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Sample records for specifically impairing heme

  1. [Multilingualism and specific language impairment].

    Science.gov (United States)

    Arkkila, Eva; Smolander, Sini; Laasonen, Marja

    2013-01-01

    Specific language impairment is one of the most common developmental disturbances in childhood. With the increase of the foreign language population group an increasing number of children assimilating several languages and causing concern in language development attend clinical examinations. Knowledge of factors underlying the specific language impairment and the specific impairment in general, special features of language development of those learning several languages, as well as the assessment and support of the linguistic skills of a multilingual child is essential. The risk of long-term problems and marginalization is high for children having specific language impairment.

  2. Heme transport and erythropoiesis

    Science.gov (United States)

    Yuan, Xiaojing; Fleming, Mark D.; Hamza, Iqbal

    2013-01-01

    In humans, systemic heme homeostasis is achieved via coordinated regulation of heme synthesis, transport and degradation. Although the heme biosynthesis and degradation pathways have been well characterized, the pathways for heme trafficking and incorporation into hemoproteins remains poorly understood. In the past few years, researchers have exploited genetic, cellular and biochemical tools, to identify heme transporters and, in the process, reveal unexpected functions for this elusive group of proteins. However, given the complexity of heme trafficking pathways, current knowledge of heme transporters is fragmented and sometimes contradictory. This review seeks to focus on recent studies on heme transporters with specific emphasis on their functions during erythropoiesis. PMID:23415705

  3. Specific Language Impairment

    Science.gov (United States)

    ... Some of the tests use interactions between the child and puppets and other toys to focus on specific rules of grammar, especially ... is not treated early, it can affect a child’s performance in school. ... language development. This kind of classroom program might enlist normally ...

  4. Multilingualism and Specific Language Impairment

    OpenAIRE

    Engel de Abreu, Pascale

    2014-01-01

    Is a multilingual education beneficial for children? What are the optimal conditions under which a child can become perfectly multilingual? When should we be concerned about a multilingual child's language skills? What are the signs of Specific Language Impairment in a child who speaks more than one language? Developmental psychologist and Associate Professor in multilingual cognitive development at the University of Luxembourg Pascale Engel de Abreu will address these questions based on what...

  5. Impairment of heme synthesis in myelin as potential trigger of multiple sclerosis.

    Science.gov (United States)

    Morelli, Alessandro; Ravera, Silvia; Calzia, Daniela; Panfoli, Isabella

    2012-06-01

    The pathogenesis of multiple sclerosis (MS), a disease characterized by demyelination and subsequent axonal degeneration, is as yet unknown. Also, the nature of the disease is as yet not established, since doubts have been cast on its autoimmune origin. Genetic and environmental factors have been implied in MS, leading to the idea of an overall multifactorial origin. An unexpected role in energizing the axon has been reported for myelin, supposed to be the site of consumption of most of oxygen in brain. Myelin would be able to perform oxidative phosphorylation to supply the axons with ATP, thanks to the expression therein of mitochondrial F(o)F(1)-ATP synthase, and respiratory chains. Interestingly, myelin expresses the pathway of heme synthesis, hence of cytochromes, that rely on heme group, in turn depending on Fe availability. Poisoning by these pollutants shares the common characteristic to bring about demyelination both in animal models and in man. Carbon monoxide (CO) and lead poisoning which cause functional imbalance of the heme group, as well as of heme synthesis, cause myelin damage. On the other hand, a lack of essential metals such as iron and copper, produces dramatic myelin decrease. Myelin is a primary target, of iron shortage, indicating that in myelin Fe-dependent processes are more active than in other tissues. The predominant spread of MS in industrialized countries where pollution by heavy metals, and CO poisoning is widespread, suggests a relationship among toxic action of metal pollutants and MS. According to the present hypothesis, MS can be primarily triggered by environmental factors acting on a genetic susceptibility, while the immune response may be a consequence of a primary oxidative damage due to reactive oxygen species produced consequently to an imbalance of cytochromes and respiratory chains in the sheath. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Pharmacological Induction of Heme Oxygenase-1 Impairs Nuclear Accumulation of Herpes Simplex Virus Capsids upon Infection

    Directory of Open Access Journals (Sweden)

    Francisco J. Ibáñez

    2017-10-01

    Full Text Available Heme oxygenase-1 (HO-1 is an inducible enzyme that is expressed in response to physical and chemical stresses, such as ultraviolet radiation, hyperthermia, hypoxia, reactive oxygen species (ROS, as well as cytokines, among others. Its activity can be positively modulated by cobalt protoporphyrin (CoPP and negatively by tin protoporphirin (SnPP. Once induced, HO-1 degrades iron-containing heme into ferrous iron (Fe2+, carbon monoxide (CO and biliverdin. Importantly, numerous products of HO-1 are cytoprotective with anti-apoptotic, anti-oxidant, anti-inflammatory, and anti-cancer effects. The products of HO-1 also display antiviral properties against several viruses, such as the human immunodeficiency virus (HIV, influenza, hepatitis B, hepatitis C, and Ebola virus. Here, we sought to assess the effect of modulating HO-1 activity over herpes simplex virus type 2 (HSV-2 infection in epithelial cells and neurons. There are no vaccines against HSV-2 and treatment options are scarce in the immunosuppressed, in which drug-resistant variants emerge. By using HSV strains that encode structural and non-structural forms of the green fluorescent protein (GFP, we found that pharmacological induction of HO-1 activity with CoPP significantly decreases virus plaque formation and the expression of virus-encoded genes in epithelial cells as determined by flow cytometry and western blot assays. CoPP treatment did not affect virus binding to the cell surface or entry into the cytoplasm, but rather downstream events in the virus infection cycle. Furthermore, we observed that treating cells with a CO-releasing molecule (CORM-2 recapitulated some of the anti-HSV effects elicited by CoPP. Taken together, these findings indicate that HO-1 activity interferes with the replication cycle of HSV and that its antiviral effects can be recapitulated by CO.

  7. Diabetes Impairs the Vascular Recruitment of Normal Stem Cells by Oxidant Damage, Reversed by Increases in pAMPK, Heme Oxygenase-1, and Adiponectin

    Science.gov (United States)

    Sambuceti, Gianmario; Morbelli, Silvia; Vanella, Luca; Kusmic, Claudia; Marini, Cecilia; Massollo, Michela; Augeri, Carla; Corselli, Mirko; Ghersi, Chiara; Chiavarina, Barbara; Rodella, Luigi F; L'Abbate, Antonio; Drummond, George; Abraham, Nader G; Frassoni, Francesco

    2009-01-01

    Background Atherosclerosis progression is accelerated in diabetes mellitus (DM) by either direct endothelial damage or reduced availability and function of endothelial progenitor cells (EPCs). Both alterations are related to increased oxidant damage. Aim We examined if DM specifically impairs vascular signaling, thereby reducing the recruitment of normal EPCs, and if increases in antioxidant levels by induction of heme oxygenase-1 (HO-1) can reverse this condition. Methods Control and diabetic rats were treated with the HO-1 inducer cobalt protoporphyrin (CoPP) once a week for 3 weeks. Eight weeks after the development of diabetes, EPCs harvested from the aorta of syngenic inbred normal rats and labeled with technetium-99m-exametazime were infused via the femoral vein to estimate their blood clearance and aortic recruitment. Circulating endothelial cells (CECs) and the aortic expression of thrombomodulin (TM), CD31, and endothelial nitric oxide synthase (eNOS) were used to measure endothelial damage. Results DM reduced blood clearance and aortic recruitment of EPCs. Both parameters were returned to control levels by CoPP treatment without affecting EPC kinetics in normal animals. These abnormalities of EPCs in DM were paralleled by reduced serum adiponectin levels, increased numbers of CECs, reduced endothelial expression of phosphorylated eNOS, and reduced levels of TM, CD31, and phosphorylated AMP-activated protein kinase (pAMPK). CoPP treatment restored all of these parameters to normal levels. Conclusion Type II DM and its related oxidant damage hamper the interaction between the vascular wall and normal EPCs by mechanisms that are, at least partially, reversed by the induction of HO-1 gene expression, adiponectin, and pAMPK levels. PMID:19038792

  8. Control of intracellular heme levels: Heme transporters and Heme oxygenases

    Science.gov (United States)

    Khan, Anwar A.; Quigley, John G.

    2011-01-01

    Heme serves as a co-factor in proteins involved in fundamental biological processes including oxidative metabolism, oxygen storage and transport, signal transduction and drug metabolism. In addition, heme is important for systemic iron homeostasis in mammals. Heme has important regulatory roles in cell biology, yet excessive levels of intracellular heme are toxic; thus, mechanisms have evolved to control the acquisition, synthesis, catabolism and expulsion of cellular heme. Recently, a number of transporters of heme and heme synthesis intermediates have been described. Here we review aspects of heme metabolism and discuss our current understanding of heme transporters, with emphasis on the function of the cell-surface heme exporter, FLVCR. Knockdown of Flvcr in mice leads to both defective erythropoiesis and disturbed systemic iron homeostasis, underscoring the critical role of heme transporters in mammalian physiology. PMID:21238504

  9. Control of intracellular heme levels: Heme transporters and heme oxygenases

    OpenAIRE

    Khan, Anwar A.; Quigley, John G.

    2011-01-01

    Heme serves as a co-factor in proteins involved in fundamental biological processes including oxidative metabolism, oxygen storage and transport, signal transduction and drug metabolism. In addition, heme is important for systemic iron homeostasis in mammals. Heme has important regulatory roles in cell biology, yet excessive levels of intracellular heme are toxic; thus, mechanisms have evolved to control the acquisition, synthesis, catabolism and expulsion of cellular heme. Recently, a number...

  10. Theory of Mind Ability in Children with Specific Language Impairment

    Science.gov (United States)

    Gillott, A.; Furniss, F.; Walter, A.

    2004-01-01

    Whilst evidence of theory of mind impairments in children with autism is well established, possible impairments in children with language disorder have only recently been investigated. Children with specific language impairment aged between eight and 12 years were matched by age and gender to high functioning children with autism and normally…

  11. Cerebellum, Language, and Cognition in Autism and Specific Language Impairment

    Science.gov (United States)

    Hodge, Steven M.; Makris, Nikos; Kennedy, David N.; Caviness, Verne S., Jr.; Howard, James; McGrath, Lauren; Steele, Shelly; Frazier, Jean A.; Tager-Flusberg, Helen; Harris, Gordon J.

    2010-01-01

    We performed cerebellum segmentation and parcellation on magnetic resonance images from right-handed boys, aged 6-13 years, including 22 boys with autism [16 with language impairment (ALI)], 9 boys with Specific Language Impairment (SLI), and 11 normal controls. Language-impaired groups had reversed asymmetry relative to unimpaired groups in…

  12. Writing Motivation of Students with Specific Language Impairments

    Science.gov (United States)

    Brouwer, Kyle Lee

    2010-01-01

    This study was designed to compare the writing motivation of students with specific language impairments with their non-disabled peers. Due to the cognitive and linguistic demands of the writing process, students with language impairments face unique difficulties during the writing process. It was hypothesized that students with specific language…

  13. Heme-coordinated histidine residues form non-specific functional "ferritin-heme" peroxidase system: Possible and partial mechanistic relevance to oxidative stress-mediated pathology in neurodegenerative diseases.

    Science.gov (United States)

    Esmaeili, Sajjad; Kooshk, Mohammad Reza Ashrafi; Asghari, Seyyed Mohsen; Khodarahmi, Reza

    2016-10-01

    Ferritin is a giant protein composed of 24 subunits which is able to sequester up to 4500 atoms of iron. We proposed two kinds of heme binding sites in mammalian ferritins and provided direct evidence for peroxidase activity of heme-ferritin, since there is the possibility that "ferritin-heme" systems display unexpected catalytic behavior like heme-containing enzymes. In the current study, peroxidase activity of heme-bound ferritin was studied using TMB(1), l-DOPA, serotonin, and dopamine, in the presence of H2O2, as oxidant substrate. The catalytic oxidation of TMB was consistent with first-order kinetics with respect to ferritin concentration. Perturbation of the binding affinity and catalytic behavior of heme-bound His-modified ferritin were also documented. We also discuss the importance of the peroxidase-/nitrative-mediated oxidation of vital molecules as well as ferritin-induced catalase inhibition using in vitro experimental system. Uncontrollable "heme-ferritin"-based enzyme activity as well as up-regulation of heme and ferritin may inspire that some oxidative stress-mediated cytotoxic effects in AD-affected cells could be correlated to ferritin-heme interaction and/or ferritin-induced catalase inhibition and describe its contribution as an important causative pathogenesis mechanism in some neurodegenerative disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. A rapid, simple method for obtaining radiochemically pure hepatic heme

    International Nuclear Information System (INIS)

    Bonkowski, H.L.; Bement, W.J.; Erny, R.

    1978-01-01

    Radioactively-labelled heme has usually been isolated from liver to which unlabelled carrier has been added by long, laborious techniques involving organic solvent extraction followed by crystallization. A simpler, rapid method is devised for obtaining radiochemically-pure heme synthesized in vivo in rat liver from delta-amino[4- 14 C]levulinate. This method, in which the heme is extracted into ethyl acetate/glacial acetic acid and in which porphyrins are removed from the heme-containing organic phase with HCl washes, does not require addition of carrier heme. The new method gives better heme recoveries than and heme specific activities identical to, those obtained using the crystallization method. In this new method heme must be synthesized from delta-amino[4- 14 C]levulinate; it is not satisfactory to use [2- 14 C]glycine substrate because non-heme counts are isolated in the heme fraction. (Auth.)

  15. Methodes for identification of specific language impairment

    Directory of Open Access Journals (Sweden)

    Toktam Maleki Shahmahmood

    2014-06-01

    Full Text Available Background and Aim: Specific language impiarment (SLI is one of the most prevalent developmental language disorders its diagnosis is a problematic issue among researchers and clinicians because of the heterogeneity of language profiles in the affected population and overlapping with other developmental language disorders. The aim of this study was to review the suggested diagnostic criteria for this disorder, controversies about these criteria and identify the most accurate diagnostic methods.Methods: Published article from 1980 to 2012 in bibliographic and publisher databases including Pubmed, Google scholar, Cochran library, Web of Science, ProQuest, Springer, Oxford, Science direct, Ovid, Iran Medex and Magiran about the diagnostic methods for discriminating preschoool children with specific language impiarment from normal developing children were reviewd in this article. These keywords were used for research: “specific language impairment”, “SLI”, “diagnosis or identification”, “standardized tests”, and “tests for language development”.Conclusion: The results of this study show inspite of agreement of researchers and clinicians about exclusionary criteria as one basic part of the diagnosis of specific language impiarment , there is no consensus about the other part, inclusionary criteria. Different studies used different inclusionary criteria which can be divided to categories of clincal judgment, discrepancy-based criteria, standardized testing, clinical markers and markers from spontaneous speech samples. Advantages, disadvantages, and clinical applicability of each diagnostic method are discussed in this article.

  16. Delayed globin synthesis leads to excess heme and the macrocytic anemia of Diamond Blackfan anemia and del(5q) myelodysplastic syndrome.

    Science.gov (United States)

    Yang, Zhantao; Keel, Siobán B; Shimamura, Akiko; Liu, Li; Gerds, Aaron T; Li, Henry Y; Wood, Brent L; Scott, Bart L; Abkowitz, Janis L

    2016-05-11

    Diamond Blackfan anemia (DBA) and myelodysplastic syndrome (MDS) with isolated del(5q) are severe macrocytic anemias; although both are associated with impaired ribosome assembly, why the anemia occurs is not known. We cultured marrow cells from DBA (n = 3) and del(5q) MDS (n = 6) patients and determined how heme (a toxic chemical) and globin (a protein) are coordinated. We show that globin translation initiates slowly, whereas heme synthesis proceeds normally. This results in insufficient globin protein, excess heme and excess reactive oxygen species in early erythroid precursors, and CFU-E (colony-forming unit-erythroid)/proerythroblast cell death. The cells that can more rapidly and effectively export heme or can slow heme synthesis preferentially survive and appropriately mature. Consistent with these observations, treatment with 10 μM succinylacetone, a specific inhibitor of heme synthesis, improved the erythroid cell output of DBA and del(5q) MDS marrow cultures by 68 to 95% (P = 0.03 to 0.05), whereas the erythroid cell output of concurrent control marrow cultures decreased by 4 to 13%. Our studies demonstrate that erythropoiesis fails when heme exceeds globin. Our data further suggest that therapies that decrease heme synthesis (or facilitate heme export) could improve the red blood cell production of persons with DBA, del(5q) MDS, and perhaps other macrocytic anemias. Copyright © 2016, American Association for the Advancement of Science.

  17. Redox active molecules cytochrome c and vitamin C enhance heme-enzyme peroxidations by serving as non-specific agents for redox relay

    International Nuclear Information System (INIS)

    Gade, Sudeep Kumar; Bhattacharya, Subarna; Manoj, Kelath Murali

    2012-01-01

    Highlights: ► At low concentrations, cytochrome c/vitamin C do not catalyze peroxidations. ► But low levels of cytochrome c/vitamin C enhance diverse heme peroxidase activities. ► Enhancement positively correlates to the concentration of peroxide in reaction. ► Reducible additives serve as non-specific agents for redox relay in the system. ► Insight into electron transfer processes in routine and oxidative-stress states. -- Abstract: We report that incorporation of very low concentrations of redox protein cytochrome c and redox active small molecule vitamin C impacted the outcome of one-electron oxidations mediated by structurally distinct plant/fungal heme peroxidases. Evidence suggests that cytochrome c and vitamin C function as a redox relay for diffusible reduced oxygen species in the reaction system, without invoking specific or affinity-based molecular interactions for electron transfers. The findings provide novel perspectives to understanding – (1) the promiscuous role of cytochrome b 5 in the metabolism mediated by liver microsomal xenobiotic metabolizing systems and (2) the roles of antioxidant molecules in affording relief from oxidative stress.

  18. Redox active molecules cytochrome c and vitamin C enhance heme-enzyme peroxidations by serving as non-specific agents for redox relay

    Energy Technology Data Exchange (ETDEWEB)

    Gade, Sudeep Kumar; Bhattacharya, Subarna [Heme and Flavo Proteins Laboratory, 204, Center for Biomedical Research, VIT University, Vellore, Tamil Nadu 632014 (India); Manoj, Kelath Murali, E-mail: satyamjayatu@yahoo.com [Heme and Flavo Proteins Laboratory, 204, Center for Biomedical Research, VIT University, Vellore, Tamil Nadu 632014 (India)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer At low concentrations, cytochrome c/vitamin C do not catalyze peroxidations. Black-Right-Pointing-Pointer But low levels of cytochrome c/vitamin C enhance diverse heme peroxidase activities. Black-Right-Pointing-Pointer Enhancement positively correlates to the concentration of peroxide in reaction. Black-Right-Pointing-Pointer Reducible additives serve as non-specific agents for redox relay in the system. Black-Right-Pointing-Pointer Insight into electron transfer processes in routine and oxidative-stress states. -- Abstract: We report that incorporation of very low concentrations of redox protein cytochrome c and redox active small molecule vitamin C impacted the outcome of one-electron oxidations mediated by structurally distinct plant/fungal heme peroxidases. Evidence suggests that cytochrome c and vitamin C function as a redox relay for diffusible reduced oxygen species in the reaction system, without invoking specific or affinity-based molecular interactions for electron transfers. The findings provide novel perspectives to understanding - (1) the promiscuous role of cytochrome b{sub 5} in the metabolism mediated by liver microsomal xenobiotic metabolizing systems and (2) the roles of antioxidant molecules in affording relief from oxidative stress.

  19. Mechanisms of heme utilization by Francisella tularensis.

    Directory of Open Access Journals (Sweden)

    Helena Lindgren

    Full Text Available Francisella tularensis is a highly virulent facultative intracellular pathogen causing the severe disease tularemia in mammals. As for other bacteria, iron is essential for its growth but very few mechanisms for iron acquisition have been identified. Here, we analyzed if and how F. tularensis can utilize heme, a major source of iron in vivo. This is by no means obvious since the bacterium lacks components of traditional heme-uptake systems. We show that SCHU S4, the prototypic strain of subspecies tularensis, grew in vitro with heme as the sole iron source. By screening a SCHU S4 transposon insertion library, 16 genes were identified as important to efficiently utilize heme, two of which were required to avoid heme toxicity. None of the identified genes appeared to encode components of a potential heme-uptake apparatus. Analysis of SCHU S4 deletion mutants revealed that each of the components FeoB, the siderophore system, and FupA, contributed to the heme-dependent growth. In the case of the former two systems, iron acquisition was impaired, whereas the absence of FupA did not affect iron uptake but led to abnormally high binding of iron to macromolecules. Overall, the present study demonstrates that heme supports growth of F. tularensis and that the requirements for the utilization are highly complex and to some extent novel.

  20. Heme Sensor Proteins*

    Science.gov (United States)

    Girvan, Hazel M.; Munro, Andrew W.

    2013-01-01

    Heme is a prosthetic group best known for roles in oxygen transport, oxidative catalysis, and respiratory electron transport. Recent years have seen the roles of heme extended to sensors of gases such as O2 and NO and cell redox state, and as mediators of cellular responses to changes in intracellular levels of these gases. The importance of heme is further evident from identification of proteins that bind heme reversibly, using it as a signal, e.g. to regulate gene expression in circadian rhythm pathways and control heme synthesis itself. In this minireview, we explore the current knowledge of the diverse roles of heme sensor proteins. PMID:23539616

  1. Analogical Reasoning in Children with Specific Language Impairment

    Science.gov (United States)

    Leroy, Sandrine; Parisse, Christophe; Maillart, Christelle

    2012-01-01

    Usage-based theory considers analogical reasoning as a cognitive process required in language development. We hypothesized that difficulties with analogical reasoning could hinder the abstraction of construction schemas, thus slowing down morphosyntactic development for children with specific language impairment (SLI). We also hypothesized, in…

  2. Do Adolescents with Specific Language Impairment Understand Driving Terminology?

    Science.gov (United States)

    Pandolfe, Jessica M.; Wittke, Kacie; Spaulding, Tammie J.

    2016-01-01

    Purpose: This study examined if adolescents with specific language impairment (SLI) understand driving vocabulary as well as their typically developing (TD) peers. Method: A total of 16 adolescents with SLI and 16 TD comparison adolescents completed a receptive vocabulary task focused on driving terminology derived from statewide driver's manuals.…

  3. Social Stress in Young People with Specific Language Impairment

    Science.gov (United States)

    Wadman, Ruth; Durkin, Kevin; Conti-Ramsden, Gina

    2011-01-01

    Social interactions can be a source of social stress for adolescents. Little is known about how adolescents with developmental difficulties, such as specific language impairment (SLI), feel when interacting socially. Participants included 28 adolescents with SLI and 28 adolescents with typical language abilities (TL). Self-report measures of…

  4. Negative Sentences in Children with Specific Language Impairment

    Science.gov (United States)

    Thornton, Rosalind; Rombough, Kelly; Martin, Jasmine; Orton, Linda

    2016-01-01

    This study used elicited production methodology to investigate the negative sentences that are produced by English-speaking children with specific language impairment (SLI). Negative sentences were elicited in contexts in which adults use the negative auxiliary verb doesn't (e.g., "It doesn't fit"). This form was targeted to see how…

  5. Specific language impairment is associated with maternal and family factors

    NARCIS (Netherlands)

    Diepeveen, F.B.; Dommelen, P. van; Oudesluys-Murphy, A.M.; Verkerk, P.H.

    2017-01-01

    Background: This study aimed to identify risk factors associated with specific language impairment (SLI). Methods: In a nested case–control design, 253 children attending special needs schools for severe speech and language difficulties in the Netherlands were matched for sex and date of birth with

  6. Executive function behaviours in children with specific language impairment (SLI)

    NARCIS (Netherlands)

    Cuperus, J.M.; Vugs, B.A.M.; Scheper, A.R.; Hendriks, M.P.H.

    2014-01-01

    Background: There is growing evidence that linguistic and non-linguistic factors may contribute to the problems associated with specific language impairment (SLI). One factor that has been implicated is executive functioning (EF). Most studies investigating EF in children with SLI use performance

  7. Which Preschool Children with Specific Language Impairment Receive Language Intervention?

    Science.gov (United States)

    Wittke, Kacie; Spaulding, Tammie J.

    2018-01-01

    Purpose: Potential biases in service provision for preschool children with specific language impairment (SLI) were explored. Method: In Study 1, children with SLI receiving treatment (SLI-T) and those with SLI not receiving treatment (SLI-NT) were compared on demographic characteristics and developmental abilities. Study 2 recruited children with…

  8. Heme synthesis in normal mouse liver and mouse liver tumors

    International Nuclear Information System (INIS)

    Stout, D.L.; Becker, F.F.

    1990-01-01

    Hepatic cancers from mice and rats demonstrate decreased levels of delta-aminolevulinic acid synthase, the rate-limiting enzyme in the heme synthetic pathway, and increased heme oxygenase, the heme-catabolizing enzyme. These findings suggest that diminution of P-450, b5, and catalase in these lesions may result from a heme supply that is limited by decreased heme synthesis and increased heme catabolism. Heme synthesis was measured in mouse liver tumors (MLT) and adjacent tumor-free lobes (BKG) by administering the radiolabeled heme precursors 55 FeCl3 and [2- 14 C]glycine and subsequently extracting the heme for determination of specific activity. Despite reduced delta-aminolevulinic acid synthase activity in MLT, both tissues incorporated [2-14C]glycine into heme at similar rates. At early time points, heme extracted from MLT contained less 55Fe than that from BKG. This was attributed to the findings that MLT took up 55Fe at a slower rate than BKG and had larger iron stores than BKG. The amount of heme per milligram of protein was also similar in both tissues. These findings militate against the hypothesis that diminished hemoprotein levels in MLT result from limited availability of heme. It is probable, therefore, that decreased hemoprotein levels in hepatic tumors are linked to a general program of dedifferentiation associated with the cancer phenotype. Diminution of hemoprotein in MLT may result in a relatively increased intracellular heme pool. delta-Aminolevulinic acid synthase and heme oxygenase are, respectively, negatively and positively regulated by heme. Thus, their alteration in MLT may be due to the regulatory influences of the heme pool

  9. Transition between acute and chronic hepatotoxicity in mice is associated with impaired energy metabolism and induction of mitochondrial heme oxygenase-1.

    Directory of Open Access Journals (Sweden)

    Aniket Nikam

    Full Text Available The formation of protein inclusions is frequently associated with chronic metabolic diseases. In mice, short-term intoxication with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC leads to hepatocellular damage indicated by elevated serum liver enzyme activities, whereas only minor morphological changes are observed. Conversely, chronic administration of DDC for several weeks results in severe morphological damage, characterized by hepatocellular ballooning, disruption of the intermediate filament cytoskeleton, and formation of Mallory-Denk bodies consisting predominantly of misfolded keratins, Sqstm1/p62, and heat shock proteins. To evaluate the mechanistic underpinnings for this dichotomy we dissected the time-course of DDC intoxication for up to 10 weeks. We determined body weight change, serum liver enzyme activities, morphologic alterations, induction of antioxidant response (heme oxygenase-1, HO-1, oxidative damage and ATP content in livers as well as respiration, oxidative damage and the presence and activity of HO-1 in endoplasmic reticulum and mitochondria (mtHO-1. Elevated serum liver enzyme activity and oxidative liver damage were already present at early intoxication stages without further subsequent increase. After 2 weeks of intoxication, mice had transiently lost 9% of their body weight, liver ATP-content was reduced to 58% of controls, succinate-driven respiration was uncoupled from ATP-production and antioxidant response was associated with the appearance of catalytically active mtHO-1. Oxidative damage was associated with both acute and chronic DDC toxicity whereas the onset of chronic intoxication was specifically associated with mitochondrial dysfunction which was maximal after 2 weeks of intoxication. At this transition stage, adaptive responses involving mtHO-1 were induced, indirectly leading to improved respiration and preventing further drop of ATP levels. Our observations clearly demonstrate principally different

  10. Hemoglobin and heme scavenger receptors

    DEFF Research Database (Denmark)

    Nielsen, Marianne Jensby; Møller, Holger Jon; Moestrup, Søren Kragh

    2010-01-01

    Heme, the functional group of hemoglobin, myoglobin, and other hemoproteins, is a highly toxic substance when it appears in the extracellular milieu. To circumvent potential harmful effects of heme from hemoproteins released during physiological or pathological cell damage (such as hemolysis...... and rhabdomyolysis), specific high capacity scavenging systems have evolved in the mammalian organism. Two major systems, which essentially function in a similar way by means of a circulating latent plasma carrier protein that upon ligand binding is recognized by a receptor, are represented by a) the hemoglobin...

  11. Mechanism governing heme synthesis reveals a GATA factor/heme circuit that controls differentiation.

    Science.gov (United States)

    Tanimura, Nobuyuki; Miller, Eli; Igarashi, Kazuhiko; Yang, David; Burstyn, Judith N; Dewey, Colin N; Bresnick, Emery H

    2016-02-01

    Metal ion-containing macromolecules have fundamental roles in essentially all biological processes throughout the evolutionary tree. For example, iron-containing heme is a cofactor in enzyme catalysis and electron transfer and an essential hemoglobin constituent. To meet the intense demand for hemoglobin assembly in red blood cells, the cell type-specific factor GATA-1 activates transcription of Alas2, encoding the rate-limiting enzyme in heme biosynthesis, 5-aminolevulinic acid synthase-2 (ALAS-2). Using genetic editing to unravel mechanisms governing heme biosynthesis, we discovered a GATA factor- and heme-dependent circuit that establishes the erythroid cell transcriptome. CRISPR/Cas9-mediated ablation of two Alas2 intronic cis elements strongly reduces GATA-1-induced Alas2 transcription, heme biosynthesis, and surprisingly, GATA-1 regulation of other vital constituents of the erythroid cell transcriptome. Bypassing ALAS-2 function in Alas2 cis element-mutant cells by providing its catalytic product 5-aminolevulinic acid rescues heme biosynthesis and the GATA-1-dependent genetic network. Heme amplifies GATA-1 function by downregulating the heme-sensing transcriptional repressor Bach1 and via a Bach1-insensitive mechanism. Through this dual mechanism, heme and a master regulator collaborate to orchestrate a cell type-specific transcriptional program that promotes cellular differentiation. © 2015 The Authors.

  12. A methodology for the characterization and diagnosis of cognitive impairments-Application to specific language impairment.

    Science.gov (United States)

    Oliva, Jesús; Serrano, J Ignacio; del Castillo, M Dolores; Iglesias, Angel

    2014-06-01

    The diagnosis of mental disorders is in most cases very difficult because of the high heterogeneity and overlap between associated cognitive impairments. Furthermore, early and individualized diagnosis is crucial. In this paper, we propose a methodology to support the individualized characterization and diagnosis of cognitive impairments. The methodology can also be used as a test platform for existing theories on the causes of the impairments. We use computational cognitive modeling to gather information on the cognitive mechanisms underlying normal and impaired behavior. We then use this information to feed machine-learning algorithms to individually characterize the impairment and to differentiate between normal and impaired behavior. We apply the methodology to the particular case of specific language impairment (SLI) in Spanish-speaking children. The proposed methodology begins by defining a task in which normal and individuals with impairment present behavioral differences. Next we build a computational cognitive model of that task and individualize it: we build a cognitive model for each participant and optimize its parameter values to fit the behavior of each participant. Finally, we use the optimized parameter values to feed different machine learning algorithms. The methodology was applied to an existing database of 48 Spanish-speaking children (24 normal and 24 SLI children) using clustering techniques for the characterization, and different classifier techniques for the diagnosis. The characterization results show three well-differentiated groups that can be associated with the three main theories on SLI. Using a leave-one-subject-out testing methodology, all the classifiers except the DT produced sensitivity, specificity and area under curve values above 90%, reaching 100% in some cases. The results show that our methodology is able to find relevant information on the underlying cognitive mechanisms and to use it appropriately to provide better

  13. Social stress in young people with specific language impairment

    OpenAIRE

    Wadman, Ruth; Durkin, Kevin; Conti-Ramsden, Gina

    2010-01-01

    Social interactions can be a source of social stress for adolescents. Little is known about how adolescents with developmental difficulties, such as specific language impairment (SLI), feel when interacting socially. Participants included 28 adolescents with SLI and 28 adolescents with typical language abilities (TL). Self-report measures of social stress, social skills and social acceptance were obtained. Participants with SLI reported experiencing significantly more social stress than did p...

  14. Working, declarative and procedural memory in specific language impairment

    OpenAIRE

    Lum, Jarrad A.G.; Conti-Ramsden, Gina; Page, Debra; Ullman, Michael T.

    2012-01-01

    According to the Procedural Deficit Hypothesis (PDH), abnormalities of brain structures underlying procedural memory largely explain the language deficits in children with specific language impairment (SLI). These abnormalities are posited to result in core deficits of procedural memory, which in turn explain the grammar problems in the disorder. The abnormalities are also likely to lead to problems with other, non-procedural functions, such as working memory, that rely at least partly on the...

  15. The acquisition of nouns in children with Specific Language Impairment

    OpenAIRE

    Krzemien, Magali; Thibaut, Jean-Pierre; Zghonda, Hela; Maillart, Christelle

    2017-01-01

    Specific Language Impairment (SLI) is a neurodevelopmental disorder that affects the language development of children with a normal nonverbal intelligence and no history of neurological disorder nor auditory deficit (Leonard, 2014). A difficulty linked to SLI is the poor language productivity and the input dependency that children display compared with their peers: they tend to use a limited variety of verbal forms compared to younger siblings (Conti-Ramsden & Jones, 1997) and use a high prop...

  16. Conflict resolution abilities in children with Specific Language Impairment.

    Science.gov (United States)

    Paula, Erica Macêdo de; Befi-Lopes, Debora Maria

    2013-01-01

    To investigate the conflict resolution abilities of children with Specific Language Impairment, and to verify whether the time of speech-language therapy correlates to the performance on the conflict resolution task. Participants included 20 children with Specific Language Impairment (Research Group) and 40 children with normal language development (Control Group), with ages ranging from 7 years to 8 years and 11 months. To assess the conflict resolution abilities, five hypothetical contexts of conflict were presented. The strategies used by the children were classified and scored by the following levels: level 0 (solutions that do not match the other levels), level 1 (physical solutions), level 2 (unilateral solutions), level 3 (cooperative solutions), and level 4 (mutual solutions). Statistical analysis showed group effect for the variable total score. There was a difference between the groups for modal development level, with higher level of modal development observed in the Control Group. There was no correlation between the period of speech-language therapy attendance and the total score. Children with Specific Language Impairment present difficulties in solving problems, in view of the fact that they mainly use physical and unilateral strategies. There was no correlation between the time of speech-language therapy and performance in the task.

  17. Aging specifically impairs switching to an allocentric navigational strategy.

    Science.gov (United States)

    Harris, Mathew A; Wiener, Jan M; Wolbers, Thomas

    2012-01-01

    Navigation abilities decline with age, partly due to deficits in numerous component processes. Impaired switching between these various processes (i.e., switching navigational strategies) is also likely to contribute to age-related navigational impairments. We tested young and old participants on a virtual plus maze task (VPM), expecting older participants to exhibit a specific strategy switching deficit, despite unimpaired learning of allocentric (place) and egocentric (response) strategies following reversals within each strategy. Our initial results suggested that older participants performed worse during place trial blocks but not response trial blocks, as well as in trial blocks following a strategy switch but not those following a reversal. However, we then separated trial blocks by both strategy and change type, revealing that these initial results were due to a more specific deficit in switching to the place strategy. Place reversals and switches to response, as well as response reversals, were unaffected. We argue that this specific "switch-to-place" deficit could account for apparent impairments in both navigational strategy switching and allocentric processing and contributes more generally to age-related decline in navigation.

  18. Identification of danthron as an isoform-specific inhibitor of HEME OXYGENASE-1/cytochrome P450 reductase interaction with anti-tumor activity.

    Science.gov (United States)

    Chou, Yi-Tai; Hsu, Fu-Fei; Hu, Dun-Yao; Chen, Ying-Chih; Hsu, Yuan-Hao; Hsu, John T-A; Chau, Lee-Young

    2018-01-23

    Heme oxygenase (HO) catalyzes NADPH-dependent degradation of heme to liberate iron, carbon monoxide and biliverdin. The interaction between HO and cytochrome P450 reductase (CPR), an electron donor, is essential for HO activity. HO-1 is a stress-inducible isoform whereas HO-2 is constitutively expressed. HO-1 induction is commonly seen in cancers and impacts disease progression, supporting the possibility of targeting HO-1 for cancer therapy. We employed a cell-based bioluminescence resonance energy transfer assay to screen compounds with ability to inhibit HO-1/CPR interaction. The effect of the identified compound on HO-1/CPR interaction was confirmed by pull down assay. Moreover, the anti-tumorigenic activity of the identified compound on HO-1-enhanced tumor growth and migration was assessed by trypan blue exclusion method and wound healing assay. Danthron was identified as an effective small molecule able to interfere with the interaction between HO-1 and CPR but not HO-2 and CPR. Additional experiments with structural analogues of danthron revealed that the positions of hydroxyl moieties significantly affected the potency of inhibition on HO-1/CPR interaction. Pull-down assay confirmed that danthron inhibited the interaction of CPR with HO-1 but not HO-2. Danthron suppressed growth and migration of HeLa cells with stable HO-1 overexpression but not mock cells. In contrast, anthrarufin, a structural analog with no ability to interfere HO-1/CPR interaction, exhibited no significant effect on HO-1-overexpressing HeLa cells. These findings demonstrate that danthron is an isoform-specific inhibitor for HO-1/CPR interaction and may serve as a lead compound for novel anticancer drug.

  19. Heme oxygenase up-regulation under ultraviolet-B radiation is not epigenetically restricted and involves specific stress-related transcriptions factors

    Directory of Open Access Journals (Sweden)

    Diego Santa-Cruz

    2017-08-01

    Full Text Available Heme oxygenase-1 (HO-1 plays a protective role against oxidative stress in plants. The mechanisms regulating its expression, however, remain unclear. Here we studied the methylation state of a GC rich HO-1 promoter region and the expression of several stress-related transcription factors (TFs in soybean plants subjected to ultraviolet-B (UV-B radiation. Genomic DNA and total RNA were isolated from leaves of plants irradiated with 7.5 and 15 kJ m-2 UV-B. A 304 bp HO-1 promoter region was amplified by PCR from sodium bisulfite-treated DNA, cloned into pGEMT plasmid vector and evaluated by DNA sequencing. Bisulfite sequencing analysis showed similar HO-1 promoter methylation levels in control and UV-B-treated plants (C: 3.4±1.3%; 7.5: 2.6±0.5%; 15: 3.1±1.1%. Interestingly, HO-1 promoter was strongly unmethylated in control plants. Quantitative RT-PCR analysis of TFs showed that GmMYB177, GmMYBJ6, GmWRKY21, GmNAC11, GmNAC20 and GmGT2A but not GmWRK13 and GmDREB were induced by UV-B radiation. The expression of several TFs was also enhanced by hemin, a potent and specific HO inducer, inferring that they may mediate HO-1 up-regulation. These results suggest that soybean HO-1 gene expression is not epigenetically regulated. Moreover, the low level of HO-1 promoter methylation suggests that this antioxidant enzyme can rapidly respond to environmental stress. Finally, this study has identified some stress-related TFs involved in HO-1 up-regulation under UV-B radiation. Keywords: Heme oxygenase, DNA methylation, Transcription factors, Ultraviolet-B radiation, Glycine max

  20. Working, declarative and procedural memory in specific language impairment

    DEFF Research Database (Denmark)

    Lum, J. A. G.; Conti-Ramsden, G.; Page, D.

    2012-01-01

    at declarative memory for visual information, and at declarative memory in the verbal domain after controlling for working memory and language. Visuo-spatial short-term memory was intact, whereas verbal working memory was impaired, even when language deficits were held constant. Correlation analyses showed......According to the Procedural Deficit Hypothesis (PDH), abnormalities of brain structures underlying procedural memory largely explain the language deficits in children with specific language impairment (SLI). These abnormalities are posited to result in core deficits of procedural memory, which...... in turn explain the grammar problems in the disorder. The abnormalities are also likely to lead to problems with other, non-procedural functions, such as working memory, that rely at least partly on the affected brain structures. In contrast, declarative memory is expected to remain largely intact...

  1. Mental fatigue impairs soccer-specific decision-making skill.

    Science.gov (United States)

    Smith, Mitchell R; Zeuwts, Linus; Lenoir, Matthieu; Hens, Nathalie; De Jong, Laura M S; Coutts, Aaron J

    2016-07-01

    This study aimed to investigate the impact of mental fatigue on soccer-specific decision-making. Twelve well-trained male soccer players performed a soccer-specific decision-making task on two occasions, separated by at least 72 h. The decision-making task was preceded in a randomised order by 30 min of the Stroop task (mental fatigue) or 30 min of reading from magazines (control). Subjective ratings of mental fatigue were measured before and after treatment, and mental effort (referring to treatment) and motivation (referring to the decision-making task) were measured after treatment. Performance on the soccer-specific decision-making task was assessed using response accuracy and time. Visual search behaviour was also assessed throughout the decision-making task. Subjective ratings of mental fatigue and effort were almost certainly higher following the Stroop task compared to the magazines. Motivation for the upcoming decision-making task was possibly higher following the Stroop task. Decision-making accuracy was very likely lower and response time likely higher in the mental fatigue condition. Mental fatigue had unclear effects on most visual search behaviour variables. The results suggest that mental fatigue impairs accuracy and speed of soccer-specific decision-making. These impairments are not likely related to changes in visual search behaviour.

  2. Heme-induced ROS in Trypanosoma cruzi activates CaMKII-like that triggers epimastigote proliferation. One helpful effect of ROS.

    Directory of Open Access Journals (Sweden)

    Natália Pereira de Almeida Nogueira

    Full Text Available Heme is a ubiquitous molecule that has a number of physiological roles. The toxic effects of this molecule have been demonstrated in various models, based on both its pro-oxidant nature and through a detergent mechanism. It is estimated that about 10 mM of heme is released during blood digestion in the blood-sucking bug's midgut. The parasite Trypanosoma cruzi, the agent of Chagas' disease, proliferates in the midgut of the insect vector; however, heme metabolism in trypanosomatids remains to be elucidated. Here we provide a mechanistic explanation for the proliferative effects of heme on trypanosomatids. Heme, but not other porphyrins, induced T. cruzi proliferation, and this phenomenon was accompanied by a marked increase in reactive oxygen species (ROS formation in epimastigotes when monitored by ROS-sensitive fluorescent probes. Heme-induced ROS production was time- and concentration-dependent. In addition, lipid peroxidation and the formation of 4-hydroxy-2-nonenal (4-HNE adducts with parasite proteins were increased in epimastigotes in the presence of heme. Conversely, the antioxidants urate and GSH reversed the heme-induced ROS. Urate also decreased parasite proliferation. Among several protein kinase inhibitors tested only specific inhibitors of CaMKII, KN93 and Myr-AIP, were able to abolish heme-induced ROS formation in epimastigotes leading to parasite growth impairment. Taken together, these data provide new insight into T. cruzi- insect vector interactions: heme, a molecule from the blood digestion, triggers epimastigote proliferation through a redox-sensitive signalling mechanism.

  3. Singing abilities in children with Specific Language Impairment (SLI

    Directory of Open Access Journals (Sweden)

    Sylvain eCLEMENT

    2015-04-01

    Full Text Available Specific Language impairment (SLI is a heritable neurodevelopmental disorder diagnosed when a child has difficulties learning to produce and/or understand speech for no apparent reason (Bishop et al., 2012. The verbal difficulties of children with SLI have been largely documented, and a growing number of studies suggest that these children may also have difficulties in processing non-verbal complex auditory stimuli (Brandt et al., 2012; Corriveau et al., 2007. In a recent study, we reported that a large proportion of children with SLI present deficits in music perception (Planchou et al, submitted. Little is known, however, about the singing abilities of children with SLI. In order to investigate whether or not the impairments in expressive language extend to the musical domain, we assessed singing abilities in 8 children with SLI and 15 children with Typical Language Development (TLD matched for age and non-verbal intelligence. To this aim, we designed a ludic activity consisting of two singing tasks: a pitch-matching and a melodic reproduction task. In the pitch-matching task, the children were requested to sing single notes. In the melodic reproduction task, children were asked to sing short melodies that were either familiar (FAM-SONG and FAM-TUNE conditions or unfamiliar (UNFAM-TUNE condition. The analysis showed that children with SLI were impaired in the pitch-matching task, with a mean pitch error of 250 cents (mean pitch error for children with TLD: 154 cents. In the melodic reproduction task, we asked 30 healthy adults to rate the quality of the sung productions of the children on a continuous rating scale. The results revealed that singing of children with SLI received lower mean ratings than the children with TLD. Our findings thus indicate that children with SLI showed impairments in musical production and are discussed in light of a general auditory-motor dysfunction in children with SLI.

  4. Heme and erythropoieis: more than a structural role.

    Science.gov (United States)

    Chiabrando, Deborah; Mercurio, Sonia; Tolosano, Emanuela

    2014-06-01

    Erythropoiesis is the biological process that consumes the highest amount of body iron for heme synthesis. Heme synthesis in erythroid cells is finely coordinated with that of alpha (α) and beta (β)-globin, resulting in the production of hemoglobin, a tetramer of 2α- and 2β-globin chains, and heme as the prosthetic group. Heme is not only the structural component of hemoglobin, but it plays multiple regulatory roles during the differentiation of erythroid precursors since it controls its own synthesis and regulates the expression of several erythroid-specific genes. Heme is synthesized in developing erythroid progenitors by the stage of proerythroblast, through a series of eight enzymatic reactions divided between mitochondria and cytosol. Defects of heme synthesis in the erythroid lineage result in sideroblastic anemias, characterized by microcytic anemia associated to mitochondrial iron overload, or in erythropoietic porphyrias, characterized by porphyrin deposition in erythroid cells. Here, we focus on the heme biosynthetic pathway and on human erythroid disorders due to defective heme synthesis. The regulatory role of heme during erythroid differentiation is discussed as well as the heme-mediated regulatory mechanisms that allow the orchestration of the adaptive cell response to heme deficiency. Copyright© Ferrata Storti Foundation.

  5. Working, declarative and procedural memory in specific language impairment

    Science.gov (United States)

    Lum, Jarrad A.G.; Conti-Ramsden, Gina; Page, Debra; Ullman, Michael T.

    2012-01-01

    According to the Procedural Deficit Hypothesis (PDH), abnormalities of brain structures underlying procedural memory largely explain the language deficits in children with specific language impairment (SLI). These abnormalities are posited to result in core deficits of procedural memory, which in turn explain the grammar problems in the disorder. The abnormalities are also likely to lead to problems with other, non-procedural functions, such as working memory, that rely at least partly on the affected brain structures. In contrast, declarative memory is expected to remain largely intact, and should play an important compensatory role for grammar. These claims were tested by examining measures of working, declarative and procedural memory in 51 children with SLI and 51 matched typically-developing (TD) children (mean age 10). Working memory was assessed with the Working Memory Test Battery for Children, declarative memory with the Children’s Memory Scale, and procedural memory with a visuo-spatial Serial Reaction Time task. As compared to the TD children, the children with SLI were impaired at procedural memory, even when holding working memory constant. In contrast, they were spared at declarative memory for visual information, and at declarative memory in the verbal domain after controlling for working memory and language. Visuo-spatial short-term memory was intact, whereas verbal working memory was impaired, even when language deficits were held constant. Correlation analyses showed neither visuo-spatial nor verbal working memory was associated with either lexical or grammatical abilities in either the SLI or TD children. Declarative memory correlated with lexical abilities in both groups of children. Finally, grammatical abilities were associated with procedural memory in the TD children, but with declarative memory in the children with SLI. These findings replicate and extend previous studies of working, declarative and procedural memory in SLI. Overall, we

  6. Cognitive functions in preschool children with specific language impairment.

    Science.gov (United States)

    Reichenbach, Katrin; Bastian, Laura; Rohrbach, Saskia; Gross, Manfred; Sarrar, Lea

    2016-07-01

    A growing body of research has focused on executive functions in children with specific language impairment (SLI). However, results show limited convergence, particularly in preschool age. The current neuropsychological study compared performance of cognitive functions focused on executive components and working memory in preschool children with SLI to typically developing controls. Performance on the measures cognitive flexibility, inhibition, processing speed and phonological short-term memory was assessed. The monolingual, Caucasian study sample consisted of 30 children with SLI (Mage = 63.3 months, SD = 4.3 months) and 30 healthy controls (Mage = 62.2 months, SD = 3.7 months). Groups were matched for age and nonverbal IQ. Socioeconomic status of the participating families was included. Children with SLI had significantly poorer abilities of phonological short-term memory than matched controls. A tendency of poorer abilities in the SLI group was found for inhibition and processing speed. We confirmed phonological short-term memory to be a reliable marker of SLI in preschoolers. Our results do not give definite support for impaired executive function in SLI, possibly owing to limited sensitivity of test instruments in this age group. We argue for a standardization of executive function tests for research use. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Later learning stages in procedural memory are impaired in children with Specific Language Impairment.

    Science.gov (United States)

    Desmottes, Lise; Meulemans, Thierry; Maillart, Christelle

    2016-01-01

    According to the Procedural Deficit Hypothesis (PDH), difficulties in the procedural memory system may contribute to the language difficulties encountered by children with Specific Language Impairment (SLI). Most studies investigating the PDH have used the sequence learning paradigm; however these studies have principally focused on initial sequence learning in a single practice session. The present study sought to extend these investigations by assessing the consolidation stage and longer-term retention of implicit sequence-specific knowledge in 42 children with or without SLI. Both groups of children completed a serial reaction time task and were tested 24h and one week after practice. Results showed that children with SLI succeeded as well as children with typical development (TD) in the early acquisition stage of the sequence learning task. However, as training blocks progressed, only TD children improved their sequence knowledge while children with SLI did not appear to evolve any more. Moreover, children with SLI showed a lack of the consolidation gains in sequence knowledge displayed by the TD children. Overall, these results were in line with the predictions of the PDH and suggest that later learning stages in procedural memory are impaired in SLI. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Heritability of specific language impairment depends on diagnostic criteria.

    Science.gov (United States)

    Bishop, D V M; Hayiou-Thomas, M E

    2008-04-01

    Heritability estimates for specific language impairment (SLI) have been inconsistent. Four twin studies reported heritability of 0.5 or more, but a recent report from the Twins Early Development Study found negligible genetic influence in 4-year-olds. We considered whether the method of ascertainment influenced results and found substantially higher heritability if SLI was defined in terms of referral to speech and language pathology services than if defined by language test scores. Further analysis showed that presence of speech difficulties played a major role in determining whether a child had contact with services. Childhood language disorders that are identified by population screening are likely to have a different phenotype and different etiology from clinically referred cases. Genetic studies are more likely to find high heritability if they focus on cases who have speech difficulties and who have been referred for intervention.

  9. Mental Fatigue Impairs Soccer-Specific Physical and Technical Performance.

    Science.gov (United States)

    Smith, Mitchell R; Coutts, Aaron J; Merlini, Michele; Deprez, Dieter; Lenoir, Matthieu; Marcora, Samuele M

    2016-02-01

    To investigate the effects of mental fatigue on soccer-specific physical and technical performance. This investigation consisted of two separate studies. Study 1 assessed the soccer-specific physical performance of 12 moderately trained soccer players using the Yo-Yo Intermittent Recovery Test, Level 1 (Yo-Yo IR1). Study 2 assessed the soccer-specific technical performance of 14 experienced soccer players using the Loughborough Soccer Passing and Shooting Tests (LSPT, LSST). Each test was performed on two occasions and preceded, in a randomized, counterbalanced order, by 30 min of the Stroop task (mentally fatiguing treatment) or 30 min of reading magazines (control treatment). Subjective ratings of mental fatigue were measured before and after treatment, and mental effort and motivation were measured after treatment. Distance run, heart rate, and ratings of perceived exertion were recorded during the Yo-Yo IR1. LSPT performance time was calculated as original time plus penalty time. LSST performance was assessed using shot speed, shot accuracy, and shot sequence time. Subjective ratings of mental fatigue and effort were higher after the Stroop task in both studies (P motivation was similar between conditions. This mental fatigue significantly reduced running distance in the Yo-Yo IR1 (P performance time were not different between conditions; however, penalty time significantly increased in the mental fatigue condition (P = 0.015). Mental fatigue also impaired shot speed (P = 0.024) and accuracy (P performance.

  10. Phase Measurement of Cognitive Impairment Specific to Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Armstrong, Carol L., E-mail: armstrongc@email.chop.edu [Children' s Hospital of Philadelphia, Philadelphia, Pennsylvania (United States); Department of Pediatrics, Division of Neuro-Oncology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania (United States); Shera, David M. [Children' s Hospital of Philadelphia, Philadelphia, Pennsylvania (United States); Department of Pediatrics, Division of Biostatistics and Epidemiology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania (United States); Lustig, Robert A. [Department of Radiation Oncology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania (United States); Phillips, Peter C. [Children' s Hospital of Philadelphia, Philadelphia, Pennsylvania (United States); Department of Pediatrics, Division of Neurology and Oncology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania (United States)

    2012-07-01

    Purpose: Memory impairment is an early-delayed effect of radiotherapy (RT). The prospective longitudinal measurement of the cognitive phase effects from RT was conducted on treated and untreated brain tumor patients. The study design investigated semantic vs. perceptual and visual vs. verbal memory to determine the most disease-specific measure of RT-related changes and understanding of the neurotoxicity from RT to the brain. Methods and Materials: Tests of memory that had previously shown RT-related phasic changes were compared with experimental tests of memory to test hypotheses about cognition targeted to the neural toxicity of RT. The results from 41 irradiated and 29 nonirradiated patients with low-grade, supratentorial tumors were analyzed. The methods controlled for comorbid white matter risk, recurrence, interval after treatment, and age (18-69 years). The effects were examined before RT and at three points after RT to 1 year using a mixed effects model that included interval, group, surgical status, medication use, practice, and individual random effects. Four new tests of memory and other candidate cognitive tests were investigated, and a post hoc analysis of a comprehensive battery of tests was performed to identify the cognitive processes most specific to RT. Results: The RT effects on memory were identified in the treated group only; among the new tests of memory and the complete neurocognitive battery, the RT effects were significant only for delayed recall (p < 0.009) and interval to recognize (p < 0.002). Tumor location was not related to the treatment effect. Memory decline was specific to retrieval of semantic memories; a double dissociation of semantic from perceptual visual memory was demonstrated in the RT group. Conclusions: These results implicate memory dependent on the semantic cortex and the hippocampal memory system. A cognitive measurement that is brief but specific to neural mechanisms is effective and feasible for studies of RT damage.

  11. Phase Measurement of Cognitive Impairment Specific to Radiotherapy

    International Nuclear Information System (INIS)

    Armstrong, Carol L.; Shera, David M.; Lustig, Robert A.; Phillips, Peter C.

    2012-01-01

    Purpose: Memory impairment is an early-delayed effect of radiotherapy (RT). The prospective longitudinal measurement of the cognitive phase effects from RT was conducted on treated and untreated brain tumor patients. The study design investigated semantic vs. perceptual and visual vs. verbal memory to determine the most disease-specific measure of RT-related changes and understanding of the neurotoxicity from RT to the brain. Methods and Materials: Tests of memory that had previously shown RT-related phasic changes were compared with experimental tests of memory to test hypotheses about cognition targeted to the neural toxicity of RT. The results from 41 irradiated and 29 nonirradiated patients with low-grade, supratentorial tumors were analyzed. The methods controlled for comorbid white matter risk, recurrence, interval after treatment, and age (18–69 years). The effects were examined before RT and at three points after RT to 1 year using a mixed effects model that included interval, group, surgical status, medication use, practice, and individual random effects. Four new tests of memory and other candidate cognitive tests were investigated, and a post hoc analysis of a comprehensive battery of tests was performed to identify the cognitive processes most specific to RT. Results: The RT effects on memory were identified in the treated group only; among the new tests of memory and the complete neurocognitive battery, the RT effects were significant only for delayed recall (p < 0.009) and interval to recognize (p < 0.002). Tumor location was not related to the treatment effect. Memory decline was specific to retrieval of semantic memories; a double dissociation of semantic from perceptual visual memory was demonstrated in the RT group. Conclusions: These results implicate memory dependent on the semantic cortex and the hippocampal memory system. A cognitive measurement that is brief but specific to neural mechanisms is effective and feasible for studies of RT

  12. Phase measurement of cognitive impairment specific to radiotherapy.

    Science.gov (United States)

    Armstrong, Carol L; Shera, David M; Lustig, Robert A; Phillips, Peter C

    2012-07-01

    Memory impairment is an early-delayed effect of radiotherapy (RT). The prospective longitudinal measurement of the cognitive phase effects from RT was conducted on treated and untreated brain tumor patients. The study design investigated semantic vs. perceptual and visual vs. verbal memory to determine the most disease-specific measure of RT-related changes and understanding of the neurotoxicity from RT to the brain. Tests of memory that had previously shown RT-related phasic changes were compared with experimental tests of memory to test hypotheses about cognition targeted to the neural toxicity of RT. The results from 41 irradiated and 29 nonirradiated patients with low-grade, supratentorial tumors were analyzed. The methods controlled for comorbid white matter risk, recurrence, interval after treatment, and age (18-69 years). The effects were examined before RT and at three points after RT to 1 year using a mixed effects model that included interval, group, surgical status, medication use, practice, and individual random effects. Four new tests of memory and other candidate cognitive tests were investigated, and a post hoc analysis of a comprehensive battery of tests was performed to identify the cognitive processes most specific to RT. The RT effects on memory were identified in the treated group only; among the new tests of memory and the complete neurocognitive battery, the RT effects were significant only for delayed recall (p measurement that is brief but specific to neural mechanisms is effective and feasible for studies of RT damage. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Working memory and novel word learning in children with hearing impairment and children with specific language impairment.

    Science.gov (United States)

    Hansson, K; Forsberg, J; Löfqvist, A; Mäki-Torkko, E; Sahlén, B

    2004-01-01

    Working memory is considered to influence a range of linguistic skills, i.e. vocabulary acquisition, sentence comprehension and reading. Several studies have pointed to limitations of working memory in children with specific language impairment. Few studies, however, have explored the role of working memory for language deficits in children with hearing impairment. The first aim was to compare children with mild-to-moderate bilateral sensorineural hearing impairment, children with a preschool diagnosis of specific language impairment and children with normal language development, aged 9-12 years, for language and working memory. The special focus was on the role of working memory in learning new words for primary school age children. The assessment of working memory included tests of phonological short-term memory and complex working memory. Novel word learning was assessed according to the methods of. In addition, a range of language tests was used to assess language comprehension, output phonology and reading. Children with hearing impairment performed significantly better than children with a preschool diagnosis of specific language impairment on tasks assessing novel word learning, complex working memory, sentence comprehension and reading accuracy. No significant correlation was found between phonological short-term memory and novel word learning in any group. The best predictor of novel word learning in children with specific language impairment and in children with hearing impairment was complex working memory. Furthermore, there was a close relationship between complex working memory and language in children with a preschool diagnosis of specific language impairment but not in children with hearing impairment. Complex working memory seems to play a significant role in vocabulary acquisition in primary school age children. The interpretation is that the results support theories suggesting a weakened influence of phonological short-term memory on novel word

  14. Fetal head circumference growth in children with specific language impairment.

    Science.gov (United States)

    Whitehouse, Andrew J O; Zubrick, Stephen R; Blair, Eve; Newnham, John P; Hickey, Martha

    2012-01-01

    To characterise fetal brain growth in children with specific language impairment (SLI). A nested case-control study. Perth, Western Australia. Thirty children meeting criteria for SLI at age 10 years were individually matched with a typically developing comparison child on sex, non-verbal ability, fetal gestational age, maternal age at conception, smoking and alcohol intake during pregnancy. Occipitofrontal head circumference (HC) was measured using ultrasonography at approximately 18 weeks gestation. Femur length provided a measure of fetal length. Occipitofrontal HC was measured at birth and at the 1-year postnatal follow-up using a precise paper tape measure, while crown-heel length acted as an index of body length at both time points. Raw data were transformed to z-scores using reference norms. The SLI group had a significantly smaller mean HC than the typically developing comparison children at birth, but there was no group difference at 18 weeks gestation or at the 1-year postnatal follow-up. Individual analyses found that 12 SLI children had an HC z-score less than -1 at birth, with three of these cases meeting criteria for microcephaly. There was no group difference in the indices of overall body size at any time point. Children with SLI are more likely to have a small HC at birth but not at 18 weeks gestation or infancy, suggesting growth asynchrony in brain development during the second half of pregnancy.

  15. Control of Auditory Attention in Children With Specific Language Impairment.

    Science.gov (United States)

    Victorino, Kristen R; Schwartz, Richard G

    2015-08-01

    Children with specific language impairment (SLI) appear to demonstrate deficits in attention and its control. Selective attention involves the cognitive control of attention directed toward a relevant stimulus and simultaneous inhibition of attention toward irrelevant stimuli. The current study examined attention control during a cross-modal word recognition task. Twenty participants with SLI (ages 9-12 years) and 20 age-matched peers with typical language development (TLD) listened to words through headphones and were instructed to attend to the words in 1 ear while ignoring the words in the other ear. They were simultaneously presented with pictures and asked to make a lexical decision about whether the pictures and auditory words were the same or different. Accuracy and reaction time were measured in 5 conditions, in which the stimulus in the unattended channel was manipulated. The groups performed with similar accuracy. Compared with their peers with TLD, children with SLI had slower reaction times overall and different within-group patterns of performance by condition. Children with TLD showed efficient inhibitory control in conditions that required active suppression of competing stimuli. Participants with SLI had difficulty exerting control over their auditory attention in all conditions, with particular difficulty inhibiting distractors of all types.

  16. Heme Gazing: Illuminating Eukaryotic Heme Trafficking, Dynamics, and Signaling with Fluorescent Heme Sensors.

    Science.gov (United States)

    Hanna, David A; Martinez-Guzman, Osiris; Reddi, Amit R

    2017-04-04

    Heme (iron protoporphyrin IX) is an essential protein prosthetic group and signaling molecule required for most life on Earth. All heme-dependent processes require the dynamic and rapid mobilization of heme from sites of synthesis or uptake to hemoproteins present in virtually every subcellular compartment. The cytotoxicity and hydrophobicity of heme necessitate that heme mobilization be carefully controlled to mitigate the deleterious effects of this essential toxin. Indeed, a number of disorders, including certain cancers, cardiovascular diseases, and aging and age-related neurodegenerative diseases, are tied to defects in heme homeostasis. However, the molecules and mechanisms that mediate heme transport and trafficking, and the dynamics of these processes, are poorly understood. This is in large part due to the lack of physical tools for probing cellular heme. Herein, we discuss the recent development of fluorescent probes that can monitor and image kinetically labile heme with respect to its mobilization and role in signaling. In particular, we will highlight how heme gazing with these tools can uncover new heme trafficking factors upon being integrated with genetic screens and illuminate the concentration, subcellular distribution, and dynamics of labile heme in various physiological contexts. Altogether, the monitoring of labile heme, along with recent biochemical and cell biological studies demonstrating the reversible regulation of certain cellular processes by heme, is challenging us to reconceptualize heme from being a static cofactor buried in protein active sites to a dynamic and mobile signaling molecule.

  17. Characteristics of early spelling of children with Specific Language Impairment.

    Science.gov (United States)

    Cordewener, Kim A H; Bosman, Anna M T; Verhoeven, Ludo

    2012-01-01

    The present study investigated active grapheme knowledge and early spelling of 59 first grade children with Specific Language Impairment (SLI). Speed, nature, and knowledge transfer of spelling acquisition were taken into account. Four orthographic characteristics that influence early spelling, namely, 'Type of Grapheme', 'Grapheme Position', 'Number of Graphemes', and 'Word Structure' were examined at the middle and at the end of first grade. At the beginning of first grade when children were between 71 and 97 months, they performed well below national norms on assessment of active grapheme knowledge. The delay in word spelling persisted, but decreased between the middle and the end of first grade. Despite this delay, the findings suggest that characteristics of early spelling for children with SLI are rather similar to those of children with typical language development. For example, children with SLI represented more graphemes at the end of first grade than at the middle of first grade, found it easier to represent the initial grapheme in words than the final or medial grapheme (Grapheme Position), were more successful spelling shorter than longer words (Number of Graphemes), and spelled words with simple structures (CVC) more accurately than those with complex structures (CVCC and CCVC; Word Structure). Finally, participants demonstrated that they can use known graphemes to spell words, but the transfer between active grapheme knowledge and word spelling was not always stable. As a result of this activity, readers will be able to explain the speed and the nature of spelling acquisition of children with SLI. As a result of this activity, readers will be able to explain what skills are most important for teachers to practice with children with SLI to improve the spelling skills of these children. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Gesture-speech integration in children with specific language impairment.

    Science.gov (United States)

    Mainela-Arnold, Elina; Alibali, Martha W; Hostetter, Autumn B; Evans, Julia L

    2014-11-01

    Previous research suggests that speakers are especially likely to produce manual communicative gestures when they have relative ease in thinking about the spatial elements of what they are describing, paired with relative difficulty organizing those elements into appropriate spoken language. Children with specific language impairment (SLI) exhibit poor expressive language abilities together with within-normal-range nonverbal IQs. This study investigated whether weak spoken language abilities in children with SLI influence their reliance on gestures to express information. We hypothesized that these children would rely on communicative gestures to express information more often than their age-matched typically developing (TD) peers, and that they would sometimes express information in gestures that they do not express in the accompanying speech. Participants were 15 children with SLI (aged 5;6-10;0) and 18 age-matched TD controls. Children viewed a wordless cartoon and retold the story to a listener unfamiliar with the story. Children's gestures were identified and coded for meaning using a previously established system. Speech-gesture combinations were coded as redundant if the information conveyed in speech and gesture was the same, and non-redundant if the information conveyed in speech was different from the information conveyed in gesture. Children with SLI produced more gestures than children in the TD group; however, the likelihood that speech-gesture combinations were non-redundant did not differ significantly across the SLI and TD groups. In both groups, younger children were significantly more likely to produce non-redundant speech-gesture combinations than older children. The gesture-speech integration system functions similarly in children with SLI and TD, but children with SLI rely more on gesture to help formulate, conceptualize or express the messages they want to convey. This provides motivation for future research examining whether interventions

  19. Music identification skills of children with specific language impairment.

    Science.gov (United States)

    Mari, Giorgia; Scorpecci, Alessandro; Reali, Laura; D'Alatri, Lucia

    2016-03-01

    To date very few studies have investigated the musical skills of children with specific language impairment (SLI). There is growing evidence that SLI affects areas other than language, and it is therefore reasonable to hypothesize that children with this disorder may have difficulties in perceiving musical stimuli appropriately. To compare melody and song identification skills in a group of children with SLI and in a control group of children with typical language development (TD); and to study possible correlations between music identification skills and language abilities in the SLI group. This is a prospective case control study. Two groups of children were enrolled: one meeting DSM-IV-TR(®) diagnostic criteria for SLI and the other comprising an age-matched group of children with TD. All children received a melody and a song identification test, together with a test battery assessing receptive and productive language abilities. 30 children with SLI (mean age = 56 ± 9 months) and 23 with TD (mean age = 60 ± 10 months) were included. Melody and song identification scores among SLI children were significantly lower than those of TD children, and in both groups song identification scores were significantly higher than melody identification scores. Song identification skills bore a significant correlation to chronological age in both groups (TD: r = 0.529, p = 0.009; SLI: r = 0.506, p = 0.004). Whereas no other variables were found explaining the variability of melody or song identification scores in either group, the correlation between language comprehension and song identification in the SLI group approached significance (r = 0.166, p = 0.076). The poorer music perception skills of SLI children as compared with TD ones suggests that SLI may also affect music perception. Therefore, training programmes that simultaneously stimulate via language and music may prove useful in the rehabilitation of children affected by SLI. © 2015 Royal College of Speech and

  20. Phonological deficits in specific language impairment and developmental dyslexia: towards a multidimensional model

    Science.gov (United States)

    Ramus, Franck; Marshall, Chloe R.; Rosen, Stuart

    2013-01-01

    An on-going debate surrounds the relationship between specific language impairment and developmental dyslexia, in particular with respect to their phonological abilities. Are these distinct disorders? To what extent do they overlap? Which cognitive and linguistic profiles correspond to specific language impairment, dyslexia and comorbid cases? At least three different models have been proposed: the severity model, the additional deficit model and the component model. We address this issue by comparing children with specific language impairment only, those with dyslexia-only, those with specific language impairment and dyslexia and those with no impairment, using a broad test battery of language skills. We find that specific language impairment and dyslexia do not always co-occur, and that some children with specific language impairment do not have a phonological deficit. Using factor analysis, we find that language abilities across the four groups of children have at least three independent sources of variance: one for non-phonological language skills and two for distinct sets of phonological abilities (which we term phonological skills versus phonological representations). Furthermore, children with specific language impairment and dyslexia show partly distinct profiles of phonological deficit along these two dimensions. We conclude that a multiple-component model of language abilities best explains the relationship between specific language impairment and dyslexia and the different profiles of impairment that are observed. PMID:23413264

  1. Declarative and Procedural Memory in Danish Speaking Children with Specific Language Impairment

    Science.gov (United States)

    Lum, Jarrad A. G.; Bleses, Dorthe

    2012-01-01

    It has been proposed that the language problems in specific language impairment (SLI) arise from basal ganglia abnormalities that lead to impairments with procedural and working memory but not declarative memory. In SLI, this profile of memory functioning has been hypothesized to underlie grammatical impairment but leave lexical knowledge…

  2. Linguistic transfer in bilingual children with specific language impairment.

    Science.gov (United States)

    Verhoeven, Ludo; Steenge, Judit; van Balkom, Hans

    2012-01-01

    In the literature so far the limited research on specific language impairment (SLI) in bilingual children has concentrated on linguistic skills in the first language (L1) and/or the second language (L2) without paying attention to the relations between the two types of skills and to the issue of linguistic transfer. To examine the first and second language proficiency of 75 Turkish-Dutch bilingual children with SLI in the age range between 7 and 11 years living in the Netherlands. A multidimensional perspective on language proficiency was taken in order to assess children's Turkish and Dutch proficiency levels, whereas equivalent tests were used in order to determine language dominance. A second aim was to find out to what extent the children's proficiency in L2 can be predicted from their L1 proficiency, while taking into account their general cognitive abilities. The children's performance on a battery of equivalent language ability tests in Turkish and Dutch was compared at three age levels. By means of analyses of variance, it was explored to what extent the factors of language and grade level as well as their interactions were significant. Bivariate correlations and partial correlations with age level partialled out were computed to examine the relationships between L1 and L2 proficiency levels. Moreover, regression analysis was conducted to find out to what extent the variance in general L2 proficiency levels could be explained by children's L1 proficiency, short-term memory and non-verbal intelligence. Repeated measures analyses showed that the children had generally higher scores on L1 as compared with L2 and that with progression of age the children's scores in L1 and L2 improved. Medium to high correlations were found between phonological memory, phonological awareness, grammatical skills and story comprehension in the two languages. Regression analysis revealed that children's L2 proficiency levels could be explained by their proficiency levels in L1

  3. Implications of Bilingual Development for Specific Language Impairments in Turkey

    Science.gov (United States)

    Topbas, Seyhun

    2011-01-01

    The potential impact of bilingualism on children's language development has emerged as a crucial concern for Turkey, but so far it has not been addressed from the point of view of language disorders. This short review examines the potential impact of bilingual language development for language impairments in Turkey, with special emphasis on the…

  4. Relationship between natural and heme-mediated antibody polyreactivity

    Energy Technology Data Exchange (ETDEWEB)

    Hadzhieva, Maya; Vassilev, Tchavdar [Stephan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Sofia 1113 (Bulgaria); Bayry, Jagadeesh; Kaveri, Srinivas; Lacroix-Desmazes, Sébastien [Sorbonne Universités, UPMC Univ Paris 06, UMR-S 1138, Centre de Recherche des Cordeliers, F-75006 Paris (France); INSERM, UMR-S 1138, F-75006 Paris (France); Université Paris Descartes, Sorbonne Paris Cité, UMR-S 1138, F-75006 Paris (France); Dimitrov, Jordan D., E-mail: jordan.dimitrov@crc.jussieu.fr [Sorbonne Universités, UPMC Univ Paris 06, UMR-S 1138, Centre de Recherche des Cordeliers, F-75006 Paris (France); INSERM, UMR-S 1138, F-75006 Paris (France); Université Paris Descartes, Sorbonne Paris Cité, UMR-S 1138, F-75006 Paris (France)

    2016-03-25

    Polyreactive antibodies represent a considerable fraction of the immune repertoires. Some antibodies acquire polyreactivity post-translationally after interaction with various redox-active substances, including heme. Recently we have demonstrated that heme binding to a naturally polyreactive antibody (SPE7) results in a considerable broadening of the repertoire of recognized antigens. A question remains whether the presence of certain level of natural polyreactivity of antibodies is a prerequisite for heme-induced further extension of antigen binding potential. Here we used a second monoclonal antibody (Hg32) with unknown specificity and absence of intrinsic polyreactivity as a model to study the potential of heme to induce polyreactivity of antibodies. We demonstrated that exposure to heme greatly extends the antigen binding potential of Hg32, suggesting that the intrinsic binding promiscuity is not a prerequisite for the induction of polyreactivity by heme. In addition we compared the kinetics and thermodynamics of the interaction of heme-exposed antibodies with a panel of unrelated antigens. These analyses revealed that the two heme-sensitive antibodies adopt different mechanisms of binding to the same set of antigens. This study contributes to understanding the phenomenon of induced antibody polyreactivity. The data may also be of importance for understanding of physiological and pathological roles of polyreactive antibodies. - Highlights: • Exposure of certain monoclonal IgE antibodies to heme results in gain of antigen binding polyreactivity. • Natural polyreactivity of antibodies is dispensable for acquisition of polyreactivity through interaction with heme. • Heme-induced monoclonal IgE antibodies differ in their thermodynamic mechanisms of antigen recognition.

  5. Mini Heme-Proteins: Designability of Structure and Diversity of Functions.

    Science.gov (United States)

    Rai, Jagdish

    2017-08-30

    Natural heme proteins may have heme bound to poly-peptide chain as a cofactor via noncovalent forces or heme as a prosthetic group may be covalently bound to the proteins. Nature has used porphyrins in diverse functions like electron transfer, oxidation, reduction, ligand binding, photosynthesis, signaling, etc. by modulating its properties through diverse protein matrices. Synthetic chemists have tried to utilize these molecules in equally diverse industrial and medical applications due to their versatile electro-chemical and optical properties. The heme iron has catalytic activity which can be modulated and enhanced for specific applications by protein matrix around it. Heme proteins can be designed into novel enzymes for sterio specific catalysis ranging from oxidation to reduction. These designed heme-proteins can have applications in industrial catalysis and biosensing. A peptide folds around heme easily due to hydrophobic effect of the large aromatic ring of heme. The directional property of co-ordinate bonding between peptide and metal ion in heme further specifies the structure. Therefore heme proteins can be easily designed for targeted structure and catalytic activity. The central aromatic chemical entity in heme viz. porphyrin is a very ancient molecule. Its presence in the prebiotic soup and in all forms of life suggests that it has played a vital role in the origin and progressive evolution of living organisms. Porphyrin macrocycles are highly conjugated systems composed of four modified pyrrole subunits interconnected at their α -carbon atoms via methine (=CH-) bridges. Initial minimalist models of hemoproteins focused on effect of heme-ligand co-ordinate bonding on chemical reactivity, spectroscopy, electrochemistry and magnetic properties of heme. The great sensitivity of these spectroscopic features of heme to its surrounding makes them extremely useful in structural elucidation of designed heme-peptide complexes. Therefore heme proteins are

  6. Heme acquisition mechanisms of Porphyromonas gingivalis - strategies used in a polymicrobial community in a heme-limited host environment.

    Science.gov (United States)

    Smalley, J W; Olczak, T

    2017-02-01

    Porphyromonas gingivalis, a main etiologic agent and key pathogen responsible for initiation and progression of chronic periodontitis requires heme as a source of iron and protoporphyrin IX for its survival and the ability to establish an infection. Porphyromonas gingivalis is able to accumulate a defensive cell-surface heme-containing pigment in the form of μ-oxo bisheme. The main sources of heme for P. gingivalis in vivo are hemoproteins present in saliva, gingival crevicular fluid, and erythrocytes. To acquire heme, P. gingivalis uses several mechanisms. Among them, the best characterized are those employing hemagglutinins, hemolysins, and gingipains (Kgp, RgpA, RgpB), TonB-dependent outer-membrane receptors (HmuR, HusB, IhtA), and hemophore-like proteins (HmuY, HusA). Proteins involved in intracellular heme transport, storage, and processing are less well characterized (e.g. PgDps). Importantly, P. gingivalis may also use the heme acquisition systems of other bacteria to fulfill its own heme requirements. Porphyromonas gingivalis displays a novel paradigm for heme acquisition from hemoglobin, whereby the Fe(II)-containing oxyhemoglobin molecule must first be oxidized to methemoglobin to facilitate heme release. This process not only involves P. gingivalis arginine- and lysine-specific gingipains, but other proteases (e.g. interpain A from Prevotella intermedia) or pyocyanin produced by Pseudomonas aeruginosa. Porphyromonas gingivalis is then able to fully proteolyze the more susceptible methemoglobin substrate to release free heme or to wrest heme from it directly through the use of the HmuY hemophore. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. The perception and expression of verb morphology in bilinguals with specific language impairment

    Directory of Open Access Journals (Sweden)

    Hourieh Ahadi

    2014-04-01

    Full Text Available Background and Aim: Most of the researches are about bilingual children with specific language impairment and importance of it in recognition and treatment. This study aimed to assess verb morphology in bilinguals with specific language impairment (SLI and compare them with normal bilinguals.Methods: Six bilingual (Azeri and Persian children with specific language impairment at the age of 7-8 years were collected from clinics of Tehran, Iran. They were evaluated about verb morphology using narrative speech and specific language impairment test and then, compared with six age-matched and six other language-matched children as control group. Children with specific language impairment were diagnosed by exhibiting a significant delay (more than one year in language that can not be explained by intelligence deficits, hearing loss or visual impairment. We used Man-Whitney test for comparing the groups.Results: Bilingual children with specific language impairment had delay in comparison with their age-matched group in subject-verb agreement (p=0.020 and articulating tense morphemes (p=0.019. They also had meaningful delay in using proper tense of verbs (past, present, and future in comparison with language-matched control group (p=0.029.Conclusion: Comparison of typical development of bilingual children and bilinguals with specific language impairment shows that verb morphology is a good clinical marker for diagnosing and treatment of these children.

  8. Hidden Language Impairments in Children: Parallels between Poor Reading Comprehension and Specific Language Impairment?

    Science.gov (United States)

    Nation, Kate; Clarke, Paula; Marshall, Catherine M.; Durand, Marianne

    2004-01-01

    This study investigates the oral language skills of 8-year-old children with impaired reading comprehension. Despite fluent and accurate reading and normal nonverbal ability, these children are poor at understanding what they have read. Tasks tapping 3 domains of oral language, namely phonology, semantics, and morphosyntax, were administered,…

  9. Alteration of the Regiospecificity of Human Heme Oxygenase-1 by Unseating of the Heme but not Disruption of the Distal Hydrogen Bonding Network†

    Science.gov (United States)

    Wang, Jinling; Evans, John P.; Ogura, Hiroshi; La Mar, Gerd N.; Ortiz de Montellano, Paul R.

    2008-01-01

    Heme oxygenase regiospecifically oxidizes heme at the α-meso position to give biliverdin IXα, CO, and iron. The heme orientation within the active site, which is thought to determine the oxidation regiospecificity, is shown here for the human enzyme (hHO1) to be largely determined by interactions between the heme carboxylic acid groups and residues Arg183 and Lys18 but not Tyr134. Mutation of either Arg183 or Lys18 individually does not significantly alter the NADPH-cytochrome P450 reductase-dependent reaction regiochemistry, but partially shifts the oxidation to the β/δ-meso positions in the reaction supported by ascorbic acid. Mutation of Glu29 to a lysine, which places a positive charge where it can interact with a heme carboxyl if the heme rotates by ~90°, causes a slight loss of regiospecificity, but combined with the R183E and K18E mutations results primarily in β/δ-meso oxidation of the heme under all conditions. NMR analysis of heme binding to the triple K18E/E29K/R183E mutant confirms rotation of the heme in the active site. Kinetic studies demonstrate that mutations of Arg183 greatly impair the rate of the P450 reductase-dependent reaction, in accord with the earlier finding that Arg183 is involved in binding of the reductase to hHO1, but have little effect on the ascorbate reaction. Mutations of Asp140 and Tyr58 that disrupt the active site hydrogen bonding network, impair catalytic rates but do not influence the oxidation regiochemistry. The results indicate both that the oxidation regiochemistry is largely controlled by ionic interactions of the heme propionic acid groups with the protein and that shifts in regiospecificity involve rotation of the heme about an axis perpendicular to the heme plane. PMID:16388581

  10. Impaired specific immunoreactivity in cows with hepatic lipidosis.

    Science.gov (United States)

    Wentink, G H; Rutten, V P; van den Ingh, T S; Hoek, A; Müller, K E; Wensing, T

    1997-05-01

    In this study, hepatic lipidosis in cows was experimentally induced by offering an energy surplus during the dry period. Liver triacylglycerol (TAG) was 16% in the experimental group. In the control group fed the same diet in restricted quantities, liver TAG was about 7%. The animals of both groups were vaccinated with tetanus vaccine at Day 3 after parturition. It was demonstrated that the cows with high liver TAG percentages had lower humoral and cellular (P hepatic lipidosis may be due to impaired immunoreactivity.

  11. Heme synthesis in the lead-intoxicated mouse embryo

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, G B; Maes, J

    1978-02-01

    Incorporation of /sup 55/Fe and of (/sup 14/C) glycine was studied in control embryos and mothers and in those which had received lead in the diet from day 7 of pregnancy. Incorporation of Fe into heme of embryonic liver which increases markedly for controls on day 17 of pregnancy was depressed greatly and showed no such increase in lead-intoxicated embryos. These embryos were retarded in growth but had normal heme concentrations in body and liver. Incorporation of glycine into embryonic heme and proteins was not affected. Data on incorporation in the mothers are also presented. It is thought that the impaired synthesis of heme in lead-intoxicated embryos limits their body growth during the late phase of pregnancy.

  12. Sequence-specific procedural learning deficits in children with specific language impairment.

    Science.gov (United States)

    Hsu, Hsinjen Julie; Bishop, Dorothy V M

    2014-05-01

    This study tested the procedural deficit hypothesis of specific language impairment (SLI) by comparing children's performance in two motor procedural learning tasks and an implicit verbal sequence learning task. Participants were 7- to 11-year-old children with SLI (n = 48), typically developing age-matched children (n = 20) and younger typically developing children matched for receptive grammar (n = 28). In a serial reaction time task, the children with SLI performed at the same level as the grammar-matched children, but poorer than age-matched controls in learning motor sequences. When tested with a motor procedural learning task that did not involve learning sequential relationships between discrete elements (i.e. pursuit rotor), the children with SLI performed comparably with age-matched children and better than younger grammar-matched controls. In addition, poor implicit learning of word sequences in a verbal memory task (the Hebb effect) was found in the children with SLI. Together, these findings suggest that SLI might be characterized by deficits in learning sequence-specific information, rather than generally weak procedural learning. © 2014 The Authors. Developmental Science Published by John Wiley & Sons Ltd.

  13. Teasing out specific language impairment from an autism spectrum disorder.

    Science.gov (United States)

    Tierney, Cheryl D; Gupta, Vidya Bhushan; Angel, Alma Patricia Del; Augustyn, Marilyn

    2012-04-01

    Marcus is a handsome, sweet, 7½-year-old boy with a significant history of delayed development, specifically in speech and language skills, as well as difficulties with social interactions that have led other specialists to be concerned about a diagnosis of an autism spectrum disorder.He has been seen in our primary care practice since birth. He was born full-term after vaginal delivery weighing 6 pounds, 6 ounces. There were no pregnancy or delivery complications noted. Genetic testing revealed normal chromosomes, fragile X, and microarray testing. Marcus was a picky eater and good sleeper and had delays in toilet training.There is no family history of attention-deficit hyperactivity disorder (ADHD), autism, or substance abuse. Maternal grandmother and mother have a history of learning difficulties, and his father and a paternal uncle have a history of depression and anxiety. Marcus lives in a supportive environment with his mother, father, and sister.Marcus was noted to have significantly delayed language, stuttering, and immediate echolalia as a toddler. Gross and fine motor milestones were met on time, but he did not talk or follow directions until 4 to 5 years old. As a younger child, he would pretend to talk on the phone or mow the grass with a pretend lawn mower, but other household activities were not of interest to Marcus.Currently, he enjoys puzzles, reading, and board games. He likes to play with other children and can interact with familiar adults. Marcus is reported to initiate social interactions, although he has difficulty in understanding personal space. Imaginative play is preferred over other types. He seeks out adult attention and will bring objects over to an adult especially to share his perceived accomplishment. Marcus has difficulty in playing cooperatively with his sister.He is independent with activities of daily living. Marcus is noted to have auditory defensiveness including covering his ears to loud noises and becoming distressed

  14. Verbal declarative memory impairments in specific language impairment are related to working memory deficits

    OpenAIRE

    Lum, Jarrad A.G.; Ullman, Michael T.; Conti-Ramsden, Gina

    2015-01-01

    This study examined verbal declarative memory functioning in SLI and its relationship to working memory. Encoding, recall, and recognition of verbal information was examined in children with SLI who had below average working memory (SLILow WM), children with SLI who had average working memory (SLIAvg. WM) and, a group of non-language impaired children with average working memory (TDAvg. WM). The SLILow WM group was significantly worse than both the SLIAvg. WM and TDAvg. WM groups at encoding ...

  15. Mental fatigue impairs soccer-specific decision-making skill

    NARCIS (Netherlands)

    Smith, Mitchell R.; Zeuwts, Linus; Lenoir, Matthieu; Hens, Nathalie; De Jong, Laura M. S.; Coutts, Aaron J.

    This study aimed to investigate the impact of mental fatigue on soccer-specific decision-making. Twelve well-trained male soccer players performed a soccer-specific decision-making task on two occasions, separated by at least 72 h. The decision-making task was preceded in a randomised order by 30

  16. Genome-based analysis of heme biosynthesis and uptake in prokaryotic systems.

    Science.gov (United States)

    Cavallaro, Gabriele; Decaria, Leonardo; Rosato, Antonio

    2008-11-01

    Heme is the prosthetic group of many proteins that carry out a variety of key biological functions. In addition, for many pathogenic organisms, heme (acquired from the host) may constitute a very important source of iron. Organisms can meet their heme demands by taking it up from external sources, by producing the cofactor through a dedicated biosynthetic pathway, or both. Here we analyzed the distribution of proteins specifically involved in the processes of heme biosynthesis and heme uptake in 474 prokaryotic organisms. These data allowed us to identify which organisms are capable of performing none, one, or both processes, based on the similarity to known systems. Some specific instances where one or more proteins along the pathways had unusual modifications were singled out. For two key protein domains involved in heme uptake, we could build a series of structural models, which suggested possible alternative modes of heme binding. Future directions for experimental work are given.

  17. Imitation of Body Postures and Hand Movements in Children with Specific Language Impairment

    Science.gov (United States)

    Marton, Klara

    2009-01-01

    Within the domain-general theory of language impairment, this study examined body posture and hand movement imitation in children with specific language impairment (SLI) and in their age-matched peers. Participants included 40 children with SLI (5 years 3 months to 6 years 10 months of age) and 40 children with typical language development (5…

  18. Procedural and Declarative Memory in Children with and without Specific Language Impairment

    Science.gov (United States)

    Lum, Jarrad A. G.; Gelgic, Celin; Conti-Ramsden, Gina

    2010-01-01

    Background: Much evidence has accumulated to indicate memory deficits in children with specific language impairment. However, most research has focused on working memory impairments in these children. Less is known about the functioning of other memory systems in this population. Aims: This study examined procedural and declarative memory in young…

  19. Spoken Word Recognition in Adolescents with Autism Spectrum Disorders and Specific Language Impairment

    Science.gov (United States)

    Loucas, Tom; Riches, Nick; Baird, Gillian; Pickles, Andrew; Simonoff, Emily; Chandler, Susie; Charman, Tony

    2013-01-01

    Spoken word recognition, during gating, appears intact in specific language impairment (SLI). This study used gating to investigate the process in adolescents with autism spectrum disorders plus language impairment (ALI). Adolescents with ALI, SLI, and typical language development (TLD), matched on nonverbal IQ listened to gated words that varied…

  20. Screening for Specific Language Impairment in Preschool Children: Evaluating a Screening Procedure Including the Token Test

    Science.gov (United States)

    Willinger, Ulrike; Schmoeger, Michaela; Deckert, Matthias; Eisenwort, Brigitte; Loader, Benjamin; Hofmair, Annemarie; Auff, Eduard

    2017-01-01

    Specific language impairment (SLI) comprises impairments in receptive and/or expressive language. Aim of this study was to evaluate a screening for SLI. 61 children with SLI (SLI-children, age-range 4-6 years) and 61 matched typically developing controls were tested for receptive language ability (Token Test-TT) and for intelligence (Wechsler…

  1. Working Memory and Learning in Children with Developmental Coordination Disorder and Specific Language Impairment

    Science.gov (United States)

    Alloway, Tracy Packiam; Archibald, Lisa

    2008-01-01

    The authors compared 6- to 11-year-olds with developmental coordination disorder (DCD) and those with specific language impairment (SLI) on measures of memory (verbal and visuospatial short-term and working memory) and learning (reading and mathematics). Children with DCD with typical language skills were impaired in all four areas of memory…

  2. Imitative Production of Regular Past Tense -Ed by English-Speaking Children with Specific Language Impairment

    Science.gov (United States)

    Dalal, Rinky Harish; Loeb, Diane Frome

    2005-01-01

    Background: Language intervention procedures often involve the speech-language pathologist highlighting or making more salient forms that are problematic for the child with a language impairment. According to limited processing accounts of specific language impairment (SLI), one way to increase the saliency of a form is to manipulate its sentence…

  3. Visual Fast Mapping in School-Aged Children with Specific Language Impairment

    Science.gov (United States)

    Alt, Mary

    2013-01-01

    Purpose: To determine whether children with specific language impairment (SLI) demonstrate impaired visual fast mapping skills compared with unimpaired peers and to test components of visual working memory that may contribute to a visual working memory deficit. Methods: Fifty children (25 SLI) played 2 computer-based visual fast mapping games…

  4. Working memory and sentence comprehension of Hong Kong Chinese children with specific language impairment.

    Science.gov (United States)

    Siu, Elaine; Man, David W K

    2006-09-01

    Children with Specific Language Impairment present with delayed language development, but do not have a history of hearing impairment, mental deficiency, or associated social or behavioral problems. Non-word repetition was suggested as an index to reflect the capacity of phonological working memory. There is a paucity of such studies among Hong Kong Chinese children. This preliminary study aimed to examine the relationship between phonological working memory and Specific Language Impairment, through the processes of non-word repetition and sentence comprehension, of children with Specific Language Impairment and pre-school children with normal language development. Both groups of children were screened by a standardized language test. A list of Cantonese (the commonest dialect used in Hong Kong) multisyllabic nonsense utterances and a set of 18 sentences were developed for this study. t-tests and Pearson correlation were used to study the relationship between non-word repetition, working memory and specific language impairment. Twenty-three pre-school children with Specific Language Impairment (mean age = 68.30 months; SD = 6.90) and another 23 pre-school children (mean age = 67.30 months; SD = 6.16) participated in the study. Significant difference performance was found between the Specific Language Impairment group and normal language group in the multisyllabic nonsense utterances repetition task and the sentence comprehension task. Length effect was noted in Specific Language Impairment group children, which is consistent with the findings of other literature. In addition, correlations were also observed between the number of nonsense utterances repeated and the number of elements comprehended. Cantonese multisyllabic nonsense utterances might be worth further developing as a screening tool for the early detection of children with Specific Language Impairment.

  5. Heme degrading protein HemS is involved in oxidative stress response of Bartonella henselae.

    Directory of Open Access Journals (Sweden)

    MaFeng Liu

    Full Text Available Bartonellae are hemotropic bacteria, agents of emerging zoonoses. These bacteria are heme auxotroph Alphaproteobacteria which must import heme for supporting their growth, as they cannot synthesize it. Therefore, Bartonella genome encodes for a complete heme uptake system allowing the transportation of this compound across the outer membrane, the periplasm and the inner membranes. Heme has been proposed to be used as an iron source for Bartonella since these bacteria do not synthesize a complete system required for iron Fe³⁺ uptake. Similarly to other bacteria which use heme as an iron source, Bartonellae must transport this compound into the cytoplasm and degrade it to allow the release of iron from the tetrapyrrole ring. For Bartonella, the gene cluster devoted to the synthesis of the complete heme uptake system also contains a gene encoding for a polypeptide that shares homologies with heme trafficking or degrading enzymes. Using complementation of an E. coli mutant strain impaired in heme degradation, we demonstrated that HemS from Bartonella henselae expressed in E. coli allows the release of iron from heme. Purified HemS from B. henselae binds heme and can degrade it in the presence of a suitable electron donor, ascorbate or NADPH-cytochrome P450 reductase. Knocking down the expression of HemS in B. henselae reduces its ability to face H₂O₂ induced oxidative stress.

  6. Declarative capacity does not trade-off with procedural capacity in children with specific language impairment

    Directory of Open Access Journals (Sweden)

    Sengottuvel Kuppuraj

    2016-10-01

    Full Text Available Background and aims The procedural deficit hypothesis attributes the language phenotype in children with specific language impairment to an impaired procedural and relatively intact declarative memory system. The declarative compensatory hypothesis is an extension of the procedural deficit hypothesis which claims that the declarative system in specific language impairment compensates for the procedural deficit. The present study’s aim was to examine the claims of the procedural deficit hypothesis and declarative compensatory hypothesis by examining these memory systems and relation between them in specific language impairment. Methods Participants were children aged 8–13 years, 30 with specific language impairment and 30 typically developing controls, who spoke Kannada (an agglutinating language of the Dravidian family. Procedural learning was assessed using a serial reaction time task. Declarative memory was assessed using two non-verbal tasks that differed at the level of encoding and retrieval: a recognition memory task after incidental encoding using real and novel object images and a recall task after intentional encoding using visual paired associates. Retrieval was examined after short (10 min and long (60 min delays after encoding on both declarative tasks. Results Findings confirmed that children with specific language impairment (SLI have impaired procedural memory on a non-verbal serial reaction time task. On recognition memory task after incidental encoding though children with specific language impairment encoded less well, they recognized items as well as typically developing controls. Both the groups retrieved more at short compared to long intervals and retrieved real (verbalizable objects better than novel objects. On visual paired associates (recall task with intentional encoding children with specific language impairment retrieved less than typically developing children (even after controlling for non-verbal ability

  7. Post-translational transformation of methionine to aspartate is catalyzed by heme iron and driven by peroxide: a novel subunit-specific mechanism in hemoglobin.

    Science.gov (United States)

    Strader, Michael Brad; Hicks, Wayne A; Kassa, Tigist; Singleton, Eileen; Soman, Jayashree; Olson, John S; Weiss, Mitchell J; Mollan, Todd L; Wilson, Michael T; Alayash, Abdu I

    2014-08-08

    A pathogenic V67M mutation occurs at the E11 helical position within the heme pockets of variant human fetal and adult hemoglobins (Hb). Subsequent post-translational modification of Met to Asp was reported in γ subunits of human fetal Hb Toms River (γ67(E11)Val → Met) and β subunits of adult Hb (HbA) Bristol-Alesha (β67(E11)Val → Met) that were associated with hemolytic anemia. Using kinetic, proteomic, and crystal structural analysis, we were able to show that the Met → Asp transformation involves heme cycling through its oxoferryl state in the recombinant versions of both proteins. The conversion to Met and Asp enhanced the spontaneous autoxidation of the mutants relative to wild-type HbA and human fetal Hb, and the levels of Asp were elevated with increasing levels of hydrogen peroxide (H2O2). Using H2(18)O2, we verified incorporation of (18)O into the Asp carboxyl side chain confirming the role of H2O2 in the oxidation of the Met side chain. Under similar experimental conditions, there was no conversion to Asp at the αMet(E11) position in the corresponding HbA Evans (α62(E11)Val → Met). The crystal structures of the three recombinant Met(E11) mutants revealed similar thioether side chain orientations. However, as in the solution experiments, autoxidation of the Hb mutant crystals leads to electron density maps indicative of Asp(E11) formation in β subunits but not in α subunits. This novel post-translational modification highlights the nonequivalence of human Hb α, β, and γ subunits with respect to redox reactivity and may have direct implications to α/β hemoglobinopathies and design of oxidatively stable Hb-based oxygen therapeutics. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. A Note on Intelligence Assessment within Studies of Specific Language Impairment.

    Science.gov (United States)

    Camarata, Stephen; Swisher, Linda

    1990-01-01

    Research procedures used to evaluate the intelligence of children with specific language impairment are reviewed. Almost half of the 167 studies did not include adequate descriptions of intelligence assessment. (Author/JDD)

  9. Language and executive functioning in the context of specific language impairment and bilingualism

    NARCIS (Netherlands)

    Laloi, A.

    2015-01-01

    The present thesis has investigated how French-speaking monolingual and bilingual children with SLI (specific language impairment) performed on various tasks examining language and executive functioning (EF) abilities, in comparison to monolingual and bilingual peers without SLI. Language was

  10. Phonological working memory and auditory processing speed in children with specific language impairment

    Directory of Open Access Journals (Sweden)

    Fatemeh Haresabadi

    2015-02-01

    Full Text Available Background and Aim: Specific language impairment (SLI, one variety of developmental language disorder, has attracted much interest in recent decades. Much research has been conducted to discover why some children have a specific language impairment. So far, research has failed to identify a reason for this linguistic deficiency. Some researchers believe language disorder causes defects in phonological working memory and affects auditory processing speed. Therefore, this study reviews the results of research investigating these two factors in children with specific language impairment.Recent Findings: Studies have shown that children with specific language impairment face constraints in phonological working memory capacity. Memory deficit is one possible cause of linguistic disorder in children with specific language impairment. However, in these children, disorder in information processing speed is observed, especially regarding the auditory aspect.Conclusion: Much more research is required to adequately explain the relationship between phonological working memory and auditory processing speed with language. However, given the role of phonological working memory and auditory processing speed in language acquisition, a focus should be placed on phonological working memory capacity and auditory processing speed in the assessment and treatment of children with a specific language impairment.

  11. Heme Synthesis and Acquisition in Bacterial Pathogens

    OpenAIRE

    Choby, Jacob E.; Skaar, Eric P.

    2016-01-01

    Bacterial pathogens require the iron-containing cofactor heme to cause disease. Heme is essential to the function of hemoproteins, which are involved in energy generation by the electron transport chain, detoxification of host immune effectors, and other processes. During infection, bacterial pathogens must synthesize heme or acquire heme from the host; however, host heme is sequestered in high-affinity hemoproteins. Pathogens have evolved elaborate strategies to acquire heme from host source...

  12. Heme requirement and intracellular trafficking in Trypanosoma cruzi epimastigotes

    International Nuclear Information System (INIS)

    Lara, F.A.; Sant'Anna, C.; Lemos, D.; Laranja, G.A.T.; Coelho, M.G.P.; Reis Salles, I.; Michel, A.; Oliveira, P.L.; Cunha-e-Silva, N.; Salmon, D.; Paes, M.C.

    2007-01-01

    Epimastigotes multiplies in the insect midgut by taking up nutrients present in the blood meal including heme bound to hemoglobin of red blood cell. During blood meal digestion by vector proteases in the posterior midgut, hemoglobin is clipped off into amino acids, peptides, and free heme. In this paper, we compared the heme and hemoglobin uptake kinetics and followed their intracellular trafficking. Addition of heme to culture medium increased epimastigote proliferation in a dose-dependent manner, while medium supplemented with hemoglobin enhanced growth after 3-day lag phase. Medium supplemented with globin-derived peptides stimulated cell proliferation in a dose-independent way. Using Palladium mesoporphyrin IX (Pd-mP) as a fluorescent heme-analog, we observed that heme internalization proceeded much faster than that observed by hemoglobin-rhodamine. Binding experiments showed that parasites accumulated the Pd-mP into the posterior region of the cell whereas hemoglobin-rhodamine stained the anterior region. Finally, using different specific inhibitors of ABC transporters we conclude that a P-glycoprotein homologue transporter is probably involved in heme transport through the plasma membrane

  13. Toward epigenetic and gene regulation models of specific language impairment: looking for links among growth, genes, and impairments

    Directory of Open Access Journals (Sweden)

    Rice Mabel L

    2012-11-01

    Full Text Available Abstract Children with specific language impairment (SLI are thought to have an inherited form of language impairment that spares other developmental domains. SLI shows strong heritability and recent linkage and association studies have replicated results for candidate genes. Regulatory regions of the genes may be involved. Behavioral growth models of language development of children with SLI reveal that the onset of language is delayed, and the growth trajectories of children with SLI parallel those of younger children without SLI. The rate of language acquisition decelerates in the pre-adolescent period, resulting in immature language levels for the children with SLI that persist into adolescence and beyond. Recent genetic and epigenetic discoveries and models relevant to language impairment are reviewed. T cell regulation of onset, acceleration, and deceleration signaling are described as potential conceptual parallels to the growth timing elements of language acquisition and impairment. A growth signaling disruption (GSD hypothesis is proposed for SLI, which posits that faulty timing mechanisms at the cellular level, intrinsic to neurocortical functioning essential for language onset and growth regulation, are at the core of the growth outcomes of SLI. The GSD highlights the need to document and account for growth patterns over childhood and suggests needed directions for future investigation.

  14. Heme isomers substantially affect heme's electronic structure and function

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2017-01-01

    Inspection of heme protein structures in the protein data bank reveals four isomers of heme characterized by different relative orientations of the vinyl side chains; remarkably, all these have been reported in multiple protein structures. Density functional theory computations explain this as du...

  15. Bacterial Nitric Oxide Synthase Is Required for the Staphylococcus aureus Response to Heme Stress.

    Science.gov (United States)

    Surdel, Matthew C; Dutter, Brendan F; Sulikowski, Gary A; Skaar, Eric P

    2016-08-12

    Staphylococcus aureus is a pathogen that causes significant morbidity and mortality worldwide. Within the vertebrate host, S. aureus requires heme as a nutrient iron source and as a cofactor for multiple cellular processes. Although required for pathogenesis, excess heme is toxic. S. aureus employs a two-component system, the heme sensor system (HssRS), to sense and protect against heme toxicity. Upon activation, HssRS induces the expression of the heme-regulated transporter (HrtAB), an efflux pump that alleviates heme toxicity. The ability to sense and respond to heme is critical for the pathogenesis of numerous Gram-positive organisms, yet the mechanism of heme sensing remains unknown. Compound '3981 was identified in a high-throughput screen as an activator of staphylococcal HssRS that triggers HssRS independently of heme accumulation. '3981 is toxic to S. aureus; however, derivatives of '3981 were synthesized that lack toxicity while retaining HssRS activation, enabling the interrogation of the heme stress response without confounding toxic effects of the parent molecule. Using '3981 derivatives as probes of the heme stress response, numerous genes required for '3981-induced activation of HssRS were uncovered. Specifically, multiple genes involved in the production of nitric oxide were identified, including the gene encoding bacterial nitric oxide synthase (bNOS). bNOS protects S. aureus from oxidative stress imposed by heme. Taken together, this work identifies bNOS as crucial for the S. aureus heme stress response, providing evidence that nitric oxide synthesis and heme sensing are intertwined.

  16. Comparison of Spontaneously Elicited Language Patterns in Specific Language Impairment and High-Functioning Autism.

    Science.gov (United States)

    Craig, Megan; Trauner, Doris

    2018-02-01

    We aimed to characterize differences in the use of language in children with specific language impairment and high-functioning autism by analyzing verbal responses on standardized tests. The overall goal was to provide clinicians with additional tools with which to aid in distinguishing the two neurodevelopmental disorders. This study included 16 children with specific language impairment, 28 children with high-functioning autism, and 52 typically developing participants between the ages of six and 14. Groups were matched for age, and specific language impairment and high-functioning autism groups were matched on verbal and performance IQ. Responses from standardized tests were examined for response length, grammatical errors, filler words, perseverations, revisions (repeated attempts to begin or continue a sentence), off-topic attention shifts (lapses in attention to the task), and rambling. Data were analyzed using parametric and nonparametric methods. Specific language impairment responses were longer and contained more filler words than did those of the other two groups, whereas high-functioning autism responses exhibited more grammatical errors, off-topic attention shifts, and rambling. Specific language impairment and high-functioning autism responses showed higher rates of perseveration compared with controls. There were no significant differences in revisions among the three groups. Differences in language patterns of participants with specific language impairment and high-functioning autism may be useful to the clinician in helping to differentiate isolated language impairment from high-functioning autism. The results also support the conclusion that the two conditions are separable, and each exhibits a different pattern of language dysfunction. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Information Processing and Proactive Interference in Children with and without Specific Language Impairment

    Science.gov (United States)

    Marton, Klara; Campanelli, Luca; Eichorn, Naomi; Scheuer, Jessica; Yoon, Jungmee

    2014-01-01

    Purpose: Increasing evidence suggests that children with specific language impairment (SLI) have a deficit in inhibition control, but research isolating specific abilities is scarce. The goal of this study was to examine whether children with SLI differ from their peers in resistance to proactive interference under different conditions. Method: An…

  18. Abnormal Functional Lateralization and Activity of Language Brain Areas in Typical Specific Language Impairment (Developmental Dysphasia)

    Science.gov (United States)

    de Guibert, Clement; Maumet, Camille; Jannin, Pierre; Ferre, Jean-Christophe; Treguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

    2011-01-01

    Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting…

  19. Autistic symptomatology and language ability in autism spectrum disorder and specific language impairment.

    Science.gov (United States)

    Loucas, Tom; Charman, Tony; Pickles, Andrew; Simonoff, Emily; Chandler, Susie; Meldrum, David; Baird, Gillian

    2008-11-01

    Autism spectrum disorders (ASD) and specific language impairment (SLI) are common developmental disorders characterised by deficits in language and communication. The nature of the relationship between them continues to be a matter of debate. This study investigates whether the co-occurrence of ASD and language impairment is associated with differences in severity or pattern of autistic symptomatology or language profile. Participants (N = 97) were drawn from a total population cohort of 56,946 screened as part of study to ascertain the prevalence of ASD, aged 9 to 14 years. All children received an ICD-10 clinical diagnosis of ASD or No ASD. Children with nonverbal IQ > or =80 were divided into those with a language impairment (language score of 77 or less) and those without, creating three groups: children with ASD and a language impairment (ALI; N = 41), those with ASD and but no language impairment (ANL; N = 31) and those with language impairment but no ASD (SLI; N = 25). Children with ALI did not show more current autistic symptoms than those with ANL. Children with SLI were well below the threshold for ASD. Their social adaptation was higher than the ASD groups, but still nearly 2 SD below average. In ALI the combination of ASD and language impairment was associated with weaker functional communication and more severe receptive language difficulties than those found in SLI. Receptive and expressive language were equally impaired in ALI, whereas in SLI receptive language was stronger than expressive. Co-occurrence of ASD and language impairment is not associated with increased current autistic symptomatology but appears to be associated with greater impairment in receptive language and functional communication.

  20. The heme-heme oxygenase system: a molecular switch in wound healing.

    NARCIS (Netherlands)

    Wagener, F.A.D.T.G.; Beurden, H.E. van; Hoff, J.W. Von den; Adema, G.J.; Figdor, C.G.

    2003-01-01

    When cells are injured they release their contents, resulting in a local accumulation of free heme proteins and heme. Here, we investigated the involvement of heme and its degrading enzyme heme oxygenase (HO) in the inflammatory process during wound healing. We observed that heme directly

  1. Heme Synthesis and Acquisition in Bacterial Pathogens.

    Science.gov (United States)

    Choby, Jacob E; Skaar, Eric P

    2016-08-28

    Bacterial pathogens require the iron-containing cofactor heme to cause disease. Heme is essential to the function of hemoproteins, which are involved in energy generation by the electron transport chain, detoxification of host immune effectors, and other processes. During infection, bacterial pathogens must synthesize heme or acquire heme from the host; however, host heme is sequestered in high-affinity hemoproteins. Pathogens have evolved elaborate strategies to acquire heme from host sources, particularly hemoglobin, and both heme acquisition and synthesis are important for pathogenesis. Paradoxically, excess heme is toxic to bacteria and pathogens must rely on heme detoxification strategies. Heme is a key nutrient in the struggle for survival between host and pathogen, and its study has offered significant insight into the molecular mechanisms of bacterial pathogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Increased Heme Levels in the Heart Lead to Exacerbated Ischemic Injury.

    Science.gov (United States)

    Sawicki, Konrad Teodor; Shang, Meng; Wu, Rongxue; Chang, Hsiang-Chun; Khechaduri, Arineh; Sato, Tatsuya; Kamide, Christine; Liu, Ting; Naga Prasad, Sathyamangla V; Ardehali, Hossein

    2015-07-31

    Heme is an essential iron-containing molecule for cardiovascular physiology, but in excess it may increase oxidative stress. Failing human hearts have increased heme levels, with upregulation of the rate-limiting enzyme in heme synthesis, δ-aminolevulinic acid synthase 2 (ALAS2), which is normally not expressed in cardiomyocytes. We hypothesized that increased heme accumulation (through cardiac overexpression of ALAS2) leads to increased oxidative stress and cell death in the heart. We first showed that ALAS2 and heme levels are increased in the hearts of mice subjected to coronary ligation. To determine the causative role of increased heme in the development of heart failure, we generated transgenic mice with cardiac-specific overexpression of ALAS2. While ALAS2 transgenic mice have normal cardiac function at baseline, their hearts display increased heme content, higher oxidative stress, exacerbated cell death, and worsened cardiac function after coronary ligation compared to nontransgenic littermates. We confirmed in cultured cardiomyoblasts that the increased oxidative stress and cell death observed with ALAS2 overexpression is mediated by increased heme accumulation. Furthermore, knockdown of ALAS2 in cultured cardiomyoblasts exposed to hypoxia reversed the increases in heme content and cell death. Administration of the mitochondrial antioxidant MitoTempo to ALAS2-overexpressing cardiomyoblasts normalized the elevated oxidative stress and cell death levels to baseline, indicating that the effects of increased ALAS2 and heme are through elevated mitochondrial oxidative stress. The clinical relevance of these findings was supported by the finding of increased ALAS2 induction and heme accumulation in failing human hearts from patients with ischemic cardiomyopathy compared to nonischemic cardiomyopathy. Heme accumulation is detrimental to cardiac function under ischemic conditions, and reducing heme in the heart may be a novel approach for protection against the

  3. Adjective production by Russian-speaking children with specific language impairment.

    Science.gov (United States)

    Tribushinina, Elena; Dubinkina, Elena

    2012-06-01

    Research on specific language impairment (SLI) has primarily focused on the acquisition of nouns and verbs. Less attention has been given to other content-word classes, such as adjectives and adverbs. This article investigates adjective production by 7- to 10-year-old Russian-speaking children with SLI and their typically developing (TD) peers and focuses on the production of antonymous adjectives and degree markers in an elicitation experiment. The results show that degree morphology is more impaired in SLI than antonymy. In antonym production, children with SLI were able to catch up with their TD peers by age 8. In the domain of degree, however, the SLI group lagged behind the TD controls across all ages studied. Error analysis indicates that language-impaired children have particular difficulty with agreement inflection and affixal negations. They also substitute adjectives with specific meanings by more general terms. The implications of this study for the morphological-richness hypothesis are discussed.

  4. Specific marker of feigned memory impairment: The activation of left superior frontal gyrus.

    Science.gov (United States)

    Chen, Zi-Xiang; Xue, Li; Liang, Chun-Yu; Wang, Li-Li; Mei, Wei; Zhang, Qiang; Zhao, Hu

    2015-11-01

    Faking memory impairment means normal people complain lots of memory problems without organic damage in forensic assessments. Using alternative forced-choice paradigm, containing digital or autobiographical information, previous neuroimaging studies have indicated that faking memory impairment could cause the activation in the prefrontal and parietal regions, and might involve a fronto-parietal-subcortical circuit. However, it is still unclear whether different memory types have influence on faking or not. Since different memory types, such as long-term memory (LTM) and short-term memory (STM), were found supported by different brain areas, we hypothesized that feigned STM or LTM impairment had distinct neural activation mapping. Besides that, some common neural correlates may act as the general characteristic of feigned memory impairment. To verify this hypothesis, the functional magnetic resonance imaging (fMRI) combined with an alternative word forced-choice paradigm were used in this study. A total of 10 right-handed participants, in this study, had to perform both STW and LTM tasks respectively under answering correctly, answering randomly and feigned memory impairment conditions. Our results indicated that the activation of the left superior frontal gyrus and the left medial frontal gyrus was associated with feigned LTM impairment, whereas the left superior frontal gyrus, the left precuneus and the right anterior cingulate cortex (ACC) were highly activated while feigning STM impairment. Furthermore, an overlapping was found in the left superior frontal gyrus, and it suggested that the activity of the left superior frontal gyrus might be acting as a specific marker of feigned memory impairment. Copyright © 2015. Published by Elsevier Ltd.

  5. Working Memory Functioning in Children with Learning Disorders and Specific Language Impairment

    Science.gov (United States)

    Schuchardt, Kirsten; Bockmann, Ann-Katrin; Bornemann, Galina; Maehler, Claudia

    2013-01-01

    Purpose: On the basis of Baddeley's working memory model (1986), we examined working memory functioning in children with learning disorders with and without specific language impairment (SLI). We pursued the question whether children with learning disorders exhibit similar working memory deficits as children with additional SLI. Method: In…

  6. Sentence Repetition in Deaf Children with Specific Language Impairment in British Sign Language

    Science.gov (United States)

    Marshall, Chloë; Mason, Kathryn; Rowley, Katherine; Herman, Rosalind; Atkinson, Joanna; Woll, Bencie; Morgan, Gary

    2015-01-01

    Children with specific language impairment (SLI) perform poorly on sentence repetition tasks across different spoken languages, but until now, this methodology has not been investigated in children who have SLI in a signed language. Users of a natural sign language encode different sentence meanings through their choice of signs and by altering…

  7. Textese and use of texting by children with typical language development and Specific Language Impairment

    NARCIS (Netherlands)

    Blom, E.; van Dijk, C.; Vasić, N.; van Witteloostuijn, M.; Avrutin, S.

    The purpose of this study was to investigate texting and textese, which is the special register used for sending brief text messages, across children with typical development (TD) and children with Specific Language Impairment (SLI). Using elicitation techniques, texting and spoken language messages

  8. Utility of the Spelling Sensitivity Score to Analyze Spellings of Children with Specific Language Impairment

    Science.gov (United States)

    Werfel, Krystal L.; Krimm, Hannah

    2015-01-01

    The purpose of this study was to examine the utility of the Spelling Sensitivity Score (SSS) beyond percentage correct scoring in analyzing the spellings of children with specific language impairment (SLI). Participants were 31 children with SLI and 28 children with typical language in grades 2-4. Spellings of individual words were scored using…

  9. Influence of Language Load on Speech Motor Skill in Children with Specific Language Impairment

    Science.gov (United States)

    Saletta, Meredith; Goffman, Lisa; Ward, Caitlin; Oleson, Jacob

    2018-01-01

    Purpose: Children with specific language impairment (SLI) show particular deficits in the generation of sequenced action--the quintessential procedural task. Practiced imitation of a sequence may become rote and require reduced procedural memory. This study explored whether speech motor deficits in children with SLI occur generally or only in…

  10. Generalized Motor Abilities and Timing Behavior in Children with Specific Language Impairment

    Science.gov (United States)

    Zelaznik, Howard N.; Goffman, Lisa

    2010-01-01

    Purpose: To examine whether children with specific language impairment (SLI) differ from normally developing peers in motor skills, especially those skills related to timing. Method: Standard measures of gross and fine motor development were obtained. Furthermore, finger and hand movements were recorded while children engaged in 4 different timing…

  11. Memory Functioning and Mental Verbs Acquisition in Children with Specific Language Impairment

    Science.gov (United States)

    Spanoudis, George C.; Natsopoulos, Demetrios

    2011-01-01

    Memory and language operate in synergy. Recent literature stresses the importance of memory functioning in interpreting language deficits. Two groups of 50 children each, ages 8-12 were studied. The first group included children with specific language impairment, while the participants in the second group were typically developing children. The…

  12. Connective processing by bilingual children and monolinguals with specific language impairment : distinct profiles

    NARCIS (Netherlands)

    Mak, W.M.; Tribushinina, E.; Lomako, Julia; Gagarina, N.; Abrosova, Ekaterina; Sanders, T.J.M.

    2017-01-01

    Production studies show that both Russian-speaking children with specific language impairment (SLI) and bilingual children for whom Russian is a non-dominant language have difficulty distinguishing between the near-synonymous connectives i ‘and’ and a ‘and/but’. I is a preferred connective when

  13. Failure to meet language milestones at two years of age is predictive of specific language impairment

    NARCIS (Netherlands)

    Diepeveen, F.B.; Dusseldorp, E.; Bol, G.W.; Oudesluys-Murphy, A.M.; Verkerk, P.H.

    2016-01-01

    This study established predictive properties of single language milestones for specific language impairment (SLI) after the age of four, as these had not previously been reported in the literature. Methods In this nested case-control study, children attending special needs schools for severe speech

  14. Working Memory Capacity and Language Processes in Children with Specific Language Impairment

    Science.gov (United States)

    Marton, Klara; Schwartz, Richard G.

    2003-01-01

    This study examined the interaction between working memory and language comprehension in children with specific language impairment (SLI), focusing on the function of the central executive component and its interaction with the phonological loop (A. D. Baddeley, 1986) in complex working memory tasks. Thirteen children with SLI and 13 age-matched…

  15. Using Pupillometry to Investigate Sentence Comprehension in Children with and without Specific Language Impairment

    Science.gov (United States)

    Lum, Jarrad A. G.; Youssef, George J.; Clark, Gillian M.

    2017-01-01

    Purpose: In this study pupillometry was used to investigate the allocation of attentional resources associated with sentence comprehension in children with and without specific language impairment (SLI). Method: Eighteen children with SLI (age: M = 6.4 years) and 18 typically developing (TD) children (age: M = 6.3 years) participated in the study.…

  16. Tense Marking and Spontaneous Speech Measures in Spanish Specific Language Impairment: A Discriminant Function Analysis

    Science.gov (United States)

    Grinstead, John; Baron, Alisa; Vega-Mendoza, Mariana; De la Mora, Juliana; Cantu-Sanchez, Myriam; Flores, Blanca

    2013-01-01

    Purpose: To test the proposal that the tense deficit that has been demonstrated for children with specific language impairment (SLI) in other languages is also found in child Spanish and that low performance on tense-related measures can distinguish Spanish-speaking children with SLI from those without. Method: The authors evaluated evidence from…

  17. Componential Skills in Second Language Development of Bilingual Children with Specific Language Impairment

    Science.gov (United States)

    Verhoeven, Ludo; Steenge, Judit; van Leeuwe, Jan; van Balkom, Hans

    2017-01-01

    In this study, we investigated which componential skills can be distinguished in the second language (L2) development of 140 bilingual children with specific language impairment in the Netherlands, aged 6-11 years, divided into 3 age groups. L2 development was assessed by means of spoken language tasks representing different language skills…

  18. Lipreading Ability and Its Cognitive Correlates in Typically Developing Children and Children with Specific Language Impairment

    Science.gov (United States)

    Heikkilä, Jenni; Lonka, Eila; Ahola, Sanna; Meronen, Auli; Tiippana, Kaisa

    2017-01-01

    Purpose: Lipreading and its cognitive correlates were studied in school-age children with typical language development and delayed language development due to specific language impairment (SLI). Method: Forty-two children with typical language development and 20 children with SLI were tested by using a word-level lipreading test and an extensive…

  19. Txt Lang: Texting, Textism Use and Literacy Abilities in Adolescents with and without Specific Language Impairment

    Science.gov (United States)

    Durkin, K.; Conti-Ramsden, G.; Walker, A. J.

    2011-01-01

    The present study examined text messaging in adolescence, in particular relationships among textism use, language and literacy skills. Forty-seven typically developing (TD) 17-year-olds and 47 adolescents of the same age with specific language impairment (SLI) participated. Participants completed standardised assessments of cognitive, language and…

  20. The impact of specific language impairment on working memory in children with ADHD combined subtype

    NARCIS (Netherlands)

    Jonsdottir, S; Bouma, A; Sergeant, JA; Scherder, EJA

    The objective of this study was to examine the impact of comorbid specific language impairment (SLI) on verbal and spatial working memory in children with DSM-IV combined subtype Attention Deficit Hyperactivity Disorder (ADHD-C). Participants were a clinical sample of 8 1/2- to 12 1/2-year-old

  1. The impact of specific language impairment on working memory in children with ADHD combined type

    NARCIS (Netherlands)

    Jondottir, S.; Bouma, A.; Sergeant, J.A.; Scherder, E.J.A.

    2005-01-01

    The objective of this study was to examine the impact of comorbid specific language impairment (SLI) on verbal and spatial working memory in children with DSM-IV combined subtype Attention Deficit Hyperactivity Disorder (ADHD-C). Participants were a clinical sample of 81/2- to 121/2-year-old

  2. The impact of specific language impairment on working memory children with ADHD combined subtype

    NARCIS (Netherlands)

    Jonsdottir, S.; Bouma, A.; Sergeant, J.A.; Scherder, E.J.A.

    2005-01-01

    The objective of this study was to examine the impact of comorbid specific language impairment (SLI) on verbal and spatial working memory in children with DSM-IV combined subtype Attention Deficit Hyperactivity Disorder (ADHD-C). Participants were a clinical sample of 81/2- to 121/2-year-old

  3. Complex Sentence Comprehension and Working Memory in Children with Specific Language Impairment

    Science.gov (United States)

    Montgomery, James W.; Evans, Julia L.

    2009-01-01

    Purpose: This study investigated the association of 2 mechanisms of working memory (phonological short-term memory [PSTM], attentional resource capacity/allocation) with the sentence comprehension of school-age children with specific language impairment (SLI) and 2 groups of control children. Method: Twenty-four children with SLI, 18 age-matched…

  4. Auxiliary BE Production by African American English-Speaking Children with and without Specific Language Impairment

    Science.gov (United States)

    Garrity, April W.; Oetting, Janna B.

    2010-01-01

    Purpose: To examine 3 forms ("am," "is," "are") of auxiliary BE production by African American English (AAE)-speaking children with and without specific language impairment (SLI). Method: Thirty AAE speakers participated: 10 six-year-olds with SLI, 10 age-matched controls, and 10 language-matched controls. BE production was examined through…

  5. Sustained Selective Attention Skills of Preschool Children with Specific Language Impairment: Evidence for Separate Attentional Capacities

    Science.gov (United States)

    Spaulding, Tammie J.; Plante, Elena; Vance, Rebecca

    2008-01-01

    Purpose: The present study was designed to investigate the performance of preschool children with specific language impairment (SLI) and their typically developing (TD) peers on sustained selective attention tasks. Method: This study included 23 children diagnosed with SLI and 23 TD children matched for age, gender, and maternal education level.…

  6. (Dis)connections between Specific Language Impairment and Dyslexia in Chinese

    Science.gov (United States)

    Wong, Anita M.-Y.; Ho, Connie S.-H.; Au, Terry K.-F.; Kidd, Joanna C.; Ng, Ashley K.-H.; Yip, Lesley P.-W.; Lam, Catherine C.-C.

    2015-01-01

    Specific language impairment (SLI) and dyslexia are found to co-occur in school-aged children learning Chinese, a non-alphabetic language (Wong, Kidd, Ho, & Au in "Sci Stud Read" 14:30--57, 2010). This paper examined the "Distinct" hypothesis--that SLI and dyslexia have different cognitive deficits and behavioural…

  7. Production and Processing of Subject-Verb Agreement in Monolingual Dutch Children with Specific Language Impairment

    Science.gov (United States)

    Blom, Elma; Vasic, Nada; de Jong, Jan

    2014-01-01

    Purpose: In this study, the authors investigated whether errors with subject-verb agreement in monolingual Dutch children with specific language impairment (SLI) are influenced by verb phonology. In addition, the productive and receptive abilities of Dutch acquiring children with SLI regarding agreement inflection were compared. Method: An SLI…

  8. Interaction of Language Processing and Motor Skill in Children with Specific Language Impairment

    Science.gov (United States)

    DiDonato Brumbach, Andrea C.; Goffman, Lisa

    2014-01-01

    Purpose: To examine how language production interacts with speech motor and gross and fine motor skill in children with specific language impairment (SLI). Method: Eleven children with SLI and 12 age-matched peers (4-6 years) produced structurally primed sentences containing particles and prepositions. Utterances were analyzed for errors and for…

  9. Persistent grammatical difficulties in Specific Language Impairment : Deficits in knowledge or in knowledge implementation?

    NARCIS (Netherlands)

    Duinmeijer, I.

    2017-01-01

    This study examines the grammatical abilities of children and adolescents with Specific Language Impairment (SLI). There were two research goals. Firstly, the persistence of grammatical problems over time was examined by comparing a younger group of children with SLI and an older group of

  10. Understanding Conservation Delays in Children with Specific Language Impairment: Task Representations Revealed in Speech and Gesture

    Science.gov (United States)

    Mainela-Arnold, Elina; Evans, Julia L.; Alibali, Martha W.

    2006-01-01

    Purpose: The authors investigated mental representations of Piagetian conservation tasks in children with specific language impairment (SLI) and typically developing peers. Children with SLI have normal nonverbal intelligence; however, they exhibit difficulties in Piagetian conservation tasks. The authors tested the hypothesis that conservation…

  11. Predictors of Growth or Attrition of the First Language in Latino Children with Specific Language Impairment

    Science.gov (United States)

    Simon-Cereijido, Gabriela; Gutierrez-Clellen, Vera F.; Sweet, Monica

    2013-01-01

    We investigated the factors that may help understand the differential rates of language development in the home language (i.e., Spanish) of Latino preschoolers with specific language impairment. Children were randomly assigned to either bilingual or English-only small group interventions and followed from preschool to kindergarten. Predictors of…

  12. Cognitive and Linguistic Precursors to Early Literacy Achievement in Children With Specific Language Impairment

    NARCIS (Netherlands)

    Weerdenburg, M.W.C. van; Verhoeven, L.T.W.; Balkom, L.J.M. van; Bosman, A.M.T.

    2009-01-01

    This study investigated the role of cognitive and language skills as predictors of early literacy skills in children with Specific Language Impairment. A range of cognitive and linguistic skills were assessed in a sample of 137 eight-year-old children with SLI at the beginning of the school year,

  13. Co-Localisation of Abnormal Brain Structure and Function in Specific Language Impairment

    Science.gov (United States)

    Badcock, Nicholas A.; Bishop, Dorothy V. M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

    2012-01-01

    We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior…

  14. Examining the Language Phenotype in Children with Typical Development, Specific Language Impairment, and Fragile X Syndrome

    Science.gov (United States)

    Haebig, Eileen; Sterling, Audra; Hoover, Jill

    2016-01-01

    Purpose: One aspect of morphosyntax, finiteness marking, was compared in children with fragile X syndrome (FXS), specific language impairment (SLI), and typical development matched on mean length of utterance (MLU). Method: Nineteen children with typical development (mean age = 3.3 years), 20 children with SLI (mean age = 4.9 years), and 17 boys…

  15. Specific Language Impairment and Executive Functioning: Parent and Teacher Ratings of Behavior

    Science.gov (United States)

    Wittke, Kacie; Spaulding, Tammie J.; Schechtman, Calli J.

    2013-01-01

    Purpose: The current study used the Behavior Rating Inventory of Executive Function--Preschool Version (BRIEF-P; Gioia, Espy, & Isquith, 2003), a rating scale designed to investigate executive behaviors in everyday activities, to examine the executive functioning of preschool children with specific language impairment (SLI) relative to their…

  16. Textese and use of texting by children with typical language development and Specific Language Impairment

    NARCIS (Netherlands)

    Blom, W.B.T.; van Dijk, Chantal; Vasic, Nada; van Witteloostuijn, Merel; Avrutin, S.

    2017-01-01

    The purpose of this study was to investigate texting and textese, which is the special register used for sending brief text messages, across children with typical development (TD) and children with Specific Language Impairment (SLI). Using elicitation techniques, texting and spoken language messages

  17. Developmental Associations between Working Memory and Language in Children with Specific Language Impairment: A Longitudinal Study

    Science.gov (United States)

    Vugs, Brigitte; Hendriks, Marc; Cuperus, Juliane; Knoors, Harry; Verhoeven, Ludo

    2017-01-01

    Purpose: This longitudinal study examined differences in the development of working memory (WM) between children with specific language impairment (SLI) and typically developing (TD) children. Further, it explored to what extent language at ages 7-8 years could be predicted by measures of language and/or WM at ages 4-5 years. Method: Thirty…

  18. Among perinatal factors, only the Apgar score is associated with specific language impairment

    NARCIS (Netherlands)

    Diepeveen, F.B.; de Kroon, M.L.A.; Dusseldorp, E.; Snik, A.F.M.

    2013-01-01

    Aim: The purpose of this study was to assess the relation of perinatal risk factors with later development of specific language impairment (SLI). Method: In a case-control study, 179 children attending special needs schools for SLI were matched with non-affected children attending mainstream

  19. Among perinatal factors, only the Apgar score is associated with specific language impairment

    NARCIS (Netherlands)

    Diepeveen, F.B.; Kroon, M.L. De; Dusseldorp, E.; Snik, A.F.M.

    2013-01-01

    AIM: The purpose of this study was to assess the relation of perinatal risk factors with later development of specific language impairment (SLI). METHOD: In a case-control study, 179 children attending special needs schools for SLI were matched with non-affected children attending mainstream

  20. Among perinatal factors, only the Apgar score is associated with specific language impairment

    NARCIS (Netherlands)

    Diepeveen, F.B.; Kroon, M.L. de; Dusseldorp, E.; Snik, A.F.

    2013-01-01

    The purpose of this study was to assess the relation of perinatal risk factors with later development of specific language impairment (SLI). METHOD: In a case-control study, 179 children attending special needs schools for SLI were matched with non-affected children attending mainstream schools.

  1. Postschool Educational and Employment Experiences of Young People with Specific Language Impairment

    Science.gov (United States)

    Conti-Ramsden, Gina; Durkin, Kevin

    2012-01-01

    Purpose: This study examined the postschool educational and employment experiences of young people with and without specific language impairment (SLI). Method: Nineteen-year-olds with (n = 50) and without (n = 50) SLI were interviewed on their education and employment experiences since finishing compulsory secondary education. Results: On average,…

  2. HemeBIND: a novel method for heme binding residue prediction by combining structural and sequence information

    Directory of Open Access Journals (Sweden)

    Hu Jianjun

    2011-05-01

    Full Text Available Abstract Background Accurate prediction of binding residues involved in the interactions between proteins and small ligands is one of the major challenges in structural bioinformatics. Heme is an essential and commonly used ligand that plays critical roles in electron transfer, catalysis, signal transduction and gene expression. Although much effort has been devoted to the development of various generic algorithms for ligand binding site prediction over the last decade, no algorithm has been specifically designed to complement experimental techniques for identification of heme binding residues. Consequently, an urgent need is to develop a computational method for recognizing these important residues. Results Here we introduced an efficient algorithm HemeBIND for predicting heme binding residues by integrating structural and sequence information. We systematically investigated the characteristics of binding interfaces based on a non-redundant dataset of heme-protein complexes. It was found that several sequence and structural attributes such as evolutionary conservation, solvent accessibility, depth and protrusion clearly illustrate the differences between heme binding and non-binding residues. These features can then be separately used or combined to build the structure-based classifiers using support vector machine (SVM. The results showed that the information contained in these features is largely complementary and their combination achieved the best performance. To further improve the performance, an attempt has been made to develop a post-processing procedure to reduce the number of false positives. In addition, we built a sequence-based classifier based on SVM and sequence profile as an alternative when only sequence information can be used. Finally, we employed a voting method to combine the outputs of structure-based and sequence-based classifiers, which demonstrated remarkably better performance than the individual classifier alone

  3. How Language Is Embodied in Bilinguals and Children with Specific Language Impairment

    Science.gov (United States)

    Adams, Ashley M.

    2016-01-01

    This manuscript explores the role of embodied views of language comprehension and production in bilingualism and specific language impairment. Reconceptualizing popular models of bilingual language processing, the embodied theory is first extended to this area. Issues such as semantic grounding in a second language and potential differences between early and late acquisition of a second language are discussed. Predictions are made about how this theory informs novel ways of thinking about teaching a second language. Secondly, the comorbidity of speech, language, and motor impairments and how embodiment theory informs the discussion of the etiology of these impairments is examined. A hypothesis is presented suggesting that what is often referred to as specific language impairment may not be so specific due to widespread subclinical motor deficits in this population. Predictions are made about how weaknesses and instabilities in speech motor control, even at a subclinical level, may disrupt the neural network that connects acoustic input, articulatory motor plans, and semantics. Finally, I make predictions about how this information informs clinical practice for professionals such as speech language pathologists and occupational and physical therapists. These new hypotheses are placed within the larger framework of the body of work pertaining to semantic grounding, action-based language acquisition, and action-perception links that underlie language learning and conceptual grounding. PMID:27582716

  4. Assessment of short-term memory in Arabic speaking children with specific language impairment.

    Science.gov (United States)

    Kaddah, F A; Shoeib, R M; Mahmoud, H E

    2010-12-15

    Children with Specific Language Impairment (SLI) may have some kind of memory disorder that could increase their linguistic impairment. This study assessed the short-term memory skills in Arabic speaking children with either Expressive Language Impairment (ELI) or Receptive/Expressive Language Impairment (R/ELI) in comparison to controls in order to estimate the nature and extent of any specific deficits in these children that could explain the different prognostic results of language intervention. Eighteen children were included in each group. Receptive, expressive and total language quotients were calculated using the Arabic language test. Assessment of auditory and visual short-term memory was done using the Arabic version of the Illinois Test of Psycholinguistic Abilities. Both groups of SLI performed significantly lower linguistic abilities and poorer auditory and visual short-term memory in comparison to normal children. The R/ELI group presented an inferior performance than the ELI group in all measured parameters. Strong association was found between most tasks of auditory and visual short-term memory and linguistic abilities. The results of this study highlighted a specific degree of deficit of auditory and visual short-term memories in both groups of SLI. These deficits were more prominent in R/ELI group. Moreover, the strong association between the different auditory and visual short-term memories and language abilities in children with SLI must be taken into account when planning an intervention program for these children.

  5. Speech Perception and Phonological Short-Term Memory Capacity in Language Impairment: Preliminary Evidence from Adolescents with Specific Language Impairment (SLI) and Autism Spectrum Disorders (ASD)

    Science.gov (United States)

    Loucas, Tom; Riches, Nick Greatorex; Charman, Tony; Pickles, Andrew; Simonoff, Emily; Chandler, Susie; Baird, Gillian

    2010-01-01

    Background: The cognitive bases of language impairment in specific language impairment (SLI) and autism spectrum disorders (ASD) were investigated in a novel non-word comparison task which manipulated phonological short-term memory (PSTM) and speech perception, both implicated in poor non-word repetition. Aims: This study aimed to investigate the…

  6. Potent heme-degrading action of antimony and antimony-containing parasiticidal agents.

    Science.gov (United States)

    Drummond, G S; Kappas, A

    1981-02-01

    The ability of antimony and antimony-containing parasiticidal agents to enhance the rate of heme degradation in liver and kidney was investigated. Trivalent antimony was shown to be an extremely potent inducer of heme oxygenase, the initial and rate-limiting enzyme in heme degradation, in both organs, whereas the pentavalent form was a weak inducer of this enzyme. The ability of antimony to induce heme oxygenase was dose-dependent, independent of the salt used, and not a result of a direct activation of the enzyme in vitro. Concomitant with heme oxygenase induction by antimony, microsomal heme and cytochrome P-450 contents decreased, the cyto-chrome P-450-dependent mixed function oxidase system was impaired, and delta-ami-nolevulinate synthase (ALAS), the rate-limiting enzyme of heme synthesis, underwent the sequential changes-initial inhibition followed by rebound induction-usually associated with the administration of transition elements such as cobalt. Antimony induction of heme oxygenase however, unlike the enzyme induction elicited by cobalt, was not prevented either by cysteine administered orally or as a cysteine metal complex, or by simultaneous zinc administration. Desferoxamine also did not block heme oxygenase induction by antimony, but this chelator did prevent the rebound increase in ALAS activity associated with antimony or cobalt treatment. Antimony-containing parasiticidal drugs were also potent inducers of heme oxygenase in liver and kidney. The heme degradative action of these drugs may be related in part to the jaundice commonly associated with the prolonged therapeutic use of these agents. The heme-oxygenase-inducing action of antimony-containing parasiticidal drugs is a newly defined biological property of these compounds. The relation between the parasiticidal and the heme-oxygenase-inducing actions of such drugs is unknown. However, certain parasites contain hemoproteins or require heme compounds during their life cycle. It may therefore be

  7. Heme Mobilization in Animals: A Metallolipid's Journey.

    Science.gov (United States)

    Reddi, Amit R; Hamza, Iqbal

    2016-06-21

    Heme is universally recognized as an essential and ubiquitous prosthetic group that enables proteins to carry out a diverse array of functions. All heme-dependent processes, from protein hemylation to heme signaling, require the dynamic and rapid mobilization of heme to hemoproteins present in virtually every subcellular compartment. The cytotoxicity and hydrophobicity of heme necessitates that heme mobilization is carefully controlled at the cellular and systemic level. However, the molecules and mechanisms that mediate heme homeostasis are poorly understood. In this Account, we provide a heuristic paradigm with which to conceptualize heme trafficking and highlight the most recent developments in the mechanisms underlying heme trafficking. As an iron-containing tetrapyrrole, heme exhibits properties of both transition metals and lipids. Accordingly, we propose its transport and trafficking will reflect principles gleaned from the trafficking of both metals and lipids. Using this conceptual framework, we follow the flow of heme from the final step of heme synthesis in the mitochondria to hemoproteins present in various subcellular organelles. Further, given that many cells and animals that cannot make heme can assimilate it intact from nutritional sources, we propose that intercellular heme trafficking pathways must exist. This necessitates that heme be able to be imported and exported from cells, escorted between cells and organs, and regulated at the organismal level via a coordinated systemic process. In this Account, we highlight recently discovered heme transport and trafficking factors and provide the biochemical foundation for the cell and systems biology of heme. Altogether, we seek to reconceptualize heme from an exchange inert cofactor buried in hemoprotein active sites to an exchange labile and mobile metallonutrient.

  8. Abnormal functional lateralization and activity of language brain areas in typical specific language impairment (developmental dysphasia)

    Science.gov (United States)

    De Guibert, Clément; Maumet, Camille; Jannin, Pierre; Ferré, Jean-Christophe; Tréguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

    2011-01-01

    Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting structural language (n=21), to a matched group of typically-developing children using a panel of four language tasks neither requiring reading nor metalinguistic skills, including two auditory lexico-semantic tasks (category fluency and responsive naming) and two visual phonological tasks based on picture naming. Data processing involved normalizing the data with respect to a matched pairs pediatric template, groups and between-groups analysis, and laterality indexes assessment within regions of interest using single and combined task analysis. Children with specific language impairment exhibited a significant lack of left lateralization in all core language regions (inferior frontal gyrus-opercularis, inferior frontal gyrus-triangularis, supramarginal gyrus, superior temporal gyrus), across single or combined task analysis, but no difference of lateralization for the rest of the brain. Between-group comparisons revealed a left hypoactivation of Wernicke’s area at the posterior superior temporal/supramarginal junction during the responsive naming task, and a right hyperactivation encompassing the anterior insula with adjacent inferior frontal gyrus and the head of the caudate nucleus during the first phonological task. This study thus provides evidence that this specific subtype of specific language impairment is associated with atypical lateralization and functioning of core language areas. PMID:21719430

  9. Structural Characterization of Heme Environmental Mutants of CgHmuT that Shuttles Heme Molecules to Heme Transporters

    Directory of Open Access Journals (Sweden)

    Norifumi Muraki

    2016-05-01

    Full Text Available Corynebacteria contain a heme uptake system encoded in hmuTUV genes, in which HmuT protein acts as a heme binding protein to transport heme to the cognate transporter HmuUV. The crystal structure of HmuT from Corynebacterium glutamicum (CgHmuT reveals that heme is accommodated in the central cleft with His141 and Tyr240 as the axial ligands and that Tyr240 forms a hydrogen bond with Arg242. In this work, the crystal structures of H141A, Y240A, and R242A mutants were determined to understand the role of these residues for the heme binding of CgHmuT. Overall and heme environmental structures of these mutants were similar to those of the wild type, suggesting that there is little conformational change in the heme-binding cleft during heme transport reaction with binding and the dissociation of heme. A loss of one axial ligand or the hydrogen bonding interaction with Tyr240 resulted in an increase in the redox potential of the heme for CgHmuT to be reduced by dithionite, though the wild type was not reduced under physiological conditions. These results suggest that the heme environmental structure stabilizes the ferric heme binding in CgHmuT, which will be responsible for efficient heme uptake under aerobic conditions where Corynebacteria grow.

  10. Electrical brain responses in language-impaired children reveal grammar-specific deficits.

    Directory of Open Access Journals (Sweden)

    Elisabeth Fonteneau

    2008-03-01

    Full Text Available Scientific and public fascination with human language have included intensive scrutiny of language disorders as a new window onto the biological foundations of language and its evolutionary origins. Specific language impairment (SLI, which affects over 7% of children, is one such disorder. SLI has received robust scientific attention, in part because of its recent linkage to a specific gene and loci on chromosomes and in part because of the prevailing question regarding the scope of its language impairment: Does the disorder impact the general ability to segment and process language or a specific ability to compute grammar? Here we provide novel electrophysiological data showing a domain-specific deficit within the grammar of language that has been hitherto undetectable through behavioural data alone.We presented participants with Grammatical(G-SLI, age-matched controls, and younger child and adult controls, with questions containing syntactic violations and sentences containing semantic violations. Electrophysiological brain responses revealed a selective impairment to only neural circuitry that is specific to grammatical processing in G-SLI. Furthermore, the participants with G-SLI appeared to be partially compensating for their syntactic deficit by using neural circuitry associated with semantic processing and all non-grammar-specific and low-level auditory neural responses were normal.The findings indicate that grammatical neural circuitry underlying language is a developmentally unique system in the functional architecture of the brain, and this complex higher cognitive system can be selectively impaired. The findings advance fundamental understanding about how cognitive systems develop and all human language is represented and processed in the brain.

  11. Sleep deprivation specifically impairs short-term olfactory memory in Drosophila.

    Science.gov (United States)

    Li, Xinjian; Yu, Feng; Guo, Aike

    2009-11-01

    Sleep is crucial to memory consolidation in humans and other animals; however, the effect of insufficient sleep on subsequent learning and memory remains largely elusive. Learning and memory after 1-day sleep deprivation (slpD) was evaluated using Pavlovian olfactory conditioning in Drosophila, and locomotor activity was measured using the Drosophila Activity Monitoring System in a 12:12 light-dark cycle. We found that slpD specifically impaired 1-h memory in wild type Canton-S flies, and this effect could persist for at least 2 h. However, alternative stresses (heat stress, oxidative stress, starvation, and rotation stress) did not result in a similar effect and left the flies' memory intact. Mechanistic studies demonstrated that flies with either silenced transmission of the mushroom body (MB) during slpD or down-regulated cAMP levels in the MB demonstrated no slpD-induced 1-h memory impairment. We found that slpD specifically impaired 1-h memory in Drosophila, and either silencing of MB transmission during slpD or down-regulation of the cAMP level in the MB protected the flies from slpD-induced impairment.

  12. Grammar predicts procedural learning and consolidation deficits in children with Specific Language Impairment.

    Science.gov (United States)

    Hedenius, Martina; Persson, Jonas; Tremblay, Antoine; Adi-Japha, Esther; Veríssimo, João; Dye, Cristina D; Alm, Per; Jennische, Margareta; Bruce Tomblin, J; Ullman, Michael T

    2011-01-01

    The Procedural Deficit Hypothesis (PDH) posits that Specific Language Impairment (SLI) can be largely explained by abnormalities of brain structures that subserve procedural memory. The PDH predicts impairments of procedural memory itself, and that such impairments underlie the grammatical deficits observed in the disorder. Previous studies have indeed reported procedural learning impairments in SLI, and have found that these are associated with grammatical difficulties. The present study extends this research by examining consolidation and longer-term procedural sequence learning in children with SLI. The Alternating Serial Reaction Time (ASRT) task was given to children with SLI and typically developing (TD) children in an initial learning session and an average of three days later to test for consolidation and longer-term learning. Although both groups showed evidence of initial sequence learning, only the TD children showed clear signs of consolidation, even though the two groups did not differ in longer-term learning. When the children were re-categorized on the basis of grammar deficits rather than broader language deficits, a clearer pattern emerged. Whereas both the grammar impaired and normal grammar groups showed evidence of initial sequence learning, only those with normal grammar showed consolidation and longer-term learning. Indeed, the grammar-impaired group appeared to lose any sequence knowledge gained during the initial testing session. These findings held even when controlling for vocabulary or a broad non-grammatical language measure, neither of which were associated with procedural memory. When grammar was examined as a continuous variable over all children, the same relationships between procedural memory and grammar, but not vocabulary or the broader language measure, were observed. Overall, the findings support and further specify the PDH. They suggest that consolidation and longer-term procedural learning are impaired in SLI, but that these

  13. Grammar Predicts Procedural Learning and Consolidation Deficits in Children with Specific Language Impairment

    Science.gov (United States)

    Hedenius, Martina; Persson, Jonas; Tremblay, Antoine; Adi-Japha, Esther; Veríssimo, João; Dye, Cristina D.; Alm, Per; Jennische, Margareta; Tomblin, J. Bruce; Ullman, Michael T.

    2011-01-01

    The Procedural Deficit Hypothesis (PDH) posits that Specific Language Impairment (SLI) can be largely explained by abnormalities of brain structures that subserve procedural memory. The PDH predicts impairments of procedural memory itself, and that such impairments underlie the grammatical deficits observed in the disorder. Previous studies have indeed reported procedural learning impairments in SLI, and have found that these are associated with grammatical difficulties. The present study extends this research by examining the consolidation and longer-term procedural sequence learning in children with SLI. The Alternating Serial Reaction Time (ASRT) task was given to children with SLI and typically-developing (TD) children in an initial learning session and an average of three days later to test for consolidation and longer-term learning. Although both groups showed evidence of initial sequence learning, only the TD children showed clear signs of consolidation, even though the two groups did not differ in longer-term learning. When the children were re-categorized on the basis of grammar deficits rather than broader language deficits, a clearer pattern emerged. Whereas both the grammar impaired and normal grammar groups showed evidence of initial sequence learning, only those with normal grammar showed consolidation and longer-term learning. Indeed, the grammar-impaired group appeared to lose any sequence knowledge gained during the initial testing session. These findings held even when controlling for vocabulary or a broad non-grammatical language measure, neither of which were associated with procedural memory. When grammar was examined as a continuous variable over all children, the same relationships between procedural memory and grammar, but not vocabulary or the broader language measure, were observed. Overall, the findings support and further specify the PDH. They suggest that consolidation and longer-term procedural learning are impaired in SLI, but that

  14. Visual-motor integration performance in children with severe specific language impairment.

    Science.gov (United States)

    Nicola, K; Watter, P

    2016-09-01

    This study investigated (1) the visual-motor integration (VMI) performance of children with severe specific language impairment (SLI), and any effect of age, gender, socio-economic status and concomitant speech impairment; and (2) the relationship between language and VMI performance. It is hypothesized that children with severe SLI would present with VMI problems irrespective of gender and socio-economic status; however, VMI deficits will be more pronounced in younger children and those with concomitant speech impairment. Furthermore, it is hypothesized that there will be a relationship between VMI and language performance, particularly in receptive scores. Children enrolled between 2000 and 2008 in a school dedicated to children with severe speech-language impairments were included, if they met the criteria for severe SLI with or without concomitant speech impairment which was verified by a government organization. Results from all initial standardized language and VMI assessments found during a retrospective review of chart files were included. The final study group included 100 children (males = 76), from 4 to 14 years of age with mean language scores at least 2SD below the mean. For VMI performance, 52% of the children scored below -1SD, with 25% of the total group scoring more than 1.5SD below the mean. Age, gender and the addition of a speech impairment did not impact on VMI performance; however, children living in disadvantaged suburbs scored significantly better than children residing in advantaged suburbs. Receptive language scores of the Clinical Evaluation of Language Fundamentals was the only score associated with and able to predict VMI performance. A small subgroup of children with severe SLI will also have poor VMI skills. The best predictor of poor VMI is receptive language scores on the Clinical Evaluation of Language Fundamentals. Children with poor receptive language performance may benefit from VMI assessment and multidisciplinary

  15. The relation between receptive grammar and procedural, declarative, and working memory in specific language impairment

    OpenAIRE

    Conti-Ramsden, Gina; Ullman, Michael T.; Lum, Jarrad A. G.

    2015-01-01

    What memory systems underlie grammar in children, and do these differ between typically developing children and children with specific language impairment (SLI)? Whilst there is substantial evidence linking certain memory deficits to the language problems in children with SLI, few studies have investigated multiple memory systems simultaneously, examining not only possible memory deficits but also memory abilities that may play a compensatory role. This study examined the extent to which proc...

  16. Statistical word learning in children with autism spectrum disorder and specific language impairment.

    Science.gov (United States)

    Haebig, Eileen; Saffran, Jenny R; Ellis Weismer, Susan

    2017-11-01

    Word learning is an important component of language development that influences child outcomes across multiple domains. Despite the importance of word knowledge, word-learning mechanisms are poorly understood in children with specific language impairment (SLI) and children with autism spectrum disorder (ASD). This study examined underlying mechanisms of word learning, specifically, statistical learning and fast-mapping, in school-aged children with typical and atypical development. Statistical learning was assessed through a word segmentation task and fast-mapping was examined in an object-label association task. We also examined children's ability to map meaning onto newly segmented words in a third task that combined exposure to an artificial language and a fast-mapping task. Children with SLI had poorer performance on the word segmentation and fast-mapping tasks relative to the typically developing and ASD groups, who did not differ from one another. However, when children with SLI were exposed to an artificial language with phonemes used in the subsequent fast-mapping task, they successfully learned more words than in the isolated fast-mapping task. There was some evidence that word segmentation abilities are associated with word learning in school-aged children with typical development and ASD, but not SLI. Follow-up analyses also examined performance in children with ASD who did and did not have a language impairment. Children with ASD with language impairment evidenced intact statistical learning abilities, but subtle weaknesses in fast-mapping abilities. As the Procedural Deficit Hypothesis (PDH) predicts, children with SLI have impairments in statistical learning. However, children with SLI also have impairments in fast-mapping. Nonetheless, they are able to take advantage of additional phonological exposure to boost subsequent word-learning performance. In contrast to the PDH, children with ASD appear to have intact statistical learning, regardless of

  17. Testing the specificity of executive functioning impairments in adolescents with ADHD, ODD/CD and ASD.

    Science.gov (United States)

    Carter Leno, Virginia; Chandler, Susie; White, Pippa; Pickles, Andrew; Baird, Gillian; Hobson, Chris; Smith, Anna B; Charman, Tony; Rubia, Katya; Simonoff, Emily

    2017-12-09

    Current diagnostic systems conceptualise attention deficit hyperactivity disorder (ADHD), oppositional defiant/conduct disorder (ODD/CD) and autism spectrum disorder (ASD) as separate diagnoses. However, all three demonstrate executive functioning (EF) impairments. Whether these impairments are trans-diagnostic or disorder-specific remains relatively unexplored. Four groups of 10-16 year-olds [typically developing (TD; N = 43), individuals clinically diagnosed with ADHD (N = 21), ODD/CD (N = 26) and ASD (N = 41)] completed Go/NoGo and Switch tasks. Group differences were tested using analysis of co-variance (ANCOVA) including age, IQ, sex, conduct problems and ADHD symptoms as co-variates. Results indicated some disorder-specificity as only the ASD group demonstrated decreased probability of inhibition in the Go/NoGo task compared to all other groups. However, shared impairments were also found; all three diagnostic groups demonstrated increased reaction time variability (RTV) compared to the TD group, and both the ODD/CD and the ASD group demonstrated increased premature responses. When controlling for ADHD symptoms and conduct problems, group differences in RTV were no longer significant; however, the ASD group continued to demonstrate increased premature responses. No group differences were found in cognitive flexibility in the Switch task. A more varied response style was present across all clinical groups, although this appeared to be accounted for by sub-threshold ODD/CD and ADHD symptoms. Only the ASD group was impaired in response inhibition and premature responsiveness relative to TD adolescents. The findings suggest that some EF impairments typically associated with ADHD may also be found in individuals with ASD.

  18. Atypical right hemisphere specialization for object representations in an adolescent with specific language impairment

    Directory of Open Access Journals (Sweden)

    Timothy T. Brown

    2014-02-01

    Full Text Available Individuals with a diagnosis of specific language impairment (SLI show abnormal spoken language occurring alongside normal nonverbal abilities. Behaviorally, people with SLI exhibit diverse profiles of impairment involving phonological, grammatical, syntactic, and semantic aspects of language. In this study, we used a multimodal neuroimaging technique called anatomically constrained magnetoencephalography (aMEG to measure the dynamic functional brain organization of an adolescent with SLI. Using single-subject statistical maps of cortical activity, we compared this patient to a sibling and to a cohort of typically developing subjects during the performance of tasks designed to evoke semantic representations of concrete objects. Localized, real-time patterns of brain activity within the language impaired patient showed marked differences from the typical functional organization, with significant engagement of right hemisphere heteromodal cortical regions generally homotopic to the left hemisphere areas that usually show the greatest activity for such tasks. Functional neuroanatomical differences were evident at early sensoriperceptual processing stages and continued through later cognitive stages, observed specifically at latencies typically associated with semantic encoding operations. Our findings show with real-time temporal specificity evidence for an atypical right hemisphere specialization for the representation of concrete entities, independent of verbal motor demands. More broadly, our results demonstrate the feasibility and potential utility of using aMEG to characterize individual patient differences in the dynamic functional organization of the brain.

  19. Cognitive deficits are a matter of emotional context: inflexible strategy use mediates context-specific learning impairments in OCD.

    Science.gov (United States)

    Zetsche, Ulrike; Rief, Winfried; Westermann, Stefan; Exner, Cornelia

    2015-01-01

    The present study examines the interplay between cognitive deficits and emotional context in obsessive-compulsive disorder (OCD) and social phobia (SP). Specifically, this study examines whether the inflexible use of efficient learning strategies in an emotional context underlies impairments in probabilistic classification learning (PCL) in OCD, and whether PCL impairments are specific to OCD. Twenty-three participants with OCD, 30 participants with SP and 30 healthy controls completed a neutral and an OCD-specific PCL task. OCD participants failed to adopt efficient learning strategies and showed fewer beneficial strategy switches than controls only in an OCD-specific context, but not in a neutral context. Additionally, OCD participants did not show any explicit memory impairments. Number of beneficial strategy switches in the OCD-specific task mediated the difference in PCL performance between OCD and control participants. Individuals with SP were impaired in both PCL tasks. In contrast to neuropsychological models postulating general cognitive impairments in OCD, the present findings suggest that it is the interaction between cognition and emotion that is impaired in OCD. Specifically, activated disorder-specific fears may impair the flexible adoption of efficient learning strategies and compromise otherwise unimpaired PCL. Impairments in PCL are not specific to OCD.

  20. Statistical Learning in Specific Language Impairment and Autism Spectrum Disorder: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Rita Obeid

    2016-08-01

    Full Text Available Impairments in statistical learning might be a common deficit among individuals with Specific Language Impairment (SLI and Autism Spectrum Disorder (ASD. Using meta-analysis, we examined statistical learning in SLI (14 studies, 15 comparisons and ASD (13 studies, 20 comparisons to evaluate this hypothesis. Effect sizes were examined as a function of diagnosis across multiple statistical learning tasks (Serial Reaction Time, Contextual Cueing, Artificial Grammar Learning, Speech Stream, Observational Learning, Probabilistic Classification. Individuals with SLI showed deficits in statistical learning relative to age-matched controls g = .47, 95% CI [.28, .66], p < .001. In contrast, statistical learning was intact in individuals with ASD relative to controls, g = –.13, 95% CI [–.34, .08], p = .22. Effect sizes did not vary as a function of task modality or participant age. Our findings inform debates about overlapping social-communicative difficulties in children with SLI and ASD by suggesting distinct underlying mechanisms. In line with the procedural deficit hypothesis (Ullman & Pierpont, 2005, impaired statistical learning may account for phonological and syntactic difficulties associated with SLI. In contrast, impaired statistical learning fails to account for the social-pragmatic difficulties associated with ASD.

  1. Impaired temporal contrast sensitivity in dyslexics is specific to retain-and-compare paradigms.

    Science.gov (United States)

    Ben-Yehudah, G; Sackett, E; Malchi-Ginzberg, L; Ahissar, M

    2001-07-01

    Developmental dyslexia is a specific reading disability that affects 5-10% of the population. Recent studies have suggested that dyslexics may experience a deficit in the visual magnocellular pathway. The most extensively studied prediction deriving from this hypothesis is impaired contrast sensitivity to transient, low-luminance stimuli at low spatial frequencies. However, the findings are inconsistent across studies and even seemingly contradictory. In the present study, we administered several different paradigms for assessing temporal contrast sensitivity, and found both impaired and normal contrast sensitivity within the same group of dyslexic participants. Under sequential presentation, in a temporal forced choice paradigm, dyslexics showed impaired sensitivity to both drifting and flickering gratings. However, under simultaneous presentation, with a spatial forced choice paradigm, dyslexics' sensitivity did not differ from that of the controls. Within each paradigm, dyslexics' sensitivity was poorer at higher temporal frequencies, consistent with the magnocellular hypothesis. These results suggest that a basic perceptual impairment in dyslexics may be their limited ability to retain-and-compare perceptual traces across brief intervals.

  2. Effective intervention for expressive grammar in children with specific language impairment.

    Science.gov (United States)

    Smith-Lock, Karen M; Leitao, Suze; Lambert, Lara; Nickels, Lyndsey

    2013-01-01

    Children with specific language impairment are known to struggle with expressive grammar. While some studies have shown successful intervention under laboratory conditions, there is a paucity of evidence for the effectiveness of grammar treatment in young children in community settings. To evaluate the effectiveness of a school-based intervention programme for expressive grammar in 5-year-olds with specific language impairment. Thirty-four 5-year-old children attending a specialized school for children with language impairment participated in the study. Nineteen children received treatment for expressive grammar (experimental group) and 15 children received a control treatment. Treatment consisted of weekly 1-h sessions of small group activities in a classroom setting for 8 weeks. Techniques included direct instruction, focused stimulation, recasting and imitation. Results were analysed at the group level and as a case series with each child as their own control in a single-subject design. There was a significant difference in grammatical performance pre- and post-treatment for children who received grammar treatment (Cohen's d = 1.24), but not for a group of children who received a control treatment. Further, no difference in performance was found in the equivalent time period prior to treatment, nor for an untreated target. Treatment success was more pronounced in children without articulation difficulties which interfered with their ability to produce the grammatical targets (Cohen's d = 1.66). Individual analyses indicated the treatment effect was significant for the majority of children. Individually targeted intervention delivered in small groups in a classroom setting was effective in improving production of expressive grammatical targets in 5-year-old children with specific language impairment. © 2013 Royal College of Speech and Language Therapists.

  3. Dietary iron controls circadian hepatic glucose metabolism through heme synthesis.

    Science.gov (United States)

    Simcox, Judith A; Mitchell, Thomas Creighton; Gao, Yan; Just, Steven F; Cooksey, Robert; Cox, James; Ajioka, Richard; Jones, Deborah; Lee, Soh-Hyun; King, Daniel; Huang, Jingyu; McClain, Donald A

    2015-04-01

    The circadian rhythm of the liver maintains glucose homeostasis, and disruption of this rhythm is associated with type 2 diabetes. Feeding is one factor that sets the circadian clock in peripheral tissues, but relatively little is known about the role of specific dietary components in that regard. We assessed the effects of dietary iron on circadian gluconeogenesis. Dietary iron affects circadian glucose metabolism through heme-mediated regulation of the interaction of nuclear receptor subfamily 1 group d member 1 (Rev-Erbα) with its cosuppressor nuclear receptor corepressor 1 (NCOR). Loss of regulated heme synthesis was achieved by aminolevulinic acid (ALA) treatment of mice or cultured cells to bypass the rate-limiting enzyme in hepatic heme synthesis, ALA synthase 1 (ALAS1). ALA treatment abolishes differences in hepatic glucose production and in the expression of gluconeogenic enzymes seen with variation of dietary iron. The differences among diets are also lost with inhibition of heme synthesis with isonicotinylhydrazine. Dietary iron modulates levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional activator of ALAS1, to affect hepatic heme. Treatment of mice with the antioxidant N-acetylcysteine diminishes PGC-1α variation observed among the iron diets, suggesting that iron is acting through reactive oxygen species signaling. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  4. RAPID NAMING IN CHILDREN WITH SPECIFIC LANGUAGE IMPAIRMENT AND IN CHILDREN WITH TYPICAL LANGUAGE DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Neda MILOSHEVIĆ

    2017-03-01

    Full Text Available Aimed at the detailed insight into the phonological ability of Serbian-speaking children of preschool age, with and without language impairment, the ability of rapid naming was examined. Method: Operationalization of the set goal was carried out by using the Test for evaluating reading and writing pre-skills. In describing and analyzing the obtained data, methods of descriptive and inferential statistics were used. The sample included 120 subjects of both gender, 40 children diagnosed with specific language impairment (SLI, age from 5,11 to 7 years, and 80 children with typical language development (TLD, age between 5,11 and 7 years, with no statistically significant differences in relation to age and gender of the participants. Results: Summing up the overall results and achievements of children with SLI and children with TLD, we concluded that there are statistically significant differences in the rapid naming between children with specific language impairment and children with typical language development. Conclusions: As it is a global trend to work on preventing disorders and obstructions, and phonological skills in this age are a timely indicator of the development of reading and writing skills, the examined children with SLI are at risk for the occurrence of obstructions and disorders in the area of reading and writing abilities.

  5. Using principles of learning to inform language therapy design for children with specific language impairment.

    Science.gov (United States)

    Alt, Mary; Meyers, Christina; Ancharski, Alexandra

    2012-01-01

    Language treatment for children with specific language impairment (SLI) often takes months to achieve moderate results. Interventions often do not incorporate the principles that are known to affect learning in unimpaired learners. To outline some key findings about learning in typical populations and to suggest a model of how they might be applied to language treatment design as a catalyst for further research and discussion. Three main principles of implicit learning are reviewed: variability, complexity and sleep-dependent consolidation. After explaining these principles, evidence is provided as to how they influence learning tasks in unimpaired learners. Information is reviewed on principles of learning as they apply to impaired populations, current treatment designs are also reviewed that conform to the principles, and ways in which principles of learning might be incorporated into language treatment design are demonstrated. This paper provides an outline for how theoretical knowledge might be applied to clinical practice in an effort to promote discussion. Although the authors look forward to more specific details on how the principles of learning relate to impaired populations, there is ample evidence to suggest that these principles should be considered during treatment design. © 2012 Royal College of Speech and Language Therapists.

  6. Awareness of rhythm patterns in speech and music in children with specific language impairments

    Directory of Open Access Journals (Sweden)

    Ruth eCumming

    2015-12-01

    Full Text Available Children with specific language impairments (SLIs show impaired perception and production of language, and also show impairments in perceiving auditory cues to rhythm (amplitude rise time [ART] and sound duration and in tapping to a rhythmic beat. Here we explore potential links between language development and rhythm perception in 45 children with SLI and 50 age-matched controls. We administered three rhythmic tasks, a musical beat detection task, a tapping-to-music task, and a novel music/speech task, which varied rhythm and pitch cues independently or together in both speech and music. Via low-pass filtering, the music sounded as though it was played from a low-quality radio and the speech sounded as though it was muffled (heard behind the door. We report data for all of the SLI children (N = 45, IQ varying, as well as for two independent subgroupings with intact IQ. One subgroup, Pure SLI, had intact phonology and reading (N=16, the other, SLI PPR (N=15, had impaired phonology and reading. When IQ varied (all SLI children, we found significant group differences in all the rhythmic tasks. For the Pure SLI group, there were rhythmic impairments in the tapping task only. For children with SLI and poor phonology (SLI PPR, group differences were found in all of the filtered speech/music AXB tasks. We conclude that difficulties with rhythmic cues in both speech and music are present in children with SLIs, but that some rhythmic measures are more sensitive than others. The data are interpreted within a ‘prosodic phrasing’ hypothesis, and we discuss the potential utility of rhythmic and musical interventions in remediating speech and language difficulties in children.

  7. A dual component heme biosensor that integrates heme transport and synthesis in bacteria.

    Science.gov (United States)

    Nobles, Christopher L; Clark, Justin R; Green, Sabrina I; Maresso, Anthony W

    2015-11-01

    Bacterial pathogens acquire host iron to power cellular processes and replication. Heme, an iron-containing cofactor bound to hemoglobin, is scavenged by bacterial proteins to attain iron. Methods to measure intracellular heme are laborious, involve complex chemistry, or require radioactivity. Such drawbacks limit the study of the mechanistic steps of heme transport and breakdown. Hypothesizing heme homeostasis could be measured with fluorescent methods, we coupled the conversion of heme to biliverdin IXα (a product of heme catabolism) by heme oxygenase 1 (HO1) with the production of near-infrared light upon binding this verdin by infrared fluorescent protein (IFP1.4). The resultant heme sensor, IFP-HO1, was fluorescent in pathogenic E. coli exposed to heme but not in the absence of the heme transporter ChuA and membrane coupling protein TonB, thereby validating their long-standing proposed role in heme uptake. Fluorescence was abolished in a strain lacking hemE, the central gene in the heme biosynthetic pathway, but stimulated by iron, signifying the sensor reports on intracellular heme production. Finally, an invasive strain of E. coli harboring the sensor was fluorescent during an active infection. This work will allow researchers to expand the molecular toolbox used to study heme and iron acquisition in culture and during infection. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Theory of Mind in Children With Specific Language Impairment: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Nilsson, Kristine Kahr; de López, Kristine Jensen

    2016-01-01

    The relation between language and theory of mind (ToM) has been debated for more than two decades. In a similar vein, ToM has been examined in children with specific language impairment (SLI), albeit with inconsistent results. This meta-analysis of 17 studies with 745 children between the ages of 4 and 12 found that children with SLI had substantially lower ToM performance compared to age-matched typically developing children (d = .98). This effect size was not moderated by age and gender. By revealing that children with SLI have ToM impairments, this finding emphasizes the need for further investigation into the developmental interface between language and ToM as well as the extended consequences of atypical language development. © 2015 The Authors. Child Development © 2015 Society for Research in Child Development, Inc.

  9. [Diagnostic Accuracy of the LiSe-DaZ for Children with Specific Language Impairment].

    Science.gov (United States)

    Stephan, T; Keilmann, A

    2015-12-01

    Currently, only few tests for the development of speech and language exist for bi- or multilingual children in Germany. One of those, the LiSe-DaZ (Linguistic performance measurement - German as a second language), was examined in a prospective study regarding its practicability and the sensitivity to detect children with specific language impairment in a group of children aged 5 to 7 who suffered from a severe language impairment according to clinical tests. 74 children (mean age: 60 months; 46% monolingual German-speaking; 54% bi- or multilingual) with severe specific language impairment were examined with the LiSe-DaZ in addition to the clinical established diagnostic during their in-patient stay in the hospital. The children, on average, showed in the receptive language abilities (LiSe-DaZ vs. TROG-D), the expressive vocabulary (LiSe-DaZ vs. AWST-R or WWT) and in the use of prepositions (LiSe-DaZ vs. Ravensburger Dysgrammatical clinical trial) significantly (pchildren were diagnosed as language impaired by clinically established tests whereas the LiSe-DaZ considered the children's language development to be normal. This difference was consistently more prominent for children with German as a second language. Compared with the clinically established tests, the informative value of the LiSe-DaZ turned out to be insufficient. The LiSe-DaZ does not detect children with the need of language therapy. Nevertheless, a norming of the established speech tests for bi- or multilingual children would be desirable to avoid unfounded judgements. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Low-dose tryptophan depletion in recovered depressed women induces impairments in autobiographical memory specificity.

    Science.gov (United States)

    Haddad, Anneke D M; Williams, J Mark G; McTavish, Sarah F B; Harmer, Catherine J

    2009-12-01

    Depressed patients perform poorly on tests of autobiographical memory specificity (AMS); this may have negative consequences for other important cognitive abilities, delays recovery from mood episodes, and, in recovered patients, may mediate vulnerability to future episodes. Although the cognitive mechanisms underlying AMS deficits are beginning to be understood, the neurobiological mechanisms remain unclear. Serotonin is implicated in both depression and long-term memory; therefore, temporary lowering of brain serotonin function via acute tryptophan depletion (ATD) offers a means of studying the role of serotonin in autobiographical memory specificity. In this study, 24 previously depressed women underwent low-dose ATD or sham depletion and completed tests of initial and delayed memory, recollection- and familiarity-based recognition, and AMS. ATD did not differentially affect state mood. Compared with sham depletion, ATD impaired immediate recall on the Auditory Verbal Learning Test. Although ATD did not differentially impair recollection- and familiarity-based recognition, it did slow recognition of positive words. ATD also reduced autobiographical memory specificity in response to negative cue words. The results confirm previous findings that low-dose ATD can reinstate depression-congruent biases in cognition without causing depressive mood in vulnerable populations. The ATD-induced reduction in memory specificity suggests that serotonergic dysfunction may mediate depressive deficits in autobiographical memory; the interaction of cognitive and neurobiological vulnerability mechanisms is discussed.

  11. Transmutation of a heme protein.

    Science.gov (United States)

    Barker, P D; Ferrer, J C; Mylrajan, M; Loehr, T M; Feng, R; Konishi, Y; Funk, W D; MacGillivray, R T; Mauk, A G

    1993-01-01

    Residue Asn57 of bovine liver cytochrome b5 has been replaced with a cysteine residue, and the resulting variant has been isolated from recombinant Escherichia coli as a mixture of four major species: A, BI, BII, and C. A combination of electronic spectroscopy, 1H NMR spectroscopy, resonance Raman spectroscopy, electrospray mass spectrometry, and direct electrochemistry has been used to characterize these four major cytochrome derivatives. The red form A (E(m) = -19 mV) is found to possess a heme group bound covalently through a thioether linkage involving Cys57 and the alpha carbon of the heme 4-vinyl group. Form BI has a covalently bound heme group coupled through a thioether linkage involving the beta carbon of the heme 4-vinyl group. Form BII is similar to BI except that the sulfur involved in the thioether linkage is oxidized to a sulfoxide. The green form C (E(m) = 175 mV) possesses a noncovalently bound prosthetic group with spectroscopic properties characteristic of a chlorin. A mechanism is proposed for the generation of these derivatives, and the implications of these observations for the biosynthesis of cytochrome c and naturally occurring chlorin prosthetic groups are discussed. PMID:8341666

  12. Specific language impairment as a maturational lag: evidence from longitudinal data on language and motor development.

    Science.gov (United States)

    Bishop, D V; Edmundson, A

    1987-08-01

    Longitudinal language-test data on 87 language-impaired children assessed at the ages of four, 4 1/2 and 5 1/2 years were converted to age-equivalent scores to compare the rates of development of children who recover from early language delay with those who have more persisting problems. On most measures, over the 18-month period all the children progressed by about 18 months. Thus although children with good and poor outcomes were distinguished in terms of initial level of performance, they did not differ in rate of progress. Speed on a peg-moving task was closely related to language performance. Children who had a good outcome after early language delay had significantly impaired scores at four years, but subsequently were indistinguishable from a control group. Quantitative but not qualitative differences in peg-moving performance were found for children with good and poor outcomes. No association was found between presumptive aetiological factors and language or pegboard performance. These findings are interpreted in terms of a theory which attributes specific language impairment to a maturational lag in neurological development.

  13. Theory of mind and specific language impairment in school-age children.

    Science.gov (United States)

    Spanoudis, George

    2016-01-01

    Research on the relationship between aspects of language development and Theory of Mind (ToM) in children with language impairments suggests that children with language impairment show a delay in ToM development. This study aimed to examine the relationships of the syntactic, semantic, and pragmatic skills with ToM in school-age children. Twenty children with Specific Language Impairment (SLI) aged 9-12 years and two control groups, one matched for chronological age (CA) and one for language ability (LA) (aged 8-10 years) were compared on a set of language tasks tapping syntactic, semantic, and pragmatic skills and on an advanced test of ToM. Results showed that children with SLI performed poorly on the ToM task compared to the CA matches. Also, analysis showed that language skills and ToM are related and that syntactic and pragmatic abilities contributed significantly to the prediction of ToM performance in the SLI group. It is concluded that the syntax/pragmatic aspects of the language impact on ToM understanding in children with SLI. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Screening for Specific Language Impairment in Preschool Children: Evaluating a Screening Procedure Including the Token Test.

    Science.gov (United States)

    Willinger, Ulrike; Schmoeger, Michaela; Deckert, Matthias; Eisenwort, Brigitte; Loader, Benjamin; Hofmair, Annemarie; Auff, Eduard

    2017-10-01

    Specific language impairment (SLI) comprises impairments in receptive and/or expressive language. Aim of this study was to evaluate a screening for SLI. 61 children with SLI (SLI-children, age-range 4-6 years) and 61 matched typically developing controls were tested for receptive language ability (Token Test-TT) and for intelligence (Wechsler Preschool-and-Primary-Scale-of-Intelligence-WPPSI). Group differences were analyzed using t tests, as well as direct and stepwise discriminant analyses. The predictive value of the WPPSI with respect to TT performance was analyzed using regression analyses. SLI-children performed significantly worse on both TT and WPPSI ([Formula: see text]). The TT alone yielded an overall classification rate of 79%, the TT and the WPPSI together yielded an overall classification rate of 80%. TT performance was significantly predicted by verbal intelligence in SLI-children and nonverbal intelligence in controls whilst WPPSI subtest arithmetic was predictive in both groups. Without further research, the Token Test cannot be seen as a valid and sufficient tool for the screening of SLI in preschool children but rather as a tool for the assessment of more general intellectual capacities. SLI-children at this age already show impairments typically associated with SLI which indicates the necessity of early developmental support or training. Token Test performance is possibly an indicator for a more general developmental factor rather than an exclusive indicator for language difficulties.

  15. Residual symptoms and specific functional impairments in euthymic patients with bipolar disorder.

    Science.gov (United States)

    Samalin, Ludovic; de Chazeron, Ingrid; Vieta, Eduard; Bellivier, Frank; Llorca, Pierre-Michel

    2016-03-01

    The aims of the present study were to confirm the impact of residual symptoms on overall functioning in a large sample of euthymic patients with bipolar disorder in real-life conditions and to explore the relationship between residual symptoms and specific areas of functional impairment. This was a multicenter, cross-sectional, non-interventional study of euthymic outpatients with bipolar disorder. The Functioning Assessment Short Test was used to assess overall and specific domains of functioning (autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time). Various residual symptoms were assessed (residual mood symptoms, emotional dysregulation, sleep and sexual disorders, stigma, and perceived cognitive impairment). Logistic regression was used to determine the best model of association between functional domains and residual symptoms. Almost half of the 468 patients included (42%) had poor overall functioning. Residual depressive symptoms appeared to have an impact on overall functioning and in nearly all areas of functioning. In addition, specific residual symptoms had significantly more negative effects on some domains of functioning in euthymic patients with bipolar disorder (residual manic symptoms and occupational stigma on autonomy, emotional inhibition on occupational functioning, residual manic symptoms on financial issues, family stigma on interpersonal relationships, and sexual function and occupational stigma on leisure time). Our findings highlight the importance of evaluating overall functioning in clinical practice as well as functional domains. They also indicate that some residuals symptoms in patients with bipolar disorder should be targeted in personalized treatment plans, in order to improve functioning in the domains in which the patient is most impaired. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Visualization of the role of host heme on the virulence of the heme auxotroph Streptococcus agalactiae.

    Science.gov (United States)

    Joubert, Laetitia; Dagieu, Jean-Baptiste; Fernandez, Annabelle; Derré-Bobillot, Aurélie; Borezée-Durant, Elise; Fleurot, Isabelle; Gruss, Alexandra; Lechardeur, Delphine

    2017-01-16

    Heme is essential for several cellular key functions but is also toxic. Whereas most bacterial pathogens utilize heme as a metabolic cofactor and iron source, the impact of host heme during bacterial infection remains elusive. The opportunist pathogen Streptococcus agalactiae does not synthesize heme but still uses it to activate a respiration metabolism. Concomitantly, heme toxicity is mainly controlled by the HrtBA efflux transporter. Here we investigate how S. agalactiae manages heme toxicity versus benefits in the living host. Using bioluminescent bacteria and heme-responsive reporters for in vivo imaging, we show that the capacity of S. agalactiae to overcome heme toxicity is required for successful infection, particularly in blood-rich organs. Host heme is simultaneously required, as visualized by a generalized infection defect of a respiration-negative mutant. In S. agalactiae, HrtBA expression responds to an intracellular heme signal via activation of the two-component system HssRS. A hssRS promoter-driven intracellular luminescent heme sensor was designed to identify host compartments that supply S. agalactiae with heme. S. agalactiae acquires heme in heart, kidneys, and liver, but not in the brain. We conclude that S. agalactiae response to heme is organ-dependent, and its efflux may be particularly relevant in late stages of infection.

  17. The modality-specific organization of grammatical categories: evidence from impaired spoken and written sentence production.

    Science.gov (United States)

    Rapp, B; Caramazza, A

    1997-02-01

    We describe the case of a brain-damaged individual whose speech is characterized by difficulty with practically all words except for elements of the closed class vocabulary. In contrast, his written sentence production exhibits a complementary impairment involving the omission of closed class vocabulary items and the relative sparing of nouns. On the basis of these differences we argue: (1) that grammatical categories constitute an organizing parameter of representation and/or processing for each of the independent, modality-specific lexicons, and (2) that these observations contribute to the growing evidence that access to the orthographic and phonological forms of words can occur independently.

  18. Emotional health in adolescents with and without a history of specific language impairment (SLI)

    OpenAIRE

    Conti-Ramsden, G.; Botting, N.

    2008-01-01

    Objective:  This study examined the emotional health of adolescents with and without specific language impairment (SLI).\\ud \\ud Method:  One hundred and thirty-nine adolescents with a history of SLI (15;10 years) and a peer group of 124 adolescents with normal language development (NLD) (15;11 years) participated, who were in their final year of compulsory schooling. The risk of emotional difficulties was assessed using the Moods and Feelings Questionnaire (MFQ) and the Child Manifest Anxiety...

  19. The impact of specific language impairment on working memory in children with ADHD combined type

    OpenAIRE

    Jondottir, S.; Bouma, A.; Sergeant, J.A.; Scherder, E.J.A.

    2005-01-01

    The objective of this study was to examine the impact of comorbid specific language impairment (SLI) on verbal and spatial working memory in children with DSM-IV combined subtype Attention Deficit Hyperactivity Disorder (ADHD-C). Participants were a clinical sample of 81/2- to 121/2-year-old children diagnosed with ADHD-C. A group of ADHD-C with SLI was compared to a group of ADHD-C without SLI, and a group of normal children, matched on age and nonverbal intelligence. The results show that A...

  20. The impact of specific language impairment on working memory children with ADHD combined subtype

    OpenAIRE

    Jonsdottir, S.; Bouma, A.; Sergeant, J.A.; Scherder, E.J.A.

    2005-01-01

    The objective of this study was to examine the impact of comorbid specific language impairment (SLI) on verbal and spatial working memory in children with DSM-IV combined subtype Attention Deficit Hyperactivity Disorder (ADHD-C). Participants were a clinical sample of 81/2- to 121/2-year-old children diagnosed with ADHD-C. A group of ADHD-C with SLI was compared to a group of ADHD-C without SLI, and a group of normal children, matched on age and nonverbal intelligence. The results show that A...

  1. Cadmium may impair prostate function as measured by Prostate Specific Antigen in semen

    DEFF Research Database (Denmark)

    Andreucci, Alessandro; Mocevic, Emina; Jönsson, Bo A

    2015-01-01

    We investigated the association between cadmium in blood and the concentration of the prostate specific antigen (PSA) in semen, including the modifying effects of zinc or the CAG polymorphism in the androgen receptor (AR). Blood and semen samples were collected from 504 partners of pregnant women.......0009). Inverse trends between cadmium and PSA were found when semen zinc concentrations were below the median value for men from Ukraine and Greenland. These outcomes suggest that cadmium may impair prostate function, as measured by PSA in semen, while high zinc levels and a low number of CAG repeats protects...

  2. Enhanced Assessment Technology and Neurocognitive Aspects of Specific Learning Disorder with Impairment in Mathematics.

    Directory of Open Access Journals (Sweden)

    Marios A. Pappas

    2018-02-01

    Full Text Available Specific Learning Disorder with impairment in Mathematics (Developmental Dyscalculia is a complex learning disorder which affects arithmetic skills, symbolic magnitude processing, alertness, flexibility in problem solving and maintained attention. Neuro-cognitive studies revealed that such difficulties in children with DD could be related to poor Working Memory and attention deficits. Furthermore, neuroimaging studies indicate that brain structure differences in children with DD compared to typically developing children could affect mathematical performance. In this study we present the cognitive profile of Dyscalculia, as well as the neuropsychological aspects of the deficit, with special reference to the utilization of enhanced assessment technology such as computerized neuropsychological tools and neuroimaging techniques.

  3. Methods for Identifying Specific Language Impairment in Bilingual Populations in Germany

    Directory of Open Access Journals (Sweden)

    Cornelia Hamann

    2017-10-01

    Full Text Available This study investigates the performance of 22 monolingual and 54 bilingual children with and without specific language impairment (SLI, in a non-word repetition task (NWRT and a sentence repetition task (SRT. Both tasks were constructed according to the principles for LITMUS tools (Language Impairment Testing in Multilingual Settings developed within COST Action IS0804 and incorporated phonological or syntactic structures that are linguistically complex and have been shown to be difficult for children with SLI across languages. For phonology these are in particular (nonwords containing consonant clusters. In morphosyntax, complexity has been attributed to factors such as embedding and/or syntactic movement. Tasks focusing on such structures are expected to identify SLI in bilinguals across language combinations. This is notoriously difficult because structures that are problematic for typically developing bilinguals (BiTDs and monolingual children with SLI (MoSLI often overlap. We show that the NWRT and the SRT are reliable tools for identification of SLI in bilingual contexts. However, interpretation of the performance of bilingual children depends on background information as provided by parental questionnaires. To evaluate the accuracy of our tasks, we recruited children in ordinary kindergartens or schools and in speech language therapy centers and verified their status with a battery of standardized language tests, assessing bilingual children in both their languages. We consider a bilingual child language impaired if she shows impairments in two language domains in both her languages. For assessment, we used tests normed for monolinguals (with one exception and adjusted the norms for bilingualism and for language dominance. This procedure established the following groups: 10 typical monolinguals (MoTD, 12 MoSLI, 46 BiTD, and 8 bilingual children with SLI (BiSLI. Our results show that both tasks target relevant structures: monolingual

  4. Cross-Linguistic Transfer Effects after Phonologically Based Cognate Therapy in a Case of Multilingual Specific Language Impairment (SLI)

    Science.gov (United States)

    Kambanaros, Maria; Michaelides, Michalis; Grohmann, Kleanthes K.

    2017-01-01

    Background: Clinicians globally recognize as exceptionally challenging the development of effective intervention practices for bi- or multilingual children with specific language impairment (SLI). Therapy in both or all of an impaired child's languages is rarely possible. An alternative is to develop treatment protocols that facilitate the…

  5. Article choice in children with High Functioning Autism (HFA) and in children with Specific Language Impairment (SLI).

    NARCIS (Netherlands)

    Schaeffer, J.; van Witteloostuijn, M.; de Haan, D.

    2014-01-01

    This study reports on the choice between a definite and an indefinite article by children with High Functioning Autism (HFA) and children with Specific Language Impairment (SLI). We carried out an elicited production task with 16 Dutch-speaking non-grammatically impaired children with HFA aged 6-13,

  6. Elicited Production of Relative Clauses in German: Evidence from Typically Developing Children and Children with Specific Language Impairment

    Science.gov (United States)

    Adani, Flavia; Stegenwallner-Schütz, Maja; Haendler, Yair; Zukowski, Andrea

    2016-01-01

    We elicited the production of various types of relative clauses in a group of German-speaking children with specific language impairment (SLI) and typically developing controls in order to test the movement optionality account of grammatical difficulty in SLI. The results show that German-speaking children with SLI are impaired in relative clause…

  7. Learning trajectories for speech motor performance in children with specific language impairment.

    Science.gov (United States)

    Richtsmeier, Peter T; Goffman, Lisa

    2015-01-01

    Children with specific language impairment (SLI) often perform below expected levels, including on tests of motor skill and in learning tasks, particularly procedural learning. In this experiment we examined the possibility that children with SLI might also have a motor learning deficit. Twelve children with SLI and thirteen children with typical development (TD) produced complex nonwords in an imitation task. Productions were collected across three blocks, with the first and second blocks on the same day and the third block one week later. Children's lip movements while producing the nonwords were recorded using an Optotrak camera system. Movements were then analyzed for production duration and stability. Movement analyses indicated that both groups of children produced shorter productions in later blocks (corroborated by an acoustic analysis), and the rate of change was comparable for the TD and SLI groups. A nonsignificant trend for more stable productions was also observed in both groups. SLI is regularly accompanied by a motor deficit, and this study does not dispute that. However, children with SLI learned to make more efficient productions at a rate similar to their peers with TD, revealing some modification of the motor deficit associated with SLI. The reader will learn about deficits commonly associated with specific language impairment (SLI) that often occur alongside the hallmark language deficit. The authors present an experiment showing that children with SLI improved speech motor performance at a similar rate compared to typically developing children. The implication is that speech motor learning is not impaired in children with SLI. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Rule-based learning of regular past tense in children with specific language impairment.

    Science.gov (United States)

    Smith-Lock, Karen M

    2015-01-01

    The treatment of children with specific language impairment was used as a means to investigate whether a single- or dual-mechanism theory best conceptualizes the acquisition of English past tense. The dual-mechanism theory proposes that regular English past-tense forms are produced via a rule-based process whereas past-tense forms of irregular verbs are stored in the lexicon. Single-mechanism theories propose that both regular and irregular past-tense verbs are stored in the lexicon. Five 5-year-olds with specific language impairment received treatment for regular past tense. The children were tested on regular past-tense production and third-person singular "s" twice before treatment and once after treatment, at eight-week intervals. Treatment consisted of one-hour play-based sessions, once weekly, for eight weeks. Crucially, treatment focused on different lexical items from those in the test. Each child demonstrated significant improvement on the untreated past-tense test items after treatment, but no improvement on the untreated third-person singular "s". Generalization to untreated past-tense verbs could not be attributed to a frequency effect or to phonological similarity of trained and tested items. It is argued that the results are consistent with a dual-mechanism theory of past-tense inflection.

  9. Impairments in site-specific AS160 phosphorylation and effects of exercise training

    DEFF Research Database (Denmark)

    Consitt, Leslie A; Van Meter, Jessica; Newton, Christopher A

    2013-01-01

    The purpose of this study was to determine if site-specific phosphorylation at the level of Akt substrate of 160 kDa (AS160) is altered in skeletal muscle from sedentary humans across a wide range of the adult lifespan (18 to 84 years) and if endurance- and/or strength-oriented exercise training ...... population and that exercise training is an effective intervention for treating these impairments.......The purpose of this study was to determine if site-specific phosphorylation at the level of Akt substrate of 160 kDa (AS160) is altered in skeletal muscle from sedentary humans across a wide range of the adult lifespan (18 to 84 years) and if endurance- and/or strength-oriented exercise training...... in whole-body insulin action were associated with impairments in insulin-induced phosphorylation of skeletal muscle AS160 on sites Ser-588, Thr-642, Ser-666 and phospho-Akt substrate (PAS), but not Ser-318 or Ser-751. Twelve weeks of either endurance- or strength-oriented exercise training increased whole...

  10. Deficits in Coordinative Bimanual Timing Precision in Children With Specific Language Impairment.

    Science.gov (United States)

    Vuolo, Janet; Goffman, Lisa; Zelaznik, Howard N

    2017-02-01

    Our objective was to delineate components of motor performance in specific language impairment (SLI); specifically, whether deficits in timing precision in one effector (unimanual tapping) and in two effectors (bimanual clapping) are observed in young children with SLI. Twenty-seven 4- to 5-year-old children with SLI and 21 age-matched peers with typical language development participated. All children engaged in a unimanual tapping and a bimanual clapping timing task. Standard measures of language and motor performance were also obtained. No group differences in timing variability were observed in the unimanual tapping task. However, compared with typically developing peers, children with SLI were more variable in their timing precision in the bimanual clapping task. Nine of the children with SLI performed greater than 1 SD below the mean on a standardized motor assessment. The children with low motor performance showed the same profile as observed across all children with SLI, with unaffected unimanual and impaired bimanual timing precision. Although unimanual timing is unaffected, children with SLI show a deficit in timing that requires bimanual coordination. We propose that the timing deficits observed in children with SLI are associated with the increased demands inherent in bimanual performance.

  11. Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice.

    Science.gov (United States)

    Zhang, Hongsheng; Kang, Eunchai; Wang, Yaqing; Yang, Chaojuan; Yu, Hui; Wang, Qin; Chen, Zheyu; Zhang, Chen; Christian, Kimberly M; Song, Hongjun; Ming, Guo-Li; Xu, Zhiheng

    2016-06-01

    Several genome- and proteome-wide studies have associated transcription and translation changes of CRMP2 (collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brain in vivo. Here we show that brain-specific Crmp2 knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory. Loss of Crmp2 in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown of crmp2 specifically in newborn neurons results in stage-dependent defects in their development during adult hippocampal neurogenesis. Our findings reveal a critical role for CRMP2 in neuronal plasticity, neural function and behavioural modulation in mice.

  12. Subordinate clause comprehension and tense/agreement inconsistency in children with specific language impairment.

    Science.gov (United States)

    Souto, Sofía M; Leonard, Laurence B; Deevy, Patricia; Fey, Marc E; Bredin-Oja, Shelley L

    2016-01-01

    Several recent studies have suggested that the production errors of children with specific language impairment (SLI) such as The girl singing may be explained by a misinterpretation of grammatical adult input containing a similar structure (e.g., The boy hears the girl singing). Thirteen children with SLI and 13 younger typically developing children with comparable sentence comprehension test scores (TD-COMP) completed a comprehension task to assess their understanding of sentences involving a nonfinite subject-verb sequence in a subordinate clause such as The dad sees the boy running. TD-COMP children were more accurate on subordinate clause items than children with SLI despite similar performance on simple transitive (e.g., The horse sees the cow) and simple progressive (e.g., The cow is eating) items. However, no relationship was found between the SLI group's specific subordinate clause comprehension level and their specific level of auxiliary is production, casting some doubt on this type of structure as a source for inconsistent use of auxiliary is. The reader will learn that children with specific language impairment (SLI): (1) have difficulty understanding complex sentences that include nonfinite subject-verb sequences; (2) that this difficulty is apparent in comparison to younger typically developing peers who have similar scores not only on a sentence comprehension test, but also on simple sentences that correspond to the component parts of the complex sentences; and (3) that this weakness is concurrent with these children's inconsistent use of auxiliary is in production. Although novel verb studies show a clear connection between how children with SLI hear new verbs and how they use them, we do not yet have evidence that this connection is tied to a poor understanding of the input sentences that house the verbs. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Temporally Regular Musical Primes Facilitate Subsequent Syntax Processing in Children with Specific Language Impairment.

    Science.gov (United States)

    Bedoin, Nathalie; Brisseau, Lucie; Molinier, Pauline; Roch, Didier; Tillmann, Barbara

    2016-01-01

    Children with developmental language disorders have been shown to be also impaired in rhythm and meter perception. Temporal processing and its link to language processing can be understood within the dynamic attending theory. An external stimulus can stimulate internal oscillators, which orient attention over time and drive speech signal segmentation to provide benefits for syntax processing, which is impaired in various patient populations. For children with Specific Language Impairment (SLI) and dyslexia, previous research has shown the influence of an external rhythmic stimulation on subsequent language processing by comparing the influence of a temporally regular musical prime to that of a temporally irregular prime. Here we tested whether the observed rhythmic stimulation effect is indeed due to a benefit provided by the regular musical prime (rather than a cost subsequent to the temporally irregular prime). Sixteen children with SLI and 16 age-matched controls listened to either a regular musical prime sequence or an environmental sound scene (without temporal regularities in event occurrence; i.e., referred to as "baseline condition") followed by grammatically correct and incorrect sentences. They were required to perform grammaticality judgments for each auditorily presented sentence. Results revealed that performance for the grammaticality judgments was better after the regular prime sequences than after the baseline sequences. Our findings are interpreted in the theoretical framework of the dynamic attending theory (Jones, 1976) and the temporal sampling (oscillatory) framework for developmental language disorders (Goswami, 2011). Furthermore, they encourage the use of rhythmic structures (even in non-verbal materials) to boost linguistic structure processing and outline perspectives for rehabilitation.

  14. Chondrocyte-specific ablation of Osterix leads to impaired endochondral ossification

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jung-Hoon [Department of Molecular Medicine, Cell and Matrix Research Institute, BK21 Medical Education Program for Human Resources, Kyungpook National University School of Medicine, Daegu (Korea, Republic of); Park, Seung-Yoon [Department of Biochemistry, School of Medicine, Dongguk University, Gyeongju 780-714 (Korea, Republic of); Crombrugghe, Benoit de [Department of Genetics, University of Texas, M.D. Anderson Cancer Center, Houston (United States); Kim, Jung-Eun, E-mail: kjeun@knu.ac.kr [Department of Molecular Medicine, Cell and Matrix Research Institute, BK21 Medical Education Program for Human Resources, Kyungpook National University School of Medicine, Daegu (Korea, Republic of)

    2012-02-24

    Highlights: Black-Right-Pointing-Pointer Conditional ablation of Osterix (Osx) in chondrocytes leads to skeletal defects. Black-Right-Pointing-Pointer Osx regulates chondrocyte differentiation and bone growth in growth plate chondrocytes. Black-Right-Pointing-Pointer Osx has an autonomous function in chondrocytes during endochondral ossification. -- Abstract: Osterix (Osx) is an essential transcription factor required for osteoblast differentiation during both intramembranous and endochondral ossification. Endochondral ossification, a process in which bone formation initiates from a cartilage intermediate, is crucial for skeletal development and growth. Osx is expressed in differentiating chondrocytes as well as osteoblasts during mouse development, but its role in chondrocytes has not been well studied. Here, the in vivo function of Osx in chondrocytes was examined in a chondrocyte-specific Osx conditional knockout model using Col2a1-Cre. Chondrocyte-specific Osx deficiency resulted in a weak and bent skeleton which was evident in newborn by radiographic analysis and skeletal preparation. To further understand the skeletal deformity of the chondrocyte-specific Osx conditional knockout, histological analysis was performed on developing long bones during embryogenesis. Hypertrophic chondrocytes were expanded, the formation of bone trabeculae and marrow cavities was remarkably delayed, and subsequent skeletal growth was reduced. The expression of several chondrocyte differentiation markers was reduced, indicating the impairment of chondrocyte differentiation and endochondral ossification in the chondrocyte-specific Osx conditional knockout. Taken together, Osx regulates chondrocyte differentiation and bone growth in growth plate chondrocytes, suggesting an autonomous function of Osx in chondrocytes during endochondral ossification.

  15. A Case of Specific Language Impairment in a Deaf Signer of American Sign Language.

    Science.gov (United States)

    Quinto-Pozos, David; Singleton, Jenny L; Hauser, Peter C

    2017-04-01

    This article describes the case of a deaf native signer of American Sign Language (ASL) with a specific language impairment (SLI). School records documented normal cognitive development but atypical language development. Data include school records; interviews with the child, his mother, and school professionals; ASL and English evaluations; and a comprehensive neuropsychological and psychoeducational evaluation, and they span an approximate period of 7.5 years (11;10-19;6) including scores from school records (11;10-16;5) and a 3.5-year period (15;10-19;6) during which we collected linguistic and neuropsychological data. Results revealed that this student has average intelligence, intact visual perceptual skills, visuospatial skills, and motor skills but demonstrates challenges with some memory and sequential processing tasks. Scores from ASL testing signaled language impairment and marked difficulty with fingerspelling. The student also had significant deficits in English vocabulary, spelling, reading comprehension, reading fluency, and writing. Accepted SLI diagnostic criteria exclude deaf individuals from an SLI diagnosis, but the authors propose modified criteria in this work. The results of this study have practical implications for professionals including school psychologists, speech language pathologists, and ASL specialists. The results also support the theoretical argument that SLI can be evident regardless of the modality in which it is communicated. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Executive functions and language in children with different subtypes of specific language impairment.

    Science.gov (United States)

    Acosta Rodríguez, V; Ramírez Santana, G M; Hernández Expósito, S

    The marked heterogeneity among children diagnosed with specific language impairment (SLI) highlights the importance of studying and describing cases based on the distinction between the expressive and receptive-expressive SLI subtypes. The main objective of this study was to examine neuropsychological, linguistic, and narrative behaviours in children with different SLI subtypes. A comprehensive battery of language and neuropsychological tests was administered to a total of 58 children (29 with SLI and 29 normal controls) between 5.60 and 11.20 years old. Both SLI subtypes performed more poorly than the control group in language skills, narrative, and executive function. Furthermore, the expressive SLI group demonstrated substantial ungrammaticality, as well as problems with verbal fluency and both verbal and spatial working memory, while the receptive-expressive SLI subtype displayed poorer neuropsychological performance in general. Our findings showed that children with either SLI subtype displayed executive dysfunctions that were not limited to verbal tasks but rather extended to nonverbal measures. This could reflect a global cognitive difficulty which, along with declining linguistic and narrative skills, illustrates the complex profile of this impairment. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Delay or deficit? Spelling processes in children with specific language impairment.

    Science.gov (United States)

    Larkin, Rebecca F; Williams, Gareth J; Blaggan, Samarita

    2013-01-01

    Few studies have explored the phonological, morphological and orthographic spellings skills of children with specific language impairment (SLI) simultaneously. Fifteen children with SLI (mean age=113.07 months, SD=8.61) completed language and spelling tasks alongside chronological-age controls and spelling-age controls. While the children with SLI showed a deficit in phonological spelling, they performed comparably to spelling-age controls on morphological spelling skills, and there were no differences between the three groups in producing orthographically legal spellings. The results also highlighted the potential importance of adequate non-word repetition skills in relation to effective spelling skills, and demonstrated that not all children with spoken language impairments show marked spelling difficulties. Findings are discussed in relation to theory, educational assessment and practice. As a result of this activity, readers will describe components of spoken language that predict children's morphological and phonological spelling performance. As a result of this activity, readers will describe how the spelling skills of children with SLI compare to age-matched and spelling age-matched control children. Readers will be able to interpret the variability in spelling performance seen in children with SLI. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. When words lead to solutions: executive function deficits in preschool children with specific language impairment.

    Science.gov (United States)

    Roello, Mara; Ferretti, Maria Letizia; Colonnello, Valentina; Levi, Gabriel

    2015-02-01

    Several studies indicate that school-age children with specific language impairment (SLI) have difficulties with tasks that rely on executive functions. Whether executive function deficits in children with SLI emerge during preschool age remains unclear. Our aim was to fill this gap by investigating executive function performances in two age groups of preschoolers with and without SLI. Children with SLI (N=60; young: 53.6±5.3 months; old: 65.4±3.8 months) and age-matched control children (N=58) were tested for problem-representation ability, using the Flexible Item Selection Task (FIST), rule-use skills, using a Stroop-like Day-Night test (D/N), and planning skills, using the Tower of London test (TOL). Older children performed better than younger children did across tasks. Children with SLI had poorer performance, compared to typically developing children, on measures of problem representation, planning skills, and use of rules. Our results clearly indicate that executive function impairment is evident during the preschool period. Although old children with SLI performed better than young children with SLI, their performances were still poor, compared to those of control peers. These findings suggest that children with SLI have altered executive functioning at 53.6 months. Copyright © 2014. Published by Elsevier Ltd.

  19. Individual differences in the production of word classes in eight specific language-impaired preschoolers.

    Science.gov (United States)

    Le Normand, M T; Chevrie-Muller, C

    1991-01-01

    The production of word classes in eight 53-62-month-old specific language-impaired (SLI) children was described and compared with that of 30 normal 24-33-month-old children in the same play situation. SLI subjects and nonimpaired children were selected within specified mean length of utterance ranges (low MLU versus high MLU). Production of word classes by subjects was evaluated in order to determine (1) whether SLI children showed a similar or a different word-class profile among themselves and when compared with non-impaired children and (2) whether MLU related to word classes would be useful as a single clinical index in assessment of language acquisition. Results showed that scores of SLI children in production of word classes reflect important individual differences among subjects. In the high-MLU sample, all SLI children produced each word class relatively within the same range as the nonimpaired group. In the low-MLU sample two SLI children were very different in their word-class profile and individual differences were further confirmed by a discriminant function analysis. Correlations between MLU and word classes were significant in nonimpaired children for all variables except Questions and Onomatopoeia and were only significant in SLI children for Verbs, Prepositions, and Personal Pronouns. Such findings contribute support to the view that there is "deviant" pattern of language in SLI children and once again questions whether MLU is one of the best discriminating indicators to use in the clinical assessment of language organization.

  20. Theory of Mind deficits and social emotional functioning in preschoolers with Specific Language Impairment

    Directory of Open Access Journals (Sweden)

    Constance Vissers

    2016-11-01

    Full Text Available Children with Specific Language Impairment (SLI often experience emotional and social difficulties. In general, problems in social emotional functioning can be cognitively explained in terms of Theory of Mind (ToM. In this mini-review, an overview is provided of studies on social-emotional functioning and ToM in preschoolers (average age from 2.3 to 6.2 years with SLI. It is concluded that, similar to school-aged children with SLI, preschoolers with SLI have several social-emotional problems and that both cognitive and affective aspects of ToM are impaired in those children. Based hereon, three possible causal models for the interrelation between language, ToM and social emotional functioning are put forward. It is proposed that future research on the construct and measurement of early ToM, social emotional functioning and language development in preschoolers with SLI is needed to achieve early detection, tailored treatment, and ultimately insight into the pathogenesis of SLI.

  1. First-order and higher order sequence learning in specific language impairment.

    Science.gov (United States)

    Clark, Gillian M; Lum, Jarrad A G

    2017-02-01

    A core claim of the procedural deficit hypothesis of specific language impairment (SLI) is that the disorder is associated with poor implicit sequence learning. This study investigated whether implicit sequence learning problems in SLI are present for first-order conditional (FOC) and higher order conditional (HOC) sequences. Twenty-five children with SLI and 27 age-matched, nonlanguage-impaired children completed 2 serial reaction time tasks. On 1 version, the sequence to be implicitly learnt comprised a FOC sequence and on the other a HOC sequence. Results showed that the SLI group learned the HOC sequence (η p ² = .285, p = .005) but not the FOC sequence (η p ² = .099, p = .118). The control group learned both sequences (FOC η p ² = .497, HOC η p 2= .465, ps < .001). The SLI group's difficulty learning the FOC sequence is consistent with the procedural deficit hypothesis. However, the study provides new evidence that multiple mechanisms may underpin the learning of FOC and HOC sequences. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  2. Interactions between working memory and language in young children with specific language impairment (SLI).

    Science.gov (United States)

    Vugs, Brigitte; Knoors, Harry; Cuperus, Juliane; Hendriks, Marc; Verhoeven, Ludo

    2016-01-01

    The underlying structure of working memory (WM) in young children with and without specific language impairment (SLI) was examined. The associations between the components of WM and the language abilities of young children with SLI were then analyzed. The Automated Working Memory Assessment and four linguistic tasks were administered to 58 children with SLI and 58 children without SLI, aged 4-5 years. The WM of the children was best represented by a model with four separate but interacting components of verbal storage, visuospatial storage, verbal central executive (CE), and visuospatial CE. The associations between the four components of WM did not differ significantly for the two groups of children. However, the individual components of WM showed varying associations with the language abilities of the children with SLI. The verbal CE component of WM was moderately to strongly associated with all the language abilities in children with SLI: receptive vocabulary, expressive vocabulary, verbal comprehension, and syntactic development. These results show verbal CE to be involved in a wide range of linguistic skills; the limited ability of young children with SLI to simultaneously store and process verbal information may constrain their acquisition of linguistic skills. Attention should thus be paid to the language problems of children with SLI, but also to the WM impairments that can contribute to their language problems.

  3. Extending Use of the NRT to Preschool-Aged Children with and without Specific Language Impairment

    Science.gov (United States)

    Deevy, Patricia; Weil, Lisa Wisman; Leonard, Laurence B.; Goffman, Lisa

    2009-01-01

    Purpose The purpose of this study was to assess the diagnostic accuracy of the Nonword Repetition Test (NRT; Dollaghan & Campbell, 1998) in a sample of four- and five-year-olds with and without specific language impairment (SLI), and to evaluate its feasibility for use in universal screening. Method The NRT was administered to 29 children with SLI and 47 age-matched children with typical development (TD). Diagnostic accuracy was computed using alternative scoring methods, which treated out-of-inventory phonemes either as errors or as unscorable. To estimate accuracy in a universal screening context, probability of identifying a child at risk for language impairment was computed using the prevalence of SLI (7%) as the base rate. Results Diagnostic accuracy was acceptable using both scoring methods. The resulting likelihood ratios (LR+ = 22.66, 19.43; LR- = .05, .05) were similar to those reported for older children. The probability of accurate detection of children with SLI in the general population increased from 7% to 61%. However this value suggests that many false positives could be expected. Conclusions The NRT yielded results similar to those reported for older children. However, despite its strengths, the NRT is not sufficient for screening the general population of four- and five-year-olds. PMID:20421612

  4. Extending use of the NRT to preschool-age children with and without specific language impairment.

    Science.gov (United States)

    Deevy, Patricia; Weil, Lisa Wisman; Leonard, Laurence B; Goffman, Lisa

    2010-07-01

    The purpose of this study was to assess the diagnostic accuracy of the Nonword Repetition Test (NRT; Dollaghan & Campbell, 1998) using a sample of 4- and 5-year-olds with and without specific language impairment (SLI) and to evaluate its feasibility for use in universal screening. The NRT was administered to 29 children with SLI and 47 age-matched children with typical development. Diagnostic accuracy was computed using alternative scoring methods, which treated out-of-inventory phonemes either as errors or as unscorable. To estimate accuracy in a universal screening context, the probability of identifying a child at risk for language impairment was computed using the prevalence of SLI (7%) as the base rate. Diagnostic accuracy was acceptable using both scoring methods. The resulting likelihood ratios (LR+ = 22.66, 19.43; LR- = .05, .05) were similar to those reported for older children. The probability of accurate detection of children with SLI in the general population increased from 7% to 61%. However, this value suggests that many false positives could be expected. The NRT yielded results similar to those reported for older children. However, despite its strengths, the NRT is not sufficient for screening the general population of 4- and 5-year-olds.

  5. Hue-specific colour memory impairment in an individual with intact colour perception and colour naming.

    Science.gov (United States)

    Jakobson, L S; Pearson, P M; Robertson, B

    2008-01-15

    Cases of hue-selective dyschomatopsias, together with the results of recent optical imaging studies [Xiao, Y., Casti, A. R. R., Xiao, J., & Kaplan, E. (2006). A spatially organized representation of colour in macaque primary visual cortex. Perception, 35, ECVP Abstract Supplement; Xiao, Y., Wang, Y., & Felleman, D. J. (2003). A spatially organized representation of colour in macaque cortical area V2. Nature, 421, 535-539], have provided support for the idea that different colours are processed in spatially distinct regions of extrastriate cortex. In the present report, we provide evidence suggesting that a similar, but distinct, map may exist for representations of colour in memory. This evidence comes from observations of a young woman (QP) who demonstrates an isolated deficit in colour memory secondary to a concussive episode. Despite having normal colour perception and colour naming skills, and above-average memory skills in other domains, QP's ability to recall visually encoded colour information over short retention intervals is dramatically impaired. Her long-term memory for colour and her colour imagery skills are also abnormal. Surprisingly, however, these impairments are not seen with all hues; specifically, her ability to remember or imagine blue shades is spared. This interesting case contributes to the literature suggesting that colour perception, naming, and memory can be clinically dissociated, and provides insights into the organization of colour information in memory.

  6. Syntactic comprehension and working memory in children with specific language impairment, autism or Down syndrome.

    Science.gov (United States)

    Fortunato-Tavares, Talita; Andrade, Claudia R F; Befi-Lopes, Debora; Limongi, Suelly O; Fernandes, Fernanda D M; Schwartz, Richard G

    2015-07-01

    This study examined syntactic assignment for predicates and reflexives as well as working memory effects in the sentence comprehension of children with Specific Language Impairment (SLI), Down syndrome (DS), high functioning Autism (HFA) and Typical Language Development (TLD). Fifty-seven children (35 boys and 22 girls) performed a computerised picture-selection sentence comprehension task. Predicate attachment and reflexive antecedent assignment (with working memory manipulations) were investigated. The results showed that SLI, HFA and DS children exhibited poorer overall performance than TLD children. Children with SLI exhibited similar performance to the DS and HFA children only when working memory demands were higher. We conclude that children with SLI, HFA and DS differ from children with TLD in their comprehension of predicate and reflexive structures where the knowledge of syntactic assignment is required. Working memory manipulation had different effects on syntactic comprehension depending on language disorder. Intelligence was not an explanatory factor for the differences observed in performance.

  7. Generalized motor abilities and timing behavior in children with specific language impairment.

    Science.gov (United States)

    Zelaznik, Howard N; Goffman, Lisa

    2010-04-01

    To examine whether children with specific language impairment (SLI) differ from normally developing peers in motor skills, especially those skills related to timing. Standard measures of gross and fine motor development were obtained. Furthermore, finger and hand movements were recorded while children engaged in 4 different timing tasks, including tapping and drawing circles in time with a metronome or a visual target. Fourteen children with SLI (age 6 to 8 years) and 14 age-matched peers who were typically developing participated. As expected, children with SLI showed poorer performance on a standardized test of gross and fine motor skill than did their normally developing peers. However, timing skill in the manual domain was equivalent to that seen in typically developing children. Consistent with earlier findings, relatively poor gross and fine motor performance is observed in children with SLI. Surprisingly, rhythmic timing is spared.

  8. Reduced autobiographical memory specificity is associated with impaired discrimination learning in anxiety disorder patients

    Science.gov (United States)

    Lenaert, Bert; Boddez, Yannick; Vervliet, Bram; Schruers, Koen; Hermans, Dirk

    2015-01-01

    Associative learning plays an important role in the development of anxiety disorders, but a thorough understanding of the variables that impact such learning is still lacking. We investigated whether individual differences in autobiographical memory specificity are related to discrimination learning and generalization. In an associative learning task, participants learned the association between two pictures of female faces and a non-aversive outcome. Subsequently, six morphed pictures functioning as generalization stimuli (GSs) were introduced. In a sample of healthy participants (Study 1), we did not find evidence for differences in discrimination learning as a function of memory specificity. In a sample of anxiety disorder patients (Study 2), individuals who were characterized by low memory specificity showed deficient discrimination learning relative to high specific individuals. In contrast to previous findings, results revealed no effect of memory specificity on generalization. These results indicate that impaired discrimination learning, previously shown in patients suffering from an anxiety disorder, may be—in part—due to limited memory specificity. Together, these studies emphasize the importance of incorporating cognitive variables in associative learning theories and their implications for the development of anxiety disorders. In addition, re-analyses of the data (Study 3) showed that patients suffering from panic disorder showed higher outcome expectancies in the presence of the stimulus that was never followed by an outcome during discrimination training, relative to patients suffering from other anxiety disorders and healthy participants. Because we used a neutral, non-aversive outcome (i.e., drawing of a lightning bolt), these data suggest that learning abnormalities in panic disorder may not be restricted to fear learning, but rather reflect a more general associative learning deficit that also manifests in fear irrelevant contexts. PMID

  9. Heme Oxygenase-1 and breast cancer resistance protein protect against heme-induced toxicity

    NARCIS (Netherlands)

    Wagener, Frank A D T G; Dankers, Anita C A; van Summeren, Frank; Scharstuhl, Alwin; van den Heuvel, Jeroen J M W; Koenderink, Jan B; Pennings, Sebastiaan W C; Russel, Frans G M; Masereeuw, R.

    2013-01-01

    Heme is the functional group of diverse hemoproteins and crucial for many cellular processes. However, heme is increasingly recognized as a culprit for a wide variety of pathologies, including sepsis, malaria, and kidney failure. Excess of free heme can be detrimental to tissues by mediating

  10. The sensitivity and specificity of the Middlesex Elderly Assessment of Mental State (MEAMS) for detecting cognitive impairment after stroke.

    Science.gov (United States)

    Cartoni, A; Lincoln, N B

    2005-03-01

    The aim of the study was to assess the sensitivity and specificity of the MEAMS (Golding, 1989) for detecting cognitive impairment after stroke. Stroke patients admitted to hospital received a cognitive screening assessment, the MEAMS, and a detailed cognitive assessment. The information obtained from the detailed assessment was summarised in a structured written report. From the conclusions in these reports, patients were classified as "impaired" or "not impaired" in perception, memory, executive function and language. The sensitivity and specificity of the MEAMS subtests and the overall number of tests passed were determined in relation to the presence of impairment, as given in the overall conclusion of the written reports. There were 30 stroke patients, aged 58 to 92 (mean 75.80, SD 7.94) years. Of these, 17 were men and 13 were women. The sensitivity of the MEAMS subtests ranged from 11% to 100% and the specificity ranged from 69% to 100%. The sensitivity of the overall MEAMS score was 52% and the specificity was 100%, using a cut-off score of 3 or more fails to indicate impairment. Three subtests, Orientation, Naming and Unusual views had 81% sensitivity and 50% specificity for detecting problems in language, perception or memory. The MEAMS was not a sensitive screen for overall cognitive impairment or for memory, perceptual, language, or executive function problems after stroke, but it was specific. Although screening for cognitive impairment is important, the MEAMS is not recommended as the sole method, as it produces an unacceptably high false negative rate. Three subtests (Orientation, Naming and Unusual views) had 81% sensitivity and 50% specificity for detecting cognitive problems in language, perception or memory after stroke.

  11. Heme A synthesis and CcO activity are essential for Trypanosoma cruzi infectivity and replication.

    Science.gov (United States)

    Merli, Marcelo L; Cirulli, Brenda A; Menéndez-Bravo, Simón M; Cricco, Julia A

    2017-06-27

    Trypanosoma cruzi , the causative agent of Chagas disease, presents a complex life cycle and adapts its metabolism to nutrients' availability. Although T. cruzi is an aerobic organism, it does not produce heme. This cofactor is acquired from the host and is distributed and inserted into different heme-proteins such as respiratory complexes in the parasite's mitochondrion. It has been proposed that T. cruzi's energy metabolism relies on a branched respiratory chain with a cytochrome c oxidase-type aa 3 (C c O) as the main terminal oxidase. Heme A, the cofactor for all eukaryotic C c O, is synthesized via two sequential enzymatic reactions catalyzed by heme O synthase (HOS) and heme A synthase (HAS). Previously, TcCox10 and TcCox15 ( Trypanosoma cruzi Cox10 and Cox15 proteins) were identified in T. cruzi They presented HOS and HAS activity, respectively, when they were expressed in yeast. Here, we present the first characterization of TcCox15 in T. cruzi , confirming its role as HAS. It was differentially detected in the different T. cruzi stages, being more abundant in the replicative forms. This regulation could reflect the necessity of more heme A synthesis, and therefore more C c O activity at the replicative stages. Overexpression of a non-functional mutant caused a reduction in heme A content. Moreover, our results clearly showed that this hindrance in the heme A synthesis provoked a reduction on C c O activity and, in consequence, an impairment on T. cruzi survival, proliferation and infectivity. This evidence supports that T. cruzi depends on the respiratory chain activity along its life cycle, being C c O an essential terminal oxidase. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  12. Language Impairments in the Development of Sign: Do They Reside in a Specific Modality or Are They Modality-Independent Deficits?

    Science.gov (United States)

    Woll, Bencie; Morgan, Gary

    2012-01-01

    Various theories of developmental language impairments have sought to explain these impairments in modality-specific ways--for example, that the language deficits in SLI or Down syndrome arise from impairments in auditory processing. Studies of signers with language impairments, especially those who are bilingual in a spoken language as well as a…

  13. A Heme-Sensing Mechanism in the Translational Regulation of Mitochondrial Cytochrome c Oxidase Biogenesis

    Science.gov (United States)

    Soto, Iliana C.; Fontanesi, Flavia; Myers, Richard S.; Hamel, Patrice; Barrientos, Antoni

    2012-01-01

    Heme plays fundamental roles as cofactor and signaling molecule in multiple pathways devoted to oxygen sensing and utilization in aerobic organisms. For cellular respiration, heme serves as a prosthetic group in electron transfer proteins and redox enzymes. Here we report that in the yeast Saccharomyces cerevisiae a heme-sensing mechanism translationally controls the biogenesis of cytochrome c oxidase (COX), the terminal mitochondrial respiratory chain enzyme. We show that Mss51, a COX1 mRNA-specific translational activator and Cox1 chaperone, which coordinates Cox1 synthesis in mitoribosomes with its assembly in COX, is a heme-binding protein. Mss51 contains two heme regulatory motifs or Cys-Pro-X domains located in its N-terminus. Using a combination of in vitro and in vivo approaches, we have demonstrated that these motifs are important for heme binding and efficient performance of Mss51 functions. We conclude that heme sensing by Mss51 regulates COX biogenesis and aerobic energy production. PMID:23217259

  14. A role for heme in Alzheimer's disease: Heme binds amyloid β and has altered metabolism

    OpenAIRE

    Atamna, Hani; Frey, William H.

    2004-01-01

    Heme is a common factor linking several metabolic perturbations in Alzheimer's disease (AD), including iron metabolism, mitochondrial complex IV, heme oxygenase, and bilirubin. Therefore, we determined whether heme metabolism was altered in temporal lobes obtained at autopsy from AD patients and age-matched nondemented subjects. AD brain demonstrated 2.5-fold more heme-b (P < 0.01) and 26% less heme-a (P = 0.16) compared with controls, resulting in a highly significant 2.9-fold decrease in he...

  15. Which are the best predictors of theory of mind delay in children with specific language impairment?

    Science.gov (United States)

    Andrés-Roqueta, Clara; Adrian, Juan E; Clemente, Rosa A; Katsos, Napoleon

    2013-01-01

    The relationship between language and theory of mind (ToM) development in participants with specific language impairment (SLI) it is far from clear due to there were differences in study design and methodologies of previous studies. This research consisted of an in-depth investigation of ToM delay in children with SLI during the typical period of acquisition, and it studied whether linguistic or information-processing variables were the best predictors of this process. It also took into account whether there were differences in ToM competence due to the degree of pragmatic impairment within the SLI group. Thirty-one children with SLI (3;5-7;5 years old) and two control groups (age matched and language matched) were assessed with False Belief (FB) tasks, a wide battery of language measures and additional information-processing measures. The members of the SLI group were less competent than their age-matched peers at solving FB tasks, but they performed similarly to the language-matched group. Regression analysis showed that overall linguistic skills of children with SLI were the best predictor of ToM performance, and especially grammar abilities. No differences between SLI subgroups were found according to their pragmatic level. A delay in ToM development in children with SLI around the critical period of acquisition is confirmed more comprehensively, and it is shown to be more strongly related to their general linguistic level than to their age and other information-processing faculties. This finding stresses the importance of early educational and clinical programmes aimed at reducing deleterious effects in later development. © 2013 Royal College of Speech and Language Therapists.

  16. Analogical reasoning in children with specific language impairment: Evidence from a scene analogy task.

    Science.gov (United States)

    Krzemien, Magali; Jemel, Boutheina; Maillart, Christelle

    2017-01-01

    Analogical reasoning is a human ability that maps systems of relations. It develops along with relational knowledge, working memory and executive functions such as inhibition. It also maintains a mutual influence on language development. Some authors have taken a greater interest in the analogical reasoning ability of children with language disorders, specifically those with specific language impairment (SLI). These children apparently have weaker analogical reasoning abilities than their aged-matched peers without language disorders. Following cognitive theories of language acquisition, this deficit could be one of the causes of language disorders in SLI, especially those concerning productivity. To confirm this deficit and its link to language disorders, we use a scene analogy task to evaluate the analogical performance of SLI children and compare them to controls of the same age and linguistic abilities. Results show that children with SLI perform worse than age-matched peers, but similar to language-matched peers. They are more influenced by increased task difficulty. The association between language disorders and analogical reasoning in SLI can be confirmed. The hypothesis of limited processing capacity in SLI is also being considered.

  17. Lexical spelling in children and adolescents with specific language impairment: variations with the writing situation.

    Science.gov (United States)

    Broc, Lucie; Bernicot, Josie; Olive, Thierry; Favart, Monik; Reilly, Judy; Quémart, Pauline; Uzé, Joël

    2013-10-01

    The goal of this study was to compare the lexical spelling performance of children and adolescents with specific language impairment (SLI) in two contrasting writing situations: a dictation of isolated words (a classic evaluative situation) and a narrative of a personal event (a communicative situation). Twenty-four children with SLI and 48 typically developing children participated in the study, split into two age groups: 7-11 and 12-18 years of age. Although participants with SLI made more spelling errors per word than typically developing participants of the same chronological age, there was a smaller difference between the two groups in the narratives than in the dictations. Two of the findings are particularly noteworthy: (1) Between 12 and 18 years of age, in communicative narration, the number of spelling errors of the SLI group was not different from that of the typically developing group. (2) In communicative narration, the participants with SLI did not make specific spelling errors (phonologically unacceptable), contrary to what was shown in the dictation. From an educational perspective or that of a remediation program, it must be stressed that the communicative narration provides children-and especially adolescents-with SLI an opportunity to demonstrate their improved lexical spelling abilities. Furthermore, the results encourage long-term lexical spelling education, as adolescents with SLI continue to show improvement between 12 and 18 years of age. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Predictors of second language acquisition in Latino children with specific language impairment.

    Science.gov (United States)

    Gutiérrez-Clellen, Vera; Simon-Cereijido, Gabriela; Sweet, Monica

    2012-02-01

    This study evaluated the extent to which the language of intervention, the child's development in Spanish, and the effects of English vocabulary, use, proficiency, and exposure predict differences in the rates of acquisition of English in Latino children with specific language impairment (SLI). In this randomized controlled trial, 188 Latino preschoolers with SLI participated in a small-group academic enrichment program for 12 weeks and were followed up 3 and 5 months later. Children were randomly assigned to either a bilingual or an English-only program. Predictors of English growth included measures of Spanish language skills and English vocabulary, use, proficiency, and exposure. Performance on English outcomes (i.e., picture description and narrative sample) was assessed over time. A series of longitudinal models were tested via multilevel modeling with baseline and posttreatment measures nested within child. Children demonstrated growth on the English outcomes over time. The language of intervention, Spanish skills, English vocabulary, and English use significantly predicted differences in rates of growth across children for specific measures of English development. This study underscores the role of the child's first language skills, the child's level of English vocabulary development, and level of English use for predicting differences in English acquisition in Latino preschoolers with SLI. These factors should be carefully considered in making clinical decisions.

  19. Impaired fear memory specificity associated with deficient endocannabinoid-dependent long-term plasticity.

    Science.gov (United States)

    Lovelace, Jonathan W; Vieira, Philip A; Corches, Alex; Mackie, Ken; Korzus, Edward

    2014-06-01

    In addition to its central role in learning and memory, N-methyl D-aspartate receptor (NMDAR)-dependent signaling regulates central glutamatergic synapse maturation and has been implicated in schizophrenia. We have transiently induced NMDAR hypofunction in infant mice during postnatal days 7-11, followed by testing fear memory specificity and presynaptic plasticity in the prefrontal cortex (PFC) in adult mice. We show that transient NMDAR hypofunction during early brain development, coinciding with the maturation of cortical plasticity results in a loss of an endocannabinoid (eCB)-mediated form of long-term depression (eCB-LTD) at adult central glutamatergic synapses, while another form of presynaptic long-term depression mediated by the metabotropic glutamate receptor 2/3 (mGluR2/3-LTD) remains intact. Mice with this selective impairment of presynaptic plasticity also showed deficits in fear memory specificity. The observed deficit in cortical presynaptic plasticity may represent a neural maladaptation contributing to network instability and abnormal cognitive functioning.

  20. Unique structure and stability of HmuY, a novel heme-binding protein of Porphyromonas gingivalis.

    Directory of Open Access Journals (Sweden)

    Halina Wójtowicz

    2009-05-01

    Full Text Available Infection, survival, and proliferation of pathogenic bacteria in humans depend on their capacity to impair host responses and acquire nutrients in a hostile environment. Among such nutrients is heme, a co-factor for oxygen storage, electron transport, photosynthesis, and redox biochemistry, which is indispensable for life. Porphyromonas gingivalis is the major human bacterial pathogen responsible for severe periodontitis. It recruits heme through HmuY, which sequesters heme from host carriers and delivers it to its cognate outer-membrane transporter, the TonB-dependent receptor HmuR. Here we report that heme binding does not significantly affect the secondary structure of HmuY. The crystal structure of heme-bound HmuY reveals a new all-beta fold mimicking a right hand. The thumb and fingers pinch heme iron through two apical histidine residues, giving rise to highly symmetric octahedral iron co-ordination. The tetrameric quaternary arrangement of the protein found in the crystal structure is consistent with experiments in solution. It shows that thumbs and fingertips, and, by extension, the bound heme groups, are shielded from competing heme-binding proteins from the host. This may also facilitate heme transport to HmuR for internalization. HmuY, both in its apo- and in its heme-bound forms, is resistant to proteolytic digestion by trypsin and the major secreted proteases of P. gingivalis, gingipains K and R. It is also stable against thermal and chemical denaturation. In conclusion, these studies reveal novel molecular properties of HmuY that are consistent with its role as a putative virulence factor during bacterial infection.

  1. Identification of the Mitochondrial Heme Metabolism Complex.

    Science.gov (United States)

    Medlock, Amy E; Shiferaw, Mesafint T; Marcero, Jason R; Vashisht, Ajay A; Wohlschlegel, James A; Phillips, John D; Dailey, Harry A

    2015-01-01

    Heme is an essential cofactor for most organisms and all metazoans. While the individual enzymes involved in synthesis and utilization of heme are fairly well known, less is known about the intracellular trafficking of porphyrins and heme, or regulation of heme biosynthesis via protein complexes. To better understand this process we have undertaken a study of macromolecular assemblies associated with heme synthesis. Herein we have utilized mass spectrometry with coimmunoprecipitation of tagged enzymes of the heme biosynthetic pathway in a developing erythroid cell culture model to identify putative protein partners. The validity of these data obtained in the tagged protein system is confirmed by normal porphyrin/heme production by the engineered cells. Data obtained are consistent with the presence of a mitochondrial heme metabolism complex which minimally consists of ferrochelatase, protoporphyrinogen oxidase and aminolevulinic acid synthase-2. Additional proteins involved in iron and intermediary metabolism as well as mitochondrial transporters were identified as potential partners in this complex. The data are consistent with the known location of protein components and support a model of transient protein-protein interactions within a dynamic protein complex.

  2. Parent-Child Interaction Therapy (PCIT) in school-aged children with specific language impairment.

    Science.gov (United States)

    Allen, Jessica; Marshall, Chloë R

    2011-01-01

    Parents play a critical role in their child's language development. Therefore, advising parents of a child with language difficulties on how to facilitate their child's language might benefit the child. Parent-Child Interaction Therapy (PCIT) has been developed specifically for this purpose. In PCIT, the speech-and-language therapist (SLT) works collaboratively with parents, altering interaction styles to make interaction more appropriate to their child's level of communicative needs. This study investigates the effectiveness of PCIT in 8-10-year-old children with specific language impairment (SLI) in the expressive domain. It aimed to identify whether PCIT had any significant impact on the following communication parameters of the child: verbal initiations, verbal and non-verbal responses, mean length of utterance (MLU), and proportion of child-to-parent utterances. Sixteen children with SLI and their parents were randomly assigned to two groups: treated or delayed treatment (control). The treated group took part in PCIT over a 4-week block, and then returned to the clinic for a final session after a 6-week consolidation period with no input from the therapist. The treated and control group were assessed in terms of the different communication parameters at three time points: pre-therapy, post-therapy (after the 4-week block) and at the final session (after the consolidation period), through video analysis. It was hypothesized that all communication parameters would significantly increase in the treated group over time and that no significant differences would be found in the control group. All the children in the treated group made language gains during spontaneous interactions with their parents. In comparison with the control group, PCIT had a positive effect on three of the five communication parameters: verbal initiations, MLU and the proportion of child-to-parent utterances. There was a marginal effect on verbal responses, and a trend towards such an effect

  3. Transfection of the Human Heme Oxygenase Gene Into Rabbit Coronary Microvessel Endothelial Cells: Protective Effect Against Heme and Hemoglobin Toxicity

    Science.gov (United States)

    Abraham, N. G.; Lavrovsky, Y.; Schwartzman, M. L.; Stoltz, R. A.; Levere, R. D.; Gerritsen, M. E.

    1995-07-01

    Heme oxygenase (HO) is a stress protein and has been suggested to participate in defense mechanisms against agents that may induce oxidative injury such as metals, endotoxin, heme/hemoglobin, and various cytokines. Overexpression of HO in cells might therefore protect against oxidative stress produced by certain of these agents, specifically heme and hemoglobin, by catalyzing their degradation to bilirubin, which itself has antioxidant properties. We report here the successful in vitro transfection of rabbit coronary microvessel endothelial cells with a functioning gene encoding the human HO enzyme. A plasmid containing the cytomegalovirus promoter and the human HO cDNA complexed to cationic liposomes (Lipofectin) was used to transfect rabbit endothelial cells. Cells transfected with human HO exhibited an ≈3.0-fold increase in enzyme activity and expressed a severalfold induction of human HO mRNA as compared with endogenous rabbit HO mRNA. Transfected and nontransfected cells expressed factor VIII antigen and exhibited similar acetylated low-density lipoprotein uptake (two important features that characterize endothelial cells) with >85% of cells staining positive for each marker. Moreover, cells transfected with the human HO gene acquired substantial resistance to toxicity produced by exposure to recombinant hemoglobin and heme as compared with nontransfected cells. The protective effect of HO overexpression against heme/hemoglobin toxicity in endothelial cells shown in these studies provides direct evidence that the inductive response of human HO to such injurious stimuli represents an important tissue adaptive mechanism for moderating the severity of cell damage produced by these blood components.

  4. An Initial Investigation of the Neural Correlates of Word Processing in Preschoolers With Specific Language Impairment.

    Science.gov (United States)

    Haebig, Eileen; Leonard, Laurence; Usler, Evan; Deevy, Patricia; Weber, Christine

    2018-03-15

    Previous behavioral studies have found deficits in lexical-semantic abilities in children with specific language impairment (SLI), including reduced depth and breadth of word knowledge. This study explored the neural correlates of early emerging familiar word processing in preschoolers with SLI and typical development. Fifteen preschoolers with typical development and 15 preschoolers with SLI were presented with pictures followed after a brief delay by an auditory label that did or did not match. Event-related brain potentials were time locked to the onset of the auditory labels. Children provided verbal judgments of whether the label matched the picture. There were no group differences in the accuracy of identifying when pictures and labels matched or mismatched. Event-related brain potential data revealed that mismatch trials elicited a robust N400 in both groups, with no group differences in mean amplitude or peak latency. However, the typically developing group demonstrated a more robust late positive component, elicited by mismatch trials. These initial findings indicate that lexical-semantic access of early acquired words, indexed by the N400, does not differ between preschoolers with SLI and typical development when highly familiar words are presented in isolation. However, the typically developing group demonstrated a more mature profile of postlexical reanalysis and integration, indexed by an emerging late positive component. The findings lay the necessary groundwork for better understanding processing of newly learned words in children with SLI.

  5. Psychomotor profile of a child with specific language impairment and Dyslexia

    Directory of Open Access Journals (Sweden)

    Dias Tânia

    2013-01-01

    Full Text Available Projecting beyond the ideia of the organic and expressive body and cementing a close relationship between motor skills, cognition and language, the current practices Psychomotricity reach a new conceptual field. In this paper of qualitative nature, it was intended to draw the psychomotor profile of a 8 years old child with Specific Language Impairment (SLI and Dyslexia, by using the Vitor da Fonseca ‘s Observation Psychomotor Battery (OPB and correlate it with the linguistic and cognitive profiles. Through the triangulation of the results obtained in psychomotor, cognitive and language tests, the data in literature was corroborated, which clearly point to the existence of co-morbidity between PEL, Dyslexia and disturbances in the psychomotor’s profile, thereby demonstrating a strong correlation between psychomotricity, cognition and language. Therefore, it’s urgent, and possible, to sensitize the family, the health and education professionals for the need to a multidisciplinary approach in the areas of psychomotricity and language, both at a prophylactic or rehabilitative level.

  6. Applying an Integrative Framework of Executive Function to Preschoolers With Specific Language Impairment.

    Science.gov (United States)

    Kapa, Leah L; Plante, Elena; Doubleday, Kevin

    2017-08-16

    The first goal of this research was to compare verbal and nonverbal executive function abilities between preschoolers with and without specific language impairment (SLI). The second goal was to assess the group differences on 4 executive function components in order to determine if the components may be hierarchically related as suggested within a developmental integrative framework of executive function. This study included 26 4- and 5-year-olds diagnosed with SLI and 26 typically developing age- and sex-matched peers. Participants were tested on verbal and nonverbal measures of sustained selective attention, working memory, inhibition, and shifting. The SLI group performed worse compared with typically developing children on both verbal and nonverbal measures of sustained selective attention and working memory, the verbal inhibition task, and the nonverbal shifting task. Comparisons of standardized group differences between executive function measures revealed a linear increase with the following order: working memory, inhibition, shifting, and sustained selective attention. The pattern of results suggests that preschoolers with SLI have deficits in executive functioning compared with typical peers, and deficits are not limited to verbal tasks. A significant linear relationship between group differences across executive function components supports the possibility of a hierarchical relationship between executive function skills.

  7. Inflectional and derivational morphological spelling abilities of children with Specific Language Impairment.

    Science.gov (United States)

    Critten, Sarah; Connelly, Vincent; Dockrell, Julie E; Walter, Kirsty

    2014-01-01

    Children with Specific Language Impairment (SLI) are known to have difficulties with spelling but the factors that underpin these difficulties, are a matter of debate. The present study investigated the impact of oral language and literacy on the bound morpheme spelling abilities of children with SLI. Thirty-three children with SLI (9-10 years) and two control groups, one matched for chronological age (CA) and one for language and spelling age (LA) (aged 6-8 years) were given dictated spelling tasks of 24 words containing inflectional morphemes and 18 words containing derivational morphemes. There were no significant differences between the SLI group and their LA matches in accuracy or error patterns for inflectional morphemes. By contrast when spelling derivational morphemes the SLI group was less accurate and made proportionately more omissions and phonologically implausible errors than both control groups. Spelling accuracy was associated with phonological awareness and reading; reading performance significantly predicted the ability to spell both inflectional and derivational morphemes. The particular difficulties experienced by the children with SLI for derivational morphemes are considered in relation to reading and oral language.

  8. The representation of roots in the spelling of children with specific language impairment.

    Science.gov (United States)

    Deacon, S Hélène; Cleave, Patricia L; Baylis, Julia; Fraser, Jillian; Ingram, Elizabeth; Perlmutter, Signy

    2014-01-01

    Children with Specific Language Impairment (SLI) have demonstrated general spelling and writing difficulties. We investigated the sensitivity of children with SLI to the consistent spelling of root morphemes, a feature to which young typically developing children demonstrate sensitivity. We asked children with SLI and two groups of typically developing children (n = 17 in each group) to spell the same letter-sound sequence (e.g., win) as a root, and as a component of inflected, derived, and control words (e.g., win, wins, winner, wink). Children with SLI and spelling-age-matched children (mean age of 9 and 7 years, respectively) were more accurate and more consistent in spelling the initial sections of the inflected and derived words than of the control words, a pattern that suggests sensitivity to the representation of roots in spelling. The absence of a group-level interaction suggests comparable sensitivity in the two groups. Our results suggest that elementary-school-aged children with SLI are sensitive to the consistent spelling of roots, at least to the extent predicted by their general spelling abilities.

  9. Brain-specific Foxp1 deletion impairs neuronal development and causes autistic-like behaviour.

    Science.gov (United States)

    Bacon, C; Schneider, M; Le Magueresse, C; Froehlich, H; Sticht, C; Gluch, C; Monyer, H; Rappold, G A

    2015-05-01

    Neurodevelopmental disorders are multi-faceted and can lead to intellectual disability, autism spectrum disorder and language impairment. Mutations in the Forkhead box FOXP1 gene have been linked to all these disorders, suggesting that it may play a central role in various cognitive and social processes. To understand the role of Foxp1 in the context of neurodevelopment leading to alterations in cognition and behaviour, we generated mice with a brain-specific Foxp1 deletion (Nestin-Cre(Foxp1-/-)mice). The mutant mice were viable and allowed for the first time the analysis of pre- and postnatal neurodevelopmental phenotypes, which included a pronounced disruption of the developing striatum and more subtle alterations in the hippocampus. More detailed analysis in the CA1 region revealed abnormal neuronal morphogenesis that was associated with reduced excitability and an imbalance of excitatory to inhibitory input in CA1 hippocampal neurons in Nestin-Cre(Foxp1-/-) mice. Foxp1 ablation was also associated with various cognitive and social deficits, providing new insights into its behavioural importance.

  10. Emergent literacy profiles of preschool-age children with specific language impairment.

    Science.gov (United States)

    Cabell, Sonia Q; Lomax, Richard G; Justice, Laura M; Breit-Smith, Allison; Skibbe, Lori E; McGinty, Anita S

    2010-12-01

    The primary aim of the present study was to explore the heterogeneity of emergent literacy skills among preschool-age children with specific language impairment (SLI) through examination of profiles of performance. Fifty-nine children with SLI were assessed on a battery of emergent literacy skills (i.e., alphabet knowledge, print concepts, emergent writing, rhyme awareness) and oral language skills (i.e., receptive/expressive vocabulary and grammar). Cluster analysis techniques identified three emergent literacy profiles: (1) Highest Emergent Literacy, Strength in Alphabet Knowledge; (2) Average Emergent Literacy, Strength in Print Concepts; and (3) Lowest Emergent Literacy across Skills. After taking into account the contribution of child age, receptive and expressive language skills made a small contribution to the prediction of profile membership. The present findings, which may be characterized as exploratory given the relatively modest sample size, suggest that preschool-age children with SLI display substantial individual differences with regard to their emergent literacy skills and that these differences cannot be fully determined by children's age or oral language performance. Replication of the present findings with a larger sample of children is needed.

  11. Behavior problems and social competence in Brazilian children with specific language impairment

    Directory of Open Access Journals (Sweden)

    Marina Leite Puglisi

    2016-01-01

    Full Text Available Abstract This study aimed to investigate the behavior and social profile of Brazilian children with specific language impairment (SLI and explore whether the severity of language deficits was associated with behavioral problems and low social competence. Twenty-four children with SLI aged from 6 to 11 years who showed substantial expressive language problems and were receiving speech-language therapy were assessed through the Child Behavior Checklist (CBCL. Children with SLI showed high rates of behavioral problems and low levels of social competence. With the exception of two subscales (“somatic” and “rule breaker”, the percentage of children with SLI at risk of behavioral problems was significantly higher than the same proportion in the general population; and almost all children with SLI (95.2 % demonstrated problems with social competence. The severity of language deficits was associated with the risk of behavioral problems according to only one criterion. No associations were found between the severity of language problems and social competence. The study provides cross-cultural evidence to support the existence of behavior problems and reduced social competence in children with SLI. Our findings point to the need of using a combination of measures to classify the severity of language problems rather than a single dimension.

  12. The Development of English as a Second Language With and Without Specific Language Impairment: Clinical Implications.

    Science.gov (United States)

    Paradis, Johanne

    2016-02-01

    The purpose of this research forum article is to provide an overview of typical and atypical development of English as a second language (L2) and to present strategies for clinical assessment with English language learners (ELLs). A review of studies examining the lexical, morphological, narrative, and verbal memory abilities of ELLs is organized around 3 topics: timeframe and characteristics of typical English L2 development, comparison of the English L2 development of children with and without specific language impairment (SLI), and strategies for more effective assessment with ELLs. ELLs take longer than 3 years to converge on monolingual norms and approach monolingual norms asynchronously across linguistic subdomains. Individual variation is predicted by age, first language, language learning aptitude, length of exposure to English in school, maternal education, and richness of the English environment outside school. ELLs with SLI acquire English more slowly than ELLs with typical development; their morphological and nonword repetition abilities differentiate them the most. Use of strategies such as parent questionnaires on first language development and ELL norm referencing can result in accurate discrimination of ELLs with SLI. Variability in the language abilities of ELLs presents challenges for clinical practice. Increased knowledge of English language learning development with and without SLI together with evidence-based alternative assessment strategies can assist in overcoming these challenges.

  13. What do children with specific language impairment do with multiple forms of DO?

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    Rice, Mabel L; Blossom, Megan

    2013-02-01

    This study was designed to examine the early usage patterns of multiple grammatical functions of DO in children with and without specific language impairment (SLI). Children's use of this plurifunctional form is informative for evaluation of theoretical accounts of the deficit in SLI. Spontaneous uses of multiple functions of DO were analyzed in language samples from 89 children: 37 children with SLI, ages 5;0-5;6 (years;months); 37 age-equivalent children; and 15 language-equivalent children, ages 2;8-4;10. Proportion correct and types of errors produced were analyzed for each function of DO. Children with SLI had significantly lower levels of proportion correct auxiliary DO use compared to both control groups, with omissions of the DO form as the primary error type. Children with SLI had near-ceiling performance on lexical DO and elliptical DO, similar to both control groups. Plurifunctionality is not problematic: Children acquire each function of DO separately. Grammatical properties of the function, rather than surface properties of the form, dictate whether children with SLI will have difficulty using the word. Overall, these results support the extended optional infinitive account of SLI and the use of auxiliary DO omissions as part of a clinical marker for SLI.

  14. Input Distribution Influences Degree of Auxiliary Use by Children with Specific Language Impairment.

    Science.gov (United States)

    Leonard, Laurence B; Deevy, Patricia

    2011-04-01

    Children with specific language impairment (SLI) show a protracted period of inconsistent use of tense/agreement morphemes. The purpose of this investigation was to determine whether this inconsistent use could be attributed to the children's misinterpretations of particular syntactic structures in the input. In Study 1, preschool-aged children with SLI and typically developing peers heard sentences containing novel verbs preceded by auxiliary was or sentences in which the novel verb formed part of a nonfinite subject-verb sequence within a larger syntactic structure (e.g., We saw the dog relling ). The children were then tested on their use of the novel verbs in contexts that obligated use of auxiliary is . The children with SLI were less accurate than their peers and more likely to produce the novel verb without is if the verb had been heard in a nonfinite subject-verb sequence. In Study 2, children with SLI and typically developing peers were tested on their comprehension of sentences such as The cow sees the horse eating. The children with SLI were less accurate than their peers and were disproportionately influenced by the nonfinite subject-verb clause at the end of the sentence. We interpret these findings within the framework of construction learning.

  15. Task-specific impairments and enhancements induced by magnetic stimulation of human visual area V5.

    Science.gov (United States)

    Walsh, V; Ellison, A; Battelli, L; Cowey, A

    1998-03-22

    Transcranial magnetic stimulation (TMS) can be used to simulate the effects of highly circumscribed brain damage permanently present in some neuropsychological patients, by reversibly disrupting the normal functioning of the cortical area to which it is applied. By using TMS we attempted to recreate deficits similar to those reported in a motion-blind patient and to assess the specificity of deficits when TMS is applied over human area V5. We used six visual search tasks and showed that subjects were impaired in a motion but not a form 'pop-out' task when TMS was applied over V5. When motion was present, but irrelevant, or when attention to colour and form were required, TMS applied to V5 enhanced performance. When attention to motion was required in a motion-form conjunction search task, irrespective of whether the target was moving or stationary, TMS disrupted performance. These data suggest that attention to different visual attributes involves mutual inhibition between different extrastriate visual areas.

  16. Impact of specific language impairment and type of school on different language subsystems.

    Science.gov (United States)

    Puglisi, Marina Leite; Befi-Lopes, Debora Maria

    2016-01-01

    This study aimed to explore quantitative and qualitative effects of type of school and specific language impairment (SLI) on different language abilities. 204 Brazilian children aged from 4 to 6 years old participated in the study. Children were selected to form three groups: 1) 63 typically developing children studying in private schools (TDPri); 2) 102 typically developing children studying in state schools (TDSta); and 39 children with SLI studying in state schools (SLISta). All individuals were assessed regarding expressive vocabulary, number morphology and morphosyntactic comprehension. All language subsystems were vulnerable to both environmental (type of school) and biological (SLI) effects. The relationship between the three language measures was exactly the same to all groups: vocabulary growth correlated with age and with the development of morphological abilities and morphosyntactic comprehension. Children with SLI showed atypical errors in the comprehension test at the age of 4, but presented a pattern of errors that gradually resembled typical development. The effect of type of school was marked by quantitative differences, while the effect of SLI was characterised by both quantitative and qualitative differences.

  17. Applying an Integrative Framework of Executive Function to Preschoolers With Specific Language Impairment

    Science.gov (United States)

    Plante, Elena; Doubleday, Kevin

    2017-01-01

    Purpose The first goal of this research was to compare verbal and nonverbal executive function abilities between preschoolers with and without specific language impairment (SLI). The second goal was to assess the group differences on 4 executive function components in order to determine if the components may be hierarchically related as suggested within a developmental integrative framework of executive function. Method This study included 26 4- and 5-year-olds diagnosed with SLI and 26 typically developing age- and sex-matched peers. Participants were tested on verbal and nonverbal measures of sustained selective attention, working memory, inhibition, and shifting. Results The SLI group performed worse compared with typically developing children on both verbal and nonverbal measures of sustained selective attention and working memory, the verbal inhibition task, and the nonverbal shifting task. Comparisons of standardized group differences between executive function measures revealed a linear increase with the following order: working memory, inhibition, shifting, and sustained selective attention. Conclusion The pattern of results suggests that preschoolers with SLI have deficits in executive functioning compared with typical peers, and deficits are not limited to verbal tasks. A significant linear relationship between group differences across executive function components supports the possibility of a hierarchical relationship between executive function skills. PMID:28724132

  18. Are children with Specific Language Impairment competent with the pragmatics and logic of quantification?

    Science.gov (United States)

    Katsos, Napoleon; Roqueta, Clara Andrés; Estevan, Rosa Ana Clemente; Cummins, Chris

    2011-04-01

    Specific Language Impairment (SLI) is understood to be a disorder that predominantly affects phonology, morphosyntax and/or lexical semantics. There is little conclusive evidence on whether children with SLI are challenged with regard to Gricean pragmatic maxims and on whether children with SLI are competent with the logical meaning of quantifying expressions. We use the comprehension of statements quantified with 'all', 'none', 'some', 'some…not', 'most' and 'not all' as a paradigm to study whether Spanish-speaking children with SLI are competent with the pragmatic maxim of informativeness, as well as with the logical meaning of these expressions. Children with SLI performed more poorly than a group of age-matched typically-developing peers, and both groups performed more poorly with pragmatics than with logical meaning. Moreover, children with SLI were disproportionately challenged by pragmatic meaning compared to their age-matched peers. However, the performance of children with SLI was comparable to that of a group of younger language-matched typically-developing children. The findings document that children with SLI do face difficulties with employing the maxim of informativeness, as well as with understanding the logical meaning of quantifiers, but also that these difficulties are in keeping with their overall language difficulties rather than exceeding them. The implications of these findings for SLI, linguistic theory, and clinical practice are discussed. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Discrimination and identification of long vowels in children with typical language development and specific language impairment

    Science.gov (United States)

    Datta, Hia; Shafer, Valerie; Kurtzberg, Diane

    2004-05-01

    Researchers have claimed that children with specific language impairment (SLI) have particular difficulties in discriminating and identifying phonetically similar and brief speech sounds (Stark and Heinz, 1966; Studdert-Kennedy and Bradley, 1997; Sussman, 1993). In a recent study (Shafer et al., 2004), children with SLI were reported to have difficulty in processing brief (50 ms), phonetically similar vowels (/I-E/). The current study investigated perception of long (250 ms), phonetically similar vowels (/I-E/) in 8- to 10-year-old children with SLI and typical language development (TLD). The purpose was to examine whether phonetic similarity in vowels leads to poorer speech-perception in the SLI group. Behavioral and electrophysiological methods were employed to examine discrimination and identification of a nine-step vowel continuum from /I/ to /E/. Similar performances in discrimination were found for both groups, indicating that lengthening vowel duration indeed improves discrimination of phonetically similar vowels. However, these children with SLI showed poor behavioral identification, demonstrating that phonetic similarity of speech sounds, irrespective of their duration, contribute to the speech perception difficulty observed in SLI population. These findings suggest that the deficit in these children with SLI is at the level of working memory or long term memory representation of speech.

  20. Interaction of language processing and motor skill in children with specific language impairment.

    Science.gov (United States)

    DiDonato Brumbach, Andrea C; Goffman, Lisa

    2014-02-01

    To examine how language production interacts with speech motor and gross and fine motor skill in children with specific language impairment (SLI). Eleven children with SLI and 12 age-matched peers (4-6 years) produced structurally primed sentences containing particles and prepositions. Utterances were analyzed for errors and for articulatory duration and variability. Standard measures of motor, language, and articulation skill were also obtained. Sentences containing particles, as compared with prepositions, were less likely to be produced in a priming task and were longer in duration, suggesting increased difficulty with this syntactic structure. Children with SLI demonstrated higher articulatory variability and poorer gross and fine motor skills compared with aged-matched controls. Articulatory variability was correlated with generalized gross and fine motor performance. Children with SLI show co-occurring speech motor and generalized motor deficits. Current theories do not fully account for the present findings, though the procedural deficit hypothesis provides a framework for interpreting overlap among language and motor domains.

  1. Influence of Language Load on Speech Motor Skill in Children With Specific Language Impairment.

    Science.gov (United States)

    Saletta, Meredith; Goffman, Lisa; Ward, Caitlin; Oleson, Jacob

    2018-03-15

    Children with specific language impairment (SLI) show particular deficits in the generation of sequenced action: the quintessential procedural task. Practiced imitation of a sequence may become rote and require reduced procedural memory. This study explored whether speech motor deficits in children with SLI occur generally or only in conditions of high linguistic load, whether speech motor deficits diminish with practice, and whether it is beneficial to incorporate conditions of high load to understand speech production. Children with SLI and typical development participated in a syntactic priming task during which they generated sentences (high linguistic load) and, then, practiced repeating a sentence (low load) across 3 sessions. We assessed phonetic accuracy, speech movement variability, and duration. Children with SLI produced more variable articulatory movements than peers with typical development in the high load condition. The groups converged in the low load condition. Children with SLI continued to show increased articulatory stability over 3 practice sessions. Both groups produced generated sentences with increased duration and variability compared with repeated sentences. Linguistic demands influence speech motor production. Children with SLI show reduced speech motor performance in tasks that require language generation but not when task demands are reduced in rote practice.

  2. Predictors of growth or attrition of the first language in Latino children with specific language impairment

    Science.gov (United States)

    Simon-Cereijido, Gabriela; Gutiérrez-Clellen, Vera F.; Sweet, Monica

    2012-01-01

    We investigated the factors that may help understand the differential rates of language development in the home language (i.e., Spanish) of Latino preschoolers with specific language impairment (SLI). Children were randomly assigned to either bilingual or English-only small group interventions and followed from preschool to kindergarten. Predictors of Spanish growth included the language of intervention, the child’s level of language development or severity, the child’s socio-emotional skills, and the child’s level of English use. Spanish performance outcomes were assessed over time using a series of longitudinal models with baseline and post-treatment measures nested within child. Children demonstrated growth on Spanish outcomes over time. The language of instruction and the child’s level of vocabulary and socio-emotional development at baseline were significant predictors of differences in rates of growth in the home language. Clinicians may need to take into consideration these factors when making clinical recommendations. PMID:24489415

  3. The complexity of narrative interferes in the use of conjunctions in children with specific language impairment.

    Science.gov (United States)

    Gonzalez, Deborah Oliveira; Cáceres, Ana Manhani; Bento-Gaz, Ana Carolina Paiva; Befi-Lopes, Debora Maria

    2012-01-01

    To verify the use of conjunctions in narratives, and to investigate the influence of stimuli's complexity over the type of conjunctions used by children with specific language impairment (SLI) and children with typical language development. Participants were 40 children (20 with typical language development and 20 with SLI) with ages between 7 and 10 years, paired by age range. Fifteen stories with increasing of complexity were used to obtain the narratives; stories were classified into mechanical, behavioral and intentional, and each of them was represented by four scenes. Narratives were analyzed according to occurrence and classification of conjunctions. Both groups used more coordinative than subordinate conjunctions, with significant decrease in the use of conjunctions in the discourse of SLI children. The use of conjunctions varied according to the type of narrative: for coordinative conjunctions, both groups differed only between intentional and behavioral narratives, with higher occurrence in behavioral ones; for subordinate conjunctions, typically developing children's performance did not show differences between narratives, while SLI children presented fewer occurrences in intentional narratives, which was different from other narratives. Both groups used more coordinative than subordinate conjunctions; however, typically developing children presented more conjunctions than SLI children. The production of children with SLI was influenced by stimulus, since more complex narratives has less use of subordinate conjunctions.

  4. Identification and phylogenetic analysis of heme synthesis genes in trypanosomatids and their bacterial endosymbionts.

    Directory of Open Access Journals (Sweden)

    João M P Alves

    Full Text Available It has been known for decades that some insect-infecting trypanosomatids can survive in culture without heme supplementation while others cannot, and that this capability is associated with the presence of a betaproteobacterial endosymbiont in the flagellate's cytoplasm. However, the specific mechanisms involved in this process remained obscure. In this work, we sequence and phylogenetically analyze the heme pathway genes from the symbionts and from their hosts, as well as from a number of heme synthesis-deficient Kinetoplastida. Our results show that the enzymes responsible for synthesis of heme are encoded on the symbiont genomes and produced in close cooperation with the flagellate host. Our evidence suggests that this synergistic relationship is the end result of a history of extensive gene loss and multiple lateral gene transfer events in different branches of the phylogeny of the Trypanosomatidae.

  5. Joint-Specific Play Controller for Upper Extremity Therapy: Feasibility Study in Children With Wrist Impairment

    Science.gov (United States)

    Wilkins, Megan M.; Basseches, Benjamin; Schwartz, Joel B.; Kerman, Karen; Trask, Christine; Brideau, Holly; Crisco, Joseph J.

    2016-01-01

    Background Challenges with any therapeutic program for children include the level of the child's engagement or adherence. Capitalizing on one of the primary learning avenues of children, play, the approach described in this article is to develop therapeutic toy and game controllers that require specific and repetitive joint movements to trigger toy/game activation. Objective The goal of this study was to evaluate a specially designed wrist flexion and extension play controller in a cohort of children with upper extremity motor impairments (UEMIs). The aim was to understand the relationship among controller play activity, measures of wrist and forearm range of motion (ROM) and spasticity, and ratings of fun and difficulty. Design This was a cross-sectional study of 21 children (12 male, 9 female; 4–12 years of age) with UEMIs. Methods All children participated in a structured in-clinic play session during which measurements of spasticity and ROM were collected. The children were fitted with the controller and played with 2 toys and 2 computer games for 5 minutes each. Wrist flexion and extension motion during play was recorded and analyzed. In addition, children rated the fun and difficulty of play. Results Flexion and extension goal movements were repeatedly achieved by children during the play session at an average frequency of 0.27 Hz. At this frequency, 15 minutes of play per day would result in approximately 1,700 targeted joint motions per week. Play activity was associated with ROM measures, specifically supination, but toy perception ratings of enjoyment and difficulty were not correlated with clinical measures. Limitations The reported results may not be representative of children with more severe UEMIs. Conclusions These outcomes indicate that the therapeutic controllers elicited repetitive goal movements and were adaptable, enjoyable, and challenging for children of varying ages and UEMIs. PMID:27197824

  6. Adenoviral transfer of the heme oxygenase-1 gene protects striatal astrocytes from heme-mediated oxidative injury.

    Science.gov (United States)

    Teng, Zhi-Ping; Chen, Jing; Chau, Lee-Young; Galunic, Nicholas; Regan, Raymond F

    2004-11-01

    Heme oxygenase-1 (HO-1) is induced in the CNS after hemorrhage, and may have an effect on injury to surrounding tissue. Hemin, the preferred substrate of HO, is a neurotoxin that is present in intracranial hematomas. In a prior study, we observed that HO inhibitors increased the vulnerability of cultured cortical astrocytes to heme-mediated oxidative injury. To investigate the effect of HO more specifically, we used an adenoviral vector encoding the human HO-1 gene to specifically increase HO-1 expression. Incubation with 100 MOI of the HO-1 adenovirus (Adv-HHO-1) for 24 h increased both HO-1 protein and HO activity; a control adenovirus lacking the HO-1 gene had no effect. Using a DNA probe that was specific for human HO-1, 80.5 +/- 7.2% of astrocytes were observed to be infected by in situ hybridization. The cell death produced by 30-60 microM hemin was significantly reduced by pretreatment with 100 MOI Adv-HHO-1, as assessed by LDH release, propidium iodide exclusion, and MTT reduction assay. The threefold increase in cell protein oxidation produced by hemin was also attenuated in cultures pretreated with Adv-HHO-1. These results support the hypothesis that HO-1 protects astrocytes from heme-mediated oxidative injury. Specifically increasing astrocytic HO-1 by gene transfer may have a beneficial effect on hemorrhagic CNS injury.

  7. Prebiotics increase heme iron bioavailability and do not affect non-heme iron bioavailability in humans.

    Science.gov (United States)

    Weinborn, Valerie; Valenzuela, Carolina; Olivares, Manuel; Arredondo, Miguel; Weill, Ricardo; Pizarro, Fernando

    2017-05-24

    The aim of this study was to establish the effect of a prebiotic mix on heme and non-heme iron (Fe) bioavailability in humans. To this purpose, twenty-four healthy women were randomized into one of two study groups. One group ate one yogurt per day for 12 days with a prebiotic mix (prebiotic group) and the other group received the same yogurt but without the prebiotic mix (control group). Before and after the intake period, the subjects participated in Fe absorption studies. These studies used 55 Fe and 59 Fe radioactive isotopes as markers of heme Fe and non-heme Fe, respectively, and Fe absorption was measured by the incorporation of radioactive Fe into erythrocytes. The results showed that there were no significant differences in heme and non-heme Fe bioavailability in the control group. Heme Fe bioavailability of the prebiotic group increased significantly by 56% post-prebiotic intake. There were no significant differences in non-heme Fe bioavailability in this group. We concluded that daily consumption of a prebiotic mix increases heme Fe bioavailability and does not affect non-heme iron bioavailability.

  8. Conservation of species, volume, and belief in patients with Alzheimer's disease: the issue of domain specificity and conceptual impairment.

    Science.gov (United States)

    Zaitchik, Deborah; Solomon, Gregg E A

    2009-09-01

    Two studies investigated whether patients with Alzheimer's disease (AD) suffer high-level and category-specific impairment in the conceptual domain of living things. In Experiment 1, AD patients and healthy young and healthy elderly controls took part in three tasks: the conservation of species, volume, and belief. All 3 tasks required tracking an object's identity in the face of irrelevant but salient transformations. Healthy young and elderly controls performed at or near ceiling on all tasks. AD patients were at or near ceiling on the volume and belief tasks, but only about half succeeded on the species task. Experiment 2 demonstrated that the results were not due to simple task demands. AD patients' failure to conserve species indicates that they are impaired in their theoretical understanding of living things, and their success on the volume and belief tasks suggests that the impairment is domain-specific. Two hypotheses are put forward to explain the phenomenon: The first, a category-specific account, holds that the intuitive theory of biology undergoes pervasive degradation; the second, a hybrid domain-general/domain-specific account, holds that impairment to domain-general processes such as executive function interacts with core cognition, the primitive elements that are the foundation of domain-specific knowledge.

  9. Heme oxygenase-1: a metabolic nike.

    Science.gov (United States)

    Wegiel, Barbara; Nemeth, Zsuzsanna; Correa-Costa, Matheus; Bulmer, Andrew C; Otterbein, Leo E

    2014-04-10

    Heme degradation, which was described more than 30 years ago, is still very actively explored with many novel discoveries on its role in various disease models every year. The heme oxygenases (HO) are metabolic enzymes that utilize NADPH and oxygen to break apart the heme moiety liberating biliverdin (BV), carbon monoxide (CO), and iron. Heme that is derived from hemoproteins can be toxic to the cells and if not removed immediately, it causes cell apoptosis and local inflammation. Elimination of heme from the milieu enables generation of three products that influences numerous metabolic changes in the cell. CO has profound effects on mitochondria and cellular respiration and other hemoproteins to which it can bind and affect their function, while BV and bilirubin (BR), the substrate and product of BV, reductase, respectively, are potent antioxidants. Sequestration of iron into ferritin and its recycling in the tissues is a part of the homeodynamic processes that control oxidation-reduction in cellular metabolism. Further, heme is an important component of a number of metabolic enzymes, and, therefore, HO-1 plays an important role in the modulation of cellular bioenergetics. In this review, we describe the cross-talk between heme oxygenase-1 (HO-1) and its products with other metabolic pathways. HO-1, which we have labeled Nike, the goddess who personified victory, dictates triumph over pathophysiologic conditions, including diabetes, ischemia, and cancer.

  10. Subject-specific regional measures of water diffusion are associated with impairment in chronic spinal cord injury.

    Science.gov (United States)

    Choe, Ann S; Sadowsky, Cristina L; Smith, Seth A; van Zijl, Peter C M; Pekar, James J; Belegu, Visar

    2017-08-01

    We aimed to identify non-invasive imaging parameters that can serve as biomarkers for the integrity of the spinal cord, which is paramount to neurological function. Diffusion tensor imaging (DTI) indices are sensitive to axonal and myelin damage, and have strong potential to serve as such biomarkers. However, averaging DTI indices over large regions of interest (ROIs), a common approach to analyzing the images of injured spinal cord, leads to loss of subject-specific information. We investigated if DTI-tractography-driven, subject-specific demarcation approach can yield measures that are more specific to impairment. In 18 individuals with chronic spinal cord injury (SCI), subject-specific demarcation of the injury region was performed using DTI tractography, which yielded three regions relative to injury (RRI; regions superior to, at, and below injury epicenter). DTI indices averaged over each RRI were correlated with measures of residual motor and sensory function, obtained using the International Standard of Neurological Classification for Spinal Cord Injury (ISNCSCI). Total ISNCSCI score (ISNCSCI-tot; sum of ISNCSCI motor and sensory scores) was significantly (p injury epicenter (IRRI), the degree of which exceeded that of those measured from the entire cervical cord-suggesting contribution from Wallerian degeneration. DTI tractography-driven, subject-specific injury demarcation approach provided measures that were more specific to impairment. Notably, DTI indices obtained from the IRRI region showed the highest specificity to impairment, demonstrating their strong potential as biomarkers for the SCI severity.

  11. Short-Term Memory Skills in Children with Specific Language Impairment: The Effect of Verbal and Nonverbal Task Content

    Science.gov (United States)

    Botting, Nicola; Psarou, Popi; Caplin, Tamara; Nevin, Laura

    2013-01-01

    Background and Design: In recent years, evidence has emerged that suggests specific language impairment (SLI) does not exclusively affect linguistic skill. Studies have revealed memory difficulties, including those measured using nonverbal tasks. However, there has been relatively little research into the nature of the verbal/nonverbal boundaries…

  12. The Relationship between Phonological Short-Term Memory, Receptive Vocabulary, and Fast Mapping in Children with Specific Language Impairment

    Science.gov (United States)

    Jackson, Emily; Leitao, Suze; Claessen, Mary

    2016-01-01

    Background: Children with specific language impairment (SLI) often experience word-learning difficulties, which are suggested to originate in the early stage of word learning: fast mapping. Some previous research indicates significantly poorer fast mapping capabilities in children with SLI compared with typically developing (TD) counterparts, with…

  13. Empirical Implications of Matching Children with Specific Language Impairment to Children with Typical Development on Nonverbal IQ

    Science.gov (United States)

    Earle, F. Sayako; Gallinat, Erica L.; Grela, Bernard G.; Lehto, Alexa; Spaulding, Tammie J.

    2017-01-01

    This study determined the effect of matching children with specific language impairment (SLI) and their peers with typical development (TD) for nonverbal IQ on the IQ test scores of the resultant groups. Studies published between January 2000 and May 2012 reporting standard nonverbal IQ scores for SLI and age-matched TD controls were categorized…

  14. Specific Language Impairment and High Functioning Autism : Evidence for Distinct Etiologies and for Modularity of Grammar and Pragmatics

    NARCIS (Netherlands)

    Creemers, A.; Schaeffer, J.C.; Perkins, L.; Dudley, R.; Gerard, J.; Hitczenko, K.

    2015-01-01

    This study investigates whether grammar and pragmatics are separate linguistic components, and whether children with Specific Language Impairment (SLI) and children with High Functioning Autism (HFA) have similar or distinct etiologies. A group of 27 children with HFA aged 6-14, age and gender

  15. Exploration of a "Double-Jeopardy" Hypothesis within Working Memory Profiles for Children with Specific Language Impairment

    Science.gov (United States)

    Briscoe, J.; Rankin, P. M.

    2009-01-01

    Background: Children with specific language impairment (SLI) often experience difficulties in the recall and repetition of verbal information. Archibald and Gathercole (2006) suggested that children with SLI are vulnerable across two separate components of a tripartite model of working memory (Baddeley and Hitch 1974). However, the hierarchical…

  16. Influence of Phonology on Morpho-Syntax in Romance Languages in Children with Specific Language Impairment (SLI)

    Science.gov (United States)

    Aguilar-Mediavilla, Eva; Sanz-Torrent, Monica; Serra-Raventos, Miquel

    2007-01-01

    Background: The profiles of children with Specific Language Impairment (SLI) differ greatly according to the language they speak. The Surface Hypothesis attempts to explain these differences through the theory that children with SLI will incorrectly produce elements in their language with low phonological weights or that are produced in a…

  17. Auditory Perception and Word Recognition in Cantonese-Chinese Speaking Children with and without Specific Language Impairment

    Science.gov (United States)

    Kidd, Joanna C.; Shum, Kathy K.; Wong, Anita M.-Y.; Ho, Connie S.-H.

    2017-01-01

    Auditory processing and spoken word recognition difficulties have been observed in Specific Language Impairment (SLI), raising the possibility that auditory perceptual deficits disrupt word recognition and, in turn, phonological processing and oral language. In this study, fifty-seven kindergarten children with SLI and fifty-three language-typical…

  18. Article choice, theory of mind, and memory in children with high-functioning autism and children with specific language impairment

    NARCIS (Netherlands)

    Schaeffer, J.; van Witteloostuijn, M.; Creemers, A.

    2017-01-01

    Previous studies show that young, typically developing (TD) children (specific language impairment (SLI; >age 5) make errors in the choice between a definite and an indefinite article. Suggested explanations for overgeneration of the definite article include failure to

  19. Do Children with Autism Have a Theory of Mind? A Non-Verbal Test of Autism vs. Specific Language Impairment

    Science.gov (United States)

    Colle, Livia; Baron-Cohen, Simon; Hill, Jacqueline

    2007-01-01

    Children with autism have delays in the development of theory of mind. However, the sub-group of children with autism who have little or no language have gone untested since false belief tests (FB) typically involve language. FB understanding has been reported to be intact in children with specific language impairment (SLI). This raises the…

  20. Language and Social Factors in the Use of Cell Phone Technology by Adolescents with and without Specific Language Impairment (SLI)

    Science.gov (United States)

    Conti-Ramsden, Gina; Durkin, Kevin; Simkin, Zoe

    2010-01-01

    Purpose: This study aimed to compare cell phone use (both oral and text-based) by adolescents with and without specific language impairment (SLI) and examine the extent to which language and social factors affect frequency of use. Method: Both interview and diary methods were used to compare oral and text-based communication using cell phones by…

  1. Linguistic and Cognitive Abilities in Children with Specific Language Impairment as Compared to Children with High-Functioning Autism

    Science.gov (United States)

    Schaeffer, Jeannette

    2018-01-01

    This study investigates the question as to whether and how the linguistic and other cognitive abilities of children with Specific Language Impairment (SLI) differ from those of children with High-Functioning Autism (HFA). To this end, 27 Dutch-speaking elementary-school-age children with SLI, 27 age-matched children with HFA, and a control group…

  2. Linguistic and other cognitive abilities in children with Specific Language Impairment as compared to children with High-Functioning Autism

    NARCIS (Netherlands)

    Schaeffer, J.

    2018-01-01

    This study investigates the question as to whether and how the linguistic and other cognitive abilities of children with Specific Language Impairment (SLI) differ from those of children with High-Functioning Autism (HFA). To this end, 27 Dutch-speaking elementary-school-age children with SLI, 27

  3. Targeting Complex Sentences in Older School Children with Specific Language Impairment: Results from an Early-Phase Treatment Study

    Science.gov (United States)

    Balthazar, Catherine H.; Scott, Cheryl M.

    2018-01-01

    Purpose: This study investigated the effects of a complex sentence treatment at 2 dosage levels on language performance of 30 school-age children ages 10-14 years with specific language impairment. Method: Three types of complex sentences (adverbial, object complement, relative) were taught in sequence in once or twice weekly dosage conditions.…

  4. Sleep deprivation during a specific 3-hour time window post-training impairs hippocampal synaptic plasticity and memory

    NARCIS (Netherlands)

    Prince, Toni-Moi; Wimmer, Mathieu; Choi, Jennifer; Havekes, Robbert; Aton, Sara; Abel, Ted

    2014-01-01

    Sleep deprivation disrupts hippocampal function and plasticity. In particular, long-term memory consolidation is impaired by sleep deprivation, suggesting that a specific critical period exists following learning during which sleep is necessary. To elucidate the impact of sleep deprivation on

  5. Divergence of Verbal Expression and Embodied Knowledge: Evidence from Speech and Gesture in Children with Specific Language Impairment.

    Science.gov (United States)

    Evans, Julia L.; Alibali, Martha W.; McNeil, Nicole M.

    2001-01-01

    Explores the extent to which children with specific language impairment (SLI) with severe phonological working memory deficits express knowledge uniquely in gesture as compared to speech. Using a paradigm in which gesture-speech relationships have been studied extensively, children with SLI and conversation judgment-matched, typically developing…

  6. Developmental Coordination Disorder in children with specific language impairment : Co-morbidity and impact on quality of life

    NARCIS (Netherlands)

    Flapper, Boudien C.T.; Schoemaker, Marina M.

    Co-morbidity of Developmental Coordination Disorder (DCD) in children with specific language impairment (SLI) and the impact of DCD on quality-of-life (QOL) was investigated in 65 5-8 year old children with SLI (43 boys, age 6.8 +/- 0.8; 22 girls, age 6.6 +/- 0.8). The prevalence of DCD was assessed

  7. How Do Children Ascribe Gender to Nouns? A Study of Spanish-Speaking Children with and without Specific Language Impairment

    Science.gov (United States)

    Anderson, Raquel T.; Lockowitz, Alison

    2009-01-01

    The purpose of this investigation was to identify how Spanish-speaking preschool children with and without specific language impairment (SLI) use the various cues available for ascribing a noun's inherent gender in the language. Via an invented word task, four types of cues were isolated and presented to each child: (1) two types of noun-internal…

  8. The Relationship between Phonological Memory, Receptive Vocabulary, and Fast Mapping in Young Children with Specific Language Impairment

    Science.gov (United States)

    Gray, Shelley

    2006-01-01

    Purpose: This study assessed the fast mapping performance of children with specific language impairment (SLI) across the preschool to kindergarten age span in relation to their phonological memory and vocabulary development. Method: Fifty-three children diagnosed with SLI and 53 children with normal language (NL) matched for age and gender (30…

  9. Heme environment in HmuY, the heme-binding protein of Porphyromonas gingivalis

    International Nuclear Information System (INIS)

    Wojtowicz, Halina; Wojaczynski, Jacek; Olczak, Mariusz; Kroliczewski, Jaroslaw; Latos-Grazynski, Lechoslaw; Olczak, Teresa

    2009-01-01

    Porphyromonas gingivalis, a Gram-negative anaerobic bacterium implicated in the development and progression of chronic periodontitis, acquires heme for growth by a novel mechanism composed of HmuY and HmuR proteins. The aim of this study was to characterize the nature of heme binding to HmuY. The protein was expressed, purified and detailed investigations using UV-vis absorption, CD, MCD, and 1 H NMR spectroscopy were carried out. Ferric heme bound to HmuY may be reduced by sodium dithionite and re-oxidized by potassium ferricyanide. Heme complexed to HmuY, with a midpoint potential of 136 mV, is in a low-spin Fe(III) hexa-coordinate environment. Analysis of heme binding to several single and double HmuY mutants with the methionine, histidine, cysteine, or tyrosine residues replaced by an alanine residue identified histidines 134 and 166 as potential heme ligands.

  10. Heme environment in HmuY, the heme-binding protein of Porphyromonas gingivalis

    Energy Technology Data Exchange (ETDEWEB)

    Wojtowicz, Halina [Laboratory of Biochemistry, Faculty of Biotechnology, University of Wroclaw, Tamka 2, 50-137 Wroclaw (Poland); Wojaczynski, Jacek [Department of Chemistry, University of Wroclaw, 50-383 Wroclaw (Poland); Olczak, Mariusz [Laboratory of Biochemistry, Faculty of Biotechnology, University of Wroclaw, Tamka 2, 50-137 Wroclaw (Poland); Kroliczewski, Jaroslaw [Laboratory of Biophysics, Faculty of Biotechnology, University of Wroclaw, 50-148 Wroclaw (Poland); Latos-Grazynski, Lechoslaw [Department of Chemistry, University of Wroclaw, 50-383 Wroclaw (Poland); Olczak, Teresa [Laboratory of Biochemistry, Faculty of Biotechnology, University of Wroclaw, Tamka 2, 50-137 Wroclaw (Poland)

    2009-05-29

    Porphyromonas gingivalis, a Gram-negative anaerobic bacterium implicated in the development and progression of chronic periodontitis, acquires heme for growth by a novel mechanism composed of HmuY and HmuR proteins. The aim of this study was to characterize the nature of heme binding to HmuY. The protein was expressed, purified and detailed investigations using UV-vis absorption, CD, MCD, and {sup 1}H NMR spectroscopy were carried out. Ferric heme bound to HmuY may be reduced by sodium dithionite and re-oxidized by potassium ferricyanide. Heme complexed to HmuY, with a midpoint potential of 136 mV, is in a low-spin Fe(III) hexa-coordinate environment. Analysis of heme binding to several single and double HmuY mutants with the methionine, histidine, cysteine, or tyrosine residues replaced by an alanine residue identified histidines 134 and 166 as potential heme ligands.

  11. Challenging Density Functional Theory Calculations with Hemes and Porphyrins

    Science.gov (United States)

    de Visser, Sam P.; Stillman, Martin J.

    2016-01-01

    In this paper we review recent advances in computational chemistry and specifically focus on the chemical description of heme proteins and synthetic porphyrins that act as both mimics of natural processes and technological uses. These are challenging biochemical systems involved in electron transfer as well as biocatalysis processes. In recent years computational tools have improved considerably and now can reproduce experimental spectroscopic and reactivity studies within a reasonable error margin (several kcal·mol−1). This paper gives recent examples from our groups, where we investigated heme and synthetic metal-porphyrin systems. The four case studies highlight how computational modelling can correctly reproduce experimental product distributions, predicted reactivity trends and guide interpretation of electronic structures of complex systems. The case studies focus on the calculations of a variety of spectroscopic features of porphyrins and show how computational modelling gives important insight that explains the experimental spectra and can lead to the design of porphyrins with tuned properties. PMID:27070578

  12. Challenging Density Functional Theory Calculations with Hemes and Porphyrins

    Directory of Open Access Journals (Sweden)

    Sam P. de Visser

    2016-04-01

    Full Text Available In this paper we review recent advances in computational chemistry and specifically focus on the chemical description of heme proteins and synthetic porphyrins that act as both mimics of natural processes and technological uses. These are challenging biochemical systems involved in electron transfer as well as biocatalysis processes. In recent years computational tools have improved considerably and now can reproduce experimental spectroscopic and reactivity studies within a reasonable error margin (several kcal·mol−1. This paper gives recent examples from our groups, where we investigated heme and synthetic metal-porphyrin systems. The four case studies highlight how computational modelling can correctly reproduce experimental product distributions, predicted reactivity trends and guide interpretation of electronic structures of complex systems. The case studies focus on the calculations of a variety of spectroscopic features of porphyrins and show how computational modelling gives important insight that explains the experimental spectra and can lead to the design of porphyrins with tuned properties.

  13. The specifics of reading to students with hearing and speech impairment in classes VI-VIII

    Directory of Open Access Journals (Sweden)

    Mustaf Morina

    2016-03-01

    Full Text Available Good reading has a very important role in the development of children with hearing impaired; also reading in explicit way is one of the crucial factors which affect the oral language development of children with hearing impaired. The best form and possibility of improvement, development of oral language, development of communicating, receipt of information, knowledge, and ideas over the world, is reading. When the auditory perception is damaged reading is poor. Hearing impairment causes a lot of problems in the development of personality of children with hearing impairment in these fields: poor development of vocabulary, poor quality of lexica, poor quality of sentences, and disorder in articulation. The purpose of this research is to verify the following: 1-Speed of reading of hearing impaired children, 2-The number of errors, 3-The kind of errors, 4-To understand the text in the context of the degree of hearing impairment, age (class, success in school and gender. This theoretical-experimental study was made with students from two schools; special school “Mother Teresa” in Prizren and Primary School “Elena Gjika” in Prishtina (class attached. The research included a total of 32 students (respondent 27 students (respondent from special schools “Mother Teresa” in Prizren and 5 elementary school students “Elena Gjika” Prishtina, all these students are with hearing impairment. From 32 students involved in the research, 23 were male and 9 female. The research was done by applying a text fables “The fox and the raven” watched and analyzed in terms of three dimensions. The research results have shown that students with hearing impairments have considerable problems in many aspects; in terms of speed of reading, students with hearing impairment have stagnated compared with their peers in the ratio 8/1. In terms of reading errors have stagnated considered being incomparable. In terms of understanding the text students with hearing

  14. Executive and intellectual functioning in school-aged children with specific language impairment.

    Science.gov (United States)

    Kuusisto, Marika A; Nieminen, Pirkko E; Helminen, Mika T; Kleemola, Leenamaija

    2017-03-01

    Earlier research and clinical practice show that specific language impairment (SLI) is often associated with nonverbal cognitive deficits and weakened skills in executive functions (EFs). Executive deficits may have a remarkable influence on a child's everyday activities in the home and school environments. However, research information is still limited on EFs in school-aged children with SLI, mostly conducted among English- and Dutch-speaking children. To study whether there are differences in EFs between Finnish-speaking children with SLI and typically developing (TD) peers at school age. EFs are compared between the groups with and without controlling for nonverbal intelligence. Parents and teachers of children with SLI (n = 22) and age- and gender-matched TD peers (n = 22) completed The Behavior Rating Inventory of Executive Functions (BRIEF). The mean age of the children was 8,2 years. BRIEF ratings of parents and teachers were compared between the children with SLI and with TD peers by paired analysis using conditional logistic regression models with and without controlling for nonverbal IQ. Intellectual functioning was assessed with the Wechsler Intelligence Scale for Children. Children with SLI had weaker scores in all parent and teacher BRIEF scales compared with TD peers. Statistically significant differences between the groups were found in BRIEF scales Shift, Emotional Control, Initiate, Working Memory, Plan/Organize and Monitor. Differences between the groups were statistically significant also in intellectual functioning. On BRIEF scales some group differences remained statistically significant after controlling for nonverbal IQ. This study provides additional evidence that also Finnish-speaking school-aged children with SLI are at risk of having deficits in EFs in daily life. EFs have been proposed to have an impact on developmental outcomes later in life. In clinical practice it is important to pay attention to EFs in school-aged children with SLI

  15. The comprehension of Italian relative clauses in poor readers and in children with Specific Language Impairment

    Directory of Open Access Journals (Sweden)

    Fabrizio Arosio

    2017-02-01

    Full Text Available Children with Specific Language Impairment (SLI and children with Developmental Dyslexia (DD have problems comprehending relative clauses (RCs and find object RCs more difficult than subject RCs, as do typically developing children. Few studies have compared these groups directly, leaving it unclear whether the problems observed in children with DD are similar to those described in SLI. Work with typically developing children has shown that the comprehension of passive RCs is less challenging than that of object RCs. It is argued that this asymmetry depends on intervention effects as modelized in a Relativized Minimality framework. Since movement is challenging for children with SLI and those with DD, examining and comparing their comprehension of object RCs and passive RCs can broaden our understanding of their language deficits. In fact, both structures involve movement, but the moved element and the movement configuration are different. In our study we investigated the comprehension of subject RCs, object RCs and passive RCs in 12 Italian monolingual children with SLI (mean age: 7;6, 13 Italian monolingual children with DD (mean age: 10;7 and 50 typically developing controls matched for age, grammar and vocabulary. Results from a picture selection task show that: (i subject RCs are unproblematic for all children; (ii object RCs are challenging for children with SLI, children with DD and younger typically developing controls; (iii passive RCs are better understood than object RCs in all groups, but still problematic for children with SLI and younger typically developing controls. Our data show that intervention effects are found in children with SLI and children with DD and that those with SLI have a deficit in transferring thematic roles to moved elements. Our results point out that some of the children with DD have a mild grammatical deficit that was undetected or escaped standardized tests.

  16. Myocyte specific overexpression of myoglobin impairs angiogenesis after hind-limb ischemia.

    Science.gov (United States)

    Hazarika, Surovi; Angelo, Michael; Li, Yongjun; Aldrich, Amy J; Odronic, Shelley I; Yan, Zhen; Stamler, Jonathan S; Annex, Brian H

    2008-12-01

    In preclinical models of peripheral arterial disease the angiogenic response is typically robust, though it can be impaired in conditions such as hypercholesterolemia and diabetes where the endothelium is dysfunctional. Myoglobin (Mb) is expressed exclusively in striated muscle cells. We hypothesized that myocyte specific overexpression of myoglobin attenuates ischemia-induced angiogenesis even in the presence of normal endothelium. Mb overexpressing transgenic (MbTg, n=59) and wild-type (WT, n=56) C57Bl/6 mice underwent unilateral femoral artery ligation/excision. Perfusion recovery was monitored using Laser Doppler. Ischemia-induced changes in muscle were assessed by protein and immunohistochemistry assays. Nitrite/nitrate and protein-bound NO, and vasoreactivity was measured. Vasoreactivity was similar between MbTg and WT. In ischemic muscle, at d14 postligation, MbTg increased VEGF-A, and activated eNOS the same as WT mice but nitrate/nitrite were reduced whereas protein-bound NO was higher. MbTg had attenuated perfusion recovery at d21 (0.37+/-0.03 versus 0.47+/-0.02, P<0.05), d28 (0.40+/-0.03 versus 0.50+/-0.04, P<0.05), greater limb necrosis (65.2% versus 15%, P<0.001), a lower capillary density, and greater apoptosis versus WT. Increased Mb expression in myocytes attenuates angiogenesis after hind-limb ischemia by binding NO and reducing its bioavailability. Myoglobin can modulate the angiogenic response to ischemia even in the setting of normal endothelium.

  17. Analogical mapping across modalities in children with specific language impairment (SLI).

    Science.gov (United States)

    Leroy, Sandrine; Maillart, Christelle; Parisse, Christophe

    2014-09-01

    Analogical mapping is a domain-general cognitive process found in language development, and more particularly in the abstraction of construction schemas. Analogical mapping is considered as the general cognitive process which consists in the alignment of two or several sequences in order to detect their common relational structure and generalize it to new items. The current study investigated analogical mapping across modalities in children with specific language impairment (SLI). Nineteen children with SLI and their age-matched peers were administered two tasks: a linguistic analogical reasoning task (composed of syllables) and a similar non-linguistic analogical reasoning task (composed of pictures). In the two tasks, the items presented were divided into two groups: items with perceptual cues and items without perceptual cues. Children had to complete a sequence sharing the same relational structure as previously presented sequences. Results showed an expected group effect with poorer performance for children with SLI compared to children with typical language development (TLD). Results corroborate hypotheses suggesting that children with SLI have difficulties with analogical mapping, which may hinder the abstraction of construction schemas. Interestingly, whereas no interaction effect between group and modality (linguistic vs. non-linguistic) was revealed, a triple interaction Group*Modality*Perceptual support was observed. In the non-linguistic task, the performance of children with SLI was the same for items with and without perceptual clues, but in the linguistic task they performed more poorly for items without perceptual cues compared to items with perceptual cues. The results and limits of the study are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. The relation between receptive grammar and procedural, declarative, and working memory in specific language impairment.

    Science.gov (United States)

    Conti-Ramsden, Gina; Ullman, Michael T; Lum, Jarrad A G

    2015-01-01

    What memory systems underlie grammar in children, and do these differ between typically developing (TD) children and children with specific language impairment (SLI)? Whilst there is substantial evidence linking certain memory deficits to the language problems in children with SLI, few studies have investigated multiple memory systems simultaneously, examining not only possible memory deficits but also memory abilities that may play a compensatory role. This study examined the extent to which procedural, declarative, and working memory abilities predict receptive grammar in 45 primary school aged children with SLI (30 males, 15 females) and 46 TD children (30 males, 16 females), both on average 9;10 years of age. Regression analyses probed measures of all three memory systems simultaneously as potential predictors of receptive grammar. The model was significant, explaining 51.6% of the variance. There was a significant main effect of learning in procedural memory and a significant group × procedural learning interaction. Further investigation of the interaction revealed that procedural learning predicted grammar in TD but not in children with SLI. Indeed, procedural learning was the only predictor of grammar in TD. In contrast, only learning in declarative memory significantly predicted grammar in SLI. Thus, different memory systems are associated with receptive grammar abilities in children with SLI and their TD peers. This study is, to our knowledge, the first to demonstrate a significant group by memory system interaction in predicting grammar in children with SLI and their TD peers. In line with Ullman's Declarative/Procedural model of language and procedural deficit hypothesis of SLI, variability in understanding sentences of varying grammatical complexity appears to be associated with variability in procedural memory abilities in TD children, but with declarative memory, as an apparent compensatory mechanism, in children with SLI.

  19. Insights on Heme Synthesis in the Malaria Parasite.

    Science.gov (United States)

    Nagaraj, Viswanathan A; Padmanaban, Govindarajan

    2017-08-01

    The malaria parasite has a functional heme-biosynthetic pathway, although it can access host hemoglobin-heme. The heme pathway is dispensable for blood stages, but essential in the mosquito stages which do not acquire hemoglobin-heme. We propose that the blood stage parasites maintain a dynamic heme pool through multiple back-up mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Mutations in the Heme Exporter FLVCR1 Cause Sensory Neurodegeneration with Loss of Pain Perception.

    Science.gov (United States)

    Chiabrando, Deborah; Castori, Marco; di Rocco, Maja; Ungelenk, Martin; Gießelmann, Sebastian; Di Capua, Matteo; Madeo, Annalisa; Grammatico, Paola; Bartsch, Sophie; Hübner, Christian A; Altruda, Fiorella; Silengo, Lorenzo; Tolosano, Emanuela; Kurth, Ingo

    2016-12-01

    Pain is necessary to alert us to actual or potential tissue damage. Specialized nerve cells in the body periphery, so called nociceptors, are fundamental to mediate pain perception and humans without pain perception are at permanent risk for injuries, burns and mutilations. Pain insensitivity can be caused by sensory neurodegeneration which is a hallmark of hereditary sensory and autonomic neuropathies (HSANs). Although mutations in several genes were previously associated with sensory neurodegeneration, the etiology of many cases remains unknown. Using next generation sequencing in patients with congenital loss of pain perception, we here identify bi-allelic mutations in the FLVCR1 (Feline Leukemia Virus subgroup C Receptor 1) gene, which encodes a broadly expressed heme exporter. Different FLVCR1 isoforms control the size of the cytosolic heme pool required to sustain metabolic activity of different cell types. Mutations in FLVCR1 have previously been linked to vision impairment and posterior column ataxia in humans, but not to HSAN. Using fibroblasts and lymphoblastoid cell lines from patients with sensory neurodegeneration, we here show that the FLVCR1-mutations reduce heme export activity, enhance oxidative stress and increase sensitivity to programmed cell death. Our data link heme metabolism to sensory neuron maintenance and suggest that intracellular heme overload causes early-onset degeneration of pain-sensing neurons in humans.

  1. Mutations in the Heme Exporter FLVCR1 Cause Sensory Neurodegeneration with Loss of Pain Perception.

    Directory of Open Access Journals (Sweden)

    Deborah Chiabrando

    2016-12-01

    Full Text Available Pain is necessary to alert us to actual or potential tissue damage. Specialized nerve cells in the body periphery, so called nociceptors, are fundamental to mediate pain perception and humans without pain perception are at permanent risk for injuries, burns and mutilations. Pain insensitivity can be caused by sensory neurodegeneration which is a hallmark of hereditary sensory and autonomic neuropathies (HSANs. Although mutations in several genes were previously associated with sensory neurodegeneration, the etiology of many cases remains unknown. Using next generation sequencing in patients with congenital loss of pain perception, we here identify bi-allelic mutations in the FLVCR1 (Feline Leukemia Virus subgroup C Receptor 1 gene, which encodes a broadly expressed heme exporter. Different FLVCR1 isoforms control the size of the cytosolic heme pool required to sustain metabolic activity of different cell types. Mutations in FLVCR1 have previously been linked to vision impairment and posterior column ataxia in humans, but not to HSAN. Using fibroblasts and lymphoblastoid cell lines from patients with sensory neurodegeneration, we here show that the FLVCR1-mutations reduce heme export activity, enhance oxidative stress and increase sensitivity to programmed cell death. Our data link heme metabolism to sensory neuron maintenance and suggest that intracellular heme overload causes early-onset degeneration of pain-sensing neurons in humans.

  2. Chloroquine Interference with Hemoglobin Endocytic Trafficking Suppresses Adaptive Heme and Iron Homeostasis in Macrophages: The Paradox of an Antimalarial Agent

    Directory of Open Access Journals (Sweden)

    Christian A. Schaer

    2013-01-01

    Full Text Available The CD163 scavenger receptor pathway for Hb:Hp complexes is an essential mechanism of protection against the toxicity of extracellular hemoglobin (Hb, which can accumulate in the vasculature and within tissues during hemolysis. Chloroquine is a lysosomotropic agent, which has been extensively used as an antimalarial drug in the past, before parasite resistance started to limit its efficacy in most parts of the world. More recent use of chloroquine is related to its immunomodulatory activity in patients with autoimmune diseases, which may also involve hemolytic disease components. In this study we examined the effects of chloroquine on the human Hb clearance pathway. For this purpose we developed a new mass-spectrometry-based method to specifically quantify intracellular Hb peptides within the endosomal-lysosomal compartment by single reaction monitoring (SRM. We found that chloroquine exposure impairs trafficking of Hb:Hp complexes through the endosomal-lysosomal compartment after internalization by CD163. Relative quantification of intracellular Hb peptides by SRM confirmed that chloroquine blocked cellular Hb:Hp catabolism. This effect suppressed the cellular heme-oxygenase-1 (HO-1 response and shifted macrophage iron homeostasis towards inappropriately high expression of the transferrin receptor with concurrent inhibition of ferroportin expression. A functional deficiency of Hb detoxification and heme-iron recycling may therefore be an adverse consequence of chloroquine treatment during hemolysis.

  3. Cytokine Response, Tract-Specific Fractional Anisotropy, and Brain Morphometry in Post-Stroke Cognitive Impairment.

    Science.gov (United States)

    Kulesh, Aleksey; Drobakha, Viktor; Kuklina, Elena; Nekrasova, Irina; Shestakov, Vladimir

    2018-07-01

    Post-stroke cognitive impairment is a clinically heterogeneous condition and its types have a different course and prognosis. The aim of the present study is to address the roles of inflammation, white matter pathology, and brain atrophy in different neuropsychological types of cognitive impairment in the acute period of ischemic stroke. In 92 patients, we performed an assessment of the cognitive status and measured concentrations of cytokines (interleukin [IL]-1β, IL-6, tumor necrosis factor-alpha, IL-10) in liquor and serum, as well as a number of magnetic resonance imaging (MRI) morphometric parameters and fractional anisotropy. The control group consisted of 14 individuals without cerebrovascular disease. All patients had a higher level of IL-10 in serum than the control group. Patients with dysexecutive cognitive impairment had a higher concentration of IL-1β and IL-10 in liquor, IL-6 level in serum, and a lower fractional anisotropy of the ipsilateral thalamus than patients with normal cognition. Patients with mixed cognitive impairment were characterized by a lower fractional anisotropy of contralateral fronto-occipital fasciculus, compared with patients with dysexecutive cognitive impairment. Patients with both dysexecutive and mixed cognitive deficit had a wide area of leukoaraiosis and a reduced fractional anisotropy of the contralateral cingulum, compared with patients without cognitive impairment. Also, we found numerous correlations between cognitive status and levels of cytokines, MRI morphometric parameters, and fractional anisotropy of certain regions of the brain. The concentrations of cytokines in serum and cerebrospinal fluid studied in combination with MRI morphometric parameters and fractional anisotropy appear to be informative biomarkers of clinical types of post-stroke cognitive impairment. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  4. The role of candidate-gene CNTNAP2 in childhood apraxia of speech and specific language impairment.

    Science.gov (United States)

    Centanni, T M; Sanmann, J N; Green, J R; Iuzzini-Seigel, J; Bartlett, C; Sanger, W G; Hogan, T P

    2015-10-01

    Childhood apraxia of speech (CAS) is a debilitating pediatric speech disorder characterized by varying symptom profiles, comorbid deficits, and limited response to intervention. Specific Language Impairment (SLI) is an inherited pediatric language disorder characterized by delayed and/or disordered oral language skills including impaired semantics, syntax, and discourse. To date, the genes associated with CAS and SLI are not fully characterized. In the current study, we evaluated behavioral and genetic profiles of seven children with CAS and eight children with SLI, while ensuring all children were free of comorbid impairments. Deletions within CNTNAP2 were found in two children with CAS but not in any of the children with SLI. These children exhibited average to high performance on language and word reading assessments in spite of poor articulation scores. These findings suggest that genetic variation within CNTNAP2 may be related to speech production deficits. © 2015 Wiley Periodicals, Inc.

  5. Nonadjacent Dependency Learning in Cantonese-Speaking Children With and Without a History of Specific Language Impairment.

    Science.gov (United States)

    Iao, Lai-Sang; Ng, Lai Yan; Wong, Anita Mei Yin; Lee, Oi Ting

    2017-03-01

    This study investigated nonadjacent dependency learning in Cantonese-speaking children with and without a history of specific language impairment (SLI) in an artificial linguistic context. Sixteen Cantonese-speaking children with a history of SLI and 16 Cantonese-speaking children with typical language development (TLD) were tested with a nonadjacent dependency learning task using artificial languages that mimic Cantonese. Children with TLD performed above chance and were able to discriminate between trained and untrained nonadjacent dependencies. However, children with a history of SLI performed at chance and were not able to differentiate trained versus untrained nonadjacent dependencies. These findings, together with previous findings from English-speaking adults and adolescents with language impairments, suggest that individuals with atypical language development, regardless of age, diagnostic status, language, and culture, show difficulties in learning nonadjacent dependencies. This study provides evidence for early impairments to statistical learning in individuals with atypical language development.

  6. Deficits in narrative abilities in child British Sign Language users with specific language impairment.

    Science.gov (United States)

    Herman, Ros; Rowley, Katherine; Mason, Kathryn; Morgan, Gary

    2014-01-01

    This study details the first ever investigation of narrative skills in a group of 17 deaf signing children who have been diagnosed with disorders in their British Sign Language development compared with a control group of 17 deaf child signers matched for age, gender, education, quantity, and quality of language exposure and non-verbal intelligence. Children were asked to generate a narrative based on events in a language free video. Narratives were analysed for global structure, information content and local level grammatical devices, especially verb morphology. The language-impaired group produced shorter, less structured and grammatically simpler narratives than controls, with verb morphology particularly impaired. Despite major differences in how sign and spoken languages are articulated, narrative is shown to be a reliable marker of language impairment across the modality boundaries. © 2014 Royal College of Speech and Language Therapists.

  7. Face-specific impairment in holistic perception following focal lesion of the right anterior temporal lobe.

    Science.gov (United States)

    Busigny, Thomas; Van Belle, Goedele; Jemel, Boutheina; Hosein, Anthony; Joubert, Sven; Rossion, Bruno

    2014-04-01

    Recent studies have provided solid evidence for pure cases of prosopagnosia following brain damage. The patients reported so far have posterior lesions encompassing either or both the right inferior occipital cortex and fusiform gyrus, and exhibit a critical impairment in generating a sufficiently detailed holistic percept to individualize faces. Here, we extended these observations to include the prosopagnosic patient LR (Bukach, Bub, Gauthier, & Tarr, 2006), whose damage is restricted to the anterior region of the right temporal lobe. First, we report that LR is able to discriminate parametrically defined individual exemplars of nonface object categories as accurately and quickly as typical observers, which suggests that the visual similarity account of prosopagnosia does not explain his impairments. Then, we show that LR does not present with the typical face inversion effect, whole-part advantage, or composite face effect and, therefore, has impaired holistic perception of individual faces. Moreover, the patient is more impaired at matching faces when the facial part he fixates is masked than when it is selectively revealed by means of gaze contingency. Altogether these observations support the view that the nature of the critical face impairment does not differ qualitatively across patients with acquired prosopagnosia, regardless of the localization of brain damage: all these patients appear to be impaired to some extent at what constitutes the heart of our visual expertise with faces, namely holistic perception at a sufficiently fine-grained level of resolution to discriminate exemplars of the face class efficiently. This conclusion raises issues regarding the existing criteria for diagnosis/classification of patients as cases of apperceptive or associative prosopagnosia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Multilingual home environment and specific language impairment: a case-control study in Chinese children.

    Science.gov (United States)

    Cheuk, Daniel Ka Leung; Wong, Virginia; Leung, Gabriel Matthew

    2005-07-01

    Specific language impairment (SLI) is a common developmental disorder in young children. To investigate the association between multilingual home environment and SLI, we conducted a case-control study in Hong Kong Chinese children over a 4-year period in the Duchess of Kent Children's Hospital. Consecutive medical records of all new referrals below 5 years of age were reviewed and children diagnosed with SLI (case) were compared with those referred with other developmental and behavioural problems who had been assessed as having normal language and overall development (control) using the Griffiths Mental Developmental Scale. SLI was defined as those with a language quotient more than one standard deviation below the mean and below the general developmental quotient in children with normal general developmental quotient, but without neurological or other organic diseases. We used binary and ordinal logistic regression to assess any association between SLI and multilingual exposure at home, adjusting for age and gender of subjects, parental age, education level and occupational status, number of siblings, family history of language delay and main caregiver at home. Multivariable linear regression was used to examine the effect of covariates on the language comprehension and expression standard scores assessed by the Reynell Developmental Language Scale. A total of 326 cases and 304 controls were included. The mean ages of cases and controls were 2.56 and 2.89 years respectively. Boys predominated in both groups (cases, 75.2%; controls, 60.2%). The children were exposed to between one and four languages at home, the major ones being Cantonese Chinese followed by English. The adjusted odds ratio (OR) of SLI was 2.94; [95% confidence interval (CI) 1.82, 4.74] for multilingual compared with monolingual exposure. A significant linear dose-response relationship was found (OR of SLI = 2.58 [1.72, 3.88] for each additional language to which the child was exposed). Male

  9. Self-esteem of adolescents with specific language impairment as they move from compulsory education.

    Science.gov (United States)

    Lindsay, Geoff; Dockrell, Julie; Palikara, Olympia

    2010-01-01

    Children with specific language impairment (SLI) are at risk of low self-esteem during their school years. However, there is a lack of evidence of the self-esteem of young people with a history of SLI during adolescence, as they transfer from compulsory schooling to post-compulsory education, employment or training. To examine the self-esteem of young people with a history of SLI at the transition from compulsory education (16 years) to the first year of post-compulsory education, employment and training (17 years) in England. A total of 54 young people identified as having SLI at 8 years were followed up at 16 and at 17 years. The young people completed two measures of self-esteem: the Self-perception Profile for Adolescents (16 years) and the Self-perception Profile for College Students (17 years). Assessments of language, literacy and non-verbal ability were also conducted. Perceptions of scholastic competence were significantly lower than the norm at 16 years; the female students also had lower self-esteem in the social and physical appearance domains and global self-worth. However, at 17 years there were no significant differences from the norm for these self-esteem domains. There was evidence of stability within self-esteem domains over this period but also an improvement in self-perceptions of scholastic and job competence, physical appearance and athletic competence, and also global self-worth, but not the three social domains. Non-verbal cognitive ability was not correlated with any measures of self-esteem, at 16 or 17 years. Language and literacy ability, especially spelling, were correlated with scholastic and job competence at 16 years but only spelling correlated at 17 years. This study has provided evidence for improvements in self-esteem for young people with SLI after they leave school and enter the world of non-compulsory education (typically at a college), employment and training. The study has also indicated the importance of addressing self

  10. [Specific language impairment and electroencephalogram: which recommendations in clinical practice? A cohort of 24 children].

    Science.gov (United States)

    Billard, C; Hassairi, I; Delteil, F

    2010-04-01

    Electroencephalographic recording (electroencephalogram [EEG]) is frequent in specific language impairment (SLI), whereas the relations between epileptiform activity (EA) and language disorders remain uncertain and the therapeutic approach undetermined. The aim of this prospective study was to clarify EEG indications and interpretation in SLI. We present a prospective study of cognitive (speech-language measures, psychological assessments) and electroencephalographic data on 24 children (20 males, 4 females; mean age: 4 years 5 months; range: 3 years to 4 years 8 months) with a diagnosis of SLI, defined as a pathologic score on at least 2 speech-language measures and IQ performance of at least 80 points, within epileptic seizures. All participants had an EEG after partial deprivation of sleep at night. When nonsporadic EA was found, 24-h EEG was performed. Antiepileptic treatment was prescribed depending on the frequency of discharges and the SLI profile. The follow-up lasted 2 years. All patients reached stage II sleep during their EEG. Seven children had abnormal electroencephalography results, including 5 children with EA. Two patients with mixed SLI prevailing on expression presented a left centrotemporal spike focus on EEG becoming subcontinuous during sleep. In the first case, the language progressed without antiepileptic treatment. The 2nd case was treated with ethosuximide; the EEG normalized on subsequent recordings, but the language disorder remained severe. The lexical and syntactic understanding and syntactic production scores were not different for children presented EA (5 cases) or without (19 cases) (Wilcoxon's test). Finally, the progression of the various linguistic skills was similar whether or not the children had EA (pactivity is more frequent in SLI than in normal children. It can be seen in all types of SLI but preferentially in the mixed forms. The longitudinal systematic evaluation of all the children with or without EA has never been

  11. Rheumatoid arthritis patients exhibit impaired Candida albicans-specific Th17 responses.

    Science.gov (United States)

    Bishu, Shrinivas; Su, Ee Wern; Wilkerson, Erich R; Reckley, Kelly A; Jones, Donald M; McGeachy, Mandy J; Gaffen, Sarah L; Levesque, Marc C

    2014-02-11

    Accumulating data implicate the CD4+ T cell subset (Th17 cells) in rheumatoid arthritis (RA). IL-17 is an inflammatory cytokine that induces tumor necrosis factor (TNF)α, IL-1β and IL-6, all of which are targets of biologic therapies used to treat RA. RA patients are well documented to experience more infections than age-matched controls, and biologic therapies further increase the risk of infection. The Th17/IL-17 axis is vital for immunity to fungi, especially the commensal fungus Candida albicans. Therefore, we were prompted to examine the relationship between RA and susceptibility to C. albicans because of the increasing interest in Th17 cells and IL-17 in driving autoimmunity, and the advent of new biologics that target this pathway. We analyzed peripheral blood and saliva from 48 RA and 33 healthy control subjects. To assess C. albicans-specific Th17 responses, PBMCs were co-cultured with heat-killed C. albicans extract, and IL-17A levels in conditioned supernatants were measured by ELISA. The frequency of Th17 and Th1 cells was determined by flow cytometry. As a measure of IL-17A-mediated effector responses, we evaluated C. albicans colonization rates in the oral cavity, salivary fungicidal activity and levels of the antimicrobial peptide β-defensin 2 (BD2) in saliva. Compared to controls, PBMCs from RA subjects exhibited elevated baseline production of IL-17A (P = 0.004), although they had similar capacity to produce IL-17A in response to Th17 cell differentiating cytokines (P = 0.91). However RA PBMCs secreted less IL-17A in response to C. albicans antigens (P = 0.006). Significantly more RA patients were colonized with C. albicans in the oral cavity than healthy subjects (P = 0.02). Concomitantly, RA saliva had reduced concentrations of salivary BD2 (P = 0.02). Nonetheless, salivary fungicidal activity was preserved in RA subjects (P = 0.70). RA subjects exhibit detectable impairments in oral immune responses to C. albicans, a

  12. The Danish Cerebral Palsy Registry. A registry on a specific impairment

    DEFF Research Database (Denmark)

    Uldall, P; Michelsen, S I; Topp, M

    2001-01-01

    are collected from paediatric departments and one special institution for disabled children. The children are included by a child neurologist and an obstetrician, and information on pregnancy, birth, neonatal period, impairments and demographic data on the child and mother are registered in a standard form...

  13. Domain-Specific Ratings of Importance and Global Self-Worth of Children with Visual Impairments

    Science.gov (United States)

    Shapiro, Deborah R.; Moffett, Aaron; Lieberman, Lauren; Dummer, Gail M.

    2008-01-01

    This study examined perceived competence; ratings of importance of physical appearance, athletic competence, and social acceptance; discrepancy scores; and global self-worth of 43 children with visual impairments. The findings revealed that the children discounted the importance of physical appearance, athletic competence, and social acceptance…

  14. Using Discrete Trial Training to Identify Specific Learning Impairments in Boys with Fragile X Syndrome

    Science.gov (United States)

    Hall, Scott S.; Hustyi, Kristin M.; Hammond, Jennifer L.; Hirt, Melissa; Reiss, Allan L.

    2014-01-01

    We examined whether "discrete trial training" (DTT) could be used to identify learning impairments in mathematical reasoning in boys with fragile X syndrome (FXS). Boys with FXS, aged 10-23 years, and age and IQ-matched controls, were trained to match fractions to pie-charts and pie-charts to decimals either on a computer or with a…

  15. Measurement of Heme Synthesis Levels in Mammalian Cells.

    Science.gov (United States)

    Hooda, Jagmohan; Alam, Maksudul; Zhang, Li

    2015-07-09

    Heme serves as the prosthetic group for a wide variety of proteins known as hemoproteins, such as hemoglobin, myoglobin and cytochromes. It is involved in various molecular and cellular processes such as gene transcription, translation, cell differentiation and cell proliferation. The biosynthesis levels of heme vary across different tissues and cell types and is altered in diseased conditions such as anemia, neuropathy and cancer. This technique uses [4-(14)C] 5-aminolevulinic acid ([(14)C] 5-ALA), one of the early precursors in the heme biosynthesis pathway to measure the levels of heme synthesis in mammalian cells. This assay involves incubation of cells with [(14)C] 5-ALA followed by extraction of heme and measurement of the radioactivity incorporated into heme. This procedure is accurate and quick. This method measures the relative levels of heme biosynthesis rather than the total heme content. To demonstrate the use of this technique the levels of heme biosynthesis were measured in several mammalian cell lines.

  16. An Investigation to Validate the Grammar and Phonology Screening (GAPS) Test to Identify Children with Specific Language Impairment

    Science.gov (United States)

    van der Lely, Heather K. J.; Payne, Elisabeth; McClelland, Alastair

    2011-01-01

    Background The extraordinarily high incidence of grammatical language impairments in developmental disorders suggests that this uniquely human cognitive function is “fragile”. Yet our understanding of the neurobiology of grammatical impairments is limited. Furthermore, there is no “gold-standard” to identify grammatical impairments and routine screening is not undertaken. An accurate screening test to identify grammatical abilities would serve the research, health and education communities, further our understanding of developmental disorders, and identify children who need remediation, many of whom are currently un-diagnosed. A potential realistic screening tool that could be widely administered is the Grammar and Phonology Screening (GAPS) test – a 10 minute test that can be administered by professionals and non-professionals alike. Here we provide a further step in evaluating the validity and accuracy (sensitivity and specificity) of the GAPS test in identifying children who have Specific Language Impairment (SLI). Methods and Findings We tested three groups of children; two groups aged 3;6–6:6, a typically developing (n = 30) group, and a group diagnosed with SLI: (n = 11) (Young (Y)-SLI), and a further group aged 6;9–8;11 with SLI (Older (O)-SLI) (n = 10) who were above the test age norms. We employed a battery of language assessments including the GAPS test to assess the children's language abilities. For Y-SLI children, analyses revealed a sensitivity and specificity at the 5th and 10th percentile of 1.00 and 0.98, respectively, and for O-SLI children at the 10th and 15th percentile .83 and .90, respectively. Conclusions The findings reveal that the GAPS is highly accurate in identifying impaired vs. non-impaired children up to 6;8 years, and has moderate-to-high accuracy up to 9 years. The results indicate that GAPS is a realistic tool for the early identification of grammatical abilities and impairment in young children. A larger

  17. Heme biosynthesis and its regulation : Toward understanding and improvement of heme biosynthesis in filamentous fungi.

    NARCIS (Netherlands)

    S. de Weert; P.J. Punt; Christien Lokman; C.A. van den Hondel; A.C. Franken; A.F. Ram

    2011-01-01

    Heme biosynthesis in fungal host strains has acquired considerable interest in relation to the production of secreted heme-containing peroxidases. Class II peroxidase enzymes have been suggested as eco-friendly replacements of polluting chemical processes in industry. These peroxidases are naturally

  18. Heme biosynthesis and its regulation: Towards understanding and improvement of heme biosynthesis in filamentous fungi

    NARCIS (Netherlands)

    Franken, A.C.W.; Lokman, B.C.; Ram, A.F.J.; Punt, P.J.; Hondel, C.A.M.J.J. van den; Weert, S. de

    2011-01-01

    Heme biosynthesis in fungal host strains has acquired considerable interest in relation to the production of secreted heme-containing peroxidases. Class II peroxidase enzymes have been suggested as eco-friendly replacements of polluting chemical processes in industry. These peroxidases are naturally

  19. Social communication disorder outside autism? A diagnostic classification approach to delineating pragmatic language impairment, high functioning autism and specific language impairment.

    Science.gov (United States)

    Gibson, Jenny; Adams, Catherine; Lockton, Elaine; Green, Jonathan

    2013-11-01

    Developmental disorders of language and communication present considerable diagnostic challenges due to overlapping of symptomatology and uncertain aetiology. We aimed to further elucidate the behavioural and linguistic profile associated with impairments of social communication occurring outside of an autism diagnosis. Six to eleven year olds diagnosed with pragmatic language impairment (PLI), high functioning autism (HFA) or specific language impairment (SLI) were compared on measures of social interaction with peers (PI), restricted and repetitive behaviours/interests (RRBIs) and language ability. Odds ratios (OR) from a multinomial logistic regression were used to determine the importance of each measure to diagnostic grouping. MANOVA was used to investigate differences in subscale scores for the PI measure. Greater degrees of PI difficulties (OR = 1.22, 95% CI = 1.05-1.41), RRBI (OR = 1.23, 95% CI = 1.06-1.42) and expressive language ability (OR = 1.16, 95% CI = 1.03-1.30) discriminated HFA from PLI. PLI was differentiated from SLI by elevated PI difficulties (OR = 0.82, 95% CI = 0.70-0.96) and higher expressive language ability (OR = 0.88, 95% CI = 0.77-0.98), but indistinguishable from SLI using RRBI (OR = 1.01, 95% CI=0.94-1.09). A significant effect of group on PI subscales was observed (θ = 1.38, F(4, 56) = 19.26, p communication disorder' in DSM-5. © 2013 The Authors Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

  20. Do children with autism have a theory of mind? A non-verbal test of autism vs. specific language impairment.

    Science.gov (United States)

    Colle, Livia; Baron-Cohen, Simon; Hill, Jacqueline

    2007-04-01

    Children with autism have delays in the development of theory of mind. However, the sub-group of children with autism who have little or no language have gone untested since false belief tests (FB) typically involve language. FB understanding has been reported to be intact in children with specific language impairment (SLI). This raises the possibility that a non-verbal FB test would distinguish children with autism vs. children with SLI. The present study tested two predictions: (1) FB understanding is to some extent independent of language ability; and (2) Children with autism with low language levels show specific impairment in theory of mind. Results confirmed both predictions. Results are discussed in terms of the role of language in the development of mindreading.

  1. The role of verbal and nonverbal memory in the Family Pictures Subtest: Data from children with specific language impairment

    OpenAIRE

    Lum, Jarrad A. G.; Conti-Ramsden, Gina; Ullman, Michael T.

    2012-01-01

    This study examined the contribution of verbal and visual memory to performance on the Family Pictures subtest of the Children's Memory Scale. This subtest purports to assess declarative memory functioning in the visual/nonverbal domain. A total of 115 nine-year-old children participated in this study. Fifty-eight had specific language impairment (SLI), whilst the remaining 57 were typically developing (TD), with no history of language difficulties. Results showed that the children with SLI, ...

  2. Atrophy-specific MRI brain template for Alzheimer's disease and mild cognitive impairment

    DEFF Research Database (Denmark)

    Fonov, Vladimir; Coupe, Pierrick; Eskildsen, Simon Fristed

    Background Rapid brain loss is characteristic for the patients with mild cognitive impairment (MCI) and Alzheimer disease (AD) [1]. Increase of the lateral ventricular volume is strongly correlated with the progression of the disease. High variability in the degree of atrophy for subjects with AD....... Alzheimer's and Dementia, 2010. 6(4, Supplement 1). [3] Fonov, V, et al. NeuroImage, 2011. 54(1).......Background Rapid brain loss is characteristic for the patients with mild cognitive impairment (MCI) and Alzheimer disease (AD) [1]. Increase of the lateral ventricular volume is strongly correlated with the progression of the disease. High variability in the degree of atrophy for subjects with AD...... of the brain and the contrast between different tissue types for the given level of atrophy. Figure 1 shows images through 6 example values of increasing RLVV. Conclusions The proposed method and resulting template will be useful tools for the development of robust automatic image processing methods targeted...

  3. Sex-specific impairment of spatial memory in rats following a reminder of predator stress.

    Science.gov (United States)

    Burke, Hanna M; Robinson, Cristina M; Wentz, Bethany; McKay, Jerel; Dexter, Kyle W; Pisansky, Julia M; Talbot, Jeffery N; Zoladz, Phillip R

    2013-07-01

    It has been suggested that cognitive impairments exhibited by people with post-traumatic stress disorder (PTSD) result from intrusive, flashback memories transiently interfering with ongoing cognitive processing. Researchers have further speculated that females are more susceptible to developing PTSD because they form stronger traumatic memories than males, hence females may be more sensitive to the negative effects of intrusive memories on cognition. We have examined how the reminder of a naturalistic stress experience would affect rat spatial memory and if sex was a contributing factor to such effects. Male and female Sprague-Dawley rats were exposed, without contact, to an adult female cat for 30 min. Five weeks later, the rats were trained to locate a hidden platform in the radial-arm water maze and given a single long-term memory test trial 24 h later. Before long-term memory testing, the rats were given a 30-min reminder of the cat exposure experienced 5 weeks earlier. The results indicated that the stress reminder impaired spatial memory in the female rats only. Control manipulations revealed that this effect was not attributable to the original cat exposure adversely impacting learning that occurred 5 weeks later, or to merely exposing rats to a novel environment or predator-related cues immediately before testing. These findings provide evidence that the reminder of a naturalistic stressful experience can impair cognitive processing in rats; moreover, since female rats were more susceptible to the memory-impairing effects of the stress reminder, the findings could lend insight into the existing sex differences in susceptibility to PTSD.

  4. Deletion of PEA-15 in mice is associated with specific impairments of spatial learning abilities

    Directory of Open Access Journals (Sweden)

    Hale Gregory

    2009-11-01

    Full Text Available Abstract Background PEA-15 is a phosphoprotein that binds and regulates ERK MAP kinase and RSK2 and is highly expressed throughout the brain. PEA-15 alters c-Fos and CREB-mediated transcription as a result of these interactions. To determine if PEA-15 contributes to the function of the nervous system we tested mice lacking PEA-15 in a series of experiments designed to measure learning, sensory/motor function, and stress reactivity. Results We report that PEA-15 null mice exhibited impaired learning in three distinct spatial tasks, while they exhibited normal fear conditioning, passive avoidance, egocentric navigation, and odor discrimination. PEA-15 null mice also had deficient forepaw strength and in limited instances, heightened stress reactivity and/or anxiety. However, these non-cognitive variables did not appear to account for the observed spatial learning impairments. The null mice maintained normal weight, pain sensitivity, and coordination when compared to wild type controls. Conclusion We found that PEA-15 null mice have spatial learning disabilities that are similar to those of mice where ERK or RSK2 function is impaired. We suggest PEA-15 may be an essential regulator of ERK-dependent spatial learning.

  5. Advocating for a Population-Specific Health Literacy for People With Visual Impairments.

    Science.gov (United States)

    Harrison, Tracie; Lazard, Allison

    2015-01-01

    Health literacy, the ability to access, process, and understand health information, is enhanced by the visual senses among people who are typically sighted. Emotions, meaning, speed of knowledge transfer, level of attention, and degree of relevance are all manipulated by the visual design of health information when people can see. When consumers of health information are blind or visually impaired, they access, process, and understand their health information in a multitude of methods using a variety of accommodations depending upon their severity and type of impairment. They are taught, or they learn how, to accommodate their differences by using alternative sensory experiences and interpretations. In this article, we argue that due to the unique and powerful aspects of visual learning and due to the differences in knowledge creation when people are not visually oriented, health literacy must be considered a unique construct for people with visual impairment, which requires a distinctive theoretical basis for determining the impact of their mind-constructed representations of health.

  6. Regiospecificity determinants of human heme oxygenase: differential NADPH- and ascorbate-dependent heme cleavage by the R183E mutant.

    Science.gov (United States)

    Wang, Jinling; Lad, Latesh; Poulos, Thomas L; Ortiz de Montellano, Paul R

    2005-01-28

    The ability of the human heme oxygenase-1 (hHO-1) R183E mutant to oxidize heme in reactions supported by either NADPH-cytochrome P450 reductase or ascorbic acid has been compared. The NADPH-dependent reaction, like that of wild-type hHO-1, yields exclusively biliverdin IXalpha. In contrast, the R183E mutant with ascorbic acid as the reductant produces biliverdin IXalpha (79 +/- 4%), IXdelta (19 +/- 3%), and a trace of IXbeta. In the presence of superoxide dismutase and catalase, the yield of biliverdin IXdelta is decreased to 8 +/- 1% with a corresponding increase in biliverdin IXalpha. Spectroscopic analysis of the NADPH-dependent reaction shows that the R183E ferric biliverdin complex accumulates, because reduction of the iron, which is required for sequential iron and biliverdin release, is impaired. Reversal of the charge at position 183 makes reduction of the iron more difficult. The crystal structure of the R183E mutant, determined in the ferric and ferrous-NO bound forms, shows that the heme primarily adopts the same orientation as in wild-type hHO-1. The structure of the Fe(II).NO complex suggests that an altered active site hydrogen bonding network supports catalysis in the R183E mutant. Furthermore, Arg-183 contributes to the regiospecificity of the wild-type enzyme, but its contribution is not critical. The results indicate that the ascorbate-dependent reaction is subject to a lower degree of regiochemical control than the NADPH-dependent reaction. Ascorbate may be able to reduce the R183E ferric and ferrous dioxygen complexes in active site conformations that cannot be reduced by NADPH-cytochrome P450 reductase.

  7. Structural and Functional Models of Non-Heme Iron Enzymes : A Study of the 2-His-1-Carboxylate Facial Triad Structural Motif

    NARCIS (Netherlands)

    Bruijnincx, P.C.A.

    2007-01-01

    The structural and functional modeling of a specific group of non-heme iron enzymes by the synthesis of small synthetic analogues is the topic of this thesis. The group of non-heme iron enzymes with the 2-His-1-carboxylate facial triad has recently been established as a common platform for the

  8. Zonation of heme synthesis enzymes in mouse liver and their regulation by β-catenin and Ha-ras.

    Science.gov (United States)

    Braeuning, Albert; Schwarz, Michael

    2010-11-01

    Cytochrome P450 (CYP) hemoproteins play an important role in hepatic biotransformation. Recently, β-catenin and Ha-ras signaling have been identified as players controlling transcription of various CYP genes in mouse liver. The aim of the present study was to analyze the role of β-catenin and Ha-ras in the regulation of heme synthesis. Heme synthesis-related gene expression was analyzed in normal liver, in transgenic mice expressing activated β-catenin or Ha-ras, and in hepatomas. Regulation of the aminolevulinate dehydratase promoter was studied in vitro. Elevated expression of mRNAs and proteins involved in heme biosynthesis was linked to β-catenin activation in perivenous hepatocytes, in transgenic hepatocytes, and in hepatocellular tumors. Stimulation of the aminolevulinate dehydratase promoter by β-catenin was independent of the β-catenin/T-cell-specific transcription factor dimer. By contrast, activation of Ha-ras repressed heme synthesis-related gene expression. The present data suggest that β-catenin enhances the expression of both CYPs and heme synthesis-related genes, thus coordinating the availability of CYP apoprotein and its prosthetic group heme. The reciprocal regulation of heme synthesis by β-catenin and Ha-ras-dependent signaling supports our previous hypothesis that antagonistic action of these pathways plays a major role in the control of zonal gene expression in healthy mouse liver and aberrant expression patterns in hepatocellular tumors.

  9. Heme and non-heme iron transporters in non-polarized and polarized cells

    Directory of Open Access Journals (Sweden)

    Yasui Yumiko

    2010-06-01

    Full Text Available Abstract Background Heme and non-heme iron from diet, and recycled iron from hemoglobin are important products of the synthesis of iron-containing molecules. In excess, iron is potentially toxic because it can produce reactive oxygen species through the Fenton reaction. Humans can absorb, transport, store, and recycle iron without an excretory system to remove excess iron. Two candidate heme transporters and two iron transporters have been reported thus far. Heme incorporated into cells is degraded by heme oxygenases (HOs, and the iron product is reutilized by the body. To specify the processes of heme uptake and degradation, and the reutilization of iron, we determined the subcellular localizations of these transporters and HOs. Results In this study, we analyzed the subcellular localizations of 2 isoenzymes of HOs, 4 isoforms of divalent metal transporter 1 (DMT1, and 2 candidate heme transporters--heme carrier protein 1 (HCP1 and heme responsive gene-1 (HRG-1--in non-polarized and polarized cells. In non-polarized cells, HCP1, HRG-1, and DMT1A-I are located in the plasma membrane. In polarized cells, they show distinct localizations: HCP1 and DMT1A-I are located in the apical membrane, whereas HRG-1 is located in the basolateral membrane and lysosome. 16Leu at DMT1A-I N-terminal cytosolic domain was found to be crucial for plasma membrane localization. HOs are located in smooth endoplasmic reticulum and colocalize with NADPH-cytochrome P450 reductase. Conclusions HCP1 and DMT1A-I are localized to the apical membrane, and HRG-1 to the basolateral membrane and lysosome. These findings suggest that HCP1 and DMT1A-I have functions in the uptake of dietary heme and non-heme iron. HRG-1 can transport endocytosed heme from the lysosome into the cytosol. These localization studies support a model in which cytosolic heme can be degraded by HOs, and the resulting iron is exported into tissue fluids via the iron transporter ferroportin 1, which is

  10. Moving the hands and feet specifically impairs working memory for arm- and leg-related action words.

    Science.gov (United States)

    Shebani, Zubaida; Pulvermüller, Friedemann

    2013-01-01

    Language and action systems of the human brain are functionally interwoven. Speaking about actions and understanding action-related speech sparks the motor system of the human brain and, conversely, motor system activation has an influence on the comprehension of action words and sentences. Although previous research has shown that motor systems become active when we understand language, a major question still remains whether these motor system activations are necessary for processing action words. We here report that rhythmic movements of either the hands or the feet lead to a differential impairment of working memory for concordant arm- and leg-related action words, with hand/arm movements predominantly impairing working memory for words used to speak about arm actions and foot/leg movements primarily impairing leg-related word memory. The resulting cross-over double dissociation demonstrates that body part specific and meaning-related processing resources in specific cortical motor systems are shared between overt movements and working memory for action-related words, thus documenting a genuine motor locus of semantic meaning. Copyright © 2011. Published by Elsevier Srl.

  11. Impaired macrophage and satellite cell infiltration occurs in a muscle-specific fashion following injury in diabetic skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Matthew P Krause

    Full Text Available Systemic elevations in PAI-1 suppress the fibrinolytic pathway leading to poor collagen remodelling and delayed regeneration of tibialis anterior (TA muscles in type-1 diabetic Akita mice. However, how impaired collagen remodelling was specifically attenuating regeneration in Akita mice remained unknown. Furthermore, given intrinsic differences between muscle groups, it was unclear if the reparative responses between muscle groups were different.Here we reveal that diabetic Akita muscles display differential regenerative responses with the TA and gastrocnemius muscles exhibiting reduced regenerating myofiber area compared to wild-type mice, while soleus muscles displayed no difference between animal groups following injury. Collagen levels in TA and gastrocnemius, but not soleus, were significantly increased post-injury versus controls. At 5 days post-injury, when degenerating/necrotic regions were present in both animal groups, Akita TA and gastrocnemius muscles displayed reduced macrophage and satellite cell infiltration and poor myofiber formation. By 10 days post-injury, necrotic regions were absent in wild-type TA but persisted in Akita TA. In contrast, Akita soleus exhibited no impairment in any of these measures compared to wild-type soleus. In an effort to define how impaired collagen turnover was attenuating regeneration in Akita TA, a PAI-1 inhibitor (PAI-039 was orally administered to Akita mice following cardiotoxin injury. PAI-039 administration promoted macrophage and satellite cell infiltration into necrotic areas of the TA and gastrocnemius. Importantly, soleus muscles exhibit the highest inducible expression of MMP-9 following injury, providing a mechanism for normative collagen degradation and injury recovery in this muscle despite systemically elevated PAI-1.Our findings suggest the mechanism underlying how impaired collagen remodelling in type-1 diabetes results in delayed regeneration is an impairment in macrophage

  12. Conversion of a heme-based oxygen sensor to a heme oxygenase by hydrogen sulfide: effects of mutations in the heme distal side of a heme-based oxygen sensor phosphodiesterase (Ec DOS)

    Czech Academy of Sciences Publication Activity Database

    Du, Y.; Liu, G.; Yan, Y.; Huang, D.; Luo, W.; Martínková, M.; Man, Petr; Shimizu, T.

    2013-01-01

    Roč. 26, č. 5 (2013), s. 839-852 ISSN 0966-0844 Institutional support: RVO:61388971 Keywords : Heme oxygenase * Heme protein * Hydrogen sulfide Subject RIV: CE - Biochemistry Impact factor: 2.689, year: 2013

  13. Gender-specific impairments on cognitive and behavioral development in mice exposed to fenvalerate during puberty.

    Science.gov (United States)

    Meng, Xiu-Hong; Liu, Ping; Wang, Hua; Zhao, Xian-Feng; Xu, Zhong-Mei; Chen, Gui-Hai; Xu, De-Xiang

    2011-06-24

    In human and rodent models, endocrine disrupting chemicals (EDCs) interfere with the development of cognition and behaviors. Fenvalerate is a potential EDC. The purpose of this study was to examine whether pubertal fenvalerate exposure altered behavioral development. Mice were orally administered with either vehicle or fenvalerate (7.5 or 30 mg/kg/day) from postnatal day (PND) 28 to PND56. Learning and memory were assessed by Morris Water Maze. Aggressive performance was evaluated by aggressive behavior test. Anxiety-related activities were detected by three tests: open-field, plus-maze and black-white alley. Sensorimotor function was analyzed using beam walking and tightrope. Results found that the impairment for spatial learning and memory was more severe in fenvalerate-exposed female mice than in male mice. In addition, pubertal fenvalerate exposure inhibited aggressive behavior in males. Moreover, pubertal fenvalerate exposure increased anxiety activities in females. Altogether, these results suggest that pubertal fenvalerate exposure impairs spatial cognition and behavioral development in a gender-dependent manner. These findings identify fenvalerate as candidate environmental risk factors for cognitive and behavioral development, especially in the critical period of development. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  14. Molecular hijacking of siroheme for the synthesis of heme and d1 heme.

    Science.gov (United States)

    Bali, Shilpa; Lawrence, Andrew D; Lobo, Susana A; Saraiva, Lígia M; Golding, Bernard T; Palmer, David J; Howard, Mark J; Ferguson, Stuart J; Warren, Martin J

    2011-11-08

    Modified tetrapyrroles such as chlorophyll, heme, siroheme, vitamin B(12), coenzyme F(430), and heme d(1) underpin a wide range of essential biological functions in all domains of life, and it is therefore surprising that the syntheses of many of these life pigments remain poorly understood. It is known that the construction of the central molecular framework of modified tetrapyrroles is mediated via a common, core pathway. Herein a further branch of the modified tetrapyrrole biosynthesis pathway is described in denitrifying and sulfate-reducing bacteria as well as the Archaea. This process entails the hijacking of siroheme, the prosthetic group of sulfite and nitrite reductase, and its processing into heme and d(1) heme. The initial step in these transformations involves the decarboxylation of siroheme to give didecarboxysiroheme. For d(1) heme synthesis this intermediate has to undergo the replacement of two propionate side chains with oxygen functionalities and the introduction of a double bond into a further peripheral side chain. For heme synthesis didecarboxysiroheme is converted into Fe-coproporphyrin by oxidative loss of two acetic acid side chains. Fe-coproporphyrin is then transformed into heme by the oxidative decarboxylation of two propionate side chains. The mechanisms of these reactions are discussed and the evolutionary significance of another role for siroheme is examined.

  15. Interactive cervical motion kinematics: sensitivity, specificity and clinically significant values for identifying kinematic impairments in patients with chronic neck pain.

    Science.gov (United States)

    Sarig Bahat, Hilla; Chen, Xiaoqi; Reznik, David; Kodesh, Einat; Treleaven, Julia

    2015-04-01

    Chronic neck pain has been consistently shown to be associated with impaired kinematic control including reduced range, velocity and smoothness of cervical motion, that seem relevant to daily function as in quick neck motion in response to surrounding stimuli. The objectives of this study were: to compare interactive cervical kinematics in patients with neck pain and controls; to explore the new measures of cervical motion accuracy; and to find the sensitivity, specificity, and optimal cutoff values for defining impaired kinematics in those with neck pain. In this cross-section study, 33 patients with chronic neck pain and 22 asymptomatic controls were assessed for their cervical kinematic control using interactive virtual reality hardware and customized software utilizing a head mounted display with built-in head tracking. Outcome measures included peak and mean velocity, smoothness (represented by number of velocity peaks (NVP)), symmetry (represented by time to peak velocity percentage (TTPP)), and accuracy of cervical motion. Results demonstrated significant and strong effect-size differences in peak and mean velocities, NVP and TTPP in all directions excluding TTPP in left rotation, and good effect-size group differences in 5/8 accuracy measures. Regression results emphasized the high clinical value of neck motion velocity, with very high sensitivity and specificity (85%-100%), followed by motion smoothness, symmetry and accuracy. These finding suggest cervical kinematics should be evaluated clinically, and screened by the provided cut off values for identification of relevant impairments in those with neck pain. Such identification of presence or absence of kinematic impairments may direct treatment strategies and additional evaluation when needed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Kidney injury and heme oxygenase-1

    Directory of Open Access Journals (Sweden)

    Hai-xing MAI

    2012-02-01

    Full Text Available     Heme oxygenase-1 (HO-1 is one of the main pathways to degrade heme in mammals, and the main degradation products are free iron (Fe2+, carbon monoxide (CO, and bilirubin. Heme plays an important role in promoting cell survival, circulation of intracellular substrates, and immune regulation. Previous studies suggest that HO-1 pathway is an important internal factor in determining the susceptibility and severity of acute kidney injury (AKI. The induction of HO-1 expression can attenuate the severity of renal ischemia-reperfusion injury (IRI, and the inhibition of HO-1 expression will aggravate IRI. The present article summarizes the latest advances in research abroad and at home on protective mechanism by which HO-1 prevents AKI to further deepen our understanding of the role of HO-1 in the treatment of AKI.   

  17. Heme and erythropoieis: more than a structural role

    OpenAIRE

    Chiabrando, Deborah; Mercurio, Sonia; Tolosano, Emanuela

    2014-01-01

    Erythropoiesis is the biological process that consumes the highest amount of body iron for heme synthesis. Heme synthesis in erythroid cells is finely coordinated with that of alpha (α) and beta (β)-globin, resulting in the production of hemoglobin, a tetramer of 2α- and 2β-globin chains, and heme as the prosthetic group. Heme is not only the structural component of hemoglobin, but it plays multiple regulatory roles during the differentiation of erythroid precursors since it controls its own ...

  18. Heme oxygenase-1 deletion affects stress erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Yu-An Cao

    Full Text Available Homeostatic erythropoiesis leads to the formation of mature red blood cells under non-stress conditions, and the production of new erythrocytes occurs as the need arises. In response to environmental stimuli, such as bone marrow transplantation, myelosuppression, or anemia, erythroid progenitors proliferate rapidly in a process referred to as stress erythropoiesis. We have previously demonstrated that heme oxygenase-1 (HO-1 deficiency leads to disrupted stress hematopoiesis. Here, we describe the specific effects of HO-1 deficiency on stress erythropoiesis.We used a transplant model to induce stress conditions. In irradiated recipients that received hmox(+/- or hmox(+/+ bone marrow cells, we evaluated (i the erythrocyte parameters in the peripheral blood; (ii the staining intensity of CD71-, Ter119-, and CD49d-specific surface markers during erythroblast differentiation; (iii the patterns of histological iron staining; and (iv the number of Mac-1(+-cells expressing TNF-α. In the spleens of mice that received hmox(+/- cells, we show (i decreases in the proerythroblast, basophilic, and polychromatophilic erythroblast populations; (ii increases in the insoluble iron levels and decreases in the soluble iron levels; (iii increased numbers of Mac-1(+-cells expressing TNF-α; and (iv decreased levels of CD49d expression in the basophilic and polychromatophilic erythroblast populations.As reflected by effects on secreted and cell surface proteins, HO-1 deletion likely affects stress erythropoiesis through the retention of erythroblasts in the erythroblastic islands of the spleen. Thus, HO-1 may serve as a therapeutic target for controlling erythropoiesis, and the dysregulation of HO-1 may be a predisposing condition for hematologic diseases.

  19. Red meat and colon cancer : how dietary heme initiates hyperproliferation

    NARCIS (Netherlands)

    IJssennagger, N.

    2012-01-01

    Colorectal cancer is a leading cause of cancer deaths in Western countries. The risk to develop colorectal cancer is associated with the intake of red meat. Red meat contains the porphyrin pigment heme. Heme is an irritant for the colonic wall and it is previously shown that the addition of heme

  20. Heme oxygenase activity increases after exercise in healthy volunteers

    Science.gov (United States)

    AbstractHeme oxygenase (HO) is an essential, rate-limiting protein which participates in the catabolism of heme to iron, carbon monoxide (CO), and biliverdin. The alpha methene bridge carbon of the heme is eliminated as CO which can be measured as blood carboxyhemoglobin (COHb)....

  1. Dibromine radical anion reactions with heme enzymes

    International Nuclear Information System (INIS)

    Gebicka, L.; Gebicki, J.L.

    1996-01-01

    Reactions of Br 2 radical anion with heme enzymes, catalase horseradish peroxidase, have been studied by pulse radiolysis. It has been found that Br 2 - does not react with the heme centre of investigated enzymes. Dibromine radical anion reacts with tryptophan residues of catalase without any influence on the activity of catalase. It is suggested that in pulse radiolysis studies, where horseradish peroxidase is at about tenfold excess toward Br 2 - , the enzyme is modified rather by Br 2 , than by Br 2 - . (author). 26 refs., 3 figs

  2. Heme Exporter FLVCR1a Regulates Heme Synthesis and Degradation and Controls Activity of Cytochromes P450

    OpenAIRE

    Vinchi, Francesca; Ingoglia, Giada; Chiabrando, Deborah; Mercurio, Sonia; Turco, Emilia; Silengo, Lorenzo; Altruda, Fiorella; Tolosano, Emanuela

    2014-01-01

    Background & Aims The liver has one of the highest rates of heme synthesis of any organ. More than 50% of the heme synthesized in the liver is used for synthesis of P450 enzymes, which metabolize exogenous and endogenous compounds that include natural products, hormones, drugs, and carcinogens. Feline leukemia virus subgroup C cellular receptor 1a (FLVCR1a) is plasma membrane heme exporter that is ubiquitously expressed and controls intracellular heme content in hematopoietic lineages. We inv...

  3. PCBP1 and NCOA4 regulate erythroid iron storage and heme biosynthesis.

    Science.gov (United States)

    Ryu, Moon-Suhn; Zhang, Deliang; Protchenko, Olga; Shakoury-Elizeh, Minoo; Philpott, Caroline C

    2017-05-01

    Developing erythrocytes take up exceptionally large amounts of iron, which must be transferred to mitochondria for incorporation into heme. This massive iron flux must be precisely controlled to permit the coordinated synthesis of heme and hemoglobin while avoiding the toxic effects of chemically reactive iron. In cultured animal cells, iron chaperones poly rC-binding protein 1 (PCBP1) and PCBP2 deliver iron to ferritin, the sole cytosolic iron storage protein, and nuclear receptor coactivator 4 (NCOA4) mediates the autophagic turnover of ferritin. The roles of PCBP, ferritin, and NCOA4 in erythroid development remain unclear. Here, we show that PCBP1, NCOA4, and ferritin are critical for murine red cell development. Using a cultured cell model of erythroid differentiation, depletion of PCBP1 or NCOA4 impaired iron trafficking through ferritin, which resulted in reduced heme synthesis, reduced hemoglobin formation, and perturbation of erythroid regulatory systems. Mice lacking Pcbp1 exhibited microcytic anemia and activation of compensatory erythropoiesis via the regulators erythropoietin and erythroferrone. Ex vivo differentiation of erythroid precursors from Pcbp1-deficient mice confirmed defects in ferritin iron flux and heme synthesis. These studies demonstrate the importance of ferritin for the vectorial transfer of imported iron to mitochondria in developing red cells and of PCBP1 and NCOA4 in mediating iron flux through ferritin.

  4. Visual attentional engagement deficits in children with specific language impairment and their role in real-time language processing.

    Science.gov (United States)

    Dispaldro, Marco; Leonard, Laurence B; Corradi, Nicola; Ruffino, Milena; Bronte, Tiziana; Facoetti, Andrea

    2013-09-01

    In order to become a proficient user of language, infants must detect temporal cues embedded within the noisy acoustic spectra of ongoing speech by efficient attentional engagement. According to the neuro-constructivist approach, a multi-sensory dysfunction of attentional engagement - hampering the temporal sampling of stimuli - might be responsible for language deficits typically shown in children with Specific Language Impairment (SLI). In the present study, the efficiency of visual attentional engagement was investigated in 22 children with SLI and 22 typically developing (TD) children by measuring attentional masking (AM). AM refers to impaired identification of the first of two sequentially presented masked objects (O1 and O2) in which the O1-O2 interval was manipulated. Lexical and grammatical comprehension abilities were also tested in both groups. Children with SLI showed a sluggish engagement of temporal attention, and individual differences in AM accounted for a significant percentage of unique variance in grammatical performance. Our results suggest that an attentional engagement deficit - probably linked to a dysfunction of the right fronto-parietal attentional network - might be a contributing factor in these children's language impairments. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Life habits of school-aged children with specific language impairment as perceived by their parents and by school professionals.

    Science.gov (United States)

    Croteau, Claire; McMahon-Morin, Paméla; Morin, Claudia; Jutras, Benoît; Trudeau, Natacha; Le Dorze, Guylaine

    2015-01-01

    Describe social participation of a group of children with specific language impairment. 26 parents of children with specific language impairment (SLI) aged from 5 to 13 years and 11 school professionals participated in the study. Data collection was performed with the adapted version for children aged from 5 to 13 years old of the Assessment of Life Habits (Fougeyrollas et al., 2001). The questionnaire encompasses 196 life habits, grouped in 12 dimensions: nutrition, fitness, personal care, communication, housing, mobility, responsibilities, interpersonal relationships, community life, education, work and recreation (Fougeyrollas, 2010). According to their parents and school professionals, children in this study carried out without difficulty life habits related to housing and mobility. However, they experienced difficulty with life habits related to interpersonal relationships, recreation and responsibilities, in addition to communication and education. Children with SLI are perceived by their parents and school professionals as having reduced social participation in many aspects of their daily life. Social participation should be considered as a major outcome when offering services in school to these children. This study proposes specific ways to help children with SLI. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  6. Progesterone impairs antigen-non-specific immune protection by CD8 T memory cells via interferon-γ gene hypermethylation.

    Science.gov (United States)

    Yao, Yushi; Li, Hui; Ding, Jie; Xia, Yixin; Wang, Lei

    2017-11-01

    Pregnant women and animals have increased susceptibility to a variety of intracellular pathogens including Listeria monocytogenes (LM), which has been associated with significantly increased level of sex hormones such as progesterone. CD8 T memory(Tm) cell-mediated antigen-non-specific IFN-γ responses are critically required in the host defense against LM. However, whether and how increased progesterone during pregnancy modulates CD8 Tm cell-mediated antigen-non-specific IFN-γ production and immune protection against LM remain poorly understood. Here we show in pregnant women that increased serum progesterone levels are associated with DNA hypermethylation of IFN-γ gene promoter region and decreased IFN-γ production in CD8 Tm cells upon antigen-non-specific stimulation ex vivo. Moreover, IFN-γ gene hypermethylation and significantly reduced IFN-γ production post LM infection in antigen-non-specific CD8 Tm cells are also observed in pregnant mice or progesterone treated non-pregnant female mice, which is a reversible phenotype following demethylation treatment. Importantly, antigen-non-specific CD8 Tm cells from progesterone treated mice have impaired anti-LM protection when adoptive transferred in either pregnant wild type mice or IFN-γ-deficient mice, and demethylation treatment rescues the adoptive protection of such CD8 Tm cells. These data demonstrate that increased progesterone impairs immune protective functions of antigen-non-specific CD8 Tm cells via inducing IFN-γ gene hypermethylation. Our findings thus provide insights into a new mechanism through which increased female sex hormone regulate CD8 Tm cell functions during pregnancy.

  7. Progesterone impairs antigen-non-specific immune protection by CD8 T memory cells via interferon-γ gene hypermethylation.

    Directory of Open Access Journals (Sweden)

    Yushi Yao

    2017-11-01

    Full Text Available Pregnant women and animals have increased susceptibility to a variety of intracellular pathogens including Listeria monocytogenes (LM, which has been associated with significantly increased level of sex hormones such as progesterone. CD8 T memory(Tm cell-mediated antigen-non-specific IFN-γ responses are critically required in the host defense against LM. However, whether and how increased progesterone during pregnancy modulates CD8 Tm cell-mediated antigen-non-specific IFN-γ production and immune protection against LM remain poorly understood. Here we show in pregnant women that increased serum progesterone levels are associated with DNA hypermethylation of IFN-γ gene promoter region and decreased IFN-γ production in CD8 Tm cells upon antigen-non-specific stimulation ex vivo. Moreover, IFN-γ gene hypermethylation and significantly reduced IFN-γ production post LM infection in antigen-non-specific CD8 Tm cells are also observed in pregnant mice or progesterone treated non-pregnant female mice, which is a reversible phenotype following demethylation treatment. Importantly, antigen-non-specific CD8 Tm cells from progesterone treated mice have impaired anti-LM protection when adoptive transferred in either pregnant wild type mice or IFN-γ-deficient mice, and demethylation treatment rescues the adoptive protection of such CD8 Tm cells. These data demonstrate that increased progesterone impairs immune protective functions of antigen-non-specific CD8 Tm cells via inducing IFN-γ gene hypermethylation. Our findings thus provide insights into a new mechanism through which increased female sex hormone regulate CD8 Tm cell functions during pregnancy.

  8. Preschool language profiles of children at family risk of dyslexia: continuities with specific language impairment

    Science.gov (United States)

    Nash, Hannah M.; Hulme, Charles; Gooch, Debbie; Snowling, Margaret J.

    2015-01-01

    Background Children at family risk of dyslexia have been reported to show phonological deficits as well as broader language delays in the preschool years. Method The preschool language skills of 112 children at family risk of dyslexia (FR) at ages 3½ and 4½ were compared with those of children with SLI and typically developing (TD) controls. Results Children at FR showed two different profiles: one third of the group resembled the children with SLI and scored poorly across multiple domains of language including phonology. As a group, the remaining children had difficulties on tasks tapping phonological skills at T1 and T2. At the individual level, we confirmed that some FR children had both phonological and broader oral language difficulties (compared with TD controls), some had only phonological difficulties and some appeared to be developing typically. Conclusions We have highlighted the early overlap between family risk of dyslexia and SLI. A family history of dyslexia carries an increased risk for SLI and the two disorders both show an increased incidence of phonological deficits which appear to a proximal risk factor for developing a reading impairment. PMID:23772651

  9. Sperm Impairment by Sperm Agglutinating Factor Isolated from Escherichia coli: Receptor Specific Interactions

    Directory of Open Access Journals (Sweden)

    Kiranjeet Kaur

    2013-01-01

    Full Text Available In an earlier work done in our laboratory, we have been able to isolate a sperm agglutinating strain of Escherichia coli from the semen sample of a male attending infertility clinic. Further, factor responsible for sperm agglutination (SAF was isolated and purified, and, using SAF as a tool, corresponding SAF binding receptor from human spermatozoa has been purified. Characterization of SAF and SAF binding receptor using MALDI-TOF showed homology to glutamate decarboxylase and MHC class I molecule, respectively. Coincubation of SAF with spermatozoa not only resulted in spermagglutination but could also compromise other sperm parameters, namely, Mg2+ dependent ATPase activity and apoptosis. Intravaginal administration of SAF could lead to infertility in Balb/c mice. SAF induced impairment of sperm parameters, and infertility was observed to be due to interaction of SAF with sperm surface receptor component as, when purified receptor was introduced, receptor completely inhibited all the detrimental effects induced by SAF. From these results, it could be concluded that interaction of SAF with spermatozoa is receptor mediated.

  10. Amnesiacs might get the gist: reduced false recognition in amnesia may be the result of impaired item-specific memory.

    Science.gov (United States)

    Nissan, Jack; Abrahams, Sharon; Sala, Sergio Della

    2013-01-01

    It is a common finding in tests of false recognition that amnesic patients recognize fewer related lures than healthy controls, and this has led to assumptions that gist memory is damaged in these patients (Schacter, Verfaellie, & Anes, 1997, Neuropsychology, 11; Schacter, Verfaellie, Anes, & Racine, 1998, Journal of Cognitive Neuroscience, 10; Schacter, Verfaellie, & Pradere, 1996, Journal of Memory and Language, 35). However, clinical observations find that amnesic patients typically hold meaningful conversations and make relevant remarks, and there is some experimental evidence highlighting preserved immediate recall of prose (Baddeley & Wilson, 2002, Neuropsychologia, 40; Gooding, Isaac, & Mayes, 2005, Neuropsychologia, 43; Rosenbaum, Gilboa, Levine, Winocur, & Moscovitch, 2009, Neuropsychologia, 47), which suggests that amnesiacs can get the gist. The present experiment used false recognition paradigms to assess whether the reduced rate of false recognition found in amnesic patients may be a consequence of their impaired item-specific memory. It examined the effect of increasing the item-specific memory of amnesic patient DA by bringing her to criterion on relevant study-lists and compared her performance on a false recognition paradigm with a group of 32 healthy young adults. Results indicated that when DA's item-specific memory was increased she was more able to gist and her performance was no different to the healthy young adults. Previous assumptions that gist memory is necessarily damaged in amnesia might therefore be revisited, since the reduced rate of false recognition could be caused by impaired item-specific memory. The experiment also highlights a positive relationship between item-specific and gist memory which has not previously been accounted for in false-recognition experiments.

  11. Mononuclear non-heme iron(III)

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 123; Issue 2. Mononuclear non-heme iron(III) complexes of linear and tripodal tridentate ligands as functional models for catechol dioxygenases: Effect of -alkyl substitution on regioselectivity and reaction rate. Mallayan Palaniandavar Kusalendiran Visvaganesan.

  12. Heme pathway evolution in kinetoplastid protists

    Czech Academy of Sciences Publication Activity Database

    Cenci, U.; Moog, D.; Curtis, B.A.; Tanifuji, G.; Eme, L.; Lukeš, Julius; Archibald, J.M.

    2016-01-01

    Roč. 16, MAY 18 (2016), č. článku 109. ISSN 1471-2148 Institutional support: RVO:60077344 Keywords : heme * kinetoplastea * Paramoeba pemaquidensis * Perkinsela * evolution * endosymbiosis * Prokinetoplastina * lateral gene transfer Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.221, year: 2016

  13. An ethane-bridged porphyrin dimer as a model of di-heme proteins: inorganic and bioinorganic perspectives and consequences of heme-heme interactions.

    Science.gov (United States)

    Sil, Debangsu; Rath, Sankar Prasad

    2015-10-07

    Interaction between heme centers has been cleverly implemented by Nature in order to regulate different properties of multiheme cytochromes, thereby allowing them to perform a wide variety of functions. Our broad interest lies in unmasking the roles played by heme-heme interactions in modulating different properties viz., metal spin state, redox potential etc., of the individual heme centers using an ethane-bridged porphyrin dimer as a synthetic model of dihemes. The large differences in the structure and properties of the diheme complexes, as compared to the monoheme analogs, provide unequivocal evidence of the role played by heme-heme interactions in the dihemes. This Perspective provides a brief account of our recent efforts to explore these interesting aspects and the subsequent outcomes.

  14. Generic and eating disorder-specific impairment in binge eating disorder with and without overvaluation of weight or shape.

    Science.gov (United States)

    Harrison, Carmel; Mond, Jonathan; Rieger, Elizabeth; Rodgers, Bryan

    2015-09-01

    We sought to elucidate the nature and extent of impairment in quality of life among individuals with binge eating disorder (BED) with and without the overvaluation of weight or shape ("overvaluation"). Subgroups of women - probable BED with overvaluation (n = 102), probable BED without overvaluation (n = 72), obese individuals reporting no binge eating ("obese control", n = 40), and "normal weight" individuals reporting no binge eating ("healthy control," n = 40) - were recruited from a community-based sample in which individuals with eating disorder symptoms were over-represented. They were compared on measures of eating disorder psychopathology and generic and disease-specific measures of quality of life. Scores on these measures among individuals with BED receiving specialist treatment were also considered. Participants with BED and overvaluation had high levels of eating disorder psychopathology and impairment in both generic and disease-specific quality of life, comparable to those of BED patients receiving specialist treatment, and significantly higher than all other subgroups, whereas participants with BED in the absence of overvaluation did not differ from obese controls on any of these measures. The findings provide further evidence for the need to consider reference to overvaluation among the diagnostic criteria for BED. The relative merits of the inclusion of overvaluation as a diagnostic criterion or as a diagnostic specifier for BED warrant greater consideration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. The Relationship between Specific Cognitive Impairment and Behaviour in Prader-Willi Syndrome

    Science.gov (United States)

    Woodcock, K. A.; Oliver, C.; Humphreys, G. W.

    2011-01-01

    Background: Individuals with Prader-Willi syndrome (PWS) have been shown to demonstrate a particular cognitive deficit in attention switching and high levels of preference for routine and temper outbursts. This study assesses whether a specific pathway between a cognitive deficit and behaviour via environmental interaction can exist in individuals…

  16. Structural Alterations of the Language Connectome in Children with Specific Language Impairment

    Czech Academy of Sciences Publication Activity Database

    Vydrová, R.; Komárek, V.; Šanda, J.; Štěrbová, K.; Jahodová, A.; Maulisová, A.; Žáčková, J.; Reissigová, Jindra; Kršek, P.; Kyncl, M.

    2015-01-01

    Roč. 151, December (2015), s. 35-41 ISSN 0093-934X Institutional support: RVO:67985807 Keywords : Specific language disorder * DTI * Arcuate fascicle * IFOF * Ventral stream Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 3.038, year: 2015

  17. The Chemistry and Biochemistry of Heme c: Functional Bases for Covalent Attachment

    OpenAIRE

    Bowman, Sarah E. J.; Bren, Kara L.

    2008-01-01

    A discussion of the literature concerning the synthesis, function, and activity of heme c-containing proteins is presented. Comparison of the properties of heme c, which is covalently bound to protein, is made to heme b, which is bound noncovalently. A question of interest is why nature uses biochemically expensive heme c in many proteins when its properties are expected to be similar to heme b. Considering the effects of covalent heme attachment on heme conformation and on the proximal histi...

  18. Disease-specific monoclonal antibodies targeting glutamate decarboxylase impair GABAergic neurotransmission and affect motor learning and behavioral functions

    Directory of Open Access Journals (Sweden)

    Mario U Manto

    2015-03-01

    Full Text Available Autoantibodies to the smaller isoform of glutamate decarboxylase can be found in patients with type 1 diabetes and a number of neurological disorders, including stiff-person syndrome, cerebellar ataxia and limbic encephalitis. The detection of disease-specific autoantibody epitopes led to the hypothesis that distinct glutamate decarboxylase autoantibodies may elicit specific neurological phenotypes. We explored the in vitro/in vivo effects of well-characterized monoclonal glutamate decarboxylase antibodies. We found that glutamate decarboxylase autoantibodies present in patients with stiff person syndrome (n = 7 and cerebellar ataxia (n = 15 recognized an epitope distinct from that recognized by glutamate decarboxylase autoantibodies present in patients with type 1 diabetes mellitus (n = 10 or limbic encephalitis (n = 4. We demonstrated that the administration of a monoclonal glutamate decarboxylase antibody representing this epitope specificity (1 disrupted in vitro the association of glutamate decarboxylase with γ-Aminobutyric acid containing synaptic vesicles, (2 depressed the inhibitory synaptic transmission in cerebellar slices with a gradual time course and a lasting suppressive effect, (3 significantly decreased conditioned eyelid responses evoked in mice, with no modification of learning curves in the classical eyeblink-conditioning task, (4 markedly impaired the facilitatory effect exerted by the premotor cortex over the motor cortex in a paired-pulse stimulation paradigm, and (5 induced decreased exploratory behavior and impaired locomotor function in rats. These findings support the specific targeting of glutamate decarboxylase by its autoantibodies in the pathogenesis of stiff-person syndrome and cerebellar ataxia. Therapies of these disorders based on selective removal of such glutamate decarboxylase antibodies could be envisioned.

  19. Task-specific impairments and enhancements induced by magnetic stimulation of human visual area V5.

    OpenAIRE

    Walsh, V; Ellison, A; Battelli, L; Cowey, A

    1998-01-01

    Transcranial magnetic stimulation (TMS) can be used to simulate the effects of highly circumscribed brain damage permanently present in some neuropsychological patients, by reversibly disrupting the normal functioning of the cortical area to which it is applied. By using TMS we attempted to recreate deficits similar to those reported in a motion-blind patient and to assess the specificity of deficits when TMS is applied over human area V5. We used six visual search tasks and showed that subje...

  20. Refining the LPS-Antigen in Salmonella Antibody Elisa for Poultry Enhanced Specificity without Impairing Sensitivity

    DEFF Research Database (Denmark)

    Lauritsen, Klara Tølbøl; Lind, Peter; Klausen, Joan

    2014-01-01

    In the Danish serological surveillance for Salmonella in poultry (serum and egg yolk) a mix-ELISA is used, based on S. typhimurium and S. enteritidis antigens (Feld et al., 2000). When we evaluated results of the test retrospectively, over the years an unacceptably large fraction of seropositive...... findings could not be confirmed by the subsequent confirmatory bacteriological sampling in the herd. Therefore we tried to enhance specificity of the ELISA, without losing sensitivity, by refining the antigens used....

  1. Prenatal stress challenge impairs fetal lung development and asthma severity sex-specifically in mice.

    Science.gov (United States)

    Zazara, Dimitra E; Perani, Clara V; Solano, María E; Arck, Petra C

    2018-02-01

    Allergic asthma is an increasing health problem worldwide. Interestingly, prenatal challenges such as stress have been associated with an increased risk for asthma during childhood. The underlying pathogenesis of how prenatal stress increases the risk for asthma still remains unclear. Potential targets could be that the fetal immune ontogeny or fetal lung development are compromised by prenatal challenges. Here, we aimed to identify whether prenatal stress challenge affects fetal lung development in mice. C57BL/6 pregnant mice were challenged with sound stress and fetal lung development was assessed histologically. Whilst prenatal stress challenge did not profoundly affect lung development in male fetuses, it resulted in less extensive terminal sacs, surrounded by thicker mesenchymal tissue in female fetuses. Thus, prenatal stress disrupted fetal lung development sex-specifically. Interestingly, upon prenatal stress challenge, the airway hyperresponsiveness and eosinophilic inflammation- two hallmarks of asthma - were significantly increased in adult female offspring, whilst regulatory CD4+ T cells were reduced. These findings strongly underpin the sex-specific association between s challenged fetal development and a sex-specific altered severity of asthma in adult offspring. Our model now allows to identify maternal markers through which the risk for asthma and possible other diseases is vertically transferred before birth in response to challenges. Such identification then opens avenues for primary disease prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Silencing of Iron and Heme-Related Genes Revealed a Paramount Role of Iron in the Physiology of the Hematophagous Vector Rhodnius prolixus

    Directory of Open Access Journals (Sweden)

    Ana B. Walter-Nuno

    2018-02-01

    Full Text Available Iron is an essential element for most organisms However, free iron and heme, its complex with protoporphyrin IX, can be extremely cytotoxic, due to the production of reactive oxygen species, eventually leading to oxidative stress. Thus, eukaryotic cells control iron availability by regulating its transport, storage and excretion as well as the biosynthesis and degradation of heme. In the genome of Rhodnius prolixus, the vector of Chagas disease, we identified 36 genes related to iron and heme metabolism We performed a comprehensive analysis of these genes, including identification of homologous genes described in other insect genomes. We observed that blood-meal modulates the expression of ferritin, Iron Responsive protein (IRP, Heme Oxygenase (HO and the heme exporter Feline Leukemia Virus C Receptor (FLVCR, components of major pathways involved in the regulation of iron and heme metabolism, particularly in the posterior midgut (PM, where an intense release of free heme occurs during the course of digestion. Knockdown of these genes impacted the survival of nymphs and adults, as well as molting, oogenesis and embryogenesis at different rates and time-courses. The silencing of FLVCR caused the highest levels of mortality in nymphs and adults and reduced nymph molting. The oogenesis was mildly affected by the diminished expression of all of the genes whereas embryogenesis was dramatically impaired by the knockdown of ferritin expression. Furthermore, an intense production of ROS in the midgut of blood-fed insects occurs when the expression of ferritin, but not HO, was inhibited. In this manner, the degradation of dietary heme inside the enterocytes may represent an oxidative challenge that is counteracted by ferritins, conferring to this protein a major antioxidant role. Taken together these results demonstrate that the regulation of iron and heme metabolism is of paramount importance for R. prolixus physiology and imbalances in the levels of

  3. A Heme-responsive Regulator Controls Synthesis of Staphyloferrin B in Staphylococcus aureus.

    Science.gov (United States)

    Laakso, Holly A; Marolda, Cristina L; Pinter, Tyler B; Stillman, Martin J; Heinrichs, David E

    2016-01-01

    Staphylococcus aureus possesses a multitude of mechanisms by which it can obtain iron during growth under iron starvation conditions. It expresses an effective heme acquisition system (the iron-regulated surface determinant system), it produces two carboxylate-type siderophores staphyloferrin A and staphyloferrin B (SB), and it expresses transporters for many other siderophores that it does not synthesize. The ferric uptake regulator protein regulates expression of genes encoding all of these systems. Mechanisms of fine-tuning expression of iron-regulated genes, beyond simple iron regulation via ferric uptake regulator, have not been uncovered in this organism. Here, we identify the ninth gene of the sbn operon, sbnI, as encoding a ParB/Spo0J-like protein that is required for expression of genes in the sbn operon from sbnD onward. Expression of sbnD-I is drastically decreased in an sbnI mutant, and the mutant does not synthesize detectable SB during early phases of growth. Thus, SB-mediated iron acquisition is impaired in an sbnI mutant strain. We show that the protein forms dimers and tetramers in solution and binds to DNA within the sbnC coding region. Moreover, we show that SbnI binds heme and that heme-bound SbnI does not bind DNA. Finally, we show that providing exogenous heme to S. aureus growing in an iron-free medium results in delayed synthesis of SB. This is the first study in S. aureus that identifies a DNA-binding regulatory protein that senses heme to control gene expression for siderophore synthesis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. A Heme-responsive Regulator Controls Synthesis of Staphyloferrin B in Staphylococcus aureus*♦

    Science.gov (United States)

    Laakso, Holly A.; Marolda, Cristina L.; Pinter, Tyler B.; Stillman, Martin J.; Heinrichs, David E.

    2016-01-01

    Staphylococcus aureus possesses a multitude of mechanisms by which it can obtain iron during growth under iron starvation conditions. It expresses an effective heme acquisition system (the iron-regulated surface determinant system), it produces two carboxylate-type siderophores staphyloferrin A and staphyloferrin B (SB), and it expresses transporters for many other siderophores that it does not synthesize. The ferric uptake regulator protein regulates expression of genes encoding all of these systems. Mechanisms of fine-tuning expression of iron-regulated genes, beyond simple iron regulation via ferric uptake regulator, have not been uncovered in this organism. Here, we identify the ninth gene of the sbn operon, sbnI, as encoding a ParB/Spo0J-like protein that is required for expression of genes in the sbn operon from sbnD onward. Expression of sbnD–I is drastically decreased in an sbnI mutant, and the mutant does not synthesize detectable SB during early phases of growth. Thus, SB-mediated iron acquisition is impaired in an sbnI mutant strain. We show that the protein forms dimers and tetramers in solution and binds to DNA within the sbnC coding region. Moreover, we show that SbnI binds heme and that heme-bound SbnI does not bind DNA. Finally, we show that providing exogenous heme to S. aureus growing in an iron-free medium results in delayed synthesis of SB. This is the first study in S. aureus that identifies a DNA-binding regulatory protein that senses heme to control gene expression for siderophore synthesis. PMID:26534960

  5. Inactivation of Dengue and Yellow Fever viruses by heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX.

    Science.gov (United States)

    Assunção-Miranda, I; Cruz-Oliveira, C; Neris, R L S; Figueiredo, C M; Pereira, L P S; Rodrigues, D; Araujo, D F F; Da Poian, A T; Bozza, M T

    2016-03-01

    To investigate the effect of heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX (CoPPIX and SnPPIX), macrocyclic structures composed by a tetrapyrrole ring with a central metallic ion, on Dengue Virus (DENV) and Yellow Fever Virus (YFV) infection. Treatment of HepG2 cells with heme, CoPPIX and SnPPIX after DENV infection reduced infectious particles without affecting viral RNA contents in infected cells. The reduction of viral load occurs only with the direct contact of DENV with porphyrins, suggesting a direct effect on viral particles. Previously incubation of DENV and YFV with heme, CoPPIX and SnPPIX resulted in viral particles inactivation in a dose-dependent manner. Biliverdin, a noncyclical porphyrin, was unable to inactivate the viruses tested. Infection of HepG2 cells with porphyrin-pretreated DENV2 results in a reduced or abolished viral protein synthesis, RNA replication and cell death. Treatment of HepG2 or THP-1 cell lineage with heme or CoPPIX after DENV infection with a very low MOI resulted in a decreased DENV replication and protection from death. Heme, CoPPIX and SnPPIX possess a marked ability to inactivate DENV and YFV, impairing its ability to infect and induce cytopathic effects on target cells. These results open the possibility of therapeutic application of porphyrins or their use as models to design new antiviral drugs against DENV and YFV. © 2016 The Society for Applied Microbiology.

  6. Specific memory impairment following neonatal encephalopathy in term-born children.

    Science.gov (United States)

    van Handel, Mariëlle; de Sonneville, Leo; de Vries, Linda S; Jongmans, Marian J; Swaab, Hanna

    2012-01-01

    This study examines short-term memory, verbal working memory, episodic long-term memory, and intelligence in 32 children with mild neonatal encephalopathy (NE), 39 children with moderate NE, 10 children with NE who developed cerebral palsy (CP), and 53 comparison children, at the age of 9 to 10 years. in addition to a global effect on intelligence, NE had a specific effect on verbal working memory, verbal and visuo-spatial long-term memory, and learning, which was associated with degree of NE. Although these memory problems occurred in children without CP, they were more pronounced when children had also developed CP.

  7. Atypical audio-visual speech perception and McGurk effects in children with specific language impairment.

    Science.gov (United States)

    Leybaert, Jacqueline; Macchi, Lucie; Huyse, Aurélie; Champoux, François; Bayard, Clémence; Colin, Cécile; Berthommier, Frédéric

    2014-01-01

    Audiovisual speech perception of children with specific language impairment (SLI) and children with typical language development (TLD) was compared in two experiments using /aCa/ syllables presented in the context of a masking release paradigm. Children had to repeat syllables presented in auditory alone, visual alone (speechreading), audiovisual congruent and incongruent (McGurk) conditions. Stimuli were masked by either stationary (ST) or amplitude modulated (AM) noise. Although children with SLI were less accurate in auditory and audiovisual speech perception, they showed similar auditory masking release effect than children with TLD. Children with SLI also had less correct responses in speechreading than children with TLD, indicating impairment in phonemic processing of visual speech information. In response to McGurk stimuli, children with TLD showed more fusions in AM noise than in ST noise, a consequence of the auditory masking release effect and of the influence of visual information. Children with SLI did not show this effect systematically, suggesting they were less influenced by visual speech. However, when the visual cues were easily identified, the profile of responses to McGurk stimuli was similar in both groups, suggesting that children with SLI do not suffer from an impairment of audiovisual integration. An analysis of percent of information transmitted revealed a deficit in the children with SLI, particularly for the place of articulation feature. Taken together, the data support the hypothesis of an intact peripheral processing of auditory speech information, coupled with a supra modal deficit of phonemic categorization in children with SLI. Clinical implications are discussed.

  8. Thyrocyte-specific Gq/G11 deficiency impairs thyroid function and prevents goiter development.

    Science.gov (United States)

    Kero, Jukka; Ahmed, Kashan; Wettschureck, Nina; Tunaru, Sorin; Wintermantel, Tim; Greiner, Erich; Schütz, Günther; Offermanns, Stefan

    2007-09-01

    The function of the adult thyroid is regulated by thyroid-stimulating hormone (TSH), which acts through a G protein-coupled receptor. Overactivation of the TSH receptor results in hyperthyroidism and goiter. The Gs-mediated stimulation of adenylyl cyclase-dependent cAMP formation has been regarded as the principal intracellular signaling mechanism mediating the action of TSH. Here we show that the Gq/G11-mediated signaling pathway plays an unexpected and essential role in the regulation of thyroid function. Mice lacking the alpha subunits of Gq and G11 specifically in thyroid epithelial cells showed severely reduced iodine organification and thyroid hormone secretion in response to TSH, and many developed hypothyroidism within months after birth. In addition, thyrocyte-specific Galphaq/Galpha11-deficient mice lacked the normal proliferative thyroid response to TSH or goitrogenic diet, indicating an essential role of this pathway in the adaptive growth of the thyroid gland. Our data suggest that Gq/G11 and their downstream effectors are promising targets to interfere with increased thyroid function and growth.

  9. Heme exporter FLVCR1a regulates heme synthesis and degradation and controls activity of cytochromes P450.

    Science.gov (United States)

    Vinchi, Francesca; Ingoglia, Giada; Chiabrando, Deborah; Mercurio, Sonia; Turco, Emilia; Silengo, Lorenzo; Altruda, Fiorella; Tolosano, Emanuela

    2014-05-01

    The liver has one of the highest rates of heme synthesis of any organ. More than 50% of the heme synthesized in the liver is used for synthesis of P450 enzymes, which metabolize exogenous and endogenous compounds that include natural products, hormones, drugs, and carcinogens. Feline leukemia virus subgroup C cellular receptor 1a (FLVCR1a) is plasma membrane heme exporter that is ubiquitously expressed and controls intracellular heme content in hematopoietic lineages. We investigated the role of Flvcr1a in liver function in mice. We created mice with conditional disruption of Mfsd7b, which encodes Flvcr1a, in hepatocytes (Flvcr1a(fl/fl);alb-cre mice). Mice were analyzed under basal conditions, after phenylhydrazine-induced hemolysis, and after induction of cytochromes P450 synthesis. Livers were collected and analyzed by histologic, quantitative real-time polymerase chain reaction, and immunoblot analyses. Hepatic P450 enzymatic activities were measured. Flvcr1a(fl/fl);alb-cre mice accumulated heme and iron in liver despite up-regulation of heme oxygenase 1, ferroportin, and ferritins. Hepatic heme export activity of Flvcr1a was closely associated with heme biosynthesis, which is required to sustain cytochrome induction. Upon cytochromes P450 stimulation, Flvcr1a(fl/fl);alb-cre mice had reduced cytochrome activity, associated with accumulation of heme in hepatocytes. The expansion of the cytosolic heme pool in these mice was likely responsible for the early inhibition of heme synthesis and increased degradation of heme, which reduced expression and activity of cytochromes P450. In livers of mice, Flvcr1a maintains a free heme pool that regulates heme synthesis and degradation as well as cytochromes P450 expression and activity. These findings have important implications for drug metabolism. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  10. Heme Exporter FLVCR1a Regulates Heme Synthesis and Degradation and Controls Activity of Cytochromes P450

    Science.gov (United States)

    Vinchi, Francesca; Ingoglia, Giada; Chiabrando, Deborah; Mercurio, Sonia; Turco, Emilia; Silengo, Lorenzo; Altruda, Fiorella; Tolosano, Emanuela

    2014-01-01

    Background & Aims The liver has one of the highest rates of heme synthesis of any organ. More than 50% of the heme synthesized in the liver is used for synthesis of P450 enzymes, which metabolize exogenous and endogenous compounds that include natural products, hormones, drugs, and carcinogens. Feline leukemia virus subgroup C cellular receptor 1a (FLVCR1a) is plasma membrane heme exporter that is ubiquitously expressed and controls intracellular heme content in hematopoietic lineages. We investigated the role of Flvcr1a in liver function in mice. Methods We created mice with conditional disruption of Mfsd7b, which encodes Flvcr1a, in hepatocytes (Flvcr1afl/fl;alb-cre mice). Mice were analyzed under basal conditions, after phenylhydrazine-induced hemolysis, and after induction of cytochromes P450 synthesis. Livers were collected and analyzed by histologic, quantitative real-time polymerase chain reaction, and immunoblot analyses. Hepatic P450 enzymatic activities were measured. Results Flvcr1afl/fl;alb-cre mice accumulated heme and iron in liver despite up-regulation of heme oxygenase 1, ferroportin, and ferritins. Hepatic heme export activity of Flvcr1a was closely associated with heme biosynthesis, which is required to sustain cytochrome induction. Upon cytochromes P450 stimulation, Flvcr1afl/fl;alb-cre mice had reduced cytochrome activity, associated with accumulation of heme in hepatocytes. The expansion of the cytosolic heme pool in these mice was likely responsible for the early inhibition of heme synthesis and increased degradation of heme, which reduced expression and activity of cytochromes P450. Conclusions In livers of mice, Flvcr1a maintains a free heme pool that regulates heme synthesis and degradation as well as cytochromes P450 expression and activity. These findings have important implications for drug metabolism. PMID:24486949

  11. Association of disease-specific causes of visual impairment and 10-year mortality amongst Indigenous Australians: the Central Australian Ocular Health Study.

    Science.gov (United States)

    Estevez, José; Kaidonis, Georgia; Henderson, Tim; Craig, Jamie E; Landers, John

    2018-01-01

    Visual impairment significantly impairs the length and quality of life, but little is known of its impact in Indigenous Australians. To investigate the association of disease-specific causes of visual impairment with all-cause mortality. A retrospective cohort analysis. A total of 1347 Indigenous Australians aged over 40 years. Participants visiting remote medical clinics underwent clinical examinations including visual acuity, subjective refraction and slit-lamp examination of the anterior and posterior segments. The major ocular cause of visual impairment was determined. Patients were assessed periodically in these remote clinics for the succeeding 10 years after recruitment. Mortality rates were obtained from relevant departments. All-cause 10-year mortality and its association with disease-specific causes of visual impairment. The all-cause mortality rate for the entire cohort was 29.3% at the 10-year completion of follow-up. Of those with visual impairment, the overall mortality rate was 44.9%. The mortality rates differed for those with visual impairment due to cataract (59.8%), diabetic retinopathy (48.4%), trachoma (46.6%), 'other' (36.2%) and refractive error (33.4%) (P visual impairment from diabetic retinopathy were any more likely to die during the 10 years of follow-up when compared with those without visual impairment (HR 1.70; 95% CI, 1.00-2.87; P = 0.049). Visual impairment was associated with all-cause mortality in a cohort of Indigenous Australians. However, diabetic retinopathy was the only ocular disease that significantly increased the risk of mortality. Visual impairment secondary to diabetic retinopathy may be an important predictor of mortality. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

  12. Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment.

    Directory of Open Access Journals (Sweden)

    Pía Villanueva

    2015-03-01

    Full Text Available Children affected by Specific Language Impairment (SLI fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile, who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations in the NFXL1 gene that confers a nonsynonymous change (N150K and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 × 10-4, 8 variants tested. Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model.

  13. Do children with dyslexia and/or specific language impairment compensate for place assimilation? Insight into phonological grammar and representations.

    Science.gov (United States)

    Marshall, Chloe R; Ramus, Franck; van der Lely, Heather

    2011-10-01

    English speakers have to recognize, for example, that te[m] in te[m] pens is a form of ten, despite place assimilation of the nasal consonant. Children with dyslexia and specific language impairment (SLI) are commonly proposed to have a phonological deficit, and we investigate whether that deficit extends to place assimilation, as a way of probing phonological representations and phonological grammar. Children with SLI plus dyslexia, SLI only, and dyslexia only listened to sentences containing a target word in different assimilatory contexts-viable, unviable, and no change-and pressed a button to report hearing the target. The dyslexia-only group did not differ from age-matched controls, but the SLI groups showed more limited ability to accurately identify words within sentences. Once this factor was taken into account, the groups did not differ in their ability to compensate for assimilation. The results add to a growing body of evidence that phonological representations are not necessarily impaired in dyslexia. SLI children's results suggest that they too are sensitive to this aspect of phonological grammar, but are more liberal in their acceptance of alternative phonological forms of words. Furthermore, these children's ability to reject alternative phonological forms seems to be primarily limited by their vocabulary size and phonological awareness abilities.

  14. Frequency of educational computer use as a longitudinal predictor of educational outcome in young people with specific language impairment.

    Directory of Open Access Journals (Sweden)

    Kevin Durkin

    Full Text Available Computer use draws on linguistic abilities. Using this medium thus presents challenges for young people with Specific Language Impairment (SLI and raises questions of whether computer-based tasks are appropriate for them. We consider theoretical arguments predicting impaired performance and negative outcomes relative to peers without SLI versus the possibility of positive gains. We examine the relationship between frequency of computer use (for leisure and educational purposes and educational achievement; in particular examination performance at the end of compulsory education and level of educational progress two years later. Participants were 49 young people with SLI and 56 typically developing (TD young people. At around age 17, the two groups did not differ in frequency of educational computer use or leisure computer use. There were no associations between computer use and educational outcomes in the TD group. In the SLI group, after PIQ was controlled for, educational computer use at around 17 years of age contributed substantially to the prediction of educational progress at 19 years. The findings suggest that educational uses of computers are conducive to educational progress in young people with SLI.

  15. Cognitive neuropsychological and regional cerebral blood flow study of a Japanese-English bilingual girl with specific language impairment (SLI).

    Science.gov (United States)

    Uno, Akira; Wydell, Taeko N; Kato, Motoichiro; Itoh, Kanae; Yoshino, Fumihiro

    2009-02-01

    We report here on an investigation into the possible factors which might have contributed to language impairment (LI) in EM, a 14-year-old Japanese-English bilingual girl. EM was born in the UK to Japanese parents with no other siblings, and used English to communicate with all other people except for her parents. A delay in her English language development was identified at primary school in the UK, which was attributed to her bilingualism. The deficiency in her English language skills persisted into her adolescence despite more than adequate educational opportunities (including additional language support). At the start of her secondary education, language ability/literacy attainment tests were conducted in both English and Japanese, and the results suggested specific language impairment (SLI) in both languages. Further, her brain Single Photon Emission Computed Tomography (SPECT) revealed significantly lower Regional Cerebral Blood Flow(rCBF) in the left temporo-parietal area, which is also similar to the area of dysfunction often found among Japanese individuals with SLI.

  16. Single or functionalized fullerenes interacting with heme group

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Wallison Chaves; Diniz, Eduardo Moraes, E-mail: eduardo.diniz@ufma.br [Departamento de Física, Universidade Federal do Maranhão, Avenida dos Portugueses, 1966, CEP 65080-805, São Luís - MA (Brazil)

    2014-09-15

    The heme group is responsible for iron transportation through the bloodstream, where iron participates in redox reactions, electron transfer, gases detection etc. The efficiency of such processes can be reduced if the whole heme molecule or even the iron is somehow altered from its original oxidation state, which can be caused by interactions with nanoparticles as fullerenes. To verify how such particles alter the geometry and electronic structure of heme molecule, here we report first principles calculations based on density functional theory of heme group interacting with single C{sub 60} fullerene or with C{sub 60} functionalized with small functional groups (−CH{sub 3}, −COOH, −NH{sub 2}, −OH). The calculations shown that the system heme + nanoparticle has a different spin state in comparison with heme group if the fullerene is functionalized. Also a functional group can provide a stronger binding between nanoparticle and heme molecule or inhibit the chemical bonding in comparison with single fullerene results. In addition heme molecule loses electrons to the nanoparticles and some systems exhibited a geometry distortion in heme group, depending on the binding energy. Furthermore, one find that such nanoparticles induce a formation of spin up states in heme group. Moreover, there exist modifications in density of states near the Fermi energy. Although of such changes in heme electronic structure and geometry, the iron atom remains in the heme group with the same oxidation state, so that processes that involve the iron might not be affected, only those that depend on the whole heme molecule.

  17. The cytoprotective enzyme heme oxygenase-1 suppresses Ebola virus replication.

    Science.gov (United States)

    Hill-Batorski, Lindsay; Halfmann, Peter; Neumann, Gabriele; Kawaoka, Yoshihiro

    2013-12-01

    Ebola virus (EBOV) is the causative agent of a severe hemorrhagic fever in humans with reported case fatality rates as high as 90%. There are currently no licensed vaccines or antiviral therapeutics to combat EBOV infections. Heme oxygenase-1 (HO-1), an enzyme that catalyzes the rate-limiting step in heme degradation, has antioxidative properties and protects cells from various stresses. Activated HO-1 was recently shown to have antiviral activity, potently inhibiting the replication of viruses such as hepatitis C virus and human immunodeficiency virus. However, the effect of HO-1 activation on EBOV replication remains unknown. To determine whether the upregulation of HO-1 attenuates EBOV replication, we treated cells with cobalt protoporphyrin (CoPP), a selective HO-1 inducer, and assessed its effects on EBOV replication. We found that CoPP treatment, pre- and postinfection, significantly suppressed EBOV replication in a manner dependent upon HO-1 upregulation and activity. In addition, stable overexpression of HO-1 significantly attenuated EBOV growth. Although the exact mechanism behind the antiviral properties of HO-1 remains to be elucidated, our data show that HO-1 upregulation does not attenuate EBOV entry or budding but specifically targets EBOV transcription/replication. Therefore, modulation of the cellular enzyme HO-1 may represent a novel therapeutic strategy against EBOV infection.

  18. Energy transfer at the active sites of heme proteins

    International Nuclear Information System (INIS)

    Dlott, D.D.; Hill, J.R.

    1995-01-01

    Experiments using a picosecond pump-probe apparatus at the Picosecond Free-electron Laser Center at Stanford University, were performed to investigate the relaxation of carbon monoxide bound to the active sites of heme proteins. The significance of these experiments is two-fold: (1) they provide detailed information about molecular dynamics occurring at the active sites of proteins; and (2) they provide insight into the nature of vibrational relaxation processes in condensed matter. Molecular engineering is used to construct various molecular systems which are studied with the FEL. We have studied native proteins, mainly myoglobin obtained from different species, mutant proteins produced by genetic engineering using recombinant DNA techniques, and a variety of model systems which mimic the structures of the active sites of native proteins, which are produced using molecular synthesis. Use of these different systems permits us to investigate how specific molecular structural changes affect dynamical processes occurring at the active sites. This research provides insight into the problems of how different species needs are fulfilled by heme proteins which have greatly different functionality, which is induced by rather small structural changes

  19. Direction-Specific Impairments in Cervical Range of Motion in Women with Chronic Neck Pain: Influence of Head Posture and Gravitationally Induced Torque.

    Science.gov (United States)

    Rudolfsson, Thomas; Björklund, Martin; Svedmark, Åsa; Srinivasan, Divya; Djupsjöbacka, Mats

    2017-01-01

    Cervical range of motion (ROM) is commonly assessed in clinical practice and research. In a previous study we decomposed active cervical sagittal ROM into contributions from lower and upper levels of the cervical spine and found level- and direction-specific impairments in women with chronic non-specific neck pain. The present study aimed to validate these results and investigate if the specific impairments can be explained by the neutral posture (defining zero flexion/extension) or a movement strategy to avoid large gravitationally induced torques on the cervical spine. Kinematics of the head and thorax was assessed in sitting during maximal sagittal cervical flexion/extension (high torque condition) and maximal protraction (low torque condition) in 120 women with chronic non-specific neck pain and 40 controls. We derived the lower and upper cervical angles, and the head centre of mass (HCM), from a 3-segment kinematic model. Neutral head posture was assessed using a standardized procedure. Previous findings of level- and direction-specific impairments in neck pain were confirmed. Neutral head posture was equal between groups and did not explain the direction-specific impairments. The relative magnitude of group difference in HCM migration did not differ between high and low torques conditions, lending no support for our hypothesis that impairments in sagittal ROM are due to torque avoidance behaviour. The direction- and level-specific impairments in cervical sagittal ROM can be generalised to the population of women with non-specific neck pain. Further research is necessary to clarify if torque avoidance behaviour can explain the impairments.

  20. Direction-Specific Impairments in Cervical Range of Motion in Women with Chronic Neck Pain: Influence of Head Posture and Gravitationally Induced Torque.

    Directory of Open Access Journals (Sweden)

    Thomas Rudolfsson

    Full Text Available Cervical range of motion (ROM is commonly assessed in clinical practice and research. In a previous study we decomposed active cervical sagittal ROM into contributions from lower and upper levels of the cervical spine and found level- and direction-specific impairments in women with chronic non-specific neck pain. The present study aimed to validate these results and investigate if the specific impairments can be explained by the neutral posture (defining zero flexion/extension or a movement strategy to avoid large gravitationally induced torques on the cervical spine.Kinematics of the head and thorax was assessed in sitting during maximal sagittal cervical flexion/extension (high torque condition and maximal protraction (low torque condition in 120 women with chronic non-specific neck pain and 40 controls. We derived the lower and upper cervical angles, and the head centre of mass (HCM, from a 3-segment kinematic model. Neutral head posture was assessed using a standardized procedure.Previous findings of level- and direction-specific impairments in neck pain were confirmed. Neutral head posture was equal between groups and did not explain the direction-specific impairments. The relative magnitude of group difference in HCM migration did not differ between high and low torques conditions, lending no support for our hypothesis that impairments in sagittal ROM are due to torque avoidance behaviour.The direction- and level-specific impairments in cervical sagittal ROM can be generalised to the population of women with non-specific neck pain. Further research is necessary to clarify if torque avoidance behaviour can explain the impairments.

  1. Jumping Stand Apparatus Reveals Rapidly Specific Age-Related Cognitive Impairments in Mouse Lemur Primates.

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    Jean-Luc Picq

    Full Text Available The mouse lemur (Microcebus murinus is a promising primate model for investigating normal and pathological cerebral aging. The locomotor behavior of this arboreal primate is characterized by jumps to and from trunks and branches. Many reports indicate insufficient adaptation of the mouse lemur to experimental devices used to evaluate its cognition, which is an impediment to the efficient use of this animal in research. In order to develop cognitive testing methods appropriate to the behavioral and biological traits of this species, we adapted the Lashley jumping stand apparatus, initially designed for rats, to the mouse lemur. We used this jumping stand apparatus to compare performances of young (n = 12 and aged (n = 8 adults in acquisition and long-term retention of visual discriminations. All mouse lemurs completed the tasks and only 25 trials, on average, were needed to master the first discrimination problem with no age-related differences. A month later, all mouse lemurs made progress for acquiring the second discrimination problem but only the young group reached immediately the criterion in the retention test of the first discrimination problem. This study shows that the jumping stand apparatus allows rapid and efficient evaluation of cognition in mouse lemurs and demonstrates that about half of the old mouse lemurs display a specific deficit in long-term retention but not in acquisition of visual discrimination.

  2. Domain-specific impairment of source memory following a right posterior medial temporal lobe lesion.

    Science.gov (United States)

    Peters, Jan; Koch, Benno; Schwarz, Michael; Daum, Irene

    2007-01-01

    This single case analysis of memory performance in a patient with an ischemic lesion affecting posterior but not anterior right medial temporal lobe (MTL) indicates that source memory can be disrupted in a domain-specific manner. The patient showed normal recognition memory for gray-scale photos of objects (visual condition) and spoken words (auditory condition). While memory for visual source (texture/color of the background against which pictures appeared) was within the normal range, auditory source memory (male/female speaker voice) was at chance level, a performance pattern significantly different from the control group. This dissociation is consistent with recent fMRI evidence of anterior/posterior MTL dissociations depending upon the nature of source information (visual texture/color vs. auditory speaker voice). The findings are in good agreement with the view of dissociable memory processing by the perirhinal cortex (anterior MTL) and parahippocampal cortex (posterior MTL), depending upon the neocortical input that these regions receive. (c) 2007 Wiley-Liss, Inc.

  3. Is Weak Oral Language Associated with Poor Spelling in School-Age Children with Specific Language Impairment, Dyslexia, or Both?

    Science.gov (United States)

    McCarthy, Jillian H.; Hogan, Tiffany P.; Catts, Hugh W.

    2013-01-01

    The purpose of this study was to test the hypothesis that word reading accuracy, not oral language, is associated with spelling performance in school-age children. We compared fourth grade spelling accuracy in children with specific language impairment (SLI), dyslexia, or both (SLI/dyslexia) to their typically developing grade-matched peers. Results of the study revealed that children with SLI performed similarly to their typically developing peers on a single word spelling task. Alternatively, those with dyslexia and SLI/dyslexia evidenced poor spelling accuracy. Errors made by both those with dyslexia and SLI/dyslexia were characterized by numerous phonologic, orthographic, and semantic errors. Cumulative results support the hypothesis that word reading accuracy, not oral language, is associated with spelling performance in typically developing school-age children and their peers with SLI and dyslexia. Findings are provided as further support for the notion that SLI and dyslexia are distinct, yet co-morbid, developmental disorders. PMID:22876769

  4. P300 as a measure of processing capacity in auditory and visual domains in specific language impairment.

    Science.gov (United States)

    Evans, Julia L; Selinger, Craig; Pollak, Seth D

    2011-05-10

    This study examined the electrophysiological correlates of auditory and visual working memory in children with Specific Language Impairments (SLI). Children with SLI and age-matched controls (11;9-14;10) completed visual and auditory working memory tasks while event-related potentials (ERPs) were recorded. In the auditory condition, children with SLI performed similarly to controls when the memory load was kept low (1-back memory load). As expected, when demands for auditory working memory were higher, children with SLI showed decreases in accuracy and attenuated P3b responses. However, children with SLI also evinced difficulties in the visual working memory tasks. In both the low (1-back) and high (2-back) memory load conditions, P3b amplitude was significantly lower for the SLI as compared to CA groups. These data suggest a domain-general working memory deficit in SLI that is manifested across auditory and visual modalities. Copyright © 2010 Elsevier B.V. All rights reserved.

  5. Linguistic and pragmatic aspects of narration in Finnish typically developing children and children with specific language impairment.

    Science.gov (United States)

    Mäkinen, Leena; Loukusa, Soile; Laukkanen, Päivi; Leinonen, Eeva; Kunnari, Sari

    2014-06-01

    This study investigates narratives of Finnish children with specific language impairment (SLI) from linguistic and pragmatic perspectives, in order to get a comprehensive overview of these children's narrative abilities. Nineteen children with SLI (mean age 6;1 years) and 19 typically developing age-matched children participated in the study. Their picture-elicited narrations were analysed for linguistic productivity and complexity, grammatical and referential accuracy, event content, the use of mental state expressions and narrative comprehension. Children with SLI showed difficulties in every aspect of narration in comparison to their peers. Only one measure of productivity, the number of communication units, did not reach statistical significance. Not only was linguistic structure fragile but also pragmatic aspects of storytelling (referencing, event content, mental state expressions and inferencing) were demanding for children with SLI. Results suggest that pragmatic aspects of narration should be taken into account more often when assessing narrative abilities of children with SLI.

  6. Rates of auxiliary is and are in African American English speaking children with specific language impairment following language treatment.

    Science.gov (United States)

    Smith, Shana; Bellon-Harn, Monica L

    2015-02-01

    The purpose of this exploratory study is to examine rates of auxiliary is and are across dialect patterns produced by African American English with specific language impairment (AAE-SLI) children following language treatment. The following research question is asked: Do AAE-SLI children exhibit rates of auxiliary is and are across dialect patterns consistent with previous reports of typically developing children and adult AAE speakers? A pre-/post-test design was used to identify patterns in which auxiliary is and are were produced at significant levels. Individual performance was included to examine variable rates of use across patterns. Group and individual results suggest children used auxiliary is and are in dialect patterns at rates consistent with typically developing child and adult AAE speakers. We conclude that rates of use may contribute to evidence-based guidelines for morphological intervention with AAE-SLI children.

  7. The production of direct object clitics in pre-school- and primary school-aged children with specific language impairments.

    Science.gov (United States)

    Guasti, Maria Teresa; Palma, Silvia; Genovese, Elisabetta; Stagi, Paolo; Saladini, Gabriella; Arosio, Fabrizio

    2016-01-01

    Third-person direct object (DO) clitic pronoun production is examined through an elicited production method in pre-school- and primary school-aged groups of Italian children with specific language impairment (SLI) to establish whether there is an improvement from age 5 years to age 7 years and whether there are qualitative differences in the two groups' responses. It was found that 5- and 7-year-old Italian children with SLI produce fewer third-person DO clitics than same-age peers. The kind of responses they provide changes: at 5 years, children with SLI tend to omit clitics, while at 7 years, they use a full noun. Production of third-person DO clitics is a persistent challenge for children with SLI and is confirmed to be a good clinical marker both at 5 and 7 years of age.

  8. Prosodic influences on speech production in children with specific language impairment and speech deficits: kinematic, acoustic, and transcription evidence.

    Science.gov (United States)

    Goffman, L

    1999-12-01

    It is often hypothesized that young children's difficulties with producing weak-strong (iambic) prosodic forms arise from perceptual or linguistically based production factors. A third possible contributor to errors in the iambic form may be biological constraints, or biases, of the motor system. In the present study, 7 children with specific language impairment (SLI) and speech deficits were matched to same age peers. Multiple levels of analysis, including kinematic (modulation and stability of movement), acoustic, and transcription, were applied to children's productions of iambic (weak-strong) and trochaic (strong-weak) prosodic forms. Findings suggest that a motor bias toward producing unmodulated rhythmic articulatory movements, similar to that observed in canonical babbling, contribute to children's acquisition of metrical forms. Children with SLI and speech deficits show less mature segmental and speech motor systems, as well as decreased modulation of movement in later developing iambic forms. Further, components of prosodic and segmental acquisition develop independently and at different rates.

  9. Elimination of Endogenous Toxin, Creatinine from Blood Plasma Depends on Albumin Conformation: Site Specific Uremic Toxicity & Impaired Drug Binding

    Science.gov (United States)

    Varshney, Ankita; Rehan, Mohd; Subbarao, Naidu; Rabbani, Gulam; Khan, Rizwan Hasan

    2011-01-01

    Uremic syndrome results from malfunctioning of various organ systems due to the retention of uremic toxins which, under normal conditions, would be excreted into the urine and/or metabolized by the kidneys. The aim of this study was to elucidate the mechanisms underlying the renal elimination of uremic toxin creatinine that accumulate in chronic renal failure. Quantitative investigation of the plausible correlations was performed by spectroscopy, calorimetry, molecular docking and accessibility of surface area. Alkalinization of normal plasma from pH 7.0 to 9.0 modifies the distribution of toxin in the body and therefore may affect both the accumulation and the rate of toxin elimination. The ligand loading of HSA with uremic toxin predicts several key side chain interactions of site I that presumably have the potential to impact the specificity and impaired drug binding. These findings provide useful information for elucidating the complicated mechanism of toxin disposition in renal disease state. PMID:21386972

  10. Fibroblast-Specific Deletion of Hypoxia Inducible Factor-1 Critically Impairs Murine Cutaneous Neovascularization and Wound Healing.

    Science.gov (United States)

    Duscher, Dominik; Maan, Zeshaan N; Whittam, Alexander J; Sorkin, Michael; Hu, Michael S; Walmsley, Graham G; Baker, Hutton; Fischer, Lauren H; Januszyk, Michael; Wong, Victor W; Gurtner, Geoffrey C

    2015-11-01

    Diabetes and aging are known risk factors for impaired neovascularization in response to ischemic insult, resulting in chronic wounds, and poor outcomes following myocardial infarction and cerebrovascular injury. Hypoxia-inducible factor (HIF)-1α, has been identified as a critical regulator of the response to ischemic injury and is dysfunctional in diabetic and elderly patients. To better understand the role of this master hypoxia regulator within cutaneous tissue, the authors generated and evaluated a fibroblast-specific HIF-1α knockout mouse model. The authors generated floxed HIF-1 mice (HIF-1) by introducing loxP sites around exon 1 of the HIF-1 allele in C57BL/6J mice. Fibroblast-restricted HIF-1α knockout (FbKO) mice were generated by breeding our HIF-1 with tamoxifen-inducible Col1a2-Cre mice (Col1a2-CreER). HIF-1α knockout was evaluated on a DNA, RNA, and protein level. Knockout and wild-type mice were subjected to ischemic flap and wound healing models, and CD31 immunohistochemistry was performed to assess vascularity of healed wounds. Quantitative real-time polymerase chain reaction of FbKO skin demonstrated significantly reduced Hif1 and Vegfa expression compared with wild-type. This finding was confirmed at the protein level (p wound closure and vascularity (p wound healing, reduced wound vascularity, and significant impairment in the ischemic neovascular response. These findings provide new insight into the importance of cell-specific responses to hypoxia during cutaneous neovascularization.

  11. One ring to rule them all: trafficking of heme and heme synthesis intermediates in the metazoans.

    Science.gov (United States)

    Hamza, Iqbal; Dailey, Harry A

    2012-09-01

    The appearance of heme, an organic ring surrounding an iron atom, in evolution forever changed the efficiency with which organisms were able to generate energy, utilize gasses and catalyze numerous reactions. Because of this, heme has become a near ubiquitous compound among living organisms. In this review we have attempted to assess the current state of heme synthesis and trafficking with a goal of identifying crucial missing information, and propose hypotheses related to trafficking that may generate discussion and research. The possibilities of spatially organized supramolecular enzyme complexes and organelle structures that facilitate efficient heme synthesis and subsequent trafficking are discussed and evaluated. Recently identified players in heme transport and trafficking are reviewed and placed in an organismal context. Additionally, older, well established data are reexamined in light of more recent studies on cellular organization and data available from newer model organisms. This article is part of a Special Issue entitled: Cell Biology of Metals. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Direction-specific impairment of stability limits and falls in children with developmental coordination disorder: Implications for rehabilitation.

    Science.gov (United States)

    Fong, Shirley S M; Ng, Shamay S M; Chung, Louisa M Y; Ki, W Y; Chow, Lina P Y; Macfarlane, Duncan J

    2016-01-01

    Limit of stability (LOS) is an important yet under-examined postural control ability in children with developmental coordination disorder (DCD). This study aimed to (1) compare the LOS and fall frequencies of children with and without DCD, and (2) explore the relationships between LOS parameters and falls in the DCD population. Thirty primary school-aged children with DCD and twenty age- and sex-matched typically-developing children participated in the study. Postural control ability, specifically LOS in standing, was evaluated using the LOS test. Reaction time, movement velocity, maximum excursion, end point excursion, and directional control were then calculated. Self-reported fall incidents in the previous week were also documented. Multivariate analysis of variance results revealed that children with DCD had shorter LOS maximum excursion in the backward direction compared to the control group (p=0.003). This was associated with a higher number of falls in daily life (rho=-0.556, p=0.001). No significant between-groups differences were found in other LOS-derived outcomes (p>0.05). Children with DCD had direction-specific postural control impairment, specifically, diminished LOS in the backward direction. This is related to their falls in daily life. Therefore, improving LOS should be factored into rehabilitation treatment for children with DCD. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Biosynthesis of heme in immature erythroid cells. The regulatory step for heme formation in the human erythron

    International Nuclear Information System (INIS)

    Gardner, L.C.; Cox, T.M.

    1988-01-01

    Heme formation in reticulocytes from rabbits and rodents is subject to end product negative feedback regulation: intracellular free heme has been shown to control acquisition of transferrin iron for heme synthesis. To identify the site of control of heme biosynthesis in the human erythron, immature erythroid cells were obtained from peripheral blood and aspirated bone marrow. After incubation with human 59Fe transferrin, 2-[14C]glycine, or 4-[14C]delta-aminolevulinate, isotopic incorporation into extracted heme was determined. Addition of cycloheximide to increase endogenous free heme, reduced incorporation of labeled glycine and iron but not delta-aminolevulinate into cell heme. Incorporation of glycine and iron was also sensitive to inhibition by exogenous hematin (Ki, 30 and 45 microM, respectively) i.e. at concentrations in the range which affect cell-free protein synthesis in reticulocyte lysates. Hematin treatment rapidly diminished incorporation of intracellular 59Fe into heme by human erythroid cells but assimilation of 4-[14C]delta-aminolevulinate into heme was insensitive to inhibition by hematin (Ki greater than 100 microM). In human reticulocytes (unlike those from rabbits), addition of ferric salicylaldehyde isonicotinoylhydrazone, to increase the pre-heme iron pool independently of the transferrin cycle, failed to promote heme synthesis or modify feedback inhibition induced by hematin. In human erythroid cells (but not rabbit reticulocytes) pre-incubation with unlabeled delta-aminolevulinate or protoporphyrin IX greatly stimulated utilization of cell 59Fe for heme synthesis and also attenuated end product inhibition. In human erythroid cells heme biosynthesis is thus primarily regulated by feedback inhibition at one or more steps which lead to delta-aminolevulinate formation

  14. Effect of lead on heme synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Neuberger, A.

    1975-01-01

    Recently, a fair amount of work has been done on the effect of lead on porphobilinogen dehydratase, which has been used as a sensitive indicator of lead poisoning. How far this is in itself harmful depends on the Michaelis constants of both the aminolaevulinic synthetase and of the dehydratase, and in addition on the relative activities of the two enzymes in a cell and also on the tissue concentration of glycine. Information on some of these points is still fragmentary, and a reliable judgement is at the present not very easy. Another step in the heme synthesis, which is sensitive to low concentrations of lead, is the incorporation of iron into protoporphyrin. Inhibition of this step may be important in accounting to a large extent for the anaemia found in individuals with lead poisoning. Reduction in the tissue concentration of heme or of heme-like compounds may also explain, through the mechanism of de-repression, the excretion of increased amounts of aminolaevulinic acid in the urine observed in cases of lead poisoning. A third step in heme synthesis, which might be sensitive to lead, is the oxidative decarboxylation of coproporphyrin to protoporphyrin, and this may explain why the former derivative is excreted in the urine. Recent work of the Harvard Medical School has indicated that greatly reduced levels of ALA dehydratase may be found in most cases of severe liver damage due to alcoholism. In most of these cases the level of lead in the blood is within normal limits, and there is no history of exposure to toxic amounts of lead. We therefore have to assume that a reduction in the blood level of this enzyme is not necessarily an indication of lead poisoning.

  15. Circulating gluten-specific FOXP3+CD39+ regulatory T cells have impaired suppressive function in patients with celiac disease.

    Science.gov (United States)

    Cook, Laura; Munier, C Mee Ling; Seddiki, Nabila; van Bockel, David; Ontiveros, Noé; Hardy, Melinda Y; Gillies, Jana K; Levings, Megan K; Reid, Hugh H; Petersen, Jan; Rossjohn, Jamie; Anderson, Robert P; Zaunders, John J; Tye-Din, Jason A; Kelleher, Anthony D

    2017-12-01

    Celiac disease is a chronic immune-mediated inflammatory disorder of the gut triggered by dietary gluten. Although the effector T-cell response in patients with celiac disease has been well characterized, the role of regulatory T (Treg) cells in the loss of tolerance to gluten remains poorly understood. We sought to define whether patients with celiac disease have a dysfunction or lack of gluten-specific forkhead box protein 3 (FOXP3) + Treg cells. Treated patients with celiac disease underwent oral wheat challenge to stimulate recirculation of gluten-specific T cells. Peripheral blood was collected before and after challenge. To comprehensively measure the gluten-specific CD4 + T-cell response, we paired traditional IFN-γ ELISpot with an assay to detect antigen-specific CD4 + T cells that does not rely on tetramers, antigen-stimulated cytokine production, or proliferation but rather on antigen-induced coexpression of CD25 and OX40 (CD134). Numbers of circulating gluten-specific Treg cells and effector T cells both increased significantly after oral wheat challenge, peaking at day 6. Surprisingly, we found that approximately 80% of the ex vivo circulating gluten-specific CD4 + T cells were FOXP3 + CD39 + Treg cells, which reside within the pool of memory CD4 + CD25 + CD127 low CD45RO + Treg cells. Although we observed normal suppressive function in peripheral polyclonal Treg cells from patients with celiac disease, after a short in vitro expansion, the gluten-specific FOXP3 + CD39 + Treg cells exhibited significantly reduced suppressive function compared with polyclonal Treg cells. This study provides the first estimation of FOXP3 + CD39 + Treg cell frequency within circulating gluten-specific CD4 + T cells after oral gluten challenge of patients with celiac disease. FOXP3 + CD39 + Treg cells comprised a major proportion of all circulating gluten-specific CD4 + T cells but had impaired suppressive function, indicating that Treg cell dysfunction might be a key

  16. Heme-based sensors in biological systems.

    Science.gov (United States)

    Rodgers, K R

    1999-04-01

    The past several years have been witness to a staggering rate of advancement in the understanding of how organisms respond to changes in the availability of diatomic molecules that are toxic and/or crucial to survival. Heme-based sensors presently constitute the majority of the proteins known to sense NO, O2 and CO and to initiate the chemistry required to adapt to changes in their availabilities. Knowledge of the three characterized members of this class, soluble guanylate cyclase, FixL and CooA, has grown substantially during the past year. The major advances have resulted from a broad range of approaches to elucidation of both function and mechanism. They include growth in the understanding of the interplay between the heme and protein in soluble guanylate cyclase, as well as alternate means for its stimulation. Insight into the O2-induced structural changes in FixL has been supplied by the single crystal structure of the heme domain of Bradyrhizobium japonicum. Finally, the ligation environment and ligand interchange that facilitates CO sensing by CooA has been established by spectroscopic and mutagenesis techniques.

  17. Role of Heme and Heme-Proteins in Trypanosomatid Essential Metabolic Pathways

    Directory of Open Access Journals (Sweden)

    Karina E. J. Tripodi

    2011-01-01

    Full Text Available Around the world, trypanosomatids are known for being etiological agents of several highly disabling and often fatal diseases like Chagas disease (Trypanosoma cruzi, leishmaniasis (Leishmania spp., and African trypanosomiasis (Trypanosoma brucei. Throughout their life cycle, they must cope with diverse environmental conditions, and the mechanisms involved in these processes are crucial for their survival. In this review, we describe the role of heme in several essential metabolic pathways of these protozoans. Notwithstanding trypanosomatids lack of the complete heme biosynthetic pathway, we focus our discussion in the metabolic role played for important heme-proteins, like cytochromes. Although several genes for different types of cytochromes, involved in mitochondrial respiration, polyunsaturated fatty acid metabolism, and sterol biosynthesis, are annotated at the Tritryp Genome Project, the encoded proteins have not yet been deeply studied. We pointed our attention into relevant aspects of these protein functions that are amenable to be considered for rational design of trypanocidal agents.

  18. Mimicking heme enzymes in the solid state: metal-organic materials with selectively encapsulated heme.

    Science.gov (United States)

    Larsen, Randy W; Wojtas, Lukasz; Perman, Jason; Musselman, Ronald L; Zaworotko, Michael J; Vetromile, Carissa M

    2011-07-13

    To carry out essential life processes, nature has had to evolve heme enzymes capable of synthesizing and manipulating complex molecules. These proteins perform a plethora of chemical reactions utilizing a single iron porphyrin active site embedded within an evolutionarily designed protein pocket. We herein report the first class of metal-organic materials (MOMs) that mimic heme enzymes in terms of both structure and reactivity. The MOMzyme-1 class is based upon a prototypal MOM, HKUST-1, into which catalytically active metalloporphyrins are selectively encapsulated in a "ship-in-a-bottle" fashion within one of the three nanoscale cages that exist in HKUST-1. MOMs offer unparalleled levels of permanent porosity and their modular nature affords enormous diversity of structures and properties. The MOMzyme-1 class could therefore represent a new paradigm for heme biomimetic catalysis since it combines the activity of a homogeneous catalyst with the stability and recyclability of heterogeneous catalytic systems within a single material.

  19. Heme metabolism as an integral part of iron homeostasis

    Directory of Open Access Journals (Sweden)

    Paweł Lipiński

    2014-01-01

    Full Text Available Heme, a ferrous iron protoporphyrin IX complex, is employed as a prosthetic group in a number of diverse heme proteins that participate in important cellular and systemic physiological processes. Provision of an adequate amount of iron for heme biosynthesis is one of the elemental hallmarks of intracellular iron homeostasis. In the cell the bioavailability of iron for the two main iron biological pathways – heme synthesis and the biogenesis of iron-sulfur clusters ([Fe-S] – is mainly regulated by the IRP/IRE posttranscriptional system. The biogenesis of [Fe-S] centers is crucial for heme synthesis because these co-factors determine the activity of IRP1 and that of ferrochelatase, an enzyme responsible for the insertion of an iron into protoporphyrin IX to produce heme. On the other hand, delivery of iron for heme and hemoglobin synthesis in erythroblasts, precursors of erythrocytes in bone marrow, is an indispensable element of body iron homeostasis. This process relies on the recovery of iron from senescent red blood cells through the enzymatic degradation of heme molecules and recycling of iron to the circulation. Molecular coordination of these processes involves the activity of heme oxygenase 1, IRP1 and IRP2 as well as the functioning of the hepcidin-ferroportin regulatory axis. Recent studies show in mammals the existence of an expanded system of proteins involved in the transport of intact heme molecules at the cellular and systemic levels. The biological role of this system is of particular importance when the concentration of free heme reaches a toxic level in the body (intravascular hemolysis as well as locally in cells having intensive heme metabolism such as erythroblasts and macrophages.

  20. [Heme metabolism as an integral part of iron homeostasis].

    Science.gov (United States)

    Lipiński, Paweł; Starzyński, Rafał R; Styś, Agnieszka; Gajowiak, Anna; Staroń, Robert

    2014-01-02

    Heme, a ferrous iron protoporphyrin IX complex, is employed as a prosthetic group in a number of diverse heme proteins that participate in important cellular and systemic physiological processes. Provision of an adequate amount of iron for heme biosynthesis is one of the elemental hallmarks of intracellular iron homeostasis. In the cell the bioavailability of iron for the two main iron biological pathways--heme synthesis and the biogenesis of iron-sulfur clusters ([Fe-S])--is mainly regulated by the IRP/IRE posttranscriptional system. The biogenesis of [Fe-S] centers is crucial for heme synthesis because these co-factors determine the activity of IRP1 and that of ferrochelatase, an enzyme responsible for the insertion of an iron into protoporphyrin IX to produce heme. On the other hand, delivery of iron for heme and hemoglobin synthesis in erythroblasts, precursors of erythrocytes in bone marrow, is an indispensable element of body iron homeostasis. This process relies on the recovery of iron from senescent red blood cells through the enzymatic degradation of heme molecules and recycling of iron to the circulation. Molecular coordination of these processes involves the activity of heme oxygenase 1, IRP1 and IRP2 as well as the functioning of the hepcidin-ferroportin regulatory axis. Recent studies show in mammals the existence of an expanded system of proteins involved in the transport of intact heme molecules at the cellular and systemic levels. The biological role of this system is of particular importance when the concentration of free heme reaches a toxic level in the body (intravascular hemolysis) as well as locally in cells having intensive heme metabolism such as erythroblasts and macrophages.

  1. Social Communication Disorder outside Autism? A Diagnostic Classification Approach to Delineating Pragmatic Language Impairment, High Functioning Autism and Specific Language Impairment

    Science.gov (United States)

    Gibson, Jenny; Adams, Catherine; Lockton, Elaine; Green, Jonathan

    2013-01-01

    Background: Developmental disorders of language and communication present considerable diagnostic challenges due to overlapping of symptomatology and uncertain aetiology. We aimed to further elucidate the behavioural and linguistic profile associated with impairments of social communication occurring outside of an autism diagnosis. Methods: Six to…

  2. Quality of life and adjustment in children and adolescents with Moebius syndrome: Evidence for specific impairments in social functioning.

    Science.gov (United States)

    Strobel, Linda; Renner, Gerolf

    2016-01-01

    Moebius syndrome is a rare congenital disorder characterized by congenital facial paralysis and impairment of ocular abduction. The absence of facial expression in people with Moebius syndrome may impair social interaction. The present study aims at replicating prior findings on psychological adjustment in children and adolescents with Moebius syndrome and providing first data on quality of life. Parents (n=26) and children and adolescents (n=14) with Moebius-Syndrome completed the KINDL(R) (Questionnaire for Measuring Health-Related Quality of Life in Children and Adolescents), the SDQ (Strengths and Difficulties Questionnaire), and a newly devised questionnaire on the global, social, and emotional impact of Moebius syndrome, including a scale that addressed what conjectures were made concerning the thoughts of other people about a child with Moebius syndrome. In comparison with normative data, quality of life was reduced for the subscale Friends (large effect for both parental ratings and self-report) and the Total Score of the KINDL(R). Parents reported elevated levels of peer problems on the respective subscale of the SDQ. In SDQ self-report data, cases classified as abnormal were observed on Peer Problems only. Moebius-specific scales showed adequate reliabilities, and were related, most notably for parent-report, to quality of life. 29% of children reported feelings of anger when being stared at, and wished that they were not affected by Moebius syndrome. Although most children and adolescents in our sample did not show behavioral problems or reduced quality of life, our results indicate that their emotional and social development should be closely monitored. Maintaining satisfying peer relationships seems to be a special challenge for children and adolescents with Moebius syndrome. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Core subjects at the end of primary school: identifying and explaining relative strengths of children with specific language impairment (SLI)

    Science.gov (United States)

    Durkin, Kevin; Mok, Pearl L H; Conti-Ramsden, Gina

    2015-01-01

    Background In general, children with specific language impairment (SLI) tend to fall behind their typically developing (TD) peers in educational attainment. Less is known about how children with SLI fare in particular areas of the curriculum and what predicts their levels of performance. Aims To compare the distributions of performance of children with SLI in three core school subjects (English, Mathematics and Science); to test the possibility that performance would vary across the core subjects; and to examine the extent to which language impairment predicts performance. Methods & Procedures This study was conducted in England and reports historical data on educational attainments. Teacher assessment and test scores of 176 eleven-year-old children with SLI were examined in the three core subjects and compared with known national norms. Possible predictors of performance were measured, including language ability at ages 7 and 11, educational placement type, and performance IQ. Outcomes & Results Children with SLI, compared with national norms, were found to be at a disadvantage in core school subjects. Nevertheless, some children attained the levels expected of TD peers. Performance was poorest in English; relative strengths were indicated in Science and, to a lesser extent, in Mathematics. Language skills were significant predictors of performance in all three core subjects. PIQ was the strongest predictor for Mathematics. For Science, both early language skills at 7 years and PIQ made significant contributions. Conclusions & Implications Language impacts on the school performance of children with SLI, but differentially across subjects. English for these children is the most challenging of the core subjects, reflecting the high levels of language demand it incurs. Science is an area of relative strength and mathematics appears to be intermediate, arguably because some tasks in these subjects can be performed with less reliance on verbal processing. Many children

  4. Moessbauer spectroscopic study of polymer-bound heme complexes

    International Nuclear Information System (INIS)

    Tsuchida, Eishun; Nishide, Hiroyuki; Yokoyama, Hiroyuki; Inoue, Hidenari; Shirai, Tsuneo.

    1984-01-01

    Moessbauer spectra were measured on the heme complexes of poly(1-vinyl- and 1-vinyl-2-methylimidazole)(PVI and PMI) and heme derivatives with covalently bound imidazoleligand (IH) and 2-methylimidazole-ligand (MIH) embedded in poly(1-vinyl-2-pyrrolidone) film. Quadrupole splitting (ΔE sub(Q)) for the carbon monoxide adduct of PMI-heme indicated large electronic field gradient at the iron nucleus, probably due to steric hindrance of the polymer chain, and this behavior agreed with its low affinity with carbon monoxide. PMI-heme formed an oxygen adduct and its isomer shift and ΔE sub(Q) values were obtained. (author)

  5. Gas-phase spectroscopy of ferric heme-NO complexes

    DEFF Research Database (Denmark)

    Wyer, J.A.; Jørgensen, Anders; Pedersen, Bjarke

    2013-01-01

    and significantly blue-shifted compared to ferric heme nitrosyl proteins (maxima between 408 and 422 nm). This is in stark contrast to the Q-band absorption where the protein microenvironment is nearly innocent in perturbing the electronic structure of the porphyrin macrocycle. Photodissociation is primarily...... maxima of heme and its complexes with amino acids and NO. Not so innocent: Weakly bound complexes between ferric heme and NO were synthesised in the gas phase, and their absorption measured from photodissociation yields. Opposite absorption trends in the Soret-band are seen upon NO addition to heme ions...

  6. The relationship between mathematics and language: academic implications for children with specific language impairment and English language learners.

    Science.gov (United States)

    Alt, Mary; Arizmendi, Genesis D; Beal, Carole R

    2014-07-01

    The present study examined the relationship between mathematics and language to better understand the nature of the deficit and the academic implications associated with specific language impairment (SLI) and academic implications for English language learners (ELLs). School-age children (N = 61; 20 SLI, 20 ELL, 21 native monolingual English [NE]) were assessed using a norm-referenced mathematics instrument and 3 experimental computer-based mathematics games that varied in language demands. Group means were compared with analyses of variance. The ELL group was less accurate than the NE group only when tasks were language heavy. In contrast, the group with SLI was less accurate than the groups with NE and ELLs on language-heavy tasks and some language-light tasks. Specifically, the group with SLI was less accurate on tasks that involved comparing numerical symbols and using visual working memory for patterns. However, there were no group differences between children with SLI and peers without SLI on language-light mathematics tasks that involved visual working memory for numerical symbols. Mathematical difficulties of children who are ELLs appear to be related to the language demands of mathematics tasks. In contrast, children with SLI appear to have difficulty with mathematics tasks because of linguistic as well as nonlinguistic processing constraints.

  7. Don't speak too fast! Processing of fast rate speech in children with specific language impairment.

    Directory of Open Access Journals (Sweden)

    Hélène Guiraud

    Full Text Available Perception of speech rhythm requires the auditory system to track temporal envelope fluctuations, which carry syllabic and stress information. Reduced sensitivity to rhythmic acoustic cues has been evidenced in children with Specific Language Impairment (SLI, impeding syllabic parsing and speech decoding. Our study investigated whether these children experience specific difficulties processing fast rate speech as compared with typically developing (TD children.Sixteen French children with SLI (8-13 years old with mainly expressive phonological disorders and with preserved comprehension and 16 age-matched TD children performed a judgment task on sentences produced 1 at normal rate, 2 at fast rate or 3 time-compressed. Sensitivity index (d' to semantically incongruent sentence-final words was measured.Overall children with SLI perform significantly worse than TD children. Importantly, as revealed by the significant Group × Speech Rate interaction, children with SLI find it more challenging than TD children to process both naturally or artificially accelerated speech. The two groups do not significantly differ in normal rate speech processing.In agreement with rhythm-processing deficits in atypical language development, our results suggest that children with SLI face difficulties adjusting to rapid speech rate. These findings are interpreted in light of temporal sampling and prosodic phrasing frameworks and of oscillatory mechanisms underlying speech perception.

  8. Don't speak too fast! Processing of fast rate speech in children with specific language impairment.

    Science.gov (United States)

    Guiraud, Hélène; Bedoin, Nathalie; Krifi-Papoz, Sonia; Herbillon, Vania; Caillot-Bascoul, Aurélia; Gonzalez-Monge, Sibylle; Boulenger, Véronique

    2018-01-01

    Perception of speech rhythm requires the auditory system to track temporal envelope fluctuations, which carry syllabic and stress information. Reduced sensitivity to rhythmic acoustic cues has been evidenced in children with Specific Language Impairment (SLI), impeding syllabic parsing and speech decoding. Our study investigated whether these children experience specific difficulties processing fast rate speech as compared with typically developing (TD) children. Sixteen French children with SLI (8-13 years old) with mainly expressive phonological disorders and with preserved comprehension and 16 age-matched TD children performed a judgment task on sentences produced 1) at normal rate, 2) at fast rate or 3) time-compressed. Sensitivity index (d') to semantically incongruent sentence-final words was measured. Overall children with SLI perform significantly worse than TD children. Importantly, as revealed by the significant Group × Speech Rate interaction, children with SLI find it more challenging than TD children to process both naturally or artificially accelerated speech. The two groups do not significantly differ in normal rate speech processing. In agreement with rhythm-processing deficits in atypical language development, our results suggest that children with SLI face difficulties adjusting to rapid speech rate. These findings are interpreted in light of temporal sampling and prosodic phrasing frameworks and of oscillatory mechanisms underlying speech perception.

  9. Interaction between Mitochondrial Reactive Oxygen Species, Heme Oxygenase, and Nitric Oxide Synthase Stimulates Phagocytosis in Macrophages

    Directory of Open Access Journals (Sweden)

    Andrea Müllebner

    2018-01-01

    Full Text Available BackgroundMacrophages are cells of the innate immune system that populate every organ. They are required not only for defense against invading pathogens and tissue repair but also for maintenance of tissue homeostasis and iron homeostasis.AimThe aim of this study is to understand whether heme oxygenase (HO and nitric oxide synthase (NOS contribute to the regulation of nicotinamide adenine dinucleotide phosphate oxidase (NOX activity and phagocytosis, two key components of macrophage function.MethodsThis study was carried out using resting J774A.1 macrophages treated with hemin or vehicle. Activity of NOS, HO, or NOX was inhibited using specific inhibitors. Reactive oxygen species (ROS formation was determined by Amplex® red assay, and phagocytosis was measured using fluorescein isothiocyanate-labeled bacteria. In addition, we analyzed the fate of the intracellular heme by using electron spin resonance.ResultsWe show that both enzymes NOS and HO are essential for phagocytic activity of macrophages. NOS does not directly affect phagocytosis, but stimulates NOX activity via nitric oxide-triggered ROS production of mitochondria. Treatment of macrophages with hemin results in intracellular accumulation of ferrous heme and an inhibition of phagocytosis. In contrast to NOS, HO products, including carbon monoxide, neither clearly affect NOX activity nor clearly affect phagocytosis, but phagocytosis is accelerated by HO-mediated degradation of heme.ConclusionBoth enzymes contribute to the bactericidal activity of macrophages independently, by controlling different pathways.

  10. Structural characterization of human heme oxygenase-1 in complex with azole-based inhibitors.

    Science.gov (United States)

    Rahman, Mona N; Vlahakis, Jason Z; Roman, Gheorghe; Vukomanovic, Dragic; Szarek, Walter A; Nakatsu, Kanji; Jia, Zongchao

    2010-03-01

    The development of inhibitors specific for heme oxygenases (HO) aims to provide powerful tools in understanding the HO system. Based on the lead structure (2S, 4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[((4-aminophenyl)thio)methyl]-1,3-dioxolane (azalanstat, QC-1) we have synthesized structural modifications to develop novel and selective HO inhibitors. The structural study of human HO-1 (hHO-1) in complex with a select group of the inhibitors was initiated using X-ray crystallographic techniques. Comparison of the structures of four such compounds each in complex with hHO-1 revealed a common binding mode, despite having different structural fragments. The compounds bind to the distal side of heme through an azole "anchor" which coordinates with the heme iron. An expansion of the distal pocket, mainly due to distal helix flexibility, allows accommodation of the compounds without displacing heme or the critical Asp140 residue. Rather, binding displaces a catalytically critical water molecule and disrupts an ordered hydrogen-bond network involving Asp140. The presence of a triazole "anchor" may provide further stability via a hydrogen bond with the protein. A hydrophobic pocket acts to stabilize the region occupied by the phenyl or adamantanyl moieties of these compounds. Further, a secondary hydrophobic pocket is formed via "induced fit" to accommodate bulky substituents at the 4-position of the dioxolane ring. Copyright 2009 Elsevier Inc. All rights reserved.

  11. Impact of visual impairment on vision-specific quality of life among older adults living in nursing home.

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    Dev, Mahesh Kumar; Paudel, Nabin; Joshi, Niraj Dev; Shah, Dev Narayan; Subba, Shishir

    2014-03-01

    Visual impairment (VI) has a significant negative impact on quality of life (QoL) amongst older people living in nursing homes. The purpose of this study was to determine the prevalence of VI and blindness and to explore the association between severity of VI and vision-specific QoL among older people living in nursing homes of Kathmandu, Nepal. This cross-sectional study involved 158 residents aged 60 years or older residing in seven nursing homes of Kathmandu Valley, Nepal. Near acuity, presenting and the best corrected distance visual acuity (VA) were assessed in each eye and considered in the better eye after adequate refraction. A complete anterior and posterior segment examination was carried out. Face-to-face interviews were conducted using a 57-item Nursing Home Vision-Targeted Health-Related Quality of Life (NHVQoL) questionnaire. The mean age of residents was 75.60 ± 7.12 years and the majority were female (66.46%). The prevalence of VI and blindness was 45.57% and its leading cause was cataract, which was followed by age-related macular degeneration, corneal opacity, glaucoma and macular scar. The mean composite score of NHVQoL questionnaire was 52.22 ± 12.49. There was a consistent overall deterioration in the mean composite score as well as each subscale score of NHVQoL questionnaire with a worsening of VA. VI and blindness are highly prevalent among older people living in nursing homes. VI has a significant negative impact on vision-specific QoL. Vision-specific QoL is reduced, and the reduction in the QoL bears a positive association with severity of VI among older people living in nursing homes.

  12. Impaired Autophagy and Defective T Cell Homeostasis in Mice with T Cell-Specific Deletion of Receptor for Activated C Kinase 1

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    Guihua Qiu

    2017-05-01

    Full Text Available Autophagy plays a central role in maintaining T cell homeostasis. Our previous study has shown that hepatocyte-specific deficiency of receptor for activated C kinase 1 (RACK1 leads to lipid accumulation in the liver, accompanied by impaired autophagy, but its in vivo role in T cells remains unclear. Here, we report that mice with T cell-specific deletion of RACK1 exhibit normal intrathymic development of conventional T cells and regulatory T (Treg cells but reduced numbers of peripheral CD4+ and CD8+ T cells. Such defects are cell intrinsic with impaired mitochondrial clearance, increased sensitivity to cell death, and decreased proliferation that could be explained by impaired autophagy. Furthermore, RACK1 is essential for invariant natural T cell development. In vivo, T cell-specific loss of RACK1 dampens concanavalin A-induced acute liver injury. Our data suggest that RACK1 is a key regulator of T cell homeostasis.

  13. Heme Recognition By a Staphylococcus Aureus IsdE

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    Grigg, J.C.; Vermeiren, C.L.; Heinrichs, D.E.; Murphy, M.E.P.

    2009-06-03

    Staphylococcus aureus is a Gram-positive bacterial pathogen and a leading cause of hospital acquired infections. Because the free iron concentration in the human body is too low to support growth, S. aureus must acquire iron from host sources. Heme iron is the most prevalent iron reservoir in the human body and a predominant source of iron for S. aureus. The iron-regulated surface determinant (Isd) system removes heme from host heme proteins and transfers it to IsdE, the cognate substrate-binding lipoprotein of an ATP-binding cassette transporter, for import and subsequent degradation. Herein, we report the crystal structure of the soluble portion of the IsdE lipoprotein in complex with heme. The structure reveals a bi-lobed topology formed by an N- and C-terminal domain bridged by a single {alpha}-helix. The structure places IsdE as a member of the helical backbone metal receptor superfamily. A six-coordinate heme molecule is bound in the groove established at the domain interface, and the heme iron is coordinated in a novel fashion for heme transporters by Met{sup 78} and His{sup 229}. Both heme propionate groups are secured by H-bonds to IsdE main chain and side chain groups. Of these residues, His{sup 299} is essential for IsdE-mediated heme uptake by S. aureus when growth on heme as a sole iron source is measured. Multiple sequence alignments of homologues from several other Gram-positive bacteria, including the human pathogens pyogenes, Bacillus anthracis, and Listeria monocytogenes, suggest that these other systems function equivalently to S. aureus IsdE with respect to heme binding and transport.

  14. Diamond Blackfan Anemia at the Crossroad between Ribosome Biogenesis and Heme Metabolism

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    Deborah Chiabrando

    2010-01-01

    Full Text Available Diamond-Blackfan anemia (DBA is a rare, pure red-cell aplasia that presents during infancy. Approximately 40% of cases are associated with other congenital defects, particularly malformations of the upper limb or craniofacial region. Mutations in the gene coding for the ribosomal protein RPS19 have been identified in 25% of patients with DBA, with resulting impairment of 18S rRNA processing and 40S ribosomal subunit formation. Moreover, mutations in other ribosomal protein coding genes account for about 25% of other DBA cases. Recently, the analysis of mice from which the gene coding for the heme exporter Feline Leukemia Virus subgroup C Receptor (FLVCR1 is deleted suggested that this gene may be involved in the pathogenesis of DBA. FLVCR1-null mice show a phenotype resembling that of DBA patients, including erythroid failure and malformations. Interestingly, some DBA patients have disease linkage to chromosome 1q31, where FLVCR1 is mapped. Moreover, it has been reported that cells from DBA patients express alternatively spliced isoforms of FLVCR1 which encode non-functional proteins. Herein, we review the known roles of RPS19 and FLVCR1 in ribosome function and heme metabolism respectively, and discuss how the deficiency of a ribosomal protein or of a heme exporter may result in the same phenotype.

  15. Mirror-drawing skill in children with specific language impairment: Improving generalization by incorporating variability into the practice session.

    Science.gov (United States)

    Desmottes, Lise; Maillart, Christelle; Meulemans, Thierry

    2017-05-01

    This study aimed to investigate the procedural deficit hypothesis (PDH) in children with specific language impairment (SLI) by using a mirror-drawing task, a sensorimotor adaptation paradigm that does not involve sequence learning and has never before been used in SLI. A total of 30 school-aged children with SLI matched to 30 typically developing (TD) control children had to trace several figures seen only in mirror-reversed view in two practice sessions separated by a one-week interval. Two practice conditions were compared: a constant condition in which children had to trace the same figure throughout the learning trials, and a variable one in which they had to trace different figures in each trial. The results revealed a similar learning pattern between SLI and TD children in both practice conditions, suggesting that initial learning for a non-sequential procedural task is preserved in SLI. However, the children with SLI generalized the mirror-drawing skill in the same way as the TD children only if there was variability in the way the material was trained (variable practice). No significant schedule effects were observed in the control group.

  16. Adolescents with a history of specific language impairment (SLI): strengths and difficulties in social, emotional and behavioral functioning.

    Science.gov (United States)

    Conti-Ramsden, Gina; Mok, Pearl L H; Pickles, Andrew; Durkin, Kevin

    2013-11-01

    Adolescents with specific language impairment (SLI) are at a greater risk of emotional and behavioral problems compared to their typically developing (TD) peers, but little is known about their self-perceived strengths and difficulties. In this study, the self-reported social, emotional and behavioral functioning of 139 adolescents with a history of SLI and 124 TD individuals at age 16 was examined. The self-report version of the Strengths and Difficulties Questionnaire (SDQ) was used to assess their prosocial behavior and levels of peer, emotional and behavioral difficulties. Associations of these areas of functioning with gender, verbal and non-verbal skills were also investigated. Adolescents with a history of SLI were more likely than their TD peers to report higher levels of peer problems, emotional symptoms, hyperactivity and conduct problems. The majority of adolescents in both groups (87% SLI and 96% TD), however, reported prosocial behavior within the typical range. Difficulty with peer relations was the strongest differentiator between the groups, with the odds of reporting borderline or abnormally high levels of peer problems being 12 times higher for individuals with a history of SLI. Adolescents with poorer receptive language skills were also more likely to report higher levels of emotional and behavioral difficulties. The findings of this study identify likely traits that may lead to referral to services. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Acoustic correlates of inflectional morphology in the speech of children with specific language impairment and their typically developing peers.

    Science.gov (United States)

    Owen, Amanda J; Goffman, Lisa

    2007-07-01

    The development of the use of the third-person singular -s in open syllable verbs in children with specific language impairment (SLI) and their typically developing peers was examined. Verbs that included overt productions of the third-person singular -s morpheme (e.g. Bobby plays ball everyday; Bear laughs when mommy buys popcorn) were contrasted with clearly bare stem contexts (e.g. Mommy, buy popcorn; I saw Bobby play ball) on both global and local measures of acoustic duration. A durational signature for verbs inflected with -s was identified separately from factors related to sentence length. These duration measures were also used to identify acoustic changes related to the omission of the -s morpheme. The omitted productions from the children with SLI were significantly longer than their correct third-person singular and bare stem productions. This result was unexpected given that the omitted productions have fewer phonemes than correctly inflected productions. Typically developing children did not show the same pattern, instead producing omitted productions that patterned most closely with bare stem forms. These results are discussed in relation to current theoretical approaches to SLI, with an emphasis on performance and speech-motor accounts.

  18. Sequential Prediction of Literacy Achievement for Specific Learning Disabilities Contrasting in Impaired Levels of Language in Grades 4 to 9.

    Science.gov (United States)

    Sanders, Elizabeth A; Berninger, Virginia W; Abbott, Robert D

    Sequential regression was used to evaluate whether language-related working memory components uniquely predict reading and writing achievement beyond cognitive-linguistic translation for students in Grades 4 through 9 ( N = 103) with specific learning disabilities (SLDs) in subword handwriting (dysgraphia, n = 25), word reading and spelling (dyslexia, n = 60), or oral and written language (oral and written language learning disabilities, n = 18). That is, SLDs are defined on the basis of cascading level of language impairment (subword, word, and syntax/text). A five-block regression model sequentially predicted literacy achievement from cognitive-linguistic translation (Block 1); working memory components for word-form coding (Block 2), phonological and orthographic loops (Block 3), and supervisory focused or switching attention (Block 4); and SLD groups (Block 5). Results showed that cognitive-linguistic translation explained an average of 27% and 15% of the variance in reading and writing achievement, respectively, but working memory components explained an additional 39% and 27% of variance. Orthographic word-form coding uniquely predicted nearly every measure, whereas attention switching uniquely predicted only reading. Finally, differences in reading and writing persisted between dyslexia and dysgraphia, with dysgraphia higher, even after controlling for Block 1 to 4 predictors. Differences in literacy achievement between students with dyslexia and oral and written language learning disabilities were largely explained by the Block 1 predictors. Applications to identifying and teaching students with these SLDs are discussed.

  19. The effect of spatio-temporal distance between visual stimuli on information processing in children with Specific Language Impairment.

    Science.gov (United States)

    Dispaldro, Marco; Corradi, Nicola

    2015-01-01

    The purpose of this study is to evaluate whether children with Specific Language Impairment (SLI) have a deficit in processing a sequence of two visual stimuli (S1 and S2) presented at different inter-stimulus intervals and in different spatial locations. In particular, the core of this study is to investigate whether S1 identification is disrupted due to a retroactive interference of S2. To this aim, two experiments were planned in which children with SLI and children with typical development (TD), matched by age and non-verbal IQ, were compared (Experiment 1: SLI n=19; TD n=19; Experiment 2: SLI n=16; TD n=16). Results show group differences in the ability to identify a single stimulus surrounded by flankers (Baseline level). Moreover, children with SLI show a stronger negative interference of S2, both for temporal and spatial modulation. These results are discussed in the light of an attentional processing limitation in children with SLI. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Perception of audio-visual speech synchrony in Spanish-speaking children with and without specific language impairment.

    Science.gov (United States)

    Pons, Ferran; Andreu, Llorenç; Sanz-Torrent, Monica; Buil-Legaz, Lucía; Lewkowicz, David J

    2013-06-01

    Speech perception involves the integration of auditory and visual articulatory information, and thus requires the perception of temporal synchrony between this information. There is evidence that children with specific language impairment (SLI) have difficulty with auditory speech perception but it is not known if this is also true for the integration of auditory and visual speech. Twenty Spanish-speaking children with SLI, twenty typically developing age-matched Spanish-speaking children, and twenty Spanish-speaking children matched for MLU-w participated in an eye-tracking study to investigate the perception of audiovisual speech synchrony. Results revealed that children with typical language development perceived an audiovisual asynchrony of 666 ms regardless of whether the auditory or visual speech attribute led the other one. Children with SLI only detected the 666 ms asynchrony when the auditory component preceded [corrected] the visual component. None of the groups perceived an audiovisual asynchrony of 366 ms. These results suggest that the difficulty of speech processing by children with SLI would also involve difficulties in integrating auditory and visual aspects of speech perception.

  1. Heme oxygenase-1, oxidation, inflammation and atherosclerosis

    Directory of Open Access Journals (Sweden)

    Jesus A Araujo

    2012-07-01

    Full Text Available Atherosclerosis is an inflammatory process of the vascular wall characterized by the infiltration of lipids and inflammatory cells. Oxidative modifications of infiltrating low density lipoproteins and induction of oxidative stress play a major role in lipid retention in the vascular wall, uptake by macrophages and generation of foam cells, a hallmark of this disorder. The vasculature has a plethora of protective resources against oxidation and inflammation, many of them regulated by the Nrf2 transcription factor. Heme oxygenase-1 (HO-1 is a Nrf2-regulated gene that plays a critical role in the prevention of vascular inflammation. It is the inducible isoform of heme oxygenase, responsible for the oxidative cleavage of heme groups leading to the generation of biliverdin, carbon monoxide and release of ferrous iron. HO-1 has important antioxidant, antiinflammatory, antiapoptotic, antiproliferative and immunomodulatory effects in vascular cells, most of which play a significant role in the protection against atherogenesis. HO-1 may also be an important feature in macrophage differentiation and polarization to certain subtypes. The biological effects of HO-1 are largely attributable to its enzymatic activity, which can be conceived as a system with three arms of action, corresponding to its three enzymatic byproducts. HO-1 mediated vascular protection may be due to a combination of systemic and vascular local effects. It is usually expressed at low levels but can be highly upregulated in the presence of several proatherogenic stimuli. The HO-1 system is amenable for use in the development of new therapies, some of them currently under experimental and clinical trials. Interestingly, in contrast to the HO-1 antiatherogenic actions, the expression of its transcriptional regulator Nrf2 leads to proatherogenic effects instead. This article reviews the evidence that supports the antiatherogenic role of HO-1, potential pathways and mechanisms mediating

  2. Heme as a danger molecule in pathogen recognition.

    Science.gov (United States)

    Wegiel, Barbara; Hauser, Carl J; Otterbein, Leo E

    2015-12-01

    Appropriate control of redox mechanisms are critical for and effective innate immune response, which employs multiple cell types, receptors and molecules that recognize danger signals when they reach the host. Recognition of pathogen-associated pattern molecules (PAMPs) is a fundamental host survival mechanism for efficient elimination of invading pathogens and resolution of the infection and inflammation. In addition to PAMPs, eukaryotic cells contain a plethora of intracellular molecules that are normally secured within the confines of the plasma membrane, but if liberated and encountered in the extracellular milieu can provoke rapid cell activation. These are known as Alarmins or Danger-Associated Molecular Patterns (DAMPs) and can be released actively by cells or passively as a result of sterile cellular injury after trauma, ischemia, or toxin-induced cell rupture. Both PAMPs and DAMPs are recognized by a series of cognate receptors that increase the generation of free radicals and activate specific signaling pathways that result in regulation of a variety of stress response, redox sensitive genes. Multiple mediators released, as cells die include, but are not limited to ATP, hydrogen peroxide, heme, formyl peptides, DNA or mitochondria provide the second signal to amplify immune responses. In this review, we will focus on how sterile and infective stimuli activate the stress response gene heme oxygenase-1 (Hmox1, HO-1), a master gene critical to an appropriate host response that is now recognized as one with enormous therapeutic potential. HO-1 gene expression is regulated in large part by redox-sensitive proteins including but not limited to nrf2. Both PAMPs and DAMPs increase the activation of nrf2 and HO-1. Heme is a powerful pro-oxidant and as such should be qualified as a DAMP. With its degradation by HO-1a molecule of carbon monoxide (CO) is generated that in turn serves as a bioactive signaling molecule. PAMPs such as bacterial endotoxin activate HO-1

  3. Dietary heme-mediated PPARα activation does not affect the heme-induced epithelial hyperproliferation and hyperplasia in mouse colon.

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    Noortje Ijssennagger

    Full Text Available Red meat consumption is associated with an increased colon cancer risk. Heme, present in red meat, injures the colon surface epithelium by luminal cytotoxicity and reactive oxygen species. This surface injury is overcompensated by hyperproliferation and hyperplasia of crypt cells. Transcriptome analysis of mucosa of heme-fed mice showed, besides stress- and proliferation-related genes, many upregulated lipid metabolism-related PPARα target genes. The aim of this study was to investigate the role of PPARα in heme-induced hyperproliferation and hyperplasia. Male PPARα KO and WT mice received a purified diet with or without heme. As PPARα is proposed to protect against oxidative stress and lipid peroxidation, we hypothesized that the absence of PPARα leads to more surface injury and crypt hyperproliferation in the colon upon heme-feeding. Heme induced luminal cytotoxicity and lipid peroxidation and colonic hyperproliferation and hyperplasia to the same extent in WT and KO mice. Transcriptome analysis of colonic mucosa confirmed similar heme-induced hyperproliferation in WT and KO mice. Stainings for alkaline phosphatase activity and expression levels of Vanin-1 and Nrf2-targets indicated a compromised antioxidant defense in heme-fed KO mice. Our results suggest that the protective role of PPARα in antioxidant defense involves the Nrf2-inhibitor Fosl1, which is upregulated by heme in PPARα KO mice. We conclude that PPARα plays a protective role in colon against oxidative stress, but PPARα does not mediate heme-induced hyperproliferation. This implies that oxidative stress of surface cells is not the main determinant of heme-induced hyperproliferation and hyperplasia.

  4. Core subjects at the end of primary school: identifying and explaining relative strengths of children with specific language impairment (SLI).

    Science.gov (United States)

    Durkin, Kevin; Mok, Pearl L H; Conti-Ramsden, Gina

    2015-01-01

    In general, children with specific language impairment (SLI) tend to fall behind their typically developing (TD) peers in educational attainment. Less is known about how children with SLI fare in particular areas of the curriculum and what predicts their levels of performance. To compare the distributions of performance of children with SLI in three core school subjects (English, Mathematics and Science); to test the possibility that performance would vary across the core subjects; and to examine the extent to which language impairment predicts performance. This study was conducted in England and reports historical data on educational attainments. Teacher assessment and test scores of 176 eleven-year-old children with SLI were examined in the three core subjects and compared with known national norms. Possible predictors of performance were measured, including language ability at ages 7 and 11, educational placement type, and performance IQ. Children with SLI, compared with national norms, were found to be at a disadvantage in core school subjects. Nevertheless, some children attained the levels expected of TD peers. Performance was poorest in English; relative strengths were indicated in Science and, to a lesser extent, in Mathematics. Language skills were significant predictors of performance in all three core subjects. PIQ was the strongest predictor for Mathematics. For Science, both early language skills at 7 years and PIQ made significant contributions. Language impacts on the school performance of children with SLI, but differentially across subjects. English for these children is the most challenging of the core subjects, reflecting the high levels of language demand it incurs. Science is an area of relative strength and mathematics appears to be intermediate, arguably because some tasks in these subjects can be performed with less reliance on verbal processing. Many children with SLI do have the potential to reach or exceed educational targets that are set

  5. Early preschool processing abilities predict subsequent reading outcomes in bilingual Spanish-Catalan children with Specific Language Impairment (SLI).

    Science.gov (United States)

    Aguilar-Mediavilla, Eva; Buil-Legaz, Lucía; Pérez-Castelló, Josep A; Rigo-Carratalà, Eduard; Adrover-Roig, Daniel

    2014-01-01

    Children with Specific Language Impairment (SLI) have severe language difficulties without showing hearing impairments, cognitive deficits, neurological damage or socio-emotional deprivation. However, previous studies have shown that children with SLI show some cognitive and literacy problems. Our study analyses the relationship between preschool cognitive and linguistic abilities and the later development of reading abilities in Spanish-Catalan bilingual children with SLI. The sample consisted of 17 bilingual Spanish-Catalan children with SLI and 17 age-matched controls. We tested eight distinct processes related to phonological, attention, and language processing at the age of 6 years and reading at 8 years of age. Results show that bilingual Spanish-Catalan children with SLI show significantly lower scores, as compared to typically developing peers, in phonological awareness, phonological memory, and rapid automatized naming (RAN), together with a lower outcome in tasks measuring sentence repetition and verbal fluency. Regarding attentional processes, bilingual Spanish-Catalan children with SLI obtained lower scores in auditory attention, but not in visual attention. At the age of 8 years Spanish-Catalan children with SLI had lower scores than their age-matched controls in total reading score, letter identification (decoding), and in semantic task (comprehension). Regression analyses identified both phonological awareness and verbal fluency at the age of 6 years to be the best predictors of subsequent reading performance at the age of 8 years. Our data suggest that language acquisition problems and difficulties in reading acquisition in bilingual children with SLI might be related to the close interdependence between a limitation in cognitive processing and a deficit at the linguistic level. After reading this article, readers will be able to: identify their understanding of the relation between language difficulties and reading outcomes; explain how processing

  6. Role of heme in bromine-induced lung injury

    Science.gov (United States)

    Lam, Adam; Vetal, Nilam; Matalon, Sadis; Aggarwal, Saurabh

    2016-01-01

    Bromine (Br2) gas inhalation poses an environmental and occupational hazard resulting in high morbidity and mortality. In this review, we underline the acute lung pathology (within 24 hours of exposure) and potential therapeutic interventions that may be utilized to mitigate Br2-induced human toxicity. We will discuss our latest published data, which suggests that an increase in heme-dependent tissue injury underlies the pathogenesis of Br2 toxicity. Our study was based on previous findings that demonstrated that Br2 upregulates the heme-degrading enzyme heme oxygenase-1 (HO-1), which converts toxic heme into billiverdin. Interestingly, following Br2 inhalation, heme levels were indeed elevated in bronchoalveolar lavage fluid, plasma, and whole lung tissue in C57BL/6 mice. High heme levels correlated with increased lung oxidative stress, lung inflammation, respiratory acidosis, lung edema, higher airway resistance, and mortality. However, therapeutic reduction of heme levels, by either scavenging with hemopexin or degradation by HO-1, improved lung function and survival. Therefore, heme attenuation may prove a useful adjuvant therapy to treat patients after Br2 exposure. PMID:27244263

  7. Heme: From quantum spin crossover to oxygen manager of life

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2016-01-01

    The review discusses how the electronic structure of heme explains its central importance to oxygen-based life on Earth. Emphasis is on the chemical bonding of heme, its spin crossover, reversible O2 binding, and O-O bond activation, put in relation to its physiological functions. The review disc...

  8. Conservation of species, volume, and belief in patients with Alzheimer’s disease: the issue of domain-specificity and conceptual impairment

    Science.gov (United States)

    Zaitchik, Deborah; Solomon, Gregg E. A.

    2009-01-01

    Two studies investigated whether patients with Alzheimer’s disease (AD) suffer high-level and category-specific impairment in the conceptual domain of living things. In Study 1, AD patients and healthy young and healthy elderly controls took part in three tasks: the Conservation of Species, Volume, and Belief. All 3 tasks required tracking an object’s identity in the face of irrelevant but salient transformations. Healthy young and elderly controls performed at or near ceiling on all tasks. AD patients were at or near ceiling on the Volume and Belief tasks, but only about half succeeded on the Species task. Study 2 demonstrated that the results were not due to simple task demands. AD patients’ failure to conserve species indicates that they are impaired in their theoretical understanding of living things, and their success on the Volume and Belief tasks suggests that the impairment is domain-specific. Two hypotheses are put forward to explain the phenomenon: the first, a category-specific account, holds that the intuitive theory of biology undergoes pervasive degradation; the second, a hybrid domain-general/domain-specific account, holds that impairment to domain-general processes such as executive function interacts with core cognition, the primitive elements that are the foundation of domain-specific knowledge. PMID:20043252

  9. Procedural learning in Parkinson's disease, specific language impairment, dyslexia, schizophrenia, developmental coordination disorder, and autism spectrum disorders: A second-order meta-analysis.

    Science.gov (United States)

    Clark, Gillian M; Lum, Jarrad A G

    2017-10-01

    The serial reaction time task (SRTT) has been used to study procedural learning in clinical populations. In this report, second-order meta-analysis was used to investigate whether disorder type moderates performance on the SRTT. Using this approach to quantitatively summarise past research, it was tested whether autism spectrum disorder, developmental coordination disorder, dyslexia, Parkinson's disease, schizophrenia, and specific language impairment differentially affect procedural learning on the SRTT. The main analysis revealed disorder type moderated SRTT performance (p=0.010). This report demonstrates comparable levels of procedural learning impairment in developmental coordination disorder, dyslexia, Parkinson's disease, schizophrenia, and specific language impairment. However, in autism, procedural learning is spared. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Identification of the receptor scavenging hemopexin-heme complexes

    DEFF Research Database (Denmark)

    Hvidberg, Vibeke; Maniecki, Maciej B; Jacobsen, Christian

    2005-01-01

    and is suggested to facilitate cellular heme metabolism. Using a ligand-affinity approach, we purified the human hemopexin-heme receptor and identified it as the low-density lipoprotein receptor-related protein (LRP)/CD91, a receptor expressed in several cell types including macrophages, hepatocytes, neurons......, and syncytiotrophoblasts. Binding experiments, including Biacore analysis, showed that hemopexin-heme complex formation elicits the high receptor affinity. Uptake studies of radio-labeled hemopexin-heme complex in LRP/CD91-expressing COS cells and confocal microscopy of the cellular processing of fluorescent hemopexin......-heme complexes are removed by a receptor-mediated pathway showing striking similarities to the CD163-mediated haptoglobin-hemoglobin clearance in macrophages. Furthermore, the data indicate a hitherto unknown role of LRP/CD91 in inflammation....

  11. Nonword repetition--a clinical marker for specific language impairment in Swedish associated with parents' language-related problems.

    Directory of Open Access Journals (Sweden)

    Nelli Kalnak

    Full Text Available First, we explore the performance of nonword repetition (NWR in children with specific language impairment (SLI and typically developing children (TD in order to investigate the accuracy of NWR as a clinical marker for SLI in Swedish-speaking school-age children. Second, we examine the relationship between NWR, family aggregation, and parental level of education in children with SLI. A sample of 61 children with SLI, and 86 children with TD, aged 8-12 years, were administered an NWR test. Family aggregation, measured as the prevalence of language and/or literacy problems (LLP in parents of the children with SLI, was based on family history interviews. The sensitivity and specificity of nonword repetition was analyzed in a binary logistic regression, cut-off values were established with ROC curves, and positive and negative likelihood ratios reported. Results from the present study show that NWR distinguishes well between Swedish-speaking school-children with and without SLI. We found 90.2% sensitivity and 97.7% specificity at a cut-off level of -2 standard deviations for binary scoring of nonwords. Differences between the SLI and TD groups showed large effect sizes for the two scoring measures binary (d = 2.11 and percent correct consonants (PCC (d = 1.79. The children with SLI were split into two subgroups: those with no parents affected with LLP (n = 12, and those with one or both parents affected (n = 49. The subgroup consisting of affected parents had a significantly lower score on NWR binary (p = .037, and there was a great difference between the subgroups (d = 0.7. When compared to the TD group, the difference from the subgroup with affected parents was almost one standard deviation larger (d = 2.47 than the difference from the TD to the subgroup consisting of non-affected parents (d = 1.57. Our study calls for further exploration of the complex interaction between family aggregation, language input, and

  12. Covalent heme attachment to the protein in human heme oxygenase-1 with selenocysteine replacing the His25 proximal iron ligand.

    Science.gov (United States)

    Jiang, Yongying; Trnka, Michael J; Medzihradszky, Katalin F; Ouellet, Hugues; Wang, Yongqiang; Ortiz de Montellano, Paul R

    2009-03-01

    To characterize heme oxygenase with a selenocysteine (SeCys) as the proximal iron ligand, we have expressed truncated human heme oxygenase-1 (hHO-1) His25Cys, in which Cys-25 is the only cysteine, in the Escherichia coli cysteine auxotroph strain BL21(DE3)cys. Selenocysteine incorporation into the protein was demonstrated by both intact protein mass measurement and mass spectrometric identification of the selenocysteine-containing tryptic peptide. One selenocysteine was incorporated into approximately 95% of the expressed protein. Formation of an adduct with Ellman's reagent (DTNB) indicated that the selenocysteine in the expressed protein was in the reduced state. The heme-His25SeCys hHO-1 complex could be prepared by either (a) supplementing the overexpression medium with heme, or (b) reconstituting the purified apoprotein with heme. Under reducing conditions in the presence of imidazole, a covalent bond is formed by addition of the selenocysteine residue to one of the heme vinyl groups. No covalent bond is formed when the heme is replaced by mesoheme, in which the vinyls are replaced by ethyl groups. These results, together with our earlier demonstration that external selenolate ligands can transfer an electron to the iron [Y. Jiang, P.R. Ortiz de Montellano, Inorg. Chem. 47 (2008) 3480-3482 ], indicate that a selenyl radical is formed in the hHO-1 His25SeCys mutant that adds to a heme vinyl group.

  13. Impaired Performance on See-Know Tasks amongst Children with Autism: Evidence of Specific Difficulties with Theory of Mind or Domain-General Task Factors?

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    Lind, Sophie E.; Bowler, Dermot M.

    2010-01-01

    It is widely assumed that children with autism have a diminished understanding of the perception-knowledge relationship, as a specific manifestation of a theory of mind (ToM) impairment. However, such a conclusion may not be justified on the basis of previous studies, which have suffered from significant methodological weaknesses. The current…

  14. The Effect of Time on Word Learning: An Examination of Decay of the Memory Trace and Vocal Rehearsal in Children with and without Specific Language Impairment

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    Alt, Mary; Spaulding, Tammie

    2011-01-01

    Purpose: The purpose of this study was to measure the effect of time to response in a fast-mapping word learning task for children with specific language impairment (SLI) and children with typically developing language skills (TD). Manipulating time to response allows us to examine decay of the memory trace, the use of vocal rehearsal, and their…

  15. Long-Term Memory: A Review and Meta-Analysis of Studies of Declarative and Procedural Memory in Specific Language Impairment

    Science.gov (United States)

    Lum, Jarrad A. G.; Conti-Ramsden, Gina

    2013-01-01

    This review examined the status of long-term memory systems in specific language impairment (SLI)--declarative memory and aspects of procedural memory in particular. Studies included in the review were identified following a systematic search of the literature and findings combined using meta-analysis. This review showed that individuals with SLI…

  16. Sensitivity to Audiovisual Temporal Asynchrony in Children with a History of Specific Language Impairment and Their Peers with Typical Development: A Replication and Follow-Up Study

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    Kaganovich, Natalya

    2017-01-01

    Purpose: Earlier, my colleagues and I showed that children with a history of specific language impairment (H-SLI) are significantly less able to detect audiovisual asynchrony compared with children with typical development (TD; Kaganovich & Schumaker, 2014). Here, I first replicate this finding in a new group of children with H-SLI and TD and…

  17. Effect of Sentence Length and Complexity on Working Memory Performance in Hungarian Children with Specific Language Impairment (SLI): A Cross-Linguistic Comparison

    Science.gov (United States)

    Marton, Klara; Schwartz, Richard G.; Farkas, Lajos; Katsnelson, Valeriya

    2006-01-01

    Background: English-speaking children with specific language impairment (SLI) perform more poorly than their typically developing peers in verbal working memory tasks where processing and storage are simultaneously required. Hungarian is a language with a relatively free word order and a rich agglutinative morphology. Aims: To examine the effect…

  18. Characterization of a gene family encoding SEA (sea-urchin sperm protein, enterokinase and agrin-domain proteins with lectin-like and heme-binding properties from Schistosoma japonicum.

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    Evaristus Chibunna Mbanefo

    Full Text Available BACKGROUND: We previously identified a novel gene family dispersed in the genome of Schistosoma japonicum by retrotransposon-mediated gene duplication mechanism. Although many transcripts were identified, no homolog was readily identifiable from sequence information. METHODOLOGY/PRINCIPAL FINDINGS: Here, we utilized structural homology modeling and biochemical methods to identify remote homologs, and characterized the gene products as SEA (sea-urchin sperm protein, enterokinase and agrin-domain containing proteins. A common extracellular domain in this family was structurally similar to SEA-domain. SEA-domain is primarily a structural domain, known to assist or regulate binding to glycans. Recombinant proteins from three members of this gene family specifically interacted with glycosaminoglycans with high affinity, with potential implication in ligand acquisition and immune evasion. Similar approach was used to identify a heme-binding site on the SEA-domain. The heme-binding mode showed heme molecule inserted into a hydrophobic pocket, with heme iron putatively coordinated to two histidine axial ligands. Heme-binding properties were confirmed using biochemical assays and UV-visible absorption spectroscopy, which showed high affinity heme-binding (K D = 1.605×10(-6 M and cognate spectroscopic attributes of hexa-coordinated heme iron. The native proteins were oligomers, antigenic, and are localized on adult worm teguments and gastrodermis; major host-parasite interfaces and site for heme detoxification and acquisition. CONCLUSIONS: The results suggest potential role, at least in the nucleation step of heme crystallization (hemozoin formation, and as receptors for heme uptake. Survival strategies exploited by parasites, including heme homeostasis mechanism in hemoparasites, are paramount for successful parasitism. Thus, assessing prospects for application in disease intervention is warranted.

  19. Characterization of a Gene Family Encoding SEA (Sea-urchin Sperm Protein, Enterokinase and Agrin)-Domain Proteins with Lectin-Like and Heme-Binding Properties from Schistosoma japonicum

    Science.gov (United States)

    Mbanefo, Evaristus Chibunna; Kikuchi, Mihoko; Huy, Nguyen Tien; Shuaibu, Mohammed Nasir; Cherif, Mahamoud Sama; Yu, Chuanxin; Wakao, Masahiro; Suda, Yasuo; Hirayama, Kenji

    2014-01-01

    Background We previously identified a novel gene family dispersed in the genome of Schistosoma japonicum by retrotransposon-mediated gene duplication mechanism. Although many transcripts were identified, no homolog was readily identifiable from sequence information. Methodology/Principal Findings Here, we utilized structural homology modeling and biochemical methods to identify remote homologs, and characterized the gene products as SEA (sea-urchin sperm protein, enterokinase and agrin)-domain containing proteins. A common extracellular domain in this family was structurally similar to SEA-domain. SEA-domain is primarily a structural domain, known to assist or regulate binding to glycans. Recombinant proteins from three members of this gene family specifically interacted with glycosaminoglycans with high affinity, with potential implication in ligand acquisition and immune evasion. Similar approach was used to identify a heme-binding site on the SEA-domain. The heme-binding mode showed heme molecule inserted into a hydrophobic pocket, with heme iron putatively coordinated to two histidine axial ligands. Heme-binding properties were confirmed using biochemical assays and UV-visible absorption spectroscopy, which showed high affinity heme-binding (K D = 1.605×10−6 M) and cognate spectroscopic attributes of hexa-coordinated heme iron. The native proteins were oligomers, antigenic, and are localized on adult worm teguments and gastrodermis; major host-parasite interfaces and site for heme detoxification and acquisition. Conclusions The results suggest potential role, at least in the nucleation step of heme crystallization (hemozoin formation), and as receptors for heme uptake. Survival strategies exploited by parasites, including heme homeostasis mechanism in hemoparasites, are paramount for successful parasitism. Thus, assessing prospects for application in disease intervention is warranted. PMID:24416467

  20. Mental health problems in pre-school children with specific language impairment: Use of the Strengths and Difficulties Questionnaire

    NARCIS (Netherlands)

    Flapper, B.C.; Bos, A.C.; Jansen, D.E.

    2011-01-01

    The prevalence of mental health problems (MHP) in children with language disorders ranges from 11 to 55%, due to additional disabilities that have a significant relationship to psychosocial difficulties. Specialists assume that children with a selective disorder [selective language impairment

  1. The comparison of perceived health-related quality of life between Australian children with severe specific language impairment to age and gender-matched peers.

    Science.gov (United States)

    Nicola, Kristy; Watter, Pauline

    2018-02-14

    Children with specific language impairment often present with multiple comorbidities, which may adversely affect both participation in play and academic performance, potentially impacting a child's health-related quality of life. This study 1) explored the suitability of the Pediatric Quality of Life Inventory™ Version 4.0 Generic Core Scales (PedsQL™) for use with a typically developing Australian control group, and 2) compared the health-related quality of life between a control group and Australian children with severe specific language impairment. Health-related quality of life data collected as part of a broader study of 43 children with severe specific language impairment (males = 35, age range 5-16, mean age = 8.79+/- 2.92) enrolled at a special school were used to explore previously unreported findings. Typically developing gender and age matched (+/- 3 months) peers were recruited from local schools. The PedsQL™ child self-report and proxy-report were individually or interviewer-administered to the control group as required, and then compared to the group with specific language impairment. The PedsQL™ was reliable and feasible for use with the control group (N = 43, males = 35, age range = 5-16 years, mean age = 8.74+/- 2.94 years). Control group performance was as expected as per the manual. Parents of the control group scored their children significantly higher than did the children themselves on all scales except the emotional functioning scale. Both the control group children and their parents scored themselves significantly higher on all scales, compared to children with severe specific language impairment and their parents. The PedsQL™ was suitable for use with the control group. Further, the recruitment of a control group provided additional clarity on the extent a severe specific language impairment impacts on an Australian child's perceived health-related quality of life, compared to the manual cut

  2. Coordination Chemistry of Linear Oligopyrrolic Fragments Inspired by Heme Metabolites

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    Gautam, Ritika

    Linear oligopyrroles are degradation products of heme, which is converted in the presence of heme oxygenase to bile pigments, such as biliverdin and bilirubin. These tetrapyrrolic oligopyrroles are ubiquitously present in biological systems and find applications in the fields of catalysis and sensing. These linear tetrapyrrolic scaffolds are further degraded into linear tripyrrolic and dipyrrolic fragments. Although these lower oligopyrroles are abundantly present, their coordination chemistry requires further characterization. This dissertation focuses mainly on two classes of bioinspired linear oligopyrroles, propentdyopent and tripyrrindione, and their transition metal complexes, which present a rich ligand-based redox chemistry. Chapter 1 offers an overview of heme degradation to different classes of linear oligopyrroles and properties of their transition metal complexes. Chapter 2 is focused on the tripyrrin-1,14-dione scaffold of the urinary pigment uroerythrin, which coordinates divalent transition metals palladium and copper with square planar geometry. Specifically, the tripyrrin-1, 14-dione ligand binds Cu(II) and Pd(II) as a dianionic organic radical under ambient conditions. The electrochemical study confirms the presence of ligand based redox chemistry, and one electron oxidation or reduction reactions do not alter the planar geometry around the metal center. The X-Ray analysis and the electron paramagnetic resonance (EPR) studies of the complexes in the solid and solution phase reveals intermolecular interactions between the ligand based unpaired electrons and therefore formation of neutral pi-pi dimers. In Chapter 3, the antioxidant activity and the fluorescence sensor properties of the tripyrrin-1,14-dione ligand in the presence of superoxide are described. We found that the tripyrrindione ligand undergoes one-electron reduction in the presence of the superoxide radical anion (O2•- ) to form highly fluorescent H3TD1•- radical anion, which emits

  3. Increase on the initial soluble heme levels in acidic conditions is an important mechanism for spontaneous heme crystallization in vitro.

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    Renata Stiebler

    Full Text Available BACKGROUND: Hemozoin (Hz is a heme crystal that represents a vital pathway for heme disposal in several blood-feeding organisms. Recent evidence demonstrated that β-hematin (βH (the synthetic counterpart of Hz formation occurs under physiological conditions near synthetic or biological hydrophilic-hydrophobic interfaces. This seems to require a heme dimer acting as a precursor of Hz crystals that would be formed spontaneously in the absence of the competing water molecules bound to the heme iron. Here, we aimed to investigate the role of medium polarity on spontaneous βH formation in vitro. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the effect of water content on spontaneous βH formation by using the aprotic solvent dimethylsulfoxide (DMSO and a series of polyethyleneglycols (PEGs. We observed that both DMSO and PEGs (3.350, 6.000, 8.000, and 22.000 increased the levels of soluble heme under acidic conditions. These compounds were able to stimulate the production of βH crystals in the absence of any biological sample. Interestingly, the effects of DMSO and PEGs on βH formation were positively correlated with their capacity to promote previous heme solubilization in acidic conditions. Curiously, a short chain polyethyleneglycol (PEG 300 caused a significant reduction in both soluble heme levels and βH formation. Finally, both heme solubilization and βH formation strongly correlated with reduced medium water activity provided by increased DMSO concentrations. CONCLUSIONS: The data presented here support the notion that reduction of the water activity is an important mechanism to support spontaneous heme crystallization, which depends on the previous increase of soluble heme levels.

  4. Dual specificity phosphatase 6 deficiency is associated with impaired systemic glucose tolerance and reversible weight retardation in mice.

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    Katrin Pfuhlmann

    Full Text Available Here, we aimed to investigate the potential role of DUSP6, a dual specificity phosphatase, that specifically inactivates extracellular signal-regulated kinase (ERK, for the regulation of body weight and glucose homeostasis. We further assessed whether metabolic challenges affect Dusp6 expression in selected brain areas or white adipose tissue. Hypothalamic Dusp6 mRNA levels remained unchanged in chow-fed lean vs. high fat diet (HFD fed obese C57Bl/6J mice, and in C57Bl/6J mice undergoing prolonged fasting or refeeding with fat free diet (FFD or HFD. Similarly, Dusp6 expression levels were unchanged in selected brain regions of Lepob mice treated with 1 mg/kg of leptin for 6 days, compared to pair-fed or saline-treated Lepob controls. Dusp6 expression levels remained unaltered in vitro in primary adipocytes undergoing differentiation, but were increased in eWAT of HFD-fed obese C57Bl/6J mice, compared to chow-fed lean controls. Global chow-fed DUSP6 KO mice displayed reduced body weight and lean mass and slightly increased fat mass at a young age, which is indicative for early-age weight retardation. Subsequent exposure to HFD led to a significant increase in lean mass and body weight in DUSP6 deficient mice, compared to WT controls. Nevertheless, after 26 weeks of high-fat diet exposure, we observed comparable body weight, fat and lean mass in DUSP6 WT and KO mice, suggesting overall normal susceptibility to develop obesity. In line with the increased weight gain to compensate for early-age weight retardation, HFD-fed DUSP6 KO displayed increased expression levels of anabolic genes involved in lipid and cholesterol metabolism in the epididymal white adipose tissue (eWAT, compared to WT controls. Glucose tolerance was perturbed in both chow-fed lean or HFD-fed obese DUSP6 KO, compared to their respective WT controls. Overall, our data indicate that DUSP6 deficiency has limited impact on the regulation of energy metabolism, but impairs systemic

  5. HIV-1 Infection Is Associated with Depletion and Functional Impairment of Mycobacterium tuberculosis-Specific CD4 T Cells in Individuals with Latent Tuberculosis Infection.

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    Day, Cheryl L; Abrahams, Deborah A; Harris, Levelle D; van Rooyen, Michele; Stone, Lynnett; de Kock, Marwou; Hanekom, Willem A

    2017-09-15

    Coinfection with HIV is the single greatest risk factor for reactivation of latent Mycobacterium tuberculosis infection (LTBI) and progression to active tuberculosis disease. HIV-associated dysregulation of adaptive immunity by depletion of CD4 Th cells most likely contributes to loss of immune control of LTBI in HIV-infected individuals, although the precise mechanisms whereby HIV infection impedes successful T cell-mediated control of M. tuberculosis have not been well defined. To further delineate mechanisms whereby HIV impairs protective immunity to M. tuberculosis , we evaluated the frequency, phenotype, and functional capacity of M. tuberculosis -specific CD4 T cells in HIV-infected and HIV-uninfected adults with LTBI. HIV infection was associated with a lower total frequency of cytokine-producing M. tuberculosis -specific CD4 T cells, and preferential depletion of a discrete subset of M. tuberculosis -specific IFN-γ + IL-2 - TNF-α + CD4 T cells. M. tuberculosis -specific CD4 T cells in HIV-infected individuals expressed significantly higher levels of Ki67, compared with HIV-uninfected individuals, thus indicating recent activation and turnover of these cells in vivo. The ex vivo proliferative capacity of M. tuberculosis -specific CD4 T cells was markedly impaired in HIV-infected individuals, compared with HIV-uninfected individuals. Moreover, HIV infection was associated with increased M. tuberculosis Ag-induced CD4 T cell death ex vivo, indicating a possible mechanism contributing to impaired proliferative capacity of M. tuberculosis -specific CD4 T cells in HIV-infected individuals. These data provide new insights into the parameters of M. tuberculosis -specific CD4 T cell immunity that are impaired in HIV-infected individuals with LTBI, which may contribute to their increased risk of developing active tuberculosis disease. Copyright © 2017 by The American Association of Immunologists, Inc.

  6. Exploration of a 'double-jeopardy' hypothesis within working memory profiles for children with specific language impairment.

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    Briscoe, J; Rankin, P M

    2009-01-01

    Children with specific language impairment (SLI) often experience difficulties in the recall and repetition of verbal information. Archibald and Gathercole (2006) suggested that children with SLI are vulnerable across two separate components of a tripartite model of working memory (Baddeley and Hitch 1974). However, the hierarchical relationship between the 'slave' systems (temporary storage) and the central executive components places a particular challenge for interpreting working memory profiles within a tripartite model. This study aimed to examine whether a 'double-jeopardy' assumption is compatible with a hierarchical relationship between the phonological loop and central executive components of the working memory model in children with SLI. If a strong double-jeopardy assumption is valid for children with SLI, it was predicted that raw scores of working memory tests thought to tap phonological loop and central executive components of tripartite working memory would be lower than the scores of children matched for chronological age and those of children matched for language level, according to independent sources of constraint. In contrast, a hierarchical relationship would imply that a weakness in a slave component of working memory (the phonological loop) would also constrain performance on tests tapping a super-ordinate component (central executive). This locus of constraint would predict that scores of children with SLI on working memory tests that tap the central executive would be weaker relative to the scores of chronological age-matched controls only. Seven subtests of the Working Memory Test Battery for Children (Digit recall, Word recall, Non-word recall, Word matching, Listening recall, Backwards digit recall and Block recall; Pickering and Gathercole 2001) were administered to 14 children with SLI recruited via language resource bases and specialist schools, as well as two control groups matched on chronological age and vocabulary level

  7. [Update on the biology of heme synthesis in erythroid cells].

    Science.gov (United States)

    Fujiwara, Tohru; Harigae, Hideo

    2015-02-01

    Heme is a prosthetic group of hemoproteins playing important roles in oxygen transport, detoxification, circadian rhythm, microRNA processing, regulation of transcription, and translation. The majority of heme (-85%) is synthesized in red blood cells mainly for hemoglobin production, whereas hepatocytes account for most of the rest, functioning primarily in the synthesis of cytochrome P450 enzymes and mitochondrial respiratory enzymes. Thus, failure of heme biosynthesis causes severe inherited or acquired disorders in humans, including porphyria and sideroblastic anemia. The heme biosynthetic pathway is composed of eight enzymes that work in either mitochondria or the cytoplasm, which have been extensively researched and frequently reviewed. On the other hand, the mechanisms governing transport and intracellular trafficking of heme intermediates, as well as their potential links to human diseases, are poorly understood. Herein, we focus on recent understanding of the heme biosynthetic pathway and on human disorders due to defective heme synthesis in erythroid cells, such as X-linked sideroblastic anemia and erythropoietic protoporphyria.

  8. Emotional and behavioural needs in children with specific language impairment and in children with autism spectrum disorder: The importance of pragmatic language impairment.

    Science.gov (United States)

    Helland, Wenche Andersen; Helland, Turid

    2017-11-01

    Language problems may negatively affect children's behaviour and have detrimental effects on the development of peer-relations. We investigated and compared emotional and behavioural profiles in children with SLI and in children with ASD aged 6-15 years and explored to what extent pragmatic language problems contributed to the emotional and behavioural needs (EBN) in these clinical groups. The ASD group consisted of 23 children (19 boys; 4 girls) and the SLI group consisted of 20 children (18 boys; 2 girls). In order to assess EBN and language abilities, the Strength and Difficulties Questionnaire (SDQ) and the Children's Communication Checklist -2 (CCC-2) were filled out by parents. Our main findings were that although EBN was common in both groups; the children in the ASD group were significantly impaired relative to the children in the SLI group. However, in both groups pragmatic language problems were found to be significantly associated with EBN. A comprehensive assessment of EBN as well as pragmatic language abilities should be an integral part of the assessment procedure. Considering the substantial influence of pragmatic language abilities on social function and in resolving interpersonal conflicts with peers further development of therapy plans and interventions targeting pragmatics is strongly needed. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  9. Isoporphyrin Intermediate in Heme Oxygenase Catalysis

    Science.gov (United States)

    Evans, John P.; Niemevz, Fernando; Buldain, Graciela; de Montellano, Paul Ortiz

    2008-01-01

    Human heme oxygenase-1 (hHO-1) catalyzes the O2- and NADPH-dependent oxidation of heme to biliverdin, CO, and free iron. The first step involves regiospecific insertion of an oxygen atom at the α-meso carbon by a ferric hydroperoxide and is predicted to proceed via an isoporphyrin π-cation intermediate. Here we report spectroscopic detection of a transient intermediate during oxidation by hHO-1 of α-meso-phenylheme-IX, α-meso-(p-methylphenyl)-mesoheme-III, and α-meso-(p-trifluoromethylphenyl)-mesoheme-III. In agreement with previous experiments (Wang, J., Niemevz, F., Lad, L., Huang, L., Alvarez, D. E., Buldain, G., Poulos, T. L., and Ortiz de Montellano, P. R. (2004) J. Biol. Chem. 279, 42593–42604), only the α-biliverdin isomer is produced with concomitant formation of the corresponding benzoic acid. The transient intermediate observed in the NADPH-P450 reductase-catalyzed reaction accumulated when the reaction was supported by H2O2 and exhibited the absorption maxima at 435 and 930 nm characteristic of an isoporphyrin. Product analysis by reversed phase high performance liquid chromatography and liquid chromatography electrospray ionization mass spectrometry of the product generated with H2O2 identified it as an isoporphyrin that, on quenching, decayed to benzoylbiliverdin. In the presence of H218O2, one labeled oxygen atom was incorporated into these products. The hHO-1-isoporphyrin complexes were found to have half-lives of 1.7 and 2.4 h for the p-trifluoromethyl- and p-methyl-substituted phenylhemes, respectively. The addition of NADPH-P450 reductase to the H2O2-generated hHO-1-isoporphyrin complex produced α-biliverdin, confirming its role as a reaction intermediate. Identification of an isoporphyrin intermediate in the catalytic sequence of hHO-1, the first such intermediate observed in hemoprotein catalysis, completes our understanding of the critical first step of heme oxidation. PMID:18487208

  10. The effect of proteins from animal source foods on heme iron bioavailability in humans.

    Science.gov (United States)

    Pizarro, Fernando; Olivares, Manuel; Valenzuela, Carolina; Brito, Alex; Weinborn, Valerie; Flores, Sebastián; Arredondo, Miguel

    2016-04-01

    Forty-five women (35-45 year) were randomly assigned to three iron (Fe) absorption sub-studies, which measured the effects of dietary animal proteins on the absorption of heme Fe. Study 1 was focused on heme, red blood cell concentrate (RBCC), hemoglobin (Hb), RBCC+beef meat; study 2 on heme, heme+fish, chicken, and beef; and study 3 on heme and heme+purified animal protein (casein, collagen, albumin). Study 1: the bioavailability of heme Fe from Hb was similar to heme only (∼13.0%). RBCC (25.0%) and RBCC+beef (21.3%) were found to be increased 2- and 1.6-fold, respectively, when compared with heme alone (pProteins from animal source foods and their digestion products did not enhance heme Fe absorption. Copyright © 2015. Published by Elsevier Ltd.

  11. Gray-white matter and cerebrospinal fluid volume differences in children with Specific Language Impairment and/or Reading Disability.

    Science.gov (United States)

    Girbau-Massana, Dolors; Garcia-Marti, Gracian; Marti-Bonmati, Luis; Schwartz, Richard G

    2014-04-01

    We studied gray-white matter and cerebrospinal fluid (CSF) alterations that may be critical for language, through an optimized voxel-based morphometry evaluation in children with Specific Language Impairment (SLI), compared to Typical Language Development (TLD). Ten children with SLI (8;5-10;9) and 14 children with TLD (8;2-11;8) participated. They received a comprehensive language and reading test battery. We also analyzed a subgroup of six children with SLI+RD (Reading Disability). Brain images from 3-Tesla MRIs were analyzed with intelligence, age, gender, and total intracranial volume as covariates. Children with SLI or SLI+RD exhibited a significant lower overall gray matter volume than children with TLD. Particularly, children with SLI showed a significantly lower volume of gray matter compared to children with TLD in the right postcentral parietal gyrus (BA4), and left and right medial occipital gyri (BA19). The group with SLI also exhibited a significantly greater volume of gray matter in the right superior occipital gyrus (BA19), which may reflect a brain reorganization to compensate for their lower volumes at medial occipital gyri. Children with SLI+RD, compared to children with TLD, showed a significantly lower volume of: (a) gray matter in the right postcentral parietal gyrus; and (b) white matter in the right inferior longitudinal fasciculus (RILF), which interconnects the temporal and occipital lobes. Children with TLD exhibited a significantly lower CSF volume than children with SLI and children with SLI+RD respectively, who had somewhat smaller volumes of gray matter allowing for more CSF volume. The significant lower gray matter volume at the right postcentral parietal gyrus and greater cerebrospinal fluid volume may prove to be unique markers for SLI. We discuss the association of poor knowledge/visual representations and language input to brain development. Our comorbid study showed that a significant lower volume of white matter in the right

  12. Semantic Differences of Definitional skills between Persian Speaking Children with Specific Language Impairment and Normal Language Developing Children

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    Mehri Mohammadi

    2011-07-01

    Full Text Available Objective: Linguistic and metalinguistic knowledge are the effective factors for definitional skills. This study investigated definitional skills both content and form in children with specific language impairment. Materials and Method: The participants were 32 Children in two groups of 16 SLI and 16 normal children, matched with age, sex and educational level. The SLI group was referred from Learning Difficulties Centers and Zarei Rehabilitation Center in Tehran, as well as the control group who was selected by randomized sampling from normal primary schools. The stimuli were 14 high frequency nouns from seven different categories. The reliability was calculated by interjudge agreement and the validity was assessed by content. Data was analyzed using independent T-test. Results: There were significant differences between mean scores of content and form of the definitional skills in two groups. The mean and SD scores of the content of word definition were M= 45.87, SD=12.22 in control group and M=33.18, SD= 17.60 for SLI one, out of possible 70 points (P= 0.025. The mean and SD scores of the form of word definition were M= 48.87, SD= 9.49 in control group and M= 38.18, SD= 12.85 for SLI one, out of 70 points (P= 0.012. Conclusion: Based on the results, it was concluded that, language problems of the SLI children may not let them semantic represention in order to form and present a complete process of word definition. Although this skill in children with SLI is inadequate, all the definitions given by SLI children were consistent with the categories of content and form of word definition used in this study. Therefore, an exact planning and intervention by speech and language pathologist can be effective for this skill. Linguistic intervention especially in semantic and grammatical aspects not only improves the definition of familiar words but also it might be useful for the definition of new words, consequently lead to educational and

  13. The relationship between phonological short-term memory, receptive vocabulary, and fast mapping in children with specific language impairment.

    Science.gov (United States)

    Jackson, Emily; Leitao, Suze; Claessen, Mary

    2016-01-01

    Children with specific language impairment (SLI) often experience word-learning difficulties, which are suggested to originate in the early stage of word learning: fast mapping. Some previous research indicates significantly poorer fast mapping capabilities in children with SLI compared with typically developing (TD) counterparts, with a range of methodological factors impacting on the consistency of this finding. Research has explored key issues that might underlie fast mapping difficulties in children with SLI, with strong theoretical support but little empirical evidence for the role of phonological short-term memory (STM). Additionally, further research is required to explore the influence of receptive vocabulary on fast mapping capabilities. Understanding the factors associated with fast mapping difficulties that are experienced by children with SLI may lead to greater theoretically driven word-learning intervention. To investigate whether children with SLI demonstrate significant difficulties with fast mapping, and to explore the related factors. It was hypothesized that children with SLI would score significantly lower on a fast mapping production task compared with TD children, and that phonological STM and receptive vocabulary would significantly predict fast mapping production scores in both groups of children. Twenty-three children with SLI (mean = 64.39 months, SD = 4.10 months) and 26 TD children (mean = 65.92 months, SD = 2.98) were recruited from specialist language and mainstream schools. All participants took part in a unique, interactive fast-mapping task whereby nine novel objects with non-word labels were presented and production accuracy was assessed. A non-word repetition test and the Peabody Picture Vocabulary Test-Fourth Edition (PPVT-IV) were also administered as measures of phonological STM capacity and receptive vocabulary, respectively. Results of the fast-mapping task indicated that children with SLI had significantly poorer fast

  14. 'MetaTaal': enhancing complex syntax in children with specific language impairment--a metalinguistic and multimodal approach.

    Science.gov (United States)

    Zwitserlood, Rob; Wijnen, Frank; van Weerdenburg, Marjolijn; Verhoeven, Ludo

    2015-01-01

    Currently, most research on the effective treatment of morphosyntax in children with specific language impairment (SLI) pertains to younger children. In the last two decades, several studies have provided evidence that intervention for older school-age children with SLI can be effective. These metalinguistic intervention approaches teach grammatical rules explicitly and use shapes and colours as two-dimensional visual support. Reading or writing activities form a substantial part of these interventions. However, some children with SLI are poor readers and might benefit more from an approach that is less dependent on literacy skills. To examine the effectiveness of a combined metalinguistic and multimodal approach in older school-age children with SLI. The intervention was adapted to suit poor readers and targeted the improvement of relative clause production, because relative clauses still pose difficulties for older children with SLI. Participants were 12 monolingual Dutch children with SLI (mean age 11;2). All children visited a special school for children with speech and language disorders in the Netherlands. A quasi-experimental multiple-baseline design was chosen to evaluate the effectiveness of the intervention. A set of tasks was constructed to test relative clause production and comprehension. Two balanced versions were alternated in order to suppress a possible learning effect from multiple presentations of the tasks. After 3 monthly baseline measurements, the children received individual treatment with a protocolled intervention programme twice a week during 5 weeks. The tests were repeated directly post-therapy and at a retention measurement 3 months later. During the intervention programme, the speech therapist delivering the treatment remained blind to the test results. No significant changes were found during the baseline measurements. However, measurement directly post-therapy showed that 5 h of intervention produced significant improvement on the

  15. Wearing red for signaling: the heme-bach axis in heme metabolism, oxidative stress response and iron immunology.

    Science.gov (United States)

    Igarashi, Kazuhiko; Watanabe-Matsui, Miki

    2014-04-01

    The connection between gene regulation and metabolism is an old issue that warrants revisiting in order to understand both normal as well as pathogenic processes in higher eukaryotes. Metabolites affect the gene expression by either binding to transcription factors or serving as donors for post-translational modification, such as that involving acetylation and methylation. The focus of this review is heme, a prosthetic group of proteins that includes hemoglobin and cytochromes. Heme has been shown to bind to several transcription factors, including Bach1 and Bach2, in higher eukaryotes. Heme inhibits the transcriptional repressor activity of Bach1, resulting in the derepression of its target genes, such as globin in erythroid cells and heme oxygenase-1 in diverse cell types. Since Bach2 is important for class switch recombination and somatic hypermutation of immunoglobulin genes as well as regulatory and effector T cell differentiation and the macrophage function, the heme-Bach2 axis may regulate the immune response as a signaling cascade. We discuss future issues regarding the topic of the iron/heme-gene regulation network based on current understanding of the heme-Bach axis, including the concept of "iron immunology" as the synthesis of the iron metabolism and the immune response.

  16. Low-level neural auditory discrimination dysfunctions in specific language impairment—A review on mismatch negativity findings

    Directory of Open Access Journals (Sweden)

    Teija Kujala

    2017-12-01

    Full Text Available In specific language impairment (SLI, there is a delay in the child’s oral language skills when compared with nonverbal cognitive abilities. The problems typically relate to phonological and morphological processing and word learning. This article reviews studies which have used mismatch negativity (MMN in investigating low-level neural auditory dysfunctions in this disorder. With MMN, it is possible to tap the accuracy of neural sound discrimination and sensory memory functions. These studies have found smaller response amplitudes and longer latencies for speech and non-speech sound changes in children with SLI than in typically developing children, suggesting impaired and slow auditory discrimination in SLI. Furthermore, they suggest shortened sensory memory duration and vulnerability of the sensory memory to masking effects. Importantly, some studies reported associations between MMN parameters and language test measures. In addition, it was found that language intervention can influence the abnormal MMN in children with SLI, enhancing its amplitude. These results suggest that the MMN can shed light on the neural basis of various auditory and memory impairments in SLI, which are likely to influence speech perception. Keywords: Specific language impairment, Auditory processing, Mismatch negativity (MMN

  17. Introduction of a covalent histidine-heme linkage in a hemoglobin: a promising tool for heme protein engineering.

    Science.gov (United States)

    Rice, Selena L; Preimesberger, Matthew R; Johnson, Eric A; Lecomte, Juliette T J

    2014-12-01

    The hemoglobins of the cyanobacteria Synechococcus and Synechocystis (GlbNs) are capable of spontaneous and irreversible attachment of the b heme to the protein matrix. The reaction, which saturates the heme 2-vinyl by addition of a histidine residue, is reproduced in vitro by preparing the recombinant apoprotein, adding ferric heme, and reducing the iron to the ferrous state. Spontaneous covalent attachment of the heme is potentially useful for protein engineering purposes. Thus, to explore whether the histidine-heme linkage can serve in such applications, we attempted to introduce it in a test protein. We selected as our target the heme domain of Chlamydomonas eugametos LI637 (CtrHb), a eukaryotic globin that exhibits less than 50% sequence identity with the cyanobacterial GlbNs. We chose two positions, 75 in the FG corner and 111 in the H helix, to situate a histidine near a vinyl group. We characterized the proteins with gel electrophoresis, absorbance spectroscopy, and NMR analysis. Both T111H and L75H CtrHbs reacted upon reduction of the ferric starting material containing cyanide as the distal ligand to the iron. With L75H CtrHb, nearly complete (>90%) crosslinking was observed to the 4-vinyl as expected from the X-ray structure of wild-type CtrHb. Reaction of T111H CtrHb also occurred at the 4-vinyl, in a 60% yield indicating a preference for the flipped heme orientation in the starting material. The work suggests that the His-heme modification will be applicable to the design of proteins with a non-dissociable heme group. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Heme orientational disorder in human adult hemoglobin reconstituted with a ring fluorinated heme and its functional consequences

    International Nuclear Information System (INIS)

    Nagao, Satoshi; Hirai, Yueki; Kawano, Shin; Imai, Kiyohiro; Suzuki, Akihiro; Yamamoto, Yasuhiko

    2007-01-01

    A ring fluorinated heme, 13,17-bis(2-carboxylatoethyl)-3,8-diethyl-2-fluoro-7,12, 18-trimethyl-porphyrin-atoiron(III), has been incorporated into human adult hemoglobin (Hb A). The heme orientational disorder in the individual subunits of the protein has been readily characterized using 19 F NMR and the O 2 binding properties of the protein have been evaluated through the oxygen equilibrium analysis. The equilibrated orientations of hemes in α- and β- subunits of the reconstituted protein were found to be almost completely opposite to each other, and hence were largely different from those of the native and the previously reported reconstituted proteins [T. Jue, G.N. La Mar, Heme orientational heterogeneity in deuterohemin-reconstituted horse and human hemoglobin characterized by proton nuclear magnetic resonance spectroscopy, Biochem. Biophys. Res. Commun. 119 (1984) 640-645]. Despite the large difference in the degree of the heme orientational disorder in the subunits of the proteins, the O 2 affinity and the cooperativity of the protein reconstituted with 2-MF were similar to those of the proteins reconstituted with a series of hemes chemically modified at the heme 3- and 8-positions [K. Kawabe, K. Imaizumi, Z. Yoshida, K. Imai, I. Tyuma, Studies on reconstituted myoglobins and hemoglobins II. Role of the heme side chains in the oxygenation of hemoglobin, J. Biochem. 92 (1982) 1713-1722], whose O 2 affinity and cooperativity were higher and lower, respectively, relative to those of native protein. These results indicated that the heme orientational disorder could exert little effect, if any, on the O 2 affinity properties of Hb A. This finding provides new insights into structure-function relationship of Hb A

  19. Expression and characterization of truncated human heme oxygenase (hHO-1) and a fusion protein of hHO-1 with human cytochrome P450 reductase.

    Science.gov (United States)

    Wilks, A; Black, S M; Miller, W L; Ortiz de Montellano, P R

    1995-04-04

    A human heme oxygenase (hHO-1) gene without the sequence coding for the last 23 amino acids has been expressed in Escherichia coli behind the pho A promoter. The truncated enzyme is obtained in high yields as a soluble, catalytically-active protein, making it available for the first time for detailed mechanistic studies. The purified, truncated hHO-1/heme complex is spectroscopically indistinguishable from that of the rat enzyme and converts heme to biliverdin when reconstituted with rat liver cytochrome P450 reductase. A self-sufficient heme oxygenase system has been obtained by fusing the truncated hHO-1 gene to the gene for human cytochrome P450 reductase without the sequence coding for the 20 amino acid membrane binding domain. Expression of the fusion protein in pCWori+ yields a protein that only requires NADPH for catalytic turnover. The failure of exogenous cytochrome P450 reductase to stimulate turnover and the insensitivity of the catalytic rate toward changes in ionic strength establish that electrons are transferred intramolecularly between the reductase and heme oxygenase domains of the fusion protein. The Vmax for the fusion protein is 2.5 times higher than that for the reconstituted system. Therefore, either the covalent tether does not interfere with normal docking and electron transfer between the flavin and heme domains or alternative but equally efficient electron transfer pathways are available that do not require specific docking.

  20. Implication for using heme methyl hyperfine shifts as indicators of heme seating as related to stereoselectivity in the catabolism of heme by heme oxygenase: in-plane heme versus axial his rotation.

    Science.gov (United States)

    Ogura, Hiroshi; Evans, John P; de Montellano, Paul R Ortiz; La Mar, Gerd N

    2008-01-08

    The triple mutant of the solubilized, 265-residue construct of human heme oxygenase, K18E/E29K/R183E-hHO, has been shown to redirect the exclusive alpha-regioselectivity of wild-type hHO to primarily beta,delta-selectivity in the cleavage of heme (Wang, J., Evans, J. P., Ogura, H., La Mar, G. N., and Ortiz de Montellano, P. R. (2006) Biochemistry 45, 61-73). The 1H NMR hyperfine shift pattern for the substrate and axial His CbetaH's and the substrate-protein contacts of the cyanide-inhibited protohemin and 2,4-dimethyldeuterohemin complexes of the triple mutant have been analyzed in detail and compared to data for the WT complex. It is shown that protein contacts for the major solution isomers for both substrates in the mutant dictate approximately 90 degrees in-plane clockwise rotation relative to that in the WT. The conventional interpretation of the pattern of substrate methyl hyperfine shifts, however, indicates substrate rotations of only approximately 50 degrees . This paradox is resolved by demonstrating that the axial His25 imidazole ring also rotates counterclockwise with respect to the protein matrix in the mutant relative to that in the WT. The axial His25 CbetaH hyperfine shifts are shown to serve as independent probes of the imidazole plane orientation relative to the protein matrix. The analysis indicates that the pattern of heme methyl hyperfine shifts cannot be used alone to determine the in-plane orientation of the substrate as it relates to the stereospecificity of heme cleavage, without explicit consideration of the orientation of the axial His imidazole plane relative to the protein matrix.

  1. Effect of a heme oxygenase-1 inducer on NADPH oxidase ...

    African Journals Online (AJOL)

    Effect of a heme oxygenase-1 inducer on NADPH oxidase expression in ... and immunohistochemistry of hepatic NOX1 and NOX4 were investigated in week 4. ... (HO-1 inhibitor) administration caused upregulation of NOX gene expression ...

  2. Heme and blood-feeding parasites: friends or foes?

    Directory of Open Access Journals (Sweden)

    Glanfield Amber

    2010-11-01

    Full Text Available Abstract Hemoparasites, like malaria and schistosomes, are constantly faced with the challenges of storing and detoxifying large quantities of heme, released from their catabolism of host erythrocytes. Heme is an essential prosthetic group that forms the reactive core of numerous hemoproteins with diverse biological functions. However, due to its reactive nature, it is also a potentially toxic molecule. Thus, the acquisition and detoxification of heme is likely to be paramount for the survival and establishment of parasitism. Understanding the underlying mechanism involved in this interaction could possibly provide potential novel targets for drug and vaccine development, and disease treatment. However, there remains a wide gap in our understanding of these mechanisms. This review summarizes the biological importance of heme for hemoparasite, and the adaptations utilized in its sequestration and detoxification.

  3. Heme and blood-feeding parasites: friends or foes?

    Science.gov (United States)

    2010-01-01

    Hemoparasites, like malaria and schistosomes, are constantly faced with the challenges of storing and detoxifying large quantities of heme, released from their catabolism of host erythrocytes. Heme is an essential prosthetic group that forms the reactive core of numerous hemoproteins with diverse biological functions. However, due to its reactive nature, it is also a potentially toxic molecule. Thus, the acquisition and detoxification of heme is likely to be paramount for the survival and establishment of parasitism. Understanding the underlying mechanism involved in this interaction could possibly provide potential novel targets for drug and vaccine development, and disease treatment. However, there remains a wide gap in our understanding of these mechanisms. This review summarizes the biological importance of heme for hemoparasite, and the adaptations utilized in its sequestration and detoxification. PMID:21087517

  4. Wiring of heme enzymes by methylene-blue labeled dendrimers

    DEFF Research Database (Denmark)

    Álvarez-Martos, Isabel; Shahdost-fard, Faezeh; Ferapontova, Elena

    2017-01-01

    Redox-modified branched 3D dendrimeric nanostructures may be considered as perspective wires for electrical connection between redox enzymes and electrodes. Here, we studied electron transfer (ET) reactions and bioelectrocatalysis of heme-containing horseradish peroxidase (HRP) and heme- and moli......Redox-modified branched 3D dendrimeric nanostructures may be considered as perspective wires for electrical connection between redox enzymes and electrodes. Here, we studied electron transfer (ET) reactions and bioelectrocatalysis of heme-containing horseradish peroxidase (HRP) and heme......- and molibdopterin-containing sulfite oxidase (SOx), wired to gold by the methylene blue (MB)-labeled polyamidoamine (PAMAM) dendrimers. The enzymes’ electrochemical transformation and bioelectrocatalytic function could be followed at both unlabeled and MB-labeled dendrimer-modified electrodes with the formal redox......, optimization of bioelectrocatalysis of complex intermembrane and, possibly, membrane enzymes....

  5. Immunolocalization of heme oxygenase-1 in periodontal diseases

    Directory of Open Access Journals (Sweden)

    G Gayathri

    2014-01-01

    Conclusion: The results of our study is an increasing evidence of involvement of antioxidant enzymes like heme oxygenase-1 in periodontal inflammation and their implication for treatment of chronic periodontitis.

  6. Systemic lipopolysaccharide administration impairs retrieval of context-object discrimination, but not spatial, memory: Evidence for selective disruption of specific hippocampus-dependent memory functions during acute neuroinflammation.

    Science.gov (United States)

    Czerniawski, Jennifer; Miyashita, Teiko; Lewandowski, Gail; Guzowski, John F

    2015-02-01

    Neuroinflammation is implicated in impairments in neuronal function and cognition that arise with aging, trauma, and/or disease. Therefore, understanding the underlying basis of the effect of immune system activation on neural function could lead to therapies for treating cognitive decline. Although neuroinflammation is widely thought to preferentially impair hippocampus-dependent memory, data on the effects of cytokines on cognition are mixed. One possible explanation for these inconsistent results is that cytokines may disrupt specific neural processes underlying some forms of memory but not others. In an earlier study, we tested the effect of systemic administration of bacterial lipopolysaccharide (LPS) on retrieval of hippocampus-dependent context memory and neural circuit function in CA3 and CA1 (Czerniawski and Guzowski, 2014). Paralleling impairment in context discrimination memory, we observed changes in neural circuit function consistent with disrupted pattern separation function. In the current study we tested the hypothesis that acute neuroinflammation selectively disrupts memory retrieval in tasks requiring hippocampal pattern separation processes. Male Sprague-Dawley rats given LPS systemically prior to testing exhibited intact performance in tasks that do not require hippocampal pattern separation processes: novel object recognition and spatial memory in the water maze. By contrast, memory retrieval in a task thought to require hippocampal pattern separation, context-object discrimination, was strongly impaired in LPS-treated rats in the absence of any gross effects on exploratory activity or motivation. These data show that LPS administration does not impair memory retrieval in all hippocampus-dependent tasks, and support the hypothesis that acute neuroinflammation impairs context discrimination memory via disruption of pattern separation processes in hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Hal Is a Bacillus anthracis Heme Acquisition Protein

    Science.gov (United States)

    Balderas, Miriam A.; Nobles, Christopher L.; Honsa, Erin S.; Alicki, Embriette R.

    2012-01-01

    The metal iron is a limiting nutrient for bacteria during infection. Bacillus anthracis, the causative agent of anthrax and a potential weapon of bioterrorism, grows rapidly in mammalian hosts, which suggests that it efficiently attains iron during infection. Recent studies have uncovered both heme (isd) and siderophore-mediated (asb) iron transport pathways in this pathogen. Whereas deletion of the asb genes results in reduced virulence, the loss of three surface components from isd had no effect, thereby leaving open the question of what additional factors in B. anthracis are responsible for iron uptake from the most abundant iron source for mammals, heme. Here, we describe the first functional characterization of bas0520, a gene recently implicated in anthrax disease progression. bas0520 encodes a single near-iron transporter (NEAT) domain and several leucine-rich repeats. The NEAT domain binds heme, despite lacking a stabilizing tyrosine common to the NEAT superfamily of hemoproteins. The NEAT domain also binds hemoglobin and can acquire heme from hemoglobin in solution. Finally, deletion of bas0520 resulted in bacilli unable to grow efficiently on heme or hemoglobin as an iron source and yielded the most significant phenotype relative to that for other putative heme uptake systems, a result that suggests that this protein plays a prominent role in the replication of B. anthracis in hematogenous environments. Thus, we have assigned the name of Hal (heme-acquisition leucine-rich repeat protein) to BAS0520. These studies advance our understanding of heme acquisition by this dangerous pathogen and justify efforts to determine the mechanistic function of this novel protein for vaccine or inhibitor development. PMID:22865843

  8. Heme and menaquinone induced electron transport in lactic acid bacteria

    OpenAIRE

    Brooijmans, Rob; Smit, Bart; Santos, Filipe; van Riel, Jan; de Vos, Willem M; Hugenholtz, Jeroen

    2009-01-01

    Abstract Background For some lactic acid bacteria higher biomass production as a result of aerobic respiration has been reported upon supplementation with heme and menaquinone. In this report, we have studied a large number of species among lactic acid bacteria for the existence of this trait. Results Heme- (and menaquinone) stimulated aerobic growth was observed for several species and genera of lactic acid bacteria. These include Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacill...

  9. Isocyanides inhibit human heme oxygenases at the verdoheme stage.

    Science.gov (United States)

    Evans, John P; Kandel, Sylvie; Ortiz de Montellano, Paul R

    2009-09-22

    Heme oxygenases (HO) catalyze the oxidative cleavage of heme to generate biliverdin, CO, and free iron. In humans, heme oxygenase-1 (hHO-1) is overexpressed in tumor tissues, where it helps to protect cancer cells from anticancer agents, while HOs in fungal pathogens, such as Candida albicans, function as the primary means of iron acquisition. Thus, HO can be considered a potential therapeutic target for certain diseases. In this study, we have examined the equilibrium binding of three isocyanides, isopropyl, n-butyl, and benzyl, to the two major human HO isoforms (hHO-1 and hHO-2), Candida albicans HO (CaHmx1), and human cytochrome P450 CYP3A4 using electronic absorption spectroscopy. Isocyanides coordinate to both ferric and ferrous HO-bound heme, with tighter binding by the more hydrophobic isocyanides and 200-300-fold tighter binding to the ferrous form. Benzyl isocyanide was the strongest ligand to ferrous heme in all the enzymes. Because the dissociation constants (KD) of the ligands for ferrous heme-hHO-1 were below the limit of accuracy for equilibrium titrations, stopped-flow kinetic experiments were used to measure the binding parameters of the isocyanides to ferrous hHO-1. Steady-state activity assays showed that benzyl isocyanide was the most potent uncompetitive inhibitor with respect to heme with a KI = 0.15 microM for hHO-1. Importantly, single turnover assays revealed that the reaction was completely stopped by coordination of the isocyanide to the verdoheme intermediate rather than to the ferric heme complex. Much tighter binding of the inhibitor to the verdoheme intermediate differentiates it from inhibition of, for example, CYP3A4 and offers a possible route to more selective inhibitor design.

  10. Isocyanides Inhibit Human Heme Oxygenases at the Verdoheme Stage†

    Science.gov (United States)

    Evans, John P.; Kandel, Sylvie; Ortiz de Montellano, Paul R.

    2010-01-01

    Heme oxygenases (HO) catalyze the oxidative cleavage of heme to generate biliverdin, CO, and free iron. In humans, heme oxygenase-1 (hHO-1) is overexpressed in tumor tissues, where it helps to protect cancer cells from anticancer agents, while HOs in fungal pathogens, such as Candida albicans, function as the primary means of iron acquisition. Thus, HO can be considered a potential therapeutic target for certain diseases. In this study, we have examined the equilibrium binding of three isocyanides; isopropyl, n-butyl, and benzyl, to the two major human HO isoforms (hHO-1 and hHO-2), Candida albicans HO (CaHmx1), and human cytochrome P450 CYP3A4 using electronic absorption spectroscopy. Isocyanides coordinate to both ferric and ferrous HO-bound heme, with tighter binding by the more hydrophobic isocyanides, and 200-300-fold tighter binding to the ferrous form. Benzyl isocyanide was the strongest ligand to ferrous heme in all the enzymes. Because the dissociation constants (KD) of the ligands for ferrous heme-hHO-1 were below the limit of accuracy for equilibrium titrations, stopped-flow kinetic experiments were used to measure the binding parameters of the isocyanides to ferrous hHO-1. Steady-state activity assays showed that benzyl isocyanide was the most potent uncompetitive inhibitor with respect to heme with a KI = 0.15 μM for hHO-1. Importantly, single turnover assays revealed that the reaction was completely stopped by coordination of the isocyanide to the verdoheme intermediate rather than to the ferric heme complex. Much tighter binding of the inhibitor to the verdoheme intermediate differentiates it from inhibition of, for example, CYP3A4 and offers a possible route to more selective inhibitor design. PMID:19694439

  11. Non-adjacent dependency learning in Cantonese-speaking\\ud children with and without a history of specific language\\ud impairment

    OpenAIRE

    Iao, L-S; Ng, LY; Wong, AMY; Lee, OT

    2017-01-01

    Purpose: This study investigated non-adjacent dependency learning in Cantonese-speaking children with and without a history of Specific Language Impairment (SLI) in an artificial linguistic context.\\ud \\ud Method: Sixteen Cantonese-speaking children with SLI history and 16 Cantonese-speaking children with typical language development (TLD) were tested with a non-adjacent dependency learning task using artificial languages that mimic Cantonese.\\ud \\ud Results: Children with TLD performed above...

  12. Acquisition of iron from transferrin regulates reticulocyte heme synthesis

    International Nuclear Information System (INIS)

    Ponka, P.; Schulman, H.M.

    1985-01-01

    Fe-salicylaldehyde isonicotinoylhydrazone (SIH), which can donate iron to reticulocytes without transferrin as a mediator, has been utilized to test the hypothesis that the rate of iron uptake from transferrin limits the rate of heme synthesis in erythroid cells. Reticulocytes take up 59 Fe from [ 59 Fe]SIH and incorporate it into heme to a much greater extent than from saturating concentrations of [ 59 Fe]transferrin. Also, Fe-SIH stimulates [2- 14 C]glycine into heme when compared to the incorporation observed with saturating levels of Fe-transferrin. In addition, delta-aminolevulinic acid does not stimulate 59 Fe incorporation into heme from either [ 59 Fe]transferrin or [ 59 Fe]SIH but does reverse the inhibition of 59 Fe incorporation into heme caused by isoniazid, an inhibitor of delta-aminolevulinic acid synthase. Taken together, these results suggest the hypothesis that some step(s) in the pathway of iron from extracellular transferrin to intracellular protoporphyrin limits the overall rate of heme synthesis in reticulocytes

  13. TMEM14C is required for erythroid mitochondrial heme metabolism.

    Science.gov (United States)

    Yien, Yvette Y; Robledo, Raymond F; Schultz, Iman J; Takahashi-Makise, Naoko; Gwynn, Babette; Bauer, Daniel E; Dass, Abhishek; Yi, Gloria; Li, Liangtao; Hildick-Smith, Gordon J; Cooney, Jeffrey D; Pierce, Eric L; Mohler, Kyla; Dailey, Tamara A; Miyata, Non; Kingsley, Paul D; Garone, Caterina; Hattangadi, Shilpa M; Huang, Hui; Chen, Wen; Keenan, Ellen M; Shah, Dhvanit I; Schlaeger, Thorsten M; DiMauro, Salvatore; Orkin, Stuart H; Cantor, Alan B; Palis, James; Koehler, Carla M; Lodish, Harvey F; Kaplan, Jerry; Ward, Diane M; Dailey, Harry A; Phillips, John D; Peters, Luanne L; Paw, Barry H

    2014-10-01

    The transport and intracellular trafficking of heme biosynthesis intermediates are crucial for hemoglobin production, which is a critical process in developing red cells. Here, we profiled gene expression in terminally differentiating murine fetal liver-derived erythroid cells to identify regulators of heme metabolism. We determined that TMEM14C, an inner mitochondrial membrane protein that is enriched in vertebrate hematopoietic tissues, is essential for erythropoiesis and heme synthesis in vivo and in cultured erythroid cells. In mice, TMEM14C deficiency resulted in porphyrin accumulation in the fetal liver, erythroid maturation arrest, and embryonic lethality due to profound anemia. Protoporphyrin IX synthesis in TMEM14C-deficient erythroid cells was blocked, leading to an accumulation of porphyrin precursors. The heme synthesis defect in TMEM14C-deficient cells was ameliorated with a protoporphyrin IX analog, indicating that TMEM14C primarily functions in the terminal steps of the heme synthesis pathway. Together, our data demonstrate that TMEM14C facilitates the import of protoporphyrinogen IX into the mitochondrial matrix for heme synthesis and subsequent hemoglobin production. Furthermore, the identification of TMEM14C as a protoporphyrinogen IX importer provides a genetic tool for further exploring erythropoiesis and congenital anemias.

  14. A Lactobacillus rhamnosus strain induces a heme oxygenase dependent increase in Foxp3+ regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Khalil Karimi

    Full Text Available We investigated the consequences of feeding with a Lactobacillus species on the immune environment in GALT, and the role of dendritic cells and heme oxygenase-1 in mediating these responses. Feeding with a specific strain of Lactobacillus rhamnosus induced a significant increase in CD4+CD25+Foxp3+ functional regulatory T cells in GALT. This increase was greatest in the mesenteric lymph nodes and associated with a marked decrease in TNF and IFNγ production. Dendritic cell regulatory function and HO-1 expression was also increased. The increase in Foxp3+ T cells could be prevented by treatment with a heme oxygenase inhibitor. However, neither inhibition of heme oxygenase nor blockade of IL-10 and TGFβ prevented the inhibition of inflammatory cytokine production. In conclusion Lactobacillus feeding induced a tolerogenic environment in GALT. HO-1 was critical to the enhancement of Foxp3+ regulatory T cells while additional, as yet unknown, pathways were involved in the down-regulation of inflammatory cytokine production by T cells.

  15. Specificity of verbal learning impairment and recovery in a marijuana-dependent male: the effects of sustained marijuana abstinence

    OpenAIRE

    Vadhan, Nehal P.; van Gorp, Wilfred G.; Levin, Frances R.

    2011-01-01

    We present the case of a young adult in treatment for marijuana dependence, with recurrent depression and a history of possible TBI, complaining of concentration, memory and initiation problems. Testing at treatment baseline revealed performance that was generally in the High Average range on measures of reaction time and attention, with a selective impairment in verbal learning (Borderline to Extremely Low range). Following 8 weeks of abstinence from marijuana, his verbal learning recovered ...

  16. Is Early-onset in Major Depression a Predictor of Specific Clinical Features with More Impaired Social Function?

    Science.gov (United States)

    Liu, Yan-Hong; Chen, Lin; Su, Yun-Ai; Fang, Yi-Ru; Srisurapanont, Manit; Hong, Jin Pyo; Hatim, Ahmad; Chua, Hong Choon; Bautista, Dianne; Si, Tian-Mei

    2015-01-01

    Background: Early-onset major depressive disorder (MDD) (EOD) is often particularly malignant due to its special clinical features, accompanying impaired social function, protracted recovery time, and frequent recurrence. This study aimed to observe the effects of age onset on clinical characteristics and social function in MDD patients in Asia. Methods: In total, 547 out-patients aged 18–65 years who were from 13 study sites in five Asian countries were included. These patients had MDD diagnose according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria. Clinical features and social function were assessed using Symptom Checklist-90-revised (SCL-90-R) and Sheehan Disability Scale (SDS). Quality of life was assessed by a 36-item Short-form Health Survey (SF-36). Analyses were performed using a continuous or dichotomous (cut-off: 30 years) age-of-onset indicator. Results: Early-onset MDD (EOD, <30 years) was associated with longer illness (P = 0.003), unmarried status (P < 0.001), higher neuroticism (P ≤ 0.002) based on the SCL-90-R, and more limited social function and mental health (P = 0.006, P = 0.007) based on the SF-36 and SDS. The impairment of social function and clinical severity were more prominent at in-patients with younger onset ages. Special clinical features and more impaired social function and quality of life were associated with EOD, as in western studies. Conclusions: EOD often follows higher levels of neuroticism. Age of onset of MDD may be a predictor of clinical features and impaired social function, allowing earlier diagnosis and treatment. PMID:25758278

  17. Is Early-onset in Major Depression a Predictor of Specific Clinical Features with More Impaired Social Function?

    Institute of Scientific and Technical Information of China (English)

    Yan-Hong Liu; Lin Chen; Yun-Ai Su; Yi-Ru Fang; Manit Srisurapanont; Jin Pyo Hong; Ahmad Hatim

    2015-01-01

    Background:Early-onset major depressive disorder (MDD) (EOD) is often particularly malignant due to its special clinical features,accompanying impaired social function,protracted recovery time,and frequent recurrence.This study aimed to observe the effects of age onset on clinical characteristics and social function in MDD patients in Asia.Methods:In total,547 out-patients aged 18-65 years who were from 13 study sites in five Asian countries were included.These patients had MDD diagnose according to the Diagnostic and Statistical Manual of Mental Disorders,4th Edition criteria.Clinical features and social function were assessed using Symptom Checklist-90-revised (SCL-90-R) and Sheehan Disability Scale (SDS).Quality of life was assessed by a 36-item Short-form Health Survey (SF-36).Analyses were performed using a continuous or dichotomous (cut-off:30 years)age-of-onset indicator.Results:Early-onset MDD (EOD,<30 years) was associated with longer illness (P =0.003),unmarried status (P < 0.001),higher neuroticism (P ≤ 0.002) based on the SCL-90-R,and more limited social function and mental health (P =0.006,P =0.007) based on the SF-36 and SDS.The impairment of social function and clinical severity were more prominent at in-patients with younger onset ages.Special clinical features and more impaired social function and quality of life were associated with EOD,as in western studies.Conclusions:EOD often follows higher levels of neuroticism.Age of onset of MDD may be a predictor of clinical features and impaired social function,allowing earlier diagnosis and treatment.

  18. Impaired decision-making under risk is associated with gaming-specific inhibition deficits among college students with Internet gaming disorder.

    Science.gov (United States)

    Yao, Yuan-Wei; Wang, Ling-Jiao; Yip, Sarah W; Chen, Pin-Ru; Li, Song; Xu, Jiansong; Zhang, Jin-Tao; Deng, Lin-Yuan; Liu, Qin-Xue; Fang, Xiao-Yi

    2015-09-30

    A growing body of evidence indicates that both inhibition and decision-making deficits play essential roles in the development and maintenance of Internet gaming disorder (IGD). Clarifying whether impaired decision-making among individuals with IGD is related to poor inhibition will advance our understanding of IGD and contribute to intervention development. However, the relationship between these two functions remains unclear. In this study, we sought to systemically examine inhibitory processes, decision-making and the relationship between the two among individuals with IGD. Thirty-four individuals with IGD and 32 matched healthy controls (HCs) were recruited. In comparison to HCs, IGD subjects demonstrated inhibition deficits during performance of the gaming-related Go/No-Go task and impaired decision-making under risk. In addition, errors on No-Go trials during the gaming-related Go/No-Go task were positively associated with decision-making impairments under risk but not under ambiguity among IGD subjects. These results suggest individuals with IGD are impaired in some aspects of inhibition and decision-making functions, and that decision-making deficits under risk are linked to poor inhibition specifically related to gaming cues, which has implications for the development of novel intervention. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Characterization of SiaA, a streptococcal heme-binding protein associated with a heme ABC transport system.

    Science.gov (United States)

    Sook, Brian R; Block, Darci R; Sumithran, Suganya; Montañez, Griselle E; Rodgers, Kenton R; Dawson, John H; Eichenbaum, Zehava; Dixon, Dabney W

    2008-02-26

    Many pathogenic bacteria require heme and obtain it from their environment. Heme transverses the cytoplasmic membrane via an ATP binding cassette (ABC) pathway. Although a number of heme ABC transport systems have been described in pathogenic bacteria, there is as yet little biophysical characterization of the proteins in these systems. The sia (hts) gene cluster encodes a heme ABC transporter in the Gram positive Streptococcus pyogenes. The lipoprotein-anchored heme binding protein (HBP) of this transporter is SiaA (HtsA). In the current study, resonance Raman (rR), magnetic circular dichroism (MCD), and nuclear magnetic resonance (NMR) spectroscopies were used to determine the coordination state and spin state of both the ferric and ferrous forms of this protein. Identifiers from these techniques suggest that the heme is six-coordinate and low-spin in both oxidation states of the protein, with methionine and histidine as axial ligands. SiaA has a pKa of 9.7 +/- 0.1, attributed to deprotonation of the axial histidine. Guanidinium titration studies show that the ferric state is less stable than the ferrous state, with DeltaG(H2O) values for the oxidized and reduced proteins of 7.3 +/- 0.8 and 16.0 +/- 3.6 kcal mol-1, respectively. The reductive and oxidative midpoint potentials determined via spectroelectrochemistry are 83 +/- 3 and 64 +/- 3 mV, respectively; the irreversibility of heme reduction suggests that redox cycling of the heme is coupled to a kinetically sluggish change in structure or conformation. The biophysical characterization described herein will significantly advance our understanding of structure-function relationships in HBP.

  20. Heme-binding plasma membrane proteins of K562 erythroleukemia cells: Adsorption to heme-microbeads, isolation with affinity chromatography

    International Nuclear Information System (INIS)

    Majuri, R.

    1989-01-01

    Heme-microbeads attached themselves to the surface of viable K562 cells in a manner inhibitable by free hemin, indicating heme-recptor interaction. The microbeads were at first evenly distributed, but after prolonged incubation at 37 deg. C they formed a cap on one pole of the cells indicating clustering of the membrane heme receptors. Membrane proteins were labeled by culturing the cells in the presence of 35 S-methionine and were then solubilized with Triton X-114. The hydrophobic proteins contained about 20% of the total bound label. The solubilized membrane proteins were subsequently adsorbed to a heme-Sepharose affinity gel. According to SDS-electrophorsis and subsequent autoradiography, the immobilized heme captures two proteins or a protein with two polypeptides of 20 000 and 32 000 daltons. The larger of these was only wekly labeled with 35 S. The same two bands were observed if the cell surface proteins were labeled with 125 I by the lactoperoxidase method and the subsequently solubilized membrane proteins were isolated with heme-Sepharose. (author)

  1. Children with Specific Language Impairment and Their Families: A Future View of Nature Plus Nurture and New Technologies for Comprehensive Language Intervention Strategies.

    Science.gov (United States)

    Rice, Mabel L

    2016-11-01

    Future perspectives on children with language impairments are framed from what is known about children with specific language impairment (SLI). A summary of the current state of services is followed by discussion of how these children can be overlooked and misunderstood and consideration of why it is so hard for some children to acquire language when it is effortless for most children. Genetic influences are highlighted, with the suggestion that nature plus nurture should be considered in present as well as future intervention approaches. A nurture perspective highlights the family context of the likelihood of SLI for some of the children. Future models of the causal pathways may provide more specific information to guide gene-treatment decisions, in ways parallel to current personalized medicine approaches. Future treatment options can build on the potential of electronic technologies and social media to provide personalized treatment methods available at a time and place convenient for the person to use as often as desired. The speech-language pathologist could oversee a wide range of treatment options and monitor evidence provided electronically to evaluate progress and plan future treatment steps. Most importantly, future methods can provide lifelong language acquisition activities that maintain the privacy and dignity of persons with language impairment, and in so doing will in turn enhance the effectiveness of speech-language pathologists. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  2. Age-Specific Associations of Renal Impairment With Magnetic Resonance Imaging Markers of Cerebral Small Vessel Disease in Transient Ischemic Attack and Stroke.

    Science.gov (United States)

    Liu, Bian; Lau, Kui Kai; Li, Linxin; Lovelock, Caroline; Liu, Ming; Kuker, Wilhelm; Rothwell, Peter M

    2018-04-01

    It has been hypothesized that cerebral small vessel disease (SVD) and chronic renal impairment may be part of a multisystem small-vessel disorder, but their association may simply be as a result of shared risk factors (eg, hypertension) rather than to a systemic susceptibility to premature SVD. However, most previous studies were hospital based, most had inadequate adjustment for hypertension, many were confined to patients with lacunar stroke, and none stratified by age. In a population-based study of transient ischemic attack and ischemic stroke (OXVASC [Oxford Vascular Study]), we evaluated the magnetic resonance imaging markers of cerebral SVD, including lacunes, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular space. We studied the age-specific associations of renal impairment (estimated glomerular filtration rate <60 mL/min per 1.73 m 2 ) and total SVD burden (total SVD score) adjusting for age, sex, vascular risk factors, and premorbid blood pressure (mean blood pressure during 15 years preevent). Of 1080 consecutive patients, 1028 (95.2%) had complete magnetic resonance imaging protocol and creatinine measured at baseline. Renal impairment was associated with total SVD score (odds ratio [OR], 2.16; 95% confidence interval [CI], 1.69-2.75; P <0.001), but only at age <60 years (<60 years: OR, 3.97; 95% CI, 1.69-9.32; P =0.002; 60-79 years: OR, 1.01; 95% CI, 0.72-1.41; P =0.963; ≥80 years: OR, 0.95; 95% CI, 0.59-1.54; P =0.832). The overall association of renal impairment and total SVD score was also attenuated after adjustment for age, sex, history of hypertension, diabetes mellitus, and premorbid average systolic blood pressure (adjusted OR, 0.76; 95% CI, 0.56-1.02; P =0.067), but the independent association of renal impairment and total SVD score at age <60 years was maintained (adjusted OR, 3.11; 95% CI, 1.21-7.98; P =0.018). Associations of renal impairment and SVD were consistent for each SVD marker at age <60 years but

  3. Heme oxygenase-1 mediates BAY 11-7085 induced ferroptosis.

    Science.gov (United States)

    Chang, Ling-Chu; Chiang, Shih-Kai; Chen, Shuen-Ei; Yu, Yung-Luen; Chou, Ruey-Hwang; Chang, Wei-Chao

    2018-03-01

    Ferroptosis is a form of oxidative cell death and has become a chemotherapeutic target for cancer treatment. BAY 11-7085 (BAY), which is a well-known IκBα inhibitor, suppressed viability in cancer cells via induction of ferroptotic death in an NF-κB-independent manner. Reactive oxygen species scavenging, relief of lipid peroxidation, replenishment of glutathione and thiol-containing agents, as well as iron chelation, rescued BAY-induced cell death. BAY upregulated a variety of Nrf2 target genes related to redox regulation, particularly heme oxygenase-1 (HO-1). Studies with specific inhibitors and shRNA interventions suggested that the hierarchy of induction is Nrf2-SLC7A11-HO-1. SLC7A11 inhibition by erastin, sulfasalazine, or shRNA interference sensitizes BAY-induced cell death. Overexperession of SLC7A11 attenuated BAY-inhibited cell viability. The ferroptotic process induced by hHO-1 overexpression further indicated that HO-1 is a key mediator of BAY-induced ferroptosis that operates through cellular redox regulation and iron accumulation. BAY causes compartmentalization of HO-1 into the nucleus and mitochondrion, and followed mitochondrial dysfunctions, leading to lysosome targeting for mitophagy. In this study, we first discovered that BAY induced ferroptosis via Nrf2-SLC7A11-HO-1 pathway and HO-1 is a key mediator by responding to the cellular redox status. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Using porphyrin-amino acid pairs to model the electrochemistry of heme proteins: experimental and theoretical investigations.

    Science.gov (United States)

    Samajdar, Rudra N; Manogaran, Dhivya; Yashonath, S; Bhattacharyya, Aninda J

    2018-04-18

    Quasi reversibility in electrochemical cycling between different oxidation states of iron is an often seen characteristic of iron containing heme proteins that bind dioxygen. Surprisingly, the system becomes fully reversible in the bare iron-porphyrin complex: hemin. This leads to the speculation that the polypeptide bulk (globin) around the iron-porphyrin active site in these heme proteins is probably responsible for the electrochemical quasi reversibility. To understand the effect of such polypeptide bulk on iron-porphyrin, we study the interaction of specific amino acids with the hemin center in solution. We choose three representative amino acids-histidine (a well-known iron coordinator in bio-inorganic systems), tryptophan (a well-known fluoroprobe for proteins), and cysteine (a redox-active organic molecule). The interactions of these amino acids with hemin are studied using electrochemistry, spectroscopy, and density functional theory. The results indicate that among these three, the interaction of histidine with the iron center is strongest. Further, histidine maintains the electrochemical reversibility of iron. On the other hand, tryptophan and cysteine interact weakly with the iron center but disturb the electrochemical reversibility by contributing their own redox active processes to the system. Put together, this study attempts to understand the molecular interactions that can control electrochemical reversibility in heme proteins. The results obtained here from the three representative amino acids can be scaled up to build a heme-amino acid interaction database that may predict the electrochemical properties of any protein with a defined polypeptide sequence.

  5. Impaired quality of the hepatitis B virus (HBV)-specific T-cell response in human immunodeficiency virus type 1-HBV coinfection.

    Science.gov (United States)

    Chang, J Judy; Sirivichayakul, Sunee; Avihingsanon, Anchalee; Thompson, Alex J V; Revill, Peter; Iser, David; Slavin, John; Buranapraditkun, Supranee; Marks, Pip; Matthews, Gail; Cooper, David A; Kent, Stephen J; Cameron, Paul U; Sasadeusz, Joe; Desmond, Paul; Locarnini, Stephen; Dore, Gregory J; Ruxrungtham, Kiat; Lewin, Sharon R

    2009-08-01

    Hepatitis B virus (HBV)-specific T cells play a key role both in the control of HBV replication and in the pathogenesis of liver disease. Human immunodeficiency virus type 1 (HIV-1) coinfection and the presence or absence of HBV e (precore) antigen (HBeAg) significantly alter the natural history of chronic HBV infection. We examined the HBV-specific T-cell responses in treatment-naïve HBeAg-positive and HBeAg-negative HIV-1-HBV-coinfected (n = 24) and HBV-monoinfected (n = 39) Asian patients. Peripheral blood was stimulated with an overlapping peptide library for the whole HBV genome, and tumor necrosis factor alpha and gamma interferon cytokine expression in CD8+ T cells was measured by intracellular cytokine staining and flow cytometry. There was no difference in the overall magnitude of the HBV-specific T-cell responses, but the quality of the response was significantly impaired in HIV-1-HBV-coinfected patients compared with monoinfected patients. In coinfected patients, HBV-specific T cells rarely produced more than one cytokine and responded to fewer HBV proteins than in monoinfected patients. Overall, the frequency and quality of the HBV-specific T-cell responses increased with a higher CD4+ T-cell count (P = 0.018 and 0.032, respectively). There was no relationship between circulating HBV-specific T cells and liver damage as measured by activity and fibrosis scores, and the HBV-specific T-cell responses were not significantly different in patients with either HBeAg-positive or HBeAg-negative disease. The quality of the HBV-specific T-cell response is impaired in the setting of HIV-1-HBV coinfection and is related to the CD4+ T-cell count.

  6. A quasi-randomized feasibility pilot study of specific treatments to improve emotion recognition and mental-state reasoning impairments in schizophrenia.

    Science.gov (United States)

    Marsh, Pamela Jane; Polito, Vince; Singh, Subba; Coltheart, Max; Langdon, Robyn; Harris, Anthony W

    2016-10-24

    Impaired ability to make inferences about what another person might think or feel (i.e., social cognition impairment) is recognised as a core feature of schizophrenia and a key determinant of the poor social functioning that characterizes this illness. The development of treatments to target social cognitive impairments as a causal factor of impaired functioning in schizophrenia is of high priority. In this study, we investigated the acceptability, feasibility, and limited efficacy of 2 programs targeted at specific domains of social cognition in schizophrenia: "SoCog" Mental-State Reasoning Training (SoCog-MSRT) and "SoCog" Emotion Recognition Training (SoCog-ERT). Thirty-one participants with schizophrenia or schizoaffective disorder were allocated to either SoCog-MSRT (n = 19) or SoCog-ERT (n = 12). Treatment comprised 12 twice-weekly sessions for 6 weeks. Participants underwent assessments of social cognition, neurocognition and symptoms at baseline, post-training and 3-months after completing training. Attendance at training sessions was high with an average of 89.29 % attendance in the SoCog-MSRT groups and 85.42 % in the SoCog-ERT groups. Participants also reported the 2 programs as enjoyable and beneficial. Both SoCog-MSRT and SoCog-ERT groups showed increased scores on a false belief reasoning task and the Reading the Mind in the Eyes test. The SoCog-MSRT group also showed reduced personalising attributional biases in a small number of participants, while the SoCog-ERT group showed improved emotion recognition. The results are promising and support the feasibility and acceptability of the 2 SoCog programs as well as limited efficacy to improve social cognitive abilities in schizophrenia. There is also some evidence that skills for the recognition of basic facial expressions need specific training. Australian New Zealand Clinical Trials Registry ACTRN12613000978763 . Retrospectively registered 3/09/2013.

  7. Mitochondrial Cytochrome c Oxidase Biogenesis Is Regulated by the Redox State of a Heme-Binding Translational Activator.

    Science.gov (United States)

    Soto, Iliana C; Barrientos, Antoni

    2016-02-20

    Mitochondrial cytochrome c oxidase (COX), the last enzyme of the respiratory chain, catalyzes the reduction of oxygen to water and therefore is essential for cell function and viability. COX is a multimeric complex, whose biogenesis is extensively regulated. One type of control targets cytochrome c oxidase subunit 1 (Cox1), a key COX enzymatic core subunit translated on mitochondrial ribosomes. In Saccharomyces cerevisiae, Cox1 synthesis and COX assembly are coordinated through a negative feedback regulatory loop. This coordination is mediated by Mss51, a heme-sensing COX1 mRNA-specific processing factor and translational activator that is also a Cox1 chaperone. In this study, we investigated whether Mss51 hemylation and Mss51-mediated Cox1 synthesis are both modulated by the reduction-oxidation (redox) environment. We report that Cox1 synthesis is attenuated under oxidative stress conditions and have identified one of the underlying mechanisms. We show that in vitro and in vivo exposure to hydrogen peroxide induces the formation of a disulfide bond in Mss51 involving CPX motif heme-coordinating cysteines. Mss51 oxidation results in a heme ligand switch, thereby lowering heme-binding affinity and promoting its release. We demonstrate that in addition to affecting Mss51-dependent heme sensing, oxidative stress compromises Mss51 roles in COX1 mRNA processing and translation. H2O2-induced downregulation of mitochondrial translation has so far not been reported. We show that high H2O2 concentrations induce a global attenuation effect, but milder concentrations specifically affect COX1 mRNA processing and translation in an Mss51-dependent manner. The redox environment modulates Mss51 functions, which are essential for regulation of COX biogenesis and aerobic energy production.

  8. The Role of Heme Chirality in the Circular Dichroism of Heme Proteins

    Science.gov (United States)

    Woody, Robert W.; Pescitelli, Gennaro

    2014-07-01

    The rotational strength (R) of the Soret transition in sperm-whale myoglobin (SW Mb), the hemoglobin from Chironomus thummi thummi (CTT Hb), and human hemoglobin (hHb) has been calculated using 20 high-resolution ( Raro > Rpep. For CTT Hb and hHB, the orders were, respectively, Rint > Rpep > Raro and Rint > Raro ≈ Rpep. Human Hb ɑ chains showed the same trend as CTT Hb. Only in the hHb β chains did Raro predominate, with the order Raro > Rint > Rpep. The total predicted Rtot for SW Mb, CTT Hb, and hHb averaged +0.77±0.10 (0.56 - 0.80), -0.37±0.12 (-0.5), and +0.31±0.17 DBM (0.23 - 0.50), respectively. (Values in parentheses are experimental values.) Thus, contrary to the currently accepted view, coupling with aromatic side-chain or peptide transitions is not the dominant factor in the Soret circular dichroism (CD) of these proteins. The Soret CD is dominated by intrinsic CD of the heme chromophore, of which vinyl torsion is the major determinant. This result suggests an explanation for the large effect of heme isomerism on the Soret CD of Mb and Hb. Rotation about the ɑ-γ axis may be associated with large changes in vinyl torsion and thus substantially alter the intrinsic CD, even reversing its sign.

  9. Cell specificity of the cytoplasmic Ca2+ response to tolbutamide is impaired in beta-cells from hyperglycemic mice

    DEFF Research Database (Denmark)

    Gustavsson, Natalia; Larsson-Nyrén, Gerd; Lindström, Per

    2006-01-01

    We recently reported that the timing and magnitude of the nutrient-induced Ca(2+) response are specific and reproducible for each isolated beta-cell. We have now used tolbutamide and arginine to test if the cell specificity exists also for the response to non-nutrient stimulation of beta-cells an...

  10. Hyperglycemia in Streptozotocin-Induced Diabetes Leads to Persistent Inflammation and Tissue Damage Following Uveitis Due to Reduced Levels of Ciliary Body Heme Oxygenase-1

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available This study investigated the heme oxygenase-1 (HO-1 and the endotoxin-induced uveitis (EIU in diabetic streptozotocin (STZ-hyperglycemic rats. STZ-hyperglycemic rats had impaired levels of the enzyme HO-1 within the ciliary bodies if compared with the nondiabetic rats. STZ-hyperglycemic rats also predisposed the eye to produce high levels of both the cytokines IL-1 β and CXCL8. Subsequent EIU further and significantly P<.01 increased the cytokines production, an effect partly prevented by hemin treatment. Most importantly, hemin, an inducer of heme oxygenase expression and activity, recovered the huge number of infiltrated polymorphonuclear leukocytes PMN within the ciliary bodies associated with STZ-hyperglycemic state and EIU damage. Impairment of the stress-sensitive enzyme HO-1 in STZ-hyperglycemic rats increases and prolongs the inflammatory response to EIU.

  11. Disorder-specific and shared neurophysiological impairments of attention and inhibition in women with attention-deficit/hyperactivity disorder and women with bipolar disorder.

    Science.gov (United States)

    Michelini, G; Kitsune, G L; Hosang, G M; Asherson, P; McLoughlin, G; Kuntsi, J

    2016-02-01

    In adults, attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) have certain overlapping symptoms, which can lead to uncertainty regarding the boundaries of the two disorders. Despite evidence of cognitive impairments in both disorders separately, such as in attentional and inhibitory processes, data on direct comparisons across ADHD and BD on cognitive-neurophysiological measures are as yet limited. We directly compared cognitive performance and event-related potential measures from a cued continuous performance test in 20 women with ADHD, 20 women with BD (currently euthymic) and 20 control women. The NoGo-N2 was attenuated in women with BD, reflecting reduced conflict monitoring, compared with women with ADHD and controls (both p < 0.05). Both ADHD and BD groups showed a reduced NoGo-P3, reflecting inhibitory control, compared with controls (both p < 0.05). In addition, the contingent negative variation was significantly reduced in the ADHD group (p = 0.05), with a trend in the BD group (p = 0.07), compared with controls. These findings indicate potential disorder-specific (conflict monitoring) and overlapping (inhibitory control, and potentially response preparation) neurophysiological impairments in women with ADHD and women with BD. The identified neurophysiological parameters further our understanding of neurophysiological impairments in women with ADHD and BD, and are candidate biomarkers that may aid in the identification of the diagnostic boundaries of the two disorders.

  12. Papua New Guinea vision-specific quality of life questionnaire: a new patient-reported outcome instrument to assess the impact of impaired vision.

    Science.gov (United States)

    Paudel, Prakash; Khadka, Jyoti; Burnett, Anthea; Hani, Yvonne; Naduvilath, Thomas; Fricke, Tim R

    2015-04-01

    The aim of this study was to develop and validate a new vision-specific quality of life (VS QoL) instrument and to assess the impact of vision impairment and eye disease on the quality of life of adults in Papua New Guinea (PNG). This study was designed as community based cross-sectional. Six hundred fourteen adults aged 18 and above were included in this study. Focus groups and interviews guided development of a 41-item instrument. Two valid subscales of the instrument were obtained using pilot data after an iterative item reduction process guided by Rasch-based parameters. The person measures (in logits) of 614 participants were used to assess quality of life using univariate and multivariate regression analysis. Rasch logits. Rasch analysis confirmed a 17-item instrument containing an 8-item activity limitation subscale and a 9-item well-being subscale. Both subscales were unidimensional and demonstrated good fit statistics, measurement precisions and absence of significant differential item functioning. A consistent deterioration in vision-specific quality of life was independently and significantly associated with levels of vision. Severity of vision impairment and ocular morbidity were independently associated with activity limitation and emotional well-being. Participants with refractive error had lower quality of life score than those with no ocular abnormality but higher score than those with cataract and other eye diseases. The 17-item PNG-VS QoL instrument is a valid and reliable instrument for the assessment of impact of impaired vision on quality of life in PNG. Vision-specific quality of life was significantly worse among participants who were older and less-educated, had lower income and have had ocular morbidities. © 2014 Royal Australian and New Zealand College of Ophthalmologists.

  13. Species-specific sensitivity to selenium-induced impairment of cortisol secretion in adrenocortical cells of rainbow trout (Oncorhynchus mykiss) and brook trout (Salvelinus fontinalis)

    International Nuclear Information System (INIS)

    Miller, L.L.; Hontela, A.

    2011-01-01

    Species differences in physiological and biochemical attributes exist even among closely related species and may underlie species-specific sensitivity to toxicants. Rainbow trout (RT) are more sensitive than brook trout (BT) to the teratogenic effects of selenium (Se), but it is not known whether all tissues exhibit this pattern of vulnerability. In this study, primary cultures of RT and BT adrenocortical cells were exposed to selenite (Na 2 SO 3 ) and selenomethionine (Se-Met) to compare cell viability and ACTH-stimulated cortisol secretion in the two fish species. Cortisol, the primary stress hormone in fish, facilitates maintenance of homeostasis when fish are exposed to stressors, including toxicants. Cell viability was not affected by Se, but selenite impaired cortisol secretion, while Se-Met did not (RT and BT EC 50 > 2000 mg/L). RT cells were more sensitive (EC 50 = 8.7 mg/L) to selenite than BT cells (EC 50 = 90.4 mg/L). To identify the targets where Se disrupts cortisol synthesis, selenite-impaired RT and BT cells were stimulated with ACTH, dbcAMP, OH-cholesterol, and pregnenolone. Selenite acted at different steps in the cortisol biosynthesis pathway in RT and BT cells, confirming a species-specific toxicity mechanism. To test the hypothesis that oxidative stress mediates Se-induced toxicity, selenite-impaired RT cells were exposed to NAC, BSO and antioxidants (DETCA, ATA, Vit A, and Vit E). Inhibition of SOD by DETCA enhanced selenite-induced cortisol impairment, indicating that oxidative stress plays a role in Se toxicity; however, modifying GSH content of the cells did not have an effect. The results of this study, with two closely related salmonids, provided additional evidence for species-specific differences in sensitivity to Se which should be considered when setting thresholds and water quality guidelines. - Research Highlights: → We investigated species-specific sensitivity to Se in trout adrenocortical cells. → Selenite, not Se-Met, disrupts

  14. Heme oxygenase activity correlates with serum indices of iron homeostasis in healthy nonsmokers

    Science.gov (United States)

    Heme oxygenase (HO) catalyzes the breakdown of heme to carbon monoxide, iron, and biliverdin. While the use of genetically altered animal models in investigation has established distinct associations between HO activity and systemic iron availability, studies have not yet confirm...

  15. Physical Impairment

    Science.gov (United States)

    Trewin, Shari

    Many health conditions can lead to physical impairments that impact computer and Web access. Musculoskeletal conditions such as arthritis and cumulative trauma disorders can make movement stiff and painful. Movement disorders such as tremor, Parkinsonism and dystonia affect the ability to control movement, or to prevent unwanted movements. Often, the same underlying health condition also has sensory or cognitive effects. People with dexterity impairments may use a standard keyboard and mouse, or any of a wide range of alternative input mechanisms. Examples are given of the diverse ways that specific dexterity impairments and input mechanisms affect the fundamental actions of Web browsing. As the Web becomes increasingly sophisticated, and physically demanding, new access features at the Web browser and page level will be necessary.

  16. Novel Insights in Mammalian Catalase Heme Maturation: Effect of NO and Thioredoxin-1

    OpenAIRE

    Chakravarti, Ritu; Gupta, Karishma; Majors, Alana; Ruple, Lisa; Aronica, Mark; Stuehr, Dennis J.

    2015-01-01

    Catalase is a tetrameric heme-containing enzyme with essential antioxidant functions in biology. Multiple factors including nitric oxide (NO) have been shown to attenuate its activity. However, the possible impact of NO in relation to the maturation of active catalase, including its heme acquisition and tetramer formation, has not been investigated. We found that NO attenuates heme insertion into catalase in both short-term and long-term incubations. The NO inhibition in catalase heme incorpo...

  17. Heme in pathophysiology: a matter of scavenging, metabolism and trafficking across cell membranes

    OpenAIRE

    Chiabrando, Deborah; Vinchi, Francesca; Fiorito, Veronica; Mercurio, Sonia; Tolosano, Emanuela

    2014-01-01

    Heme (iron-protoporphyrin IX) is an essential co-factor involved in multiple biological processes: oxygen transport and storage, electron transfer, drug and steroid metabolism, signal transduction, and micro RNA processing. However, excess free-heme is highly toxic due to its ability to promote oxidative stress and lipid peroxidation, thus leading to membrane injury and, ultimately, apoptosis. Thus, heme metabolism needs to be finely regulated. Intracellular heme amount is controlled at multi...

  18. Staphylococcus aureus HemX Modulates Glutamyl-tRNA Reductase Abundance To Regulate Heme Biosynthesis

    OpenAIRE

    Jacob E. Choby; Caroline M. Grunenwald; Arianna I. Celis; Svetlana Y. Gerdes; Jennifer L. DuBois; Eric P. Skaar; Kimberly A. Kline

    2018-01-01

    Staphylococcus aureus is responsible for a significant amount of devastating disease. Its ability to colonize the host and cause infection is supported by a variety of proteins that are dependent on the cofactor heme. Heme is a porphyrin used broadly across kingdoms and is synthesized de novo from common cellular precursors and iron. While heme is critical to bacterial physiology, it is also toxic in high concentrations, requiring that organisms encode regulatory processes to control heme hom...

  19. Human heme oxygenase oxidation of 5- and 15-phenylhemes.

    Science.gov (United States)

    Wang, Jinling; Niemevz, Fernando; Lad, Latesh; Huang, Liusheng; Alvarez, Diego E; Buldain, Graciela; Poulos, Thomas L; de Montellano, Paul R Ortiz

    2004-10-08

    Human heme oxygenase-1 (hHO-1) catalyzes the O2-dependent oxidation of heme to biliverdin, CO, and free iron. Previous work indicated that electrophilic addition of the terminal oxygen of the ferric hydroperoxo complex to the alpha-meso-carbon gives 5-hydroxyheme. Earlier efforts to block this reaction with a 5-methyl substituent failed, as the reaction still gave biliverdin IXalpha. Surprisingly, a 15-methyl substituent caused exclusive cleavage at the gamma-meso-rather than at the normal, unsubstituted alpha-meso-carbon. No CO was formed in these reactions, but the fragment cleaved from the porphyrin eluded identification. We report here that hHO-1 cleaves 5-phenylheme to biliverdin IXalpha and oxidizes 15-phenylheme at the alpha-meso position to give 10-phenylbiliverdin IXalpha. The fragment extruded in the oxidation of 5-phenylheme is benzoic acid, one oxygen of which comes from O2 and the other from water. The 2.29- and 2.11-A crystal structures of the hHO-1 complexes with 1- and 15-phenylheme, respectively, show clear electron density for both the 5- and 15-phenyl rings in both molecules of the asymmetric unit. The overall structure of 15-phenylheme-hHO-1 is similar to that of heme-hHO-1 except for small changes in distal residues 141-150 and in the proximal Lys18 and Lys22. In the 5-phenylheme-hHO-1 structure, the phenyl-substituted heme occupies the same position as heme in the heme-HO-1 complex but the 5-phenyl substituent disrupts the rigid hydrophobic wall of residues Met34, Phe214, and residues 26-42 near the alpha-meso carbon. The results provide independent support for an electrophilic oxidation mechanism and support a role for stereochemical control of the reaction regiospecificity.

  20. MK-801 impairs cognitive coordination on a rotating arena (Carousel and contextual specificity of hippocampal immediate-early gene expression in a rat model of psychosis

    Directory of Open Access Journals (Sweden)

    Štěpán eKubík

    2014-03-01

    Full Text Available Flexible behavior in dynamic, real-world environments requires more than static spatial learning and memory. Discordant and unstable cues must be organized in coherent subsets to give rise to meaningful spatial representations. We model this form of cognitive coordination on a rotating arena - Carousel where arena- and room-bound spatial cues are dissociated. Hippocampal neuronal ensemble activity can repeatedly switch between multiple representations of such an environment. Injection of tetrodotoxin into one hippocampus prevents cognitive coordination during avoidance of a stationary room-defined place on the Carousel and increases coactivity of previously unrelated neurons in the uninjected hippocampus. Place avoidance on the Carousel is impaired after systemic administration of non-competitive NMDAr blockers (MK-801 used to model schizophrenia in animals and people. We tested if this effect is due to cognitive disorganization or other effect of NMDAr antagonism such as hyperlocomotion, spatial memory impairment, or general learning deficit. We also examined if the same dose of MK-801 alters patterns of immediate-early gene (IEG expression in the hippocampus. IEG expression is triggered in neuronal nuclei in a context-specific manner after behavioral exploration and it is used to map activity in neuronal populations. IEG expression is critical for maintenance of synaptic plasticity and memory consolidation. We show that the same dose of MK-801 that impairs spatial coordination of rats on the Carousel also eliminates contextual specificity of IEG expression in hippocampal CA1 ensembles. This effect is due to increased similarity between ensembles activated in different environments, consistent with the idea that it is caused by increased coactivity between neurons, which did not fire together before. Our data support the proposition of the Hypersynchrony theory that cognitive disorganization in psychosis is due to increased coactivity between

  1. MK-801 Impairs Cognitive Coordination on a Rotating Arena (Carousel) and Contextual Specificity of Hippocampal Immediate-Early Gene Expression in a Rat Model of Psychosis.

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    Kubík, Stěpán; Buchtová, Helena; Valeš, Karel; Stuchlík, Aleš

    2014-01-01

    Flexible behavior in dynamic, real-world environments requires more than static spatial learning and memory. Discordant and unstable cues must be organized in coherent subsets to give rise to meaningful spatial representations. We model this form of cognitive coordination on a rotating arena - Carousel where arena- and room-bound spatial cues are dissociated. Hippocampal neuronal ensemble activity can repeatedly switch between multiple representations of such an environment. Injection of tetrodotoxin into one hippocampus prevents cognitive coordination during avoidance of a stationary room-defined place on the Carousel and increases coactivity of previously unrelated neurons in the uninjected hippocampus. Place avoidance on the Carousel is impaired after systemic administration of non-competitive NMDAr blockers (MK-801) used to model schizophrenia in animals and people. We tested if this effect is due to cognitive disorganization or other effect of NMDAr antagonism such as hyperlocomotion, spatial memory impairment, or general learning deficit. We also examined if the same dose of MK-801 alters patterns of immediate-early gene (IEG) expression in the hippocampus. IEG expression is triggered in neuronal nuclei in a context-specific manner after behavioral exploration and it is used to map activity in neuronal populations. IEG expression is critical for maintenance of synaptic plasticity and memory consolidation. We show that the same dose of MK-801 that impairs spatial coordination of rats on the Carousel also eliminates contextual specificity of IEG expression in hippocampal CA1 ensembles. This effect is due to increased similarity between ensembles activated in different environments, consistent with the idea that it is caused by increased coactivity between neurons, which did not previously fire together. Our data support the proposition of the Hypersynchrony theory that cognitive disorganization in psychosis is due to increased coactivity between unrelated

  2. MK-801 Impairs Cognitive Coordination on a Rotating Arena (Carousel) and Contextual Specificity of Hippocampal Immediate-Early Gene Expression in a Rat Model of Psychosis

    Science.gov (United States)

    Kubík, Štěpán; Buchtová, Helena; Valeš, Karel; Stuchlík, Aleš

    2014-01-01

    Flexible behavior in dynamic, real-world environments requires more than static spatial learning and memory. Discordant and unstable cues must be organized in coherent subsets to give rise to meaningful spatial representations. We model this form of cognitive coordination on a rotating arena – Carousel where arena- and room-bound spatial cues are dissociated. Hippocampal neuronal ensemble activity can repeatedly switch between multiple representations of such an environment. Injection of tetrodotoxin into one hippocampus prevents cognitive coordination during avoidance of a stationary room-defined place on the Carousel and increases coactivity of previously unrelated neurons in the uninjected hippocampus. Place avoidance on the Carousel is impaired after systemic administration of non-competitive NMDAr blockers (MK-801) used to model schizophrenia in animals and people. We tested if this effect is due to cognitive disorganization or other effect of NMDAr antagonism such as hyperlocomotion, spatial memory impairment, or general learning deficit. We also examined if the same dose of MK-801 alters patterns of immediate-early gene (IEG) expression in the hippocampus. IEG expression is triggered in neuronal nuclei in a context-specific manner after behavioral exploration and it is used to map activity in neuronal populations. IEG expression is critical for maintenance of synaptic plasticity and memory consolidation. We show that the same dose of MK-801 that impairs spatial coordination of rats on the Carousel also eliminates contextual specificity of IEG expression in hippocampal CA1 ensembles. This effect is due to increased similarity between ensembles activated in different environments, consistent with the idea that it is caused by increased coactivity between neurons, which did not previously fire together. Our data support the proposition of the Hypersynchrony theory that cognitive disorganization in psychosis is due to increased coactivity between unrelated

  3. Impaired intervertebral disc development and premature disc degeneration in mice with notochord-specific deletion of CCN2.

    Science.gov (United States)

    Bedore, Jake; Sha, Wei; McCann, Matthew R; Liu, Shangxi; Leask, Andrew; Séguin, Cheryle A

    2013-10-01

    Currently, our ability to treat intervertebral disc (IVD) degeneration is hampered by an incomplete understanding of disc development and aging. The specific function of matricellular proteins, including CCN2, during these processes remains an enigma. The aim of this study was to determine the tissue-specific localization of CCN proteins and to characterize their role in IVD tissues during embryonic development and age-related degeneration by using a mouse model of notochord-specific CCN2 deletion. Expression of CCN proteins was assessed in IVD tissues from wild-type mice beginning on embryonic day 15.5 to 17 months of age. Given the enrichment of CCN2 in notochord-derived tissues, we generated notochord-specific CCN2-null mice to assess the impact on the IVD structure and extracellular matrix composition. Using a combination of histologic evaluation and magnetic resonance imaging (MRI), IVD health was assessed. Loss of the CCN2 gene in notochord-derived cells disrupted the formation of IVDs in embryonic and newborn mice, resulting in decreased levels of aggrecan and type II collagen and concomitantly increased levels of type I collagen within the nucleus pulposus. CCN2-knockout mice also had altered expression of CCN1 (Cyr61) and CCN3 (Nov). Mirroring its role during early development, notochord-specific CCN2 deletion accelerated age-associated degeneration of IVDs. Using a notochord-specific gene targeting strategy, this study demonstrates that CCN2 expression by nucleus pulposus cells is essential to the regulation of IVD development and age-associated tissue maintenance. The ability of CCN2 to regulate the composition of the intervertebral disc suggests that it may represent an intriguing clinical target for the treatment of disc degeneration. Copyright © 2013 by the American College of Rheumatology.

  4. Atypical profiles and modulations of heme-enzymes catalyzed outcomes by low amounts of diverse additives suggest diffusible radicals' obligatory involvement in such redox reactions.

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    Manoj, Kelath Murali; Parashar, Abhinav; Venkatachalam, Avanthika; Goyal, Sahil; Satyalipsu; Singh, Preeti Gunjan; Gade, Sudeep K; Periyasami, Kalaiselvi; Jacob, Reeba Susan; Sardar, Debosmita; Singh, Shanikant; Kumar, Rajan; Gideon, Daniel A

    2016-06-01

    Peroxidations mediated by heme-enzymes have been traditionally studied under a single-site (heme distal pocket), non-sequential (ping-pong), two-substrates binding scheme of Michaelis-Menten paradigm. We had reported unusual modulations of peroxidase and P450 reaction outcomes and explained it invoking diffusible reactive species [Manoj, 2006; Manoj et al., 2010; Andrew et al., 2011, Parashar et al., 2014 & Venkatachalam et al., 2016]. A systematic investigation of specific product formation rates was undertaken to probe the hypothesis that involvement of diffusible reactive species could explain undefined substrate specificities and maverick modulations (sponsored by additives) of heme-enzymes. When the rate of specific product formation was studied as a function of reactants' concentration or environmental conditions, we noted marked deviations from normal profiles. We report that heme-enzyme mediated peroxidations of various substrates are inhibited (or activated) by sub-equivalent concentrations of diverse redox-active additives and this is owing to multiple redox equilibriums in the milieu. At low enzyme and peroxide concentrations, the enzyme is seen to recycle via a one-electron (oxidase) cycle, which does not require the substrate to access the heme centre. Schemes are provided that explain the complex mechanistic cycle, kinetics & stoichiometry. It is not obligatory for an inhibitor or substrate to interact with the heme centre for influencing overall catalysis. Roles of diffusible reactive species explain catalytic outcomes at low enzyme and reactant concentrations. The current work highlights the scope/importance of redox enzyme reactions that could occur "out of the active site" in biological or in situ systems. Copyright © 2016 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.

  5. Sequential Prediction of Literacy Achievement for Specific Learning Disabilities Contrasting in Impaired Levels of Language in Grades 4 to 9

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    Sanders, Elizabeth A.; Berninger, Virginia W.; Abbott, Robert D.

    2018-01-01

    Sequential regression was used to evaluate whether language-related working memory components uniquely predict reading and writing achievement beyond cognitive-linguistic translation for students in Grades 4 through 9 (N = 103) with specific learning disabilities (SLDs) in subword handwriting (dysgraphia, n = 25), word reading and spelling…

  6. Management of oxidative stress by heme oxygenase-1 in cisplatin-induced toxicity in renal tubular cells.

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    Schaaf, G J; Maas, R F M; de Groene, E M; Fink-Gremmels, J

    2002-08-01

    Induction of heme oxygenase-1 (HO-1) may serve as an immediate protective response during treatment with the cytostatic drug cisplatin (CDDP). Oxidative pathways participate in the characteristic nephrotoxicity of CDDP. In the present study, cultured tubular cells (LLC-PK1) were used to investigate whether induction of HO provided protection against CDDP by maintaining the cellular redox balance. The antioxidants, alpha-tocopherol (TOCO) and N-acetylcysteine (NAC), were used to demonstrate that elevation of ROS levels contribute to the development of CDDP-induced cytotoxicity. Chemical modulators of HO activity were used to investigate the role of HO herein. Hemin was used to specifically induce HO-1, while exposure of the cells to tin-protoporphyrin (SnPP) was shown to inhibit HO activity. Hemin treatment prior to CDDP-exposure significantly decreased the generation of ROS to control levels, while inhibition of HO increased the ROS levels beyond the levels measured in cells treated with CDDP alone. Furthermore, HO induction protected significantly against the cytotoxicity of CDDP, although this protection was limited. Similar results were obtained when the cells were preincubated with TOCO, suggesting that mechanisms other than impairment of the redox ratio are important in CDDP-induced loss of cell viability in vitro. In addition, SnPP treatment exacerbated the oxidative response and cytotoxicity of CDDP, especially at low CDDP concentrations. We therefore conclude that HO is able to directly limit the CDDP-induced oxidative stress response and thus serves as safeguard of the cellular redox balance.

  7. Malaria parasite-synthesized heme is essential in the mosquito and liver stages and complements host heme in the blood stages of infection.

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    Viswanathan Arun Nagaraj

    Full Text Available Heme metabolism is central to malaria parasite biology. The parasite acquires heme from host hemoglobin in the intraerythrocytic stages and stores it as hemozoin to prevent free heme toxicity. The parasite can also synthesize heme de novo, and all the enzymes in the pathway are characterized. To study the role of the dual heme sources in malaria parasite growth and development, we knocked out the first enzyme, δ-aminolevulinate synthase (ALAS, and the last enzyme, ferrochelatase (FC, in the heme-biosynthetic pathway of Plasmodium berghei (Pb. The wild-type and knockout (KO parasites had similar intraerythrocytic growth patterns in mice. We carried out in vitro radiolabeling of heme in Pb-infected mouse reticulocytes and Plasmodium falciparum-infected human RBCs using [4-(14C] aminolevulinic acid (ALA. We found that the parasites incorporated both host hemoglobin-heme and parasite-synthesized heme into hemozoin and mitochondrial cytochromes. The similar fates of the two heme sources suggest that they may serve as backup mechanisms to provide heme in the intraerythrocytic stages. Nevertheless, the de novo pathway is absolutely essential for parasite development in the mosquito and liver stages. PbKO parasites formed drastically reduced oocysts and did not form sporozoites in the salivary glands. Oocyst production in PbALASKO parasites recovered when mosquitoes received an ALA supplement. PbALASKO sporozoites could infect mice only when the mice received an ALA supplement. Our results indicate the potential for new therapeutic interventions targeting the heme-biosynthetic pathway in the parasite during the mosquito and liver stages.

  8. The role of social cognition and prosocial behaviour in relation to the socio-emotional functioning of primary aged children with specific language impairment.

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    Bakopoulou, Ioanna; Dockrell, Julie E

    2016-01-01

    Children with language impairments often experience difficulties with their socio-emotional functioning and poorly developed prosocial behaviour. However, the nature of the association between language impairment and difficulties with socio-emotional functioning remains unclear. The social cognition skills of a group of primary-aged children (6-11 years old) with Specific Language Impairment (SLI) were examined in relation to their teachers' ratings of socio-emotional functioning. Forty-two children with SLI were individually matched with 42 children for chronological age and non-verbal cognitive ability, and 42 children for receptive language ability. The children all attended mainstream primary schools or one Language Unit. Four aspects of social cognition were directly assessed: emotion identification, emotion labelling, inferring the causes of emotions, and knowledge of conflict resolution strategies. The children's socio-emotional functioning was assessed using the Strengths and Difficulties questionnaire (SDQ), a standardised measure, completed by their teachers. Associations between children's performance on tasks of social cognition and children's socio-emotional functioning were explored. Significant group differences were found for all social cognition tasks. The SLI group was rated to experience significantly more problems with socio-emotional functioning by their teachers than both control groups, indicating problems with all aspects of socio-emotional functioning. Social cognition and prosocial behaviour, but not language ability, predicted teacher-rated behavioural, emotional and social difficulties for the SLI group. The results challenge current understanding of socio-emotional functioning in children with SLI by pointing to the crucial role of social cognition and prosocial behaviour. Factors other than expressive and receptive language play a role in the socio-emotional functioning of children with SLI. Copyright © 2015 Elsevier Ltd. All rights

  9. Impaired spatial learning strategies and novel object recognition in mice haploinsufficient for the dual specificity tyrosine-regulated kinase-1A (Dyrk1A.

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    Glòria Arqué

    Full Text Available BACKGROUND: Pathogenic aneuploidies involve the concept of dosage-sensitive genes leading to over- and underexpression phenotypes. Monosomy 21 in human leads to mental retardation and skeletal, immune and respiratory function disturbances. Most of the human condition corresponds to partial monosomies suggesting that critical haploinsufficient genes may be responsible for the phenotypes. The DYRK1A gene is localized on the human chromosome 21q22.2 region, and has been proposed to participate in monosomy 21 phenotypes. It encodes a dual-specificity kinase involved in neuronal development and in adult brain physiology, but its possible role as critical haploinsufficient gene in cognitive function has not been explored. METHODOLOGY/PRINCIPAL FINDINGS: We used mice heterozygous for a Dyrk1A targeted mutation (Dyrk1A+/- to investigate the implication of this gene in the cognitive phenotypes of monosomy 21. Performance of Dyrk1A+/- mice was assayed 1/ in a navigational task using the standard hippocampally related version of the Morris water maze, 2/ in a swimming test designed to reveal potential kinesthetic and stress-related behavioral differences between control and heterozygous mice under two levels of aversiveness (25 degrees C and 17 degrees C and 3/ in a long-term novel object recognition task, sensitive to hippocampal damage. Dyrk1A+/- mice showed impairment in the development of spatial learning strategies in a hippocampally-dependent memory task, they were impaired in their novel object recognition ability and were more sensitive to aversive conditions in the swimming test than euploid control animals. CONCLUSIONS/SIGNIFICANCE: The present results are clear examples where removal of a single gene has a profound effect on phenotype and indicate that haploinsufficiency of DYRK1A might contribute to an impairment of cognitive functions and stress coping behavior in human monosomy 21.

  10. Parental phonological memory contributes to prediction of outcome of late talkers from 20 months to 4 years: a longitudinal study of precursors of specific language impairment

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    Bishop Dorothy VM

    2012-02-01

    Full Text Available Abstract Background Many children who are late talkers go on to develop normal language, but others go on to have longer-term language difficulties. In this study, we considered which factors were predictive of persistent problems in late talkers. Methods Parental report of expressive vocabulary at 18 months of age was used to select 26 late talkers and 70 average talkers, who were assessed for language and cognitive ability at 20 months of age. Follow-up at 4 years of age was carried out for 24 late and 58 average talkers. A psychometric test battery was used to categorize children in terms of language status (unimpaired or impaired and nonverbal ability (normal range or more than 1 SD below average. The vocabulary and non-word repetition skills of the accompanying parent were also assessed. Results Among the late talkers, seven (29% met our criteria for specific language impairment (SLI at 4 years of age, and a further two (8% had low nonverbal ability. In the group of average talkers, eight (14% met the criteria for SLI at 4 years, and five other children (8% had low nonverbal ability. Family history of language problems was slightly better than late-talker status as a predictor of SLI.. The best predictors of SLI at 20 months of age were score on the receptive language scale of the Mullen Scales of Early Learning and the parent's performance on a non-word repetition task. Maternal education was not a significant predictor of outcome. Conclusions In this study, around three-quarters of late talkers did not have any language difficulties at 4 years of age, provided there was no family history of language impairment. A family history of language-literacy problems was found to be a significant predictor for persisting problems. Nevertheless, there are children with SLI for whom prediction is difficult because they did not have early language delay.

  11. Heme and menaquinone induced electron transport in lactic acid bacteria

    NARCIS (Netherlands)

    Brooijmans, R.J.W.; Smit, B.; Santos, dos F.; Riel, van J.; Vos, de W.M.; Hugenholtz, J.

    2009-01-01

    ABSTRACT: BACKGROUND: For some lactic acid bacteria higher biomass production as a result of aerobic respiration has been reported upon supplementation with heme and menaquinone. In this report, we have studied a large number of species among lactic acid bacteria for the existence of this trait.

  12. Cysteine-independent activation/inhibition of heme oxygenase-2

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    Dragic Vukomanovic

    2016-01-01

    Full Text Available Reactive thiols of cysteine (cys residues in proteins play a key role in transforming chemical reactivity into a biological response. The heme oxygenase-2 (HO-2 isozyme contains two cys residues that have been implicated in binding of heme and also the regulation of its activity. In this paper, we address the question of a role for cys residues for the HO-2 inhibitors or activators designed in our laboratory. We tested the activity of full length recombinant human heme oxygenase-2 (FL-hHO-2 and its analog in which cys265 and cys282 were both replaced by alanine to determine the effect on activation by menadione (MD and inhibition by QC-2350. Similar inhibition by QC-2350 and almost identical activation by MD was observed for both recombinant FL-hHO-2s. Our findings are interpreted to mean that thiols of FL-hHO-2s are not involved in HO-2 activation or inhibition by the compounds that have been designed and identified by us. Activation or inhibition of HO-2 by our compounds should be attributed to a mechanism other than altering binding affinity of HO-2 for heme through cys265 and cys282.

  13. Heme and HO-1 inhibition of HCV, HBV, and HIV

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    Warren N Schmidt

    2012-10-01

    Full Text Available Hepatitis C virus, human immunodeficiency virus, and hepatitis B virus are chronic viral infections that cause considerable morbidity and mortality throughout the world. In the decades following the identification and sequencing of these viruses, in vitro experiments demonstrated that heme oxygenase-1, its oxidative products, and related compounds of the heme oxygenase system are virucidal for all three viruses. The purpose of this review is to critically evaluate and summarize the seminal studies that described and characterized this remarkable behavior. It will also discuss more recent work that discovered the antiviral mechanisms and target sites of these unique antiviral agents. In spite of the fact that these viruses are diverse pathogens with quite profound differences in structure and life cycle, it is significant that heme and related compounds show striking similarity for viral target sites across all three species. Collectively, these findings strongly indicate that we should move forward and develop heme and related tetrapyrroles into versatile antiviral agents that could be used therapeutically in patients with single or multiple viral infections.

  14. Cysteine-independent activation/inhibition of heme oxygenase-2.

    Science.gov (United States)

    Vukomanovic, Dragic; Rahman, Mona N; Maines, Mahin D; Ozolinš, Terence Rs; Szarek, Walter A; Jia, Zongchao; Nakatsu, Kanji

    2016-03-01

    Reactive thiols of cysteine (cys) residues in proteins play a key role in transforming chemical reactivity into a biological response. The heme oxygenase-2 (HO-2) isozyme contains two cys residues that have been implicated in binding of heme and also the regulation of its activity. In this paper, we address the question of a role for cys residues for the HO-2 inhibitors or activators designed in our laboratory. We tested the activity of full length recombinant human heme oxygenase-2 (FL-hHO-2) and its analog in which cys265 and cys282 were both replaced by alanine to determine the effect on activation by menadione (MD) and inhibition by QC-2350. Similar inhibition by QC-2350 and almost identical activation by MD was observed for both recombinant FL-hHO-2s. Our findings are interpreted to mean that thiols of FL-hHO-2s are not involved in HO-2 activation or inhibition by the compounds that have been designed and identified by us. Activation or inhibition of HO-2 by our compounds should be attributed to a mechanism other than altering binding affinity of HO-2 for heme through cys265 and cys282.

  15. AN ELISA ASSAY FOR HEME OXYGENASE (HO-1)

    Science.gov (United States)

    An ELISA assay for heme oxygenase (HO-l ) Abstract A double antibody capture ELISA for the HO-l protein has been developed to separately quantitate HO-I protein. The use of 2.5% NP40 detergent greatly assists in freeing HO-l protein from membranes and/or other cel...

  16. Improved Method for the Incorporation of Heme Cofactors into Recombinant Proteins Using Escherichia coli Nissle 1917.

    Science.gov (United States)

    Fiege, Kerstin; Querebillo, Christine Joy; Hildebrandt, Peter; Frankenberg-Dinkel, Nicole

    2018-05-15

    Recombinant production of heme proteins in Escherichia coli is often limited by the availability of heme in the host. Therefore, several methods, including the reconstitution of heme proteins after production but prior to purification or the HPEX system, conferring the ability to take up external heme have been developed and used in the past. Here we describe the use of the apathogenic E. coli strain Nissle 1917 (EcN) as a suitable host for the recombinant production of heme proteins. EcN has an advantage over commonly used lab strains in that it is able to take up heme from the environment through the heme receptor ChuA. Expression of several heme proteins from different prokaryotic sources led to high yield and quantitative incorporation of the cofactor when heme was supplied in the growth medium. Comparative UV-vis and resonance Raman measurements revealed that the method employed has significant influence on heme coordination with the EcN system representing the most native situation. Therefore, the use of EcN as a host for recombinant heme protein production represents an inexpensive and straightforward method to facilitate further investigations of structure and function.

  17. Coordinate expression of heme and globin is essential for effective erythropoiesis.

    Science.gov (United States)

    Doty, Raymond T; Phelps, Susan R; Shadle, Christina; Sanchez-Bonilla, Marilyn; Keel, Siobán B; Abkowitz, Janis L

    2015-12-01

    Erythropoiesis requires rapid and extensive hemoglobin production. Heme activates globin transcription and translation; therefore, heme synthesis must precede globin synthesis. As free heme is a potent inducer of oxidative damage, its levels within cellular compartments require stringent regulation. Mice lacking the heme exporter FLVCR1 have a severe macrocytic anemia; however, the mechanisms that underlie erythropoiesis dysfunction in these animals are unclear. Here, we determined that erythropoiesis failure occurs in these animals at the CFU-E/proerythroblast stage, a point at which the transferrin receptor (CD71) is upregulated, iron is imported, and heme is synthesized--before ample globin is produced. From the CFU-E/proerythroblast (CD71(+) Ter119(-) cells) stage onward, erythroid progenitors exhibited excess heme content, increased cytoplasmic ROS, and increased apoptosis. Reducing heme synthesis in FLVCR1-defient animals via genetic and biochemical approaches improved the anemia, implying that heme excess causes, and is not just associated with, the erythroid marrow failure. Expression of the cell surface FLVCR1 isoform, but not the mitochondrial FLVCR1 isoform, restored normal rbc production, demonstrating that cellular heme export is essential. Together, these studies provide insight into how heme is regulated to allow effective erythropoiesis, show that erythropoiesis fails when heme is excessive, and emphasize the importance of evaluating Ter119(-) erythroid cells when studying erythroid marrow failure in murine models.

  18. ATP-binding cassette B10 regulates early steps of heme synthesis.

    Science.gov (United States)

    Bayeva, Marina; Khechaduri, Arineh; Wu, Rongxue; Burke, Michael A; Wasserstrom, J Andrew; Singh, Neha; Liesa, Marc; Shirihai, Orian S; Langer, Nathaniel B; Paw, Barry H; Ardehali, Hossein

    2013-07-19

    Heme plays a critical role in gas exchange, mitochondrial energy production, and antioxidant defense in cardiovascular system. The mitochondrial transporter ATP-binding cassette (ABC) B10 has been suggested to export heme out of the mitochondria and is required for normal hemoglobinization of erythropoietic cells and protection against ischemia-reperfusion injury in the heart; however, its primary function has not been established. The aim of this study was to identify the function of ABCB10 in heme synthesis in cardiac cells. Knockdown of ABCB10 in cardiac myoblasts significantly reduced heme levels and the activities of heme-containing proteins, whereas supplementation with δ-aminolevulinic acid reversed these defects. Overexpression of mitochondrial δ-aminolevulinic acid synthase 2, the rate-limiting enzyme upstream of δ-aminolevulinic acid export, failed to restore heme levels in cells with ABCB10 downregulation. ABCB10 and heme levels were increased by hypoxia, and reversal of ABCB10 upregulation caused oxidative stress and cell death. Furthermore, ABCB10 knockdown in neonatal rat cardiomyocytes resulted in a significant delay of calcium removal from the cytoplasm, suggesting a relaxation defect. Finally, ABCB10 expression and heme levels were altered in failing human hearts and mice with ischemic cardiomyopathy. ABCB10 plays a critical role in heme synthesis pathway by facilitating δ-aminolevulinic acid