture. The Selfrac test from Mont Terri showed the change in transmissivity with effective normal stress. This work showed that fracture transmissivity decreased with increasing normal load and that an effective normal stress of 2.5 MPa is sufficient to yield a transmissivity similar to that seen in intact Opalinus clay (OPA). Therefore fracture closure because of normal stresses has been proven to be a quite efficient mechanism in OPA. A new shear rig was designed to investigate the detail of fracture transmissivity in OPA. The experimental configuration uses two prepared blocks that are 60 x 60 mm in size and approximately 20 mm thick. The first test sample had machine ground surfaces in contact with each other, with pore fluid being delivered through the centre of the top block directly to the fracture surface. The experimental programme included two distinct stages. In the first normal load was altered to investigate fracture transmissivity

  17. Partition functions. I. Improved partition functions and thermodynamic quantities for normal, equilibrium, and ortho and para molecular hydrogen

    Science.gov (United States)

    Popovas, A.; Jørgensen, U. G.

    2016-11-01

    Context. Hydrogen is the most abundant molecule in the Universe. Its thermodynamic quantities dominate the physical conditions in molecular clouds, protoplanetary disks, etc. It is also of high interest in plasma physics. Therefore thermodynamic data for molecular hydrogen have to be as accurate as possible in a wide temperature range. Aims: We here rigorously show the shortcomings of various simplifications that are used to calculate the total internal partition function. These shortcomings can lead to errors of up to 40 percent or more in the estimated partition function. These errors carry on to calculations of thermodynamic quantities. Therefore a more complicated approach has to be taken. Methods: Seven possible simplifications of various complexity are described, together with advantages and disadvantages of direct summation of experimental values. These were compared to what we consider the most accurate and most complete treatment (case 8). Dunham coefficients were determined from experimental and theoretical energy levels of a number of electronically excited states of H2. Both equilibrium and normal hydrogen was taken into consideration. Results: Various shortcomings in existing calculations are demonstrated, and the reasons for them are explained. New partition functions for equilibrium, normal, and ortho and para hydrogen are calculated and thermodynamic quantities are reported for the temperature range 1-20 000 K. Our results are compared to previous estimates in the literature. The calculations are not limited to the ground electronic state, but include all bound and quasi-bound levels of excited electronic states. Dunham coefficients of these states of H2 are also reported. Conclusions: For most of the relevant astrophysical cases it is strongly advised to avoid using simplifications, such as a harmonic oscillator and rigid rotor or ad hoc summation limits of the eigenstates to estimate accurate partition functions and to be particularly careful when

  18. Mesiodistal angulation of the lateral teeth to the functional occlusal plane in normal occlusions

    Directory of Open Access Journals (Sweden)

    Hiroshi Ueda

    2016-01-01

    Full Text Available Introduction: Crowding is a malocclusion with irregularly positioned teeth caused by arch length discrepancy (ALD. Its incidence is high compared with the various malocclusions. In a previous study the crowns of the maxillary lateral teeth had erupted mesially in relation to the functional occlusal plane (FOP in patients with Angle Class I malocclusion and highly erupted canines, which had been uprighted by non-extraction orthodontic treatment, yet these results were based on only two cases evaluated by using plaster models. Therefore, the aim of this study was to assess the mesiodistal angulations of both maxillary and mandibular teeth relative to the FOP in normal occlusion by means of cephalograms and identifying the teeth axial factors contributing to the normal dentitions with the least ALD. Materials and Methods: Thirty Japanese young adult patients (6 males, 24 females with normal occlusion were selected to participate in this study; cephalograms were procured from each and the FOP was used as a reference plane for measuring the changes in the axial angulation along with other indicators of vertical growth. Results: Progressive mesial tipping of the maxillary lateral teeth was observed. First premolars tended to express this more than the second premolars but the tipping values were roughly 90° relative to the FOP on the first molars. Conclusion: The maxillary lateral teeth are more mesially angulated compared to the mandibular ones relative to the FOP. Furthermore, progressive mesial tipping of the maxillary lateral teeth was detected, of which axial angulations were significantly correlated to each other, in spite the mandibular premolars and molars being angulated in a similar fashion.

  19. Aerobic Glycolysis Is Essential for Normal Rod Function and Controls Secondary Cone Death in Retinitis Pigmentosa.

    Science.gov (United States)

    Petit, Lolita; Ma, Shan; Cipi, Joris; Cheng, Shun-Yun; Zieger, Marina; Hay, Nissim; Punzo, Claudio

    2018-05-29

    Aerobic glycolysis accounts for ∼80%-90% of glucose used by adult photoreceptors (PRs); yet, the importance of aerobic glycolysis for PR function or survival remains unclear. Here, we further established the role of aerobic glycolysis in murine rod and cone PRs. We show that loss of hexokinase-2 (HK2), a key aerobic glycolysis enzyme, does not affect PR survival or structure but is required for normal rod function. Rods with HK2 loss increase their mitochondrial number, suggesting an adaptation to the inhibition of aerobic glycolysis. In contrast, cones adapt without increased mitochondrial number but require HK2 to adapt to metabolic stress conditions such as those encountered in retinitis pigmentosa, where the loss of rods causes a nutrient shortage in cones. The data support a model where aerobic glycolysis in PRs is not a necessity but rather a metabolic choice that maximizes PR function and adaptability to nutrient stress conditions. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  20. Potential influence of the phthalates on normal liver function and cardiometabolic risk in males.

    Science.gov (United States)

    Milošević, Nataša; Milić, Nataša; Živanović Bosić, Dragana; Bajkin, Ivana; Perčić, Ivanka; Abenavoli, Ludovico; Medić Stojanoska, Milica

    2017-12-13

    Phthalates are ubiquitous environmental contaminants, massively used in industry as plasticizers and additives in cosmetics, which may impair the human endocrine system inducing fertility problems, respiratory diseases, obesity, and neuropsychological disorders. The aim of this study was to examine the influence of the monoethyl phthalate (MEP) and mono-(2-ethylhexyl) phthalate (MEHP) on the liver function and cardiometabolic risk factors in males. In this research, 102 male participants (51 normal weight and 51 overweight/obese) were enrolled and examined for phthalate metabolites exposure in urine samples after 12 h of fasting. MEP was found in 28.43% (29/102) volunteers, while MEHP was detected among 20.59% (21/102) participants. Statistically significant increment in transaminase serum levels was observed in MEP-positive normal weight subgroup. Linear correlation was obtained between MEP concentration in urine samples and triglyceride (TG) serum levels (r 2  = 0.33; p adiposity index (VAI) (r 2  = 0.41; p HDL) ratio (r 2  = 0.40, p body mass index (p = 0.03) compared to MEHP-negative participants. Urine MEHP concentrations were negatively correlated with HDL serum levels (r 2  = 0.31; p correlated with increased TG and decreased HDL cholesterol serum levels and associated with indicators of cardiometabolic risk and insulin resistance as LAP and VAI.

  1. Effects of dopamine on renal haemodynamics tubular function and sodium excretion in normal humans

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal

    1998-01-01

    The renal functional changes following infusion of dopamine are well documented. The most pronounced effect is the increase in renal blood flow and a marked natriuretic response. Due to its specific renal effects, dopamine has become one of the most frequently used drugs in the treatment...... of critically ill patients with low cardiac output states and/or acute oliguric renal failure. Pharmacological effects of dopamine are dose dependent. Low doses of dopamine predominantly stimulate dopaminergic receptors, but with increasing doses actions secondary to stimulation of adrenergic beta(1) and alpha...... indirectly may dilate the vessels by inhibition of norepinephrine release. Consistent with previous results in animals, the present haemodynamic studies revealed that dopamine in normal subjects elicits a dose dependent biphasic effect on the mean arterial blood pressure. With 1 and 2 micrograms...

  2. Overall renal and tubular function during infusion of amino acids in normal man

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Hansen, J M; Ladefoged, S D

    1990-01-01

    sodium concentration] increased by 40% (P less than 0.001). Plasma renin concentration did not change significantly. 4. The results suggest that amino acids increase GFR by a primary effect on renal haemodynamics or, less likely, by reducing the signal to the tubuloglomerular feedback mechanism......1. Amino acids have been used to test renal reserve filtration capacity. Previous studies suggest that amino acids increase glomerular filtration rate (GFR) by reducing distal tubular flow and tubuloglomerular feedback activity. 2. Glomerular function and the renal tubular handling of sodium during...... infusion of amino acids was studied in 12 normal volunteers. 3. Clearance of sodium (CNa) was unchanged. Effective renal plasma flow increased slightly, but significantly, by 9% (P less than 0.05). GFR was increased by 13% (P less than 0.001). Clearance of lithium (CLi) (used as an index of proximal...

  3. Circadian Rhythm Neuropeptides in Drosophila: Signals for Normal Circadian Function and Circadian Neurodegenerative Disease.

    Science.gov (United States)

    He, Qiankun; Wu, Binbin; Price, Jeffrey L; Zhao, Zhangwu

    2017-04-21

    Circadian rhythm is a ubiquitous phenomenon in many organisms ranging from prokaryotes to eukaryotes. During more than four decades, the intrinsic and exogenous regulations of circadian rhythm have been studied. This review summarizes the core endogenous oscillation in Drosophila and then focuses on the neuropeptides, neurotransmitters and hormones that mediate its outputs and integration in Drosophila and the links between several of these (pigment dispersing factor (PDF) and insulin-like peptides) and neurodegenerative disease. These signaling molecules convey important network connectivity and signaling information for normal circadian function, but PDF and insulin-like peptides can also convey signals that lead to apoptosis, enhanced neurodegeneration and cognitive decline in flies carrying circadian mutations or in a senescent state.

  4. Kidney function in normal man during short-term growth hormone infusion

    DEFF Research Database (Denmark)

    Parving, H H; Noer, I; Mogensen, C E

    1978-01-01

    Kidney function was studied in 9 normal males before and during a 2 h growth hormone (GH) infusion of 50 ng/kg/min. The following variables were measured during each 20 min clearance period: glomerular filtration rate, GFR, effective renal plasma flow, RPF (steady state infusion technique...... with urinary collections using [125I]iothalamate and [131I]iodohippurate), and urinary albumin and beta2-microglobulin excretion rates (radioimmunoassays). The GH infusion resulted in a 10-fold increase in plasma GH concentration. All the above mentioned variables remained practically unchanged during...... the infusion except for a small (-5%) but significant decrease in renal plasma flow (P less than 0.01). Our negative results contrast to the findings of increased GFR and RPF during prolonged GH administration and suggest that GH requires several hours or days for its renal effects to become manifest....

  5. Intrathoracic toxic thyroid nodule causing hyperthyroidism with a multinodular normal functional cervical thyroid gland

    International Nuclear Information System (INIS)

    Serim, Burcu Dirlik; Korkmaz, Ulku; Can, Unal; Altun, Gulay Durmus

    2016-01-01

    Radionuclide scintigraphy with I-131 and Tc-99m pertechnetate ( 99 mTc0 4 ) has been widely used in detecting toxic nodules. Intrathoracic goiter usually presents as an anterior mediastinal mass. Mostly the connection between intrathoracic mass and the cervical thyroid gland is clearly and easily identified occurring as a result of inferior extension of thyroid tissue in the neck, which is called as secondary intrathoracic goiter. Completely separated, aberrant or in other words primary intrathoracic goiters arise as a result of abnormal embryologic migration of ectopic thyroid closely associated with aortic sac and descend into the mediastinum. Intrathoracic goiters are generally nontoxic nodules existing with mass effect without causing hyperthyroidism. However, mostly reported cases had enlarged thyroid glands in the neck. This report demonstrates the usefulness of I-131 and 99 mTc0 4 scintigraphy for detecting intrathoracic goiter causing hyperthyroidism with a normal functioned cervical thyroid gland

  6. Glutamine supplementation maintains intramuscular glutamine concentrations and normalizes lymphocyte function in infected early weaned pigs.

    Science.gov (United States)

    Yoo, S S; Field, C J; McBurney, M I

    1997-11-01

    Numerous studies in humans and rats have shown that glutamine supplementation during stressful conditions has favorable outcomes. However, the requirements for glutamine during weaning are unknown. Thus, the effects of glutamine supplementation in healthy and infected weaned pigs were investigated. At 21 d of age, pigs were weaned to an elemental diet supplemented with glutamine (+Gln) or an isonitrogenous diet containing nonessential amino acids (-Gln). At 26 d of age, pigs were intraperitoneally injected with Escherichia coli (+Ecoli) or buffered saline (-Ecoli) and killed at 28 d of age. Infection decreased (P Ecoli+Gln pigs were greater (P Ecoli-Gln pigs and not different than those of noninfected pigs. Hence, glutamine supplementation maintained muscular glutamine concentrations and normalized lymphocyte function in infected pigs.

  7. Functional magnetic resonance imaging of the normal and abnormal visual system in early life

    DEFF Research Database (Denmark)

    Born, A.P.; Miranda Gimenez-Ricco, Maria Jo; Rostrup, Egill

    2000-01-01

    in very young infants and in infants with brain damage. We examined 15 preterm infants, 12 children suspected of having a cerebral visual impairment and 10 children with a normal visual system, all of whom were either spontaneously asleep or sedated with chloral hydrate. Cortical response to stroboscopic...... showed a signal decrease. The activated cortical volumes showed a linear relation to age for healthy children younger than 90 weeks PMA, but were small in children with visual impairment. In two children with unilateral damage to the optic radiations, activation was strongly asymmetrical with greatest......Functional magnetic resonance imaging (fMRI) in young children may provide information about the development of the visual cortex, and may have predictive value for later visual performance. The purpose of this study was to evaluate the usefulness of fMRI for examining cerebral processing of vision...

  8. Trimester specific reference intervals for thyroid function tests in normal Indian pregnant women.

    Science.gov (United States)

    Sekhri, Tarun; Juhi, Juhi Agarwal; Wilfred, Reena; Kanwar, Ratnesh S; Sethi, Jyoti; Bhadra, Kuntal; Nair, Sirimavo; Singh, Satveer

    2016-01-01

    Accurate assessment of thyroid function during pregnancy is critical, for initiation of thyroid hormone therapy, as well as for adjustment of thyroid hormone dose in hypothyroid cases. We evaluated pregnant women who had no past history of thyroid disorders and studied their thyroid function in each trimester. 86 normal pregnant women in the first trimester of pregnancy were selected for setting reference intervals. All were healthy, euthyroid and negative for thyroid peroxidase antibody (TPOAb). These women were serially followed throughout pregnancy. 124 normal nonpregnant subjects were selected for comparison. Thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and anti-TPO were measured using Roche Elecsys 1010 analyzer. Urinary iodine content was determined by simple microplate method. The 2.5th and 97.5th percentiles were calculated as the reference intervals for thyroid hormone levels during each trimester. SPSS (version 14.0, SPSS Inc., Chicago, IL, USA) was used for data processing and analysis. The reference intervals for the first, second and third trimesters for the following parameters: TSH 0.09-6.65, 0.51-6.66, 0.91-4.86 µIU/mL, FT4 9.81-18.53, 8.52-19.43, 7.39-18.28 pM/L and FT3 3.1-6.35, 2.39-5.12, 2.57-5.68 pM/L respectively. Thyroid hormone concentrations significantly differed during pregnancy at different stages of gestation. The pregnant women in the study had median urinary iodine concentration of 150-200 µg/l during each trimester. The trimester-specific reference intervals for thyroid tests during pregnancy have been established for pregnant Indian women serially followed during pregnancy using 2.5th and 97.5th percentiles.

  9. NORMAL VALUES AND FACTORS AFFECTING FUNCTIONAL REACH TEST IN SAUDI ARABIA SCHOOL CHILDREN WITH TYPICAL DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Hatem A. Emara

    2015-10-01

    Full Text Available Background: The most critical feature of motor development is the ability to balance the body in sitting or standing. Impaired balance limits a child’s ability to recover from unexpected threats to stability. The functional reach test (FRT defines the maximal distance an individual is able to reach forward beyond arm’s length in a standing position without loss of balance, taking a step, or touching the wall. The Purpose of this study was to establish the normal values for FRT in Saudi Arabia school children with typical development and to study the correlation of anthropometric measures with FRT values. Methods: This cross-sectional study was conducted in Almadinah Almonawarah, Kingdom of Saudi Arabia. A total of 280 children without disabilities aged 6 to 12 years were randomly selected. Functional reach was assessed by having subjects extend their arms to 90 degrees and reach as far forward as they could without taking a step. Reach distance was recorded by noting the beginning and final position of the subject's extended arm parallel to a yard stick attached to the wall. Three successive trials of FRT were performed and the mean of the three trials was calculated. Pearson product moment correlation was used to examine the association of FR to age, and anthropometric measures. Results: Normal mean values of FR ranged from 24.2cm to 33.95cm. Age, height and weight significantly correlate with FRT. Conclusion: The FRT is a feasible test to examine the balance of 6-12 year-old children. FRT may be useful for detecting balance impairment, change in balance performance over time.

  10. Effect of laryngeal anesthesia on pulmonary function testing in normal subjects.

    Science.gov (United States)

    Kuna, S T; Woodson, G E; Sant'Ambrogio, G

    1988-03-01

    Pulmonary function tests (PFT) were performed on 11 normal subjects before and after topical anesthesia of the larynx. The PFT consisted of flow volume loops and body box determinations of functional residual capacity and airway resistance, each performed in triplicate. After the first set of tests, cotton pledgets soaked in 4% lidocaine were held in the pyriform sinuses for 2 min to block the superior laryngeal nerves. In addition, 1.5 ml of 10% cocaine was dropped on the vocal cords via indirect laryngoscopy. PFT were repeated 5 min after anesthesia. Besides routine analysis of the flow volume loops, areas under the inspiratory (Area I) and expiratory (Area E) portions of the loops were calculated by planimetry. Area I, peak inspiratory flow (PIF), as well as forced inspiratory flow at 25, 50, and 75% forced vital capacity (FVC), decreased after anesthesia. Peak expiratory flow decreased after anesthesia, but Area E and forced expiratory flow at 25, 50, and 75% FVC were unchanged. This protocol also was performed in 12 normal subjects with isotonic saline being substituted for the lidocaine and cocaine. In this group, no significant differences were observed when flow volume loop parameters were compared before and after topical application of saline. In 5 spontaneously breathing anesthetized dogs, posterior cricoarytenoid muscle and afferent superior laryngeal nerve activity were recorded before and after laryngeal anesthesia performed with the same procedure used in the human subjects. Laryngeal anesthesia resulted in a substantial decrease or a complete disappearance of afferent SLN activity recorded during unobstructed and obstructed respiration. The data suggest that laryngeal receptors help modulate upper airway patency in man.

  11. Cholera toxin can catalyze ADP-ribosylation of cytoskeletal proteins

    International Nuclear Information System (INIS)

    Kaslow, H.R.; Groppi, V.E.; Abood, M.E.; Bourne, H.R.

    1981-01-01

    Cholera toxin catalyzes transfer of radiolabel from [ 32 P]NAD + to several peptides in particulate preparations of human foreskin fibroblasts. Resolution of these peptides by two-dimensional gel electrophoresis allowed identification of two peptides of M/sub r/ = 42,000 and 52,000 as peptide subunits of a regulatory component of adenylate cyclase. The radiolabeling of another group of peptides (M/sub r/ = 50,000 to 65,000) suggested that cholera toxin could catalyze ADP-ribosylation of cytoskeletal proteins. This suggestion was confirmed by showing that incubation with cholera toxin and [ 32 P]NAD + caused radiolabeling of purified microtubule and intermediate filament proteins

  12. Assessment of Eustachian tube function in patients with tympanic membrane retraction and in normal subjects.

    Science.gov (United States)

    Canali, Inesângela; Petersen Schmidt Rosito, Letícia; Siliprandi, Bruno; Giugno, Cláudia; Selaimen da Costa, Sady

    The diagnosis of Eustachian tube dysfunctions is essential for better understanding of the pathogenesis of chronic otitis media. A series of tests to assess tube function are described in the literature; however, they are methodologically heterogeneous, with differences ranging from application protocols to standardization of tests and their results. To evaluate the variation in middle ear pressure in patients with tympanic membrane retraction and in normal patients during tube function tests, as well as to evaluate intra-individual variation between these tests. An observational, contemporary, cross-sectional study was conducted, in which the factor under study was the variation in middle ear pressure during tube function tests (Valsalva maneuver, sniff test, Toynbee maneuver) in healthy patients and in patients with mild and moderate/severe tympanic retraction. A total of 38 patients (76 ears) were included in the study. Patients underwent tube function tests at two different time points to determine pressure measurements after each maneuver. Statistical analysis was performed using SPSS software, version 18.0, considering p-values <0.05 as statistically significant. Mean (standard deviation) age was 11 (2.72) years; 55.3% of patients were male and 44.7% female. The prevalence of type A tympanogram was higher among participants with healthy ears and those with mild retraction, whereas type C tympanograms were more frequent in the moderate/severe retraction group. An increase in middle ear pressure was observed during the Valsalva maneuver at the first time point evaluated in all three groups of ears (p=0.012). The variation in pressure was not significant either for the sniff test or for the Toynbee maneuver at the two time points evaluated (p≥0.05). Agreement between measurements obtained at the two different time points was weak to moderate for all tests in all three groups of ears, and the variations in discrepancy between measurements were higher in ears

  13. Normal differential renal function does not indicate a normal kidney after partial ureteropelvic obstruction and subsequent relief in 2-week-old piglets

    Energy Technology Data Exchange (ETDEWEB)

    Dissing, Thomas H.; Mikkelsen, Mette Marie; Pedersen, Michael; Froekiaer, Joergen; Djurhuus, Jens Christian [University of Aarhus, Institute of Clinical Medicine, Aarhus (Denmark); Eskild-Jensen, Anni [Aarhus University Hospital, Department of Nuclear Medicine, Aarhus Sygehus, Aarhus (Denmark); Gordon, Isky [University College London, Institute of Child Health, London (United Kingdom); University College London, Radiology and Physics Unit, Institute of Child Health, London (United Kingdom)

    2008-09-15

    We investigated the functional consequences of relieving ureteric obstruction in young pigs with experimental hydronephrosis (HN) induced by partial unilateral ureteropelvic obstruction. Three groups of animals were followed from the age of 2 weeks to the age of 14 weeks: Eight animals had severe or grades 3-4 HN throughout the study. Six animals had relief of the obstruction after 4 weeks. Six animals received sham operations at both ages. Morphological and functional examinations were performed at age 6 weeks and again at age 14 weeks and consisted of magnetic resonance imaging (MRI), technetium-diethylenetriaminepentaaceticacid ({sup 99m}Tc-DTPA) renography, renal technetium-dimercaptosuccinicacid ({sup 99m}Tc-DMSA) scintigraphy, and glomerular filtration rate (GFR) measurement. After relief of the partial obstruction, there was reduction of the pelvic diameter and improvement of urinary drainage. Global and relative kidney function was not significantly affected by either obstruction or its relief. Renal {sup 99m}Tc-DMSA scintigraphy showed a change in both the appearance of the kidney and a change in the distribution within kidneys even after relief of obstruction. This study shows that partial ureteric obstruction in young pigs may be associated with little effect on global and differential kidney function. However, even after relief of HN, the distribution of {sup 99m}Tc-DMSA in the kidney remains abnormal suggesting that a normal differential renal function may not represent a normal kidney. (orig.)

  14. Antacid-induced hypermagnesemia in a patient with normal renal function and bowel obstruction.

    Science.gov (United States)

    McLaughlin, S A; McKinney, P E

    1998-03-01

    To report a case of severe hypermagnesemia caused by magnesium hydroxide in a woman with normal renal function. A 42-year-old Hispanic woman with schizophrenia and bipolar affective disorder was transported from jail to the emergency department with confusion, abdominal pain, vomiting, and constipation. She had been treated in jail with magnesium hydroxide, ordered as milk of magnesia 30 mL po each night and Maalox 30 mL po three times daily. Additional medications included lithium carbonate 300 mg po three times daily, chlorpromazine 150 mg po three times daily, benztropine mesylate 1 mg po twice daily, and docusate sodium 100 mg po each morning. Her temperature was 35.1 degrees C, blood pressure 108/58 mm Hg, heart rate 112 beats/min, and respiratory rate 24 breaths/min. She would respond only briefly to voice or painful stimuli. Her abdomen was distended and diffusely tender. Laboratory tests included serum magnesium concentration 9.1 mEq/L (normal 1.3-2), blood urea nitrogen 16 mg/dL (8-22), creatinine 0.9 mg/dL (0.5-1.1), calcium 3.9 mEq/L (4.2-5.2), and lithium 1.0 mEq/L. A laparotomy was performed, and an adhesive band from a previous oophorectomy was found to be compressing the sigmoid colon. Hypermagnesemia, hypothermia, and hypotension continued in the intensive care unit. Despite successful treatment of the hypermagnesemia with calcium, intravenous fluids, and furosemide, the patient's cardiac rhythm degenerated into fatal, pulseless electrical activity on postoperative day 2. This case of severe hypermagnesemia from magnesium hydroxide ingestion illustrates many of the risk factors for hypermagnesemia in patients with normal renal function. People using magnesium-containing medications for relief of gastrointestinal distress may be at increased risk for hypermagnesemia. A brief review of magnesium physiology, clinical effects, and treatment is provided. Frequent use of the laboratory to identify hypermagnesemia is encouraged because it is often a

  15. An accurate higher order displacement model with shear and normal deformations effects for functionally graded plates

    Energy Technology Data Exchange (ETDEWEB)

    Jha, D.K., E-mail: dkjha@barc.gov.in [Civil Engineering Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Kant, Tarun [Department of Civil Engineering, Indian Institute of Technology Bombay, Powai, Mumbai 400 076 (India); Srinivas, K. [Civil Engineering Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Singh, R.K. [Reactor Safety Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)

    2013-12-15

    Highlights: • We model through-thickness variation of material properties in functionally graded (FG) plates. • Effect of material grading index on deformations, stresses and natural frequency of FG plates is studied. • Effect of higher order terms in displacement models is studied for plate statics. • The benchmark solutions for the static analysis and free vibration of thick FG plates are presented. -- Abstract: Functionally graded materials (FGMs) are the potential candidates under consideration for designing the first wall of fusion reactors with a view to make best use of potential properties of available materials under severe thermo-mechanical loading conditions. A higher order shear and normal deformations plate theory is employed for stress and free vibration analyses of functionally graded (FG) elastic, rectangular, and simply (diaphragm) supported plates. Although FGMs are highly heterogeneous in nature, they are generally idealized as continua with mechanical properties changing smoothly with respect to spatial coordinates. The material properties of FG plates are assumed here to vary through thickness of plate in a continuous manner. Young's modulii and material densities are considered to be varying continuously in thickness direction according to volume fraction of constituents which are mathematically modeled here as exponential and power law functions. The effects of variation of material properties in terms of material gradation index on deformations, stresses and natural frequency of FG plates are investigated. The accuracy of present numerical solutions has been established with respect to exact three-dimensional (3D) elasticity solutions and the other models’ solutions available in literature.

  16. Distinguishing patients with Parkinson's disease subtypes from normal controls based on functional network regional efficiencies.

    Directory of Open Access Journals (Sweden)

    Delong Zhang

    Full Text Available Many studies have demonstrated that the pathophysiology and clinical symptoms of Parkinson's disease (PD are inhomogeneous. However, the symptom-specific intrinsic neural activities underlying the PD subtypes are still not well understood. Here, 15 tremor-dominant PD patients, 10 non-tremor-dominant PD patients, and 20 matched normal controls (NCs were recruited and underwent resting-state functional magnetic resonance imaging (fMRI. Functional brain networks were constructed based on randomly generated anatomical templates with and without the cerebellum. The regional network efficiencies (i.e., the local and global efficiencies were further measured and used to distinguish subgroups of PD patients (i.e., with tremor-dominant PD and non-tremor-dominant PD from the NCs using linear discriminant analysis. The results demonstrate that the subtype-specific functional networks were small-world-organized and that the network regional efficiency could discriminate among the individual PD subgroups and the NCs. Brain regions involved in distinguishing between the study groups included the basal ganglia (i.e., the caudate and putamen, limbic regions (i.e., the hippocampus and thalamus, the cerebellum, and other cerebral regions (e.g., the insula, cingulum, and calcarine sulcus. In particular, the performances of the regional local efficiency in the functional network were better than those of the global efficiency, and the performances of global efficiency were dependent on the inclusion of the cerebellum in the analysis. These findings provide new evidence for the neurological basis of differences between PD subtypes and suggest that the cerebellum may play different roles in the pathologies of different PD subtypes. The present study demonstrated the power of the combination of graph-based network analysis and discrimination analysis in elucidating the neural basis of different PD subtypes.

  17. Renal function evaluation in the aged with normal blood pressure and high blood pressure

    International Nuclear Information System (INIS)

    Jacob Filho, W.; Carvalho Filho, E.T. de; Papaleo Netto, M.; Baptista, M.C.

    1986-01-01

    Thirty-four patients older than 65 years were divided into two groups according to their ages: I - 66 to 74 years (17 patients), II - 75 and over (17 patients). These elderly patients were also divided according to their arterial blood pressure level (BP): A - normal BP (14 patients), B high BP (20 patients). None of these patients presented any other disease that could affect kidney function, nor have used drugs that could interfere on the BP or on the kidney function. Glomerular filtration rate (GFR) and effective renal plasmatic flow (ERPF) were analysed by radioisotopic techniques. Furthermore the filtration fraction (FF) was evaluated by the GFR/ERPF ratio. The observed GFR, ERPF and FF variations in the age groups or in normotensive and hypertensive patients were not significant, but we could assume that the physiopathological mechanisms that cause a decreased GFR in consequence of age or of systemic hypertension could be of different origins. Thus in the old hypertensive patients, alterations in the autoregulated hemodynamic mechanism could occur. (author) [pt

  18. Structural and functional changes associated with normal and abnormal fundus autofluorescence in patients with retinitis pigmentosa.

    Science.gov (United States)

    Greenstein, Vivienne C; Duncker, Tobias; Holopigian, Karen; Carr, Ronald E; Greenberg, Jonathan P; Tsang, Stephen H; Hood, Donald C

    2012-02-01

    To analyze the structure and visual function of regions bordering the hyperautofluorescent ring/arcs in retinitis pigmentosa. Twenty-one retinitis pigmentosa patients (21 eyes) with rings/arcs and 21 normal individuals (21 eyes) were studied. Visual sensitivity in the central 10° was measured with microperimetry. Retinal structure was evaluated with spectral-domain optical coherence tomography. The distance from the fovea to disruption/loss of the inner outer segment (IS/OS) junction and thicknesses of the total receptor plus retinal pigment epithelial complex and outer segment plus retinal pigment epithelial complex layers were measured. Results were compared with measurements of the distance from the fovea to the inner and outer borders of the ring/arc seen on fundus autofluorescence. Disruption/loss of the inner outer segment junction occurred closer to the inner border of the ring/arc and it was closer to the fovea in eight eyes. For 19 eyes, outer segment plus and receptor plus RPE complex thicknesses were significantly decreased at locations closer to the fovea than the appearance of the inner border of hyperautofluorescence. Mean visual sensitivity was decreased inside, across, and outside the ring/arc by 3.5 ± 3.8, 8.9 ± 4.8, and 17.0 ± 2.4 dB, respectively. Structural and functional changes can occur inside the hyperfluorescent ring/arc in retinitis pigmentosa.

  19. Diffusion tensor tractography of language functional areas and fiber pathways in normal human brain

    International Nuclear Information System (INIS)

    Sun Xuejin; Dai Jianping; Chen Hongyan; Gao Peiyi; Ai Lin; Tian Shengyong; Pang Ruilin

    2007-01-01

    Objective: To demonstrate the fiber pathways of Broca area to the other functional brain areas with diffusion tensor imaging and fiber tracking. Methods: Conventionality MRI, diffusion tensor imaging (DTI) and fiber tracking were performed using 3.0 T MRI in 20 healthy person. The fiber bundles and tracts were analyzed in Broca area and contralateral normal area. Results: The left-side fiber bundles were 428 and the right-side were 416 in B45 area, there were no statistically significant differences between both sides (t=0.216, P>0.05). The left-side fiber bundles were 432 and the right-side were 344 in B44 area,there were statistically significant (t=2.314, P 0.05). Differences of the arcuate fascicule between both sides were not statistically significant (t=-0.465, P>0.05), the mean FA on the left was higher than the right (t=1.912, P<0.05). DTI and fiber tracking exhibited that the fiber bundles from Broca area were distributed superoanteriorly to the lateral foreside of the frontal lobe, lateroinferiorly to the occipital lobe through external capsule, and went down through globus pallidus and internal capsule. Conclusion: The fiber tracts bewteen Broca area and other brain areas were the fundamental structures for performing language function of the human brain. (authors)

  20. The Effect of Executive Function on Science Achievement Among Normally Developing 10-Year Olds

    Science.gov (United States)

    Lederman, Sheri G.

    Executive function (EF) is an umbrella term used to identify a set of discrete but interrelated cognitive abilities that enable individuals to engage in goal-directed, future-oriented action in response to a novel context. Developmental studies indicate that EF is predictive of reading and math achievement in middle childhood. The purpose of this study was to identify the association between EF and science achievement among normally developing 10 year olds. A sample of fifth grade students from a Northeastern suburban community participated in tests of EF, science, and intelligence. Consistent with adult models of EF, principal components analysis identified a three-factor model of EF organization in middle childhood, including cognitive flexibility, working memory, and inhibition. Multiple regression analyses revealed that executive function processes of cognitive flexibility, working memory, and inhibition were all predictive of science performance. Post hoc analyses revealed that high-performing science students differed significantly from low-performing students in both cognitive flexibility and working memory. These findings suggest that complex academic demands specific to science achievement rely on the emergence and maturation of EF components.

  1. Neurofeedback training produces normalization in behavioural and electrophysiological measures of high-functioning autism.

    Science.gov (United States)

    Pineda, Jaime A; Carrasco, Karen; Datko, Mike; Pillen, Steven; Schalles, Matt

    2014-01-01

    Autism spectrum disorder (ASD) is a neurodevelopmental condition exhibiting impairments in behaviour, social and communication skills. These deficits may arise from aberrant functional connections that impact synchronization and effective neural communication. Neurofeedback training (NFT), based on operant conditioning of the electroencephalogram (EEG), has shown promise in addressing abnormalities in functional and structural connectivity. We tested the efficacy of NFT in reducing symptoms in children with ASD by targeting training to the mirror neuron system (MNS) via modulation of EEG mu rhythms. The human MNS has provided a neurobiological substrate for understanding concepts in social cognition relevant to behavioural and cognitive deficits observed in ASD. Furthermore, mu rhythms resemble MNS phenomenology supporting the argument that they are linked to perception and action. Thirty hours of NFT on ASD and typically developing (TD) children were assessed. Both groups completed an eyes-open/-closed EEG session as well as a mu suppression index assessment before and after training. Parents filled out pre- and post-behavioural questionnaires. The results showed improvements in ASD subjects but not in TDs. This suggests that induction of neuroplastic changes via NFT can normalize dysfunctional mirroring networks in children with autism, but the benefits are different for TD brains.

  2. Functional mapping of language networks in the normal brain using a word-association task

    International Nuclear Information System (INIS)

    Ghosh, Shantanu; Basu, Amrita; Kumaran, Senthil S; Khushu, Subash

    2010-01-01

    Language functions are known to be affected in diverse neurological conditions, including ischemic stroke, traumatic brain injury, and brain tumors. Because language networks are extensive, interpretation of functional data depends on the task completed during evaluation. The aim was to map the hemodynamic consequences of word association using functional magnetic resonance imaging (fMRI) in normal human subjects. Ten healthy subjects underwent fMRI scanning with a postlexical access semantic association task vs lexical processing task. The fMRI protocol involved a T2*-weighted gradient-echo echo-planar imaging (GE-EPI) sequence (TR 4523 ms, TE 64 ms, flip angle 90°) with alternate baseline and activation blocks. A total of 78 scans were taken (interscan interval = 3 s) with a total imaging time of 587 s. Functional data were processed in Statistical Parametric Mapping software (SPM2) with 8-mm Gaussian kernel by convolving the blood oxygenation level-dependent (BOLD) signal with an hemodynamic response function estimated by general linear method to generate SPM{t} and SPM{F} maps. Single subject analysis of the functional data (FWE-corrected, P≤0.001) revealed extensive activation in the frontal lobes, with overlaps among middle frontal gyrus (MFG), superior, and inferior frontal gyri. BOLD activity was also found in the medial frontal gyrus, middle occipital gyrus (MOG), anterior fusiform gyrus, superior and inferior parietal lobules, and to a smaller extent, the thalamus and right anterior cerebellum. Group analysis (FWE-corrected, P≤0.001) revealed neural recruitment of bilateral lingual gyri, left MFG, bilateral MOG, left superior occipital gyrus, left fusiform gyrus, bilateral thalami, and right cerebellar areas. Group data analysis revealed a cerebellar–occipital–fusiform–thalamic network centered around bilateral lingual gyri for word association, thereby indicating how these areas facilitate language comprehension by activating a semantic

  3. Functional mapping of language networks in the normal brain using a word-association task

    Directory of Open Access Journals (Sweden)

    Ghosh Shantanu

    2010-01-01

    Full Text Available Background: Language functions are known to be affected in diverse neurological conditions, including ischemic stroke, traumatic brain injury, and brain tumors. Because language networks are extensive, interpretation of functional data depends on the task completed during evaluation. Aim: The aim was to map the hemodynamic consequences of word association using functional magnetic resonance imaging (fMRI in normal human subjects. Materials and Methods: Ten healthy subjects underwent fMRI scanning with a postlexical access semantic association task vs lexical processing task. The fMRI protocol involved a T2FNx01-weighted gradient-echo echo-planar imaging (GE-EPI sequence (TR 4523 ms, TE 64 ms, flip angle 90º with alternate baseline and activation blocks. A total of 78 scans were taken (interscan interval = 3 s with a total imaging time of 587 s. Functional data were processed in Statistical Parametric Mapping software (SPM2 with 8-mm Gaussian kernel by convolving the blood oxygenation level-dependent (BOLD signal with an hemodynamic response function estimated by general linear method to generate SPM{t} and SPM{F} maps. Results: Single subject analysis of the functional data (FWE-corrected, P≤0.001 revealed extensive activation in the frontal lobes, with overlaps among middle frontal gyrus (MFG, superior, and inferior frontal gyri. BOLD activity was also found in the medial frontal gyrus, middle occipital gyrus (MOG, anterior fusiform gyrus, superior and inferior parietal lobules, and to a smaller extent, the thalamus and right anterior cerebellum. Group analysis (FWE-corrected, P≤0.001 revealed neural recruitment of bilateral lingual gyri, left MFG, bilateral MOG, left superior occipital gyrus, left fusiform gyrus, bilateral thalami, and right cerebellar areas. Conclusions: Group data analysis revealed a cerebellar-occipital-fusiform-thalamic network centered around bilateral lingual gyri for word association, thereby indicating how these

  4. Cytoskeletal Components Define Protein Location to Membrane Microdomains*

    Science.gov (United States)

    Szymanski, Witold G.; Zauber, Henrik; Erban, Alexander; Gorka, Michal; Wu, Xu Na; Schulze, Waltraud X.

    2015-01-01

    The plasma membrane is an important compartment that undergoes dynamic changes in composition upon external or internal stimuli. The dynamic subcompartmentation of proteins in ordered low-density (DRM) and disordered high-density (DSM) membrane phases is hypothesized to require interactions with cytoskeletal components. Here, we systematically analyzed the effects of actin or tubulin disruption on the distribution of proteins between membrane density phases. We used a proteomic screen to identify candidate proteins with altered submembrane location, followed by biochemical or cell biological characterization in Arabidopsis thaliana. We found that several proteins, such as plasma membrane ATPases, receptor kinases, or remorins resulted in a differential distribution between membrane density phases upon cytoskeletal disruption. Moreover, in most cases, contrasting effects were observed: Disruption of actin filaments largely led to a redistribution of proteins from DRM to DSM membrane fractions while disruption of tubulins resulted in general depletion of proteins from the membranes. We conclude that actin filaments are necessary for dynamic movement of proteins between different membrane phases and that microtubules are not necessarily important for formation of microdomains as such, but rather they may control the protein amount present in the membrane phases. PMID:26091700

  5. Cytoskeletal Reorganization Drives Mesenchymal Condensation and Regulates Downstream Molecular Signaling.

    Directory of Open Access Journals (Sweden)

    Poulomi Ray

    Full Text Available Skeletal condensation occurs when specified mesenchyme cells self-organize over several days to form a distinctive cartilage template. Here, we determine how and when specified mesenchyme cells integrate mechanical and molecular information from their environment, forming cartilage condensations in the pharyngeal arches of chick embryos. By disrupting cytoskeletal reorganization, we demonstrate that dynamic cell shape changes drive condensation and modulate the response of the condensing cells to Fibroblast Growth Factor (FGF, Bone Morphogenetic Protein (BMP and Transforming Growth Factor beta (TGF-β signaling pathways. Rho Kinase (ROCK-driven actomyosin contractions and Myosin II-generated differential cell cortex tension regulate these cell shape changes. Disruption of the condensation process inhibits the differentiation of the mesenchyme cells into chondrocytes, demonstrating that condensation regulates the fate of the mesenchyme cells. We also find that dorsal and ventral condensations undergo distinct cell shape changes. BMP signaling is instructive for dorsal condensation-specific cell shape changes. Moreover, condensations exhibit ventral characteristics in the absence of BMP signaling, suggesting that in the pharyngeal arches ventral morphology is the ground pattern. Overall, this study characterizes the interplay between cytoskeletal dynamics and molecular signaling in a self-organizing system during tissue morphogenesis.

  6. Visualization of cytoskeletal elements by the atomic force microscope

    International Nuclear Information System (INIS)

    Berdyyeva, T.; Woodworth, C.D.; Sokolov, I.

    2005-01-01

    We describe a novel application of atomic force microscopy (AFM) to directly visualize cytoskeletal fibers in human foreskin epithelial cells. The nonionic detergent Triton X-100 in a low concentration was used to remove the membrane, soluble proteins, and organelles from the cell. The remaining cytoskeleton can then be directly visualized in either liquid or air-dried ambient conditions. These two types of scanning provide complimentary information. Scanning in liquid visualizes the surface filaments of the cytoskeleton, whereas scanning in air shows both the surface filaments and the total 'volume' of the cytoskeletal fibers. The smallest fibers observed were ca. 50 nm in diameter. The lateral resolution of this technique was ca.20 nm, which can be increased to a single nanometer level by choosing sharper AFM tips. Because the AFM is a true 3D technique, we are able to quantify the observed cytoskeleton by its density and volume. The types of fibers can be identified by their size, similar to electron microscopy

  7. TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Tansey Malú G

    2008-10-01

    Full Text Available Abstract The role of tumor necrosis factor (TNF as an immune mediator has long been appreciated but its function in the brain is still unclear. TNF receptor 1 (TNFR1 is expressed in most cell types, and can be activated by binding of either soluble TNF (solTNF or transmembrane TNF (tmTNF, with a preference for solTNF; whereas TNFR2 is expressed primarily by microglia and endothelial cells and is preferentially activated by tmTNF. Elevation of solTNF is a hallmark of acute and chronic neuroinflammation as well as a number of neurodegenerative conditions including ischemic stroke, Alzheimer's (AD, Parkinson's (PD, amyotrophic lateral sclerosis (ALS, and multiple sclerosis (MS. The presence of this potent inflammatory factor at sites of injury implicates it as a mediator of neuronal damage and disease pathogenesis, making TNF an attractive target for therapeutic development to treat acute and chronic neurodegenerative conditions. However, new and old observations from animal models and clinical trials reviewed here suggest solTNF and tmTNF exert different functions under normal and pathological conditions in the CNS. A potential role for TNF in synaptic scaling and hippocampal neurogenesis demonstrated by recent studies suggest additional in-depth mechanistic studies are warranted to delineate the distinct functions of the two TNF ligands in different parts of the brain prior to large-scale development of anti-TNF therapies in the CNS. If inactivation of TNF-dependent inflammation in the brain is warranted by additional pre-clinical studies, selective targeting of TNFR1-mediated signaling while sparing TNFR2 activation may lessen adverse effects of anti-TNF therapies in the CNS.

  8. SALPETER NORMALIZATION OF THE STELLAR INITIAL MASS FUNCTION FOR MASSIVE GALAXIES AT z ∼ 1

    International Nuclear Information System (INIS)

    Shetty, Shravan; Cappellari, Michele

    2014-01-01

    The stellar initial mass function (IMF) is a key parameter for studying galaxy evolution. Here we measure the IMF mass normalization for a sample of 68 field galaxies in the redshift range 0.7-0.9 within the Extended Groth Strip. To do this we derive the total (stellar + dark matter) mass-to-light [(M/L)] ratio using axisymmetric dynamical models. Within the region where we have kinematics (about one half-light radius), the models assume (1) that mass follows light, implying negligible differences between the slope of the stellar and total density profiles, (2) constant velocity anisotropy (β z ≡1−σ z 2 /σ R 2 =0.2), and (3) that galaxies are seen at the average inclination for random orientations (i.e., i = 60°, where i = 90° represents edge-on). The dynamical models are based on anisotropic Jeans equations, constrained by Hubble Space Telescope/Advanced Camera for Surveys imaging and the central velocity dispersion of the galaxies, extracted from good-quality spectra taken by the DEEP2 survey. The population (M/L) are derived from full-spectrum fitting of the same spectra with a grid of simple stellar population models. Recent dynamical modeling results from the ATLAS 3D project and numerical simulations of galaxy evolution indicate that the dark matter fraction within the central regions of our galaxies should be small. This suggests that our derived total (M/L) should closely approximate the stellar M/L. Our comparison of the dynamical (M/L) and the population (M/L) then implies that for galaxies with stellar mass M * ≳ 10 11 M ☉ , the average normalization of the IMF is consistent with a Salpeter slope, with a substantial scatter. This is similar to what is found within a similar mass range for nearby galaxies

  9. Serum erythropoietin level in anemic and non-anemic nephrotic children with normal kidney functions

    International Nuclear Information System (INIS)

    Moustafa, A.M.E.; Moawad, A.T.; Gad, A.A.; Ahmed, S.M.

    2005-01-01

    Nephrotic syndrome (NS) is associated with a significant alteration in protein metabolism. While lowering the concentration of certain proteins, the disease often raises the level of certain other proteins. The current study aimed to investigate the serum erythropoietin (EPO) levels in children with NS either anemic or non-anemic and to compare them to children with iron deficiency anemia (IDA) and healthy controls with normal hemoglobin level (NHB). Sixteen nephrotic children with anemia (NS-A) and 15 nephrotic children with normal hemoglobin level (NS-NHB) were examined and compared with 10 children with iron deficiency anemia (IDA) and 10 healthy controls (NHB). Circulating serum EPO levels, blood indices and iron status were measured in nephrotic patients with anemia (NS-A) and compared to those nephrotic patients with normal HE (NS-NHB). Most NS-A children were steroid resistant. The NS-A children showed greater EPO levels than those without anemia (21.01 ±4.02 mlU/ml versus 9.18 ± 0.79 mlU/ml; P < 0.001) but their response to treatment of anemia was inappropriately low when compared to IDA (EPO 96.9 ±4.9 mlU/ml) despite similar HB concentration. A significant positive correlation was observed between serum EPO and serum albumin in NS-A (r = 0.84, P < 0.001) and in NS-NHB group (r = 0.89, P < 0.001). Moreover, a significant positive correlation was observed between serum EPO and HB in the nephrotic groups indicating a blunted EPO response to anemia in NS-A (r 0.63, P < 0.05) and in NS-NHB group (r = 0.80, P < 0.001). In conclusion, anemia is a common feature of NS and is present even before the worsening of kidney function. Depletion of the iron stores due to loss of iron and transferrin in urine due to massive proteinurea may contribute to the development of anemia, but it was found that iron replacement was ineffective alone

  10. Why is cytoskeletal contraction required for cardiac fusion before but not after looping begins?

    Science.gov (United States)

    Shi, Yunfei; Varner, Victor D.; Taber, Larry A.

    2015-02-01

    Cytoskeletal contraction is crucial to numerous morphogenetic processes, but its role in early heart development is poorly understood. Studies in chick embryos have shown that inhibiting myosin-II-based contraction prior to Hamburger-Hamilton (HH) stage 10 (33 h incubation) impedes fusion of the mesodermal heart fields that create the primitive heart tube (HT), as well as the ensuing process of cardiac looping. If contraction is inhibited at or after looping begins at HH10, however, fusion and looping proceed relatively normally. To explore the mechanisms behind this seemingly fundamental change in behavior, we measured spatiotemporal distributions of tissue stiffness, stress, and strain around the anterior intestinal portal (AIP), the opening to the foregut where contraction and cardiac fusion occur. The results indicate that stiffness and tangential tension decreased bilaterally along the AIP with distance from the embryonic midline. The gradients in stiffness and tension, as well as strain rate, increased to peaks at HH9 (30 h) and decreased afterward. Exposure to the myosin II inhibitor blebbistatin reduced these effects, suggesting that they are mainly generated by active cytoskeletal contraction, and finite-element modeling indicates that the measured mechanical gradients are consistent with a relatively uniform contraction of the endodermal layer in conjunction with constraints imposed by the attached mesoderm. Taken together, our results suggest that, before HH10, endodermal contraction pulls the bilateral heart fields toward the midline where they fuse to create the HT. By HH10, however, the fusion process is far enough along to enable apposing cardiac progenitor cells to keep ‘zipping’ together during looping without the need for continued high contractile forces. These findings should shed new light on a perplexing question in early heart development.

  11. Why is cytoskeletal contraction required for cardiac fusion before but not after looping begins?

    International Nuclear Information System (INIS)

    Shi, Yunfei; Taber, Larry A; Varner, Victor D

    2015-01-01

    Cytoskeletal contraction is crucial to numerous morphogenetic processes, but its role in early heart development is poorly understood. Studies in chick embryos have shown that inhibiting myosin-II-based contraction prior to Hamburger–Hamilton (HH) stage 10 (33 h incubation) impedes fusion of the mesodermal heart fields that create the primitive heart tube (HT), as well as the ensuing process of cardiac looping. If contraction is inhibited at or after looping begins at HH10, however, fusion and looping proceed relatively normally. To explore the mechanisms behind this seemingly fundamental change in behavior, we measured spatiotemporal distributions of tissue stiffness, stress, and strain around the anterior intestinal portal (AIP), the opening to the foregut where contraction and cardiac fusion occur. The results indicate that stiffness and tangential tension decreased bilaterally along the AIP with distance from the embryonic midline. The gradients in stiffness and tension, as well as strain rate, increased to peaks at HH9 (30 h) and decreased afterward. Exposure to the myosin II inhibitor blebbistatin reduced these effects, suggesting that they are mainly generated by active cytoskeletal contraction, and finite-element modeling indicates that the measured mechanical gradients are consistent with a relatively uniform contraction of the endodermal layer in conjunction with constraints imposed by the attached mesoderm. Taken together, our results suggest that, before HH10, endodermal contraction pulls the bilateral heart fields toward the midline where they fuse to create the HT. By HH10, however, the fusion process is far enough along to enable apposing cardiac progenitor cells to keep ‘zipping’ together during looping without the need for continued high contractile forces. These findings should shed new light on a perplexing question in early heart development. (paper)

  12. Functional and histological assessment of the radiobiology of normal rat lung in BNCT

    International Nuclear Information System (INIS)

    Kiger, J.L.; Riley, K.J.; Binns, P.J.; Harling, O.K.; Coderre, J.A.; Kiger, W.S. III; Patel, H.

    2006-01-01

    This study investigated the radiobiology and sensitivity of the normal rat lung to Boron Neutron Capture Therapy (BNCT) radiation. Rat thorax irradiations were carried out with x-rays or with neutrons in the presence or absence of p-boronophenylalanine (BPA). Lung damage were assessed functionally with breathing rate measurement up to 180 days after irradiation and then histologically. Breathing rates 20% (∼3 σ) above the control group (sham-irradiated rats) mean were considered as positive responses to lung radiation damage. Though most responding animals demonstrated radiation induced pneumonitis (≤110 days) as well as pulmonary fibrosis (>110 days), some animals receiving neutrons plus BPA showed only the latter. The breathing rate dose response data were fit using probit analysis. The ED 50 values measured for x-rays, neutron beam only, and neutrons plus BPA were 11.5±0.4 Gy, 9.2±0.5 Gy, and 6.7±0.4 Gy, respectively. The biological weighting factors for the neutron beam (n+γ), the thermal neutron dose component, and the 10 B dose component were determined to be 1.2±0.1, 2.2±0.4, and 2.3±0.3, respectively. The histological dose response curves were linear. Consistent with the functional assay, the weighting factors measured histologically were 1.2±0.1 for the thermal neutron beam and 1.9±0.2 for the 10 B dose component. (author)

  13. The relationship of theory of mind and executive functions in normal, deaf and cochlear-implanted children

    Directory of Open Access Journals (Sweden)

    Farideh Nazarzadeh

    2014-08-01

    Full Text Available Background and Aim : Theory of mind refers to the ability to understand the others have mental states that can be different from one's own mental states or facts. This study aimed to investigate the relationship of theory of mind and executive functions in normal hearing, deaf, and cochlear-implanted children.Methods: The study population consisted of normal, deaf and cochlear-implanted girl students in Mashhad city, Iran. Using random sampling, 30 children (10 normal, 10 deaf and 10 cochlear-implanted in age groups of 8-12 years old were selected. To measure the theoty of mind, theory of mind 38-item scale and to assess executive function, Coolidge neuropsychological and personality test was used. Research data were analyzed using the Spearman correlation coefficient, analysis of variance and Kruskal-Wallis tests.Results: There was a significant difference between the groups in the theory of mind and executive function subscales, organization, planning-decision-making, and inhibition. Between normal and deaf groups (p=0.01, as well as cochlear-implanted and deaf groups (p=0.01, there was significant difference in planning decision-making subscale. There was not any significant relationship between the theory of mind and executive functions generally or the theory of mind and executive function subscales in these three groups independently.Conclusion: Based on our findings, cochlear-implanted and deaf children have lower performance in theory of mind and executive function compared with normal hearing children.

  14. Periodontal disease characterization in dogs with normal renal function or chronic renal failure

    Directory of Open Access Journals (Sweden)

    Barbudo-Selmi Glenda Ramalho

    2004-01-01

    Full Text Available The purpose of this study was to evaluate periodontal disease (PD in dogs with chronic renal failure (CRF and to compare it to PD in dogs with normal renal function (NRF. Twelve dogs with CRF and 24 dogs with NRF, all presenting dental pocket formation, were compared. In all dogs, serum creatinine, blood urea nitrogen, urine specific gravity and total red and white blood cells were determined. A complete oral examination was also performed including evaluation of bacterial plaque, gingivitis, gingival recession, pocket, calculus, dental mobility, dental loss, and ulcers. These data were used to calculate plaque index (PI, gingival index (GI and periodontal destruction index (PDI. PD was graded as mild, moderate or severe based on the results. Mild, moderate or severe PD was observed in dogs with NRF, whereas dogs with CRF presented either mild or severe PD. Dogs with NRF showed higher involvement of the maxillary teeth, whereas dogs with CRF showed a higher involvement of the mandibular teeth. Plaque index was significantly higher in dogs with NRF. It was concluded that lesion distribution and periodontal disease progression may be altered in dogs with CRF, and gingival inflammatory response differs in dogs with NRF and CRF regarding to the stage of periodontal disease.

  15. Microvascular resistance in response to iodinated contrast media in normal and functionally impaired kidneys.

    Science.gov (United States)

    Kurihara, Osamu; Takano, Masamichi; Uchiyama, Saori; Fukuizumi, Isamu; Shimura, Tetsuro; Matsushita, Masato; Komiyama, Hidenori; Inami, Toru; Murakami, Daisuke; Munakata, Ryo; Ohba, Takayoshi; Hata, Noritake; Seino, Yoshihiko; Shimizu, Wataru

    2015-12-01

    Contrast-induced nephropathy (CIN) is considered to result from intrarenal vasoconstriction, and occurs more frequently in impaired than in normal kidneys. It was hypothesized that iodinated contrast media would markedly change renal blood flow and vascular resistance in functionally impaired kidneys. Thirty-six patients were enrolled (32 men; mean age, 75.3 ± 7.6 years) undergoing diagnostic coronary angiography and were divided into two groups based on the presence of chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) of contrast media. The APV and the RI were positively and inversely correlated with the eGFR at baseline, respectively (APV, R = 0.545, P = 0.001; RI, R = -0.627, P contrast media administration in the non-CKD group, but not in the CKD group (APV, P = 0.258; RI, P = 0.707). Although renal arterial resistance was higher in patients with CKD, it was not affected by contrast media administration, suggesting that patients with CKD could have an attenuated response to contrast media. © 2015 The Authors. Clinical and Experimental Pharmacology and Physiology Published by Wiley Publishing Asia Pty Ltd.

  16. Impaired cognitive functions in mild traumatic brain injury patients with normal and pathologic magnetic resonance imaging

    International Nuclear Information System (INIS)

    Kurca, E.; Sivak, S.; Kucera, P.

    2006-01-01

    Mild traumatic brain injury (MTBI) is a common neurological (neurotraumatological) diagnosis. As well as different subjective symptoms, many patients develop neuropsychological dysfunction with objective impairment of attention, memory and certain executive functions. Magnetic resonance imaging (MRI) is not routinely used in MTBI patients despite its proven greater sensitivity and specificity in comparison with computed tomography (CT). The patient group consisted of 30 persons with MTBI and the control group consisted of 30 sex- and age-matched healthy volunteers. Both groups underwent neurological examination, neuropsychological testing (including the Postconcussion Symptoms Scale questionnaire, PCSS) and brain MRI (the patient group within 96 h after injury). The analyzed groups did not differ significantly in terms of sex, age, or level or duration of education. MRI pathological findings (traumatic and nonspecific) were present in nine patients. Traumatic lesions were found in seven patients. Nonspecific white matter lesions were found in five healthy controls. There were significant differences between MTBI patients and controls in terms of subjective symptoms (PCSS) and selected neuropsychological tests. Statistically significant neuropsychological differences were found between MTBI patients with true traumatic lesions and MTBI patients with nonspecific lesions. There is evidence that MTBI patients with true traumatic MRI lesions are neuropsychologically different from MTBI patients with nonspecific MRI lesions or normal brain MRI. These results support the hypothesis that some acute MTBI signs and symptoms have a real organic basis which can be detected by selected new MRI modalities. (orig.)

  17. Relational Stability in the Expression of Normality, Variation, and Control of Thyroid Function

    Science.gov (United States)

    Hoermann, Rudolf; Midgley, John E. M.; Larisch, Rolf; Dietrich, Johannes W.

    2016-01-01

    Thyroid hormone concentrations only become sufficient to maintain a euthyroid state through appropriate stimulation by pituitary thyroid-stimulating hormone (TSH). In such a dynamic system under constant high pressure, guarding against overstimulation becomes vital. Therefore, several defensive mechanisms protect against accidental overstimulation, such as plasma protein binding, conversion of T4 into the more active T3, active transmembrane transport, counter-regulatory activities of reverse T3 and thyronamines, and negative hypothalamic–pituitary–thyroid feedback control of TSH. TSH has gained a dominant but misguided role in interpreting thyroid function testing in assuming that its exceptional sensitivity thereby translates into superior diagnostic performance. However, TSH-dependent thyroid disease classification is heavily influenced by statistical analytic techniques such as uni- or multivariate-defined normality. This demands a separation of its conjoint roles as a sensitive screening test and accurate diagnostic tool. Homeostatic equilibria (set points) in healthy subjects are less variable and do not follow a pattern of random variation, rather indicating signs of early and progressive homeostatic control across the euthyroid range. In the event of imminent thyroid failure with a reduced FT4 output per unit TSH, conversion efficiency increases in order to maintain FT3 stability. In such situations, T3 stability takes priority over set point maintenance. This suggests a concept of relational stability. These findings have important implications for both TSH reference limits and treatment targets for patients on levothyroxine. The use of archival markers is proposed to facilitate the homeostatic interpretation of all parameters. PMID:27872610

  18. The effects of detomidine, romifidine or acepromazine on echocardiographic measurements and cardiac function in normal horses.

    Science.gov (United States)

    Buhl, Rikke; Ersbøll, Annette K; Larsen, Nanna H; Eriksen, Lis; Koch, Jørgen

    2007-01-01

    To evaluate by echo- and electrocardiography the cardiac effects of sedation with detomidine hydrochloride, romifidine hydrochloride or acepromazine maleate in horses. An experimental study using a cross-over design without randomization. Eight clinically normal Standardbred trotters. Echocardiographic examinations (two-dimensional, guided M-mode and colour Doppler) were recorded on five different days. Heart rate (HR) and standard limb lead electrocardiograms were also obtained. Subsequently, horses were sedated with detomidine (0.01 mg kg(-1)), romifidine (0.04 mg kg(-1)) or acepromazine (0.1 mg kg(-1)) administered intravenously and all examinations repeated. Heart rate before treatment with the three drugs did not differ significantly (p = 0.98). Both detomidine and romifidine induced a significant decrease (p detomidine, there was a significant increase in LVIDd (left ventricular internal diameter in diastole; p = 0.034) and LVIDs (left ventricular internal diameter in systole; p detomidine and to a lesser extent romifidine at the doses given in this study has a significant effect on heart function, echocardiographic measurements of heart dimensions and the occurrence of valvular regurgitation. Although the clinical significance of these results may be minimal, the potential effects of sedative drugs should be taken into account when echocardiographic variables are interpreted in clinical cases.

  19. Impaired cognitive functions in mild traumatic brain injury patients with normal and pathologic magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kurca, E.; Sivak, S. [Comenius University, Clinic of Neurology, Jessenius Faculty of Medicine, Martin (Slovakia); Kucera, P. [Comenius University, 1st Clinic of Neurology, Faculty of Medicine, Bratislava (Slovakia)

    2006-09-15

    Mild traumatic brain injury (MTBI) is a common neurological (neurotraumatological) diagnosis. As well as different subjective symptoms, many patients develop neuropsychological dysfunction with objective impairment of attention, memory and certain executive functions. Magnetic resonance imaging (MRI) is not routinely used in MTBI patients despite its proven greater sensitivity and specificity in comparison with computed tomography (CT). The patient group consisted of 30 persons with MTBI and the control group consisted of 30 sex- and age-matched healthy volunteers. Both groups underwent neurological examination, neuropsychological testing (including the Postconcussion Symptoms Scale questionnaire, PCSS) and brain MRI (the patient group within 96 h after injury). The analyzed groups did not differ significantly in terms of sex, age, or level or duration of education. MRI pathological findings (traumatic and nonspecific) were present in nine patients. Traumatic lesions were found in seven patients. Nonspecific white matter lesions were found in five healthy controls. There were significant differences between MTBI patients and controls in terms of subjective symptoms (PCSS) and selected neuropsychological tests. Statistically significant neuropsychological differences were found between MTBI patients with true traumatic lesions and MTBI patients with nonspecific lesions. There is evidence that MTBI patients with true traumatic MRI lesions are neuropsychologically different from MTBI patients with nonspecific MRI lesions or normal brain MRI. These results support the hypothesis that some acute MTBI signs and symptoms have a real organic basis which can be detected by selected new MRI modalities. (orig.)

  20. Gene expression and functional studies of the optic nerve head astrocyte transcriptome from normal African Americans and Caucasian Americans donors.

    Directory of Open Access Journals (Sweden)

    Haixi Miao

    2008-08-01

    Full Text Available To determine whether optic nerve head (ONH astrocytes, a key cellular component of glaucomatous neuropathy, exhibit differential gene expression in primary cultures of astrocytes from normal African American (AA donors compared to astrocytes from normal Caucasian American (CA donors.We used oligonucleotide Affymetrix microarray (HG U133A & HG U133A 2.0 chips to compare gene expression levels in cultured ONH astrocytes from twelve CA and twelve AA normal age matched donor eyes. Chips were normalized with Robust Microarray Analysis (RMA in R using Bioconductor. Significant differential gene expression levels were detected using mixed effects modeling and Statistical Analysis of Microarray (SAM. Functional analysis and Gene Ontology were used to classify differentially expressed genes. Differential gene expression was validated by quantitative real time RT-PCR. Protein levels were detected by Western blots and ELISA. Cell adhesion and migration assays tested physiological responses. Glutathione (GSH assay detected levels of intracellular GSH.Multiple analyses selected 87 genes differentially expressed between normal AA and CA (P<0.01. The most relevant genes expressed in AA were categorized by function, including: signal transduction, response to stress, ECM genes, migration and cell adhesion.These data show that normal astrocytes from AA and CA normal donors display distinct expression profiles that impact astrocyte functions in the ONH. Our data suggests that differences in gene expression in ONH astrocytes may be specific to the development and/or progression of glaucoma in AA.

  1. Hierarchical Distribution of the Tau Cytoskeletal Pathology in the Thalamus of Alzheimer's Disease Patients

    NARCIS (Netherlands)

    Rueb, Udo; Stratmann, Katharina; Heinsen, Helmut; Del Turco, Domenico; Ghebremedhin, Estifanos; Seidel, Kay; den Dunnen, Wilfred; Korf, Horst-Werner

    2015-01-01

    In spite of considerable progress in neuropathological research on Alzheimer's disease (AD), knowledge regarding the exact pathoanatomical distribution of the tau cytoskeletal pathology in the thalamus of AD patients in the advanced Braak and Braak AD stages V or VI of the cortical cytoskeletal

  2. The cerebral functional location in normal subjects when they listened to a story in unfamiliar Japanese

    International Nuclear Information System (INIS)

    Sun Da; Xu Wei; Zhang Hongwei; Liu Hongbiao; Liu Qichang

    2004-01-01

    Purpose: To detect the cerebral functional location when normal subjects listened to a story in unfamiliar Japanese. Methods: 7 normal young students of the medical collage of Zhejiang University, 22-24 years old, 4 male and 3 female. The first they underwent a 99mTc-ECD brain imaging at rest using a dual-head gamma camera with fan beam collimators. After 2-4 days they were asked to listen a story in unfamiliar Japanese carefully on a tap for 20 minters. 99mTc-ECD was administered in the first 3 minutes during they listened the story. The brain imaging was performed in 30-60 minutes after the tracer was administered. Results: To compare the rest state, during listen to the story in unfamiliar Japanese the right superior temporal in 5 cases, left superior temporal in 2 cases, right inferior temporal in 2 cases, and left inferior temporal in 1 case were activated. Among them, dual temporal were activated in 2 cases, only right temporal in 4 cases and left temporal in 1 case. Although they were no asked to remember the plot of the story, the frontal lobes were activated lightly in all 9 subjects. Among them dual inferior frontal and/or medial frontal lobes (3 cases), right inferior frontal and/or medial frontal lobes (2 cases), left inferior frontal (5 cases), right inferior frontal (1 case), right superior frontal (3 cases) were activated. The were activated in 6 subjects, and dual occipital in 5 cases, left occipital in 1 case. Other regions that were activated included parietal lobes (right in 2 cases and left in 1 case), and left occipital lobes (in 1 case) were activated. Conclusion: During listened to the story in unfamiliar Japanese the auditory association cortex in the superior temporal and some right midtemporal (it is more in right than in left) were activated. The frontal lobes were activated widely too, and mainly in left inferior frontal lobes (Broca's area), and in the frontal eye fields and the superolateral prefrontal cortex. It is consistent with the

  3. Resveratrol Treatment Normalizes the Endothelial Function and Blood Pressure in Ovariectomized Rats.

    Science.gov (United States)

    Fabricio, Victor; Oishi, Jorge Camargo; Biffe, Bruna Gabriele; Ruffoni, Leandro Dias Gonçalves; Silva, Karina Ana da; Nonaka, Keico Okino; Rodrigues, Gerson Jhonatan

    2017-02-01

    Despite knowing that resveratrol has effects on blood vessels, blood pressure and that phytostrogens can also improve the endothelium-dependent relaxation/vasodilation, there are no reports of reveratrol's direct effect on the endothelial function and blood pressure of animals with estrogen deficit (mimicking post-menopausal increased blood pressure). To verify the effect of two different periods of preventive treatment with resveratrol on blood pressure and endothelial function in ovariectomized young adult rats. 3-month old female Wistar rats were used and distributed in 6 groups: intact groups with 60 or 90 days, ovariectomized groups with 60 or 90 days, and ovariectomized treated with resveratrol (10 mg/kg of body weight per day) for 60 or 90 days. The number of days in each group corresponds to the duration of the experimental period. Vascular reactivity study was performed in abdominal aortic rings, systolic blood pressure was measured and serum nitric oxide (NO) concentration was quantified. Ovariectomy induced blood pressure increase 60 and 90 days after surgery, whereas the endothelial function decreased only 90 days after surgery, with no difference in NO concentration among the groups. Only longer treatment (90 days) with resveratrol was able to improve the endothelial function and normalize blood pressure. Our results suggest that 90 days of treatment with resveratrol is able to improve the endothelial function and decrease blood pressure in ovariectomized rats. Apesar de se saber que o resveratrol apresenta efeitos sobre a pressão arterial e os vasos sanguíneos, e que os fitoestrógenos podem melhorar o relaxamento/vasodilatação dependente do endotélio, não há relatos do efeito direto do resveratrol sobre a pressão arterial e a função endotelial em animais com deficiência de estrógeno (mimetizando a pressão arterial aumentada pós-menopausa). Verificar o efeito de dois diferentes períodos de tratamento preventivo com resveratrol sobre a

  4. Higher Fasting Plasma Glucose Levels, within the Normal Range, are Associated with Decreased Processing Speed in High Functioning Young Elderly

    OpenAIRE

    Raizes, Meytal; Elkana, Odelia; Franko, Motty; Springer, Ramit Ravona; Segev, Shlomo; Beeri, Michal Schnaider

    2016-01-01

    We explored the association of plasma glucose levels within the normal range with processing speed in high functioning young elderly, free of type 2 diabetes mellitus (T2DM). A sample of 41 participants (mean age = 64.7, SD = 10; glucose 94.5 mg/dL, SD = 9.3), were examined with a computerized cognitive battery. Hierarchical linear regression analysis showed that higher plasma glucose levels, albeit within the normal range (

  5. Modulators of cytoskeletal reorganization in CA1 hippocampal neurons show increased expression in patients at mid-stage Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Patricia F Kao

    2010-10-01

    Full Text Available During the progression of Alzheimer's disease (AD, hippocampal neurons undergo cytoskeletal reorganization, resulting in degenerative as well as regenerative changes. As neurofibrillary tangles form and dystrophic neurites appear, sprouting neuronal processes with growth cones emerge. Actin and tubulin are indispensable for normal neurite development and regenerative responses to injury and neurodegenerative stimuli. We have previously shown that actin capping protein beta2 subunit, Capzb2, binds tubulin and, in the presence of tau, affects microtubule polymerization necessary for neurite outgrowth and normal growth cone morphology. Accordingly, Capzb2 silencing in hippocampal neurons resulted in short, dystrophic neurites, seen in neurodegenerative diseases including AD. Here we demonstrate the statistically significant increase in the Capzb2 expression in the postmortem hippocampi in persons at mid-stage, Braak and Braak stage (BB III-IV, non-familial AD in comparison to controls. The dynamics of Capzb2 expression in progressive AD stages cannot be attributed to reactive astrocytosis. Moreover, the increased expression of Capzb2 mRNA in CA1 pyramidal neurons in AD BB III-IV is accompanied by an increased mRNA expression of brain derived neurotrophic factor (BDNF receptor tyrosine kinase B (TrkB, mediator of synaptic plasticity in hippocampal neurons. Thus, the up-regulation of Capzb2 and TrkB may reflect cytoskeletal reorganization and/or regenerative response occurring in hippocampal CA1 neurons at a specific stage of AD progression.

  6. Maturation of Speech and Language Functional Neuroanatomy in Pediatric Normal Controls

    Science.gov (United States)

    Devous, Michael D., Sr.; Altuna, Dianne; Furl, Nicholas, Cooper, William; Gabbert, Gretchen; Ngai, Wei Tat; Chiu, Stephanie; Scott, Jack M., III; Harris, Thomas S.; Payne, J. Kelly; Tobey, Emily A.

    2006-01-01

    Purpose: This study explores the relationship between age and resting-state regional cerebral blood flow (rCBF) in regions associated with higher order language skills using a population of normal children, adolescents, and young adults. Method: rCBF was measured in 33 normal participants between the ages of 7 and 19 years using single photon…

  7. Cell elasticity with altered cytoskeletal architectures across multiple cell types.

    Science.gov (United States)

    Grady, Martha E; Composto, Russell J; Eckmann, David M

    2016-08-01

    The cytoskeleton is primarily responsible for providing structural support, localization and transport of organelles, and intracellular trafficking. The structural support is supplied by actin filaments, microtubules, and intermediate filaments, which contribute to overall cell elasticity to varying degrees. We evaluate cell elasticity in five different cell types with drug-induced cytoskeletal derangements to probe how actin filaments and microtubules contribute to cell elasticity and whether it is conserved across cell type. Specifically, we measure elastic stiffness in primary chondrocytes, fibroblasts, endothelial cells (HUVEC), hepatocellular carcinoma cells (HUH-7), and fibrosarcoma cells (HT 1080) subjected to two cytoskeletal destabilizers: cytochalasin D and nocodazole, which disrupt actin and microtubule polymerization, respectively. Elastic stiffness is measured by atomic force microscopy (AFM) and the disruption of the cytoskeleton is confirmed using fluorescence microscopy. The two cancer cell lines showed significantly reduced elastic moduli values (~0.5kPa) when compared to the three healthy cell lines (~2kPa). Non-cancer cells whose actin filaments were disrupted using cytochalasin D showed a decrease of 60-80% in moduli values compared to untreated cells of the same origin, whereas the nocodazole-treated cells showed no change in elasticity. Overall, we demonstrate actin filaments contribute more to elastic stiffness than microtubules but this result is cell type dependent. Cancer cells behaved differently, exhibiting increased stiffness as well as stiffness variability when subjected to nocodazole. We show that disruption of microtubule dynamics affects cancer cell elasticity, suggesting therapeutic drugs targeting microtubules be monitored for significant elastic changes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Functional brain imaging with SPECT in normal again and dementia. Methodological, pathophysiological, and diagnostic aspects

    International Nuclear Information System (INIS)

    Waldemar, G.

    1996-03-01

    New developments in instrumentation, radiochemistry, and data analysis, particularly the introduction of 99m Tc-labeled brain-retained tracers for perfusion studies, have opened up a new era of single photon emission computed tomography (SPECT). In this review critical methodological issues relating to the SPECT instrument, the radioactive tracers, the scanning procedure, the data analysis and interpretation of data, and subject selection are discussed together with the changes in regional cerebral blood flow (rCBF) observed in normal aging. An overview is given of the topography and the pathophysiological and diagnostic significance of focal rCBF deficits in Alzheimer's disease and in other dementia disorders, in which SPECT is capable of early or preclinical disease detection. In Alzheimer's disease, the diagnostic sensitivity and specificity of focal rCBF deficits measured with SPECT and brain-retained tracers are very high, in particular when combined with medial temporal lob atrophy on CT. Together with neuropsychological testing, SPECT serves to map the topography of brain dysfunction. Thus, in the clinical setting, SPECT provides information that is supplemental to that obtained in other studies. Future applications include neuroreceptor studies and treatment studies, in which SPECT may serve as a diagnostic aid in the selection of patients and as a potential mean for monitoring treatment effects. Although positron emission tomography is the best characterized tool for addressing some of these clinical and research issues in dementia, only the less expensive and technically simpler SPECT technique will have the potential of being available as a screening diagnostic instrument in the clinical setting. It is concluded that, properly approached, functional brain imaging with SPECT represents an important tool in the diagnosis, management, and research of dementia disorders. (au) 251 refs

  9. Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation.

    Science.gov (United States)

    Baumgartner, Christine; da Costa, Bruno R; Collet, Tinh-Hai; Feller, Martin; Floriani, Carmen; Bauer, Douglas C; Cappola, Anne R; Heckbert, Susan R; Ceresini, Graziano; Gussekloo, Jacobijn; den Elzen, Wendy P J; Peeters, Robin P; Luben, Robert; Völzke, Henry; Dörr, Marcus; Walsh, John P; Bremner, Alexandra; Iacoviello, Massimo; Macfarlane, Peter; Heeringa, Jan; Stott, David J; Westendorp, Rudi G J; Khaw, Kay-Tee; Magnani, Jared W; Aujesky, Drahomir; Rodondi, Nicolas

    2017-11-28

    Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF. We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF. Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4; P for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease. In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF. © 2017 American Heart Association, Inc.

  10. Left ventricular diastolic performance at rest in patients with angina and normal systolic function - assessment by equilibrium radionuclide angiography

    International Nuclear Information System (INIS)

    Maini, C.L.; Bonetti, M.G.; Valle, G.; Antonelli Incalzi, R.; Montenero, A.S.

    1985-01-01

    The aim of the study was to correlate diastolic function, as evaluated by peak filling rate (PFR) and relative time (TPFR), with the severity of ischemic heart disease, as evaluated by exercise electrocardiography. Accordingly, 83 ischemic patients with effort angina, but normal ejection function at rest and normal left ventricular size, were studied by equilibrium radionuclide angiocardiography within two weeks from the exercise ECG. Diastolic dysfunction, as determined from PFR and, to a lesser extent, from TPFR, is common in patients with ischemic heart disease and normal systolic function. The prevalence and severity of such dysfunction is related more to the severity of the ischemia, as evaluated by the exercise ECG, than to the presence of an old myocardial infarction. Such findings are consistent with the hypothesis that PFR reflects mainly the early diastolic active uncoupling process. (orig.) [de

  11. Prognostic Value of Normal Perfusion but Impaired Left Ventricular Function in the Diabetic Heart on Quantitative Gated Myocardial Perfusion SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Hwanjeong; Choi, Sehun; Han, Yeonhee [Research Institute of Chonbuk National Univ. Medical School and Hospitial, Jeonju (Korea, Republic of); Lee, Dong Soo; Lee, Hoyoung; Chung, Junekey [Seoul National Univ., Seoul (Korea, Republic of)

    2013-09-15

    This study aimed at identifying the predictive parameters on quantitative gated myocardial perfusion single-photon emission computed tomography (QG-SPECT) in diabetic patients with normal perfusion but impaired function. Methods Among the 533 consecutive diabetic patients, 379 patients with normal perfusion on rest Tl-201/dipyridamole-stress Tc-{sup 99m} sestamibi Gated SPECT were enrolled. Patients were grouped into those with normal post-stress left ventricular function (Group I) and those with impaired function (EF <50 or impaired regional wall motion, Group II). We investigated cardiac events and cause of death by chart review and telephone interview. Survival analysis and Cox proportional hazard model analysis were performed. Between the Group I and II, cardiac events as well as chest pain symptoms, smoking, diabetic complications were significantly different (P<0.05). On survival analysis, event free survival rate in Group II was significantly lower than in Group I (P=0.016). In univariate Cox proportional hazard analysis on overall cardiac event, Group (II over I), diabetic nephropathy, summed motion score (SMS), summed systolic thickening score (STS), numbers of abnormal segmental wall motion and systolic thickening predicted more cardiac events (P<0.05). Multivariate analysis showed that STS was the only independent predictor cardiac event. The functional parameter, especially summed systolic thickening score on QG-SPECT had prognostic values, despite normal perfusion, in predicting cardiac events in diabetic patients, and QG-SPECT provides clinically useful risk stratification in diabetic patients with normal perfusion.

  12. ASSOCIATION BETWEEN VISUAL FUNCTION AND SUBRETINAL DRUSENOID DEPOSITS IN NORMAL AND EARLY AGE-RELATED MACULAR DEGENERATION EYES.

    Science.gov (United States)

    Neely, David; Zarubina, Anna V; Clark, Mark E; Huisingh, Carrie E; Jackson, Gregory R; Zhang, Yuhua; McGwin, Gerald; Curcio, Christine A; Owsley, Cynthia

    2017-07-01

    To examine the association between subretinal drusenoid deposits (SDDs) identified by multimodal retinal imaging and visual function in older eyes with normal macular health or in the earliest phases of age-related macular degeneration (AMD). Age-related macular degeneration status for each eye was defined according to the Age-Related Eye Disease Study (AREDS) 9-step classification system (normal = Step 1, early AMD = Steps 2-4) based on color fundus photographs. Visual functions measured were best-corrected photopic visual acuity, contrast and light sensitivity, mesopic visual acuity, low-luminance deficit, and rod-mediated dark adaptation. Subretinal drusenoid deposits were identified through multimodal imaging (color fundus photographs, infrared reflectance and fundus autofluorescence images, and spectral domain optical coherence tomography). The sample included 1,202 eyes (958 eyes with normal health and 244 eyes with early AMD). In normal eyes, SDDs were not associated with any visual function evaluated. In eyes with early AMD, dark adaptation was markedly delayed in eyes with SDDs versus no SDD (a 4-minute delay on average), P = 0.0213. However, this association diminished after age adjustment, P = 0.2645. Other visual functions in early AMD eyes were not associated with SDDs. In a study specifically focused on eyes in normal macular health and in the earliest phases of AMD, early AMD eyes with SDDs have slower dark adaptation, largely attributable to the older ages of eyes with SDD; they did not exhibit deficits in other visual functions. Subretinal drusenoid deposits in older eyes in normal macular health are not associated with any visual functions evaluated.

  13. Higher Fasting Plasma Glucose Levels, within the Normal Range, are Associated with Decreased Processing Speed in High Functioning Young Elderly.

    Science.gov (United States)

    Raizes, Meytal; Elkana, Odelia; Franko, Motty; Ravona Springer, Ramit; Segev, Shlomo; Beeri, Michal Schnaider

    2016-01-01

    We explored the association of plasma glucose levels within the normal range with processing speed in high functioning young elderly, free of type 2 diabetes mellitus (T2DM). A sample of 41 participants (mean age = 64.7, SD = 10; glucose 94.5 mg/dL, SD = 9.3), were examined with a computerized cognitive battery. Hierarchical linear regression analysis showed that higher plasma glucose levels, albeit within the normal range (levels may have an impact on cognitive function.

  14. Inhibition of phospholipase C disrupts cytoskeletal organization and gravitropic growth in Arabidopsis roots.

    Science.gov (United States)

    Andreeva, Zornitza; Barton, Deborah; Armour, William J; Li, Min Y; Liao, Li-Fen; McKellar, Heather L; Pethybridge, Kylie A; Marc, Jan

    2010-10-01

    The phospholipase protein superfamily plays an important role in hormonal signalling and cellular responses to environmental stimuli. There is also growing evidence for interactions between phospholipases and the cytoskeleton. In this report we used a pharmacological approach to investigate whether inhibiting a member of the phospholipase superfamily, phospholipase C (PLC), affects microtubules and actin microfilaments as well as root growth and morphology of Arabidopsis thaliana seedlings. Inhibiting PLC activity using the aminosteroid U73122 significantly inhibited root elongation and disrupted root morphology in a concentration-dependent manner, with the response being saturated at 5 μM, whereas the inactive analogue U73343 was ineffective. The primary root appeared to lose growth directionality accompanied by root waving and formation of curls. Immunolabelling of roots exposed to increasingly higher U73122 concentrations revealed that the normal transverse arrays of cortical microtubules in the elongation zone became progressively more disorganized or depolymerized, with the disorganization appearing within 1 h of incubation. Likewise, actin microfilament arrays also were disrupted. Inhibiting PLC using an alternative inhibitor, neomycin, caused similar disruptions to both cytoskeletal organization and root morphology. In seedlings gravistimulated by rotating the culture plates by 90°, both U73122 and neomycin disrupted the normal gravitropic growth of roots and etiolated hypocotyls. The effects of PLC inhibitors are therefore consistent with the notion that, as with phospholipases A and D, PLC likewise interacts with the cytoskeleton, alters growth morphology, and is involved in gravitropism.

  15. Predicting social functioning in children with a cochlear implant and in normal-hearing children: the role of emotion regulation.

    Science.gov (United States)

    Wiefferink, Carin H; Rieffe, Carolien; Ketelaar, Lizet; Frijns, Johan H M

    2012-06-01

    The purpose of the present study was to compare children with a cochlear implant and normal hearing children on aspects of emotion regulation (emotion expression and coping strategies) and social functioning (social competence and externalizing behaviors) and the relation between emotion regulation and social functioning. Participants were 69 children with cochlear implants (CI children) and 67 normal hearing children (NH children) aged 1.5-5 years. Parents answered questionnaires about their children's language skills, social functioning, and emotion regulation. Children also completed simple tasks to measure their emotion regulation abilities. Cochlear implant children had fewer adequate emotion regulation strategies and were less socially competent than normal hearing children. The parents of cochlear implant children did not report fewer externalizing behaviors than those of normal hearing children. While social competence in normal hearing children was strongly related to emotion regulation, cochlear implant children regulated their emotions in ways that were unrelated with social competence. On the other hand, emotion regulation explained externalizing behaviors better in cochlear implant children than in normal hearing children. While better language skills were related to higher social competence in both groups, they were related to fewer externalizing behaviors only in cochlear implant children. Our results indicate that cochlear implant children have less adequate emotion-regulation strategies and less social competence than normal hearing children. Since they received their implants relatively recently, they might eventually catch up with their hearing peers. Longitudinal studies should further explore the development of emotion regulation and social functioning in cochlear implant children. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. Bowman Capsule Volume and Related Factors in Adults With Normal Renal Function

    Directory of Open Access Journals (Sweden)

    Takaya Sasaki

    2018-03-01

    Conclusion: In the normal adult kidney, there may be an optimal BV to GV ratio for maintaining effective filtration in a variety of clinical situations, including advanced age, obesity, and hypertension.

  17. The cerebral functional location in normal subjects with Chinese classical national music auditory stimulus

    International Nuclear Information System (INIS)

    Sun Da; Xu Wei; Zhan Hongwei; Liu Hongbiao

    2004-01-01

    Purpose: To detect the cerebral functional location in normal subjects with Chinese classical national music auditory stimulus. Methods: 10 normal young students of the medical collage of Zhejiang University,22-24 years old,5 male and 5 female. The first they underwent a 99mTc-ECD brain imaging during a rest state using a dual detectors gamma camera with fan beam collimators. After 2-4 days they were asked to listen a Chinese classical national music that was played by Erhu and Guzheng for 20 minters. They were also asked to pay special attention to the name of the music, what musical instruments they played and what imagination was opened out in the music. 99mTc-ECD was administered in the first 3 minutes during thy listened the music. The brain imaging was performed in 30-60 minutes after the tracer was administered. Results: To compare the rest state, during listening the Chinese classical national music and paying special attention to the imagination of music the right midtemporal in 6 cases, left midtemporal in 2 cases, right superior temporal in 2 cases, left superior temporal in 6 cases, and right inferior temporal in 2 cases were activated. Among them, dual temporal were activated in 6 cases, right temporal in 3 cases and left temporal in 1 case. It is very interesting that the inferior frontal and/or medial frontal lobes were activated in all 10 subjects, and the activity was markedly higher in frontal than in temporal. Among them dual frontal lobes were activated in 9 subjects, and only right frontal in 1 case. The right superior frontal lobes were activated in 2 cases. The occipital lobes were activated in 4 subjects, and dual occipital in 3 cases, right occipital in 1 case. These 4 subjects stated after listening that they imagined the natural landscape and imagination that was opened out in the music follow the music. Other regions that were activated included parietal lobes (right and left in 1 respectively), pre-cingulated gyms (in 2 cases), and left

  18. The cerebral functional location in normal subjects when they listened to story in Chinese

    International Nuclear Information System (INIS)

    Sun Da; Zhan Hongwei; Xu Wei; Liu Hongbiao; Bao Chengkan

    2004-01-01

    Purpose: To detect the cerebral functional location when normal subjects listened to a story in Chinese. Methods: 9 normal young students of the medical collage of Zhejiang University, 23-24 years old, 5 male and 4 female. The first they underwent a 99m Tc-ECD brain imaging at rest using a dual-head gamma camera with fan beam collimators. After 2-4 days they were asked to listen a story in Chinese on a tap for 20 minters. The related an emotional story about a young president of a radio station and his girlfriend as well as his audience and fan, a young girl. They were also asked to pay special attention to the name of the personage in the story, what time and site did the story open out. They were also asked to imagine the imagination of the story. 99m Tc-ECD was administered in the first 3 minutes during they listened the story. The brain imaging was performed in 30-60 minutes after the tracer was administered. Results: To compare the rest state, during listen to the story in Chinese and asked to remember the imagination of story the right superior temporal in 5 cases, left superior temporal in 3 cases, right mid temporal in 2 cases were activated. Among them, dual temporal were activated in l case, only right temporal in 6 cases and left temporal in 2 cases. It is very interesting that the inferior frontal and/or medial frontal lobes were activated lightly in all 9 subjects. Among them dual frontal lobes were activated in 5 subjects, and only right frontal in 3 cases and left frontal in 1 case. The occipital lobes were activated in 6 subjects, and dual occipital in 5 cases, left occipital in 1 case. Other regions that were activated included pre-cingulated gyrus (in 1 case), and left thalamic (in 1 case). Conclusion: During listened to the story in Chinese and asked remember the plot of the story the auditory association cortex in the superior temporal (it is more in right than in left) and some right mid temporal were activated. The inferior frontal and

  19. Heart Failure Increases the Risk of Adverse Renal Outcomes in Patients With Normal Kidney Function.

    Science.gov (United States)

    George, Lekha K; Koshy, Santhosh K G; Molnar, Miklos Z; Thomas, Fridtjof; Lu, Jun L; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P

    2017-08-01

    Heart failure (HF) is associated with poor cardiac outcomes and mortality. It is not known whether HF leads to poor renal outcomes in patients with normal kidney function. We hypothesized that HF is associated with worse long-term renal outcomes. Among 3 570 865 US veterans with estimated glomerular filtration rate (eGFR) ≥60 mL min -1 1.73 m -2 during October 1, 2004 to September 30, 2006, we identified 156 743 with an International Classification of Diseases , Ninth Revision , diagnosis of HF. We examined the association of HF with incident chronic kidney disease (CKD), the composite of incident CKD or mortality, and rapid rate of eGFR decline (slopes steeper than -5 mL min -1 1.73 m -2 y -1 ) using Cox proportional hazard analyses and logistic regression. Adjustments were made for various confounders. The mean±standard deviation baseline age and eGFR of HF patients were 68±11 years and 78±14 mL min -1 1.73 m -2 and in patients without HF were 59±14 years and 84±16 mL min -1 1.73 m -2 , respectively. HF patients had higher prevalence of hypertension, diabetes mellitus, cardiac, peripheral vascular and chronic lung diseases, stroke, and dementia. Incidence of CKD was 69.0/1000 patient-years in HF patients versus 14.5/1000 patient-years in patients without HF, and 22% of patients with HF had rapid decline in eGFR compared with 8.5% in patients without HF. HF patients had a 2.12-, 2.06-, and 2.13-fold higher multivariable-adjusted risk of incident CKD, composite of CKD or mortality, and rapid eGFR decline, respectively. HF is associated with significantly higher risk of incident CKD, incident CKD or mortality, and rapid eGFR decline. Early diagnosis and management of HF could help reduce the risk of long-term renal complications. © 2017 American Heart Association, Inc.

  20. Roles and regulation of brain glutamate transporters in normal and pathological brain function

    International Nuclear Information System (INIS)

    O'Shea, R.D.

    2001-01-01

    Full text: Glutamate (Glu) is the major excitatory neurotransmitter in the mammalian CNS. Synaptically released Glu acts on both ionotropic (iGluR) and metabotropic receptors, and excessive iGluR activation results in neuronal death (termed excitotoxicity). Removal of Glu from the synapse is thus critical for normal transmission and to prevent excitotoxicity, and is performed exclusively by a family of excitatory amino acid transporters (EAATs, also known as glutamate transporters). Disregulation of Glu transport may contribute to the pathogenesis of many neurodegenerative conditions, and altered expression or function of EAATs has been identified in a number of these pathologies. These studies investigated the functional and pathological effects of EAAT inhibitors in vitro, and developed a novel screening assay for compounds with activity at EAATs. Astrocytic EAATs are responsible for the majority of Glu uptake in brain, so preparations containing both astrocytes and neurones are required to analyse the contribution of EAATs to neuroprotection. Organotypic hippocampal cultures (OHCs), which exhibit many of the features of the intact CNS, were prepared from 11-14 day old Sprague Dawley rats (anaesthetised with halothane). Hippocampal slices (350 μm thick) were maintained on culture well inserts in chemically defined medium. After 2 weeks, cultures were treated with EAAT inhibitors for 3-7 days in the presence or absence of 300 μM Glu. Treatment with most EAAT inhibitors resulted in cell death that was proportional to the Glu concentration in the medium. In contrast, (2S,3S,4R)-2-(carboxycyclopropyl)glycine (L-CCG-III), a competitive substrate at EAATs (and possibly an antagonist at the kainate subtype of iGluR), appeared to be neuroprotective: increased Glu was not toxic in the presence of this drug. These results demonstrate the sensitivity of OHCs to inhibition of Glu uptake, highlighting the importance of EAATs in preventing excitotoxicity. Since modulation of

  1. Selective ablation of the androgen receptor in mouse sertoli cells affects sertoli cell maturation, barrier formation and cytoskeletal development.

    Directory of Open Access Journals (Sweden)

    Ariane Willems

    2010-11-01

    Full Text Available The observation that mice with a selective ablation of the androgen receptor (AR in Sertoli cells (SC (SCARKO mice display a complete block in meiosis supports the contention that SC play a pivotal role in the control of germ cell development by androgens. To delineate the physiological and molecular mechanism responsible for this control, we compared tubular development in pubertal SCARKO mice and littermate controls. Particular attention was paid to differences in SC maturation, SC barrier formation and cytoskeletal organization and to the molecular mediators potentially involved. Functional analysis of SC barrier development by hypertonic perfusion and lanthanum permeation techniques and immunohistochemical analysis of junction formation showed that SCARKO mice still attempt to produce a barrier separating basal and adluminal compartment but that barrier formation is delayed and defective. Defective barrier formation was accompanied by disturbances in SC nuclear maturation (immature shape, absence of prominent, tripartite nucleoli and SC polarization (aberrant positioning of SC nuclei and cytoskeletal elements such as vimentin. Quantitative RT-PCR was used to study the transcript levels of genes potentially related to the described phenomena between day 8 and 35. Differences in the expression of SC genes known to play a role in junction formation could be shown from day 8 for Cldn11, from day 15 for Cldn3 and Espn, from day 20 for Cdh2 and Jam3 and from day 35 for ZO-1. Marked differences were also noted in the transcript levels of several genes that are also related to cell adhesion and cytoskeletal dynamics but that have not yet been studied in SC (Actn3, Ank3, Anxa9, Scin, Emb, Mpzl2. It is concluded that absence of a functional AR in SC impedes the remodeling of testicular tubules expected at the onset of spermatogenesis and interferes with the creation of the specific environment needed for germ cell development.

  2. Stimulus-Dominance Effects and Lateral Asymmetries for Language in Normal Subjects and in Patients with a Single Functional Hemisphere

    Science.gov (United States)

    Di Stefano, Marirosa; Marano, Elena; Viti, Marzia

    2004-01-01

    The assessment of language laterality by the dichotic fused-words test may be impaired by interference effects revealed by the dominant report of one member of the stimuli-pair. Stimulus-dominance and ear asymmetry were evaluated in normal population (48 subjects of both sex and handedness) and in 2 patients with a single functional hemisphere.…

  3. Repetitive in vivo treatment with human recombinant interleukin-1 beta modifies beta-cell function in normal rats

    DEFF Research Database (Denmark)

    Wogensen, L D; Reimers, J; Nerup, J

    1992-01-01

    It is unknown whether interleukin-1 exerts a bimodal effect on Beta-cell function in vivo, and whether interleukin-1 has a diabetogenic action in normal animals. We therefore studied: (a) acute effects 2 h after an intraperitoneal bolus injection of 4 micrograms of recombinant human interleukin-1...

  4. Speech recognition in normal hearing and sensorineural hearing loss as a function of the number of spectral channels

    NARCIS (Netherlands)

    Baskent, Deniz

    Speech recognition by normal-hearing listeners improves as a function of the number of spectral channels when tested with a noiseband vocoder simulating cochlear implant signal processing. Speech recognition by the best cochlear implant users, however, saturates around eight channels and does not

  5. SU-E-J-178: A Normalization Method Can Remove Discrepancy in Ventilation Function Due to Different Breathing Patterns

    Energy Technology Data Exchange (ETDEWEB)

    Qu, H; Yu, N; Stephans, K; Xia, P [Cleveland Clinic, Cleveland, OH (United States)

    2014-06-01

    Purpose: To develop a normalization method to remove discrepancy in ventilation function due to different breathing patterns. Methods: Twenty five early stage non-small cell lung cancer patients were included in this study. For each patient, a ten phase 4D-CT and the voluntarily maximum inhale and exhale CTs were acquired clinically and retrospectively used for this study. For each patient, two ventilation maps were calculated from voxel-to-voxel CT density variations from two phases of the quiet breathing and two phases of the extreme breathing. For the quiet breathing, 0% (inhale) and 50% (exhale) phases from 4D-CT were used. An in-house tool was developed to calculate and display the ventilation maps. To enable normalization, the whole lung of each patient was evenly divided into three parts in the longitude direction at a coronal image with a maximum lung cross section. The ratio of cumulated ventilation from the top one-third region to the middle one-third region of the lung was calculated for each breathing pattern. Pearson's correlation coefficient was calculated on the ratios of the two breathing patterns for the group. Results: For each patient, the ventilation map from the quiet breathing was different from that of the extreme breathing. When the cumulative ventilation was normalized to the middle one-third of the lung region for each patient, the normalized ventilation functions from the two breathing patterns were consistent. For this group of patients, the correlation coefficient of the normalized ventilations for the two breathing patterns was 0.76 (p < 0.01), indicating a strong correlation in the ventilation function measured from the two breathing patterns. Conclusion: For each patient, the ventilation map is dependent of the breathing pattern. Using a regional normalization method, the discrepancy in ventilation function induced by the different breathing patterns thus different tidal volumes can be removed.

  6. SU-E-J-178: A Normalization Method Can Remove Discrepancy in Ventilation Function Due to Different Breathing Patterns

    International Nuclear Information System (INIS)

    Qu, H; Yu, N; Stephans, K; Xia, P

    2014-01-01

    Purpose: To develop a normalization method to remove discrepancy in ventilation function due to different breathing patterns. Methods: Twenty five early stage non-small cell lung cancer patients were included in this study. For each patient, a ten phase 4D-CT and the voluntarily maximum inhale and exhale CTs were acquired clinically and retrospectively used for this study. For each patient, two ventilation maps were calculated from voxel-to-voxel CT density variations from two phases of the quiet breathing and two phases of the extreme breathing. For the quiet breathing, 0% (inhale) and 50% (exhale) phases from 4D-CT were used. An in-house tool was developed to calculate and display the ventilation maps. To enable normalization, the whole lung of each patient was evenly divided into three parts in the longitude direction at a coronal image with a maximum lung cross section. The ratio of cumulated ventilation from the top one-third region to the middle one-third region of the lung was calculated for each breathing pattern. Pearson's correlation coefficient was calculated on the ratios of the two breathing patterns for the group. Results: For each patient, the ventilation map from the quiet breathing was different from that of the extreme breathing. When the cumulative ventilation was normalized to the middle one-third of the lung region for each patient, the normalized ventilation functions from the two breathing patterns were consistent. For this group of patients, the correlation coefficient of the normalized ventilations for the two breathing patterns was 0.76 (p < 0.01), indicating a strong correlation in the ventilation function measured from the two breathing patterns. Conclusion: For each patient, the ventilation map is dependent of the breathing pattern. Using a regional normalization method, the discrepancy in ventilation function induced by the different breathing patterns thus different tidal volumes can be removed

  7. Neurocognitive functions in pathological gambling: A comparison with alcohol dependence, Tourette syndrome and normal controls.

    NARCIS (Netherlands)

    Goudriaan, A.E.; Oosterlaan, J.; Beurs, de P.; Brink, van den W.

    2006-01-01

    Aims Neurocognitive functions in pathological gambling have relevance for the aetiology and treatment of this disorder, yet are poorly understood. This study therefore investigated neurocognitive impairments of executive functions in a group of carefully screened Diagnostic and Statistical Manual

  8. Insulin resistance according to β-cell function in women with polycystic ovary syndrome and normal glucose tolerance.

    Science.gov (United States)

    Song, Do Kyeong; Hong, Young Sun; Sung, Yeon-Ah; Lee, Hyejin

    2017-01-01

    Polycystic ovary syndrome (PCOS) is associated with insulin resistance (IR) and compensatory hyperinsulinemia. IR is recognized as a major risk factor for the development of type 2 diabetes mellitus. However, few studies have investigated IR in women with PCOS and normal glucose tolerance. The objective of this study was to evaluate IR and β-cell function in women with PCOS and normal glucose tolerance. Additionally, we sought to evaluate the usefulness of oral glucose tolerance test (OGTT)-derived IR indices in lean women with PCOS. We recruited 100 women with PCOS and normal glucose tolerance and 100 age- and BMI-matched women as controls. IR and insulin secretory indices, including the homeostasis-model assessment (HOMA)-IR, HOMA-M120, HOMA-F and the Stumvoll index, were calculated from an OGTT. Increased β-cell function was defined as>75th percentile for the HOMA-F in control women. Women with PCOS had higher values for post-load 2-hour glucose, fasting insulin, post-load 2-hour insulin, HOMA-IR, HOMA-M120, HOMA-F and lower values for the Stumvoll index than the controls (all PsWomen with PCOS and increased β-cell function showed lower Stumvoll index values than the matched controls (Plean women with PCOS (all PsWomen with PCOS and normal glucose tolerance showed higher IR than controls matched for age, BMI, and β-cell function. β-cell function was increased in women with PCOS when compared to the matched controls, but not when the lean subjects were compared to the matched controls separately. Therefore, early evaluation of IR in women with PCOS and normal glucose tolerance may be needed.

  9. Cognitive functioning and its influence on sexual behavior in normal aging and dementia

    NARCIS (Netherlands)

    Hartmans, C.; Comijs, H.; Jonker, C.

    2014-01-01

    Objective Motivational aspects, emotional factors, and cognition, all of which require intact cognitive functioning may be essential in sexual functioning. However, little is known about the association between cognitive functioning and sexual behavior. The aim of this article is to review the

  10. Directional output distance functions: endogenous directions based on exogenous normalization constraints

    Science.gov (United States)

    In this paper we develop a model for computing directional output distance functions with endogenously determined direction vectors. We show how this model is related to the slacks-based directional distance function introduced by Fare and Grosskopf and show how to use the slacks-based function to e...

  11. The law of distribution of light beam direction fluctuations in telescopes. [normal density functions

    Science.gov (United States)

    Divinskiy, M. L.; Kolchinskiy, I. G.

    1974-01-01

    The distribution of deviations from mean star trail directions was studied on the basis of 105 star trails. It was found that about 93% of the trails yield a distribution in agreement with the normal law. About 4% of the star trails agree with the Charlier distribution.

  12. Normal state resistivity of single crystalline V3Si as a function of neutron irradiation

    International Nuclear Information System (INIS)

    Caton, R.; Viswanathan, R.

    1978-01-01

    Analysis of the normal state resistivity of a neutron damaged single crystal of V 3 Si shows two different regions of behavior: one for T/sub c/ equal to or greater than 10 0 K and another for T/sub c/ equal to or less than 10 0 K

  13. Early cytoskeletal protein modifications precede overt structural degeneration in the DBA/2J mouse model of glaucoma

    Directory of Open Access Journals (Sweden)

    Gina Nicole Wilson

    2016-11-01

    Full Text Available Axonal transport deficits precede structural loss in glaucoma and other neurodegenerations. Impairments in structural support, including modified cytoskeletal proteins and microtubule-destabilizing elements, could be initiating factors in glaucoma pathogenesis. We investigated the time course of changes in protein levels and post-translational modifications in the DBA/2J mouse model of glaucoma. Using anterograde tract tracing of the retinal projection, we assessed major cytoskeletal and transported elements as a function of transport integrity in different stages of pathological progression. Using capillary-based electrophoresis, single- and multiplex immunosorbent assays, and immunofluorescence, we quantified hyperphosphorylated neurofilament-heavy chain, phosphorylated tau (ptau, calpain-mediated spectrin breakdown product (145/150kDa, β –tubulin, and amyloid-β42 proteins based on age and transport outcome to the superior colliculus (SC, the main retinal target in mice. Phosphorylated neurofilament-heavy chain (pNF-H was elevated within the optic nerve (ON and SC of 8-10 month-old DBA/2J mice, but was not evident in the retina until 12-15 months, suggesting that cytoskeletal modifications first appear in the distal retinal projection. As expected, higher pNF-H levels in the SC and retina were correlated with axonal transport deficits. Elevations in hyperphosphorylated tau (ptau occurred in ON and SC between 3-8 month of age while retinal ptau accumulations occurred at 12-15 months in DBA/2J mice. In vitro co-immunoprecipitation experiments suggested increased affinity of ptau for the retrograde motor complex protein, dynactin. We observed a transport-related decrease of β-tubulin in ON of 10-12 month-old DBA/2J mice, suggesting destabilized microtubule array. Elevations in calpain-mediated spectrin breakdown product were seen in ON and SC at the earliest age examined, well before axonal transport loss is evident. Finally, transport

  14. Communication: Density functional theory model for multi-reference systems based on the exact-exchange hole normalization.

    Science.gov (United States)

    Laqua, Henryk; Kussmann, Jörg; Ochsenfeld, Christian

    2018-03-28

    The correct description of multi-reference electronic ground states within Kohn-Sham density functional theory (DFT) requires an ensemble-state representation, employing fractionally occupied orbitals. However, the use of fractional orbital occupation leads to non-normalized exact-exchange holes, resulting in large fractional-spin errors for conventional approximative density functionals. In this communication, we present a simple approach to directly include the exact-exchange-hole normalization into DFT. Compared to conventional functionals, our model strongly improves the description for multi-reference systems, while preserving the accuracy in the single-reference case. We analyze the performance of our proposed method at the example of spin-averaged atoms and spin-restricted bond dissociation energy surfaces.

  15. Communication: Density functional theory model for multi-reference systems based on the exact-exchange hole normalization

    Science.gov (United States)

    Laqua, Henryk; Kussmann, Jörg; Ochsenfeld, Christian

    2018-03-01

    The correct description of multi-reference electronic ground states within Kohn-Sham density functional theory (DFT) requires an ensemble-state representation, employing fractionally occupied orbitals. However, the use of fractional orbital occupation leads to non-normalized exact-exchange holes, resulting in large fractional-spin errors for conventional approximative density functionals. In this communication, we present a simple approach to directly include the exact-exchange-hole normalization into DFT. Compared to conventional functionals, our model strongly improves the description for multi-reference systems, while preserving the accuracy in the single-reference case. We analyze the performance of our proposed method at the example of spin-averaged atoms and spin-restricted bond dissociation energy surfaces.

  16. Active Polar Gels: a Paradigm for Cytoskeletal Dynamics

    Science.gov (United States)

    Julicher, Frank

    2006-03-01

    The cytoskeleton of eucaryotic cells is an intrinsically dynamic network of rod-like filaments. Active processes on the molecular scale such as the action of motor proteins and the polymerization and depolymerization of filaments drive active dynamic behaviors while consuming chemical energy in the form of a fuel. Such emergent dynamics is regulated by the cell and is important for many cellular processes such as cell locomotion and cell division. From a general point of view the cytoskeleton represents an active gel-like material with interesting material properties. We present a general theory of active viscoelastic materials made of polar filaments which is motivated by the the cytoskeleton. The continuous consumption of a fuel generates a non- equilibrium state characterized by the generation of flows and stresses. Our theory can be applied to experiments in which cytoskeletal patterns are set in motion by active processes such as those which are at work in cells. It can also capture generic aspects of the flows and stress profiles which occur during cell locomotion.

  17. Hand function with touch screen technology in children with normal hand formation, congenital differences, and neuromuscular disease.

    Science.gov (United States)

    Shin, David H; Bohn, Deborah K; Agel, Julie; Lindstrom, Katy A; Cronquist, Sara M; Van Heest, Ann E

    2015-05-01

    To measure and compare hand function for children with normal hand development, congenital hand differences (CHD), and neuromuscular disease (NMD) using a function test with touch screen technology designed as an iPhone application. We measured touch screen hand function in 201 children including 113 with normal hand formation, 43 with CHD, and 45 with NMD. The touch screen test was developed on the iOS platform using an Apple iPhone 4. We measured 4 tasks: touching dots on a 3 × 4 grid, dragging shapes, use of the touch screen camera, and typing a line of text. The test takes 60 to 120 seconds and includes a pretest to familiarize the subject with the format. Each task is timed independently and the overall time is recorded. Children with normal hand development took less time to complete all 4 subtests with increasing age. When comparing children with normal hand development with those with CHD or NMD, in children aged less than 5 years we saw minimal differences; those aged 5 to 6 years with CHD took significantly longer total time; those aged 7 to 8 years with NMD took significantly longer total time; those aged 9 to 11 years with CHD took significantly longer total time; and those aged 12 years and older with NMD took significantly longer total time. Touch screen technology has becoming increasingly relevant to hand function in modern society. This study provides standardized age norms and shows that our test discriminates between normal hand development and that in children with CHD or NMD. Diagnostic III. Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  18. Antibodies to cytoskeletal proteins as evidenced by immunofluorescence microscopy and radioimmunoassay

    International Nuclear Information System (INIS)

    Zugehoer, M.; Struy, H.; Morenz, J.

    1987-01-01

    In patients suffering from chronic hepatitis, collagenosis and infectious mononucleosis, resp., as well as in blood donors antibodies against cytoskeletal antigens such as actin, myosin, actinin, desmin, keratin, and tubulin were determined by radioimmunoassay

  19. Changes in cytoskeletal dynamics and nonlinear rheology with metastatic ability in cancer cell lines

    International Nuclear Information System (INIS)

    Coughlin, Mark F; Fredberg, Jeffrey J

    2013-01-01

    Metastatic outcome is impacted by the biophysical state of the primary tumor cell. To determine if changes in cancer cell biophysical properties facilitate metastasis, we quantified cytoskeletal biophysics in well-characterized human skin, bladder, prostate and kidney cell line pairs that differ in metastatic ability. Using magnetic twisting cytometry with optical detection, cytoskeletal dynamics was observed through spontaneous motion of surface bound marker beads and nonlinear rheology was characterized through large amplitude forced oscillations of probe beads. Measurements of cytoskeletal dynamics and nonlinear rheology differed between strongly and weakly metastatic cells. However, no set of biophysical parameters changed systematically with metastatic ability across all cell lines. Compared to their weakly metastatic counterparts, the strongly metastatic kidney cancer cells exhibited both increased cytoskeletal dynamics and stiffness at large deformation which are thought to facilitate the process of vascular invasion. (paper)

  20. Antibodies to cytoskeletal proteins as evidenced by immunofluorescence microscopy and radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Zugehoer, M; Struy, H; Morenz, J

    1987-01-01

    In patients suffering from chronic hepatitis, collagenosis and infectious mononucleosis, resp., as well as in blood donors antibodies against cytoskeletal antigens such as actin, myosin, actinin, desmin, keratin, and tubulin were determined by radioimmunoassay.

  1. Normal axonal ion channel function in large peripheral nerve fibers following chronic ciguatera sensitization.

    Science.gov (United States)

    Vucic, Steve; Kiernan, Matthew C

    2008-03-01

    Although the acute clinical effects of ciguatera poisoning, due to ingestion of ciguatoxin, are mediated by activation of transient Na+ channels, the mechanisms underlying ciguatera sensitization remain undefined. Axonal excitability studies were performed by stimulating the median motor and sensory nerves in two patients with ciguatera sensitization. Excitability parameters were all within normal limits, thereby arguing against dysfunction of axonal membrane ion channels in large-diameter fibers in ciguatera sensitization.

  2. Liver histology and follow up of 68 patients with ulcerative colitis and normal liver function tests.

    OpenAIRE

    Broomé, U; Glaumann, H; Hultcrantz, R

    1990-01-01

    Hepatobiliary disorders are well known complications in patients with ulcerative colitis but it is not possible to predict those patients with ulcerative colitis who will eventually develop liver disease. In this study, liver biopsies from 74 patients with ulcerative colitis have been reevaluated. None of the patients showed clinical or biochemical signs of liver disease at the time of biopsy. Thirty seven (50%) had a completely normal liver biopsy. The others showed minimal portal inflammati...

  3. The Drosophila HEM-2/NAP1 homolog KETTE controls axonal pathfinding and cytoskeletal organization.

    Science.gov (United States)

    Hummel, T; Leifker, K; Klämbt, C

    2000-04-01

    In Drosophila, the correct formation of the segmental commissures depends on neuron-glial interactions at the midline. The VUM midline neurons extend axons along which glial cells migrate in between anterior and posterior commissures. Here, we show that the gene kette is required for the normal projection of the VUM axons and subsequently disrupts glial migration. Axonal projection defects are also found for many other moto- and interneurons. In addition, kette affects the cell morphology of mesodermal and epidermal derivatives, which show an abnormal actin cytoskeleton. The KETTE protein is homologous to the transmembrane protein HEM-2/NAP1 evolutionary conserved from worms to vertebrates. In vitro analysis has shown a specific interaction of the vertebrate HEM-2/NAP1 with the SH2-SH3 adapter protein NCK and the small GTPase RAC1, which both have been implicated in regulating cytoskeleton organization and axonal growth. Hypomorphic kette mutations lead to axonal defects similar to mutations in the Drosophila NCK homolog dreadlocks. Furthermore, we show that kette and dock mutants genetically interact. NCK is thought to interact with the small G proteins RAC1 and CDC42, which play a role in axonal growth. In line with these observations, a kette phenocopy can be obtained following directed expression of mutant DCDC42 or DRAC1 in the CNS midline. In addition, the kette mutant phenotype can be partially rescued by expression of an activated DRAC1 transgene. Our data suggest an important role of the HEM-2 protein in cytoskeletal organization during axonal pathfinding.

  4. Distinct and shared cognitive functions mediate event- and time-based prospective memory impairment in normal ageing

    Science.gov (United States)

    Gonneaud, Julie; Kalpouzos, Grégoria; Bon, Laetitia; Viader, Fausto; Eustache, Francis; Desgranges, Béatrice

    2011-01-01

    Prospective memory (PM) is the ability to remember to perform an action at a specific point in the future. Regarded as multidimensional, PM involves several cognitive functions that are known to be impaired in normal aging. In the present study, we set out to investigate the cognitive correlates of PM impairment in normal aging. Manipulating cognitive load, we assessed event- and time-based PM, as well as several cognitive functions, including executive functions, working memory and retrospective episodic memory, in healthy subjects covering the entire adulthood. We found that normal aging was characterized by PM decline in all conditions and that event-based PM was more sensitive to the effects of aging than time-based PM. Whatever the conditions, PM was linked to inhibition and processing speed. However, while event-based PM was mainly mediated by binding and retrospective memory processes, time-based PM was mainly related to inhibition. The only distinction between high- and low-load PM cognitive correlates lays in an additional, but marginal, correlation between updating and the high-load PM condition. The association of distinct cognitive functions, as well as shared mechanisms with event- and time-based PM confirms that each type of PM relies on a different set of processes. PMID:21678154

  5. Angiotensin infusion effects on left ventricular function. Assessment in normal subjects and in patients with coronary disease.

    Science.gov (United States)

    Bianco, J A; Laskey, W K; Makey, D G; Shafer, R B

    1980-02-01

    Radionuclide multigating of the cardiac cycle was employed to assess effects of angiotensin infusion on left ventricular function. In six normal subjects, angiotensin infusion decreased heart rate (HR) from 72 +/- SEM 2 to 57 +/- 2 beats/min (P less than 0.001); while systolic blood pressure (BP) increased from 119 +/- 2 to 178 +/- 1 mm Hg (P less than 0.001), and ejection fraction (EF) declined from 58 +/- 1 to 47 +/- 2 percent (P less than 0.05). In contrast, in 11 normal subjects, supine exercise increased HR and systolic BP by 55 and 49 percent, whereas EF increased from 64 +/- 1 to 71 +/- 1 (P less than 0.001). In ten patients with CAD, angiotensin infusion produced no change in HR, increased systolic BP by 34 percent, and decreased EF by 11 percent. Angiotensin infusion induced left ventricular depression in normal subjects and in patients with CAD. It cannot substitute for exercise in intervention radionuclide ventriculography.

  6. Lower extremity function in normal cognitive aging, mild cognitive impairment, and Alzheimer’s disease

    NARCIS (Netherlands)

    Eggermont, L.H.P.; Gavett, B.E.; Volkers, K.M.; Blankevoort, C.G.; Scherder, E.J.A.; Jefferson, A.L.; Steinberg, E.; Nair, A.; Green, R.C.; Stern, R.A.

    2010-01-01

    Eggermont LH, Gavett BE, Volkers KM, Blankevoort CG, Scherder EJ, Jefferson AL, Steinberg E, Nair A, Green RC, Stern RA. Lower-extremity function in cognitively healthy aging, mild cognitive impairment, and Alzheimer's disease. Objective: To examine differences in lower-extremity function in

  7. Pregnancy outcomes are not altered by variation in thyroid function within the normal range in women free of thyroid disease.

    Science.gov (United States)

    Veltri, Flora; Kleynen, Pierre; Grabczan, Lidia; Salajan, Alexandra; Rozenberg, Serge; Pepersack, Thierry; Poppe, Kris

    2018-02-01

    In the recently revised guidelines on the management of thyroid dysfunction during pregnancy, treatment with thyroid hormone (LT4) is not recommended in women without thyroid autoimmunity (TAI) and TSH levels in the range 2.5-4.0 mIU/L, and in a recent study in that particular group of pregnant women, more complications were observed when a treatment with LT4 was given. The objective of the study was therefore to investigate whether variation in thyroid function within the normal (non-pregnant) range in women free of thyroid disease was associated with altered pregnancy outcomes? Cross-sectional data analysis of 1321 pregnant women nested within an ongoing prospective collection of pregnant women's data in a single centre in Brussels, Belgium. Thyroid peroxidase antibodies (TPO-abs), thyroid-stimulating hormone (TSH), free T4 (FT4) and ferritin levels were measured and baseline characteristics were recorded. Women taking LT4, with TAI and thyroid function outside the normal non-pregnant range were excluded. Pregnancy outcomes and baseline characteristics were correlated with all TSH and FT4 levels within the normal range and compared between two groups (TSH cut-off 500 mL) was inversely associated with serum FT4 levels (OR: 0.35; CI 95%: 0.13-0.96); P  = 0.040. Also 10% of women free of thyroid disease had serum TSH levels ≥2.5 mIU/L. Variation in thyroid function during the first trimester within the normal (non-pregnant) range in women free of thyroid disease was not associated with altered pregnancy outcomes. These results add evidence to the recommendation against LT4 treatment in pregnant women with high normal TSH levels and without TPO antibodies. © 2018 European Society of Endocrinology.

  8. Non-postural serial changes in renal function during the third trimester of normal human pregnancy.

    Science.gov (United States)

    Ezimokhai, M; Davison, J M; Philips, P R; Dunlop, W

    1981-05-01

    Seventeen healthy women were investigated near the beginning and again near the end of the third trimester of their normal pregnancies. Infusion studies were performed in the left lateral position. There was a highly significant decrease in effective renal plasma flow but not in glomerular filtration rate, measured as inulin clearance. Plasma creatinine concentration increased significantly, but the renal handling of creatinine was unchanged; simultaneous 24-hour creatinine clearance showed a tendency to decrease. Serum urate concentration also increased significantly, apparently due to an increase in net tubular reabsorption of urate.

  9. Secondary Myelitis in Dermal Sinus Causing Paraplegia in a Child with Previously Normal Neurological Function

    Directory of Open Access Journals (Sweden)

    Sakina Rashid

    2016-01-01

    Full Text Available Neural tube defects result from failure of neural tube fusion during early embryogenesis, the fourth week after conception. The spectrum of severity is not uniform across the various forms of this congenital anomaly as certain presentations are not compatible with extrauterine life (anencephaly while, on the other hand, other defects may remain undiagnosed as they are entirely asymptomatic (occult spina bifida. We report a child with previously normal neurological development, a devastating clinical course following superinfection of a subtle spina bifida defect which resulted in a flaccid paralysis below the level of the lesion and permanent neurological deficits following resolution of the acute infection and a back closure surgery.

  10. Nuclear shape changes are induced by knockdown of the SWI/SNF ATPase BRG1 and are independent of cytoskeletal connections.

    Directory of Open Access Journals (Sweden)

    Karen M Imbalzano

    Full Text Available Changes in nuclear morphology occur during normal development and have been observed during the progression of several diseases. The shape of a nucleus is governed by the balance of forces exerted by nuclear-cytoskeletal contacts and internal forces created by the structure of the chromatin and nuclear envelope. However, factors that regulate the balance of these forces and determine nuclear shape are poorly understood. The SWI/SNF chromatin remodeling enzyme ATPase, BRG1, has been shown to contribute to the regulation of overall cell size and shape. Here we document that immortalized mammary epithelial cells show BRG1-dependent nuclear shape changes. Specifically, knockdown of BRG1 induced grooves in the nuclear periphery that could be documented by cytological and ultrastructural methods. To test the hypothesis that the observed changes in nuclear morphology resulted from altered tension exerted by the cytoskeleton, we disrupted the major cytoskeletal networks and quantified the frequency of BRG1-dependent changes in nuclear morphology. The results demonstrated that disruption of cytoskeletal networks did not change the frequency of BRG1-induced nuclear shape changes. These findings suggest that BRG1 mediates control of nuclear shape by internal nuclear mechanisms that likely control chromatin dynamics.

  11. Effect of fatty acids on functional properties of normal wheat and waxy wheat starches: A structural basis.

    Science.gov (United States)

    Wang, Shujun; Wang, Jinrong; Yu, Jinglin; Wang, Shuo

    2016-01-01

    The effects of three saturated fatty acids on functional properties of normal wheat and waxy wheat starches were investigated. The complexing index (CI) of normal wheat starch-fatty acid complexes decreased with increasing carbon chain length. In contrast, waxy wheat starch-fatty acid complexes presented much lower CI. V-type crystalline polymorphs were formed between normal wheat starch and three fatty acids, with shorter chain fatty acids producing more crystalline structure. FTIR and Raman spectroscopy presented the similar results with XRD. The formation of amylose-fatty acid complex inhibited granule swelling, gelatinization progression, retrogradation and pasting development of normal wheat starch, with longer chain fatty acids showing greater inhibition. Amylopectin can also form complexes with fatty acids, but the amount of complex was too little to be detected by XRD, FTIR, Raman and DSC. As a consequence, small changes were observed in the functional properties of waxy wheat starch with the addition of fatty acids. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Dehydroepiandrosterone substitution in female adrenal failure: no impact on endothelial function and cardiovascular parameters despite normalization of androgen status

    DEFF Research Database (Denmark)

    Christiansen, Jens Juel; Andersen, Niels Holmark; Sørensen, Keld E

    2007-01-01

    because of skin side effects and anxiety, respectively. All patients had low circulating androgens baseline and normal range androgens during DHEA treatment. We examined patients with noninvasive endothelial cell function, magnetic resonance imaging (MRI)-based cardiac output, echocardiography, ambulatory...... 24-h blood pressure and maximal oxygen consumption. RESULTS: DHEA treatment normalized androgen status to levels seen in healthy women. DHEA and placebo treatment had no effect on echocardiographic parameters of myocardial dimensions or systolic and diastolic function, noninvasive endothelial cell...... in vascular endothelium has been described and in vitro studies have shown involvement of DHEA in NO dependent pathways. AIM: To evaluate effects of DHEA substitution on cardiovascular parameters. DESIGN: Six months randomized, double-blind, placebo-controlled crossover study. Treatment consisted of DHEA 50...

  13. Signal-to-background-ratio preferences of normal-hearing listeners as a function of music

    Science.gov (United States)

    Barrett, Jillian G.

    2005-04-01

    The primary purpose of speech is to convey a message. Many factors affect the listener's overall reception, several of which have little to do with the linguistic content itself, but rather with the delivery (e.g., prosody, intonation patterns, pragmatics, paralinguistic cues). Music, however, may convey a message either with or without linguistic content. In instances in which music has lyrics, one cannot assume verbal content will take precedence over sonic properties. Lyric emphasis over other aspects of music cannot be assumed. Singing introduces distortion of the vowel-consonant temporal ratio of speech, emphasizing vowels and de-emphasizing consonants. The phonemic production alterations of singing make it difficult for even those with normal hearing to understand the singer. This investigation was designed to identify singer-to-background-ratio (SBR) prefer- ences for normal hearing adult listeners (as opposed to SBR levels maxi-mizing speech discrimination ability). Stimuli were derived from three different original songs, each produced in two different genres and sung by six different singers. Singer and genre were the two primary contributors to significant differences in SBR preferences, though results clearly indicate genre, style and singer interact in different combinations for each song, each singer, and for each subject in an unpredictable manner.

  14. Normal function of the hypothalamic-pituitary growth axis in three dwarf Friesian foals.

    Science.gov (United States)

    de Graaf-Roelfsema, E; Back, W; Keizer, H A; Stout, T A E; van der Kolk, J H

    2009-09-26

    Serial blood samples were collected from three dwarf Friesian foals to examine their endogenous growth hormone (GH) profiles, and the integrity of the GH-insulin-like growth factor-1 (IGF-1) axis was tested in one of them by examining its responses to the administration of GH-releasing hormone (GHRH) and to 10 days of treatment with recombinant equine GH. The basal serum concentrations of IGF-1 in the three dwarf foals were compared with those in nine age-matched normal foals. All the dwarf foals secreted endogenous GH. Stimulation with 7.0 microg/kg GHRH led to a 1400 per cent increase in plasma GH concentration in the dwarf foal tested, and 10 daily subcutaneous treatments with 20 microg/kg recombinant equine GH led to a 100 per cent increase in its serum IGF-1 concentration. The basal serum concentrations of IGF-1 in the dwarf foals were not significantly different from those of the normal foals.

  15. Transient Ischemic Attack and Ischemic Stroke in Danon Disease with Formation of Left Ventricular Apical Thrombus despite Normal Systolic Function

    OpenAIRE

    Tsuda, Takeshi; Shillingford, Amanda J.; Vetter, Jane; Kandula, Vinay; Jain, Badal; Temple, Joel

    2017-01-01

    Danon disease is a rare X-linked dominant skeletal and cardiac muscle disorder presenting with hypertrophic cardiomyopathy, Wolf-Parkinson-White syndrome, skeletal myopathy, and mild intellectual disability. Early morbidity and mortality due to heart failure or sudden death are known in Danon disease, more in males than in females. Here, we present a 17-year-old female adolescent with Danon disease and severe concentric hypertrophy with normal left ventricular (LV) systolic function, who has ...

  16. Integrin β1 regulates leiomyoma cytoskeletal integrity and growth

    Science.gov (United States)

    Malik, Minnie; Segars, James; Catherino, William H.

    2014-01-01

    Uterine leiomyomas are characterized by an excessive extracellular matrix, increased mechanical stress, and increased active RhoA. Previously, we observed that mechanical signaling was attenuated in leiomyoma, but the mechanisms responsible remain unclear. Integrins, especially integrin β1, are transmembrane adhesion receptors that couple extracellular matrix stresses to the intracellular cytoskeleton to influence cell proliferation and differentiation. Here we characterized integrin and laminin to signaling in leiomyoma cells. We observed a 2.25 ± 0.32 fold increased expression of integrin β1 in leiomyoma cells, compared to myometrial cells. Antibody-mediated inhibition of integrin β1 led to significant growth inhibition in leiomyoma cells and a loss of cytoskeletal integrity. Specifically, polymerization of actin filaments and formation of focal adhesions were reduced by inhibition of integrin p1. Inhibition of integrin β1 in leiomyoma cells led to 0.81 ± 0.02 fold decrease in active RhoA, and resembled levels found in serum-starved cells. Likewise, inhibition of integrin β1 was accompanied by a decrease in phospho-ERK. Compared to myometrial cells, leiomyoma cells demonstrated increased expression of integrin α6 subunit to laminin receptor (1.91 ± 0.11 fold), and increased expression of laminin 5α (1.52±0.02), laminin 5β (3.06±0.92), and laminin 5γ (1.66 ± 0.06). Of note, leiomyoma cells grown on laminin matrix appear to realign themselves. Taken together, the findings reveal that the attenuated mechanical signaling in leiomyoma cells is accompanied by an increased expression and a dependence on integrin β1 signaling in leiomyoma cells, compared to myometrial cells. PMID:23023061

  17. Transient Ischemic Attack and Ischemic Stroke in Danon Disease with Formation of Left Ventricular Apical Thrombus despite Normal Systolic Function

    Directory of Open Access Journals (Sweden)

    Takeshi Tsuda

    2017-01-01

    Full Text Available Danon disease is a rare X-linked dominant skeletal and cardiac muscle disorder presenting with hypertrophic cardiomyopathy, Wolf-Parkinson-White syndrome, skeletal myopathy, and mild intellectual disability. Early morbidity and mortality due to heart failure or sudden death are known in Danon disease, more in males than in females. Here, we present a 17-year-old female adolescent with Danon disease and severe concentric hypertrophy with normal left ventricular (LV systolic function, who has been complaining of intermittent headache and weakness for about 3 years, initially diagnosed with hemiplegic migraine. Subsequently, her neurological manifestation progressed to transient ischemic attack (TIA and eventually to ischemic stroke confirmed by CT scan with 1-day history of expressive aphasia followed by persistent left side weakness and numbness. Detailed echocardiogram for the first time revealed a small LV apical thrombus with unchanged severe biventricular hypertrophy and normal systolic function. This unexpected LV apical thrombus may be associated with a wide spectrum of neurological deficits ranging from TIA to ischemic stroke in Danon disease. Possibility of cerebral ischemic events should be suspected in Danon disease when presenting with neurological deficits even with normal systolic function. Careful assessment for LV apical thrombus is warranted in such cases.

  18. The influence of right ventricular apical pacing on left atrial volume in patients with normal left ventricular function

    Directory of Open Access Journals (Sweden)

    AR Moaref1

    2008-03-01

    Full Text Available Background: Right ventricular apical (RVA pacing has been reported to induce several deleterious effects particularly in the presence of structural heart disease but can also involve patients with normal left ventricular (LV function. Left atrial (LA enlargement is one of these effects, but the majority of studies have measured LA dimension rather than volume.Objective: The present prospective study was designed to assess the effect of RVA pacing on LA volume in patients with normal LV function.Patients and Methods: The study comprised 41 consecutive patients with LV ejection fraction ≥ 45% and LV end diastolic dimension ≤ 56 mm who underwent single-or dual- chamber pacemaker implantation in RVA and followed for LA volume measurement and pacemaker analysis at least during the ensuing 4.2 months. Results: In all, 21 patients were excluded from the study due to five spontaneous wide QRS complex (≥120msec, one recent acute coronary syndrome,one significant valvular heart disease, three pacing frequency <90%, eight death or losing follow up in three cases. In remaining 20 patients, LA volume ragned from 21 to 54 mm3 with mean of 37.3±9.7 mm3 prior to pacemaker implantation that increased to 31 to 103 mm3 (54.3±17.0 during follow-up (P<0.001.Conclusion: RVA pacing might lead to an increase in LA volume even in patients with normal LV function.

  19. A study of nephron function in normal tropical residents using the creatinine and lithium clearances

    Science.gov (United States)

    Arthur, S. K.; Nyarko, A. K.; Asaku, J. Y.; Akyeampong, A. Y.

    The kidney bears the brunt of the demands of a tropical climate for water and electrolyte homeostasis. We hypothesised that a tropical climate may cause adaptive changes in the entire organism leading to altered renal function in our subjects. Hence renal function data for residents of a temperate climate may not be applic- able to tropical residents. We therefore sought to elucidate renal function in subjects residing in a tropical climate. We used lithium clearance, CLi, a non-invasive tool for assessing proximal tubular function in humans, and endogenous creatinine clearance, CCr, to estimate proximal tubular function and glomerular function, respectively, in our subjects. We did this in order to establish whether or not nephron function in our subjects differs from that for residents of a temperate climate. Nineteen male and 12 female Ghanaian subjects aged between 15 and 48 years were studied. The estimated GCr was 117.3+/-6.6 ml/min for male subjects and 97+/-6.4 ml/min for female subjects. CLi was 20.3+/-1.6 ml/min for male and 19.1+/-0.4 ml/min for female subjects, respectively. The estimated absolute reabsorption rate of fluid of proximal tubules was 97.0+/-6.0 ml/min for males and 78.1+/-6.0 ml/min for females. The percentage proximal fluid reabsorption for male and female subjects was 81.2+/-1.4 and 79.5+/-1.6, respectively. The differences between male and female values (mean+/-SEM) were not statistically significant. The data suggest that the proximal tubule in residents of a tropical climate may reabsorb more fluid compared to that in residents of a temperate climate. Our values for proximal tubular reabsorption are higher than those reported for residents of a temperature climate. Our estimate of glomerular filtration, however, is similar to published data for Caucasians. The difference in proximal tubular function may reflect possible renal adaptation to a hot, humid climate. We conclude that renal function of tropical residents differs from that of

  20. Thyroid Function Within the Normal Range and Risk of Coronary Heart Disease

    DEFF Research Database (Denmark)

    Åsvold, Bjørn O; Vatten, Lars J; Bjøro, Trine

    2015-01-01

    documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD). OBJECTIVE: To assess the association between differences in thyroid function within the reference range and CHD risk. DESIGN...... known thyroid or cardiovascular disease at baseline. EXPOSURES: Thyroid function as expressed by serum thyrotropin levels at baseline. MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status....... This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased CHD risk does not appear to be a reason for lowering the upper thyrotropin reference limit....

  1. Normal saline influences coagulation and endothelial function after traumatic brain injury and hemorrhagic shock in pigs

    DEFF Research Database (Denmark)

    Dekker, Simone E; Sillesen, Martin; Bambakidis, Ted

    2014-01-01

    ), colloids (Hextend [HEX]), and fresh frozen plasma (FFP) resuscitation are associated with differential effects on coagulation and endothelial systems. METHODS: We subjected 15 Yorkshire swine to TBI and HS (40% blood volume), and kept in HS for 2 hours before resuscitation with NS, HEX, or FFP. Markers......BACKGROUND: Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of trauma-related deaths. These insults disrupt coagulation and endothelial systems. This study investigated whether previously reported differences in lesion size and brain swelling during normal saline (NS...... of endothelial activation (E-selectin, Intercellular adhesion molecule [ICAM]-1), coagulation activation (prothrombin fragment 1 + 2), and natural anticoagulation (activated protein C [aPC]) were determined in serum and brain whole cell lysates. RESULTS: Serum levels of aPC were greater in the NS group (203 ± 30...

  2. The acyl-CoA binding protein is required for normal epidermal barrier function in mice

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Bek, Signe; Marcher, Ann-Britt

    2012-01-01

    (+/+) and ACBP(-/-) mice showed very similar composition, except for a significant and specific decrease in the very long chain free fatty acids (VLC-FFA) in stratum corneum of ACBP(-/-) mice. This finding indicates that ACBP is critically involved in the processes that lead to production of stratum corneum VLC......The acyl-CoA binding protein (ACBP) is a 10 kDa intracellular protein expressed in all eukaryotic species. Mice with targeted disruption of Acbp (ACBP(-/-) mice) are viable and fertile but present a visible skin and fur phenotype characterized by greasy fur and development of alopecia and scaling...... with age. Morphology and development of skin and appendages are normal in ACBP(-/-) mice; however, the stratum corneum display altered biophysical properties with reduced proton activity and decreased water content. Mass spectrometry analyses of lipids from epidermis and stratum corneum of ACBP...

  3. Impaired hematopoietic stem cell functioning after serial transplantation and during normal aging

    NARCIS (Netherlands)

    Kamminga, LM; Van Os, R; Ausema, A; Noach, EJK; Weersing, E; Dontje, B; Vellenga, E; De Haan, G

    Adult somatic stem cells possess extensive self-renewal capacity, as their primary role is to replenish aged and functionally impaired tissues. We have previously shown that the stem cell pool in short-lived DBA/2 (D2) mice is reduced during aging, in contrast to long-lived C57BL/6 (136) mice. This

  4. The Effect of Executive Function on Science Achievement among Normally Developing 10-Year Olds

    Science.gov (United States)

    Lederman, Sheri G.

    2012-01-01

    Executive function (EF) is an umbrella term used to identify a set of discrete but interrelated cognitive abilities that enable individuals to engage in goal-directed, future-oriented action in response to a novel context. Developmental studies indicate that EF is predictive of reading and math achievement in middle childhood. The purpose of this…

  5. Role of C-type natriuretic peptide in the function of normal human sperm

    Directory of Open Access Journals (Sweden)

    Hui Xia

    2016-01-01

    Full Text Available C-type natriuretic peptide (CNP is a newly discovered type of local regulatory factor that mediates its biological effects through the specific, membrane-bound natriuretic peptide receptor-B (NPR-B. Recent studies have established that CNP is closely related to male reproductive function. The aims of this study were to determine the distribution of CNP/NPR-B in human ejaculated spermatozoa through different methods (such as immunolocalization, real time polymerase chain reaction and Western Blot, and then to evaluate the influence of CNP on sperm function i n vitro, such as motility and acrosome reaction. Human semen samples were collected from consenting donors who met the criteria of the World Health Organization for normozoospermia. Our results show that the specific receptor NPR-B of CNP is localized in the acrosomal region of the head and the membrane of the front-end tail of the sperm, and there is no signal of CNP in human sperm. Compared with the control, CNP can induce a significant dose-dependent increase in spermatozoa motility and acrosome reaction. In summary, CNP/NPR-B can affect sperm motility and acrosome reaction, thus regulating the reproductive function of males. CNP may be a new key factor in regulating sperm function.

  6. Pharmacokinetics and pharmacodynamics of candesartan cilexetil in patients with normal to severely impaired renal function

    NARCIS (Netherlands)

    Buter, H; Navis, GY; Woittiez, AJJ; de Zeeuw, D; de Jong, PE

    Objective: We studied the pharmacokinetics and pharmacodynamics of single and multiple doses of candesartan cilexetil 8 mg per day in hypertensive patients with different degrees of renal function impairment. Candesartan is an angiotensin II subtype I (AT1) receptor antagonist that is administered

  7. Insulin resistance according to β-cell function in women with polycystic ovary syndrome and normal glucose tolerance.

    Directory of Open Access Journals (Sweden)

    Do Kyeong Song

    Full Text Available Polycystic ovary syndrome (PCOS is associated with insulin resistance (IR and compensatory hyperinsulinemia. IR is recognized as a major risk factor for the development of type 2 diabetes mellitus. However, few studies have investigated IR in women with PCOS and normal glucose tolerance. The objective of this study was to evaluate IR and β-cell function in women with PCOS and normal glucose tolerance. Additionally, we sought to evaluate the usefulness of oral glucose tolerance test (OGTT-derived IR indices in lean women with PCOS.We recruited 100 women with PCOS and normal glucose tolerance and 100 age- and BMI-matched women as controls. IR and insulin secretory indices, including the homeostasis-model assessment (HOMA-IR, HOMA-M120, HOMA-F and the Stumvoll index, were calculated from an OGTT. Increased β-cell function was defined as>75th percentile for the HOMA-F in control women.Women with PCOS had higher values for post-load 2-hour glucose, fasting insulin, post-load 2-hour insulin, HOMA-IR, HOMA-M120, HOMA-F and lower values for the Stumvoll index than the controls (all Ps<0.05. Women with PCOS and increased β-cell function showed lower Stumvoll index values than the matched controls (P<0.05. The HOMA-F was significantly associated with the HOMA-M120 and Stumvoll index when adjusted for age and BMI in a multiple regression analysis (all Ps<0.05. The HOMA-M120 was positively correlated with triglycerides and free testosterone, and the Stumvoll index was negatively correlated with triglycerides and free testosterone in lean women with PCOS (all Ps<0.05.Women with PCOS and normal glucose tolerance showed higher IR than controls matched for age, BMI, and β-cell function. β-cell function was increased in women with PCOS when compared to the matched controls, but not when the lean subjects were compared to the matched controls separately. Therefore, early evaluation of IR in women with PCOS and normal glucose tolerance may be needed.

  8. Estimating functional liver reserve following hepatic irradiation: Adaptive normal tissue response models

    International Nuclear Information System (INIS)

    Stenmark, Matthew H.; Cao, Yue; Wang, Hesheng; Jackson, Andrew; Ben-Josef, Edgar; Ten Haken, Randall K.; Lawrence, Theodore S.; Feng, Mary

    2014-01-01

    Purpose: To estimate the limit of functional liver reserve for safe application of hepatic irradiation using changes in indocyanine green, an established assay of liver function. Materials and methods: From 2005 to 2011, 60 patients undergoing hepatic irradiation were enrolled in a prospective study assessing the plasma retention fraction of indocyanine green at 15-min (ICG-R15) prior to, during (at 60% of planned dose), and after radiotherapy (RT). The limit of functional liver reserve was estimated from the damage fraction of functional liver (DFL) post-RT [1 − (ICG-R15 pre-RT /ICG-R15 post-RT )] where no toxicity was observed using a beta distribution function. Results: Of 48 evaluable patients, 3 (6%) developed RILD, all within 2.5 months of completing RT. The mean ICG-R15 for non-RILD patients pre-RT, during-RT and 1-month post-RT was 20.3%(SE 2.6), 22.0%(3.0), and 27.5%(2.8), and for RILD patients was 6.3%(4.3), 10.8%(2.7), and 47.6%(8.8). RILD was observed at post-RT damage fractions of ⩾78%. Both DFL assessed by during-RT ICG and MLD predicted for DFL post-RT (p < 0.0001). Limiting the post-RT DFL to 50%, predicted a 99% probability of a true complication rate <15%. Conclusion: The DFL as assessed by changes in ICG during treatment serves as an early indicator of a patient’s tolerance to hepatic irradiation

  9. Natural history of autoimmune primary ovarian insufficiency in patients with Addison's disease: from normal ovarian function to overt ovarian dysfunction.

    Science.gov (United States)

    De Bellis, Annamaria; Bellastella, Giuseppe; Falorni, Alberto; Aitella, Ernesto; Barrasso, Mariluce; Maiorino, Maria Ida; Bizzarro, Elio; Bellastella, Antonio; Giugliano, Dario; Esposito, Katherine

    2017-10-01

    Women with autoimmune Addison's disease with normal ovulatory cycles but positive for steroid cell antibodies (StCA) have been considered at risk of premature ovarian insufficiency (POI). Thirty-three women younger than 40 years, with subclinical-clinical autoimmune Addison's disease but with normally ovulatory menses, were followed up for 10 years to evaluate the long-term time-related variations of StCA, ovarian function and follicular reserve. All patients and 27 control women were investigated at the start and every year for the presence and titre of StCA (by indirect immunofluorescence), serum concentrations of anti-Mullerian hormone (AMH) and ovarian function at four consecutive menses every year. At the start of the study StCA were present in 16 women (group 1), at low/middle titres (≤1:32) in seven of them (43.8%, group 1A), at high titres (>1:32) in the remaining nine patients (group 1B, 56.2%), while they were absent from 17 patients (group 2). During the follow-up period, all women in group 1A remained StCA-positive at low/middle titres with normal ovulatory menses and normal gonadotrophin and AMH levels, while all patients in group 1B showed a further increase of StCA titres (1:128-1:256) and progressed through three stages of ovarian function. None of the patients in group 2 and controls showed the appearance of StCA or ovarian dysfunction during the follow-up. The presence of StCA at high titres can be considered a good predictive marker of subsequent development of autoimmune POI. To single out the stages of autoimmune POI may allow a timely therapeutic choice in the subclinical and early clinical stages. © 2017 European Society of Endocrinology.

  10. Estradiol influences the mechanical properties of human fetal osteoblasts through cytoskeletal changes

    International Nuclear Information System (INIS)

    Muthukumaran, Padmalosini; Lim, Chwee Teck; Lee, Taeyong

    2012-01-01

    Highlights: ► Estradiol induced stiffness changes of osteoblasts were quantified using AFM. ► Estradiol causes significant decrease in the stiffness of osteoblasts. ► Decreased stiffness was caused by decreased density of f-actin network. ► Stiffness changes were not associated with mineralized matrix of osteoblasts. ► Estradiol increases inherent alkaline phosphatase activity of osteoblasts. -- Abstract: Estrogen is known to have a direct effect on bone forming osteoblasts and bone resorbing osteoclasts. The cellular and molecular effects of estrogen on osteoblasts and osteoblasts-like cells have been extensively studied. However, the effect of estrogen on the mechanical property of osteoblasts has not been studied yet. It is important since mechanical property of the mechanosensory osteoblasts could be pivotal to its functionality in bone remodeling. This is the first study aimed to assess the direct effect of estradiol on the apparent elastic modulus (E ∗ ) and corresponding cytoskeletal changes of human fetal osteoblasts (hFOB 1.19). The cells were cultured in either medium alone or medium supplemented with β-estradiol and then subjected to Atomic Force Microscopy indentation (AFM) to determine E ∗ . The underlying changes in cytoskeleton were studied by staining the cells with TRITC-Phalloidin. Following estradiol treatment, the cells were also tested for proliferation, alkaline phosphatase activity and mineralization. With estradiol treatment, E ∗ of osteoblasts significantly decreased by 43–46%. The confocal images showed that the changes in f-actin network observed in estradiol treated cells can give rise to the changes in the stiffness of the cells. Estradiol also increases the inherent alkaline phosphatase activity of the cells. Estradiol induced stiffness changes of osteoblasts were not associated with changes in the synthesized mineralized matrix of the cells. Thus, a decrease in osteoblast stiffness with estrogen treatment was

  11. Estradiol influences the mechanical properties of human fetal osteoblasts through cytoskeletal changes

    Energy Technology Data Exchange (ETDEWEB)

    Muthukumaran, Padmalosini [Department of Bioengineering, National University of Singapore (Singapore); Lim, Chwee Teck [Department of Bioengineering, National University of Singapore (Singapore); Department of Mechanical Engineering, National University of Singapore (Singapore); Mechanobiology Institute, National University of Singapore (Singapore); Singapore-MIT Alliance for Research and Technology (SMART), National University of Singapore (Singapore); Lee, Taeyong, E-mail: bielt@nus.edu.sg [Department of Bioengineering, National University of Singapore (Singapore)

    2012-07-06

    Highlights: Black-Right-Pointing-Pointer Estradiol induced stiffness changes of osteoblasts were quantified using AFM. Black-Right-Pointing-Pointer Estradiol causes significant decrease in the stiffness of osteoblasts. Black-Right-Pointing-Pointer Decreased stiffness was caused by decreased density of f-actin network. Black-Right-Pointing-Pointer Stiffness changes were not associated with mineralized matrix of osteoblasts. Black-Right-Pointing-Pointer Estradiol increases inherent alkaline phosphatase activity of osteoblasts. -- Abstract: Estrogen is known to have a direct effect on bone forming osteoblasts and bone resorbing osteoclasts. The cellular and molecular effects of estrogen on osteoblasts and osteoblasts-like cells have been extensively studied. However, the effect of estrogen on the mechanical property of osteoblasts has not been studied yet. It is important since mechanical property of the mechanosensory osteoblasts could be pivotal to its functionality in bone remodeling. This is the first study aimed to assess the direct effect of estradiol on the apparent elastic modulus (E{sup Asterisk-Operator }) and corresponding cytoskeletal changes of human fetal osteoblasts (hFOB 1.19). The cells were cultured in either medium alone or medium supplemented with {beta}-estradiol and then subjected to Atomic Force Microscopy indentation (AFM) to determine E{sup Asterisk-Operator }. The underlying changes in cytoskeleton were studied by staining the cells with TRITC-Phalloidin. Following estradiol treatment, the cells were also tested for proliferation, alkaline phosphatase activity and mineralization. With estradiol treatment, E{sup Asterisk-Operator} of osteoblasts significantly decreased by 43-46%. The confocal images showed that the changes in f-actin network observed in estradiol treated cells can give rise to the changes in the stiffness of the cells. Estradiol also increases the inherent alkaline phosphatase activity of the cells. Estradiol induced stiffness

  12. Obese adults with primary growth hormone resistance (Laron Syndrome) have normal endothelial function.

    Science.gov (United States)

    Shechter, M; Ginsberg, S; Scheinowitz, M; Feinberg, M S; Laron, Z

    2007-04-01

    Classic Laron Syndrome (LS) is a recessive disease of insulin-like growth factor I (IGF-I) deficiency and primary growth hormone insensitivity, clinically characterized by dwarfism and marked obesity. The aim of the current study was to investigate the impact of long-term IGF-I deficiency on flow-mediated dilation (FMD) in 11 non-IGF-I-treated LS adults with long-term IGF-I deficiency who on stress echocardiography were found to have reduced cardiac dimensions and output, but normal left ventricular (LV) ejection fraction at rest and LV contractile reserve following stress. Following an overnight fast we assessed percent improvement in endothelium-dependent FMD (%FMD) and endothelium-independent nitroglycerin (%NTG)-mediated vasodilation non-invasively in the brachial artery, using high resolution ultrasound in 11 non-treated adult patients with LS without known coronary artery disease, and compared them to 11 age- and sex-matched healthy controls. All subjects underwent symptom-limited exercise testing (Bruce protocol). LS patients had a significantly higher body mass index (29+/-6 vs. 25+/-2 kg/m(2), p=0.04), lower low-density lipoprotein cholesterol (142+/-28 vs. 176+/-12 mg/dl, p=0.03) and a smaller mean brachial artery diameter (4.63+/-0.72 vs. 5.70+/-1.06 mm, p=0.01) compared to controls. However, brachial artery %FMD and %NTG were not significantly different between the LS patients and controls (13.1+/-6.2% vs. 15.4+/-5.2%, p=0.28 and 22.3+/-6.0% vs. 18.9+/-6.2%, p=0.30; respectively). Cardiac performance, assessed by exercise duration time and metabolic equivalents (METs), was significantly greater in control subjects than in LS patients (10.3+/-2.0 vs. 6.0+/-1.4 min, p<0.01 and 10.2+/-2.0 vs. 7.2+/-1.4 METs, p<0.01; respectively). FMD was found to be within normal limits in non-IGF-I-treated adult patients with LS, despite congenital absence of IGF-I and obesity.

  13. [Structure and function of suburothelial myofibroblasts in the human urinary bladder under normal and pathological conditions].

    Science.gov (United States)

    Neuhaus, J; Heinrich, M; Schlichting, N; Oberbach, A; Fitzl, G; Schwalenberg, T; Horn, L-C; Stolzenburg, J-U

    2007-09-01

    Myofibroblasts play a pivotal role in numerous pathological alterations. Clarification of the structure and function and of the cellular plasticity of this cell type in the bladder may lead to new insights into the pathogenesis of lower urinary tract disorders. Bladder biopsies from patients with bladder carcinoma and interstitial cystitis were used to analyse the morphology and receptor expression using confocal immunofluorescence and electron microscopy. Cytokine effects and coupling behavior were tested in cultured myofibroblasts and detrusor smooth muscle cells. Myofibroblasts are in close contact with the suburothelial capillary network. They express Cx43 and form functional syncytia. The expression of muscarinic and purinergic receptors is highly variable. Dye coupling experiments showed differences to detrusor myocytes. Upregulation of smooth muscle cell alpha-actin and/or transdifferentiation into smooth muscle cells may contribute to the etiology of urge incontinence. A multi-step model is presented as a working hypothesis.

  14. Diagnosis and surgical outcomes of intraparotid facial nerve schwannoma showing normal facial nerve function.

    Science.gov (United States)

    Lee, D W; Byeon, H K; Chung, H P; Choi, E C; Kim, S-H; Park, Y M

    2013-07-01

    The findings of intraparotid facial nerve schwannoma (FNS) using preoperative diagnostic tools, including ultrasonography (US)-guided fine needle aspiration biopsy, computed tomography (CT) scan, and magnetic resonance imaging (MRI), were analyzed to determine if there are any useful findings that might suggest the presence of a lesion. Treatment guidelines are suggested. The medical records of 15 patients who were diagnosed with an intraparotid FNS were retrospectively analyzed. US and CT scans provide clinicians with only limited information; gadolinium enhanced T1-weighted images from MRI provide more specific findings. Tumors could be removed successfully with surgical exploration, preserving facial nerve function at the same time. Gadolinium-enhanced T1-weighted MRI showed more characteristic findings for the diagnosis of intraparotid FNS. Intraparotid FNS without facial palsy can be diagnosed with MRI preoperatively, and surgical exploration is a suitable treatment modality which can remove the tumor and preserve facial nerve function. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  15. Thermodynamic functions of ion solvation in normal alcohols of aliphatic series

    International Nuclear Information System (INIS)

    Sergeeva, I.A.

    1978-01-01

    Thermodynamic functions of ion solvation of alkali, alkaline earth metals and halogenides in 9 alcohols are calculated using the earlier suggested method. It is shown that summary values are in good accord with experimental ones, the deviations do not surpass 0-5%, solvation energies of one and the same electrolyte in the series of n-alcohols do not change, enthalpy and entropy of solvation increase from lower alcohols to higher ones

  16. Quaternary ammonium-functionalized silica sorbents for the solid-phase extraction of aromatic amines under normal phase conditions.

    Science.gov (United States)

    Vidal, Lorena; Robin, Orlane; Parshintsev, Jevgeni; Mikkola, Jyri-Pekka; Riekkola, Marja-Liisa

    2013-04-12

    Quaternary ammonium-functionalized silica materials were synthesized and applied for solid-phase extraction (SPE) of aromatic amines, which are classified as priority pollutants by US Environmental Protection Agency. Hexamethylenetetramine used for silica surface modification for the first time was employed as SPE sorbent under normal phase conditions. Hexaminium-functionalized silica demonstrated excellent extraction efficiencies for o-toluidine, 4-ethylaniline and quinoline (recoveries 101-107%), while for N,N-dimethylaniline and N-isopropylaniline recoveries were from low to moderate (14-46%). In addition, the suitability of 1-alkyl-3-(propyl-3-sulfonate) imidazolium-functionalized silica as SPE sorbent was tested under normal phase conditions. The recoveries achieved for the five aromatic amines ranged from 89 to 99%. The stability of the sorbent was evaluated during and after 150 extractions. Coefficients of variation between 4.5 and 10.2% proved a high stability of the synthesized sorbent. Elution was carried out using acetonitrile in the case of hexaminium-functionalized silica and water for 1-alkyl-3-(propyl-3-sulfonate) imidazolium-functionalized silica sorbent. After the extraction the analytes were separated and detected by liquid chromatography ultraviolet detection (LC-UV). The retention mechanism of the materials was primarily based on polar hydrogen bonding and π-π interactions. Comparison made with activated silica proved the quaternary ammonium-functionalized materials to offer different selectivity and better extraction efficiencies for aromatic amines. Finally, 1-alkyl-3-(propyl-3-sulfonate) imidazolium-functionalized silica sorbent was successfully tested for the extraction of wastewater and soil samples. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Hierarchical Distribution of the Tau Cytoskeletal Pathology in the Thalamus of Alzheimer's Disease Patients.

    Science.gov (United States)

    Rüb, Udo; Stratmann, Katharina; Heinsen, Helmut; Del Turco, Domenico; Ghebremedhin, Estifanos; Seidel, Kay; den Dunnen, Wilfred; Korf, Horst-Werner

    2016-01-01

    In spite of considerable progress in neuropathological research on Alzheimer's disease (AD), knowledge regarding the exact pathoanatomical distribution of the tau cytoskeletal pathology in the thalamus of AD patients in the advanced Braak and Braak AD stages V or VI of the cortical cytoskeletal pathology is still fragmentary. Investigation of serial 100 μm-thick brain tissue sections through the thalamus of clinically diagnosed AD patients with Braak and Braak AD stage V or VI cytoskeletal pathologies immunostained with the anti-tau AT8 antibody, along with the affection of the extraterritorial reticular nucleus of the thalamus, reveals a consistent and severe tau immunoreactive cytoskeletal pathology in the limbic nuclei of the thalamus (e.g., paraventricular, anterodorsal and laterodorsal nuclei, limitans-suprageniculate complex). The thalamic nuclei integrated into the associative networks of the human brain (e.g., ventral anterior and mediodorsal nuclei) are only mildly affected, while its motor precerebellar (ventral lateral nucleus) and sensory nuclei (e.g., lateral and medial geniculate bodies, ventral posterior medial and lateral nuclei, parvocellular part of the ventral posterior medial nucleus) are more or less spared. The highly stereotypical and characteristic thalamic distribution pattern of the AD-related tau cytoskeletal pathology represents an anatomical mirror of the hierarchical topographic distribution of the cytoskeletal pathology in the interconnected regions of the cerebral cortex of AD patients. These pathoanatomical parallels support the pathophysiological concept of a transneuronal spread of the disease process of AD along anatomical pathways. The AD-related tau cytoskeletal pathology in the thalamus most likely contributes substantially to the neuropsychiatric disease symptoms (e.g., dementia), attention deficits, oculomotor dysfunctions, altered non-discriminative aspects of pain experience of AD patients, and the disruption of their

  18. Response of mitochondrial function to hypothyroidism in normal and regenerated rat skeletal muscle.

    Science.gov (United States)

    Zoll, J; Ventura-Clapier, R; Serrurier, B; Bigard, A X

    2001-01-01

    Although thyroid hormones induce a well known decrease in muscle oxidative capacity, nothing is known concerning their effects on mitochondrial function and regulation in situ. Similarly, the influence of regeneration process is not completely understood. We investigated the effects of hypothyroidism on mitochondrial function in fast gastrocnemius (GS) and slow soleus (SOL) muscles either intact or having undergone a cycle of degeneration/regeneration (Rg SOL) following a local injection of myotoxin. Thyroid hormone deficiency was induced by thyroidectomy and propylthiouracyl via drinking water. Respiration was measured in muscle fibres permeabilised by saponin in order to assess the oxidative capacity of the muscles and the regulation of mitochondria in situ. Oxidative capacities were 8.9 in SOL, 8.5 in Rg SOL and 5.9 micromol O2/min/g dry weight in GS and decreased by 52, 42 and 39% respectively (P hypothyroid rats. Moreover, the Km of mitochondrial respiration for the phosphate acceptor ADP exhibited a two-fold decrease in Rg SOL and intact SOL by hypothyroidism (P hypothyroidism markedly altered the sensitivity of mitochondrial respiration to ADP but not to creatine in SOL muscles, suggesting that mitochondrial regulation could be partially controlled by thyroid hormones. On the other hand, mitochondrial function completely recovered following regeneration/degeneration, suggesting that thyroid hormones are not involved in the regeneration process per se.

  19. A new formula for normal tissue complication probability (NTCP) as a function of equivalent uniform dose (EUD).

    Science.gov (United States)

    Luxton, Gary; Keall, Paul J; King, Christopher R

    2008-01-07

    To facilitate the use of biological outcome modeling for treatment planning, an exponential function is introduced as a simpler equivalent to the Lyman formula for calculating normal tissue complication probability (NTCP). The single parameter of the exponential function is chosen to reproduce the Lyman calculation to within approximately 0.3%, and thus enable easy conversion of data contained in empirical fits of Lyman parameters for organs at risk (OARs). Organ parameters for the new formula are given in terms of Lyman model m and TD(50), and conversely m and TD(50) are expressed in terms of the parameters of the new equation. The role of the Lyman volume-effect parameter n is unchanged from its role in the Lyman model. For a non-homogeneously irradiated OAR, an equation relates d(ref), n, v(eff) and the Niemierko equivalent uniform dose (EUD), where d(ref) and v(eff) are the reference dose and effective fractional volume of the Kutcher-Burman reduction algorithm (i.e. the LKB model). It follows in the LKB model that uniform EUD irradiation of an OAR results in the same NTCP as the original non-homogeneous distribution. The NTCP equation is therefore represented as a function of EUD. The inverse equation expresses EUD as a function of NTCP and is used to generate a table of EUD versus normal tissue complication probability for the Emami-Burman parameter fits as well as for OAR parameter sets from more recent data.

  20. A new formula for normal tissue complication probability (NTCP) as a function of equivalent uniform dose (EUD)

    International Nuclear Information System (INIS)

    Luxton, Gary; Keall, Paul J; King, Christopher R

    2008-01-01

    To facilitate the use of biological outcome modeling for treatment planning, an exponential function is introduced as a simpler equivalent to the Lyman formula for calculating normal tissue complication probability (NTCP). The single parameter of the exponential function is chosen to reproduce the Lyman calculation to within ∼0.3%, and thus enable easy conversion of data contained in empirical fits of Lyman parameters for organs at risk (OARs). Organ parameters for the new formula are given in terms of Lyman model m and TD 50 , and conversely m and TD 50 are expressed in terms of the parameters of the new equation. The role of the Lyman volume-effect parameter n is unchanged from its role in the Lyman model. For a non-homogeneously irradiated OAR, an equation relates d ref , n, v eff and the Niemierko equivalent uniform dose (EUD), where d ref and v eff are the reference dose and effective fractional volume of the Kutcher-Burman reduction algorithm (i.e. the LKB model). It follows in the LKB model that uniform EUD irradiation of an OAR results in the same NTCP as the original non-homogeneous distribution. The NTCP equation is therefore represented as a function of EUD. The inverse equation expresses EUD as a function of NTCP and is used to generate a table of EUD versus normal tissue complication probability for the Emami-Burman parameter fits as well as for OAR parameter sets from more recent data

  1. Signal-to-background ratio preferences of normal-hearing listeners as a function of music

    Science.gov (United States)

    Barrett, Jillian Gallant

    The purpose of this study was to identify listeners' signal-to-background-ratio (SBR) preference levels for vocal music and to investigate whether or not SBR differences existed for different music genres. The ``signal'' was the singer's voice, and the ``background'' was the accompanying music. Three songs were each produced in two different genres (total of 6 genres represented). Each song was performed by three male and three female singers. Analyses addressed influences of musical genre, singing style, and singer timbre on listener's SBR choices. Fifty-three normal-hearing California State University of Northridge students ranging in age from 20-52 years participated as subjects. Subjects adjusted the overall music loudness to a comfortable listening level, and manipulated a second gain control which affected only the singer's voice. Subjects listened to 72 stimuli and adjusted the singer's voice to the level they felt sounded appropriate in comparison to the background music. Singer and Genre were the two primary contributors to significant differences in subject's SBR preferences, although the results clearly indicate Genre, Style and Singer interact in different combinations under different conditions. SBR differences for each song, each singer, and each subject did not occur in a predictable manner, and support the hypothesis that SBR preferences are neither fixed nor dependent merely upon music application or setting. Further investigations regarding psychoacoustical bases responsible for differences in SBR preferences are warranted.

  2. Absolute quantification of pharmacokinetic distribution of RES colloids in individuals with normal liver function

    International Nuclear Information System (INIS)

    Herzog, H.; Spohr, G.; Notohamiprodjo, G.; Feinendegen, L.E.

    1987-01-01

    Estimates of the radiation dose resulting from liver-spleen scintigraphy 99 TCsup(m)-labelled colloids are based on pharmacokinetic data mainly determined in animals. The aim of this study was to check the pharmacokinetic data by direct, absolute in vivo quantification in man. Liver and spleen activities were directly measured using a double-energy window technique. Activities in other organs were quantified by conjugate whole-body scans. All measurement procedures were checked using the whole-body Alderson phantom. Pharmacokinetic data for sulphur colloid, tin colloid, human serum albumin (HSA) millimicrospheres, and phytate were obtained in 13 to 20 normal subjects for each type of colloid. Depending on the colloid type liver uptake was between 54 and 75% of the total administered dose (TAD) and spleen uptake was 3.5 to 21% TAD. Activity measured in blood, urine, lung and thyroid proved to be far from negligible. The results of this work suggest a correction of the animal-based data of colloid distribution and radiation dose on the basis of the direct measurement of absolute uptake in man. (author)

  3. On the Comparison of Cognitive Function in Substance Abusers and Addicts under Methadone Treatment with Normal Individuals

    Directory of Open Access Journals (Sweden)

    reza mohammadzadeghan

    2015-09-01

    Full Text Available Objective: This study was an attempt to compare cognitive functioning in substance abusers and addicts under methadone treatment with normal individuals. Method: The current study was a causal-comparative one. The statistical population of this research consisted of all male substance abusers who had referred to addiction treatment centers of Khoy city in 2013. The total of 40 addicts under methadone treatment, 40 active drug users, and 40 non-addicts were selected as the participants of this study via convenience sampling method. Wisconsin Card Sorting Test and Wechsler Memory Scale were administered to the three groups for data collection purposes. Results: The results showed that the substance abusers’ scores in Wisconsin card sorting test and Wechsler memory scale were significantly different from those of addicts under methadone treatment and normal individuals. In the same way, there was a significant difference between addicts under methadone treatment and normal individuals in terms of cognitive function however, there was no significant difference between these two groups in terms of perseveration error. Conclusion: It can be concluded that chronic use of psychoactive substances causes damage to multiple brain regions such as prefrontal cortex and hippocampus and, thereby, it leads to cognitive malfunctioning in these areas.

  4. Covalent modification of cytoskeletal proteins in neuronal cells by tryptamine-4,5-dione

    Directory of Open Access Journals (Sweden)

    Yoji Kato

    2014-01-01

    Full Text Available Serotonin, 5-hydroxytryptamine, is a systemic bioactive amine that acts in the gut and brain. As a substrate of myeloperoxidase in vitro, serotonin is oxidized to tryptamine-4,5-dione (TD, which is highly reactive with thiols. In this work, we successively prepared a monoclonal antibody to quinone-modified proteins and found that the antibody preferentially recognizes the TD–thiol adduct. Using the antibody, we observed that the chloride ion, the predominant physiological substrate for myeloperoxidase in vivo, is not competitive toward the enzyme catalyzed serotonin oxidation process, suggesting that serotonin is a plausible physiological substrate for the enzyme in vivo. Immunocytochemical analyses revealed that TD staining was observed in the cytosol of SH-SY5Y neuroblastoma cells while blot analyses showed that some cellular proteins were preferentially modified. Pull-down analyses confirmed that the cytoskeletal proteins tubulins, vimentin, and neurofilament-L were modified. When pure tubulins were exposed to micromolar levels of synthetic TD, self-polymerization was initially enhanced and then suppressed. These results suggest that serotonin oxidation by myeloperoxidase or the action of other oxidants could cause functional alteration of cellular proteins, which may be related to neurodegeneration processes or irritable bowel syndrome.

  5. Oestradiol and progesterone differentially alter cytoskeletal protein expression and flame cell morphology in Taenia crassiceps.

    Science.gov (United States)

    Ambrosio, Javier R; Ostoa-Saloma, Pedro; Palacios-Arreola, M Isabel; Ruíz-Rosado, Azucena; Sánchez-Orellana, Pedro L; Reynoso-Ducoing, Olivia; Nava-Castro, Karen E; Martínez-Velázquez, Nancy; Escobedo, Galileo; Ibarra-Coronado, Elizabeth G; Valverde-Islas, Laura; Morales-Montor, Jorge

    2014-09-01

    We examined the effects of oestradiol (E2) and progesterone (P4) on cytoskeletal protein expression in the helminth Taenia crassiceps - specifically actin, tubulin and myosin. These proteins assemble into flame cells, which constitute the parasite excretory system. Total protein extracts were obtained from E2- and P4-treated T. crassiceps cysticerci and untreated controls, and analysed by one- and two-dimensional protein electrophoresis, flow cytometry, immunofluorescence and videomicroscopy. Exposure of T. crassiceps cysticerci to E2 and P4 induced differential protein expression patterns compared with untreated controls. Changes in actin, tubulin and myosin expression were confirmed by flow cytometry of parasite cells and immunofluorescence. In addition, parasite morphology was altered in response to E2 and P4 versus controls. Flame cells were primarily affected at the level of the ciliary tuft, in association with the changes in actin, tubulin and myosin. We conclude that oestradiol and progesterone act directly on T. crassiceps cysticerci, altering actin, tubulin and myosin expression and thus affecting the assembly and function of flame cells. Our results increase our understanding of several aspects of the molecular crosstalk between host and parasite, which might be useful in designing anthelmintic drugs that exclusively impair parasitic proteins which mediate cell signaling and pathogenic reproduction and establishment. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  6. Hes6 is required for actin cytoskeletal organization in differentiating C2C12 myoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Malone, Caroline M.P.; Domaschenz, Renae; Amagase, Yoko [MRC Cancer Cell Unit, Hutchison-MRC Research Centre, Addenbrooke' s Hospital, Cambridge CB2 0XZ (United Kingdom); Dunham, Ian [EMBL-European Bioinformatics Institute (EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD (United Kingdom); Murai, Kasumi [MRC Cancer Cell Unit, Hutchison-MRC Research Centre, Addenbrooke' s Hospital, Cambridge CB2 0XZ (United Kingdom); Jones, Philip H., E-mail: phj20@cam.ac.uk [MRC Cancer Cell Unit, Hutchison-MRC Research Centre, Addenbrooke' s Hospital, Cambridge CB2 0XZ (United Kingdom)

    2011-07-01

    Hes6 is a member of the hairy-enhancer-of-split family of transcription factors that regulate proliferating cell fate in development and is known to be expressed in developing muscle. Here we investigate its function in myogenesis in vitro. We show that Hes6 is a direct transcriptional target of the myogenic transcription factors MyoD and Myf5, indicating that it is integral to the myogenic transcriptional program. The localization of Hes6 protein changes during differentiation, becoming predominantly nuclear. Knockdown of Hes6 mRNA levels by siRNA has no effect on cell cycle exit or induction of myosin heavy chain expression in differentiating C2C12 myoblasts, but F-actin filament formation is disrupted and both cell motility and myoblast fusion are reduced. The knockdown phenotype is rescued by expression of Hes6 cDNA resistant to siRNA. These results define a novel role for Hes6 in actin cytoskeletal dynamics in post mitotic myoblasts.

  7. Hes6 is required for actin cytoskeletal organization in differentiating C2C12 myoblasts

    International Nuclear Information System (INIS)

    Malone, Caroline M.P.; Domaschenz, Renae; Amagase, Yoko; Dunham, Ian; Murai, Kasumi; Jones, Philip H.

    2011-01-01

    Hes6 is a member of the hairy-enhancer-of-split family of transcription factors that regulate proliferating cell fate in development and is known to be expressed in developing muscle. Here we investigate its function in myogenesis in vitro. We show that Hes6 is a direct transcriptional target of the myogenic transcription factors MyoD and Myf5, indicating that it is integral to the myogenic transcriptional program. The localization of Hes6 protein changes during differentiation, becoming predominantly nuclear. Knockdown of Hes6 mRNA levels by siRNA has no effect on cell cycle exit or induction of myosin heavy chain expression in differentiating C2C12 myoblasts, but F-actin filament formation is disrupted and both cell motility and myoblast fusion are reduced. The knockdown phenotype is rescued by expression of Hes6 cDNA resistant to siRNA. These results define a novel role for Hes6 in actin cytoskeletal dynamics in post mitotic myoblasts.

  8. Mycoplasma pneumoniae cytoskeletal protein HMW2 and the architecture of the terminal organelle.

    Science.gov (United States)

    Bose, Stephanie R; Balish, Mitchell F; Krause, Duncan C

    2009-11-01

    The terminal organelle of Mycoplasma pneumoniae mediates cytadherence and gliding motility and functions in cell division. The defining feature of this complex membrane-bound cell extension is an electron-dense core of two segmented rods oriented longitudinally and enlarging to form a bulb at the distal end. While the components of the core have not been comprehensively identified, previous evidence suggested that the cytoskeletal protein HMW2 forms parallel bundles oriented lengthwise to yield the major rod of the core. In the present study, we tested predictions emerging from that model by ultrastructural and immunoelectron microscopy analyses of cores from wild-type M. pneumoniae and mutants producing HMW2 derivatives. Antibodies specific for the N or C terminus of HMW2 labeled primarily peripheral to the core along its entire length. Furthermore, truncation of HMW2 did not correlate specifically with core length. However, mutant analysis correlated specific HMW2 domains with core assembly, and examination of core-enriched preparations confirmed that HMW2 was a major component of these fractions. Taken together, these findings yielded a revised model for HMW2 in terminal organelle architecture.

  9. Mycoplasma pneumoniae Cytoskeletal Protein HMW2 and the Architecture of the Terminal Organelle▿

    Science.gov (United States)

    Bose, Stephanie R.; Balish, Mitchell F.; Krause, Duncan C.

    2009-01-01

    The terminal organelle of Mycoplasma pneumoniae mediates cytadherence and gliding motility and functions in cell division. The defining feature of this complex membrane-bound cell extension is an electron-dense core of two segmented rods oriented longitudinally and enlarging to form a bulb at the distal end. While the components of the core have not been comprehensively identified, previous evidence suggested that the cytoskeletal protein HMW2 forms parallel bundles oriented lengthwise to yield the major rod of the core. In the present study, we tested predictions emerging from that model by ultrastructural and immunoelectron microscopy analyses of cores from wild-type M. pneumoniae and mutants producing HMW2 derivatives. Antibodies specific for the N or C terminus of HMW2 labeled primarily peripheral to the core along its entire length. Furthermore, truncation of HMW2 did not correlate specifically with core length. However, mutant analysis correlated specific HMW2 domains with core assembly, and examination of core-enriched preparations confirmed that HMW2 was a major component of these fractions. Taken together, these findings yielded a revised model for HMW2 in terminal organelle architecture. PMID:19717588

  10. Normal endothelial function after meals rich in olive or safflower oil previously used for deep frying.

    Science.gov (United States)

    Williams, M J; Sutherland, W H; McCormick, M P; Yeoman, D; de Jong, S A; Walker, R J

    2001-06-01

    Polyunsaturated fats are more susceptible to oxidation during heating than monounsaturated fats but their effects on endothelial function when heated are unknown. The aim of this study was to compare the effect of meals rich in heat-modified safflower and olive oils on postprandial flow-mediated endothelium-dependent dilation (EDD) in healthy men. Flow-mediated EDD and glyceryltrinitrate-induced endothelium-independent dilation of the brachial artery were investigated in 14 subjects before and 4 hours after meals rich in olive oil and safflower oil used hourly for deep-frying for 8 hours in a double-blind crossover study design. There were high levels of lipid oxidation products (peroxides and carbonyls) in both heated oils. Plasma triglycerides were markedly increased at 4 hours after heated olive oil (1.26 +/- 0.43 vs 2.06 +/- 0.97 mmol/L) and heated safflower oil (1.44 +/- 0.63 vs 1.99 +/- 0.88 mmol/L). There was no change in EDD between fasting and postprandial studies and the response during the postprandial period was not significantly (p = 0.51) different between the meals (heated olive oil: 4.9 +/- 2.2% vs 4.9 +/- 2.5%; heated safflower oil: 5.1 +/- 3.1% vs 5.6 +/- 3.4%). Meals rich in olive and safflower oils previously used for deep frying and containing high levels of lipid oxidation products increase postprandial serum triglycerides without affecting endothelial function. These findings suggest that relatively short-term use of these vegetable oils for frying may not adversely affect postprandial endothelial function when foods containing the heat-modified oils are consumed.

  11. Fibroblast growth factor receptor signaling is essential for normal mammary gland development and stem cell function.

    Science.gov (United States)

    Pond, Adam C; Bin, Xue; Batts, Torey; Roarty, Kevin; Hilsenbeck, Susan; Rosen, Jeffrey M

    2013-01-01

    Fibroblast growth factor (FGF) signaling plays an important role in embryonic stem cells and adult tissue homeostasis, but the function of FGFs in mammary gland stem cells is less well defined. Both FGFR1 and FGFR2 are expressed in basal and luminal mammary epithelial cells (MECs), suggesting that together they might play a role in mammary gland development and stem cell dynamics. Previous studies have demonstrated that the deletion of FGFR2 resulted only in transient developmental defects in branching morphogenesis. Using a conditional deletion strategy, we investigated the consequences of FGFR1 deletion alone and then the simultaneous deletion of both FGFR1 and FGFR2 in the mammary epithelium. FGFR1 deletion using a keratin 14 promoter-driven Cre-recombinase resulted in an early, yet transient delay in development. However, no reduction in functional outgrowth potential was observed following limiting dilution transplantation analysis. In contrast, a significant reduction in outgrowth potential was observed upon the deletion of both FGFR1 and FGFR2 in MECs using adenovirus-Cre. Additionally, using a fluorescent reporter mouse model to monitor Cre-mediated recombination, we observed a competitive disadvantage following transplantation of both FGFR1/R2-null MECs, most prominently in the basal epithelial cells. This correlated with the complete loss of the mammary stem cell repopulating population in the FGFR1/R2-attenuated epithelium. FGFR1/R2-null MECs were partially rescued in chimeric outgrowths containing wild-type MECs, suggesting the potential importance of paracrine mechanisms involved in the maintenance of the basal epithelial stem cells. These studies document the requirement for functional FGFR signaling in mammary stem cells during development. Copyright © 2012 AlphaMed Press.

  12. Impaired skeletal muscle mitochondrial function in morbidly obese patients is normalized one year after bariatric surgery.

    Science.gov (United States)

    Vijgen, Guy H E J; Bouvy, Nicole D; Hoeks, Joris; Wijers, Sander; Schrauwen, Patrick; van Marken Lichtenbelt, Wouter D

    2013-01-01

    Obesity and type 2 diabetes are associated with impaired skeletal muscle mitochondrial metabolism. As an intrinsic characteristic of an individual, skeletal muscle mitochondrial dysfunction could be a risk factor for weight gain and obesity-associated co-morbidities, such as type 2 diabetes. On the other hand, impaired skeletal muscle metabolism could be a consequence of obesity. We hypothesize that marked weight loss after bariatric surgery recovers skeletal muscle mitochondrial function. Skeletal muscle mitochondrial function as assessed by high-resolution respirometry was measured in 8 morbidly obese patients (body mass index [BMI], 41.3±4.7 kg/m(2); body fat, 48.3%±5.2%) before and 1 year after bariatric surgery (mean weight loss: 35.0±8.6 kg). The results were compared with a lean (BMI 22.8±1.1 kg/m(2); body fat, 15.6%±4.7%) and obese (BMI 33.5±4.2 kg/m(2); body fat, 34.1%±6.3%) control group. Before surgery, adenosine diphosphate (ADP)-stimulated (state 3) respiration on glutamate/succinate was decreased compared with lean patients (9.5±2.4 versus 15.6±4.4 O2 flux/mtDNA; Psurgery, mitochondrial function was comparable to that of lean controls (after weight loss, 12.3±5.5; lean, 15.6±4.4 O2 flux/mtDNA). In addition, we observed an increased state 3 respiration on a lipid substrate after weight loss (10.0±3.2 versus 14.0±6.6 O2 flux/mtDNA; Pweight loss. Copyright © 2013 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  13. Effect of chronic fish oil supplementation on renal function of normal and cachectic rats

    Directory of Open Access Journals (Sweden)

    R. Fernandez

    2004-10-01

    Full Text Available In the present study we determined the effect of chronic diet supplementation with n-3 PUFA on renal function of healthy and cachectic subjects by providing fish oil (1 g/kg body weight to female rats throughout pregnancy and lactation and then to their offspring post-weaning and examined its effect on renal function parameters during their adulthood. The animals were divided into four groups of 5-10 rats in each group: control, control supplemented with fish oil (P, cachectic Walker 256 tumor-bearing (W, and W supplemented with fish oil (WP. Food intake was significantly lower in the W group compared to control (12.66 ± 4.24 vs 25.30 ± 1.07 g/day. Treatment with fish oil significantly reversed this reduction (22.70 ± 2.94 g/day. Tumor growth rate was markedly reduced in the P group (16.41 ± 2.09 for WP vs 24.06 ± 2.64 g for W. WP group showed a significant increase in mean glomerular filtration rate compared to P and control (1.520 ± 0.214 ml min-1 kg body weight-1; P < 0.05. Tumor-bearing groups had low urine osmolality compared to control rats. The fractional sodium excretion decreased in the W group compared to control (0.43 ± 0.16 vs 2.99 ± 0.87%; P < 0.05, and partially recovered in the WP group (0.90 ± 0.20%. In summary, the chronic supplementation with fish oil used in this study increased the amount of fat in the diet by only 0.1%, but caused remarkable changes in tumor growth rate and cachexia, also showing a renoprotective function.

  14. Function and importance of p63 in normal oral mucosa and squamous cell carcinoma of the head and neck

    DEFF Research Database (Denmark)

    Thurfjell, Niklas; Coates, Philip J; Boldrup, Linda

    2005-01-01

    BACKGROUND/AIMS: Squamous cell carcinoma of the head and neck (HNSCC) is the 6th most common malignancy worldwide with a 5-year survival that has not improved over the last 20-25 years. Factors of prognostic significance for this tumour type include the presence of regional lymph node metastasis...... and amplification of chromosome 3q21-29, where the p63 gene is located. This gene encodes 6 proteins and is crucial for formation of the oral mucosa, teeth, salivary glands and skin. Each of the 6 different p63 proteins has different characteristics and functions, where some resemble the tumour suppressor protein p......53, whilst others have functions that oppose p53. METHODS: To understand the function and importance of p63 in oral mucosa and tumour development we have studied protein as well as mRNA expression in normal oral mucosa and tumours. RESULTS/CONCLUSION: Expression of p63 proteins differs between...

  15. Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging

    Energy Technology Data Exchange (ETDEWEB)

    Marks, Shawn M. [Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; Lockhart, Samuel N. [Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; Baker, Suzanne L. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging; Jagust, William J. [Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging

    2017-03-22

    Normal aging is associated with a decline in episodic memory and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe (MTL) structures crucial to memory formation. Although some evidence suggests that Aβ is associated with aberrant neural activity, the relationships among these two aggregated proteins, neural function, and brain structure are poorly understood. Using in vivo human Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant fMRI activity in the MTL during memory encoding in cognitively normal older adults. This pathological neural activity was in turn associated with worse memory performance and atrophy within the MTL. A mediation analysis revealed that the relationship with regional atrophy was explained by MTL tau. These findings broaden the concept of cognitive aging to include evidence of Alzheimer’s disease-related protein aggregation as an underlying mechanism of age-related memory impairment.

  16. Normal endothelial function in patients with mild-to-moderate psoriasis: a case-control study

    DEFF Research Database (Denmark)

    Jensen, Peter R; Zachariae, Claus; Hansen, Peter

    2011-01-01

    Evidence is increasing that severe psoriasis is an independent cardiovascular risk factor. Results from case-control studies of endothelial dysfunction, a marker of early atherosclerosis, in patients with moderate-to-severe psoriasis have been conflicting and were conducted with operator-dependen......Evidence is increasing that severe psoriasis is an independent cardiovascular risk factor. Results from case-control studies of endothelial dysfunction, a marker of early atherosclerosis, in patients with moderate-to-severe psoriasis have been conflicting and were conducted with operator......-dependent and technically demanding ultrasound measurement of brachial artery flow-mediated vasodilation. Therefore, we decided to measure endothelial function and other cardiovascular risk factors in patients with mild-to-moderate psoriasis (n = 30) and controls (n = 30) using a newer and relatively operator......-independent technique. No difference was detected between the groups with regards to endothelial function. However, despite the patients experiencing rather mild psoriasis they did exhibit higher levels of certain cardiovascular risk factors, including waist circumference, resting heart rate, systolic and diastolic...

  17. Persistence of normal cardiac function and myocardial perfusion in irradiated long-term survivors of Hodgkin's disease

    International Nuclear Information System (INIS)

    Constine, L.S.; Schwartz, R.G.; Savage, D.E.; King, V.; Muhs, A.; Rubin, P.

    1996-01-01

    Purpose: The risk of myocardial infarction and cardiac dysfunction following mantle irradiation (RT) for Hodgkin's disease is controversial. The relative risk of fatal myocardial infarction is 2.8 in our Hodgkin's patients, similar to other reports. Sensitive evaluations of cardiac function and myocardial perfusion might be expected to reveal pre-clinical abnormalities of potential significance. We hypothesized the presence of pre-clinical cardiac toxicity and progressive deterioration of left ventricular performance and myocardial ischemia over time in long-term survivors of Hodgkin's disease. The data reported herein extend our previous study in patient number (n=50) and follow-up duration (mean 16.5 years). Materials and Methods: Equilibrium radionuclide angiocardiography (ERNA) was used to quantify left ventricular (LV) systolic and diastolic function with LV ejection fraction (LVEF) and peak filling rate (PFR), respectively. Quantitative myocardial perfusion scintigraphy (MPS) and ECG stress testing with exercise or dipyridamole were used to assess myocardial perfusion and electrical function. Patients at least 1.0 year after RT were eligible if ≤ 50 years old at RT and without known Hodgkin's or cardiac disease. Fifty patients, ages 10-46 years (mean 26.0) at RT, were tested 1.1 to 29.1 years (mean 9.1) after RT. Seventeen patients were tested 2 - 3 times separated by 0.5 - 6.5 years (mean 3.3). The mean central cardiac RT dose was 35.1 Gy (range 18.5 - 47.5) in daily 1.5-2.0 Gy fractions. Twelve patients were additionally irradiated to the left ventricle (LVRT), usually through partial transmission left lung shields (range 14.3-21.3 Gy). Results: No patient had symptomatic cardiac disease at the time of evaluation. The mean LVEF (first test, n = 50) was 60 ± 6% (range 42-73%) [normal ≥ 50%], and PFR (first test, n=44) was 3.43 ± 0.83 end diastolic volume per second (range 1.5-5.2 EDV/sec) [normal ≥ 2.54 EDV/sec] with 2 and 7 patients below normal

  18. Physiological antioxidant system and oxidative stress in stomach cancer patients with normal renal and hepatic function

    Directory of Open Access Journals (Sweden)

    E Prabhakar Reddy

    2010-04-01

    Full Text Available Role of free radicals has been proposed in the pathogenesis of many diseases. Gastric cancer is a common disease worldwide, and leading cause of cancer death in India. Severe oxidative stress produces reactive oxygen species (ROS and induces uncontrolled lipid peroxidation. Albumin, uric acid (UA and Bilirubin are important physiological antioxidants. We aimed to evaluate and assess the role of oxidative stress (OS and physiological antioxidant system in stomach cancer patients. Lipid peroxidation measured as plasma Thio Barbituric Acid Reactive substances (TBARS, was found to be elevated significantly (p=0.001 in stomach cancer compared to controls along with a decrease in plasma physiological antioxidant system. The documented results were due to increased lipid peroxidation and involvement of physiological antioxidants in scavenging free radicals but not because of impaired hepatic and renal functions.

  19. Normal endothelial function in patients with mild-to-moderate psoriasis: a case-control study

    DEFF Research Database (Denmark)

    Jensen, Peter R; Zachariae, Claus; Hansen, Peter

    2011-01-01

    -dependent and technically demanding ultrasound measurement of brachial artery flow-mediated vasodilation. Therefore, we decided to measure endothelial function and other cardiovascular risk factors in patients with mild-to-moderate psoriasis (n = 30) and controls (n = 30) using a newer and relatively operator......Evidence is increasing that severe psoriasis is an independent cardiovascular risk factor. Results from case-control studies of endothelial dysfunction, a marker of early atherosclerosis, in patients with moderate-to-severe psoriasis have been conflicting and were conducted with operator...... blood pressures, and plasma levels of triglycerides, very-low-density lipoprotein cholesterol and glycated glucose, compared with controls. This indicates that even mild-to-moderate psoriasis may be regarded as a systemic inflammatory disease, and that an increased risk of cardiovascular morbidity may...

  20. The multifaceted functions of C/EBPα in normal and malignant haematopoiesis

    DEFF Research Database (Denmark)

    Ohlsson, E; Schuster, M B; Hasemann, M

    2016-01-01

    . CCAAT/enhancer-binding protein-α (C/EBPα) was originally identified 30 years ago as a transcription factor that binds both promoter and enhancer regions. Most of the early work focused on the role of C/EBPα in regulating transcriptional processes as well as on its functions in key differentiation...... promoting differentiation. Lineage branching is further directed by groups of cooperating and counteracting genes forming complex networks of lineage-specific transcription factors. Imbalances in such networks can result in blockage of differentiation, lineage reprogramming and malignant transformation...... processes during liver, adipogenic and haematopoietic development. Specifically, C/EBPα was shown to control differentiation by its ability to coordinate transcriptional output with cell cycle progression. Later, its role as an important tumour suppressor, mainly in acute myeloid leukaemia (AML...

  1. Assembly of the MreB-associated cytoskeletal ring of Escherichia coli.

    Science.gov (United States)

    Vats, Purva; Shih, Yu-Ling; Rothfield, Lawrence

    2009-04-01

    The Escherichia coli actin homologue MreB is part of a helical cytoskeletal structure that winds around the cell between the two poles. It has been shown that MreB redistributes during the cell cycle to form circumferential ring structures that flank the cytokinetic FtsZ ring and appear to be associated with division and segregation of the helical cytoskeleton. We show here that the MreB cytoskeletal ring also contains the MreC, MreD, Pbp2 and RodA proteins. Assembly of MreB, MreC, MreD and Pbp2 into the ring structure required the FtsZ ring but no other known components of the cell division machinery, whereas assembly of RodA into the cytoskeletal ring required one or more additional septasomal components. Strikingly, MreB, MreC, MreD and RodA were each able to independently assemble into the cytoskeletal ring and coiled cytoskeletal structures in the absence of any of the other ring components. This excludes the possibility that one or more of these proteins acts as a scaffold for incorporation of the other proteins into these structures. In contrast, incorporation of Pbp2 required the presence of MreC, which may provide a docking site for Pbp2 entry.

  2. TiO2 nanoparticles disrupt cell adhesion and the architecture of cytoskeletal networks of human osteoblast-like cells in a size dependent manner.

    Science.gov (United States)

    Ibrahim, Mohamed; Schoelermann, Julia; Mustafa, Kamal; Cimpan, Mihaela R

    2018-04-30

    Human exposure to titanium dioxide nanoparticles (nano-TiO 2 ) is increasing. An internal source of nano-TiO 2 is represented by titanium-based orthopedic and dental implants can release nanoparticles (NPs) upon abrasion. Little is known about how the size of NPs influences their interaction with cytoskeletal protein networks and the functional/homeostatic consequences that might follow at the implant-bone interface with regard to osteoblasts. We investigated the effects of size of anatase nano-TiO 2 on SaOS-2 human osteoblast-like cells exposed to clinically relevant concentrations (0.05, 0.5, 5 mg/L) of 5 and 40 nm spherical nano-TiO 2 . Cell viability and proliferation, adhesion, spread and migration were assessed, as well as the orientation of actin and microtubule cytoskeletal networks. The phosphorylation of focal adhesion kinase (p-FAK Y397 ) and the expression of vinculin in response to nano-TiO 2 were also assessed. Treatment with nano-TiO 2 disrupted the actin and microtubule cytoskeletal networks leading to morphological modifications of SaOS-2 cells. The phosphorylation of p-FAK Y397 and the expression of vinculin were also modified depending on the particle size, which affected cell adhesion. Consequently, the cell migration was significantly impaired in the 5 nm-exposed cells compared to unexposed cells. The present work shows that the orientation of cytoskeletal networks and the focal adhesion proteins and subsequently the adhesion, spread and migration of SaOS-2 cells were affected by the selected nano-TiO 2 in a size dependent manner. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  3. Genetic variants in the choline acetyltransferase (ChAT) gene are modestly associated with normal cognitive function in the elderly

    DEFF Research Database (Denmark)

    Mengel-From, J; Christensen, K; Thinggaard, M

    2011-01-01

    Genetic variants in the choline acetyltransferase (ChAT) gene have been suggested as risk factors for neurodegenerative Alzheimer's disease (AD). Here we tested the importance of genetic variants in the ChAT gene in normal cognitive function of elderly in a study sample of Danish twins...... and singletons (N = 2070). The ChAT rs3810950 A allele, which has been associated with increased risk for AD, was found to be associated with a decrease cognitive status evaluated by a five-component cognitive composite score [P = 0.03, regression coefficient -0.30, 95% confidence interval (CI) -0.57 to -0...

  4. Highly active antiretroviral therapy normalizes the function of progenitor cells in human immunodeficiency virus-infected patients

    DEFF Research Database (Denmark)

    Dam Nielsen, S.; Ersbøll, A. K.; Mathiesen, L.

    1998-01-01

    -infected patients were determined prior to HAART and after 2, 4, 8, and 12 weeks of therapy. The mean number of colony-forming units (cells) per milliliter (cfu/mL) was 15.0 prior to HAART vs. 109.8 in healthy controls (P.../mL eliminated the differences between HIV-infected patients and controls. Significant increases in numbers of CD34 cells were not detected. Of importance, the cloning efficiency of CD34 cells increased from 1.7% prior to therapy to a peak at 18.7% (P=.003). In conclusion, HAART normalized CD34 cell function...

  5. Intelligence or years of education: which is better correlated with memory function in normal elderly Japanese subjects?

    Science.gov (United States)

    Murayama, Norio; Iseki, Eizo; Tagaya, Hirokuni; Ota, Kazumi; Kasanuki, Koji; Fujishiro, Hiroshige; Arai, Heii; Sato, Kiyoshi

    2013-03-01

    We compared differences in intelligence and memory function between normal elderly Japanese subjects with more years of education and those with fewer years of education. We also investigated clinical and neuropsychological factors that are strongly correlated with memory function. There were 118 normal elderly subjects who underwent the Mini-Mental State Examination, Wechsler Adult Intelligence Scale, 3rd edition (WAIS-III), and Wechsler Memory Scale Revised. Subjects with at least 13 years of education were categorized as the H group, and those with 12 years of education or less were categorized as the L group. Age and Mini-Mental State Examination scores were not significantly different between the two groups. On the WAIS-III, there were significant differences between the two groups in Verbal IQ and Full Scale IQ. On the Wechsler Memory Scale Revised, there were significant differences between the two groups in Visual Memory, General Memory, and Delayed Recall. Correlation coefficients between memory function and the other factors demonstrated significant but weak correlations between years of education and General Memory (R = 0.22) and between years of education and Delayed Recall (R = 0.20). Strong correlations were found between Verbal IQ and Verbal Memory (R = 0.45), between Verbal IQ and General Memory (R = 0.49), between Full Scale IQ and General Memory (R = 0.50) and between Full Scale IQ and Delayed Recall (R = 0.48). In normal elderly Japanese subjects, years of education weakly correlated with memory function while Verbal IQ, Full Scale IQ and Verbal Comprehension on WAIS-III had stronger correlations with memory function. Verbal IQ and Verbal Comprehension on WAIS-III were found to be insusceptible to the cognitive decline characteristic of Alzheimer's disease or amnestic mild cognitive impairment. Therefore, verbal intelligence, as measured by Verbal IQ and Verbal Comprehension, may be the most useful factor for inferring premorbid memory function

  6. Clues to γ-secretase, huntingtin and Hirano body normal function using the model organism Dictyostelium discoideum

    Directory of Open Access Journals (Sweden)

    Myre Michael A

    2012-04-01

    Full Text Available Abstract Many neurodegenerative disorders, although related by their destruction of brain function, display remarkable cellular and/or regional pathogenic specificity likely due to a deregulated functionality of the mutant protein. However, neurodegenerative disease genes, for example huntingtin (HTT, the ataxins, the presenilins (PSEN1/PSEN2 are not simply localized to neurons but are ubiquitously expressed throughout peripheral tissues; it is therefore paramount to properly understand the earliest precipitating events leading to neuronal pathogenesis to develop effective long-term therapies. This means, in no unequivocal terms, it is crucial to understand the gene's normal function. Unfortunately, many genes are often essential for embryogenesis which precludes their study in whole organisms. This is true for HTT, the β-amyloid precursor protein (APP and presenilins, responsible for early onset Alzheimer's disease (AD. To better understand neurological disease in humans, many lower and higher eukaryotic models have been established. So the question arises: how reasonable is the use of organisms to study neurological disorders when the model of choice does not contain neurons? Here we will review the surprising, and novel emerging use of the model organism Dictyostelium discoideum, a species of soil-living amoeba, as a valuable biomedical tool to study the normal function of neurodegenerative genes. Historically, the evidence on the usefulness of simple organisms to understand the etiology of cellular pathology cannot be denied. But using an organism without a central nervous system to understand diseases of the brain? We will first introduce the life cycle of Dictyostelium, the presence of many disease genes in the genome and how it has provided unique opportunities to identify mechanisms of disease involving actin pathologies, mitochondrial disease, human lysosomal and trafficking disorders and host-pathogen interactions. Secondly, I will

  7. Molecular Dynamic Simulation Insights into the Normal State and Restoration of p53 Function

    Directory of Open Access Journals (Sweden)

    Jianzhong Chen

    2012-08-01

    Full Text Available As a tumor suppressor protein, p53 plays a crucial role in the cell cycle and in cancer prevention. Almost 50 percent of all human malignant tumors are closely related to a deletion or mutation in p53. The activity of p53 is inhibited by over-active celluar antagonists, especially by the over-expression of the negative regulators MDM2 and MDMX. Protein-protein interactions, or post-translational modifications of the C-terminal negative regulatory domain of p53, also regulate its tumor suppressor activity. Restoration of p53 function through peptide and small molecular inhibitors has become a promising strategy for novel anti-cancer drug design and development. Molecular dynamics simulations have been extensively applied to investigate the conformation changes of p53 induced by protein-protein interactions and protein-ligand interactions, including peptide and small molecular inhibitors. This review focuses on the latest MD simulation research, to provide an overview of the current understanding of interactions between p53 and its partners at an atomic level.

  8. Study on cerebral activation areas during repetition with functional MRI in normal adults

    International Nuclear Information System (INIS)

    Koseki, Yohju

    2009-01-01

    For cerebral activation of speech areas in functional MRI (f-MRI) study, the usefulness of an optical microphone, which made it possible to perform task repetition at real time during scanning, was examined. Subjects were 25 healthy adults (mean age, 27.1±5.6 years), who consisted of 15 right-handed and 10 left-handed or ambidextrous persons. Tasks comprised repetition of monosyllables, non-words, words and sentences. The repetition tasks were covertly performed during scanning of f-MRI by using an optical microphone. In both the right-handed and non-right-handed groups, activations in the left superior temporal gyrus (sensory speech area) were most frequently observed during all of the tasks. In the right-handed group, activations in the left inferior frontal (motor speech area) and superior temporal gyri were significantly more often observed than those in the right inferior frontal and superior temporal gyri. From an assessment of the laterality index (LI), left-side dominant activation was frequently seen in most of the cerebral regions including sensory and motor speech areas, although right-side and bilateral dominant activations were observed in a few cases. In both groups, activations in regions associated with sensory speech were significantly more often seen than those in regions associated with motor speech. The present predominant activations in regions involved in sensory speech indicate that the optical microphone is useful in f-MRI studies using task repetition. (author)

  9. Cardiopulmonary determinants of functional capacity in patients with chronic heart failure compared with normals.

    Science.gov (United States)

    Meyer, K; Westbrook, S; Schwaibold, M; Hajric, R; Lehmann, M; Roskamm, H

    1996-12-01

    Patients with chronic heart failure (CHF) are characterized by abnormal gas exchange and ventilatory responses to exercise. This study compares variables obtained from cardiopulmonary exercise testing in 35 patients with CHF with 35 age- and weight-matched healthy subjects. A second goal was to obtain cardiopulmonary variables measured at ventilatory threshold to distinguish patient changes from those of healthy subjects. Exercise testing was carried out using bicycle ergometry with ramplike protocol (work rate increments 12.5 W/min). Gas exchange and ventilation were measured breath by breath. Compared with healthy subjects, the VO2 in patients was lower at identical work rates (p rate, the variables for VO2, VCO2, ventilation, O2 pulse, ventilatory equivalents for O2 and CO2, and VD/VT (physiologic deadspace to tidal volume ratio), as well as lactate differed significantly at identical work rates. With the exception of VD/VT, all cardiopulmonary variables showed significant differences in their slopes during exercise. By means of a discriminant analysis, VCO2 and ventilation proved to be the most distinguishing variables at ventilatory threshold between patients with CHF and healthy subjects. These results indicate the clinical usefulness of cardiopulmonary exercise testing when assessing functional impairment due to CHF. For treatment evaluation, not only VO2 but also VCO2 and ventilation responses to exercise should be considered.

  10. Improved normal tissue sparing in head and neck radiotherapy using biological cost function based-IMRT.

    Science.gov (United States)

    Anderson, N; Lawford, C; Khoo, V; Rolfo, M; Joon, D L; Wada, M

    2011-12-01

    Intensity-modulated radiotherapy (IMRT) has reduced the impact of acute and late toxicities associated with head and neck radiotherapy. Treatment planning system (TPS) advances in biological cost function based optimization (BBO) and improved segmentation techniques have increased organ at risk (OAR) sparing compared to conventional dose-based optimization (DBO). A planning study was undertaken to compare OAR avoidance in DBO and BBO treatment planning. Simultaneous integrated boost treatment plans were produced for 10 head and neck patients using both planning systems. Plans were compared for tar get coverage and OAR avoidance. Comparisons were made using the BBO TPS Monte Carlo dose engine to eliminate differences due to inherent algorithms. Target coverage (V95%) was maintained for both solutions. BBO produced lower OAR doses, with statistically significant improvement to left (12.3%, p = 0.005) and right parotid mean dose (16.9%, p = 0.004), larynx V50_Gy (71.0%, p = 0.005), spinal cord (21.9%, p < 0.001) and brain stem dose maximums (31.5%, p = 0.002). This study observed improved OAR avoidance with BBO planning. Further investigations will be undertaken to review any clinical benefit of this improved planned dosimetry.

  11. Cognitive function predicts listening effort performance during complex tasks in normally aging adults

    Directory of Open Access Journals (Sweden)

    Jennine Harvey

    2017-01-01

    Full Text Available Purpose: This study examines whether cognitive function, as measured by the subtests of the Woodcock–Johnson III (WCJ-III assessment, predicts listening-effort performance during dual tasks across the adults of varying ages. Materials and Methods: Participants were divided into two groups. Group 1 consisted of 14 listeners (number of females = 11 who were 41–61 years old [mean = 53.18; standard deviation (SD = 5.97]. Group 2 consisted of 15 listeners (number of females = 9 who were 63–81 years old (mean = 72.07; SD = 5.11. Participants were administered the WCJ-III Memory for Words, Auditory Working Memory, Visual Matching, and Decision Speed subtests. All participants were tested in each of the following three dual-task experimental conditions, which were varying in complexity: (1 auditory word recognition + visual processing, (2 auditory working memory (word + visual processing, and (3 auditory working memory (sentence + visual processing in noise. Results: A repeated measures analysis of variance revealed that task complexity significantly affected the performance measures of auditory accuracy, visual accuracy, and processing speed. Linear regression revealed that the cognitive subtests of the WCJ-III test significantly predicted performance across dependent variable measures. Conclusion: Listening effort is significantly affected by task complexity, regardless of age. Performance on the WCJ-III test may predict listening effort in adults and may assist speech-language pathologist (SLPs to understand challenges faced by participants when subjected to noise.

  12. Morning and Evening Blue-Enriched Light Exposure Alters Metabolic Function in Normal Weight Adults.

    Directory of Open Access Journals (Sweden)

    Ivy N Cheung

    Full Text Available Increasing evidence points to associations between light-dark exposure patterns, feeding behavior, and metabolism. This study aimed to determine the acute effects of 3 hours of morning versus evening blue-enriched light exposure compared to dim light on hunger, metabolic function, and physiological arousal. Nineteen healthy adults completed this 4-day inpatient protocol under dim light conditions (<20lux. Participants were randomized to 3 hours of blue-enriched light exposure on Day 3 starting either 0.5 hours after wake (n = 9; morning group or 10.5 hours after wake (n = 10; evening group. All participants remained in dim light on Day 2 to serve as their baseline. Subjective hunger and sleepiness scales were collected hourly. Blood was sampled at 30-minute intervals for 4 hours in association with the light exposure period for glucose, insulin, cortisol, leptin, and ghrelin. Homeostatic model assessment of insulin resistance (HOMA-IR and area under the curve (AUC for insulin, glucose, HOMA-IR and cortisol were calculated. Comparisons relative to baseline were done using t-tests and repeated measures ANOVAs. In both the morning and evening groups, insulin total area, HOMA-IR, and HOMA-IR AUC were increased and subjective sleepiness was reduced with blue-enriched light compared to dim light. The evening group, but not the morning group, had significantly higher glucose peak value during blue-enriched light exposure compared to dim light. There were no other significant differences between the morning or the evening groups in response to blue-enriched light exposure. Blue-enriched light exposure acutely alters glucose metabolism and sleepiness, however the mechanisms behind this relationship and its impacts on hunger and appetite regulation remain unclear. These results provide further support for a role of environmental light exposure in the regulation of metabolism.

  13. Androgen receptor signalling in peritubular myoid cells is essential for normal differentiation and function of adult Leydig cells

    DEFF Research Database (Denmark)

    Welsh, M.; Moffat, L.; Belling, Kirstine Christensen

    2012-01-01

    Testosterone synthesis depends on normal Leydig cell (LC) development, but the mechanisms controlling this development remain unclear. We recently demonstrated that androgen receptor (AR) ablation from a proportion of testicular peritubular myoid cells (PTM-ARKO) did not affect LC number, but res......Testosterone synthesis depends on normal Leydig cell (LC) development, but the mechanisms controlling this development remain unclear. We recently demonstrated that androgen receptor (AR) ablation from a proportion of testicular peritubular myoid cells (PTM-ARKO) did not affect LC number......’ subpopulation that had arrested development and only weakly expressed INSL3, luteinizing hormone receptor, and several steroidogenic enzymes. Furthermore, unlike ‘normal’ LCs in PTM-ARKOs, the ‘abnormal’ LCs did not involute as expected in response to exogenous testosterone. Differential function of these LC...... sub-populations is likely to mean that the ‘normal’ LCs work harder to compensate for the ‘abnormal’ LCs to maintain normal serum testosterone. These findings reveal new paracrine mechanisms underlying adult LC development, which can be further investigated using PTM-ARKOs....

  14. Improvement in social function and health-related quality of life after shunt surgery for idiopathic normal-pressure hydrocephalus.

    Science.gov (United States)

    Petersen, Jakob; Hellström, Per; Wikkelsø, Carsten; Lundgren-Nilsson, Asa

    2014-10-01

    To investigate the impact of shunt surgery on the activity, participation, autonomy, and health-related quality of life (HRQOL) of patients with idiopathic normal-pressure hydrocephalus (iNPH) as well as the effect on caregiver burden. Thirty-seven patients (median age 70 years, range 50-89 years) with iNPH were evaluated before and 6 months after surgery. Symptoms and signs were assessed by the iNPH scale, activities of daily living (ADL) with the Functional Independence Measure (FIM) and Assessment of Motor and Process Skills (AMPS), autonomy and participation with Impact on Participation and Autonomy (IPA), and caregiver burden with the Caregiver Burden Scale (CBS). HRQOL was evaluated with the EQ-5D (EuroQol Group-5 Dimension health survey). Twenty-four patients (65%) improved clinically (iNPH scale score) and 31 (86%) improved their HRQOL after surgery, almost to the same level as found in the normal population. The patients became more independent in physical and cognitive activities, and participation and autonomy improved. The caregiver burden was decreased among caregivers to male patients but remained unchanged on the overall group level. After shunt surgery, patients with iNPH showed improvement in most aspects of social life, they became more independent, and their quality of life returned to nearly normal.

  15. Evaluating the normal individual cardiac function in different imaging phases post exercise and rest by gated SPECT myocardial perfusion

    International Nuclear Information System (INIS)

    Hua, W.; Li, S.J.; Liu, J.Z.; Li, X.F.; Jin, C.R.; Hu, G.; Wang, J.

    2007-01-01

    Full text: Objectives: To evaluate the normal individual cardiac function in the different imaging phases post-exercise and rest by GSPECT. Methods: 46 normal individuals underwent exercise/rest GSPECT using 99mTc-MIBI by 2- day program. Sequential imaging was started 15, 35 and 120 minutes after exercise and rest imaging was performed the following day. The left ventricular EF and EDV, ESV values were calculated with the Cedars-Sinai program. Results: The EF values of post- exercise at 15, 35, and 120m was 64.48±7.43%, 65.02±7.66%, and 60.98±7.28% respectively, and the rest EF value was 61.46±7.23%. The post exercise EF at 15m and 35m was higher than EF at post- exercise 120m and rest, but there is a significant difference only between post exercise 35m and rest (P< 0.05), and all post exercise EF did not increase at least 5% from EF at-rest. The EDV and ESV values did not have statistically significant differences at 15, 35,120m post-exercise and rest. The heart rate at 15,35m post- exercise was higher significantly than at rest. Conclusions: The different imaging phases after exercise with 99mTc-MIBI GSPECT affects LVEF in normal individuals, the 35m post- exercise EF is highest. (author)

  16. Effect of intravenous glucose infusion on renal function in normal man and in insulin-dependent diabetics

    DEFF Research Database (Denmark)

    Frandsen, M; Parving, H H; Christiansen, JS

    1981-01-01

    The effect of intravenous glucose infusion on glomerular filtration rate and renal plasma flow (constant infusion technique using 125I-iothalamate and 131I-hippuran) and on urinary excretion of albumin and beta-2-microglobulin were studied in ten normal subjects and seven metabolically well......-controlled insulin-dependent diabetics. Following glucose infusion in normal subjects (n = 10) blood glucose increased from 4.7 +/- 0.1 to 10.9 +/- 0.4 mmol/l (SEM) (p less than or equal to 0.01). Glomerular filtration rate increased from 116 +/- 2 to 123 +/- 3 ml/mi x 1.73 m2 (p less than or equal to 0.01), while...... no change in renal plasma flow was seen - 552 +/- 11 versus 553 +/- 18 ml/min x 1.73 m2. Volume expansion with intravenous saline infusion in six of the normal subjects induced no changes in blood glucose or kidney function. In seven strictly controlled insulin-dependent diabetics, blood glucose values were...

  17. Quantitative Evaluation of Stomatal Cytoskeletal Patterns during the Activation of Immune Signaling in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Masaki Shimono

    Full Text Available Historically viewed as primarily functioning in the regulation of gas and water vapor exchange, it is now evident that stomata serve an important role in plant immunity. Indeed, in addition to classically defined functions related to cell architecture and movement, the actin cytoskeleton has emerged as a central component of the plant immune system, underpinning not only processes related to cell shape and movement, but also receptor activation and signaling. Using high resolution quantitative imaging techniques, the temporal and spatial changes in the actin microfilament array during diurnal cycling of stomatal guard cells has revealed a highly orchestrated transition from random arrays to ordered bundled filaments. While recent studies have demonstrated that plant stomata close in response to pathogen infection, an evaluation of stimulus-induced changes in actin cytoskeletal dynamics during immune activation in the guard cell, as well as the relationship of these changes to the function of the actin cytoskeleton and stomatal aperture, remains undefined. In the current study, we employed quantitative cell imaging and hierarchical clustering analyses to define the response of the guard cell actin cytoskeleton to pathogen infection and the elicitation of immune signaling. Using this approach, we demonstrate that stomatal-localized actin filaments respond rapidly, and specifically, to both bacterial phytopathogens and purified pathogen elicitors. Notably, we demonstrate that higher order temporal and spatial changes in the filament array show distinct patterns of organization during immune activation, and that changes in the naïve diurnal oscillations of guard cell actin filaments are perturbed by pathogens, and that these changes parallel pathogen-induced stomatal gating. The data presented herein demonstrate the application of a highly tractable and quantifiable method to assign transitions in actin filament organization to the activation of

  18. On the normalization of total wave function of the system of an atom and a colliding electron

    International Nuclear Information System (INIS)

    Nashlenas, Eh.P.; Trinkunas, G.P.

    1976-01-01

    The scattering of an electron by an atom is considered which causes an excitation of fine structure levels. For this purpose the wave function of a system consisting of an atom and an uncoupled electron is constructed. Boundary conditions formulated in the form of an asymptotic expression are taken into account for such a function by means of scattering amplitudes. To determine scattering amplitudes it is suggested to make use of the condition of wave function normalization into the Dirac delta function. After certain mathematical transformations the unknown relations between the scattering amplitudes are obtained. The special cases of the relations obtained are discussed. When quantum numbers of the wave functions coincide, the resulting relations express the equality of fluxes of converging and diverging waves for a certain value of the total angular momentum. In the limiting case when there are no electrons in an atom (it corresponds to elastic scattering of an electron on a potential) the relations obtained express the unitarity conditions of the scattering matrix

  19. Heart rate variability and QT dispersion study in brain death patients and comatose patients with normal brainstem function

    International Nuclear Information System (INIS)

    Vakilian, A.R.; Iranmanesh, F.; Nadimi, A.E.; Kahnali, J.A.

    2011-01-01

    To compare heart rate variability (HRV) and QT dispersion in comatose patients with normal brainstem function and with brain death. Fourteen brain death patients with clinical signs of imminent brain death and 15 comatose patients were examined by neurologist in intensive care unit. HRV, RR interval and QT dispersion on ECG were assessed for 24 hours in both groups. Independent t-test and chi-square test were used for statistical analysis to determine significance which was set at p < 0.05. According to Holter findings, mean of standard deviation of RR-interval in the comatose and brain death groups was 48.33 and 35 respectively (p = 0.045). Mean of covariance coefficient of RR-interval was 0.065 in the comatose group and 0.043 in the brain deaths (p = 0.006). QT dispersion was not significant difference in two groups. HRV and RR-interval analysis appeared as an early finding for the diagnosis of brainstem death in comparison to comatose patients with normal brainstem function. QT dispersion had not significant in this regard. (author)

  20. Tumor suppressor function of Syk in human MCF10A in vitro and normal mouse mammary epithelium in vivo.

    Directory of Open Access Journals (Sweden)

    You Me Sung

    2009-10-01

    Full Text Available The normal function of Syk in epithelium of the developing or adult breast is not known, however, Syk suppresses tumor growth, invasion, and metastasis in breast cancer cells. Here, we demonstrate that in the mouse mammary gland, loss of one Syk allele profoundly increases proliferation and ductal branching and invasion of epithelial cells through the mammary fat pad during puberty. Mammary carcinomas develop by one year. Syk also suppresses proliferation and invasion in vitro. siRNA or shRNA knockdown of Syk in MCF10A breast epithelial cells dramatically increased proliferation, anchorage independent growth, cellular motility, and invasion, with formation of functional, extracellular matrix-degrading invadopodia. Morphological and gene microarray analysis following Syk knockdown revealed a loss of luminal and differentiated epithelial features with epithelial to mesenchymal transition and a gain in invadopodial cell surface markers CD44, CD49F, and MMP14. These results support the role of Syk in limiting proliferation and invasion of epithelial cells during normal morphogenesis, and emphasize the critical role of Syk as a tumor suppressor for breast cancer. The question of breast cancer risk following systemic anti-Syk therapy is raised since only partial loss of Syk was sufficient to induce mammary carcinomas.

  1. Investigation of olfactory function in normal volunteers and patients with anosmia : analysis of brain perfusion SPECTs using statistical parametric mapping

    International Nuclear Information System (INIS)

    Chung, Y. A.; Kim, S. H.; Sohn, H. S.; Chung, S. K.

    2002-01-01

    The purpose of this study was to investigate olfactory function with Tc-99m ECD brain perfusion SPECT using statistical parametric mapping (SPM) analysis in normal volunteers and patients with anosmia. The study populations were 8 subjects matched healthy volunteers and 16 subjects matched patients with anosmia. We obtaibed baseline and post-stimulation (3% butanol) brain perfusion SPECTs in the silent dark room. We analyzed the all SPECTs using SPM. The difference between two sets of brain perfusion SPECTs were compared with t-test. The voxels with p-value of less than 0.01 were considered to be significantly different. We demonstrated increased perfusion in the both cingulated gyri, right middle temporal gyrus, right superior and inferior frontal gyri, right lingual gyrus and right fusiform gyrus on post-stimulation brain SPECT in normal volunteers, and demonstrated decreased perfusion in the both cingulate gyri, right middle temporal gyrus, right rectal gyrus and both superior and inferior frontal gyri in the 10 patients with anosmia. No significant hypoperfusion area was observed in the other 6 patients with anosmia. The baseline and post-stimulation brain perfusion SPECTs can helpful in the evaluation of olfactory function and be useful in the diagnosis of anosmia

  2. Investigation of olfactory function in normal volunteers and patients with anosmia : analysis of brain perfusion SPECTs using statistical parametric mapping

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Y. A.; Kim, S. H.; Sohn, H. S.; Chung, S. K. [Catholic University College of Medicine, Seoul (Korea, Republic of)

    2002-07-01

    The purpose of this study was to investigate olfactory function with Tc-99m ECD brain perfusion SPECT using statistical parametric mapping (SPM) analysis in normal volunteers and patients with anosmia. The study populations were 8 subjects matched healthy volunteers and 16 subjects matched patients with anosmia. We obtaibed baseline and post-stimulation (3% butanol) brain perfusion SPECTs in the silent dark room. We analyzed the all SPECTs using SPM. The difference between two sets of brain perfusion SPECTs were compared with t-test. The voxels with p-value of less than 0.01 were considered to be significantly different. We demonstrated increased perfusion in the both cingulated gyri, right middle temporal gyrus, right superior and inferior frontal gyri, right lingual gyrus and right fusiform gyrus on post-stimulation brain SPECT in normal volunteers, and demonstrated decreased perfusion in the both cingulate gyri, right middle temporal gyrus, right rectal gyrus and both superior and inferior frontal gyri in the 10 patients with anosmia. No significant hypoperfusion area was observed in the other 6 patients with anosmia. The baseline and post-stimulation brain perfusion SPECTs can helpful in the evaluation of olfactory function and be useful in the diagnosis of anosmia.

  3. Investigation of olfactory function in normal volunteers by Tc-99m ECD Brain SPECT: Analysis using statistical parametric mapping

    International Nuclear Information System (INIS)

    Chung, Y.A.; Kim, S.H.; Park, Y.H.; Lee, S.Y.; Sohn, H.S.; Chung, S.K.

    2002-01-01

    The purpose of this study was to investigate olfactory function according to Tc-99m ECD uptake pattern in brain perfusion SPET of normal volunteer by means of statistical parametric mapping (SPM) analysis. The study population was 8 healthy volunteer subjects (M:F = 6:2, age range: 22-54 years, mean 34 years). We performed baseline brain perfusion SPET using 555 MBq of Tc-99m ECD in a silent dark room. Two hours later, we obtained brain perfusion SPET using 1110 MBq of Tc-99m ECD after 3% butanol solution under the same condition. All SPET images were spatially transformed to standard space smoothed and globally normalized. The differences between the baseline and odor-identification SPET images were statistically analyzed using SPM-99 software. The difference between two sets of brain perfusion SPET was considered significant at a threshold of uncorrected p values less than 0.01. SPM analysis revealed significant hyper-perfusion in both cingulated gyri, right middle temporal gyrus, right superior and inferior frontal gyri, right lingual gyrus and right fusiform gyrus on odor-identification SPET. This study shows that brain perfusion SPET can securely support other diagnostic techniques in the evaluation of olfactory function

  4. Registration-based assessment of regional lung function via volumetric CT images of normal subjects vs. severe asthmatics

    Science.gov (United States)

    Choi, Sanghun; Hoffman, Eric A.; Wenzel, Sally E.; Tawhai, Merryn H.; Yin, Youbing; Castro, Mario

    2013-01-01

    The purpose of this work was to explore the use of image registration-derived variables associated with computed tomographic (CT) imaging of the lung acquired at multiple volumes. As an evaluation of the utility of such an imaging approach, we explored two groups at the extremes of population ranging from normal subjects to severe asthmatics. A mass-preserving image registration technique was employed to match CT images at total lung capacity (TLC) and functional residual capacity (FRC) for assessment of regional air volume change and lung deformation between the two states. Fourteen normal subjects and thirty severe asthmatics were analyzed via image registration-derived metrics together with their pulmonary function test (PFT) and CT-based air-trapping. Relative to the normal group, the severely asthmatic group demonstrated reduced air volume change (consistent with air trapping) and more isotropic deformation in the basal lung regions while demonstrating increased air volume change associated with increased anisotropic deformation in the apical lung regions. These differences were found despite the fact that both PFT-derived TLC and FRC in the two groups were nearly 100% of predicted values. Data suggest that reduced basal-lung air volume change in severe asthmatics was compensated by increased apical-lung air volume change and that relative increase in apical-lung air volume change in severe asthmatics was accompanied by enhanced anisotropic deformation. These data suggest that CT-based deformation, assessed via inspiration vs. expiration scans, provides a tool for distinguishing differences in lung mechanics when applied to the extreme ends of a population range. PMID:23743399

  5. Amyloid precursor protein is required for normal function of the rod and cone pathways in the mouse retina.

    Directory of Open Access Journals (Sweden)

    Tracy Ho

    Full Text Available Amyloid precursor protein (APP is a transmembrane glycoprotein frequently studied for its role in Alzheimer's disease. Our recent study in APP knockout (KO mice identified an important role for APP in modulating normal neuronal development in the retina. However the role APP plays in the adult retina and whether it is required for vision is unknown. In this study we evaluated the role of APP in retinal function and morphology comparing adult wildtype (WT and APP-KO mice. APP was expressed on neuronal cells of the inner retina, including horizontal, cone bipolar, amacrine and ganglion cells in WT mice. The function of the retina was assessed using the electroretinogram and although the rod photoreceptor responses were similar in APP-KO and WT mice, the post-photoreceptor, inner retinal responses of both the rod and cone pathways were reduced in APP-KO mice. These changes in inner retinal function did not translate to a substantial change in visual acuity as assessed using the optokinetic response or to changes in the gross cellular structure of the retina. These findings indicate that APP is not required for basic visual function, but that it is involved in modulating inner retinal circuitry.

  6. Precortical phase of Alzheimer’s disease (AD)-related tau cytoskeletal pathology

    Science.gov (United States)

    Stratmann, Katharina; Heinsen, Helmut; Korf, Horst-Werner; Del Turco, Domenico; Ghebremedhin, Estifanos; Seidel, Kay; Bouzrou, Mohamed; Grinberg, Lea T.; Bohl, Jürgen; Wharton, Stephen B; den Dunnen, Wilfred; Rüb, Udo

    2015-01-01

    Alzheimer’s disease (AD) represents the most frequent progressive neuropsychiatric disorder worldwide leading to dementia and accounts for 60 to 70% of demented individuals. In view of the early appearance of neuronal deposits of the hyperphosphorylated cytoskeletal protein tau in the transentorhinal and entorhinal regions of the allocortex (i.e. in Braak and Braak AD stage I in the evolution of the AD-related cortical tau cytoskeletal pathology) it has been believed for a long time that these allocortical regions represent the first brain targets of the AD-related tau cytoskeletal pathology. However, recent pathoanatomical studies suggested that the subcortical brain nuclei that send efferent projections to the transentorhinal and entorhinal regions may also comprise AD-related cytoskeletal changes already at very early Braak and Braak AD stages. In order to corroborate these initial results we systematically investigated the presence and extent of the AD-related cytoskeletal pathology in serial thick tissue sections through all the subcortical nuclei known to send efferent projections to these vulnerable allocortical regions of three individuals with Braak and Braak AD stage 0 and fourteen individuals with Braak and Braak AD stage I by means of immunostainings with the anti-tau antibody AT8. These investigations revealed consistent AT8 immunoreactive neuronal tau cytoskeletal pathology in a subset of these subcortical nuclei (i.e. medial septal nucleus, nuclei of the vertical and horizontal limbs of the diagonal band of Broca, basal nucleus of Meynert; claustrum; hypothalamic ventromedial, tuberomamillary and supramamillary nuclei, perifornical region and lateral area; thalamic central medial, laterodorsal, subparafascicular, and central lateral nuclei, medial pulvinar and limitans-suprageniculate complex; peripeduncular nucleus, dopaminergic substantia nigra and ventral tegmental area, periaqueductal gray, midbrain and pontine dorsal raphe nuclei, locus

  7. Screen-Space Normal Distribution Function Caching for Consistent Multi-Resolution Rendering of Large Particle Data

    KAUST Repository

    Ibrahim, Mohamed; Wickenhauser, Patrick; Rautek, Peter; Reina, Guido; Hadwiger, Markus

    2017-01-01

    Molecular dynamics (MD) simulations are crucial to investigating important processes in physics and thermodynamics. The simulated atoms are usually visualized as hard spheres with Phong shading, where individual particles and their local density can be perceived well in close-up views. However, for large-scale simulations with 10 million particles or more, the visualization of large fields-of-view usually suffers from strong aliasing artifacts, because the mismatch between data size and output resolution leads to severe under-sampling of the geometry. Excessive super-sampling can alleviate this problem, but is prohibitively expensive. This paper presents a novel visualization method for large-scale particle data that addresses aliasing while enabling interactive high-quality rendering. We introduce the novel concept of screen-space normal distribution functions (S-NDFs) for particle data. S-NDFs represent the distribution of surface normals that map to a given pixel in screen space, which enables high-quality re-lighting without re-rendering particles. In order to facilitate interactive zooming, we cache S-NDFs in a screen-space mipmap (S-MIP). Together, these two concepts enable interactive, scale-consistent re-lighting and shading changes, as well as zooming, without having to re-sample the particle data. We show how our method facilitates the interactive exploration of real-world large-scale MD simulation data in different scenarios.

  8. Normalization of aberrant resting state functional connectivity in fibromyalgia patients following a three month physical exercise therapy.

    Science.gov (United States)

    Flodin, P; Martinsen, S; Mannerkorpi, K; Löfgren, M; Bileviciute-Ljungar, I; Kosek, E; Fransson, P

    2015-01-01

    Physical exercise is one of the most efficient interventions to mitigate chronic pain symptoms in fibromyalgia (FM). However, little is known about the neurophysiological mechanisms mediating these effects. In this study we investigated resting-state connectivity using functional magnetic resonance imaging (fMRI) before and after a 15 week standardized exercise program supervised by physical therapists. Our aim was to gain an understanding of how physical exercise influences previously shown aberrant patterns of intrinsic brain activity in FM. Fourteen FM patients and eleven healthy controls successfully completed the physical exercise treatment. We investigated post- versus pre-treatment changes of brain connectivity, as well as changes in clinical symptoms in the patient group. FM patients reported improvements in symptom severity. Although several brain regions showed a treatment-related change in connectivity, only the connectivity between the right anterior insula and the left primary sensorimotor area was significantly more affected by the physical exercise among the fibromyalgia patients compared to healthy controls. Our results suggest that previously observed aberrant intrinsic brain connectivity patterns in FM are partly normalized by the physical exercise therapy. However, none of the observed normalizations in intrinsic brain connectivity were significantly correlated with symptom changes. Further studies conducted in larger cohorts are warranted to investigate the precise relationship between improvements in fibromyalgia symptoms and changes in intrinsic brain activity.

  9. Frontopolar and anterior temporal cortex activation in a moral judgment task. Preliminary functional MRI results in normal subjects

    International Nuclear Information System (INIS)

    Moll, Jorge; Oliveira-Souza, Ricardo de

    2001-01-01

    The objective was to study the brain areas which are activated when normal subjects make moral judgments. Ten normal adults underwent BOLD functional magnetic resonance imaging (fMRI) during the auditory presentation of sentences that they were instructed to silently judge as either 'right' or 'wrong'. Half of the sentences had an explicit moral content ('We break the law when necessary'), the other half comprised factual statements devoid of moral connotation ('Stones are made of water'). After scanning, each subject rated the moral content, emotional valence, and judgment difficulty of each sentence on Likert-like scales. To exclude the effect of emotion on the activation results, individual responses were hemo dynamically modeled for event-related f MRI analysis. The general linear model was used to evaluate the brain areas activated by moral judgment. Regions activated during moral judgment included the frontopolar cortex (FPC), medial frontal gyrus, right anterior temporal cortex, lenticular nucleus, and cerebellum. Activation of FPC and medial frontal gyrus (B A 10/46 and 9) were largely independent of emotional experience and represented the largest areas of activation. These results concur with clinical observations assigning a critical role for the frontal poles and right anterior temporal cortex in the mediation of complex judgment processes according to moral constraints. The FPC may work in concert with the orbitofrontal and dorsolateral cortex in the regulation of human social conduct. (author)

  10. Normalization of aberrant resting state functional connectivity in fibromyalgia patients following a three month physical exercise therapy

    Directory of Open Access Journals (Sweden)

    P. Flodin

    2015-01-01

    Full Text Available Physical exercise is one of the most efficient interventions to mitigate chronic pain symptoms in fibromyalgia (FM. However, little is known about the neurophysiological mechanisms mediating these effects. In this study we investigated resting-state connectivity using functional magnetic resonance imaging (fMRI before and after a 15 week standardized exercise program supervised by physical therapists. Our aim was to gain an understanding of how physical exercise influences previously shown aberrant patterns of intrinsic brain activity in FM. Fourteen FM patients and eleven healthy controls successfully completed the physical exercise treatment. We investigated post- versus pre-treatment changes of brain connectivity, as well as changes in clinical symptoms in the patient group. FM patients reported improvements in symptom severity. Although several brain regions showed a treatment-related change in connectivity, only the connectivity between the right anterior insula and the left primary sensorimotor area was significantly more affected by the physical exercise among the fibromyalgia patients compared to healthy controls. Our results suggest that previously observed aberrant intrinsic brain connectivity patterns in FM are partly normalized by the physical exercise therapy. However, none of the observed normalizations in intrinsic brain connectivity were significantly correlated with symptom changes. Further studies conducted in larger cohorts are warranted to investigate the precise relationship between improvements in fibromyalgia symptoms and changes in intrinsic brain activity.

  11. Classification of Normal and Apoptotic Cells from Fluorescence Microscopy Images Using Generalized Polynomial Chaos and Level Set Function.

    Science.gov (United States)

    Du, Yuncheng; Budman, Hector M; Duever, Thomas A

    2016-06-01

    Accurate automated quantitative analysis of living cells based on fluorescence microscopy images can be very useful for fast evaluation of experimental outcomes and cell culture protocols. In this work, an algorithm is developed for fast differentiation of normal and apoptotic viable Chinese hamster ovary (CHO) cells. For effective segmentation of cell images, a stochastic segmentation algorithm is developed by combining a generalized polynomial chaos expansion with a level set function-based segmentation algorithm. This approach provides a probabilistic description of the segmented cellular regions along the boundary, from which it is possible to calculate morphological changes related to apoptosis, i.e., the curvature and length of a cell's boundary. These features are then used as inputs to a support vector machine (SVM) classifier that is trained to distinguish between normal and apoptotic viable states of CHO cell images. The use of morphological features obtained from the stochastic level set segmentation of cell images in combination with the trained SVM classifier is more efficient in terms of differentiation accuracy as compared with the original deterministic level set method.

  12. Recovery of normal esophageal function in a kitten with diffuse megaesophagus and an occult lower esophageal stricture.

    Science.gov (United States)

    Schneider, Jaycie; Ames, Marisa; DiCicco, Michael; Savage, Mason; Atkins, Clarke; Wood, Michael; Gookin, Jody L

    2015-06-01

    An 8-week-old male domestic shorthair was presented to the Internal Medicine Service at North Carolina State University for regurgitation. Radiographic diagnosis of generalized esophageal dilation and failure of esophageal peristalsis were compatible with diagnosis of congenital megaesophagus. Endoscopic examination of the esophagus revealed a fibrous stricture just orad to the lower esophageal sphincter. Conservative management to increase the body condition and size of the kitten consisted of feeding through a gastrostomy tube, during which time the esophagus regained normal peristaltic function, the stricture orifice widened in size and successful balloon dilatation of the stricture was performed. Esophageal endoscopy should be considered to rule out a stricture near the lower esophageal sphincter in kittens with radiographic findings suggestive of congenital megaesophagus. Management of such kittens by means of gastrostomy tube feeding may be associated with a return of normal esophageal motility and widening of the esophageal stricture, and facilitate subsequent success of interventional dilation of the esophageal stricture. © ISFM and AAFP 2014.

  13. Screen-Space Normal Distribution Function Caching for Consistent Multi-Resolution Rendering of Large Particle Data

    KAUST Repository

    Ibrahim, Mohamed

    2017-08-28

    Molecular dynamics (MD) simulations are crucial to investigating important processes in physics and thermodynamics. The simulated atoms are usually visualized as hard spheres with Phong shading, where individual particles and their local density can be perceived well in close-up views. However, for large-scale simulations with 10 million particles or more, the visualization of large fields-of-view usually suffers from strong aliasing artifacts, because the mismatch between data size and output resolution leads to severe under-sampling of the geometry. Excessive super-sampling can alleviate this problem, but is prohibitively expensive. This paper presents a novel visualization method for large-scale particle data that addresses aliasing while enabling interactive high-quality rendering. We introduce the novel concept of screen-space normal distribution functions (S-NDFs) for particle data. S-NDFs represent the distribution of surface normals that map to a given pixel in screen space, which enables high-quality re-lighting without re-rendering particles. In order to facilitate interactive zooming, we cache S-NDFs in a screen-space mipmap (S-MIP). Together, these two concepts enable interactive, scale-consistent re-lighting and shading changes, as well as zooming, without having to re-sample the particle data. We show how our method facilitates the interactive exploration of real-world large-scale MD simulation data in different scenarios.

  14. Frontopolar and anterior temporal cortex activation in a moral judgment task. Preliminary functional MRI results in normal subjects

    Energy Technology Data Exchange (ETDEWEB)

    Moll, Jorge [LABS and Rede D' Or Hospitais, Rio de Janeiro RJ (Brazil). Grupo de Neuroimagem e Neurologia do Comportamento; Eslinger, Paul J. [Pensylvania State Univ. (United States). College of Medicine. Div. of Neurology and Behavioral Science; The Milton S. Hershey Medical Center, Hershey, PN (United States); Oliveira-Souza, Ricardo de [Universidade do Rio de Janeiro (UNI-Rio), RJ (Brazil). Hospital Universitario Gaffree e Guinle]. E-mail: neuropsychiatry@hotmail.com

    2001-09-01

    The objective was to study the brain areas which are activated when normal subjects make moral judgments. Ten normal adults underwent BOLD functional magnetic resonance imaging (fMRI) during the auditory presentation of sentences that they were instructed to silently judge as either 'right' or 'wrong'. Half of the sentences had an explicit moral content ('We break the law when necessary'), the other half comprised factual statements devoid of moral connotation ('Stones are made of water'). After scanning, each subject rated the moral content, emotional valence, and judgment difficulty of each sentence on Likert-like scales. To exclude the effect of emotion on the activation results, individual responses were hemo dynamically modeled for event-related f MRI analysis. The general linear model was used to evaluate the brain areas activated by moral judgment. Regions activated during moral judgment included the frontopolar cortex (FPC), medial frontal gyrus, right anterior temporal cortex, lenticular nucleus, and cerebellum. Activation of FPC and medial frontal gyrus (B A 10/46 and 9) were largely independent of emotional experience and represented the largest areas of activation. These results concur with clinical observations assigning a critical role for the frontal poles and right anterior temporal cortex in the mediation of complex judgment processes according to moral constraints. The FPC may work in concert with the orbitofrontal and dorsolateral cortex in the regulation of human social conduct. (author)

  15. Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function

    DEFF Research Database (Denmark)

    Nielsen, Lene Ryom; Mocroft, A.; Kirk, O.

    2013-01-01

    Background. Several antiretroviral agents (ARVs) are associated with chronic renal impairment, but the extent of such adverse events among human immunodeficiency virus (HIV)-positive persons with initially normal renal function is unknown.Methods. D:A:D study participants with an estimated...... glomerular filtration rate (eGFR) of ≥90 mL/min after 1 January 2004 were followed until they had a confirmed eGFR of ≤70 mL/min (the threshold below which we hypothesized that renal interventions may begin to occur) or ≤60 mL/min (a value indicative of moderately severe chronic kidney disease [CKD...... [95% CI, 1.16-1.28], respectively). Associations were unaffected by censoring for concomitant ARV use but diminished after discontinuation of these ARVs.Conclusions. Tenofovir, ritonavir-boosted atazanavir, and ritonavir-boosted lopinavir use were independent predictors of chronic renal impairment...

  16. An Investigation of Spatial Hearing in Children with Normal Hearing and with Cochlear Implants and the Impact of Executive Function

    Science.gov (United States)

    Misurelli, Sara M.

    The ability to analyze an "auditory scene"---that is, to selectively attend to a target source while simultaneously segregating and ignoring distracting information---is one of the most important and complex skills utilized by normal hearing (NH) adults. The NH adult auditory system and brain work rather well to segregate auditory sources in adverse environments. However, for some children and individuals with hearing loss, selectively attending to one source in noisy environments can be extremely challenging. In a normal auditory system, information arriving at each ear is integrated, and thus these binaural cues aid in speech understanding in noise. A growing number of individuals who are deaf now receive cochlear implants (CIs), which supply hearing through electrical stimulation to the auditory nerve. In particular, bilateral cochlear implants (BICIs) are now becoming more prevalent, especially in children. However, because CI sound processing lacks both fine structure cues and coordination between stimulation at the two ears, binaural cues may either be absent or inconsistent. For children with NH and with BiCIs, this difficulty in segregating sources is of particular concern because their learning and development commonly occurs within the context of complex auditory environments. This dissertation intends to explore and understand the ability of children with NH and with BiCIs to function in everyday noisy environments. The goals of this work are to (1) Investigate source segregation abilities in children with NH and with BiCIs; (2) Examine the effect of target-interferer similarity and the benefits of source segregation for children with NH and with BiCIs; (3) Investigate measures of executive function that may predict performance in complex and realistic auditory tasks of source segregation for listeners with NH; and (4) Examine source segregation abilities in NH listeners, from school-age to adults.

  17. PTP-PEST controls EphA3 activation and ephrin-induced cytoskeletal remodelling.

    Science.gov (United States)

    Mansour, Mariam; Nievergall, Eva; Gegenbauer, Kristina; Llerena, Carmen; Atapattu, Lakmali; Hallé, Maxime; Tremblay, Michel L; Janes, Peter W; Lackmann, Martin

    2016-01-15

    Eph receptors and their corresponding membrane-bound ephrin ligands regulate cell positioning and establish tissue patterns during embryonic and oncogenic development. Emerging evidence suggests that assembly of polymeric Eph signalling clusters relies on cytoskeletal reorganisation and underlies regulation by protein tyrosine phosphatases (PTPs). PTP-PEST (also known as PTPN12) is a central regulator of actin cytoskeletal dynamics. Here, we demonstrate that an N-terminal fragment of PTP-PEST, generated through an ephrinA5-triggered and spatially confined cleavage mediated by caspase-3, attenuates EphA3 receptor activation and its internalisation. Isolation of EphA3 receptor signalling clusters within intact plasma membrane fragments obtained by detergent-free cell fractionation reveals that stimulation of cells with ephrin triggers effective recruitment of this catalytically active truncated form of PTP-PEST together with key cytoskeletal and focal adhesion proteins. Importantly, modulation of actin polymerisation using pharmacological and dominant-negative approaches affects EphA3 phosphorylation in a similar manner to overexpression of PTP-PEST. We conclude that PTP-PEST regulates EphA3 activation both by affecting cytoskeletal remodelling and through its direct action as a PTP controlling EphA3 phosphorylation, indicating its multifaceted regulation of Eph signalling. © 2016. Published by The Company of Biologists Ltd.

  18. Ras1 interacts with multiple new signaling and cytoskeletal loci in Drosophila eggshell patterning and morphogenesis.

    Science.gov (United States)

    Schnorr, J D; Holdcraft, R; Chevalier, B; Berg, C A

    2001-10-01

    Little is known about the genes that interact with Ras signaling pathways to regulate morphogenesis. The synthesis of dorsal eggshell structures in Drosophila melanogaster requires multiple rounds of Ras signaling followed by dramatic epithelial sheet movements. We took advantage of this process to identify genes that link patterning and morphogenesis; we screened lethal mutations on the second chromosome for those that could enhance a weak Ras1 eggshell phenotype. Of 1618 lethal P-element mutations tested, 13 showed significant enhancement, resulting in forked and fused dorsal appendages. Our genetic and molecular analyses together with information from the Berkeley Drosophila Genome Project reveal that 11 of these lines carry mutations in previously characterized genes. Three mutations disrupt the known Ras1 cell signaling components Star, Egfr, and Blistered, while one mutation disrupts Sec61beta, implicated in ligand secretion. Seven lines represent cell signaling and cytoskeletal components that are new to the Ras1 pathway; these are Chickadee (Profilin), Tec29, Dreadlocks, POSH, Peanut, Smt3, and MESK2, a suppressor of dominant-negative Ksr. A twelfth insertion disrupts two genes, Nrk, a "neurospecific" receptor tyrosine kinase, and Tpp, which encodes a neuropeptidase. These results suggest that Ras1 signaling during oogenesis involves novel components that may be intimately associated with additional signaling processes and with the reorganization of the cytoskeleton. To determine whether these Ras1 Enhancers function upstream or downstream of the Egf receptor, four mutations were tested for their ability to suppress an activated Egfr construct (lambdatop) expressed in oogenesis exclusively in the follicle cells. Mutations in Star and l(2)43Bb had no significant effect upon the lambdatop eggshell defect whereas smt3 and dock alleles significantly suppressed the lambdatop phenotype.

  19. Differential anti-ischaemic effects of muscarinic receptor blockade in patients with obstructive coronary artery disease; impaired vs normal left ventricular function.

    NARCIS (Netherlands)

    A.F. van den Heuvel; D.J. van Veldhuisen (Dirk); G.L. Bartels; M. van der Ent (Martin); W.J. Remme (Willem)

    1999-01-01

    textabstractAIMS: In patients with coronary artery disease acetylcholine (a muscarinic agonist) causes vasoconstriction. The effect of atropine (a muscarinic antagonist) on coronary vasotone in patients with normal or impaired left ventricular function is unknown.

  20. Quinolinic acid neurotoxicity: Differential roles of astrocytes and microglia via FGF-2-mediated signaling in redox-linked cytoskeletal changes.

    Science.gov (United States)

    Pierozan, Paula; Biasibetti, Helena; Schmitz, Felipe; Ávila, Helena; Parisi, Mariana M; Barbe-Tuana, Florencia; Wyse, Angela T S; Pessoa-Pureur, Regina

    2016-12-01

    QUIN is a glutamate agonist playing a role in the misregulation of the cytoskeleton, which is associated with neurodegeneration in rats. In this study, we focused on microglial activation, FGF2/Erk signaling, gap junctions (GJs), inflammatory parameters and redox imbalance acting on cytoskeletal dynamics of the in QUIN-treated neural cells of rat striatum. FGF-2/Erk signaling was not altered in QUIN-treated primary astrocytes or neurons, however cytoskeleton was disrupted. In co-cultured astrocytes and neurons, QUIN-activated FGF2/Erk signaling prevented the cytoskeleton from remodeling. In mixed cultures (astrocyte, neuron, microglia), QUIN-induced FGF-2 increased level failed to activate Erk and promoted cytoskeletal destabilization. The effects of QUIN in mixed cultures involved redox imbalance upstream of Erk activation. Decreased connexin 43 (Cx43) immunocontent and functional GJs, was also coincident with disruption of the cytoskeleton in primary astrocytes and mixed cultures. We postulate that in interacting astrocytes and neurons the cytoskeleton is preserved against the insult of QUIN by activation of FGF-2/Erk signaling and proper cell-cell interaction through GJs. In mixed cultures, the FGF-2/Erk signaling is blocked by the redox imbalance associated with microglial activation and disturbed cell communication, disrupting the cytoskeleton. Thus, QUIN signal activates differential mechanisms that could stabilize or destabilize the cytoskeleton of striatal astrocytes and neurons in culture, and glial cells play a pivotal role in these responses preserving or disrupting a combination of signaling pathways and cell-cell interactions. Taken together, our findings shed light into the complex role of the active interaction of astrocytes, neurons and microglia in the neurotoxicity of QUIN. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Cooperation of the BTB-Zinc finger protein, Abrupt, with cytoskeletal regulators in Drosophila epithelial tumorigenesis

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    Nezaket Turkel

    2015-08-01

    Full Text Available The deregulation of cell polarity or cytoskeletal regulators is a common occurrence in human epithelial cancers. Moreover, there is accumulating evidence in human epithelial cancer that BTB-ZF genes, such as Bcl6 and ZBTB7A, are oncogenic. From our previous studies in the vinegar fly, Drosophila melanogaster, we have identified a cooperative interaction between a mutation in the apico-basal cell polarity regulator Scribble (Scrib and overexpression of the BTB-ZF protein Abrupt (Ab. Herein, we show that co-expression of ab with actin cytoskeletal regulators, RhoGEF2 or Src64B, in the developing eye-antennal epithelial tissue results in the formation of overgrown amorphous tumours, whereas ab and DRac1 co-expression leads to non-cell autonomous overgrowth. Together with ab, these genes affect the expression of differentiation genes, resulting in tumours locked in a progenitor cell fate. Finally, we show that the expression of two mammalian genes related to ab, Bcl6 and ZBTB7A, which are oncogenes in mammalian epithelial cancers, significantly correlate with the upregulation of cytoskeletal genes or downregulation of apico-basal cell polarity neoplastic tumour suppressor genes in colorectal, lung and other human epithelial cancers. Altogether, this analysis has revealed that upregulation of cytoskeletal regulators cooperate with Abrupt in Drosophila epithelial tumorigenesis, and that high expression of human BTB-ZF genes, Bcl6 and ZBTB7A, shows significant correlations with cytoskeletal and cell polarity gene expression in specific epithelial tumour types. This highlights the need for further investigation of the cooperation between these genes in mammalian systems.

  2. Mechanical muscle function and lean body mass during supervised strength training and testosterone therapy in aging men with low-normal testosterone levels

    DEFF Research Database (Denmark)

    Kvorning, Thue; Christensen, Louise L; Madsen, Klavs

    2013-01-01

    To examine the effect of strength training and testosterone therapy on mechanical muscle function and lean body mass (LBM) in aging men with low-normal testosterone levels in a randomized, double-blind, placebo-controlled 24-week study.......To examine the effect of strength training and testosterone therapy on mechanical muscle function and lean body mass (LBM) in aging men with low-normal testosterone levels in a randomized, double-blind, placebo-controlled 24-week study....

  3. Gadolinium based contrast agents in current practice: Risks of accumulation and toxicity in patients with normal renal function

    Directory of Open Access Journals (Sweden)

    Anju Ranga

    2017-01-01

    Full Text Available Despite being decked as the most prized compounds in the nugget box of contrast agents for clinical radiologists, and carrying an indisputable tag of safety of the US Food and Drug Administration for close to three decades, all may not be seemingly well with the family of gadolinium compounds. If the first signs of violations of primum non nocere in relation to gadolinium-based contrast agents (GBCAs appeared in the millennium year with the first published report of skin fibrosis in patients with compromised renal function, the causal relationship between the development of nephrogenic systemic fibrosis (NSF and GBCAs, first proposed by two European groups in 2006, further precluded their use in renocompromised patients. The toxicity, pharmacokinetics, and pharmacodynamics of GBCAs, however, has come under hawk-eyed scrutiny with recent reports that gadolinium tends to deposit cumulatively in the brain of patients with normal hepatobiliary function and intact blood–brain barrier. While the jury on the long-term hazard significance of this critical scientific finding is still out, the use of GBCAs must be guided by due clinical diligence, avoidance of repeated doses, and preferring GBCAs with the best safety profiles.

  4. Assessment of normal left atrial appendage anatomy and function over gender and ages by dynamic cardiac CT

    International Nuclear Information System (INIS)

    Boucebci, Samy; Velasco, Stephane; Duboe, Pier-Olivier; Tasu, Jean-Pierre; Pambrun, Thomas; Ingrand, Pierre

    2016-01-01

    The aim of this study was to evaluate variations in anatomy and function according to age and gender using cardiac computed tomography (CT) in a large prospective cohort of healthy patients. The left atrial appendage (LAA) is considered the most frequent site of intracardiac thrombus formation. However, variations in normal in vivo anatomy and function according to age and gender remain largely unknown. Three-dimensional (3D) cardiac reconstructions of the LAA were performed from CT scans of 193 consecutive patients. Parameters measured included LAA number of lobes, anatomical position of the LAA tip, angulation measured between the proximal and distal portions, minimum (iVol min ) and maximum (iVol max ) volumes indexed to body surface area (BSA), and ejection fraction (LAAEF). Relationship with age was assessed for each parameter. We found that men had longer and wider LAAs. The iVol min and iVol max increased by 0.23 and 0.19 ml per decade, respectively, while LAAEF decreased by 2 % per decade in both sexes. Although LAA volumes increase, LAAEF decreases with age in both sexes. (orig.)

  5. Functional brain response to food images in successful adolescent weight losers compared with normal-weight and overweight controls.

    Science.gov (United States)

    Jensen, Chad D; Kirwan, C Brock

    2015-03-01

    Research conducted with adults suggests that successful weight losers demonstrate greater activation in brain regions associated with executive control in response to viewing high-energy foods. No previous studies have examined these associations in adolescents. Functional neuroimaging was used to assess brain response to food images among groups of overweight (OW), normal-weight (NW), and successful weight-losing (SWL) adolescents. Eleven SWL, 12 NW, and 11 OW participants underwent functional magnetic resonance imaging while viewing images of high- and low-energy foods. When viewing high-energy food images, SWLs demonstrated greater activation in the dorsolateral prefrontal cortex (DLPFC) compared with OW and NW controls. Compared with NW and SWL groups, OW individuals demonstrated greater activation in the ventral striatum and anterior cingulate in response to food images. Adolescent SWLs demonstrated greater neural activation in the DLPFC compared with OW/NW controls when viewing high-energy food stimuli, which may indicate enhanced executive control. OW individuals' brain responses to food stimuli may indicate greater reward incentive processes than either SWL or NW groups. © 2015 The Obesity Society.

  6. Assessment of normal left atrial appendage anatomy and function over gender and ages by dynamic cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Boucebci, Samy; Velasco, Stephane; Duboe, Pier-Olivier; Tasu, Jean-Pierre [University of Poitiers, University Hospital, Department of Radiology, Poitiers (France); Pambrun, Thomas [University of Poitiers, University Hospital, Department of Cardiology, Poitiers (France); Ingrand, Pierre [University of Poitiers, University Institute of Public Health, Poitiers (France)

    2016-05-15

    The aim of this study was to evaluate variations in anatomy and function according to age and gender using cardiac computed tomography (CT) in a large prospective cohort of healthy patients. The left atrial appendage (LAA) is considered the most frequent site of intracardiac thrombus formation. However, variations in normal in vivo anatomy and function according to age and gender remain largely unknown. Three-dimensional (3D) cardiac reconstructions of the LAA were performed from CT scans of 193 consecutive patients. Parameters measured included LAA number of lobes, anatomical position of the LAA tip, angulation measured between the proximal and distal portions, minimum (iVol{sub min}) and maximum (iVol{sub max}) volumes indexed to body surface area (BSA), and ejection fraction (LAAEF). Relationship with age was assessed for each parameter. We found that men had longer and wider LAAs. The iVol{sub min} and iVol{sub max} increased by 0.23 and 0.19 ml per decade, respectively, while LAAEF decreased by 2 % per decade in both sexes. Although LAA volumes increase, LAAEF decreases with age in both sexes. (orig.)

  7. THE COMPARISON OF THE LUMBAR MULTIFIDUS MUSCLES FUNCTION BETWEEN GYMNASTIC ATHLETES WITH SWAY-BACK POSTURE AND NORMAL POSTURE.

    Science.gov (United States)

    Mahdavie, Elnaz; Rezasoltani, Asghar; Simorgh, Leila

    2017-08-01

    The prevalence of sway back posture (SBP) is very high among elite gymnasts. This posture may be partly due to the improper function of lumbar multifidus muscles (LMM) as lumbar stabilizers muscles. The aim of this study was to compare the thicknesses of LMM measured at rest and during the contraction elicited during an arm lift between elite gymnasts with SBP and normal posture. Observational, descriptive, comparative. The participants consist of twenty gymnasts between the ages of 17 and 30 who had trained in gymnastics for more than ten years. They were assigned to two groups: SBP (n=10) and control (n=10). Posture analysis with grid paper and plumb line was performed for all subjects. The thickness of LMM on dominant side of spinal column was measured by a real-time ultrasound at five lumbar levels. The thickness of the LMM was measured both at rest and during the contraction elicited during an arm lift. The variation between the LMM thickness between the muscle at rest and muscle at the peak of contraction was regarded as LMM muscle function. The thickness of LMM was less in SBP group than the control group at all lumbar segments. The variation in LMM thickness between the state of rest and muscle contraction was significantly less in athletes with SBP than controls when compared at all levels of the lumbar spine (p antigravity and stabilizing muscle group was decreased during arm raising in gymnasts with SBP. 3a.

  8. A histological and functional study on hippocampal formation of normal and diabetic rats [v1; ref status: indexed, http://f1000r.es/y9

    Directory of Open Access Journals (Sweden)

    Shaimaa N Amin

    2013-07-01

    Full Text Available Background: The hippocampus is a key brain area for many forms of learning and memory and is particularly sensitive to changes in glucose homeostasis. Aim of the work: To investigate in experimentally induced type 1 and 2 diabetes mellitus in rat model the effect of  diabetes mellitus on cognitive functions and related markers of hippocampal synaptic plasticity, and the possible impact of blocking N-methyl-D-aspartic acid (NMDA receptors by memantine. Materials and methods: Seven rat groups were included: non-diabetic control and non-diabetic receiving memantine; type-1 diabetic groups - untreated, treated with insulin alone and treated with insulin and memantine; and type 2 diabetic groups - untreated and memantine treated. Cognitive functions were assessed by the Morris Water Maze and passive avoidance test. Biochemical analysis was done for serum glucose, serum insulin and insulin resistance. Routine histological examination was done, together with immunohistochemistry for detection of the hippocampal learning and memory plasticity marker, namely activity regulated cytoskeletal-associated protein (Arc, and the astrocytes reactivity marker, namely glial fibrillary acidic protein (GFAP.  Results: Both type 1 and 2 untreated diabetic groups showed significantly impaired cognitive performance compared to the non-diabetic group. Treating the type 1 diabetic group with insulin alone significantly improved cognitive performance, but significantly decreased GFAP and Arc compared to the untreated type 1 group. In addition, the type 2 diabetic groups showed a significant decrease in hippocampus GFAP and Arc compared to the non-diabetic groups. Blocking NMDA receptors by memantine significantly increased cognitive performance, GFAP and Arc in the type 1 insulin-memantine group compared to the type 1-insulin group and significantly increased Arc in the type 2-memantine group compared to the untreated type 2 diabetic group. The non-diabetic group

  9. Macrophage functions measured by magnetic microparticles in vivo and in vitro

    International Nuclear Information System (INIS)

    Moeller, Winfried; Kreyling, Wolfgang G.; Kohlhaeufl, Martin; Haeussinger, Karl; Heyder, Joachim

    2001-01-01

    Monodisperse ferrimagnetic iron-oxide particles of 1.4 μm geometric diameter were used to study alveolar macrophage functions (phagocytosis, phagosome transport) and cytoskeletal integrity in healthy subjects and in patients with idiopathic pulmonary fibrosis as well as in cultured macrophages. Dysfunctions in phagocytosis, in phagosome transport and cytoskeletal integrity correlated with an impaired alveolar clearance and could be induced in vitro by cytoskeletal drugs

  10. Macrophage functions measured by magnetic microparticles in vivo and in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, Winfried E-mail: moeller@gsf.de; Kreyling, Wolfgang G.; Kohlhaeufl, Martin; Haeussinger, Karl; Heyder, Joachim

    2001-07-01

    Monodisperse ferrimagnetic iron-oxide particles of 1.4 {mu}m geometric diameter were used to study alveolar macrophage functions (phagocytosis, phagosome transport) and cytoskeletal integrity in healthy subjects and in patients with idiopathic pulmonary fibrosis as well as in cultured macrophages. Dysfunctions in phagocytosis, in phagosome transport and cytoskeletal integrity correlated with an impaired alveolar clearance and could be induced in vitro by cytoskeletal drugs.

  11. Zearalenone altered the cytoskeletal structure via ER stress- autophagy- oxidative stress pathway in mouse TM4 Sertoli cells.

    Science.gov (United States)

    Zheng, Wanglong; Wang, Bingjie; Si, Mengxue; Zou, Hui; Song, Ruilong; Gu, Jianhong; Yuan, Yan; Liu, Xuezhong; Zhu, Guoqiang; Bai, Jianfa; Bian, Jianchun; Liu, ZongPing

    2018-02-20

    The aim of this study was to investigate the molecular mechanisms of the destruction of cytoskeletal structure by Zearalenone (ZEA) in mouse-derived TM4 cells. In order to investigate the role of autophagy, oxidative stress and endoplasmic reticulum(ER) stress in the process of destruction of cytoskeletal structure, the effects of ZEA on the cell viability, cytoskeletal structure, autophagy, oxidative stress, ER stress, MAPK and PI3K- AKT- mTOR signaling pathways were studied. The data demonstrated that ZEA damaged the cytoskeletal structure through the induction of autophagy that leads to the alteration of cytoskeletal structure via elevated oxidative stress. Our results further showed that the autophagy was stimulated by ZEA through PI3K-AKT-mTOR and MAPK signaling pathways in TM4 cells. In addition, ZEA also induced the ER stress which was involved in the induction of the autophagy through inhibiting the ERK signal pathway to suppress the phosphorylation of mTOR. ER stress was involved in the damage of cytoskeletal structure through induction of autophagy by producing ROS. Taken together, this study revealed that ZEA altered the cytoskeletal structure via oxidative stress - autophagy- ER stress pathway in mouse TM4 Sertoli cells.

  12. Association Between Thyroid Hormones, Thyroid Antibodies, and Cardiometabolic Factors in Non-Obese Individuals With Normal Thyroid Function

    Directory of Open Access Journals (Sweden)

    Jia Liu

    2018-04-01

    Full Text Available BackgroundHypothyroidism is an important risk factor for cardiovascular diseases, and autoimmune thyroiditis (AIT is the leading cause of hypothyroidism. Recent studies showed that even AIT patients with euthyroidism still had an increased number of early atherosclerotic lesions. However, the precise mechanism is not yet known. This study aimed to investigate the association of thyroid function, thyroid autoimmunity, and cardiometabolic risk factors in non-obese AIT patients with euthyroidism.MethodsA total of 5,608 non-obese individuals including 1,402 AIT patient and 4,206 sex-, age-, and body mass index (BMI-matched healthy controls were recruited.ResultsThe AIT patients had significantly lower free T3 and free T4 levels, and higher TSH, antithyroid peroxidase antibodies (TPOAb and TgAb levels. The elevated levels of high sensitivity C reactive protein (hsCRP and homeostasis model assessment of insulin resistance (HOMA-IR were observed in the AIT patients than the controls [hsCRP: 0.65 (0.27–1.33 vs. 0.20 (0.03–0.74 mg/L; HOMA-IR: 2.78 ± 1.60 vs. 2.33 ± 1.49; all P < 0.05]. Thyroid function was not associated with metabolic parameters and inflammatory makers, while the TPOAb titer was positively associated with the HOMA-IR and hsCRP levels after adjustment for confounding factors (all P < 0.05. Multivariate regression analysis demonstrated that the TPOAb level was an independent influencing factor for the HOMA-IR and hsCRP levels (HOMA-IR: β = 0.058, P < 0.05; hsCRP: β = 0.108, P < 0.05.ConclusionThe TPOAb level is associated with HOMA-IR and hsCRP levels independently of thyroid function in non-obese individuals. Mild deviation of thyroid function within the normal range, chronic inflammation, and insulin resistance may be the links between AIT and atherosclerosis in the non-obese population.

  13. Smart Aging Platform for Evaluating Cognitive Functions in Aging: A Comparison with the MoCA in a Normal Population

    Directory of Open Access Journals (Sweden)

    Sara Bottiroli

    2017-11-01

    Full Text Available Background: Smart Aging is a Serious games (SGs platform in a 3D virtual environment in which users perform a set of screening tests that address various cognitive skills. The tests are structured as 5 tasks of activities of daily life in a familiar environment. The main goal of the present study is to compare a cognitive evaluation made with Smart Aging with those of a classic standardized screening test, the Montreal Cognitive Assessment (MoCA.Methods: One thousand one-hundred thirty-one healthy adults aged between 50 and 80 (M = 64.3 ± 8.3 were enrolled in the study. They received a cognitive evaluation with the MoCA and the Smart Aging platform. Participants were grouped according to their MoCA global and specific cognitive domain (i.e., memory, executive functions, working memory, visual spatial elaboration, language, and orientation scores and we explored differences among these groups in the Smart Aging indices.Results: One thousand eighty-six older adults (M = 64.0 ± 8.0 successfully completed the study and were stratified according to their MoCA score: Group 1 with MoCA < 27 (n = 360; Group 2 with 27 ≥ MoCA < 29 (n = 453; and Group 3 with MoCA ≥ 29 (n = 273. MoCA groups significantly differed in most of the Smart Aging indices considered, in particular as concerns accuracy (ps < 0.001 and time (ps < 0.001 for completing most of the platform tasks. Group 1 was outperformed by the other two Groups and was slower than them in these tasks, which were those supposed to assess memory and executive functions. In addition, significant differences across groups also emerged when considering the single cognitive domains of the MoCA and the corresponding performances in each Smart Aging task. In particular, this platform seems to be a good proxy for assessing memory, executive functions, working memory, and visual spatial processes.Conclusion: These findings demonstrate the validity of Smart Aging for assessing cognitive functions in normal

  14. Assessment of the influence of osteopathic myofascial techniques on normalization of the vocal tract functions in patients with occupational dysphonia.

    Science.gov (United States)

    Marszałek, Sławomir; Niebudek-Bogusz, Ewa; Woźnicka, Ewelina; Malińska, Joanna; Golusiński, Wojciech; Śliwińska-Kowalska, Mariola

    2012-06-01

    Occupational voice disorders are accompanied by increased tension of the external laryngeal muscle which changes the position of the larynx and consequently disturbs the conditions of functioning of the vocal tract. The aim of the study is to assess the use of osteopathic procedures in the diagnosis and treatment of occupational dysphonia. Study subjects included 40 teachers with chronic diseases of the voice organ (38 women and 2 men) aged from 39 to 59 (mean age: 48.25). Before and after the voice therapy the osteopathic examination according to Libermann's protocol was performed as well as phoniatric examination including laryngovideostroboscopy (LVSS), assessment of the maximum phonation time (MPT) and the Voice Handicap Index (VHI) score. The voice therapy, scheduled and supervised by a laryngologist-phoniatrician and conducted by a speech-language pathologist, was supplemented with osteopathic myofascial rehabilitation of the larynx. The chi-square McNemar test and non-parametric Wilcoxon matched pairs test were applied in the statistical assessment. The applied interdisciplinary treatment including osteopathic and vocal therapy resulted in a statistically significant decrease in tenderness of muscles raising the larynx (cricothyroid ligament, sternocleidomastoid muscles, and pharyngeal constrictor muscles) and in lowering the tonus (geniohyoid muscles, pharyngeal constrictor muscles and sternocleidomastoid muscles). A significant improvement was also observed in the case of dysfunction of the cricothyroid joint examined during glissando and yawning, as well as in asymmetry of the thyrohyoid apparatus. Moreover, the therapy resulted in significantly better normalization of the head position and better control of the centre of gravity of the body. Statistically significant post-therapy improvement was observed in the phoniatric examination, including VHI scores, MPT results and parameters of videostroboscopic examination. The use of osteopathic therapy helps

  15. Spirometry and volumetric capnography in lung function assessment of obese and normal-weight individuals without asthma.

    Science.gov (United States)

    Ferreira, Mariana S; Mendes, Roberto T; Marson, Fernando A L; Zambon, Mariana P; Antonio, Maria A R G M; Paschoal, Ilma A; Toro, Adyléia A D C; Severino, Silvana D; Ribeiro, Maria A G O; Ribeiro, José D

    To analyze and compare lung function of obese and healthy, normal-weight children and adolescents, without asthma, through spirometry and volumetric capnography. Cross-sectional study including 77 subjects (38 obese) aged 5-17 years. All subjects underwent spirometry and volumetric capnography. The evaluations were repeated in obese subjects after the use of a bronchodilator. At the spirometry assessment, obese individuals, when compared with the control group, showed lower values of forced expiratory volume in the first second by forced vital capacity (FEV 1 /FVC) and expiratory flows at 75% and between 25 and 75% of the FVC (p11 years (p<0.05). Even without the diagnosis of asthma by clinical criteria and without response to bronchodilator use, obese individuals showed lower FEV 1 /FVC values and forced expiratory flow, indicating the presence of an obstructive process. Volumetric capnography showed that obese individuals had higher alveolar tidal volume, with no alterations in ventilation homogeneity, suggesting flow alterations, without affecting lung volumes. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  16. Density functional study of a typical thiol tethered on a gold surface: ruptures under normal or parallel stretch

    International Nuclear Information System (INIS)

    Wang, Guan M; Sandberg, William C; Kenny, Steven D

    2006-01-01

    The mechanical and dynamical properties of a model Au(111)/thiol surface system were investigated by using localized atomic-type orbital density functional theory in the local density approximation. Relaxing the system gives a configuration where the sulfur atom forms covalent bonds to two adjacent gold atoms as the lowest energy structure. Investigations based on ab initio molecular dynamics simulations at 300, 350 and 370 K show that this tethering system is stable. The rupture behaviour between the thiol and the surface was studied by displacing the free end of the thiol. Calculated energy profiles show a process of multiple successive ruptures that account for experimental observations. The process features successive ruptures of the two Au-S bonds followed by the extraction of one S-bonded Au atom from the surface. The force required to rupture the thiol from the surface was found to be dependent on the direction in which the thiol was displaced, with values comparable with AFM measurements. These results aid the understanding of failure dynamics of Au(111)-thiol-tethered biosurfaces in microfluidic devices where fluidic shear and normal forces are of concern

  17. Fractional excretion of beta-2-microglobulin in the urine of patients with normal or reduced renal function and hepatic coma

    DEFF Research Database (Denmark)

    Hansen, P B; Dalhoff, K; Joffe, P

    1991-01-01

    The purpose of this prospective study was to evaluate beta-2-microglobulin (beta 2m) as a differential diagnostic indicator between hepatic nephropathy (HN) and acute tubulointerstitial nephropathy (ATIN) in patients with reduced renal function and hepatic coma, and to determine whether beta 2m...... excretion could be used as a marker of renal impairment before increased serum creatinine (S-Cr) concentration or decreased creatinine clearance (Cr-Cl). Finally, the use of beta 2m as a prognostic indicator was investigated. Eighteen patients in hepatic coma grade III-IV were entered in the study and were...... to the small number of patients. FE-beta 2m could not predict the development of renal failure earlier than the increase in S-Cr or decrease in Cr-Cl. However, a few patients who survived paracetamol intoxication had increased FE-beta 2M in the beginning of the coma and normal S-Cr and Cr-Cl. Patients who died...

  18. Chronic stress effects on hippocampal structure and synaptic function: relevance for depression and normalization by anti-glucocorticoid treatment

    Directory of Open Access Journals (Sweden)

    Harmen J Krugers

    2010-07-01

    Full Text Available Exposure of an organism to environmental challenges activates two hormonal systems that help the organism to adapt. As part of this adaptational process, brain processes are changed such that appropriate behavioral strategies are selected that allow optimal performance at the short term, while relevant information is stored for the future. Over the past years it has become evident that chronic uncontrollable and unpredictable stress also exerts profound effects on structure and function of limbic neurons, but the impact of chronic stress is not a mere accumulation of repeated episodes of acute stress exposure. Dendritic trees are reduced in some regions but expanded in others, and cells are generally exposed to a higher calcium load upon depolarization. Synaptic strengthening is largely impaired. Neurotransmitter responses are also changed, e.g. responses to serotonin. We here discuss: a the main cellular effects after chronic stress with emphasis on the hippocampus, b how such effects could contribute to the development of psychopathology in genetically vulnerable individuals, and c their normalization by brief treatment with anti-glucocorticoids.

  19. Fully automatic quantitative assessment of emphysema in computed tomography: comparison with pulmonary function testing and normal values

    International Nuclear Information System (INIS)

    Heussel, C.P.; Hantusch, R.; Hartlieb, S.; Herth, F.J.F.; Kappes, J.; Eberhardt, R.; Weinheimer, O.; Kauczor, H.U.

    2009-01-01

    Characterisation and quantification of emphysema are necessary for planning of local treatment and monitoring. Sensitive, easy to measure, and stable parameters have to be established and their relation to the well-known pulmonary function testing (PFT) has to be investigated. A retrospective analysis of 221 nonenhanced thin-section MDCT with a corresponding PFT was carried out, with a subgroup analysis in 102 COPD stage III+IV, 44 COPD stage 0, and 33 investigations into interstitial lung disease (ILD). The in-house YACTA software was used for automatic quantification of lung and emphysema volume [l], emphysema index, mean lung density (MLD [HU]) and 15 th percentile [HU]. CT-derived lung volume is significantly smaller in ILD (3.8) and larger in COPD (7.2) than in controls (5.9, p th percentile are significantly smaller in COPD (-877/-985, p th percentile lower than -950 might be regarded as normal (thin-section, nonenhanced, B40, YACTA). These ranges might be helpful in the judgement of individual measures. (orig.)

  20. Cytoskeletal stability in the auditory organ in vivo

    DEFF Research Database (Denmark)

    Anttonen, Tommi; Belevich, Ilya; Laos, Maarja

    2017-01-01

    Wound healing in the inner ear sensory epithelia is performed by the apical domains of supporting cells (SCs). Junctional F-actin belts of SCs are thin during development but become exceptionally thick during maturation. The functional significance of the thick belts is not fully understood. We h...

  1. Cytoskeletal stability and metabolic alterations in primary human macrophages in long-term microgravity.

    Directory of Open Access Journals (Sweden)

    Svantje Tauber

    Full Text Available The immune system is one of the most affected systems of the human body during space flight. The cells of the immune system are exceptionally sensitive to microgravity. Thus, serious concerns arise, whether space flight associated weakening of the immune system ultimately precludes the expansion of human presence beyond the Earth's orbit. For human space flight, it is an urgent need to understand the cellular and molecular mechanisms by which altered gravity influences and changes the functions of immune cells. The CELLBOX-PRIME (= CellBox-Primary Human Macrophages in Microgravity Environment experiment investigated for the first time microgravity-associated long-term alterations in primary human macrophages, one of the most important effector cells of the immune system. The experiment was conducted in the U.S. National Laboratory on board of the International Space Station ISS using the NanoRacks laboratory and Biorack type I standard CELLBOX EUE type IV containers. Upload and download were performed with the SpaceX CRS-3 and the Dragon spaceship on April 18th, 2014 / May 18th, 2014. Surprisingly, primary human macrophages exhibited neither quantitative nor structural changes of the actin and vimentin cytoskeleton after 11 days in microgravity when compared to 1g controls. Neither CD18 or CD14 surface expression were altered in microgravity, however ICAM-1 expression was reduced. The analysis of 74 metabolites in the cell culture supernatant by GC-TOF-MS, revealed eight metabolites with significantly different quantities when compared to 1g controls. In particular, the significant increase of free fucose in the cell culture supernatant was associated with a significant decrease of cell surface-bound fucose. The reduced ICAM-1 expression and the loss of cell surface-bound fucose may contribute to functional impairments, e.g. the activation of T cells, migration and activation of the innate immune response. We assume that the surprisingly small

  2. Human embryonic stem cell (hES derived dendritic cells are functionally normal and are susceptible to HIV-1 infection

    Directory of Open Access Journals (Sweden)

    Bandi Sriram

    2008-01-01

    Full Text Available Abstract Background Human embryonic stem (hES cells hold considerable promise for cell replacement and gene therapies. Their remarkable properties of pluripotency, self-renewal, and tractability for genetic modification potentially allows for the production of sizeable quantities of therapeutic cells of the hematopoietic lineage. Dendritic cells (DC arise from CD34+ hematopoietic progenitor cells (HPCs and are important in many innate and adaptive immune functions. With respect to HIV-1 infection, DCs play an important role in the efficient capture and transfer of the virus to susceptible cells. With an aim of generating DCs from a renewable source for HIV-1 studies, here we evaluated the capacity of hES cell derived CD34+ cells to give rise to DCs which can support HIV-1 infection. Results Undifferentiated hES cells were cultured on S17 mouse bone marrow stromal cell layers to derive CD34+ HPCs which were subsequently grown in specific cytokine differentiation media to promote the development of DCs. The hES derived DCs (hES-DC were subjected to phenotypic and functional analyses and compared with DCs derived from fetal liver CD34+ HPC (FL-DC. The mature hES-DCs displayed typical DC morphology consisting of veiled stellate cells. The hES-DCs also displayed characteristic phenotypic surface markers CD1a, HLA-DR, B7.1, B7.2, and DC-SIGN. The hES-DCs were found to be capable of antigen uptake and stimulating naïve allogeneic CD4+ T cells in a mixed leukocyte reaction assay. Furthermore, the hES-DCs supported productive HIV-1 viral infection akin to standard DCs. Conclusion Phenotypically normal and functionally competent DCs that support HIV-1 infection can be derived from hES cells. hES-DCs can now be exploited in applied immunology and HIV-1 infection studies. Using gene therapy approaches, it is now possible to generate HIV-1 resistant DCs from anti-HIV gene transduced hES-CD34+ hematopoietic progenitor cells.

  3. The cerebral functional location in normal subjects during listening to a story in Chinese, English or Japanese

    International Nuclear Information System (INIS)

    Sun Da; Zhan Hongwei; Xu Wei; Liu Hongbiao; Bao Chengkan

    2004-01-01

    Objectives: To compare the cerebral functional location in normal subjects during listening to a story in Chinese (native language), English (learned language) or Japanese (unfamiliar language). Methods: 9, 14,7 normal young students were asked to listen an emotional story in Chinese, the deeds of life of Aiyinsitan in English, and a dialogue in unfamiliar Japanese on a tap for 20 minters respectively. They were also asked to pay special attention to the name of the personage, time and site during listening Chinese or English story. 99mTc-ECD was administered in the first 3 minutes during they listened the story. The brain imaging was performed in 30 60 minutes after the tracer was administered. The results were compared with their brain imaging at rest respectively. Results: During listened to the story in Chinese, learned English, and unfamiliar Japanese, the auditory association cortex in the dual superior temporal and some midtemporal were activated. The inferior frontal and/or medial frontal lobes were activated too, special during listening to familiar language, and asked to remember the plot of the story, such as Chinese and English. But to compare with listening English, the activity in right frontal lobe was higher than in left during listened to the Chinese. During listened to unfamiliar Japanese, the frontal lobes were activated widely too. Conclusions: The results of our study shows that besides the auditory association cortex in the superior temporal and midtemporal, language can activates, the left inferior frontal (Broca s area), and in right and left frontal eye field, midtemporal, and superior frontal lobes were activated by language too. These regions in frontal have a crucial role in the decoding of familiar spoken language. And the attempt to decode unfamiliar spoken languages activates more auditory association areas. The left hemisphere is dominance hemisphere for language. But in our study, right temporal and frontal lobes were activated more

  4. Diversity of Histologic Patterns and Expression of Cytoskeletal Proteins in Canine Skeletal Osteosarcoma.

    Science.gov (United States)

    Nagamine, E; Hirayama, K; Matsuda, K; Okamoto, M; Ohmachi, T; Kadosawa, T; Taniyama, H

    2015-09-01

    Osteosarcoma (OS), the most common bone tumor, includes OS of the head (OSH) and appendicular OS (OSA). In dogs, it is classified into 6 histologic subtypes: osteoblastic, chondroblastic, fibroblastic, telangiectatic, giant cell, and poorly differentiated. This study investigated the significance of the histologic classification relevant to clinical outcome and the histologic and immunohistochemical relationships between pleomorphism and expression of cytoskeletal proteins in 60 cases each of OSH and OSA. Most neoplasms exhibited histologic diversity, and 64% of OS contained multiple subtypes. In addition to the above 6 subtypes, myxoid, round cell, and epithelioid subtypes were observed. Although the epithelioid subtypes were observed in only OSH, no significant difference in the frequency of other subtypes was observed. Also, no significant relevance was observed between the clinical outcome and histologic subtypes. Cytokeratin (CK) was expressed in both epithelioid and sarcomatoid tumor cells in various subtypes, and all CK-positive tumor cells also expressed vimentin. Vimentin and α-smooth muscle actin (SMA) were expressed in all subtypes. A few SMA-positive spindle-shaped tumor cells exhibited desmin expression. Glial fibrillary acidic protein-positive tumor cells were observed in many subtypes, and some of these cells showed neurofilament expression. Although OSH exhibited significantly stronger immunoreactivity for SMA than OSA, no significant difference in other cytoskeletal proteins was observed. Some tumor cells had cytoskeletal protein expression compatible with the corresponding histologic subtypes, such as CK in the epithelioid subtype and SMA in the fibroblastic subtype. Thus, canine skeletal OS is composed of pleomorphic and heterogenous tumor cells as is reflected in the diversity of histologic patterns and expression of cytoskeletal proteins. © The Author(s) 2015.

  5. The cytoskeletal binding domain of band 3 is required for multiprotein complex formation and retention during erythropoiesis

    Science.gov (United States)

    Satchwell, Timothy J; Hawley, Bethan R; Bell, Amanda J; Ribeiro, M. Leticia; Toye, Ashley M

    2015-01-01

    Band 3 is the most abundant protein in the erythrocyte membrane and forms the core of a major multiprotein complex. The absence of band 3 in human erythrocytes has only been reported once, in the homozygous band 3 Coimbra patient. We used in vitro culture of erythroblasts derived from this patient, and separately short hairpin RNA-mediated depletion of band 3, to investigate the development of a band 3-deficient erythrocyte membrane and to specifically assess the stability and retention of band 3 dependent proteins in the absence of this core protein during terminal erythroid differentiation. Further, using lentiviral transduction of N-terminally green fluorescent protein-tagged band 3, we demonstrated the ability to restore expression of band 3 to normal levels and to rescue secondary deficiencies of key proteins including glycophorin A, protein 4.2, CD47 and Rh proteins arising from the absence of band 3 in this patient. By transducing band 3-deficient erythroblasts from this patient with band 3 mutants with absent or impaired ability to associate with the cytoskeleton we also demonstrated the importance of cytoskeletal connectivity for retention both of band 3 and of its associated dependent proteins within the reticulocyte membrane during the process of erythroblast enucleation. PMID:25344524

  6. Vacuolar and cytoskeletal dynamics during elicitor-induced programmed cell death in tobacco BY-2 cells.

    Science.gov (United States)

    Higaki, Takumi; Kadota, Yasuhiro; Goh, Tatsuaki; Hayashi, Teruyuki; Kutsuna, Natsumaro; Sano, Toshio; Hasezawa, Seiichiro; Kuchitsu, Kazuyuki

    2008-09-01

    Responses of plant cells to environmental stresses often involve morphological changes, differentiation and redistribution of various organelles and cytoskeletal network. Tobacco BY-2 cells provide excellent model system for in vivo imaging of these intracellular events. Treatment of the cell cycle-synchronized BY-2 cells with a proteinaceous oomycete elicitor, cryptogein, induces highly synchronous programmed cell death (PCD) and provide a model system to characterize vacuolar and cytoskeletal dynamics during the PCD. Sequential observation revealed dynamic reorganization of the vacuole and actin microfilaments during the execution of the PCD. We further characterized the effects cryptogein on mitotic microtubule organization in cell cycle-synchronized cells. Cryptogein treatment at S phase inhibited formation of the preprophase band, a cortical microtubule band that predicts the cell division site. Cortical microtubules kept their random orientation till their disruption that gradually occurred during the execution of the PCD twelve hours after the cryptogein treatment. Possible molecular mechanisms and physiological roles of the dynamic behavior of the organelles and cytoskeletal network in the pathogenic signal-induced PCD are discussed.

  7. Acute fluoride poisoning alters myocardial cytoskeletal and AMPK signaling proteins in rats.

    Science.gov (United States)

    Panneerselvam, Lakshmikanthan; Raghunath, Azhwar; Perumal, Ekambaram

    2017-02-15

    Our previous findings revealed that increased oxidative stress, apoptosis and necrosis were implicated in acute fluoride (F - ) induced cardiac dysfunction apart from hypocalcemia and hyperkalemia. Cardiac intermediate filaments (desmin and vimentin) and cytoskeleton linker molecule vinculin plays an imperative role in maintaining the architecture of cardiac cytoskeleton. In addition, AMPK is a stress activated kinase that regulates the energy homeostasis during stressed state. The present study was aimed to examine the role of cytoskeletal proteins and AMPK signaling molecules in acute F - induced cardiotoxicity in rats. In order to study this, male Wistar rats were treated with single oral doses of 45 and 90mg/kgF - for 24h. Acute F - intoxicated rats showed declined cytoskeletal protein expression of desmin, vimentin and vinculin in a dose dependent manner compared to control. A significant increase in phosphorylation of AMPKα (Thr172), AMPKß1 (Ser108) and Acetyl-coA carboxylase (ACC) (Ser79) in the myocardium and associated ATP deprivation were found in acute F - intoxicated rats. Further, ultra-structural studies confirmed myofibril lysis with interruption of Z lines, dilated sarcoplasmic reticulum and damaged mitochondrion were observed in both the groups of F - intoxicated rats. Taken together, these findings reveal that acute F - exposure causes sudden heart failure by altering the expression of cytoskeletal proteins and AMPK signaling molecules. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Differential Modulation of Transcription Factors and Cytoskeletal Proteins in Prostate Carcinoma Cells by a Bacterial Lactone

    Directory of Open Access Journals (Sweden)

    Senthil R. Kumar

    2018-01-01

    Full Text Available The present study tested the effect of a bacterial lactone N-(3-oxododecanoyl-homoserine lactone (C12-HSL on the cytoskeletal and transcriptional genes and proteins in prostate adenocarcinoma (PA cells (DU145 and LNCaP and prostate small cell neuroendocrine carcinoma (SCNC PC3 cells including their cellular viability and apoptosis. Our data indicate that cell migration and colony formation were affected in the presence of C12-HSL. C12-HSL induced apoptosis and altered viability of both PA and SCNC cells in a concentration dependent manner as measured by fluorescence and chemiluminescence assays. Compared to PCa cells, noncancerous prostate epithelial cells (RWPE1 were resistant to modification by C12-HSL. Further, the viability of PC3 cells in 3D matrix was suppressed by C12-HSL treatment as detected using calcein AM fluorescence in situ. C12-HSL treatment induced cytoskeletal associated protein expression of vinculin and RhoC, which may have implications in cancer cell motility, adhesion, and metastasis. IQGAP protein expression was reduced in DU145 and RWPE1 cells in the presence of C12-HSL. C12-HSL decreased STAT3 phosphorylation in DU145 cells but increased STAT1 protein phosphorylation in PC3 and LNCaP cells. Overall, these studies indicate that C12-HSL can trigger changes in transcription factors and cytoskeletal proteins and thereby modulate growth and migration properties of PCa cells.

  9. Cytoskeletal Configuration Modulates Mechanically Induced Changes in Mesenchymal Stem Cell Osteogenesis, Morphology, and Stiffness

    Science.gov (United States)

    Pongkitwitoon, Suphannee; Uzer, Gunes; Rubin, Janet; Judex, Stefan

    2016-10-01

    Mesenchymal stem cells (MSC) responding to mechanical cues generated by physical activity is critical for skeletal development and remodeling. Here, we utilized low intensity vibrations (LIV) as a physiologically relevant mechanical signal and hypothesized that the confined cytoskeletal configuration imposed by 2D culture will enable human bone marrow MSCs (hBMSC) to respond more robustly when LIV is applied in-plane (horizontal-LIV) rather than out-of-plane (vertical-LIV). All LIV signals enhanced hBMSC proliferation, osteogenic differentiation, and upregulated genes associated with cytoskeletal structure. The cellular response was more pronounced at higher frequencies (100 Hz vs 30 Hz) and when applied in the horizontal plane. Horizontal but not vertical LIV realigned the cell cytoskeleton, culminating in increased cell stiffness. Our results show that applying very small oscillatory motions within the primary cell attachment plane, rather than perpendicular to it, amplifies the cell’s response to LIV, ostensibly facilitating a more effective transfer of intracellular forces. Transcriptional and structural changes in particular with horizontal LIV, together with the strong frequency dependency of the signal, emphasize the importance of intracellular cytoskeletal configuration in sensing and responding to high-frequency mechanical signals at low intensities.

  10. The influence of social activity on regional cerebral blood flow and mental function in the normal aged volunteers

    International Nuclear Information System (INIS)

    Kobayashi, Shotai; Yamaguchi, Shuhei; Katsube, Tomoko; Kitani, Kohaku; Okada, Masanori

    1983-01-01

    The infuence of social activity on regional cerebral blood flow (rCBF) and mental function was studied by Xe133 inhalation method in normal aged volunteers. Subjects: The first group consisted of 33 aged volunteers living in nursing home and exposed to little social stimuli. There were 15 males (mean age of 77 years) and 18 females (77 years). The second group consisted of 49 aged community volunteers who were confirmed socially active. There were 25 males (76 years) and 24 females (72 years). All subjects were healthy persons without a past hitory of cerebral diseases and lung diseases. There were no difference in blood pressure and hematocrit between the two groups. Method: The rCBF was measured by 16-ch-Novo-cerebrograph. Verbal intelligence was evaluated by the Hasegawa Simple Intelligence Scale for Aged. Performance intelligence was evaluated with the Kohs' Block Design Test. Results: 1) The mean rCBF in group I showed significantly lower value than that of group II, especially in the frontotemporal region. The performance intelligence was decreased in group I. However, there were no significant difference in the verbal intelligence between the two groups. 2) The aging effect on rCBF and intelligences was more prominent in group II. 3) In males, hemispheric rCBF of group I decreased bilaterally associated with the decrease of both intelligences. While the left hemispheric rCBF in females was relatively preserved as well as the preservation of verbal intelligence. These results indicate that the social environmental factors may have significant influence to aging of the brain especially in the males. (author)

  11. Oral administration of soybean peptide Vglycin normalizes fasting glucose and restores impaired pancreatic function in Type 2 diabetic Wistar rats.

    Science.gov (United States)

    Jiang, Hua; Feng, Jueping; Du, Zhongxia; Zhen, Hui; Lin, Mei; Jia, Shaohui; Li, Tao; Huang, Xinyuan; Ostenson, Claes-Goran; Chen, Zhengwang

    2014-09-01

    Vglycin, a natural 37-residue polypeptide isolated from pea seeds in which six half-cysteine residues are embedded in three pairs of disulfide bonds, is resistant to digestive enzymes and has antidiabetic potential. To investigate the pharmacological activity of Vglycin in vivo and to examine the mechanisms involved, the therapeutic effect of Vglycin in diabetic rats was examined. Diabetes was induced in Wistar rats by high-fat diet and multiple streptozotocin intraperitoneal injections. Diabetic rats were treated daily with Vglycin for 4 weeks. Body weight, food intake, fasting plasma glucose and insulin levels were assayed weekly. Glucose and insulin tolerance tests were conducted on Day 29. Subsequently, levels of p-Akt in the liver and pancreas and cleaved PARP, Pdx-1 and insulin in the pancreas were detected by immunoblotting. The morphology of the pancreas and the insulin expression in the pancreas were analyzed by hematoxylin-eosin staining and immunohistochemistry, respectively. Furthermore, human liver-derived cell lines were used to explore the in vitro effects of Vglycin on insulin sensitivity and glucose uptake. Chronic treatment with Vglycin normalized fasting glucose levels in diabetic rats. The improvement in glucose homeostasis and the increased insulin sensitivity mediated by restored insulin signaling likely contributed to decreased food intake and reduced body weight. Vglycin protected pancreatic cells from damage by streptozotocin. Although insulin synthesis and secretion in impaired β-cell were not significantly elevated, islets morphology was improved in the Vglycin-treated groups. These results suggest that Vglycin could be useful in Type 2 diabetes for restoring impaired insulin signaling, glucose tolerance and pancreatic function. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Novel approach to select genes from RMA normalized microarray data using functional hearing tests in aging mice

    Science.gov (United States)

    D'Souza, Mary; Zhu, Xiaoxia; Frisina, Robert D.

    2008-01-01

    Presbycusis – age-related hearing loss – is the number one communicative disorder and one of the top three chronic medical condition of our aged population. High-throughput technologies potentially can be used to identify differentially expressed genes that may be better diagnostic and therapeutic targets for sensory and neural disorders. Here we analyzed gene expression for a set of GABA receptors in the cochlea of aging CBA mice using the Affymetrix GeneChip MOE430A. Functional phenotypic hearing measures were made, including auditory brainstem response (ABR) thresholds and distortion-product otoacoustic emission (DPOAE) amplitudes (four age groups). Four specific criteria were used to assess gene expression changes from RMA normalized microarray data (40 replicates). Linear regression models were used to fit the neurophysiological hearing measurements to probe-set expression profiles. These data were first subjected to one-way ANOVA, and then linear regression was performed. In addition, the log signal ratio was converted to fold change, and selected gene expression changes were confirmed by relative real-time PCR. Major findings: expression of GABA-A receptor subunit α6 was upregulated with age and hearing loss, whereas subunit α1 was repressed. In addition, GABA-A receptor associated protein like-1 and GABA-A receptor associated protein like-2 were strongly downregulated with age and hearing impairment. Lastly, gene expression measures were correlated with pathway/network relationships relevant to the inner ear using Pathway Architect, to identify key pathways consistent with the gene expression changes observed. PMID:18455804

  13. Changes in the functional characteristics of tumor and normal cells after treatment with extracts of white dead-nettle.

    Science.gov (United States)

    Veleva, Ralitsa; Petkova, Bela; Moskova-Doumanova, Veselina; Doumanov, Jordan; Dimitrova, Milena; Koleva, Petya; Mladenova, Kirilka; Petrova, Svetla; Yordanova, Zhenya; Kapchina-Toteva, Veneta; Topouzova-Hristova, Tanya

    2015-01-02

    Lamium album L. is a perennial herb widely used in folk medicine. It possesses a wide spectrum of therapeutic activities (anti-inflammatory, astringent, antiseptic, antibiotic, antispasmodic, antioxidant and anti-proliferative). Preservation of medicinal plant could be done by in vitro propagation to avoid depletion from their natural habitat. It is important to know whether extracts from L. album plants grown in vitro possess similar properties as extracts from plants grown in vivo . For these reasons, it is important to examine changes in the composition of secondary metabolites during in vitro cultivation of the plant and how they affect the biological activity. We used A549 human cancer cell line and normal kidney epithelial cells MDCKII (Madin-Darby canine kidney cells II) as controls in assessing the anti-cancer effect of plant extracts. To elucidate changes in some key functional characteristics, adhesion test, MTT (3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyl tetrazolium bromide), transepithelial resistance (TER), immunofluorescence staining and trypan blue exclusion test were performed. Methanol and chloroform extracts of in vivo and in vitro propagated plants affected differently cancerous and non-cancerous cells. The most pronounced differences were observed in the morphological analysis and in the cell adhesive properties. We also detected suppressed epithelial transmembrane electrical resistance of MDCK II cells, by treatment with plant extracts, compared to non-treated MDCK II cells. A549 cells did not polarize under the same conditions. Altered organization of actin filaments in both cell types were noticed suggesting that extracts from L. album L. change TER and actin filaments, and somehow may block cell mechanisms, leading to the polarization of MDCK II cells.

  14. Study on the insulin resistance and β-cell function in individuals with normal and those with abnormal glucose metabolism

    International Nuclear Information System (INIS)

    Wei Zikun

    2006-01-01

    Objective: To study the insulin resistance and β-cell function in individuals with normal glucose tolerance (NGT) and those with glucose metabolism dysfunction. Methods: Insulin resistance and β-cell function were studied with oral glucose tolerance test and the following parameters: 2h insulin/2h plasma glucose (2hIns/2hPG), insulin resistance index (IRI), insulin sensitivity index (ISI) and 30 min net increment of insulin/30min net increment of glucose (AI 30 /AG 30 ) were examined in 44 individuals with NGT, 45 subjects with impaired glucose tolerance (IGT), 66 recently diagnosed diabetics and 175 well-established diabetics. Results: The insulin resistance index (IRI) increased progressively from that in NGT individuals to that in recently diabetics (20 ± 1. 5→3.1 ± 1.6→4.1 ± 1.8), while the 2hIns/2hPG, ΔI 30 /ΔG 30 and ISI decreased progressively with significant differences between those in successive groups (P 30 /ΔG 30 and ISI kept decreasing (values in patients with disease history less than 3 yrs vs those in patients with disease over 3yrs: 2.9 ± 3.2 vs 2.4 + 2.3, 30.2 + 1.1 vs 23.4 ± 2.3, P 30 /ΔG 30 were significantly correlated with ISI (F =96.3, 58.4 and 47.5 respectively). For principal component analysis display, the cumulative contribution rate of four parameters (2hIns/2hPG, ISI, ΔI 30 /ΔG 30 and 2h C-peptide) exceeded 85% (86.5%). Conclusion: As the dysfunction of glucose metabolism proceeded from IGT to well established diabetes, the IR increased first with decrease of β-cell secretion followed. The parameters 2hIns/2hPG, ISI, 2h C-peptide ΔI 30 /ΔG 30 were especially useful for the investigation . (authors)

  15. Cytoskeletal Regulation by AUTS2 in Neuronal Migration and Neuritogenesis

    Directory of Open Access Journals (Sweden)

    Kei Hori

    2014-12-01

    Full Text Available Mutations in the Autism susceptibility candidate 2 gene (AUTS2, whose protein is believed to act in neuronal cell nuclei, have been associated with multiple psychiatric illnesses, including autism spectrum disorders, intellectual disability, and schizophrenia. Here we show that cytoplasmic AUTS2 is involved in the regulation of the cytoskeleton and neural development. Immunohistochemistry and fractionation studies show that AUTS2 localizes not only in nuclei, but also in the cytoplasm, including in the growth cones in the developing brain. AUTS2 activates Rac1 to induce lamellipodia but downregulates Cdc42 to suppress filopodia. Our loss-of-function and rescue experiments show that a cytoplasmic AUTS2-Rac1 pathway is involved in cortical neuronal migration and neuritogenesis in the developing brain. These findings suggest that cytoplasmic AUTS2 acts as a regulator of Rho family GTPases to contribute to brain development and give insight into the pathology of human psychiatric disorders with AUTS2 mutations.

  16. Combination of exercise training and diet restriction normalizes limited exercise capacity and impaired skeletal muscle function in diet-induced diabetic mice.

    Science.gov (United States)

    Suga, Tadashi; Kinugawa, Shintaro; Takada, Shingo; Kadoguchi, Tomoyasu; Fukushima, Arata; Homma, Tsuneaki; Masaki, Yoshihiro; Furihata, Takaaki; Takahashi, Masashige; Sobirin, Mochamad A; Ono, Taisuke; Hirabayashi, Kagami; Yokota, Takashi; Tanaka, Shinya; Okita, Koichi; Tsutsui, Hiroyuki

    2014-01-01

    Exercise training (EX) and diet restriction (DR) are essential for effective management of obesity and insulin resistance in diabetes mellitus. However, whether these interventions ameliorate the limited exercise capacity and impaired skeletal muscle function in diabetes patients remains unexplored. Therefore, we investigated the effects of EX and/or DR on exercise capacity and skeletal muscle function in diet-induced diabetic mice. Male C57BL/6J mice that were fed a high-fat diet (HFD) for 8 weeks were randomly assigned for an additional 4 weeks to 4 groups: control, EX, DR, and EX+DR. A lean group fed with a normal diet was also studied. Obesity and insulin resistance induced by a HFD were significantly but partially improved by EX or DR and completely reversed by EX+DR. Although exercise capacity decreased significantly with HFD compared with normal diet, it partially improved with EX and DR and completely reversed with EX+DR. In parallel, the impaired mitochondrial function and enhanced oxidative stress in the skeletal muscle caused by the HFD were normalized only by EX+DR. Although obesity and insulin resistance were completely reversed by DR with an insulin-sensitizing drug or a long-term intervention, the exercise capacity and skeletal muscle function could not be normalized. Therefore, improvement in impaired skeletal muscle function, rather than obesity and insulin resistance, may be an important therapeutic target for normalization of the limited exercise capacity in diabetes. In conclusion, a comprehensive lifestyle therapy of exercise and diet normalizes the limited exercise capacity and impaired muscle function in diabetes mellitus.

  17. Liver transplantation nearly normalizes brain spontaneous activity and cognitive function at 1 month: a resting-state functional MRI study.

    Science.gov (United States)

    Cheng, Yue; Huang, Lixiang; Zhang, Xiaodong; Zhong, Jianhui; Ji, Qian; Xie, Shuangshuang; Chen, Lihua; Zuo, Panli; Zhang, Long Jiang; Shen, Wen

    2015-08-01

    To investigate the short-term brain activity changes in cirrhotic patients with Liver transplantation (LT) using resting-state functional MRI (fMRI) with regional homogeneity (ReHo) method. Twenty-six cirrhotic patients as transplant candidates and 26 healthy controls were included in this study. The assessment was repeated for a sub-group of 12 patients 1 month after LT. ReHo values were calculated to evaluate spontaneous brain activity and whole brain voxel-wise analysis was carried to detect differences between groups. Correlation analyses were performed to explore the relationship between the change of ReHo with the change of clinical indexes pre- and post-LT. Compared to pre-LT, ReHo values increased in the bilateral inferior frontal gyrus (IFG), right inferior parietal lobule (IPL), right supplementary motor area (SMA), right STG and left middle frontal gyrus (MFG) in patients post-LT. Compared to controls, ReHo values of post-LT patients decreased in the right precuneus, right SMA and increased in bilateral temporal pole, left caudate, left MFG, and right STG. The changes of ReHo in the right SMA, STG and IFG were correlated with change of digit symbol test (DST) scores (P brain activity of most brain regions with decreased ReHo in pre-LT was substantially improved and nearly normalized, while spontaneous brain activity of some brain regions with increased ReHo in pre-LT continuously increased. ReHo may provide information on the neural mechanisms of LT' effects on brain function.

  18. Arrhythmogenic Right Ventricular Cardiomyopathy in an Endurance Athlete Presenting with Ventricular Tachycardia and Normal Right Ventricular Function.

    Science.gov (United States)

    Hedley, Jeffrey S; Al Mheid, Ibhar; Alikhani, Zoubin; Pernetz, Maria A; Kim, Jonathan H

    2017-08-01

    Arrhythmogenic right ventricular cardiomyopathy, a genetically inherited disease that results in fibrofatty replacement of normal cardiac myocytes, has been associated with sudden cardiac death in athletes. Long-term participation in endurance exercise hastens the development of both the arrhythmic and structural arrhythmogenic right ventricular cardiomyopathy phenotypes. We describe the unusual case of a 34-year-old, symptomatic, female endurance athlete who had arrhythmogenic right ventricular cardiomyopathy in the presence of a structurally normal right ventricle. Clinicians should be aware of this infrequent presentation when evaluating athletic patients who have ventricular arrhythmias and normal findings on cardiac imaging studies.

  19. The cerebral functional location in normal subjects when they listened to a story in English as a second language

    International Nuclear Information System (INIS)

    Sun Da; Zhan Hongwei; Xu Wei; Liu Hongbiao; He Guangqiang

    2004-01-01

    Purpose: To detect the cerebral functional location when normal subjects listened to a story in English as a second language. Methods: 14 normal young students of the medical collage of Zhejiang University, 22-24 years old, 8 male and 6 female. The first they underwent a 99mTc-ECD brain imaging at rest using a dual-head gamma camera with fan beam collimators. After 2-4 days they were asked to listen a story in English as a second language on a tap for 20 minters. The content of the story is about the deeds of life of a well-known physicist, Aiyinsitan. They were also asked to pay special attention to the name of the personage in the story, what time and place did the story stated. 99mTc-ECD was administered in the first 3 minutes during they listened the story. The brain imaging was performed in 30-60 minutes after the tracer was administered. Their hearing was fell into bad, middle, and good according to the restate content. Results: To compare the rest state, during listen to the story in Chinese and asked to remember the content of story the superior temporal were activated in all 14 subjects, among them, dual in 4 cases, right in 5 cases, and left in 5 cases. The midtemporal (right in 5 cases), inferior temporal (right in 2 cases and left in 3 cases), and pre-temporal (in 1 case) were activated too. The auditory associated areas in frontal lobes were activated in different level, among them left post-inferior frontal (Broca's area) in 8 cases, right post-inferior frontal (Broca's area) in 3 cases, superior frontal in 6 cases (dual in 3 and right in 3), pre-inferior frontal and/or medial frontal lobes in 9 cases (dual in 6 and right in 3). Other regions that were activated included the parietal lobes (right in 4 and left in 1), the occipital lobes (dual in 4,right in 2 and left in 4)and pre-cingulated gyms (in 1 case). According to the hearing in sequence (bad, middle and good), the activated rate of the occipital lobes is decreasing (100%,75% and 57

  20. Expression and function of the protein tyrosine phosphatase receptor J (PTPRJ in normal mammary epithelial cells and breast tumors.

    Directory of Open Access Journals (Sweden)

    Chanel E Smart

    Full Text Available The protein tyrosine phosphatase receptor J, PTPRJ, is a tumor suppressor gene that has been implicated in a range of cancers, including breast cancer, yet little is known about its role in normal breast physiology or in mammary gland tumorigenesis. In this paper we show that PTPRJ mRNA is expressed in normal breast tissue and reduced in corresponding tumors. Meta-analysis revealed that the gene encoding PTPRJ is frequently lost in breast tumors and that low expression of the transcript associated with poorer overall survival at 20 years. Immunohistochemistry of PTPRJ protein in normal human breast tissue revealed a distinctive apical localisation in the luminal cells of alveoli and ducts. Qualitative analysis of a cohort of invasive ductal carcinomas revealed retention of normal apical PTPRJ localization where tubule formation was maintained but that tumors mostly exhibited diffuse cytoplasmic staining, indicating that dysregulation of localisation associated with loss of tissue architecture in tumorigenesis. The murine ortholog, Ptprj, exhibited a similar localisation in normal mammary gland, and was differentially regulated throughout lactational development, and in an in vitro model of mammary epithelial differentiation. Furthermore, ectopic expression of human PTPRJ in HC11 murine mammary epithelial cells inhibited dome formation. These data indicate that PTPRJ may regulate differentiation of normal mammary epithelia and that dysregulation of protein localisation may be associated with tumorigenesis.

  1. Microvillar ion channels: cytoskeletal modulation of ion fluxes.

    Science.gov (United States)

    Lange, K

    2000-10-21

    movement of the system (electro-mechanical coupling). Because ionic transmission through linear polyelectrolytes is very slow compared with electronic conduction, only low-frequency electromagnetic fields can interact with the condensed counterion systems of linear polyelectrolytes. The delineated characteristics of microvillar ion conduction are strongly supported by the phenomenon of electro-mechanical coupling (reverse transduction) in microvilli of the audioreceptor (hair) cells and the recently reported dynamics of Ca(2+)signaling in microvilli of audio- and photoreceptor cells. Due to the cell-specific expression of different types and combinations of ion channels and transporters in the microvillar tip membrane of differentiated cells, the functional properties of this cell surface organelle are highly variable serving a multitude of different cellular functions including receptor-mediated effects such as Ca(2+)signaling, regulation of glucose and amino acid transport, as well as modulation of membrane potential. Even mechanical channel activation involved in cell volume regulation can be deduced from the systematic properties of the microvillar channel concept. In addition, the specific ion conduction properties of microfilaments combined with their proposed role in Ca(2+)signaling make microvilli the most likely cellular site for the interaction with external electric and magnetic fields. Copyright 2000 Academic Press.

  2. Hepatic and renal extraction of circulating type I procollagen aminopropeptide in patients with normal liver function and in patients with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Schytte, S; Hansen, M; Møller, S

    1999-01-01

    40-65, palcoholic cirrhosis. Size-chromatography revealed no significant change in the ratio of the high and low molecular forms of PINP following extraction in liver and kidney......The circulating level and splanchnic and renal extraction of serum type I procollagen aminoterminal propeptide (PINP) was studied in 20 patients with normal liver function and in 15 patients with alcoholic liver cirrhosis. In patients with alcoholic cirrhosis, the concentration of PINP....... It is concluded that circulating PINP is extracted in the normal liver and kidney, and that the serum concentration of PINP is significantly higher in patients with alcoholic cirrhosis than in patients with normal liver function. Both the hepatic and the renal clearance of PINP are seriously impaired...

  3. Assessing joint space and condylar position in the people with normal function of temporomandibular joint with cone-beam computed tomography

    Directory of Open Access Journals (Sweden)

    Zahra Dalili

    2012-01-01

    Conclusion: The assessment of joint spaces in right and left sides should be done independently. Overall, the measured joint spaces except Sjs are not different in two sexes. The data from this study could be a useful and comparable reference for the clinical assessment of condylar position in patients with normal functional joints.

  4. Low normal thyroid function attenuates serum alanine aminotransferase elevations in the context of metabolic syndrome and insulin resistance in white people

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; van den Berg, Eline H.; van der Klauw, Melanie; Blokzijl, Hans

    Objectives: Thyroid hormones play a key role in hepatic lipid metabolism. Although hypothyroidismis associated with increased prevalence of non-alcoholic fatty liver disease (NAFLD), the relationship of NAFLD with low normal thyroid function is unclear. We tested the association of serum alanine

  5. Quasiparticle Green's function theory of the Josephson effect in chiral p-wave superconductor/diffusive normal metal/chiral p-wave superconductor junctions

    NARCIS (Netherlands)

    Sawa, Y.; Yokoyama, T.; Tanaka, Y.; Golubov, Alexandre Avraamovitch

    2007-01-01

    We study the Josephson effect in chiral p-wave superconductor/diffusive normal metal (DN)/chiral p-wave superconductor (CP/DN/CP) junctions using quasiclassical Green's function formalism with proper boundary conditions. The px+ipy-wave symmetry of superconducting order parameter is chosen which is

  6. Age and gender specific normal values of left ventricular mass, volume and function for gradient echo magnetic resonance imaging: a cross sectional study

    Directory of Open Access Journals (Sweden)

    Allansdotter-Johnsson Ase

    2009-01-01

    Full Text Available Abstract Background Knowledge about age-specific normal values for left ventricular mass (LVM, end-diastolic volume (EDV, end-systolic volume (ESV, stroke volume (SV and ejection fraction (EF by cardiac magnetic resonance imaging (CMR is of importance to differentiate between health and disease and to assess the severity of disease. The aims of the study were to determine age and gender specific normal reference values and to explore the normal physiological variation of these parameters from adolescence to late adulthood, in a cross sectional study. Methods Gradient echo CMR was performed at 1.5 T in 96 healthy volunteers (11–81 years, 50 male. Gender-specific analysis of parameters was undertaken in both absolute values and adjusted for body surface area (BSA. Results Age and gender specific normal ranges for LV volumes, mass and function are presented from the second through the eighth decade of life. LVM, ESV and EDV rose during adolescence and declined in adulthood. SV and EF decreased with age. Compared to adult females, adult males had higher BSA-adjusted values of EDV (p = 0.006 and ESV (p Conclusion LV volumes, mass and function vary over a broad age range in healthy individuals. LV volumes and mass both rise in adolescence and decline with age. EF showed a rapid decline in adolescence compared to changes throughout adulthood. These findings demonstrate the need for age and gender specific normal ranges for clinical use.

  7. A comparative study of functional properties of normal and wooden breast broiler chicken meat with NaCl addition.

    Science.gov (United States)

    Xing, Tong; Zhao, Xue; Han, Minyi; Cai, Linlin; Deng, Shaolin; Zhou, Guanghong; Xu, Xinglian

    2017-09-01

    The selection of broilers for augmented growth rate and breast has brought about wooden-breast (WB) muscle abnormalities, which caused substantial economic losses. The objective of this study was to compare water holding capacity, water mobility and distribution, salt-soluble protein (SSP) content, and protein profiles of normal and WB chicken meat with different additions of NaCl. Thirty WB and 30 normal chicken breasts were selected from a deboning line of a major Chinese processing plant at 2 to 3 h post mortem. Two different meat batters were formulated to 150 mg/g meat protein and different NaCl contents (0%, 1%, 2%, 3%, and 4%). Results indicated that as NaCl contents increased, the cooking loss of meat batters decreased (P meat showed different protein profiles, with myosin heavy chain exhibiting a higher intensity at ≥3% salt level. Low-field nuclear magnetic resonance (LF-NMR)revealed an increased T22 and higher P22 in raw WB meat compared to normal meat (P meat batters, WB meat batters had reduced T21 and lower immobilized water proportions at low NaCl contents (meat gels. Meat gels prepared from WB had a lower proportion of water within the myofibrillar protein matrix and a greater proportion of exuded bulk water at NaCl contents meat, meat batters and gels, water distribution and mobility of WB exhibited significant differences compared to normal meat. The addition of NaCl affected water mobility and distributions in meat batters, with a level of 3% NaCl eliminating the differences between processed normal and WB meat products. © 2017 Poultry Science Association Inc.

  8. Cytoskeletal dynamics in interphase, mitosis and cytokinesis analysed through Agrobacterium-mediated transient transformation of tobacco BY-2 cells.

    Science.gov (United States)

    Buschmann, H; Green, P; Sambade, A; Doonan, J H; Lloyd, C W

    2011-04-01

    Transient transformation with Agrobacterium is a widespread tool allowing rapid expression analyses in plants. However, the available methods generate expression in interphase and do not allow the routine analysis of dividing cells. Here, we present a transient transformation method (termed 'TAMBY2') to enable cell biological studies in interphase and cell division. Agrobacterium-mediated transient gene expression in tobacco BY-2 was analysed by Western blotting and quantitative fluorescence microscopy. Time-lapse microscopy of cytoskeletal markers was employed to monitor cell division. Double-labelling in interphase and mitosis enabled localization studies. We found that the transient transformation efficiency was highest when BY-2/Agrobacterium co-cultivation was performed on solid medium. Transformants produced in this way divided at high frequency. We demonstrated the utility of the method by defining the behaviour of a previously uncharacterized microtubule motor, KinG, throughout the cell cycle. Our analyses demonstrated that TAMBY2 provides a flexible tool for the transient transformation of BY-2 with Agrobacterium. Fluorescence double-labelling showed that KinG localizes to microtubules and to F-actin. In interphase, KinG accumulates on microtubule lagging ends, suggesting a minus-end-directed function in vivo. Time-lapse studies of cell division showed that GFP-KinG strongly labels preprophase band and phragmoplast, but not the metaphase spindle. © 2010 The Authors. New Phytologist © 2010 New Phytologist Trust.

  9. Beta-actin deficiency with oxidative posttranslational modifications in Rett syndrome erythrocytes: insights into an altered cytoskeletal organization.

    Directory of Open Access Journals (Sweden)

    Alessio Cortelazzo

    Full Text Available Beta-actin, a critical player in cellular functions ranging from cell motility and the maintenance of cell shape to transcription regulation, was evaluated in the erythrocyte membranes from patients with typical Rett syndrome (RTT and methyl CpG binding protein 2 (MECP2 gene mutations. RTT, affecting almost exclusively females with an average frequency of 1∶10,000 female live births, is considered the second commonest cause of severe cognitive impairment in the female gender. Evaluation of beta-actin was carried out in a comparative cohort study on red blood cells (RBCs, drawn from healthy control subjects and RTT patients using mass spectrometry-based quantitative analysis. We observed a decreased expression of the beta-actin isoforms (relative fold changes for spots 1, 2 and 3: -1.82±0.15, -2.15±0.06, and -2.59±0.48, respectively in pathological RBCs. The results were validated by western blotting and immunofluorescence microscopy. In addition, beta-actin from RTT patients also showed a dramatic increase in oxidative posttranslational modifications (PTMs as the result of its binding with the lipid peroxidation product 4-hydroxy-2-nonenal (4-HNE. Our findings demonstrate, for the first time, a beta-actin down-regulation and oxidative PTMs for RBCs of RTT patients, thus indicating an altered cytoskeletal organization.

  10. Cytoskeletal dynamics

    DEFF Research Database (Denmark)

    Bendix, Pól Martin

    2015-01-01

    I worked with reconstitutted contractile acto-myosin systems containing mainly actin, actin cross-linkers and myosin motors. Contractility and rheology of such systems was studied using confocal microscopy and rheology.......I worked with reconstitutted contractile acto-myosin systems containing mainly actin, actin cross-linkers and myosin motors. Contractility and rheology of such systems was studied using confocal microscopy and rheology....

  11. Comparison of Visual Function in Older Eyes in the Earliest Stages of Age-related Macular Degeneration to Those in Normal Macular Health.

    Science.gov (United States)

    Owsley, Cynthia; Huisingh, Carrie; Clark, Mark E; Jackson, Gregory R; McGwin, Gerald

    2016-01-01

    To compare the ability of several visual functional tests in terms of the strength of their associations with the earliest phases of age-related macular degeneration (AMD), which bears on their potential to serve as functional endpoints in evaluating treatments for early AMD and prevention strategies. Eyes from adults ≥60 years old were identified as being in normal macular health or in the earliest stages of AMD (steps 2, 3 or 4) through grading of color stereo-fundus photos by an experienced grader masked to all other study variables who used the 9-step Age-Related Eye Disease Study (AREDS) classification system for AMD severity. Visual function was assessed using the following tests: best-corrected visual acuity, low luminance visual acuity, spatial contrast sensitivity, macular cone-mediated light sensitivity and rod-mediated dark adaptation. A total of 1260 eyes were tested from 640 participants; 1007 eyes were in normal macular health (defined as step 1 in AREDS system) and 253 eyes had early AMD (defined as steps 2, 3 or 4). Adjusting for age and gender, early AMD eyes had two times the odds of having delayed rod-mediated dark adaptation than eyes in normal macular health (p = 0.0019). Visual acuity, low luminance acuity, spatial contrast sensitivity and macular light sensitivity did not differ between normal eyes and early AMD eyes. Eyes in the earliest phases of AMD were two times more likely to have delayed rod-mediated dark adaptation, as assessed by the rod-intercept, as compared to older eyes in normal macular health, whereas there was no difference in early AMD versus normal eyes in tests of visual acuity, low luminance acuity, macular light sensitivity and spatial contrast sensitivity.

  12. Induction of Plant Curvature by Magnetophoresis and Cytoskeletal Changes during Root Graviresponse

    Science.gov (United States)

    Hasenstein, Karl H.; Kuznetsov, Oleg A.; Blancaflor, Eilson B.

    1996-01-01

    High gradient magnetic fields (HGMF) induce curvature in roots and shoots. It is considered that this response is likely to be based on the intracellular displacement of bulk starch (amyloplasts) by the ponderomotive force generated by the HGMF. This process is called magnetophoresis. The differential elongation during the curvature along the concave and convex flanks of growing organs may be linked to the microtubular and/or microfilament cytoskeleton. The possible existence of an effect of the HGMF on the cytoskeleton was tested for, but none was found. The application of cytoskeletal stabilizers or depolymerizers showed that neither microtubules, nor microfilaments, are involved in the graviresponse.

  13. The effect of the cytoskeletal inhibitors on the splenic lymphocyte traffic and homing in rats

    International Nuclear Information System (INIS)

    Yang Huibin

    1989-01-01

    The rat splenic lymphocyte traffic and homing in vivo and the effect of cytoskeletal inhibitors on this process were investigated using the technique of γ-counting of 51 Cr-labelled lymphocytes. The results suggests that:(1) After 2 of intravenous injection, the 51 Cr-labelled lymphocytes from donor rat spleen mainly home to recipient rat spleen, liver, lungs, mesenteric lymph modes (MLN) and gut-associated lymphoid tissues. (2) A significant inhibiting effect on the ability of preferential homing of splenic lymphocytes treated with sodium azide, cytochalasin B or colchicine shows that microtubles and microfilaments play an important role in the lymphocyte traffic and homing

  14. The phosphorylation status and cytoskeletal remodeling of striatal astrocytes treated with quinolinic acid

    International Nuclear Information System (INIS)

    Pierozan, Paula; Ferreira, Fernanda; Ortiz de Lima, Bárbara; Gonçalves Fernandes, Carolina; Totarelli Monteforte, Priscila; Castro Medaglia, Natalia de; Bincoletto, Claudia; Soubhi Smaili, Soraya; Pessoa-Pureur, Regina

    2014-01-01

    Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions. In this study we treated striatal astrocytes in culture with QUIN and assayed the endogenous phosphorylating system associated with glial fibrillary acidic protein (GFAP) and vimentin as well as cytoskeletal remodeling. After 24 h incubation with 100 µM QUIN, cells were exposed to 32 P-orthophosphate and/or protein kinase A (PKA), protein kinase dependent of Ca 2+ /calmodulin II (PKCaMII) or protein kinase C (PKC) inhibitors, H89 (20 μM), KN93 (10 μM) and staurosporin (10 nM), respectively. Results showed that hyperphosphorylation was abrogated by PKA and PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to ionotropic NMDA and non-NMDA (50 µM DL-AP5 and CNQX, respectively) glutamate receptors as well as to metabotropic glutamate receptor (mGLUR; 50 µM MCPG), mGLUR1 (100 µM MPEP) and mGLUR5 (10 µM 4C3HPG) prevented the hyperphosphorylation provoked by QUIN. Also, intra and extracellular Ca 2+ quelators (1 mM EGTA; 10 µM BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca 2+ influx through voltage-dependent Ca 2+ channel type L (L-VDCC) (blocker: 10 µM verapamil) is not implicated in this effect. Morphological analysis showed dramatically altered actin cytoskeleton with concomitant change of morphology to fusiform and/or flattened cells with retracted cytoplasm and disruption of the GFAP meshwork, supporting misregulation of actin cytoskeleton. Both hyperphosphorylation and cytoskeletal remodeling were reversed 24 h after QUIN removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte cytoskeleton may have important implications for understanding the neurotoxicity of QUIN in neurodegenerative disorders. - Highlights:

  15. The phosphorylation status and cytoskeletal remodeling of striatal astrocytes treated with quinolinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Pierozan, Paula; Ferreira, Fernanda; Ortiz de Lima, Bárbara; Gonçalves Fernandes, Carolina [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003 (Brazil); Totarelli Monteforte, Priscila; Castro Medaglia, Natalia de; Bincoletto, Claudia; Soubhi Smaili, Soraya [Departamento de Farmacologia, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, SP (Brazil); Pessoa-Pureur, Regina, E-mail: rpureur@ufrgs.br [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003 (Brazil)

    2014-04-01

    Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions. In this study we treated striatal astrocytes in culture with QUIN and assayed the endogenous phosphorylating system associated with glial fibrillary acidic protein (GFAP) and vimentin as well as cytoskeletal remodeling. After 24 h incubation with 100 µM QUIN, cells were exposed to {sup 32}P-orthophosphate and/or protein kinase A (PKA), protein kinase dependent of Ca{sup 2+}/calmodulin II (PKCaMII) or protein kinase C (PKC) inhibitors, H89 (20 μM), KN93 (10 μM) and staurosporin (10 nM), respectively. Results showed that hyperphosphorylation was abrogated by PKA and PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to ionotropic NMDA and non-NMDA (50 µM DL-AP5 and CNQX, respectively) glutamate receptors as well as to metabotropic glutamate receptor (mGLUR; 50 µM MCPG), mGLUR1 (100 µM MPEP) and mGLUR5 (10 µM 4C3HPG) prevented the hyperphosphorylation provoked by QUIN. Also, intra and extracellular Ca{sup 2+} quelators (1 mM EGTA; 10 µM BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca{sup 2+} influx through voltage-dependent Ca{sup 2+} channel type L (L-VDCC) (blocker: 10 µM verapamil) is not implicated in this effect. Morphological analysis showed dramatically altered actin cytoskeleton with concomitant change of morphology to fusiform and/or flattened cells with retracted cytoplasm and disruption of the GFAP meshwork, supporting misregulation of actin cytoskeleton. Both hyperphosphorylation and cytoskeletal remodeling were reversed 24 h after QUIN removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte cytoskeleton may have important implications for understanding the neurotoxicity of QUIN in neurodegenerative

  16. Estimating the basilar-membrane input-output function in normal-hearing and hearing-impaired listeners

    DEFF Research Database (Denmark)

    Jepsen, Morten Løve; Dau, Torsten

    To partly characterize the function of cochlear processing in humans, the basilar membrane (BM) input-output function can be estimated. In recent studies, forward masking has been used to estimate BM compression. If an on-frequency masker is processed compressively, while an off-frequency masker...... is transformed more linearly, the ratio between the slopes of growth of masking (GOM) functions provides an estimate of BM compression at the signal frequency. In this study, this paradigm is extended to also estimate the knee-point of the I/O-function between linear rocessing at low levels and compressive...... processing at medium levels. If a signal can be masked by a low-level on-frequency masker such that signal and masker fall in the linear region of the I/O-function, then a steeper GOM function is expected. The knee-point can then be estimated in the input level region where the GOM changes significantly...

  17. Theory of mind and emotion-recognition functioning in autistic spectrum disorders and in psychiatric control and normal children.

    Science.gov (United States)

    Buitelaar, J K; van der Wees, M; Swaab-Barneveld, H; van der Gaag, R J

    1999-01-01

    The hypothesis was tested that weak theory of mind (ToM) and/or emotion recognition (ER) abilities are specific to subjects with autism. Differences in ToM and ER performance were examined between autistic (n = 20), pervasive developmental disorder-not otherwise specified (PDD-NOS) (n = 20), psychiatric control (n = 20), and normal children (n = 20). The clinical groups were matched person-to-person on age and verbal IQ. We used tasks for the matching and the context recognition of emotional expressions, and a set of first- and second-order ToM tasks. Autistic and PDD-NOS children could not be significantly differentiated from each other, nor could they be differentiated from the psychiatric controls with a diagnosis of ADHD (n = 9). The psychiatric controls with conduct disorder or dysthymia performed about as well as normal children. The variance in second-order ToM performance contributed most to differences between diagnostic groups.

  18. Normal versus anomalous self-diffusion in two-dimensional fluids: Memory function approach and generalized asymptotic Einstein relation

    Science.gov (United States)

    Shin, Hyun Kyung; Choi, Bongsik; Talkner, Peter; Lee, Eok Kyun

    2014-12-01

    Based on the generalized Langevin equation for the momentum of a Brownian particle a generalized asymptotic Einstein relation is derived. It agrees with the well-known Einstein relation in the case of normal diffusion but continues to hold for sub- and super-diffusive spreading of the Brownian particle's mean square displacement. The generalized asymptotic Einstein relation is used to analyze data obtained from molecular dynamics simulations of a two-dimensional soft disk fluid. We mainly concentrated on medium densities for which we found super-diffusive behavior of a tagged fluid particle. At higher densities a range of normal diffusion can be identified. The motion presumably changes to sub-diffusion for even higher densities.

  19. Characteristics and function of bone marrow stromal adherent cells in normal and irradiated mice and guinea pigs

    Energy Technology Data Exchange (ETDEWEB)

    Changyu, Zheng; Ji, Liu; Xiaoying, Bi

    1986-04-01

    It has been shown from cytochemical and other characteristic studies of bone marrow stromal cells in CFU-F that there are seven types of stromal cells in the stromal adherent cell layer of normal and irradiated C/sub 57/ mice whereas there are only six types in guinea pigs. On the other hand, a radioresistant cell subtype appears in adherent layer after irradiation of both C/sub 57/ mice and guinea pig since the supernatant of cultured CFU-F of the normal and irradiated C/sub 57/ mice can stimulate production of CFU-Gm. It is justifiable that the bone marrow stromal adherent cells of the C/sub 57/ mice could produce CSF.

  20. A generalized L1-approach for a kernel estimator of conditional quantile with functional regressors: Consistency and asymptotic normality

    OpenAIRE

    2009-01-01

    Abstract A kernel estimator of the conditional quantile is defined for a scalar response variable given a covariate taking values in a semi-metric space. The approach generalizes the median?s L1-norm estimator. The almost complete consistency and asymptotic normality are stated. correspondance: Corresponding author. Tel: +33 320 964 933; fax: +33 320 964 704. (Lemdani, Mohamed) (Laksaci, Ali) mohamed.lemdani@univ-lill...

  1. Normal foot and ankle

    International Nuclear Information System (INIS)

    Weissman, S.D.

    1989-01-01

    The foot may be thought of as a bag of bones tied tightly together and functioning as a unit. The bones re expected to maintain their alignment without causing symptomatology to the patient. The author discusses a normal radiograph. The bones must have normal shape and normal alignment. The density of the soft tissues should be normal and there should be no fractures, tumors, or foreign bodies

  2. The cytoskeletal inhibitors latrunculin A and blebbistatin exert antitumorigenic properties in human hepatocellular carcinoma cells by interfering with intracellular HuR trafficking

    Energy Technology Data Exchange (ETDEWEB)

    Doller, Anke; Badawi, Amel [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Schmid, Tobias; Brauß, Thilo [Institut für Biochemie I (Pathobiochemie), Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Pleli, Thomas [Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Meyer zu Heringdorf, Dagmar [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Piiper, Albrecht [Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Pfeilschifter, Josef [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Eberhardt, Wolfgang, E-mail: w.eberhardt@em.uni-frankfurt.de [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany)

    2015-01-01

    The impact of the RNA-binding protein HuR for the post-transcriptional deregulation of tumor-relevant genes is well established. Despite of elevations in HuR expression levels, an increase in cytoplasmic HuR abundance in many cases correlates with a high grade of malignancy. Here, we demonstrated that administration of the actin-depolymerizing macrolide latrunculin A, or blebbistatin, an inhibitor of myosin II ATPase activity, caused a dose- and time-dependent reduction in the high cytoplasmic HuR content of HepG2 and Huh7 hepatocellular carcinoma (HCC) cells. Subcellular fractionation revealed that in addition, both inhibitors strongly attenuated cytoskeletal and membrane-bound HuR abundance and conversely increased the HuR amount in nuclear cell fractions. Concomitant with changes in intracellular HuR localization, both cytoskeletal inhibitors markedly decreased the half-lives of cyclooxygenase-2 (COX-2), cyclin A and cyclin D{sub 1} encoding mRNAs resulting in a significant reduction in their expression levels in HepG2 cells. Importantly, a similar reduction in the expression of these HuR targets was achieved by a RNA interference (RNAi)-mediated knockdown of either HuR or nonmuscle myoin IIA. Using polysomal fractionation, we further demonstrate that the decrease in cytoplasmic HuR by latrunculin A or blebbistatin is accompanied by a marked change in the allocation of HuR and its mRNA cargo from polysomes to ribonucleoprotein (RNP) particles. Functionally, the basal migration and prostaglandin E{sub 2} synthesis are similarly impaired in inhibitor-treated and stable HuR-knockdown HepG2 cells. Our data demonstrate that interfering with the actomyosin-dependent HuR trafficking may comprise a valid therapeutic option for antagonizing pathologic posttranscriptional gene expression by HuR and furthermore emphasize the potential benefit of HuR inhibitory strategies for treatment of HCC. - Highlights: • We tested the effects of latrunculin A and blebbistatin on

  3. The cytoskeletal inhibitors latrunculin A and blebbistatin exert antitumorigenic properties in human hepatocellular carcinoma cells by interfering with intracellular HuR trafficking

    International Nuclear Information System (INIS)

    Doller, Anke; Badawi, Amel; Schmid, Tobias; Brauß, Thilo; Pleli, Thomas; Meyer zu Heringdorf, Dagmar; Piiper, Albrecht; Pfeilschifter, Josef; Eberhardt, Wolfgang

    2015-01-01

    The impact of the RNA-binding protein HuR for the post-transcriptional deregulation of tumor-relevant genes is well established. Despite of elevations in HuR expression levels, an increase in cytoplasmic HuR abundance in many cases correlates with a high grade of malignancy. Here, we demonstrated that administration of the actin-depolymerizing macrolide latrunculin A, or blebbistatin, an inhibitor of myosin II ATPase activity, caused a dose- and time-dependent reduction in the high cytoplasmic HuR content of HepG2 and Huh7 hepatocellular carcinoma (HCC) cells. Subcellular fractionation revealed that in addition, both inhibitors strongly attenuated cytoskeletal and membrane-bound HuR abundance and conversely increased the HuR amount in nuclear cell fractions. Concomitant with changes in intracellular HuR localization, both cytoskeletal inhibitors markedly decreased the half-lives of cyclooxygenase-2 (COX-2), cyclin A and cyclin D 1 encoding mRNAs resulting in a significant reduction in their expression levels in HepG2 cells. Importantly, a similar reduction in the expression of these HuR targets was achieved by a RNA interference (RNAi)-mediated knockdown of either HuR or nonmuscle myoin IIA. Using polysomal fractionation, we further demonstrate that the decrease in cytoplasmic HuR by latrunculin A or blebbistatin is accompanied by a marked change in the allocation of HuR and its mRNA cargo from polysomes to ribonucleoprotein (RNP) particles. Functionally, the basal migration and prostaglandin E 2 synthesis are similarly impaired in inhibitor-treated and stable HuR-knockdown HepG2 cells. Our data demonstrate that interfering with the actomyosin-dependent HuR trafficking may comprise a valid therapeutic option for antagonizing pathologic posttranscriptional gene expression by HuR and furthermore emphasize the potential benefit of HuR inhibitory strategies for treatment of HCC. - Highlights: • We tested the effects of latrunculin A and blebbistatin on different Hu

  4. Haemodynamic effects of dual-chamber pacing versus ventricular pacing during a walk test in patients with depressed or normal left ventricular function

    Energy Technology Data Exchange (ETDEWEB)

    Ferro, Adele; Salvatore, Marco; Cuocolo, Alberto [University Federico II, Department of Biomorphological and Functional Sciences, Institute of Biostructure and Bioimages of the National Council of Research, Naples (Italy); Duilio, Carlo; Santomauro, Maurizio [University Federico II, Department of Clinical Medicine, Cardiovascular and Immunological Sciences, Naples (Italy)

    2005-09-01

    Dual-chamber rate-modulated pacing provides haemodynamic benefits compared with ventricular pacing at rest, but it is unclear whether this also holds true during physical exercise in patients with heart failure. This study assessed the haemodynamic response to a walk test during dual-chamber pacing and ventricular pacing in patients with depressed or normal left ventricular (LV) function. Twelve patients with an LV ejection fraction <50% and 11 patients with an LV ejection fraction {>=}50% underwent two randomised 6-min walk tests under dual-chamber rate-modulated pacing and ventricular pacing at a fixed rate of 70 beats/min. All patients had a dual-chamber pacemaker implanted for complete heart block. LV function was monitored by a radionuclide ambulatory system. In patients with depressed LV function, the change from dual-chamber pacing to ventricular pacing induced a decrease in end-systolic volume at the peak of the walk test (P<0.05), with no difference in end-diastolic volume. As a consequence, higher increases in LV ejection fraction (P<0.0001) and stroke volume (P<0.01) were observed during ventricular pacing. No difference in cardiac output was found between the two pacing modes. In patients with normal LV function, the change from dual-chamber pacing to ventricular pacing induced a significant decrease in cardiac output (P<0.005 at rest and P<0.05 at the peak of the walk test). Compared with dual-chamber rate-modulated pacing, ventricular pacing improves cardiac function and does not affect cardiac output during physical activity in patients with depressed LV function, whereas it impairs cardiac output in those with normal function. (orig.)

  5. Haemodynamic effects of dual-chamber pacing versus ventricular pacing during a walk test in patients with depressed or normal left ventricular function

    International Nuclear Information System (INIS)

    Ferro, Adele; Salvatore, Marco; Cuocolo, Alberto; Duilio, Carlo; Santomauro, Maurizio

    2005-01-01

    Dual-chamber rate-modulated pacing provides haemodynamic benefits compared with ventricular pacing at rest, but it is unclear whether this also holds true during physical exercise in patients with heart failure. This study assessed the haemodynamic response to a walk test during dual-chamber pacing and ventricular pacing in patients with depressed or normal left ventricular (LV) function. Twelve patients with an LV ejection fraction <50% and 11 patients with an LV ejection fraction ≥50% underwent two randomised 6-min walk tests under dual-chamber rate-modulated pacing and ventricular pacing at a fixed rate of 70 beats/min. All patients had a dual-chamber pacemaker implanted for complete heart block. LV function was monitored by a radionuclide ambulatory system. In patients with depressed LV function, the change from dual-chamber pacing to ventricular pacing induced a decrease in end-systolic volume at the peak of the walk test (P<0.05), with no difference in end-diastolic volume. As a consequence, higher increases in LV ejection fraction (P<0.0001) and stroke volume (P<0.01) were observed during ventricular pacing. No difference in cardiac output was found between the two pacing modes. In patients with normal LV function, the change from dual-chamber pacing to ventricular pacing induced a significant decrease in cardiac output (P<0.005 at rest and P<0.05 at the peak of the walk test). Compared with dual-chamber rate-modulated pacing, ventricular pacing improves cardiac function and does not affect cardiac output during physical activity in patients with depressed LV function, whereas it impairs cardiac output in those with normal function. (orig.)

  6. Comparison of skin barrier function and sensory nerve electric current perception threshold between IgE-high extrinsic and IgE-normal intrinsic types of atopic dermatitis.

    Science.gov (United States)

    Mori, T; Ishida, K; Mukumoto, S; Yamada, Y; Imokawa, G; Kabashima, K; Kobayashi, M; Bito, T; Nakamura, M; Ogasawara, K; Tokura, Y

    2010-01-01

    Background Two types of atopic dermatitis (AD) have been proposed, with different pathophysiological mechanisms underlying this seemingly heterogeneous disorder. The extrinsic type shows high IgE levels presumably as a consequence of skin barrier damage and feasible allergen permeation, whereas the intrinsic type exhibits normal IgE levels and is not mediated by allergen-specific IgE. Objectives To investigate the relationship between pruritus perception threshold and skin barrier function of patients with AD in a comparison between the extrinsic and intrinsic types. Methods Enrolled in this study were 32 patients with extrinsic AD, 17 with intrinsic AD and 24 healthy individuals. The barrier function of the stratum corneum was assessed by skin surface hydration and transepidermal water loss (TEWL), and pruritus perception was evaluated by the electric current perception threshold (CPT) of sensory nerves upon neuroselective transcutaneous electric stimulation. Results Skin surface hydration was significantly lower and TEWL was significantly higher in extrinsic AD than intrinsic AD or normal controls. Although there was no statistically significant difference in CPT among extrinsic AD, intrinsic AD and normal controls, CPT was significantly correlated with skin surface hydration and inversely with TEWL in intrinsic AD and normal controls, but not extrinsic AD. Finally, CPT was correlated with the visual analogue scale of itch in the nonlesional skin of patients with extrinsic but not intrinsic AD. Conclusions Patients with extrinsic AD have an impaired barrier, which increases the pre-existing pruritus but rather decreases sensitivity to external stimuli. In contrast, patients with intrinsic AD retain a normal barrier function and sensory reactivity to external pruritic stimuli.

  7. Regional frontal gray matter volume associated with executive function capacity as a risk factor for vehicle crashes in normal aging adults.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Sakai

    Full Text Available Although low executive functioning is a risk factor for vehicle crashes among elderly drivers, the neural basis of individual differences in this cognitive ability remains largely unknown. Here we aimed to examine regional frontal gray matter volume associated with executive functioning in normal aging individuals, using voxel-based morphometry (VBM. To this end, 39 community-dwelling elderly volunteers who drove a car on a daily basis participated in structural magnetic resonance imaging, and completed two questionnaires concerning executive functioning and risky driving tendencies in daily living. Consequently, we found that participants with low executive function capacity were prone to risky driving. Furthermore, VBM analysis revealed that lower executive function capacity was associated with smaller gray matter volume in the supplementary motor area (SMA. Thus, the current data suggest that SMA volume is a reliable predictor of individual differences in executive function capacity as a risk factor for vehicle crashes among elderly persons. The implication of our results is that regional frontal gray matter volume might underlie the variation in driving tendencies among elderly drivers. Therefore, detailed driving behavior assessments might be able to detect early neurodegenerative changes in the frontal lobe in normal aging adults.

  8. MAL Overexpression Leads to Disturbed Expression of Genes That Influence Cytoskeletal Organization and Differentiation of Schwann Cells

    Directory of Open Access Journals (Sweden)

    Daniela Schmid

    2014-09-01

    Full Text Available In the developing peripheral nervous system, a coordinated reciprocal signaling between Schwann cells and axons is crucial for accurate myelination. The myelin and lymphocyte protein MAL is a component of lipid rafts that is important for targeting proteins and lipids to distinct domains. MAL overexpression impedes peripheral myelinogenesis, which is evident by a delayed onset of myelination and reduced expression of the myelin protein zero (Mpz/P0 and the low-affinity neurotrophin receptor p75NTR . This study shows that MAL overexpression leads to a significant reduction of Mpz and p75NTR expression in primary mouse Schwann cell cultures, which was already evident before differentiation, implicating an effect of MAL in early Schwann cell development. Their transcription was robustly reduced, despite normal expression of essential transcription factors and receptors. Further, the cAMP response element-binding protein (CREB and phosphoinositide 3-kinase signaling pathways important for Schwann cell differentiation were correctly induced, highlighting that other so far unknown rate limiting factors do exist. We identified novel genes expressed by Schwann cells in a MAL-dependent manner in vivo and in vitro. A number of those, including S100a4, RhoU and Krt23, are implicated in cytoskeletal organization and plasma membrane dynamics. We showed that S100a4 is predominantly expressed by nonmyelinating Schwann cells, whereas RhoU was localized within myelin membranes, and Krt23 was detected in nonmyelinating as well as in myelinating Schwann cells. Their differential expression during early peripheral nerve development further underlines their possible role in influencing Schwann cell differentiation and myelination.

  9. Executive functions differences in normal scholars, with Attention deficit-hyperactivity disorder, disorder of arithmetical skills and comorbid condition

    OpenAIRE

    Gaitán Chipatecua, Alexandra; Rey-Anacona, César-Armando

    2013-01-01

    El objetivo del presente estudio descriptivo-comparativo fue comparar el desempeño en funciones ejecutivas de escolares entre ocho y trece años con trastorno por déficit de atención e hiperactividad (TDAH), trastorno del cálculo (TC), TDAH+TC y controles normales. Los diagnósticos se confirmaron a través de una entrevista clínica semiestructurada, un cuestionario clínico de déficit atencional y pruebas de cálculo matemático. Se encontraron diferencias estadísticamente significativas entre los...

  10. Compartive Assessment of Functional Cerebral Lateralization of Mentally Retarded Children having Mental Age of 5 to 6 Old with Normal Ones

    Directory of Open Access Journals (Sweden)

    Seyyed Behnamedin Jame'ei

    2003-01-01

    Full Text Available Objective: Study of the children psychomotor development, is and interdisciplinary interest among medical and rehabilitation specialist. The psychomotor development is mostly dependent on normal ontogenetically evolution of the brain, thus it is reasonable that any defects in this complicated process would be able to cause irreversible cognitive, sensory and motor dysfunction. In addition to mental deficiency in Mental Retarded (MR children, some other notable defects in motor abilities including gross and fine movement and equilibrium also exist in these children. Hemispheric dominancy or lateralization is an important stage in normal brain development which thought to be affected in MR children, and thus affects the outcome of rehabilitation treatment for these children. The present research work is designed to study functional cerebral lateralization between mentally retarded children having mental age of 5 to 6 years old and normal ones of the same age. Materials & Methods: By using the Neurological Developmental Questionnaire of Delacatom the functional lateralization parameters including footedness, handedness, and eye and ear preference were considered in this study. Results: Statistical analysis of the results showed significant differences in above mentioned parameters among MR and normal children of the same age. Conclusion: On the bases of these results, we believe that different pattern of lateralization in MR children could affect the rehabilitation management and should be noted in therapeutic plan.

  11. Cytoskeletal proteins in the cerebrospinal fluid as biomarker of multiple sclerosis.

    Science.gov (United States)

    Madeddu, Roberto; Farace, Cristiano; Tolu, Paola; Solinas, Giuliana; Asara, Yolande; Sotgiu, Maria Alessandra; Delogu, Lucia Gemma; Prados, Jose Carlos; Sotgiu, Stefano; Montella, Andrea

    2013-02-01

    The axonal cytoskeleton is a finely organized system, essential for maintaining the integrity of the axon. Axonal degeneration is implicated in the pathogenesis of unremitting disability of multiple sclerosis (MS). Purpose of this study is to evaluate levels of cytoskeletal proteins such as neurofilament light protein (NFL), glial fibrillary acidic protein (GFAP), and β-tubulin (β-Tub) isoforms II and III in the cerebrospinal fluid (CSF) of MS patients and their correlation with MS clinical indices. CSF levels of cytoskeletal proteins were determined in 51 patients: 33 with MS and 18 with other neurological diseases (OND). NFL, GFAP and β-Tub II proteins were significantly higher (p 0.05) was found between MS and OND with regard to β-Tub III. Interestingly, levels of β-Tub III and NFL were higher in progressive than in remitting MS forms; on the contrary, higher levels of β-Tub II and GFAP were found in remitting MS forms. However, with the exception of β-Tub III, all proteins tend to decrease their CSF levels concomitantly with the increasing disability (EDSS) score. Overall, our results might indicate β-Tub II as a potential candidate for diagnostic and β-Tub III as a possible prognostic biomarker of MS. Therefore, further analyses are legitimated and desirable.

  12. Intracellular Transport of Cargo in a Sub-diffusive Environment over an Explicit Cytoskeletal Network

    Science.gov (United States)

    Maelfeyt, Bryan; Gopinathan, Ajay

    Intracellular transport occurs in nearly all eukaryotic cells, where materials such as proteins, lipids, carbohydrates, and nucleic acids travel to target locations through phases of passive, diffusion-based transport and active, motor-driven transport along filaments that make up the cell's cytoskeleton.We develop a computational model of the process with explicit cytoskeletal filament networks. In the active transport phase, cargo moves in straight lines along these filaments that are spread throughout the cell. To model the passive transport phase of cargo in the cytoplasm, where anomalous sub-diffusion is thought to take place, we implement a continuous-time random walk. We use this approach to provide a stepping stone to a predictive model where we can determine transport properties over a cytoskeletal network provided by experimental images of real filaments. We illustrate our approach by modeling the transport of insulin out of the cell and determining the impact of network geometry, anomalous sub-diffusion and motor number on the first-passage time distributions for insulin granules reaching their target destinations on the membrane.

  13. Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure

    Science.gov (United States)

    Maniotis, A. J.; Chen, C. S.; Ingber, D. E.

    1997-01-01

    We report here that living cells and nuclei are hard-wired such that a mechanical tug on cell surface receptors can immediately change the organization of molecular assemblies in the cytoplasm and nucleus. When integrins were pulled by micromanipulating bound microbeads or micropipettes, cytoskeletal filaments reoriented, nuclei distorted, and nucleoli redistributed along the axis of the applied tension field. These effects were specific for integrins, independent of cortical membrane distortion, and were mediated by direct linkages between the cytoskeleton and nucleus. Actin microfilaments mediated force transfer to the nucleus at low strain; however, tearing of the actin gel resulted with greater distortion. In contrast, intermediate filaments effectively mediated force transfer to the nucleus under both conditions. These filament systems also acted as molecular guy wires to mechanically stiffen the nucleus and anchor it in place, whereas microtubules acted to hold open the intermediate filament lattice and to stabilize the nucleus against lateral compression. Molecular connections between integrins, cytoskeletal filaments, and nuclear scaffolds may therefore provide a discrete path for mechanical signal transfer through cells as well as a mechanism for producing integrated changes in cell and nuclear structure in response to changes in extracellular matrix adhesivity or mechanics.

  14. Clarifying Normalization

    Science.gov (United States)

    Carpenter, Donald A.

    2008-01-01

    Confusion exists among database textbooks as to the goal of normalization as well as to which normal form a designer should aspire. This article discusses such discrepancies with the intention of simplifying normalization for both teacher and student. This author's industry and classroom experiences indicate such simplification yields quicker…

  15. CT findings after normal and unsuccessful functional endoscopic sinus surgery; Ruolod della tomografia computerizzata dopo chirurgia funzionale dei seni paranasali: rilievi normali e valutazioni degli insuccessi chirurgici

    Energy Technology Data Exchange (ETDEWEB)

    Scribano, E.; Ascenti, G.; Bellinvia, A.; Mazziotti, S.; Lamberto, S. [Messina Univ., Messina (Italy). Ist. di Scienze Radiologiche; Cascio, F. [Messina Univ., Messina (Italy). Ist. di Otorinolaringoiatria

    1999-09-01

    The paper investigates the functional endoscopic sinus surgery with the Messer-linger's technique which treats benign or inflammatory diseases of paranasal sinuses resistant to medical therapy. The goal of this type of surgery is to open the obstructed sinus ostia and restore normal aeration and mucociliary clearance. The computerized tomography permits an accurate assessment of extension and results of functional endoscopic sinus surgery. [Italian] L'articolo discute l'uso della tecnica di Messerklinger nella chirurgia funzionale endoscopica dei seni paranasali per il trattamento delle malattie benigne e delle infiammazioni croniche. Essa disostruisce gli osti sinusali ripristinando la normale areazione e la pulizia mucociliare. La tomografia computerizzata consente di valutare l'estensione e i risultati del trattamento chirurgico funzionale, soprattutto nel caso di insuccesso terapeutico, rilevando malattia nasosinusale ricorrente e-o recidiva.

  16. Función del diafragma durante la colocación de cargas sobre el abdomen en sujetos normales Study of diaphragmatic muscle function during abdominal weight in normal subjects

    Directory of Open Access Journals (Sweden)

    Sergio G. Monteiro

    2012-04-01

    Full Text Available Los efectos de las cargas en el abdomen con el objeto de producir entrenamiento del diafragma, no han sido suficientemente evaluados. Estudiamos la función del diafragma durante la colocación de cargas sobre el abdomen y con cambios en el patrón respiratorio. Se estudiaron 6 voluntarios normales. Se obtuvo flujo en la boca, presión gástrica (Pga, presión esofágica (Pes, movimiento torácico (TX y abdominal (AB, presión inspiratoria máxima (PImax y presión transdiafragmática media (Pdi y máxima (Pdimax. Se calculó la relación Pdi/Pdimax y el índice tensión-tiempo del diafragma (TTdi. Etapas: patrón normal (PN, patrón abdominal (PA y carga de 1, 2, 4 y 6 kg con PN y PA. El PA fue facilitado por las cargas sobre el abdomen. Solo con 6 kg (PN y PA la Pga a capacidad residual funcional aumentó significativamente (p 0.001. La Pdi siguió a las variaciones de la Pga y aumentó con todos los PA (p The effects of the abdominal weight with the intention of producing training of the diaphragm, have not been sufficiently evaluated. We studied the function of the diaphragm during the abdominal weight training and during associated changes in the respiratory pattern. Six normal volunteers were studied. Flow at the mouth at functional residual capacity (FRC was obtained as well as gastric pressure (Pga, esophageal pressure (Pes, thoracic and abdominal movements, maximal inspiratory pressure and mean and maximal transdiaphragmatic pressure (Pdi and Pdi max. Pdi/Pdimax and the diaphragm tension-time index (TTdi were calculated. Studied steps: normal pattern (NP, abdominal pattern (AP and weight of 1, 2, 4 and 6 kg with NP and AP as well. We found 1 The AP was facilitated by the abdominal weight, 2 Only with 6 kg (NP and AP the Pga at FRC increased significantly (p 0.001, 3 the Pdi followed the variations of the Pga and increased with all the AP (p < 0.001, 4 The index TTdi load reached a value of 0.05 ± 0.02 (p < 0.001. The charges did not

  17. Automatic extraction analysis of the anatomical functional area for normal brain 18F-FDG PET imaging

    International Nuclear Information System (INIS)

    Guo Wanhua; Jiang Xufeng; Zhang Liying; Lu Zhongwei; Li Peiyong; Zhu Chengmo; Zhang Jiange; Pan Jiapu

    2003-01-01

    Using self-designed automatic extraction software of brain functional area, the grey scale distribution of 18 F-FDG imaging and the relationship between the 18 F-FDG accumulation of brain anatomic function area and the 18 F-FDG injected dose, the level of glucose, the age, etc., were studied. According to the Talairach coordinate system, after rotation, drift and plastic deformation, the 18 F-FDG PET imaging was registered into the Talairach coordinate atlas, and then the average gray value scale ratios between individual brain anatomic functional area and whole brain area was calculated. Further more the statistics of the relationship between the 18 F-FDG accumulation of every brain anatomic function area and the 18 F-FDG injected dose, the level of glucose and the age were tested by using multiple stepwise regression model. After images' registration, smoothing and extraction, main cerebral cortex of the 18 F-FDG PET brain imaging can be successfully localized and extracted, such as frontal lobe, parietal lobe, occipital lobe, temporal lobe, cerebellum, brain ventricle, thalamus and hippocampus. The average ratios to the inner reference of every brain anatomic functional area were 1.01 ± 0.15. By multiple stepwise regression with the exception of thalamus and hippocampus, the grey scale of all the brain functional area was negatively correlated to the ages, but with no correlation to blood sugar and dose in all areas. To the 18 F-FDG PET imaging, the brain functional area extraction program could automatically delineate most of the cerebral cortical area, and also successfully reflect the brain blood and metabolic study, but extraction of the more detailed area needs further investigation

  18. Tissue-specific expression of transgenic secreted ACE in vasculature can restore normal kidney functions, but not blood pressure, of Ace-/- mice.

    Directory of Open Access Journals (Sweden)

    Saurabh Chattopadhyay

    Full Text Available Angiotensin-converting enzyme (ACE regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS. Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE.

  19. Tissue-specific expression of transgenic secreted ACE in vasculature can restore normal kidney functions, but not blood pressure, of Ace-/- mice.

    Science.gov (United States)

    Chattopadhyay, Saurabh; Kessler, Sean P; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C

    2014-01-01

    Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE.

  20. PedsQL relates to function and behavior in very low and normal birth weight 2- and 3-year-olds from a regional cohort.

    Science.gov (United States)

    Palta, Mari; Sadek-Badawi, Mona

    2008-06-01

    To compare PedsQL scores in young children who were very low (2,500 g) and to examine the relationship of the PedsQL score to behavioral and functional scores. The PedsQL, Achenbach Child Behavior Checklist and the PEDI functional scales were telephone administered to parents of a regional cohort of 672 very low birth weight and 455 normal birth weight children, 2- and 3-years old. PedsQL scales were regressed on behavior, function and health conditions. Mean (SD) overall PedsQL score was 91 (8.4) for normal birth weight and 87 (12) for very low birth weight children, and changed little when standardized to the race/ethnicity and maternal education of corresponding Wisconsin births. Mobility function and the CBCL explained 58% of the variance in PedsQL, but the relationship was curvilinear. The PedsQL is sensitive to health problems of very low birth weight in young children. The PedsQL is quite strongly related to mobility and behavior problems, but scales these differently than do standard instruments. Parents either do not think of subtle issues with child function and behavior without specific prompting or do not perceive them as problems affecting quality of life.

  1. Biosynthesis of intestinal microvillar proteins. Rapid expression of cytoskeletal components in microvilli of pig small intestinal mucosal explants

    DEFF Research Database (Denmark)

    Cowell, G M; Danielsen, E M

    1984-01-01

    Using alkaline extraction to separate cytoskeletal and membrane proteins of intestinal microvilli, the kinetics of assembly of these two microvillar protein compartments was studied by pulse-chase labelling of pig small intestinal mucosal explants, kept in organ culture. Following a 10 min pulse...... of [35S]methionine, the membrane proteins did not appear in the microvillar fraction until after 40-60 min of chase. In contrast, the cytoskeletal components, of which the 110-kDa protein and villin were immunologically identified, were expressed in the microvillar fraction immediately after the 10 min...

  2. Weight preoccupation as a function of observed physical attractiveness: ethnic differences among normal-weight adolescent females.

    Science.gov (United States)

    Colabianchi, Natalie; Ievers-Landis, Carolyn E; Borawski, Elaine A

    2006-09-01

    To examine the association between observer ratings of physical attractiveness and weight preoccupation for female adolescents, and to explore any ethnic differences between Caucasian, African-American, and Hispanic females. Normal-weight female adolescents who had participated in the National Longitudinal Study of Adolescent Health in-home Wave II survey were included (n = 4,324). Physical attractiveness ratings were made in vivo by interviewers. Using logistic regression models stratified by ethnicity, the associations between observer-rated attractiveness and weight preoccupation were examined after controlling for demographics, measured body mass index (BMI) and psychosocial factors. Caucasian female adolescents perceived as being more attractive reported significantly greater weight preoccupation compared with those rated as being less attractive. Observed attractiveness did not relate to weight preoccupation among African-American or Hispanic youth when controlling for other factors. For Caucasian female adolescents, being perceived by others as more attractive may be a risk factor for disordered eating.

  3. Human CD4 restores normal T cell development and function in mice deficient in murine CD4

    OpenAIRE

    1994-01-01

    The ability of a human coreceptor to function in mice was investigated by generating human CD4 (hCD4)-expressing transgenic mice on a mouse CD4-deficient (mCD4-/-) background. From developing thymocyte to matured T lymphocyte functions, hCD4 was shown to be physiologically active. By examining the expansion and deletion of specific V beta T cell families in mutated mice with and without hCD4, it was found that hCD4 can participate in positive and negative selection. Mature hCD4 single positiv...

  4. Age and gender specific normal values of left ventricular mass, volume and function for gradient echo magnetic resonance imaging: a cross sectional study

    International Nuclear Information System (INIS)

    Cain, Peter A; Ahl, Ragnhild; Hedstrom, Erik; Ugander, Martin; Allansdotter-Johnsson, Ase; Friberg, Peter; Arheden, Hakan

    2009-01-01

    Knowledge about age-specific normal values for left ventricular mass (LVM), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF) by cardiac magnetic resonance imaging (CMR) is of importance to differentiate between health and disease and to assess the severity of disease. The aims of the study were to determine age and gender specific normal reference values and to explore the normal physiological variation of these parameters from adolescence to late adulthood, in a cross sectional study. Gradient echo CMR was performed at 1.5 T in 96 healthy volunteers (11–81 years, 50 male). Gender-specific analysis of parameters was undertaken in both absolute values and adjusted for body surface area (BSA). Age and gender specific normal ranges for LV volumes, mass and function are presented from the second through the eighth decade of life. LVM, ESV and EDV rose during adolescence and declined in adulthood. SV and EF decreased with age. Compared to adult females, adult males had higher BSA-adjusted values of EDV (p = 0.006) and ESV (p < 0.001), similar SV (p = 0.51) and lower EF (p = 0.014). No gender differences were seen in the youngest, 11–15 year, age range. LV volumes, mass and function vary over a broad age range in healthy individuals. LV volumes and mass both rise in adolescence and decline with age. EF showed a rapid decline in adolescence compared to changes throughout adulthood. These findings demonstrate the need for age and gender specific normal ranges for clinical use

  5. Mitochondrial histone-like DNA-binding proteins are essential for normal cell growth and mitochondrial function in Crithidia fasciculata

    Czech Academy of Sciences Publication Activity Database

    Avliyakulov, N. K.; Lukeš, Julius; Ray, D. S.

    2004-01-01

    Roč. 3, č. 2 (2004), s. 518-526 ISSN 1535-9778 R&D Projects: GA AV ČR IAA5022302 Institutional research plan: CEZ:AV0Z6022909 Keywords : cell growth * mitochondrial function * Kinetoplastida Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.954, year: 2004

  6. Fractional excretion of beta-2-microglobulin in the urine of patients with normal or reduced renal function and hepatic coma

    DEFF Research Database (Denmark)

    Hansen, P B; Dalhoff, K; Joffe, P

    1991-01-01

    The purpose of this prospective study was to evaluate beta-2-microglobulin (beta 2m) as a differential diagnostic indicator between hepatic nephropathy (HN) and acute tubulointerstitial nephropathy (ATIN) in patients with reduced renal function and hepatic coma, and to determine whether beta 2m e...

  7. Normally Oriented Adhesion versus Friction Forces in Bacterial Adhesion to Polymer-Brush Functionalized Surfaces Under Fluid Flow

    NARCIS (Netherlands)

    Swartjes, Jan J. T. M.; Veeregowda, Deepak H.; van der Mei, Henny C.; Busscher, Henk J.; Sharma, Prashant K.

    2014-01-01

    Bacterial adhesion is problematic in many diverse applications. Coatings of hydrophilic polymer chains in a brush configuration reduce bacterial adhesion by orders of magnitude, but not to zero. Here, the mechanism by which polymer-brush functionalized surfaces reduce bacterial adhesion from a

  8. Normal hematopoietic stem cell function in mice with enforced expression of the Hippo signaling effector YAP1.

    Directory of Open Access Journals (Sweden)

    Lina Jansson

    Full Text Available The Hippo pathway has recently been implicated in the regulation of organ size and stem cells in multiple tissues. The transcriptional cofactor yes-associated protein 1 (Yap1 is the most downstream effector of Hippo signaling and is functionally repressed by the upstream components of the pathway. Overexpression of YAP1 stimulates proliferation of stem and progenitor cells in many tissues, consistent with inhibition of Hippo signaling. To study the role of Hippo signaling in hematopoietic stem cells (HSCs, we created a transgenic model with inducible YAP1 expression exclusively within the hematopoietic system. Following 3 months induction, examination of blood and bone marrow in the induced mice revealed no changes in the distribution of the hematopoietic lineages compared to control mice. Moreover, the progenitor cell compartment was unaltered as determined by colony forming assays and immunophenotyping. To address whether YAP1 affects the quantity and function of HSCs we performed competitive transplantation experiments. We show that ectopic YAP1 expression does not influence HSC function neither during steady state nor in situations of hematopoietic stress. This is in sharp contrast to effects seen on stem- and progenitor cells in other organs and suggests highly tissue specific functions of the Hippo pathway in regulation of stem cells.

  9. Transporter function and cyclic AMP turnover in normal colonic mucosa from patients with and without colorectal neoplasia

    DEFF Research Database (Denmark)

    Kleberg, Karen; Jensen, Gerda Majgaard; Christensen, Dan Ploug

    2012-01-01

    The pathogenesis of colorectal neoplasia is still unresolved but has been associated with alterations in epithelial clearance of xenobiotics and metabolic waste products. The aim of this study was to functionally characterize the transport of cyclic nucleotides in colonic biopsies from patients...

  10. Differences in brain functional connectivity at resting state in neonates born to healthy obese or normal-weight mothers

    Science.gov (United States)

    Recent studies have shown associations between maternal obesity at pre- or early pregnancy and long-term neurodevelopment in children, suggesting in utero effects of maternal obesity on offspring brain development. In this study, we examined whether brain functional connectivity to the prefrontal lo...

  11. Left ventricular function impairment in patients with normal-weight obesity: contribution of abdominal fat deposition, profibrotic state, reduced insulin sensitivity, and proinflammatory activation.

    Science.gov (United States)

    Kosmala, Wojciech; Jedrzejuk, Diana; Derzhko, Roksolana; Przewlocka-Kosmala, Monika; Mysiak, Andrzej; Bednarek-Tupikowska, Grazyna

    2012-05-01

    Obesity predisposes to left ventricular (LV) dysfunction and heart failure; however, the risk of these complications has not been assessed in patients with a normal body mass index (BMI) but increased body fat content (normal-weight obesity, NWO). We hypothesized that LV performance in NWO may be impaired and sought to investigate potential contributors to cardiac functional abnormalities. One hundred sixty-eight subjects (age, 38±7 years) with BMI affecting the myocardium were classified on the basis of body fat content into 2 groups: with NWO and without NWO. Echocardiographic indices of LV systolic and diastolic function, including myocardial velocities and deformation, serological fibrosis markers, indicators of proinflammatory activation, and metabolic control, were evaluated. Subjects with NWO demonstrated impaired LV systolic and diastolic function, increased fibrosis intensity (assessed by procollagen type I carboxy-terminal propeptide [PICP]), impaired insulin sensitivity, and increased proinflammatory activation as compared with individuals with normal body fat. The independent correlates of LV systolic and diastolic function variables were as follows: for strain, IL-18 (β=-0.17, P<0.006), C-reactive protein (β=-0.20, P<0.002) and abdominal fat deposit (β=-0.20, P<0.003); for tissue S velocity, PICP (β=-0.21, P<0.002) and abdominal fat deposit (β=-0.43, P<0.0001); for tissue E velocity, abdominal fat deposit (β=-0.30, P<0.0001), PICP (β=-0.31, P<0.0001) and homeostasis model assessment of insulin resistance index (HOMA IR; β=-0.20, P<0.002); and for E/e'-PICP, IL-18 (both β=0.18, P<0.01) and HOMA IR (β=0.16, P<0.04). In patients with NWO, subclinical disturbances of LV function are independently associated with the extent of abdominal fat deposit, profibrotic state (as reflected by circulating PICP), reduced insulin sensitivity, and proinflammatory activation.

  12. The comparison of Updating function of Working Memory in Three Groups of Substance Abusers (Heroin, Opium, Those Treated with Methadone and normal controls

    Directory of Open Access Journals (Sweden)

    Gholamrezayee S

    2016-11-01

    Full Text Available Introduction: Chronic use of opiates is associated with a wide range of neuropsychological deficits. Therefore, this study aimed to evaluate one of the neuropsychological functions, updating function of working memory, in three groups, including substance abusers (heroin and opium, those under treatment with methadone, and normal controls. Methods:The method of this study was causal-comparative. Ninty individuals in three groups, including substance abusers (n = 30, those under treatment with methadone (n = 30, and normal controls (n = 30 were selected from people referred to the addiction treatment Clinics in Shiraz (2015 with the purposeful sampling method. All subjects were evaluated regarding working memory updating and self-reported mental effort scale and the results were analyzed by Multiple Analysis of Variance (MANOVA test and Tukey post hoc test with SPSS software (version 23. Results:The results showed a significant difference between the three groups in the updating function of working memory; so that effectiveness and efficiency of processing in the normal group was better than the other two groups and the performance effectiveness and efficiency of processing in the group under methadone treatment was better than substance abusers group. conclusions:substance abuse has a negative effect on neurological function. Given that the group of methadone treatment had better performance in the updating function of working memory than the group of substance abusers, these results provide hope that the effects of examined drugs on working memory is not permanent and we can look for psychological interventions to treat these patients and prevent problems recurrence.

  13. Clinical Dosing Regimen of Selinexor Maintains Normal Immune Homeostasis and T-cell Effector Function in Mice: Implications for Combination with Immunotherapy.

    Science.gov (United States)

    Tyler, Paul M; Servos, Mariah M; de Vries, Romy C; Klebanov, Boris; Kashyap, Trinayan; Sacham, Sharon; Landesman, Yosef; Dougan, Michael; Dougan, Stephanie K

    2017-03-01

    Selinexor (KPT-330) is a first-in-class nuclear transport inhibitor currently in clinical trials as an anticancer agent. To determine how selinexor might affect antitumor immunity, we analyzed immune homeostasis in mice treated with selinexor and found disruptions in T-cell development, a progressive loss of CD8 T cells, and increases in inflammatory monocytes. Antibody production in response to immunization was mostly normal. Precursor populations in bone marrow and thymus were unaffected by selinexor, suggesting that normal immune homeostasis could recover. We found that a high dose of selinexor given once per week preserved nearly normal immune functioning, whereas a lower dose given 3 times per week did not restore immune homeostasis. Both naïve and effector CD8 T cells cultured in vitro showed impaired activation in the presence of selinexor. These experiments suggest that nuclear exportins are required for T-cell development and function. We determined the minimum concentration of selinexor required to block T-cell activation and showed that T-cell-inhibitory effects of selinexor occur at levels above 100 nmol/L, corresponding to the first 24 hours post-oral dosing. In a model of implantable melanoma, selinexor treatment at 10 mg/kg with a 4-day drug holiday led to intratumoral IFNγ + , granzyme B + cytotoxic CD8 T cells that were comparable with vehicle-treated mice. Overall, selinexor treatment leads to transient inhibition of T-cell activation, but clinically relevant once and twice weekly dosing schedules that incorporate sufficient drug holidays allow for normal CD8 T-cell functioning and development of antitumor immunity. Mol Cancer Ther; 16(3); 428-39. ©2017 AACR See related article by Farren et al., p. 417 . ©2017 American Association for Cancer Research.

  14. Clinical dosing regimen of selinexor maintains normal immune homeostasis and T cell effector function in mice: implications for combination with immunotherapy

    Science.gov (United States)

    Tyler, Paul M.; Servos, Mariah M.; de Vries, Romy C.; Klebanov, Boris; Kashyap, Trinayan; Sacham, Sharon; Landesman, Yosef; Dougan, Michael; Dougan, Stephanie K.

    2017-01-01

    Selinexor (KPT-330) is a first in class nuclear transport inhibitor currently in clinical trials as an anti-cancer agent. To determine how selinexor might impact anti-tumor immunity, we analyzed immune homeostasis in mice treated with selinexor and found disruptions in T cell development, a progressive loss of CD8 T cells and increases in inflammatory monocytes. Antibody production in response to immunization was mostly normal. Precursor populations in bone marrow and thymus were unaffected by selinexor, suggesting that normal immune homeostasis could recover. We found that a high dose of selinexor given once per week preserved nearly normal immune functioning, whereas a lower dose given 3 times per week did not restore immune homeostasis. Both naïve and effector CD8 T cells cultured in vitro showed impaired activation in the presence of selinexor. These experiments suggest that nuclear exportins are required for T cell development and function. We determined the minimum concentration of selinexor required to block T cell activation, and showed that T cell inhibitory effects of selinexor occur at levels above 100nM, corresponding to the first 24 hours post-oral dosing. In a model of implantable melanoma, selinexor treatment at 10 mg/kg with a 5 day drug holiday led to intratumoral IFNγ+, granzyme B+ cytotoxic CD8 T cells that were comparable to vehicle treated mice. Overall, selinexor treatment leads to transient inhibition of T cell activation but clinically relevant once and twice weekly dosing schedules that incorporate sufficient drug holidays allow for normal CD8 T cell functioning and development of anti-tumor immunity. PMID:28148714

  15. Low Left Atrial Compliance Contributes to the Clinical Recurrence of Atrial Fibrillation after Catheter Ablation in Patients with Structurally and Functionally Normal Heart.

    Science.gov (United States)

    Park, Junbeom; Yang, Pil-sung; Kim, Tae-Hoon; Uhm, Jae-Sun; Kim, Joung-Youn; Joung, Boyoung; Lee, Moon-Hyoung; Hwang, Chun; Pak, Hui-Nam

    2015-01-01

    Stiff left atrial (LA) syndrome was initially reported in post-cardiac surgery patients and known to be associated with low LA compliance. We investigated the physiological and clinical implications of LA compliance by estimating LA pulse pressure (LApp) among patients with atrial fibrillation (AF) and structurally and functionally normal heart. Among 1038 consecutive patients with LA pressure measurements before AF ablation, we included 334 patients with structurally and functionally normal heart (81.7% male, 54.1±10.6 years, 77.0% paroxysmal AF) after excluding those with hypertension, diabetes, and previous ablation or cardiac surgery. We measured LApp (peak-nadir LA pressure) at the beginning of the ablation procedure and compared the values with clinical parameters and the AF recurrence rate. AF patients with normal heart were younger and more frequently male and had paroxysmal AF, a lower body mass index, and a lower LApp compared to others (all p<0.05). Based on the median value, the low LA compliance group (LApp≥13 mmHg) had a smaller LA volume index and lower LA voltage (all p<0.05) compared to the high LA compliance group. During a mean follow-up of 16.7±11.8 months, low LA compliance was independently associated with two fold-higher risk of clinical AF recurrence (HR:2.202; 95%CI:1.077-4.503; p = 0.031). Low LA compliance, as determined by an elevated LApp, was associated with a smaller LA volume index and lower LA voltage and independently associated with higher clinical recurrence after catheter ablation in AF patients with structurally and functionally normal heart.

  16. Cognitive Function in Normal-Weight, Overweight, and Obese Older Adults: An Analysis of the Advanced Cognitive Training for Independent and Vital Elderly Cohort

    Science.gov (United States)

    Kuo, Hsu-Ko; Jones, Richard N.; Milberg, William P.; Tennstedt, Sharon; Talbot, Laura; Morris, John N.; Lipsitz, Lewis A.

    2010-01-01

    OBJECTIVES To assess how elevated body mass index (BMI) affects cognitive function in elderly people. DESIGN Cross-sectional study. SETTING Data for this cross-sectional study were taken from a multicenter randomized controlled trial, the Advanced Cognitive Training for Independent and Vital Elderly trial. PARTICIPANTS The analytic sample included 2,684 normal-weight, overweight, or obese subjects aged 65 to 94. MEASUREMENTS Evaluation of cognitive abilities was performed in several domains: global cognition, memory, reasoning, and speed of processing. Cross-sectional association between body weight status and cognitive functions was analyzed using multiple linear regression. RESULTS Overweight subjects had better performance on a reasoning task (β = 0.23, standard error (SE) = 0.11, P = .04) and the Useful Field of View (UFOV) measure (β = −39.46, SE = 12.95, P = .002), a test of visuospatial speed of processing, after controlling for age, sex, race, years of education, intervention group, study site, and cardiovascular risk factors. Subjects with class I (BMI 30.0–34.9 kg/m2) and class II (BMI>35.0 kg/m2) obesity had better UFOV measure scores (β = −38.98, SE = 14.77, P = .008; β = −35.75, SE = 17.65, and P = .04, respectively) in the multivariate model than normal-weight subjects. The relationships between BMI and individual cognitive domains were nonlinear. CONCLUSION Overweight participants had better cognitive performance in terms of reasoning and visuospatial speed of processing than normal-weight participants. Obesity was associated with better performance in visuospatial speed of processing than normal weight. The relationship between BMI and cognitive function should be studied prospectively. PMID:16420204

  17. Volumetric correlates of memory and executive function in normal elderly, mild cognitive impairment and Alzheimer’s disease

    Science.gov (United States)

    Duarte, Audrey; Hayasaka, Satoru; Du, Antao; Schuff, Norbert; Jahng, Geon-Ho; Kramer, Joel; Miller, Bruce; Weiner, Michael

    2007-01-01

    In Alzheimer’s disease (AD), atrophy negatively impacts cognition while in healthy adults, inverse relationships between brain volume and cognition may occur. We investigated correlations between gray matter volume and cognition in elderly controls, AD and mild cognitive impairment (MCI) patients with memory and executive deficits. AD demonstrated substantial loss in temporal, parietal and frontal regions while MCI exhibited moderate volume loss in temporal and frontal regions. In controls, memory and executive function were negatively correlated with frontal regions, while in AD, memory was positively correlated with temporal and frontal gyri, and executive function with frontal regions. The combination of the two patterns may explain the lack of correlations in MCI. Developmental versus pathological contributions to these relationships are discussed. PMID:16904823

  18. Direct assignment of molecular vibrations via normal mode analysis of the neutron dynamic pair distribution function technique

    International Nuclear Information System (INIS)

    Fry-Petit, A. M.; Sheckelton, J. P.; McQueen, T. M.; Rebola, A. F.; Fennie, C. J.; Mourigal, M.; Valentine, M.; Drichko, N.

    2015-01-01

    For over a century, vibrational spectroscopy has enhanced the study of materials. Yet, assignment of particular molecular motions to vibrational excitations has relied on indirect methods. Here, we demonstrate that applying group theoretical methods to the dynamic pair distribution function analysis of neutron scattering data provides direct access to the individual atomic displacements responsible for these excitations. Applied to the molecule-based frustrated magnet with a potential magnetic valence-bond state, LiZn 2 Mo 3 O 8 , this approach allows direct assignment of the constrained rotational mode of Mo 3 O 13 clusters and internal modes of MoO 6 polyhedra. We anticipate that coupling this well known data analysis technique with dynamic pair distribution function analysis will have broad application in connecting structural dynamics to physical properties in a wide range of molecular and solid state systems

  19. Dystrophin is required for the normal function of the cardio-protective K(ATP channel in cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Laura Graciotti

    Full Text Available Duchenne and Becker muscular dystrophy patients often develop a cardiomyopathy for which the pathogenesis is still unknown. We have employed the murine animal model of Duchenne muscular dystrophy (mdx, which develops a cardiomyopathy that includes some characteristics of the human disease, to study the molecular basis of this pathology. Here we show that the mdx mouse heart has defects consistent with alteration in compounds that regulate energy homeostasis including a marked decrease in creatine-phosphate (PC. In addition, the mdx heart is more susceptible to anoxia than controls. Since the cardio-protective ATP sensitive potassium channel (K(ATP complex and PC have been shown to interact we investigated whether deficits in PC levels correlate with other molecular events including K(ATP ion channel complex presence, its functionality and interaction with dystrophin. We found that this channel complex is present in the dystrophic cardiac cell membrane but its ability to sense a drop in the intracellular ATP concentration and consequently open is compromised by the absence of dystrophin. We further demonstrate that the creatine kinase muscle isoform (CKm is displaced from the plasma membrane of the mdx cardiac cells. Considering that CKm is a determinant of K(ATP channel complex function we hypothesize that dystrophin acts as a scaffolding protein organizing the K(ATP channel complex and the enzymes necessary for its correct functioning. Therefore, the lack of proper functioning of the cardio-protective K(ATP system in the mdx cardiomyocytes may be part of the mechanism contributing to development of cardiac disease in dystrophic patients.

  20. Normalization of aberrant resting state functional connectivity in fibromyalgia patients following a three month physical exercise therapy

    OpenAIRE

    P. Flodin; S. Martinsen; K. Mannerkorpi; M. Löfgren; I. Bileviciute-Ljungar; E. Kosek; P. Fransson

    2015-01-01

    Physical exercise is one of the most efficient interventions to mitigate chronic pain symptoms in fibromyalgia (FM). However, little is known about the neurophysiological mechanisms mediating these effects. In this study we investigated resting-state connectivity using functional magnetic resonance imaging (fMRI) before and after a 15 week standardized exercise program supervised by physical therapists. Our aim was to gain an understanding of how physical exercise influences previously shown ...

  1. Effect of Ferula assa-foetida oleo-gum-resin on renal function in normal Wistar rats

    Directory of Open Access Journals (Sweden)

    S M Bagheri

    2016-01-01

    Full Text Available In traditional Iranian medicine, asafoetida, an oleo-gum-resin obtained from the roots of Ferula assa-foetida, has been prescribed as a diuretic. This study was undertaken to investigate the diuretic effect of asafoetida in normal rats. Asafoetida was administered orally at the doses of 25 and 50 mg/kg and furosemide (10 mg/kg, intraperitoneal was used as positive control. The diuretic effect was evaluated by measuring urine volume and sodium, potassium, urea, and creatinine content in urine and serum. Urine volume, excretion of sodium, and potassium were significantly increased by asafoetida as compared to the control group. A significant increase in creatinine clearance was observed in the groups treated with asafoetida at the doses of 25 and 50 mg/kg (P < 0.05. We conclude that asafoetida induced a diuretic effect comparable to that produced by the reference diuretic furosemide. This study provides a quantitative basis for explaining the folkloric use of asafoetida as a diuretic agent.

  2. Early Infantile Epileptic Encephalopathy in an STXBP1 Patient with Lactic Acidemia and Normal Mitochondrial Respiratory Chain Function

    Directory of Open Access Journals (Sweden)

    Dong Li

    2016-01-01

    Full Text Available A wide range of clinical findings have been associated with mutations in Syntaxin Binding Protein 1 (STXBP1, including multiple forms of epilepsy, nonsyndromic intellectual disability, and movement disorders. STXBP1 mutations have recently been associated with mitochondrial pathology, although it remains unclear if this phenotype is a part of the core feature for this gene disorder. We report a 7-year-old boy who presented for diagnostic evaluation of intractable epilepsy, episodic ataxia, resting tremor, and speech regression following a period of apparently normal early development. Mild lactic acidemia was detected on one occasion at the time of an intercurrent illness. Due to the concern for mitochondrial disease, ophthalmologic evaluation was performed that revealed bilateral midperiphery pigmentary mottling. Optical coherence tomography (OCT testing demonstrated a bilaterally thickened ganglion cell layer in the perifovea. Skeletal muscle biopsy analysis showed no mitochondrial abnormalities or respiratory chain dysfunction. Exome sequencing identified a de novo c.1651C>T (p.R551C mutation in STXBP1. Although mitochondrial dysfunction has been reported in some individuals, our proband had only mild lactic acidemia and no skeletal muscle tissue evidence of mitochondrial disease pathology. Thus, mitochondrial dysfunction is not an obligate feature of STXBP1 disease.

  3. Amygdalo-cortical sprouting continues into early adulthood: implications for the development of normal and abnormal function during adolescence.

    Science.gov (United States)

    Cunningham, Miles Gregory; Bhattacharyya, Sujoy; Benes, Francine Mary

    2002-11-11

    Adolescence is a critical stage for the development of emotional maturity and diverse forms of psychopathology. The posterior basolateral nucleus of the amygdala is known to mediate fear and anxiety and is important in assigning emotional valence to cognitive processes. The medial prefrontal cortex, a homologue of the human anterior cingulate cortex, mediates emotional, attentional, and motivational behaviors at the cortical level. We postulate that the development of connectivity between these two corticolimbic regions contributes to an enhanced integration of emotion and cognition during the postnatal period. In order to characterize the development of this relay, injections of the anterograde tracer biocytin were stereotaxically placed within the posterior basolateral nucleus of the amygdala of rats at successive postnatal time points (postnatal days 6-120). Labeled fibers in the medial prefrontal cortex were evaluated using a combination of brightfield, confocal, and electron microscopy. We found that the density of labeled fibers originating from the posterior basolateral nucleus shows a sharp curvilinear increase within layers II and V of the anterior cingulate cortex and the infralimbic subdivisions of medial prefrontal cortex during the late postweanling period. This increase was paralleled by a linear rise in the number of axospinous and axodendritic synapses present in the neuropil. Based on these results, we propose that late maturation of amygdalo-cortical connectivity may provide an anatomical basis for the development and integration of normal and possibly abnormal emotional behavior during adolescence and early adulthood. Copyright 2002 Wiley-Liss, Inc.

  4. Normal value of functional parameters in gated myocardial perfusion SPECT in patients with low risk of coronary artery disease: emory cardiac tool box program

    Energy Technology Data Exchange (ETDEWEB)

    Kang, D. Y.; Kim, M. H.; Kim, Y. D.; Kim, D. K. [Donga University College of Medicine, Busan (Korea, Republic of)

    2002-07-01

    Absolute value of the functional data of gated myocardial perfusion SPECT is necessary to determine that individual patient is normal or not. Tc-99m MIBI gated myocardial perfusion SPECT was performed using emory cardiac tool box program. All patients (M:F=15:36, age 64{+-}10 yrs) showed normal myocardial perfusion. The patients with following characteristics were excluded; previous angina or MI, ECG change with Q wave or ST-T change, diabetes mellitus, hypercholesterolemia, typical chest pain and hypertension. In all patients, myocardial mass is 117{+-}23 g in stress gated SPECT, 106{+-}22 g in stress ungated SPECT and 102{+-}21 g in rest ungated SPECT. EDV is 90{+-}28 ml, ESV 26{+-}20 ml, SV 66{+-}21 ml, EF 73{+-}10 % and TID 1.06{+-}0.14. Myocardial mass in rest ungated SPECT is significantly different between men and women (p=0.025). Myocardial mass is significantly different between stress gated SPECT and stress ungated SPECT (p=0.000), and between stress ungated SPECT and rest ungated SPECT (p=0.003). We provide normal value of functional parameters to determine the abnormality of individual patients in patients with low risk of coronary artery disease.

  5. Capability of differentiating smokers with normal pulmonary function from COPD patients: a comparison of CT pulmonary volume analysis and MR perfusion imaging

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Li; Xia, Yi; Guan, Yu; Yu, Hong; Liu, Shi-yuan [Changzheng Hospital of the Second Military Medical University, Department of Radiology, Shanghai (China); Zhang, Tie-feng; Li, Bing [Changzheng Hospital of the Second Military Medical University, Department of Respiration Medicine, Shanghai (China)

    2013-05-15

    To compare CT volume analysis with MR perfusion imaging in differentiating smokers with normal pulmonary function (controls) from COPD patients. Sixty-two COPD patients and 17 controls were included. The total lung volume (TLV), total emphysema volume (TEV) and emphysema index (EI) were quantified by CT. MR perfusion evaluated positive enhancement integral (PEI), maximum slope of increase (MSI), maximum slope of decrease (MSD), signal enhancement ratio (SER) and signal intensity ratio (R{sub SI}) of perfusion defects to normal lung. There were 19 class I, 17 class II, 14 class III and 12 class IV COPD patients. No differences were observed in TLV, TEV and EI between control and class I COPD. The control was different from class II, III and IV COPD in TEV and EI. The control was different from each class of COPD in R{sub SI,} MSI, PEI and MSD. Differences were found in R{sub SI} between class I and III, I and IV, and II and IV COPD. Amongst controls, MR detected perfusion defects more frequently than CT detected emphysema. Compared with CT, MR perfusion imaging shows higher potential to distinguish controls from mild COPD and appears more sensitive in identifying abnormalities amongst smokers with normal pulmonary function (controls). (orig.)

  6. Plasma Renalase is Not Associated with Blood Pressure and Brachial-Ankle Pulse Wave Velocity in Chinese Adults With Normal Renal Function

    Directory of Open Access Journals (Sweden)

    Yang Wang

    2016-11-01

    Full Text Available Background/Aims: This study aimed to investigate the association of renalase with blood pressure (BP and brachial-ankle pulse wave velocity (baPWV in order to better understand the role of renalase in the pathogenesis of hypertension and atherosclerosis. Methods: A total of 344 subjects with normal kidney function were recruited from our previously established cohort in Shaanxi Province, China. They were divided into the normotensive (NT and hypertensive (HT groups or high baPWV and normal baPWV on the basis of BP levels or baPWV measured with an automatic waveform analyzer. Plasma renalase was determined through an enzyme-linked immunosorbent assay. Results: Plasma renalase did not significantly differ between HT and NT groups (3.71 ± 0.69 µg/mL vs. 3.72 ± 0.73 μg/mL, P = 0.905 and between subjects with and without high baPWV (3.67 ± 0.66 µg/mL vs. 3.73 ± 0.74 µg/mL, P = 0.505. However, baPWV was significantly higher in the HT group than in the NT group (1460.4 ± 236.7 vs. 1240.7 ± 174.5 cm/s, P Conclusion: Plasma renalase may not be associated with BP and baPWV in Chinese subjects with normal renal function.

  7. Capability of differentiating smokers with normal pulmonary function from COPD patients: a comparison of CT pulmonary volume analysis and MR perfusion imaging

    International Nuclear Information System (INIS)

    Fan, Li; Xia, Yi; Guan, Yu; Yu, Hong; Liu, Shi-yuan; Zhang, Tie-feng; Li, Bing

    2013-01-01

    To compare CT volume analysis with MR perfusion imaging in differentiating smokers with normal pulmonary function (controls) from COPD patients. Sixty-two COPD patients and 17 controls were included. The total lung volume (TLV), total emphysema volume (TEV) and emphysema index (EI) were quantified by CT. MR perfusion evaluated positive enhancement integral (PEI), maximum slope of increase (MSI), maximum slope of decrease (MSD), signal enhancement ratio (SER) and signal intensity ratio (R SI ) of perfusion defects to normal lung. There were 19 class I, 17 class II, 14 class III and 12 class IV COPD patients. No differences were observed in TLV, TEV and EI between control and class I COPD. The control was different from class II, III and IV COPD in TEV and EI. The control was different from each class of COPD in R SI, MSI, PEI and MSD. Differences were found in R SI between class I and III, I and IV, and II and IV COPD. Amongst controls, MR detected perfusion defects more frequently than CT detected emphysema. Compared with CT, MR perfusion imaging shows higher potential to distinguish controls from mild COPD and appears more sensitive in identifying abnormalities amongst smokers with normal pulmonary function (controls). (orig.)

  8. Producing Conditional Mutants for Studying Plant Microtubule Function

    Energy Technology Data Exchange (ETDEWEB)

    Richard Cyr

    2009-09-29

    The cytoskeleton, and in particular its microtubule component, participates in several processes that directly affect growth and development in higher plants. Normal cytoskeletal function requires the precise and orderly arrangement of microtubules into several cell cycle and developmentally specific arrays. One of these, the cortical array, is notable for its role in directing the deposition of cellulose (the most prominent polymer in the biosphere). An understanding of how these arrays form, and the molecular interactions that contribute to their function, is incomplete. To gain a better understanding of how microtubules work, we have been working to characterize mutants in critical cytoskeletal genes. This characterization is being carried out at the subcellular level using vital microtubule gene constructs. In the last year of funding colleagues have discovered that gamma-tubulin complexes form along the lengths of cortical microtubules where they act to spawn new microtubules at a characteristic 40 deg angle. This finding complements nicely the finding from our lab (which was funded by the DOE) showing that microtubule encounters are angle dependent; high angles encounters results in catastrophic collisions while low angle encounters result in favorable zippering. The finding of a 40 deg spawn of new microtubules from extant microtubule, together with aforementioned rules of encounters, insures favorable co-alignment in the array. I was invited to write a New and Views essay on this topic and a PDF is attached (News and Views policy does not permit funding acknowledgments and so I was not allowed to acknowledge support from the DOE).

  9. The Effects of a Normal Rate versus a Slow Intervalled Rate of Oral Nutrient Intake and Intravenous Low Rate Macronutrient Application on Psychophysical Function – Two Pilot Studies

    Directory of Open Access Journals (Sweden)

    Melanie Y. Denzer-Lippmann

    2017-06-01

    Full Text Available Stomach distension and energy per time are factors influencing satiety. Moreover, different rates of nutrient intake induce different stomach distension. The goal of our studies was to elucidate the influence of different oral rates of nutrient intake (normal rate versus slow intervalled rate; study I and intravenous low rate macronutrient application (protein, carbohydrate, fat or placebo (study II on psychophysical function. The pilot studies investigated the effects of 1 study I: a mixed nutrient solution (1/3 protein, 1/3 fat, 1/3 carbohydrates 2 study II: intravenous macronutrient infusions (protein, carbohydrate, fat or placebo on psychophysical function (mood, hunger, food craving, alertness, smell intensity ratings and hedonic ratings in human subjects. In study I 10 male subjects (age range: 21–30 years completed the study protocol participating in both test conditions and in study II 20 male subjects (age range: 19–41 years completed the study protocol participating in all test conditions. Additionally, metabolic function was analyzed and cognitive and olfactory tests were conducted twice starting 100 min before the beginning of the intervention and 240 min after. Psychophysical (mood, hunger, fat-, protein-, carbohydrate-, sweets- and vegetable-craving, alertness and metabolic function tests were performed seven times on each examination day. Greater effects on hunger and food cravings were observed for normal rate of intake compared to slow intervalled rate of intake and intravenous low rate macronutrient application. Our findings potentially confirm that volume of the food ingested and a higher rate of energy per time contribute to satiety during normal rate of food intake, while slow intervalled rate of food intake and intravenous low rate macronutrient application showed no effects on satiation. Our results motivate the view that a certain amount of volume of the food ingested and a certain energy per time ratio are necessary

  10. Birkhoff normalization

    NARCIS (Netherlands)

    Broer, H.; Hoveijn, I.; Lunter, G.; Vegter, G.

    2003-01-01

    The Birkhoff normal form procedure is a widely used tool for approximating a Hamiltonian systems by a simpler one. This chapter starts out with an introduction to Hamiltonian mechanics, followed by an explanation of the Birkhoff normal form procedure. Finally we discuss several algorithms for

  11. Analysis of renal blood flow and renal volume in normal fetuses and in fetuses with a solitary functioning kidney.

    Science.gov (United States)

    Hindryckx, An; Raaijmakers, Anke; Levtchenko, Elena; Allegaert, Karel; De Catte, Luc

    2017-12-01

    To evaluate renal blood flow and renal volume for the prediction of postnatal renal function in fetuses with solitary functioning kidney (SFK). Seventy-four SFK fetuses (unilateral renal agenesis [12], multicystic dysplastic kidney [36], and severe renal dysplasia [26]) were compared with 58 healthy fetuses. Peak systolic velocity (PSV), pulsatility index (PI), and resistance index (RI) of the renal artery (RA) were measured; 2D and 3D (VOCAL) volumes were calculated. Renal length and glomerular filtration rate (GFR) were obtained in SFK children (2 years). Compared with the control group, the PSV RA was significantly lower in nonfunctioning kidneys and significantly higher in SFK. Volume measurements indicated a significantly larger volume of SFK compared with healthy kidneys. All but 4 children had GFR above 70 mL/min/1.73 m 2 , and compensatory hypertrophy was present in 69% at 2 years. PSV RA and SFK volume correlated with postnatal renal hypertrophy. No correlation between prenatal and postnatal SFK volume and GFR at 2 years was demonstrated. Low PSV RA might have a predictive value for diagnosing a nonfunctioning kidney in fetuses with a SFK. We demonstrated a higher PSV RA and larger renal volume in the SFK compared with healthy kidneys. © 2017 John Wiley & Sons, Ltd.

  12. Normal p21Ras/MAP kinase pathway expression and function in PBMC from patients with polycystic ovary disease.

    Science.gov (United States)

    Buchs, A; Chagag, P; Weiss, M; Kish, E; Levinson, R; Aharoni, D; Rapoport, M J

    2004-04-01

    Polycystic ovary disease (PCOD) is associated with insulin resistance and increased prevalence of type II diabetes mellitus (T2DM). The p21Ras/MAP kinase is a major intracellular signaling pathway mediating insulin signaling in insulin responsive tissues. The expression, regulation and function of the p21Ras/MAP kinase pathway in PCOD patients were examined. Peripheral blood mononuclear cells (PBMC) were isolated from ten patients with PCOD and ten controls. The expression of p21Ras and its regulatory proteins; hSOS1 and p120GAP were studied. The basal and phytohemaglutinin (PHA) or insulin stimulated phosphorylation of MAP kinase was determined. Expression of p21Ras, and its regulatory proteins hSOS1 and p120GAP were similar in PCOD patients and controls. Basal, PHA and insulin stimulated phosphorylation of MAP kinase, were also comparable in the two groups as well as their PBMC proliferative response. These data indicate that the expression and overall function of the p21Ras/MAP kinase pathway remain intact in non-diabetic patients with PCOD.

  13. Location of and post-mortem changes in some cytoskeletal proteins in pork and cod muscle

    DEFF Research Database (Denmark)

    Morrison, E.H.; Bremner, Allan; Purslow, P.P.

    2000-01-01

    The cytoskeletal proteins actin, nebulin, spectrin, desmin, vinculin and talin were labelled immunohistochemically in sections of muscle from commercially available pigs and cod (Gadus morhua) taken pre-rigor and from samples stored for several days. Actin, nebulin and spectrin gave similar...... labelling patterns in both pork and cod muscle which remained the same in stored samples. Desmin was intensely labelled at the cell boundaries and within the body of the cells in both pork and cod in the initial and the stored samples. Vinculin was readily labelled in pork muscle but showed only diffuse...... labelling in fish. Labelling for talin in pork muscle was intense at the sarcolemma but was not present in samples stored for 4 days. In contrast, the label for talin was concentrated at the myotendinous junction of the cod muscle throughout the storage period. These are the first reports of the detection...

  14. Effects of cathodal trans-spinal direct current stimulation on lower urinary tract function in normal and spinal cord injury mice with overactive bladder

    Science.gov (United States)

    Ahmed, Zaghloul

    2017-10-01

    Objective. Lower urinary tract (LUT) dysfunction is a monumental problem affecting quality of life following neurotrauma, such as spinal cord injury (SCI). Proper function of the bladder and its associated structures depends on coordinated activity of the neuronal circuitry in the spinal cord and brain. Disconnection between the spinal and brain centers controlling the LUT causes fundamental changes in the mechanisms involved in the micturition and storage reflexes. We investigated the effects of cathodal trans-spinal direct current stimulation (c-tsDCS) of the lumbosacral spine on bladder and external urinary sphincter (EUS) functions. Approach. We used cystometry and electromyography (EMG), in mice with and without SCI. Main results. c-tsDCS caused initiation of the micturition reflex in urethane-anesthetized normal mice with depressed micturition reflexes. This effect was associated with normalized EUS-EMG activity. Moreover, in urethane-anesthetized normal mice with expressed micturition reflexes, c-tsDCS increased the firing frequency, amplitude, and duration of EUS-EMG activity. These effects were associated with increased maximum intravesical pressure (P max) and intercontraction interval (ICI). In conscious normal animals, c-tsDCS caused significant increases in P max, ICI, threshold pressure (P thres), baseline pressure (P base), and number and amplitude of non-voiding contractions (NVCnumb and P im, respectively). In conscious mice with severe contusive SCI and overactive bladder, c-tsDCS increased P max, ICI, and P thres, but decreased P base, NVCnumb, and P im. c-tsDCS reduced the detrusor-overactivity/cystometry ratio, which is a measure of bladder overactivity associated with renal deterioration. Significance. These results indicate that c-tsDCS induces robust modulation of the lumbosacral spinal-cord circuitry that controls the LUT.

  15. Comparison of range of motion and function of subjects with reverse anatomy Bayley-Walker shoulder replacement with those of normal subjects.

    Science.gov (United States)

    Masjedi, Milad; Lovell, Cara; Johnson, Garth R

    2011-12-01

    Patients with rotator cuff tear and degenerative shoulder joint disease commonly experience severe pain and reduced performance during activities of daily living. A popular way to treat these patients is by means of reverse anatomy shoulder prosthesis. Studying the kinematics of subjects with reverse anatomy implant would be useful in order to gain knowledge about functionality of different designs. It is hypothesized that the kinematics of these subjects, in the absence of rotator cuff muscles, differs from that of normal subjects. In this study the upper limb kinematics of 12 subjects with a Bayley-Walker reverse anatomy shoulder prosthesis while performing tasks common in everyday activities and those that represent the range of motion was analyzed and compared to that of 12 normal subjects. Each patient also completed an Oxford Shoulder Score. Substantial reduction in the Bayley-Walker subjects' ranges of motion was observed compared to normal subjects. The mean abduction angle decreased from 109° (±20) for normal subjects to 64° (±25). A similar trend was observed during flexion and axial rotation tasks. Furthermore, the normal group showed less variable ranges of motion performing the standard tasks, whereas for the prosthetic group this varied greatly, which is likely to be dependent on muscle strength. Although the decreased range of motion was prominent, subjects were able to complete most of the tasks by compensating with their elbow and trunk. The most challenging task for Bayley-Walker subjects was lifting an object to head height. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Distribution of cytoskeletal proteins, integrins, leukocyte adhesion molecules and extracellular matrix proteins in plastic-embedded human and rat kidneys

    NARCIS (Netherlands)

    van Goor, H; Coers, W; van der Horst, MLC; Suurmeijer, AJH

    2001-01-01

    OBJECTIVE: To study the distribution of cytoskeletal proteins (actin, alpha -actinin, vinculin, beta -tubulin, keratin, vimentin, desmin), adhesion molecules for cell-matrix interations (very later antigens [VLA1-6], beta1, beta2 [CD18], vitronectin receptor [alphav beta3], CD 11b), leukocyte

  17. Magnolol inhibits migration of vascular smooth muscle cells via cytoskeletal remodeling pathway to attenuate neointima formation

    International Nuclear Information System (INIS)

    Karki, Rajendra; Kim, Seong-Bin; Kim, Dong-Wook

    2013-01-01

    Background: Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. The objective of this study was to investigate the effect of magnolol on VSMC migration. Methods: The proteolytic activity of matrix metalloproteinases (MMPs) in tumor necrosis factor alpha (TNF-α) stimulated VSMCs was performed by gelatin zymography. VSMC migration was assessed by wound healing and Boyden chamber methods. Collagen induced VSMC adhesion was determined by spectrofluorimeter and stress fibers formation was evaluated by fluorescence microscope. The expression of signaling molecules involved in stress fibers formation was determined by western blot. The phosphorylation of myosin light chain (MLC20) was determined by urea-glycerol polyacrylamide gel electrophoresis. Immunohistochemistry was performed to determine the expression of β1-integrin and collagen type I in the injured carotid arteries of rats on day 35 after vascular injury. Results: VSMC migration was strongly inhibited by magnolol without affecting MMPs expression. Also, magnolol inhibited β1-integrin expression, FAK phosphorylation and RhoA and Cdc42 activation to inhibit the collagen induced stress fibers formation. Moreover, magnolol inhibited the phosphorylation of MLC20. Our in vivo results showed that magnolol inhibited β1-integrin expression, collagen type I deposition and FAK phosphorylation in injured carotid arteries without affecting MMP-2 activity. Conclusions: Magnolol inhibited VSMC migration via inhibition of cytoskeletal remodeling pathway to attenuate neointima formation. General significance: This study provides a rationale for further evaluation of magnolol for the management of atherosclerosis and restenosis. - Highlights: • Magnolol strongly inhibited migration of VSMCs. • Magnolol inhibited stress fibers formation. • MLC20 phosphorylation was also inhibited by magnolol. • Anti

  18. Expression analysis of cellulose synthase and main cytoskeletal protein genes in flax (Linum usitatissimum L.).

    Science.gov (United States)

    Galinousky, Dmitry; Padvitski, Tsimafei; Bayer, Galina; Pirko, Yaroslav; Pydiura, Nikolay; Anisimova, Natallia; Nikitinskaya, Tatyana; Khotyleva, Liubov; Yemets, Alla; Kilchevsky, Aleksandr; Blume, Yaroslav

    2017-08-09

    Fiber flax is an important source of natural fiber and a comprehensive model for the plant fiber biogenesis studies. Cellulose-synthase (CesA) and cytoskeletal genes are known to be important for the cell wall biogenesis in general and for the biogenesis of flax fibers in particular. Currently, knowledge about activity of these genes during the plant growth is limited. In this study, we have investigated flax fiber biogenesis by measuring expression of CesA and cytoskeletal genes at two stages of the flax development (seedlings and stems at the rapid growth stage) in several flax subspecies (elongatum, mediterraneum, crepitans). RT-qPCR has been used to quantify the expression of LusСesA1, LusСesA4, LusСesA7, LusСesA6, Actin, and α-Tubulin genes in plant samples. We report that CesA genes responsible for the secondary cell wall synthesis (LusCesA4, LusCesA7) have different expression pattern compared with CesA genes responsible for the primary cell wall synthesis (LusCesA1, LusCesA6): an average expression of LusCesA4 and LusCesA7 genes is relatively high in seedlings and further increases in stems at the rapid growth stage, whereas an average expression of LusCesA1 and LusCesA6 genes decreases. Interestingly, LusCesA1 is the only studied gene with different expression dynamics between the flax subspecies: its expression decreases by 5.2-10.7 folds in elongatum and mediterraneum but does not change in crepitans subspecies when the rapid growth stage and seedlings are compared. The expression of cytoskeleton genes (coding actin and α-tubulin) is relatively stable and significantly higher than the expression of cellulose-synthase genes in all the studied samples. © 2017 International Federation for Cell Biology.

  19. Quinolinic acid induces disrupts cytoskeletal homeostasis in striatal neurons. Protective role of astrocyte-neuron interaction.

    Science.gov (United States)

    Pierozan, Paula; Ferreira, Fernanda; de Lima, Bárbara Ortiz; Pessoa-Pureur, Regina

    2015-02-01

    Quinolinic acid (QUIN) is an endogenous metabolite of the kynurenine pathway involved in several neurological disorders. Among the several mechanisms involved in QUIN-mediated toxicity, disruption of the cytoskeleton has been demonstrated in striatally injected rats and in striatal slices. The present work searched for the actions of QUIN in primary striatal neurons. Neurons exposed to 10 µM QUIN presented hyperphosphorylated neurofilament (NF) subunits (NFL, NFM, and NFH). Hyperphosphorylation was abrogated in the presence of protein kinase A and protein kinase C inhibitors H89 (20 μM) and staurosporine (10 nM), respectively, as well as by specific antagonists to N-methyl-D-aspartate (50 µM DL-AP5) and metabotropic glutamate receptor 1 (100 µM MPEP). Also, intra- and extracellular Ca(2+) chelators (10 µM BAPTA-AM and 1 mM EGTA, respectively) and Ca(2+) influx through L-type voltage-dependent Ca(2+) channel (10 µM verapamil) are implicated in QUIN-mediated effects. Cells immunostained for the neuronal markers βIII-tubulin and microtubule-associated protein 2 showed altered neurite/neuron ratios and neurite outgrowth. NF hyperphosphorylation and morphological alterations were totally prevented by conditioned medium from QUIN-treated astrocytes. Cocultured astrocytes and neurons interacted with one another reciprocally, protecting them against QUIN injury. Cocultured cells preserved their cytoskeletal organization and cell morphology together with unaltered activity of the phosphorylating system associated with the cytoskeleton. This article describes cytoskeletal disruption as one of the most relevant actions of QUIN toxicity in striatal neurons in culture with soluble factors secreted by astrocytes, with neuron-astrocyte interaction playing a role in neuroprotection. © 2014 Wiley Periodicals, Inc.

  20. Magnolol inhibits migration of vascular smooth muscle cells via cytoskeletal remodeling pathway to attenuate neointima formation

    Energy Technology Data Exchange (ETDEWEB)

    Karki, Rajendra [Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City (United States); Department of Oriental Medicine Resources, Mokpo National University (Korea, Republic of); Kim, Seong-Bin [Jeollanamdo Development Institute for Korean Traditional Medicine, Jangheung gun, Jeollanamdo (Korea, Republic of); Kim, Dong-Wook, E-mail: dbkim@mokpo.ac.kr [Department of Oriental Medicine Resources, Mokpo National University (Korea, Republic of)

    2013-12-10

    Background: Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. The objective of this study was to investigate the effect of magnolol on VSMC migration. Methods: The proteolytic activity of matrix metalloproteinases (MMPs) in tumor necrosis factor alpha (TNF-α) stimulated VSMCs was performed by gelatin zymography. VSMC migration was assessed by wound healing and Boyden chamber methods. Collagen induced VSMC adhesion was determined by spectrofluorimeter and stress fibers formation was evaluated by fluorescence microscope. The expression of signaling molecules involved in stress fibers formation was determined by western blot. The phosphorylation of myosin light chain (MLC20) was determined by urea-glycerol polyacrylamide gel electrophoresis. Immunohistochemistry was performed to determine the expression of β1-integrin and collagen type I in the injured carotid arteries of rats on day 35 after vascular injury. Results: VSMC migration was strongly inhibited by magnolol without affecting MMPs expression. Also, magnolol inhibited β1-integrin expression, FAK phosphorylation and RhoA and Cdc42 activation to inhibit the collagen induced stress fibers formation. Moreover, magnolol inhibited the phosphorylation of MLC20. Our in vivo results showed that magnolol inhibited β1-integrin expression, collagen type I deposition and FAK phosphorylation in injured carotid arteries without affecting MMP-2 activity. Conclusions: Magnolol inhibited VSMC migration via inhibition of cytoskeletal remodeling pathway to attenuate neointima formation. General significance: This study provides a rationale for further evaluation of magnolol for the management of atherosclerosis and restenosis. - Highlights: • Magnolol strongly inhibited migration of VSMCs. • Magnolol inhibited stress fibers formation. • MLC20 phosphorylation was also inhibited by magnolol. • Anti

  1. Normal Families of A Kind of Holomorphic Functions Concerning Derivatives%涉及导数的一类全纯函数的正规族

    Institute of Scientific and Technical Information of China (English)

    姜云波

    2011-01-01

    主要使用Zalcman引理来研究全纯函数的正规族,得到了如下的结论:令F为|z|<1内的一族全纯函数,n是一个正整数,a,b是两个复数且满足a≠0,∞,b≠∞.若F满足:Ⅰ)(A)f∈F,如f有零点,则f的零点重级大于等于3;和Ⅱ)当n≥4时,对F的每一对函数G和日,G″-aGn1与H″-aHn分担b.则F在|z|<1内正规.%In this paper,we mainly use Zalcman lemna to investigate normal families of holomorphic functions, and gets the following results: let (F) e a family of holomorphic functions in |z| < 1,n is a positive integer, a, b are two complex numbers and satisfies α≠0, ∞, b≠ ∞, If (F) satisfies: (Ⅰ) for (V)f ∈(F),if f has zeros, then the multiplicity of zeros of f is greater than or equal to 3; and (Ⅱ)when n ≥ 4,for every pair of functions G and H belong to (F), G11 - aGn and H11 - aHn share b. then (F) is normal in |z| < 1.

  2. Measurement of intestinal progression of a meal and its residues in normal subjects and patients with functional diarrhoea by a dual isotope technique

    Energy Technology Data Exchange (ETDEWEB)

    Jian, R; Najean, Y; Bernier, J J [Hopital Saint-Lazare, 75 - Paris (France). Service de Medecine; Hopital Saint-Louis, 75 - Paris (France))

    1984-07-01

    A new double isotopic method was used to measure the gastrointestinal progression of a meal in nine healthy subjects and seven patients with functional diarrhoea. 51 Chromium chloride (colonic marker) was ingested eight hours before the beginning of the scintigraphic study so that it was by then located in the colon at that time. A second marker, 99m Technetium sulphur colloid labelled the meal. Scintigraphic images were taken before and after the meal for two hours, detecting simultaneously the two isotopes. In the 51Cr window right colon was localised and intracolonic propulsion was studied; and in the 99m Tc window gastric emptying and colon filling of the meal marker was quantified. A propulsive gastrocolic reflex was evidenced in five of the seven patients with functional diarrhoea but in none of the normal subjects. Unabsorbed residues of the meal are propelled rapidly in the ileocaecal region. Small intestinal transit of the meal marker was twice as rapid in patients with functional diarrhoea as in normal subjects.

  3. Foxp3+ Treg expanded from patients with established diabetes reduce Helios expression while retaining normal function compared to healthy individuals.

    Directory of Open Access Journals (Sweden)

    Weiting Du

    Full Text Available Foxp3(+ regulatory T cells (Treg play a crucial role in regulating immune tolerance. The use of Treg to restore immune tolerance is considered an attractive novel approach to inhibit autoimmune disease, including type 1 diabetes (T1D, and to prevent rejection of organ transplants. In view of the goal of developing autologous Treg-based cell therapy for patients with long-term (>15 years T1D, it will be necessary to expand a sufficient amount of functional Treg in vitro in order to study and compare Treg from T1D patients and healthy subjects. Our results have demonstrated that there is a comparable frequency of Treg in the peripheral blood lymphocytes (PBLs of patients with long-term T1D relative to those in healthy subjects; however, Th1 cells, but not Th17 cells, were increased in the T1D patients. Further, more Treg in PBLs from T1D patients than from healthy subjects expressed the CD45RO(+ memory cell phenotype, suggesting they were antigen-experienced cells. After isolation, Treg from both T1D patients and healthy subjects were successfully expanded with high purity. Although there was no difference in Helios expression on Treg in PBLs, in vitro expansion led to fewer Helios-expressing Treg from T1D patients than healthy subjects. While more Th1-like Treg expressing IFN-γ or TNF-α were found in the PBLs of T1D patients than healthy controls, there was no such difference in the expanded Treg. Importantly, expanded Treg from both subject groups were able to suppress autologous or allogeneic CD8(+ effector T cells equally well. Our findings demonstrate that a large number of ex vivo expanded functional Treg can be obtained from long-term T1D patients, although fewer expanded Treg expressed a high level of Helios. Thus, based on the positive outcomes, these potent expanded Treg from diabetic human patients may be useful in treating T1D or preventing islet graft rejection.

  4. Probabilistic Models and Generative Neural Networks: Towards an Unified Framework for Modeling Normal and Impaired Neurocognitive Functions.

    Science.gov (United States)

    Testolin, Alberto; Zorzi, Marco

    2016-01-01

    Connectionist models can be characterized within the more general framework of probabilistic graphical models, which allow to efficiently describe complex statistical distributions involving a large number of interacting variables. This integration allows building more realistic computational models of cognitive functions, which more faithfully reflect the underlying neural mechanisms at the same time providing a useful bridge to higher-level descriptions in terms of Bayesian computations. Here we discuss a powerful class of graphical models that can be implemented as stochastic, generative neural networks. These models overcome many limitations associated with classic connectionist models, for example by exploiting unsupervised learning in hierarchical architectures (deep networks) and by taking into account top-down, predictive processing supported by feedback loops. We review some recent cognitive models based on generative networks, and we point out promising research directions to investigate neuropsychological disorders within this approach. Though further efforts are required in order to fill the gap between structured Bayesian models and more realistic, biophysical models of neuronal dynamics, we argue that generative neural networks have the potential to bridge these levels of analysis, thereby improving our understanding of the neural bases of cognition and of pathologies caused by brain damage.

  5. Transporter function and cyclic AMP turnover in normal colonic mucosa from patients with and without colorectal neoplasia

    Directory of Open Access Journals (Sweden)

    Kleberg Karen

    2012-06-01

    Full Text Available Abstract Background The pathogenesis of colorectal neoplasia is still unresolved but has been associated with alterations in epithelial clearance of xenobiotics and metabolic waste products. The aim of this study was to functionally characterize the transport of cyclic nucleotides in colonic biopsies from patients with and without colorectal neoplasia. Methods Cyclic nucleotides were used as model substrates shared by some OATP- and ABC-transporters, which in part are responsible for clearance of metabolites and xenobiotics from the colonic epithelium. On colonic biopsies from patients with and without colorectal neoplasia, molecular transport was electrophysiologically registered in Ussing-chamber set-ups, mRNA level of selected transporters was quantified by rt-PCR, and subcellular location of transporters was determined by immunohistochemistry. Results Of four cyclic nucleotides, dibuturyl-cAMP induced the largest short circuit current in both patient groups. The induced short circuit current was significantly lower in neoplasia-patients (p = 0.024. The observed altered transport of dibuturyl-cAMP in neoplasia-patients could not be directly translated to an observed increased mRNA expression of OATP4A1 and OATP2B1 in neoplasia patients. All other examined transporters were expressed to similar extents in both patient groups. Conclusions OATP1C1, OATP4A1, OATP4C1 seem to be involved in the excretory system of human colon. ABCC4 is likely to be involved from an endoplasmic-Golgi complex and basolateral location in goblet cells. ABCC5 might be directly involved in the turnover of intracellular cAMP at the basolateral membrane of columnar epithelial cells, while OATP2B1 is indirectly related to the excretory system. Colorectal neoplasia is associated with lower transport or sensitivity to cyclic nucleotides and increased expression of OATP2B1 and OATP4A1 transporters, known to transport PGE2.

  6. Resting-state functional connectivity predicts the strength of hemispheric lateralization for language processing in temporal lobe epilepsy and normals.

    Science.gov (United States)

    Doucet, Gaëlle E; Pustina, Dorian; Skidmore, Christopher; Sharan, Ashwini; Sperling, Michael R; Tracy, Joseph I

    2015-01-01

    In temporal lobe epilepsy (TLE), determining the hemispheric specialization for language before surgery is critical to preserving a patient's cognitive abilities post-surgery. To date, the major techniques utilized are limited by the capacity of patients to efficiently realize the task. We determined whether resting-state functional connectivity (rsFC) is a reliable predictor of language hemispheric dominance in right and left TLE patients, relative to controls. We chose three subregions of the inferior frontal cortex (pars orbitalis, pars triangularis, and pars opercularis) as the seed regions. All participants performed both a verb generation task and a resting-state fMRI procedure. Based on the language task, we computed a laterality index (LI) for the resulting network. This revealed that 96% of the participants were left-hemisphere dominant, although there remained a large degree of variability in the strength of left lateralization. We tested whether LI correlated with rsFC values emerging from each seed. We revealed a set of regions that was specific to each group. Unique correlations involving the epileptic mesial temporal lobe were revealed for the right and left TLE patients, but not for the controls. Importantly, for both TLE groups, the rsFC emerging from a contralateral seed was the most predictive of LI. Overall, our data depict the broad patterns of rsFC that support strong versus weak left hemisphere language laterality. This project provides the first evidence that rsFC data may potentially be used on its own to verify the strength of hemispheric dominance for language in impaired or pathologic populations. © 2014 Wiley Periodicals, Inc.

  7. Neurokinin B is critical for normal timing of sexual maturation but dispensable for adult reproductive function in female mice.

    Science.gov (United States)

    True, Cadence; Nasrin Alam, Sayeda; Cox, Kimberly; Chan, Yee-Ming; Seminara, Stephanie B

    2015-04-01

    Humans carrying mutations in neurokinin B (NKB) or the NKB receptor fail to undergo puberty due to decreased secretion of GnRH. Despite this pubertal delay, many of these patients go on to achieve activation of their hypothalamic-pituitary-gonadal axis in adulthood, a phenomenon termed reversal, indicating that NKB signaling may play a more critical role for the timing of pubertal development than adult reproductive function. NKB receptor-deficient mice are hypogonadotropic but have no defects in the timing of sexual maturation. The current study has performed the first phenotypic evaluation of mice bearing mutations in Tac2, the gene encoding the NKB ligand, to determine whether they have impaired sexual development similar to their human counterparts. Male Tac2-/- mice showed no difference in the timing of sexual maturation or fertility compared with wild-type littermates and were fertile. In contrast, Tac2-/- females had profound delays in sexual maturation, with time to vaginal opening and first estrus occurring significantly later than controls, and initial abnormalities in estrous cycles. However, cycling recovered in adulthood and Tac2-/- females were fertile, although they produced fewer pups per litter. Thus, female Tac2-/- mice parallel humans harboring NKB pathway mutations, with delayed sexual maturation and activation of the reproductive cascade later in life. Moreover, direct comparison of NKB ligand and receptor-deficient females confirmed that only NKB ligand-deficient animals have delayed sexual maturation, suggesting that in the absence of the NKB receptor, NKB may regulate the timing of sexual maturation through other tachykinin receptors.

  8. Normal hematopoiesis and lack of β-catenin activation in osteoblasts of patients and mice harboring Lrp5 gain-of-function mutations.

    Science.gov (United States)

    Galán-Díez, Marta; Isa, Adiba; Ponzetti, Marco; Nielsen, Morten Frost; Kassem, Moustapha; Kousteni, Stavroula

    2016-03-01

    Osteoblasts are emerging regulators of myeloid malignancies since genetic alterations in them, such as constitutive activation of β-catenin, instigate their appearance. The LDL receptor-related protein 5 (LRP5), initially proposed to be a co-receptor for Wnt proteins, in fact favors bone formation by suppressing gut-serotonin synthesis. This function of Lrp5 occurring in the gut is independent of β-catenin activation in osteoblasts. However, it is unknown whether Lrp5 can act directly in osteoblast to influence other functions that require β-catenin signaling, particularly, the deregulation of hematopoiesis and leukemogenic properties of β-catenin activation in osteoblasts, that lead to development of acute myeloid leukemia (AML). Using mice with gain-of-function (GOF) Lrp5 alleles (Lrp5(A214V)) that recapitulate the human high bone mass (HBM) phenotype, as well as patients with the T253I HBM Lrp5 mutation, we show here that Lrp5 GOF mutations in both humans and mice do not activate β-catenin signaling in osteoblasts. Consistent with a lack of β-catenin activation in their osteoblasts, Lrp5(A214V) mice have normal trilinear hematopoiesis. In contrast to leukemic mice with constitutive activation of β-catenin in osteoblasts (Ctnnb1(CAosb)), accumulation of early myeloid progenitors, a characteristic of AML, myeloid-blasts in blood, and segmented neutrophils or dysplastic megakaryocytes in the bone marrow, are not observed in Lrp5(A214V) mice. Likewise, peripheral blood count analysis in HBM patients showed normal hematopoiesis, normal percentage of myeloid cells, and lack of anemia. We conclude that Lrp5 GOF mutations do not activate β-catenin signaling in osteoblasts. As a result, myeloid lineage differentiation is normal in HBM patients and mice. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survi