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Production of trichodiene by Trichoderma harzianum alters the perception of this biocontrol strain by plants and antagonized fungi.
PubMed
Malmierca, Mónica G; McCormick, Susan P; Cardoza, Rosa E; Alexander, Nancy J; Monte, Enrique; Gutiérrez, Santiago
2015-08-01
Trichothecenes are phytotoxic sesquiterpenic mycotoxins that can act as virulence factors in plant diseases. Harzianum A (HA) is a non-phytotoxic trichothecene produced by Trichoderma arundinaceum. The first step in HA biosynthesis is the conversion of farnesyl diphosphate to trichodiene (TD), a volatile organic compound (VOC), catalysed by a sesquiterpene synthase encoded by the tri5 gene. Expression of tri5 in the biocontrol strain Trichoderma harzianum CECT 2413 resulted in production of TD in parallel with a reduction of ergosterol biosynthesis and an unexpected increase in the level of squalene. Transformants expressing tri5 displayed low chitinase activity and induced expression of Botrytis cinerea BOT genes, although their total antagonistic potential against phytopathogenic fungi was not reduced. VOCs released by the tri5-transformant induced expression of tomato defence genes related to salicylic acid (SA), and TD itself strongly induced the expression of SA-responsive genes and reduced the development of lateral roots. Together, these results suggest that TD acts as a signalling VOC in the interactions of Trichoderma with plants and other microorganisms by modulating the perception of this fungus to a given environment. Moreover, the TD ability to induce systemic defences indicates that complex trichothecene structures may not be necessary for inducing such responses. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.
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Vocal Interaction between Children with Down syndrome and their Parents
PubMed Central
Thiemann-Bourque, Kathy S.; Warren, Steven F.; Brady, Nancy; Gilkerson, Jill; Richards, Jeffrey A.
2014-01-01
Purpose The purpose of this study was to describe differences in parent input and child vocal behaviors of children with Down syndrome (DS) compared to typically developing (TD) children. The goals were to describe the language learning environments at distinctly different ages in early childhood. Method Nine children with DS and 9 age-matched TD children participated; four children in each group were ages 9–11 months and five were between 25–54 months. Measures were derived from automated vocal analysis. A digital language processer measured the richness of the child’s language environment, including number of adult words, conversational turns, and child vocalizations. Results Analyses indicated no significant differences in words spoken by parents of younger vs. older children with DS, and significantly more words spoken by parents of TD children than parents of children with DS. Differences between the DS and TD groups were observed in rates of all vocal behaviors; with no differences noted between the younger vs. older children with DS, and the younger TD children did not vocalize significantly more than the younger DS children. Conclusions Parents of children with DS continue to provide consistent levels of input across the early language learning years; however, child vocal behaviors remain low after the age of 24 months suggesting the need for additional and alternative intervention approaches. PMID:24686777
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I Think We're Alone Now: Solitary Social Behaviors in Adolescents with Autism Spectrum Disorder.
PubMed
Zane, Emily; Neumeyer, Kayla; Mertens, Julia; Chugg, Amanda; Grossman, Ruth B
2017-10-10
Research into emotional responsiveness in Autism Spectrum Disorder (ASD) has yielded mixed findings. Some studies report uniform, flat and emotionless expressions in ASD; others describe highly variable expressions that are as or even more intense than those of typically developing (TD) individuals. Variability in findings is likely due to differences in study design: some studies have examined posed (i.e., not spontaneous expressions) and others have examined spontaneous expressions in social contexts, during which individuals with ASD-by nature of the disorder-are likely to behave differently than their TD peers. To determine whether (and how) spontaneous facial expressions and other emotional responses are different from TD individuals, we video-recorded the spontaneous responses of children and adolescents with and without ASD (between the ages of 10 and 17 years) as they watched emotionally evocative videos in a non-social context. Researchers coded facial expressions for intensity, and noted the presence of laughter and other responsive vocalizations. Adolescents with ASD displayed more intense, frequent and varied spontaneous facial expressions than their TD peers. They also produced significantly more emotional vocalizations, including laughter. Individuals with ASD may display their emotions more frequently and more intensely than TD individuals when they are unencumbered by social pressure. Differences in the interpretation of the social setting and/or understanding of emotional display rules may also contribute to differences in emotional behaviors between groups.
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Parents' strategies to elicit autobiographical memories in autism spectrum disorders, developmental language disorders and typically developing children.
PubMed
Goldman, Sylvie; DeNigris, Danielle
2015-05-01
Conversations about the past support the development of autobiographical memory. Parents' strategies to elicit child's participation and recall during past event conversations were compared across three school-age diagnostic groups: autism spectrum disorder (ASD, n = 11), developmental language disorders (n = 11) and typically developing (TD, n = 11). We focused on the prevalence of directives versus enrichment of events. Groups did not differ in number of events, length, and total turns. However, parents of children with ASD produced more direct questions, corrections, and unrelated turns than parents of TD children. Results highlight how parents adjusted their conversational style to their child's communication difficulties to maximize interactions and how these strategies may affect the development of personal conversations.
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Don’t speak too fast! Processing of fast rate speech in children with specific language impairment
PubMed Central
Bedoin, Nathalie; Krifi-Papoz, Sonia; Herbillon, Vania; Caillot-Bascoul, Aurélia; Gonzalez-Monge, Sibylle; Boulenger, Véronique
2018-01-01
Background 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. Method 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. Results 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. Conclusion 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. PMID:29373610
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Achilles tendon moment arm length is smaller in children with cerebral palsy than in typically developing children.
PubMed
Kalkman, Barbara M; Bar-On, Lynn; Cenni, Francesco; Maganaris, Constantinos N; Bass, Alfie; Holmes, Gill; Desloovere, Kaat; Barton, Gabor J; O'Brien, Thomas D
2017-05-03
When studying muscle and whole-body function in children with cerebral palsy (CP), knowledge about both internal and external moment arms is essential since they determine the mechanical advantage of a muscle over an external force. Here we asked if Achilles tendon moment arm (MA AT ) length is different in children with CP and age-matched typically developing (TD) children, and if MA AT can be predicted from anthropometric measurements. Sixteen children with CP (age: 10y 7m±3y, 7 hemiplegia, 12 diplegia, GMFCS level: I (11) and II (8)) and twenty TD children (age: 10y 6m±3y) participated in this case-control study. MA AT was calculated at 20° plantarflexion by differentiating calcaneus displacement with respect to ankle angle. Seven anthropometric variables were measured and related to MA AT . We found normalized MA AT to be 15% (∼7mm) smaller in children with CP compared to TD children (p=0.003). MA AT could be predicted by all anthropometric measurements with tibia length explaining 79% and 72% of variance in children with CP and TD children, respectively. Our findings have important implications for clinical decision making since MA AT influences the mechanical advantage about the ankle, which contributes to movement function and is manipulated surgically. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Children with autism respond differently to spontaneous, elicited and deferred imitation.
PubMed
Heimann, M; Nordqvist, E; Strid, K; Connant Almrot, J; Tjus, T
2016-05-01
Imitation, a key vehicle for both cognitive and social development, is often regarded as more difficult for children with autism spectrum disorders (ASD) than for children with Down syndrome (DS) or typically developing (TD) children. The current study investigates similarities and differences in observed elicited, spontaneous and deferred imitation using both actions with objects and gestures as imitation tasks in these groups. Imitation among 19 children with autism was compared with 20 children with DS and 23 TD children matched for mental and language age. Elicited imitation resulted in significantly lower scores for the ASD group compared with the other two groups, an effect mainly carried by a low level of gesture imitation among ASD children. We observed no differences among the groups for spontaneous imitation. However, children with ASD or DS displayed less deferred imitation than the TD group. Proneness to imitate also differed among groups: only 10 (53%) of the children with autism responded in the elicited imitation condition compared with all children with DS and almost all TD children (87%). These findings add to our understanding of the kind of imitation difficulties children with ASD might have. They also point to the necessity of not equating various imitation measures because these may capture different processes and be differently motivating for children with autism. © 2016 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.
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Specificity of Dyspraxia in Children with Autism
PubMed Central
MacNeil, Lindsey K.; Mostofsky, Stewart H.
2012-01-01
Objective To explore the specificity of impaired praxis and postural knowledge to autism by examining three samples of children, including those with autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and typically developing (TD) children. Method Twenty-four children with ASD, 24 children with ADHD, and 24 TD children, ages 8–13, completed measures assessing basic motor control (the Physical and Neurological Exam for Subtle Signs; PANESS), praxis (performance of skilled gestures to command, with imitation, and tool use) and the ability to recognize correct hand postures necessary to perform these skilled gestures (the Postural Knowledge Test; PKT). Results Children with ASD performed significantly worse than TD children on all three assessments. In contrast, children with ADHD performed significantly worse than TD controls on PANESS but not on the praxis examination or PKT. Furthermore, children with ASD performed significantly worse than children with ADHD on both the praxis examination and PKT, but not on the PANESS. Conclusions Whereas both children with ADHD and children with ASD show impairments in basic motor control, impairments in performance and recognition of skilled motor gestures, consistent with dyspraxia, appear to be specific to autism. The findings suggest that impaired formation of perceptual-motor action models necessary to development of skilled gestures and other goal directed behavior is specific to autism; whereas, impaired basic motor control may be a more generalized finding. PMID:22288405
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A Psychometric Evaluation of the Danish Version of the Theory of Mind Storybook for 8-14 Year-Old Children.
PubMed
Clemmensen, Lars; Bartels-Velthuis, Agna A; Jespersen, Rókur Av F; van Os, Jim; Blijd-Hoogewys, Els M A; Ankerstrøm, Lise; Væver, Mette; Daniel, Peter F; Drukker, Marjan; Jeppesen, Pia; Jepsen, Jens R M
2016-01-01
Theory-of-Mind (ToM) keeps on developing in late childhood and early adolescence, and the study of ToM development later in childhood had to await the development of sufficiently sensitive tests challenging more mature children. The current study aimed to investigate the psychometric properties of the Danish version of the Theory-of-Mind Storybook Frederik (ToM-Frederik). We assessed whether ToM-Frederik scores differed between a group of 41 typically developing (TD) children and a group of 33 children with High Functioning Autism Spectrum Disorder (HFASD). A lower mean ToM-Frederik score was expected in the HFASD group. To determine the convergent validity of ToM-Frederik, potential associations with Strange Stories and Animated Triangles (AT) were analyzed. Furthermore, potential associations between ToM-Frederik and the Social Responsiveness Scale (SRS) and between ToM-Frederik and the Social Emotional Evaluation (SEE) Total score were analyzed. A significantly higher ToM-Frederik score was observed in the TD group compared to the HFASD group. Furthermore, the convergent validity of ToM-Frederik as a measure of ToM was supported by significant and positive associations with the Strange Stories and the AT scores in the HFASD group, whereas ToM-Frederik was significantly correlated with Strange Stories, but not with AT in the TD group. ToM-Frederik was not significantly associated with SRS in neither the HFASD nor the TD group. The findings are supportive of ToM-Frederik as a valid indicator of deficits at the group level in children with HFASD between 7 and 14 years of age. Furthermore, the convergent validity is supported.
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A Psychometric Evaluation of the Danish Version of the Theory of Mind Storybook for 8–14 Year-Old Children
PubMed Central
Clemmensen, Lars; Bartels-Velthuis, Agna A.; Jespersen, Rókur av F.; van Os, Jim; Blijd-Hoogewys, Els M. A.; Ankerstrøm, Lise; Væver, Mette; Daniel, Peter F.; Drukker, Marjan; Jeppesen, Pia; Jepsen, Jens R. M.
2016-01-01
Background: Theory-of-Mind (ToM) keeps on developing in late childhood and early adolescence, and the study of ToM development later in childhood had to await the development of sufficiently sensitive tests challenging more mature children. The current study aimed to investigate the psychometric properties of the Danish version of the Theory-of-Mind Storybook Frederik (ToM-Frederik). Methods: We assessed whether ToM-Frederik scores differed between a group of 41 typically developing (TD) children and a group of 33 children with High Functioning Autism Spectrum Disorder (HFASD). A lower mean ToM-Frederik score was expected in the HFASD group. To determine the convergent validity of ToM-Frederik, potential associations with Strange Stories and Animated Triangles (AT) were analyzed. Furthermore, potential associations between ToM-Frederik and the Social Responsiveness Scale (SRS) and between ToM-Frederik and the Social Emotional Evaluation (SEE) Total score were analyzed. Results: A significantly higher ToM-Frederik score was observed in the TD group compared to the HFASD group. Furthermore, the convergent validity of ToM-Frederik as a measure of ToM was supported by significant and positive associations with the Strange Stories and the AT scores in the HFASD group, whereas ToM-Frederik was significantly correlated with Strange Stories, but not with AT in the TD group. ToM-Frederik was not significantly associated with SRS in neither the HFASD nor the TD group. Conclusion: The findings are supportive of ToM-Frederik as a valid indicator of deficits at the group level in children with HFASD between 7 and 14 years of age. Furthermore, the convergent validity is supported. PMID:27014139
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Do not forget the boys – gender differences in children living in high HIV-affected communities in South Africa and Malawi in a longitudinal, community-based study
PubMed Central
Hensels, I. S.; Sherr, L.; Skeen, S.; Macedo, A.; Roberts, K. J.; Tomlinson, M.
2016-01-01
ABSTRACT Gender is an important factor in child development. Especially in sub-Saharan Africa, girls have often been shown to be less likely to access education compared to boys. The consequence of this has been that that programmes addressing child development are often aimed at girls in order to redress gender imbalances. This study examines the effect of gender on the development of children attending community-based organisations in high HIV-affected areas, and explores whether community-based organisation attendance was associated with any changes in gender differences over time. Baseline data from 989 children and 12–15 month follow from 854 (86% response rate) were used to examine gender differences in children from Malawi and South Africa. At baseline, where there were differences by gender, these tended to disadvantage boys. It was found that boys were significantly more often found to be subjected to violence. Boys showed worse performance at school and more behavioural problems than girls. These gender differences persisted from baseline to follow-up. At follow-up, boys self-reported significantly worse average quality of life than girls. Only harsh discipline differed by gender in progression over time: boys experienced a stronger reduction in harsh physical discipline than girls from baseline to follow-up. Since harsh discipline was associated with boys’ worse educational outcomes and behavioural problems, our data cautiously suggests that gender differences could be reduced over time. In conclusion, our data suggests that, perhaps due to the narrow equity approach focusing on provision for girls, boys may be overlooked. As a result, there are some specific experiences where boys are generally worse off. These differences have distinct ramifications for the educational and emotional development of boys. A broader equity approach to child development might be warranted to ensure that the needs of both girls and boys are considered, and that boys are not overlooked. PMID:27392005
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RNA-Binding Protein L1TD1 Interacts with LIN28 via RNA and is Required for Human Embryonic Stem Cell Self-Renewal and Cancer Cell Proliferation
PubMed Central
Närvä, Elisa; Rahkonen, Nelly; Emani, Maheswara Reddy; Lund, Riikka; Pursiheimo, Huha-Pekka; Nästi, Juuso; Autio, Reija; Rasool, Omid; Denessiouk, Konstantin; Lähdesmäki, Harri; Rao, Anjana; Lahesmaa, Ritta
2012-01-01
Human embryonic stem cells (hESC) have a unique capacity to self-renew and differentiate into all the cell types found in human body. Although the transcriptional regulators of pluripotency are well studied, the role of cytoplasmic regulators is still poorly characterized. Here, we report a new stem cell-specific RNA-binding protein L1TD1 (ECAT11, FLJ10884) required for hESC self-renewal and cancer cell proliferation. Depletion of L1TD1 results in immediate downregulation of OCT4 and NANOG. Furthermore, we demonstrate that OCT4, SOX2, and NANOG all bind to the promoter of L1TD1. Moreover, L1TD1 is highly expressed in seminomas, and depletion of L1TD1 in these cancer cells influences self-renewal and proliferation. We show that L1TD1 colocalizes and interacts with LIN28 via RNA and directly with RNA helicase A (RHA). LIN28 has been reported to regulate translation of OCT4 in complex with RHA. Thus, we hypothesize that L1TD1 is part of the L1TD1-RHA-LIN28 complex that could influence levels of OCT4. Our results strongly suggest that L1TD1 has an important role in the regulation of stemness. PMID:22162396
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Impact of tire debris on in vitro and in vivo systems
PubMed Central
Gualtieri, Maurizio; Andrioletti, Manuela; Mantecca, Paride; Vismara, Claudio; Camatini, Marina
2005-01-01
Background It is estimated that over 80% of respirable particulate matter (PM10) in cities comes from road transport and that tire and brake wear are responsible for the 3–7% emission of it. Data on the indicators of environmental impact of tire debris (TD), originated from the tire abrasion on roads, are extremely scarce, even though TD contains chemicals (zinc and organic compounds) which can be released in the environment. Methods TD particle morphology was analysed with SEM, TEM and FIB instruments. TD eluates and TD organic extracts were tested at dilution series on human cell lines and Xenopus laevis embryos. 50 and 100 g/L TD were used for the eluates obtained after 24 h at pH 3 and the quantity of zinc present was measured with a ICP-AES. Eluates diluted to 1%, 10%, 50% in culture media and undiluted were used on X. laevis embryos in the FETAX test. HepG2 cells were exposed for 24 h to 0.05 – 50 μg/ml of zinc salt while A549 cells were exposed for 24, 48 and 72 h to 10, 50, 60, or 75 μg/ml of TD extract. X. laevis embryos were exposed to 50, 80, 100, or 120 μg/ml TD extract. Results The solution of undiluted 50 g/L TD produced 80.2% mortality (p < 0.01) in X. laevis embryos and this toxic effect was three times greater than that produced by 100 g/L TD. Zn accumulation in HepG2 cells was evident after 4 h exposure. A549 cells exposed to TD organic extract for 72 h presented a modified morphology, a decrease in cell proliferation and an increase in DNA damage as shown by comet assay. The dose 80 μg/ml of TD extract produced 14.6% mortality in X. laevis embryos and 15.9% mortality at 120 μg/ml. Treatment with 80, 100, or 120 μg/ml TD organic extract increased from 14.8% to 37.8% malformed larvae percentages compared to 5.6% in the control. Conclusion Since the amount of Zn leached from TD is related to pH, aggregation of particles and elution process, the quantity of TD present in the environment has to be taken into account. Moreover the atmospheric conditions, which may deeply influence the particle properties, have to be considered. The TD organic fraction was toxic for cells and organisms. Thus, because of its chemical components, TD may have a potential environmental impact and has to be further investigated. PMID:15813962
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Grammar Is Differentially Impaired in Subgroups of Autism Spectrum Disorders: Evidence from an Investigation of Tense Marking and Morphosyntax
PubMed Central
Modyanova, Nadezhda; Perovic, Alexandra; Wexler, Ken
2017-01-01
Deficits in the production of verbal inflection (tense marking, or finiteness) are part of the Optional Infinitive (OI) stage of typical grammatical development. They are also a hallmark of language impairment: they have been used as biomarkers in guiding genetic studies of Specific Language Impairment (SLI), and have also been observed in autism spectrum disorders (ASD). To determine the detailed nature of finiteness abilities in subgroups of ASD [autism with impaired language (ALI) vs. autism with normal language (ALN)], we compared tense marking abilities in 46 children with ALI and 37 children with ALN with that of two groups of nonverbal mental age (MA) and verbal MA-matched typically developing (TD) controls, the first such study described in the literature. Our participants' performance on two elicited production tasks, probing third-person-singular -s and past tense -ed, from the Rice/Wexler Test of Early Grammatical Impairment (TEGI, Rice and Wexler, 2001), revealed extensive deficits in the ALI group: their ability to correctly mark tense was significantly worse than their much younger TD controls', and significantly worse than that of the ALN group. In contrast, the ALN group performed similarly to their TD controls. We found good knowledge of the meaning of tense, and of case and agreement, in both ASD groups. Similarly, both ASD groups showed distributions of null or overt subjects with nonfinite and finite verbs in line with those found in young TD children. A key difference, however, was that the ALI group used (rather than simply omitted) the wrong tense in some sentences, a feature not reported in the OI stage for TD or SLI children. Our results confirm a clear distinction in the morphosyntactic abilities of the two subgroups of children with ASD: the language system responsible for finiteness in the ALN group seems to be functioning comparably to that of the TD children, whereas the ALI group, despite showing knowledge of case and agreement, seems to experience an extensive grammatical deficit with respect to finiteness which does not seem to improve with age. Crucially, our ALI group seems to have worse grammatical abilities even than those reported for SLI. PMID:28400738
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Everyday executive functions in Down syndrome from early childhood to young adulthood: evidence for both unique and shared characteristics compared to youth with sex chromosome trisomy (XXX and XXY).
PubMed
Lee, Nancy Raitano; Anand, Payal; Will, Elizabeth; Adeyemi, Elizabeth I; Clasen, Liv S; Blumenthal, Jonathan D; Giedd, Jay N; Daunhauer, Lisa A; Fidler, Deborah J; Edgin, Jamie O
2015-01-01
Executive functions (EF) are thought to be impaired in Down syndrome (DS) and sex chromosome trisomy (Klinefelter and Trisomy X syndromes; +1X). However, the syndromic specificity and developmental trajectories associated with EF difficulties in these groups are poorly understood. The current investigation (a) compared everyday EF difficulties in youth with DS, +1X, and typical development (TD); and (b) examined relations between age and EF difficulties in these two groups and a TD control group cross-sectionally. Study 1 investigated the syndromic specificity of EF profiles on the Behavior Rating Inventory of Executive Function (BRIEF) in DS (n = 30), +1X (n = 30), and a TD group (n = 30), ages 5-18 years. Study 2 examined age effects on EF in the same cross-sectional sample of participants included in Study 1. Study 3 sought to replicate Study 2's findings for DS by examining age-EF relations in a large independent sample of youth with DS (n = 85) and TD (n = 43), ages 4-24 years. Study 1 found evidence for both unique and shared EF impairments for the DS and +1X groups. Most notably, youth with +1X had relatively uniform EF impairments on the BRIEF scales, while the DS group showed an uneven BRIEF profile with relative strengths and weaknesses. Studies 2 and 3 provided support for fairly similar age-EF relations in the DS and TD groups. In contrast, for the +1X group, findings were mixed; 6 BRIEF scales showed similar age-EF relations to the TD group and 2 showed greater EF difficulties at older ages for +1X. These findings will be discussed within the context of efforts to identify syndrome specific cognitive-behavioral profiles for youth with different genetic syndromes in order to inform basic science investigations into the etiology of EF difficulties in these groups and to develop treatment approaches that are tailored to the needs of these groups.
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Everyday executive functions in Down syndrome from early childhood to young adulthood: evidence for both unique and shared characteristics compared to youth with sex chromosome trisomy (XXX and XXY)
PubMed Central
Lee, Nancy Raitano; Anand, Payal; Will, Elizabeth; Adeyemi, Elizabeth I.; Clasen, Liv S.; Blumenthal, Jonathan D.; Giedd, Jay N.; Daunhauer, Lisa A.; Fidler, Deborah J.; Edgin, Jamie O.
2015-01-01
Executive functions (EF) are thought to be impaired in Down syndrome (DS) and sex chromosome trisomy (Klinefelter and Trisomy X syndromes; +1X). However, the syndromic specificity and developmental trajectories associated with EF difficulties in these groups are poorly understood. The current investigation (a) compared everyday EF difficulties in youth with DS, +1X, and typical development (TD); and (b) examined relations between age and EF difficulties in these two groups and a TD control group cross-sectionally. Study 1 investigated the syndromic specificity of EF profiles on the Behavior Rating Inventory of Executive Function (BRIEF) in DS (n = 30), +1X (n = 30), and a TD group (n = 30), ages 5–18 years. Study 2 examined age effects on EF in the same cross-sectional sample of participants included in Study 1. Study 3 sought to replicate Study 2's findings for DS by examining age-EF relations in a large independent sample of youth with DS (n = 85) and TD (n = 43), ages 4–24 years. Study 1 found evidence for both unique and shared EF impairments for the DS and +1X groups. Most notably, youth with +1X had relatively uniform EF impairments on the BRIEF scales, while the DS group showed an uneven BRIEF profile with relative strengths and weaknesses. Studies 2 and 3 provided support for fairly similar age-EF relations in the DS and TD groups. In contrast, for the +1X group, findings were mixed; 6 BRIEF scales showed similar age-EF relations to the TD group and 2 showed greater EF difficulties at older ages for +1X. These findings will be discussed within the context of efforts to identify syndrome specific cognitive-behavioral profiles for youth with different genetic syndromes in order to inform basic science investigations into the etiology of EF difficulties in these groups and to develop treatment approaches that are tailored to the needs of these groups. PMID:26539087
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Immunogenicity and safety of the new reduced-dose tetanus-diphtheria vaccine in healthy Korean adolescents: A comparative active control, double-blind, randomized, multicenter phase III study.
PubMed
Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Kim, Sang Yong; Kim, Jong-Hyun; Kim, Hyun-Hee; Lee, Kyung-Yil; Kim, Hwang Min; Choi, Young Youn; Ma, Sang Hyuk; Kim, Chun Soo; Kim, Dong Ho; Ahn, Dong Ho; Kang, Jin Han
2017-04-01
A new reduced-dose tetanus-diphtheria (Td) vaccine was developed in Korea, and phase I and II clinical trials were successfully undertaken. We conducted this double-blind, randomized, multicenter phase III clinical trial to assess the immunogenicity and safety of the new Td vaccine. Healthy adolescents 11-12 years of age were enrolled and randomized to receive the new Td vaccine (study group) or a commercially available Td vaccine (control group). Blood samples were collected prior to and 4 weeks after the vaccination. Between the study and control groups, seroprotection rate, booster response, and geometric mean titer of antibodies against diphtheria and tetanus toxoids were compared after the vaccination. All solicited and unsolicited adverse events and serious adverse events during the 6-week study period were monitored. A total of 164 adolescents received vaccination, and 156 of them were evaluated to assess immunogenicity. The seroprotection rate and geometric mean titer for antibodies against diphtheria were significantly higher in the study group, whereas those against tetanus were significantly higher in the control group. However, all seroprotection rates against diphtheria and tetanus in the study and control groups were high: 100% against diphtheria and tetanus in the study group, and 98.7% against diphtheria and 100% against tetanus in the control group. No significant differences in the frequency of solicited and unsolicited adverse events were observed between the two vaccine groups. The new Td vaccine is highly immunogenic and safe, and this new Td vaccine can be effectively used for preventing diphtheria and tetanus. Copyright © 2015. Published by Elsevier B.V.
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Abnormal social reward processing in autism as indexed by pupillary responses to happy faces
PubMed Central
2012-01-01
Background Individuals with Autism Spectrum Disorders (ASD) typically show impaired eye contact during social interactions. From a young age, they look less at faces than typically developing (TD) children and tend to avoid direct gaze. However, the reason for this behavior remains controversial; ASD children might avoid eye contact because they perceive the eyes as aversive or because they do not find social engagement through mutual gaze rewarding. Methods We monitored pupillary diameter as a measure of autonomic response in children with ASD (n = 20, mean age = 12.4) and TD controls (n = 18, mean age = 13.7) while they looked at faces displaying different emotions. Each face displayed happy, fearful, angry or neutral emotions with the gaze either directed to or averted from the subjects. Results Overall, children with ASD and TD controls showed similar pupillary responses; however, they differed significantly in their sensitivity to gaze direction for happy faces. Specifically, pupillary diameter increased among TD children when viewing happy faces with direct gaze as compared to those with averted gaze, whereas children with ASD did not show such sensitivity to gaze direction. We found no group differences in fixation that could explain the differential pupillary responses. There was no effect of gaze direction on pupil diameter for negative affect or neutral faces among either the TD or ASD group. Conclusions We interpret the increased pupillary diameter to happy faces with direct gaze in TD children to reflect the intrinsic reward value of a smiling face looking directly at an individual. The lack of this effect in children with ASD is consistent with the hypothesis that individuals with ASD may have reduced sensitivity to the reward value of social stimuli. PMID:22958650
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Exploring the binding of 4-thiothymidine with human serum albumin by spectroscopy, atomic force microscopy, and molecular modeling methods.
PubMed
Zhang, Juling; Gu, Huaimin; Zhang, Xiaohui
2014-01-30
The interaction of 4-thiothymidine (S(4)TdR) with human serum albumin (HSA) was studied by equilibrium dialysis under normal physiological conditions. In this work, the mechanism of the interaction between S(4)TdR and human serum albumin (HSA) was exploited by fluorescence, UV, CD circular, and SERS spectroscopic. Fluorescence and UV spectroscopy suggest that HSA intensities are significantly decreased when adding S(4)TdR to HAS, and the quenching mechanism of the fluorescence is static. Also, the ΔG, ΔH, and ΔS values across temperature indicated that hydrophobic interaction was the predominant binding force. The CD circular results show that there is little change in the secondary structure of HSA except the environment of amino acid changes when adding S(4)TdR to HSA. The surface-enhanced Raman scattering (SERS) shows that the interaction between S(4)TdR and HSA can be achieved through different binding sites which are probably located in the II A and III A hydrophobic pockets of HSA which correspond to Sudlow's I and II binding sites. In addition, the molecular modeling displays that S(4)TdR-HSA complex is stabilized by hydrophobic forces, which result from amino acid residues. The atomic force microscopy results revealed that the single HSA molecular dimensions were larger after interaction of 4-thiothymidine. This work would be useful to understand the state of the transportation, distribution, and metabolism of the anticancer drugs in the human body, and it could provide a useful biochemistry parameter for the development of new anti-cancer drugs and research of pharmacology mechanisms. Copyright © 2013 Elsevier Ltd. All rights reserved.
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CXCR2 inverse agonism detected by arrestin redistribution.
PubMed
Kredel, Simone; Wolff, Michael; Wiedenmann, Jörg; Moepps, Barbara; Nienhaus, G Ulrich; Gierschik, Peter; Kistler, Barbara; Heilker, Ralf
2009-10-01
To study CXCR2 modulated arrestin redistribution, the authors employed arrestin as a fusion protein containing either the Aequorea victoria-derived enhanced green fluorescent protein (EGFP) or a recently developed mutant of eqFP611, a red fluorescent protein derived from Entacmaea quadricolor. This mutant, referred to as RFP611, had earlier been found to assume a dimeric quarternary structure. It was therefore employed in this work as a "tandem" (td) construct for pseudo-monomeric fusion protein labeling. Both arrestin fusion proteins, containing either td-RFP611 (Arr-td-RFP611) or enhanced green fluorescent protein (EGFP; Arr-EGFP), were found to colocalize with internalized fluorescently labeled Gro-alpha a few minutes after Gro-alpha addition. Intriguingly, however, Arr-td-RFP611 and Arr-EGFP displayed distinct cellular distribution patterns in the absence of any CXCR2-activating ligand. Under these conditions, Arr-td-RFP611 showed a largely homogeneous cytosolic distribution, whereas Arr-EGFP segregated, to a large degree, into granular spots. These observations indicate a higher sensitivity of Arr EGFP to the constitutive activity of CXCR2 and, accordingly, an increased arrestin redistribution to coated pits and endocytic vesicles. In support of this interpretation, the authors found the known CXCR2 antagonist Sch527123 to act as an inverse agonist with respect to Arr-EGFP redistribution. The inverse agonistic properties of Sch527123 were confirmed in vitro in a guanine nucleotide binding assay, revealing an IC(50) value similar to that observed for Arr-EGFP redistribution. Thus, the redistribution assay, when based on Arr-EGFP, enables the profiling of antagonistic test compounds with respect to inverse agonism. When based on Arr-td-RFP611, the assay may be employed to study CXCR2 agonism or neutral antagonism.