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Greater Activation (greater + activation)
Selected AbstractsGreater Activation in Left Hemisphere Language-Related Regions During Simple Judgment Tasks Among Substance-Dependent Patients in Treatment for AlcoholismALCOHOLISM, Issue 2 2010Jodi M. Gilman Background:, Alcoholism is often associated with impaired emotional control. Alcoholics have also been found to have deficits in frontal lobe executive functions. Recent functional imaging studies have suggested that alcoholics show greater activation than nonalcoholics in circuits involving frontal lobes, as well as more posterior brain regions, when engaged in executive-type tasks. In this study, we compared brain activations of alcohol-dependent patients and healthy nonalcoholics while they performed 2 simple judgment tasks designed to activate frontal circuits involved in a basic form of decision making. Participants completed 1 judgment task that required an emotional judgment and 1 task that did not, which enabled us to study whether alcoholics had greater brain activation while performing executive tasks, and to determine if emotional tasks elicited even greater activation than nonemotional tasks. Methods:, We performed functional magnetic resonance imaging scans while alcoholic patients and nonalcoholic controls viewed pictures from the International Affective Picture System. In 3 separate runs, participants viewed the images without making a judgment, determined whether the images were indoor or outdoor scenes, or decided if they liked or disliked the images. Results:, There was little difference in brain activation between alcoholics and controls when no judgment was required. When participants made judgments about either the location or whether they liked or disliked an image, however, we observed significantly increased activation in frontal, limbic, and temporal regions in the patients relative to the controls. Increases were particularly robust in the frontal lobe and in areas of the brain associated with language. When we compared the emotional to the nonemotional judgment, the alcoholics, but not the controls, showed greater activation in the ventral mesial frontal cortex. Conclusions:, Alcoholic patients appear to use brain language areas more than nonalcoholics while making judgments about the setting or liking of emotionally arousing visual images. This increased activation may reflect a compensatory recruitment of brain regions to perform simple decision-making tasks. [source] A developmental fMRI study of self-regulatory controlHUMAN BRAIN MAPPING, Issue 11 2006Rachel Marsh Abstract We used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of self-regulatory control across development in healthy individuals performing the Stroop interference task. Proper performance of the task requires the engagement of self-regulatory control to inhibit an automatized response (reading) in favor of another, less automatic response (color naming). Functional MRI scans were acquired from a sample of 70 healthy individuals ranging in age from 7 to 57 years. We measured task-related regional signal changes across the entire cerebrum and conducted correlation analyses to assess the associations of signal activation with age and with behavioral performance. The magnitude of fMRI signal change increased with age in the right inferolateral prefrontal cortex (Brodmann area [BA] 44/45) and right lenticular nucleus. Greater activation of the right inferolateral prefrontal cortex also accompanied better performance. Activity in the right frontostriatal systems increased with age and with better response inhibition, consistent with the known functions of frontostriatal circuits in self-regulatory control. Age-related deactivations in the mesial prefrontal cortex (BA 10), subgenual anterior cingulate cortex (BA 24), and posterior cingulate cortex (BA 31) likely represented the greater engagement of adults in self-monitoring and free associative thought processes during the easier baseline task, consistent with the improved performance on this task in adults compared with children. Although we cannot exclude the possibility that age-related changes in reading ability or in the strategies used to optimize task performance were responsible for our findings, the correlations of brain activation with performance suggest that changes in frontostriatal activity with age underlie the improvement in self-regulatory control that characterizes normal human development. Hum Brain Mapp, 2006. © 2006 Wiley-Liss, Inc. [source] Neural correlates of movement generation in the ,at-risk mental state'ACTA PSYCHIATRICA SCANDINAVICA, Issue 4 2010M. R. Broome Broome MR, Matthiasson P, Fusar-Poli P, Woolley JB, Johns LC, Tabraham P, Bramon E, Valmaggia L, Williams SCR, Brammer MJ, Chitnis X, McGuire PK. Neural correlates of movement generation in the ,at-risk mental state'. Objective:, People with ,prodromal' symptoms have a very high risk of developing psychosis. We examined the neurocognitive basis of this vulnerability by using functional MRI to study subjects with an at-risk mental state (ARMS) while they performed a random movement generation task. Method:, Cross-sectional comparison of individuals with an ARMS (n = 17), patients with first episode schizophreniform psychosis (n = 10) and healthy volunteers (n = 15). Subjects were studied using functional MRI while they performed a random movement generation paradigm. Results:, During random movement generation, the ARMS group showed less activation in the left inferior parietal cortex than controls, but greater activation than in the first episode group. Conclusion:, The ARMS is associated with abnormalities of regional brain function that are qualitatively similar to those in patients who have recently presented with psychosis but less severe. [source] The effects of age and sex on mental rotation performance, verbal performance, and brain electrical activityDEVELOPMENTAL PSYCHOBIOLOGY, Issue 4 2002Jonathan E. Roberts Abstract This study examined the effects of age and sex on mental rotation performance, verbal performance, and brain-wave activity. Thirty-two 8-year-olds (16 boys) and 32 college students (16 men) had EEG recorded at baseline and while performing four computerized tasks: a two-dimensional (2D) gingerbread man mental rotation, a 2D alphanumeric mental rotation, of three-dimensional (3D) basketball player mental rotation, and lexical decision making. Additionally, participants completed a paper- and pencil water level task and an oral verbal fluency task. On the 2D alphanumeric and 3D basketball player mental rotation tasks, men performed better than boys, but the performance of women and girls did not differ. On the water level task, men performed better than women whereas there was no difference between boys and girls. No sex differences were found on the 2D gingerbread man mental rotation, lexical decision-making, and verbal fluency tasks. EEG analyses indicated that men exhibited left posterior temporal activation during the 2D alphanumeric task and that men and boys both exhibited greater left parietal activation than women and girls during the 2D gingerbread man task. On the 3D basketball player mental rotation task, all participants exhibited greater activation of the right parietal area than the left parietal area. These data give insight into the brain activity and cognitive development changes that occur between childhood and adulthood. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 40: 391,407, 2002. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/dev.10039 [source] Inactivation of phosphorylase is a major component of the mechanism by which insulin stimulates hepatic glycogen synthesisFEBS JOURNAL, Issue 13 2003Susan Aiston Multiple signalling pathways are involved in the mechanism by which insulin stimulates hepatic glycogen synthesis. In this study we used selective inhibitors of glycogen synthase kinase-3 (GSK-3) and an allosteric inhibitor of phosphorylase (CP-91149) that causes dephosphorylation of phosphorylase a, to determine the relative contributions of inactivation of GSK-3 and dephosphorylation of phosphorylase a as alternative pathways in the stimulation of glycogen synthesis by insulin in hepatocytes. GSK-3 inhibitors (SB-216763 and Li+) caused a greater activation of glycogen synthase than insulin (90% vs. 40%) but a smaller stimulation of glycogen synthesis (30% vs. 150%). The contribution of GSK-3 inactivation to insulin stimulation of glycogen synthesis was estimated to be less than 20%. Dephosphorylation of phosphorylase a with CP-91149 caused activation of glycogen synthase and translocation of the protein from a soluble to a particulate fraction and mimicked the stimulation of glycogen synthesis by insulin. The stimulation of glycogen synthesis by phosphorylase inactivation cannot be explained by either inhibition of glycogen degradation or activation of glycogen synthase alone and suggests an additional role for translocation of synthase. Titrations with the phosphorylase inactivator showed that stimulation of glycogen synthesis by insulin can be largely accounted for by inactivation of phosphorylase over a wide range of activities of phosphorylase a. We conclude that a signalling pathway involving dephosphorylation of phosphorylase a leading to both activation and translocation of glycogen synthase is a critical component of the mechanism by which insulin stimulates hepatic glycogen synthesis. Selective inactivation of phosphorylase can mimic insulin stimulation of hepatic glycogen synthesis. [source] CX3CL1-CX3CR1 interaction prevents carbon tetrachloride-induced liver inflammation and fibrosis in mice,HEPATOLOGY, Issue 4 2010Tomonori Aoyama Chronic liver disease is associated with hepatocyte injury, inflammation, and fibrosis. Chemokines and chemokine receptors are key factors for the migration of inflammatory cells such as macrophages and noninflammatory cells such as hepatic stellate cells (HSCs). The expression of CX3CR1 and its ligand, CX3CL1, is up-regulated in chronic liver diseases such as chronic hepatitis C. However, the precise role of CX3CR1 in the liver is still unclear. Here we investigated the role of the CX3CL1-CX3CR1 interaction in a carbon tetrachloride (CCl4),induced liver inflammation and fibrosis model. CX3CR1 was dominantly expressed in Kupffer cells in the liver. In contrast, the main source of CX3CL1 was HSCs. Mice deficient in CX3CR1 showed significant increases in inflammatory cell recruitment and cytokine production [including tumor necrosis factor , (TNF-,); monocyte chemoattractant protein 1; macrophage inflammatory protein 1,; and regulated upon activation, normal T cell expressed, and secreted (RANTES)] after CCl4 treatment versus wild-type (WT) mice. This suggested that CX3CR1 signaling prevented liver inflammation. Kupffer cells in CX3CR1-deficient mice after CCl4 treatment showed increased expression of TNF-, and transforming growth factor , and reduced expression of the anti-inflammatory markers interleukin-10 (IL-10) and arginase-1. Coculture experiments showed that HSCs experienced significantly greater activation by Kupffer cells from CCl4 -treated CX3CR1-deficient mice versus WT mice. Indeed, augmented fibrosis was observed in CX3CR1-deficient mice versus WT mice after CCl4 treatment. Finally, CX3CL1 treatment induced the expression of IL-10 and arginase-1 in WT cultured Kupffer cells through CX3CR1, which in turn suppressed HSC activation. Conclusion: The CX3CL1-CX3CR1 interaction inhibits inflammatory properties in Kupffer cells/macrophages and results in decreased liver inflammation and fibrosis. (Hepatology 2010) [source] Being liked activates primary reward and midline self-related brain regionsHUMAN BRAIN MAPPING, Issue 4 2010Christopher G. Davey Abstract The experience of being liked is a key social event and fundamental to motivating human behavior, though little is known about its neural underpinnings. In this study, we examined the experience of being liked in a group of 15- to 24-year-old: a cohort for whom forming friendships has a great degree of salience, and for whom the explicit representation of relationships is familiar from their frequent use of social networking technologies. Study participants (n = 19) were led to believe that other participants had formed an opinion on their likability based on their appearance in a photograph, and during fMRI scanning viewed the photographs of people who had purportedly responded favorably to them (alongside photographs of control participants). Results indicated that being liked activated primary reward- and self-related regions, including the nucleus accumbens, midbrain (in an area corresponding to the ventral tegmentum), ventromedial prefrontal cortex, posterior cingulate cortex (including retrosplenial cortex), amygdala, and insula/opercular cortex. Participants showed greater activation of ventromedial prefrontal cortex and amygdala in response to being liked by people that they regarded highly compared to those they regarded less so. Finally, being liked by the opposite compared to the same gender activated the right caudal orbitofrontal cortex and right anterior insula: areas important for the representation of primary somatic rewards. This study demonstrates that neural response to being liked has features that are consistent with response to other rewarding events, but it has additional features that reflect its intrinsically interpersonal character. Hum Brain Mapp, 2010. © 2009 Wiley-Liss, Inc. [source] The neural response to changing semantic and perceptual complexity during language processingHUMAN BRAIN MAPPING, Issue 3 2010David J. Sharp Abstract Speech comprehension involves processing at different levels of analysis, such as acoustic, phonetic, and lexical. We investigated neural responses to manipulating the difficulty of processing at two of these levels. Twelve subjects underwent positron emission tomographic scanning while making decisions based upon the semantic relatedness between heard nouns. We manipulated perceptual difficulty by presenting either clear or acoustically degraded speech, and semantic difficulty by varying the degree of semantic relatedness between words. Increasing perceptual difficulty was associated with greater activation of the left superior temporal gyrus, an auditory-perceptual region involved in speech processing. Increasing semantic difficulty was associated with reduced activity in both superior temporal gyri and increased activity within the left angular gyrus, a heteromodal region involved in accessing word meaning. Comparing across all the conditions, we also observed increased activation within the left inferior prefrontal cortex as the complexity of language processing increased. These results demonstrate a flexible system for language processing, where activity within distinct parts of the network is modulated as processing demands change. Hum Brain Mapp, 2010. © 2009 Wiley-Liss, Inc. [source] Neural basis of first and second language processing of sentence-level linguistic prosodyHUMAN BRAIN MAPPING, Issue 2 2007Jackson Gandour Abstract A fundamental question in multilingualism is whether the neural substrates are shared or segregated for the two or more languages spoken by polyglots. This study employs functional MRI to investigate the neural substrates underlying the perception of two sentence-level prosodic phenomena that occur in both Mandarin Chinese (L1) and English (L2): sentence focus (sentence-initial vs. -final position of contrastive stress) and sentence type (declarative vs. interrogative modality). Late-onset, medium proficiency Chinese-English bilinguals were asked to selectively attend to either sentence focus or sentence type in paired three-word sentences in both L1 and L2 and make speeded-response discrimination judgments. L1 and L2 elicited highly overlapping activations in frontal, temporal, and parietal lobes. Furthermore, region of interest analyses revealed that for both languages the sentence focus task elicited a leftward asymmetry in the supramarginal gyrus; both tasks elicited a rightward asymmetry in the mid-portion of the middle frontal gyrus. A direct comparison between L1 and L2 did not show any difference in brain activation in the sentence type task. In the sentence focus task, however, greater activation for L2 than L1 occurred in the bilateral anterior insula and superior frontal sulcus. The sentence focus task also elicited a leftward asymmetry in the posterior middle temporal gyrus for L1 only. Differential activation patterns are attributed primarily to disparities between L1 and L2 in the phonetic manifestation of sentence focus. Such phonetic divergences lead to increased computational demands for processing L2. These findings support the view that L1 and L2 are mediated by a unitary neural system despite late age of acquisition, although additional neural resources may be required in task-specific circumstances for unequal bilinguals. Hum. Brain Mapp, 2007. © 2006 Wiley-Liss, Inc. [source] Brain,behavior correlation in children depends on the neurocognitive networkHUMAN BRAIN MAPPING, Issue 2 2004James R. Booth We examined brain,behavior correlations in 12 children (age range 9.3 to 11.7 years) during a selective attention task that required the visual search of a conjunction of features and during a response inhibition task that required the inhibition of a pre-potent response during "no-go" blocks. We found that the association between performance in these tasks and brain activation as measured by functional magnetic resonance imaging (fMRI) depended on the neurocognitive network. Specifically, better performance during the no-go task was associated with greater activation in the response inhibition network including the prefrontal cortex and basal ganglia. In contrast, better performance during the visual search task was associated with less activation in the selective attention network including superior parietal lobule and lateral premotor cortex. These results show that the relation of performance to the magnitude of neural activation is complex and may display differential relationships based on the cognitive domain, anatomical region, and perhaps also developmental stage. Hum Brain Mapping 23:99,108, 2004. © 2004 Wiley-Liss, Inc. [source] Activating Seniors to Improve Chronic Disease Care: Results from a Pilot Intervention StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 8 2010Dominick L. Frosch PhD OBJECTIVES: To evaluate the effect of an activation intervention delivered in community senior centers to improve health outcomes for chronic diseases that disproportionately affect older adults. DESIGN: Two-group quasi-experimental study. SETTING: Two Los Angeles community senior centers. PARTICIPANTS: One hundred sixteen senior participants. INTERVENTION: Participants were invited to attend group screenings of video programs intended to inform about and motivate self-management of chronic conditions common in seniors. Moderated discussions reinforcing active patient participation in chronic disease management followed screenings. Screenings were scheduled over the course of 12 weeks. MEASUREMENTS: One center was assigned by coin toss to an encouragement condition in which participants received a $50 gift card if they attended at least three group screenings. Participants in the nonencouraged center received no incentive for attendance. Validated study measures for patient activation, physical activity, and health-related quality of life were completed at baseline and 12 weeks and 6 months after enrollment. RESULTS: Participants attending the encouraged senior center were more likely to attend three or more group screenings (77.8% vs 47.2%, P=.001). At 6-month follow-up, participants from either center who attended three or more group screenings (n=74, 64%) reported significantly greater activation (P<.001), more minutes walking (P<.001) and engaging in vigorous physical activity (P=.006), and better health-related quality of life (Medical Outcomes Study 12-item Short-Form Survey (SF-12) mental component summary, P<.001; SF-12 physical component summary, P=.002). CONCLUSION: Delivering this pilot intervention in community senior centers is a potentially promising approach to activating seniors that warrants further investigation for improving chronic disease outcomes. [source] Activation of NF-KB signalling and TNF,-expression in THP-1 macrophages by TiAlV- and polyethylene-wear particlesJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2005Bernd Baumann Abstract Wear particles are believed to induce periprosthetic inflammation which contributes to periprosthetic osteolysis. TNF, plays a pivotal role in the pathogenesis of this process. The molecular mechanisms leading to the development of periprosthetic inflammation with upregulated TNF, expression in monocytic cells in response to different wear particles have yet to be defined. In this study we evaluated the effects of polyethylene- and TiAlV-particles on activation of NF-kB signalling pathways and TNF, biosynthesis and release in monocytic cells with respect to periprosthetic osteoclastogenesis. THP-1 monocytic cells were differentiated to macrophage-like cells and exposed to LPS-detoxified polyethylene and prosthesis-derived TiAlV-particles. TNF, release was analyzed in culture supernatant by ELISA. NF-kB activation was examined by electrophoretic mobility shift assay (EMSA), and NF-kB target promoter activities including transactivation of the TNF, promoter were determined by luciferase reporter gene assays. Differentiated THP-1 macrophages were exposed to increasing numbers of particles for 0, 60, 180 and 360 min. Both, polyethylene- and TiAlV-particles induced a significant activation of both NF-kB and TNF, promoters at 180 min. A significant TNF, release was detected after 360 min exposure to polyethylene- and TiAlV-particles in a dose dependent manner. In comparison, LPS induced a much greater activation of NF-kB and TNF, promoters, and TNF, secretion into the supernatant was strongly induced. These results provide evidence that induction of the NF-kB signal transduction pathway in macrophages plays a major role in initiating and mediating the inflammatory response leading to periprosthetic osteolysis. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Greater Activation in Left Hemisphere Language-Related Regions During Simple Judgment Tasks Among Substance-Dependent Patients in Treatment for AlcoholismALCOHOLISM, Issue 2 2010Jodi M. Gilman Background:, Alcoholism is often associated with impaired emotional control. Alcoholics have also been found to have deficits in frontal lobe executive functions. Recent functional imaging studies have suggested that alcoholics show greater activation than nonalcoholics in circuits involving frontal lobes, as well as more posterior brain regions, when engaged in executive-type tasks. In this study, we compared brain activations of alcohol-dependent patients and healthy nonalcoholics while they performed 2 simple judgment tasks designed to activate frontal circuits involved in a basic form of decision making. Participants completed 1 judgment task that required an emotional judgment and 1 task that did not, which enabled us to study whether alcoholics had greater brain activation while performing executive tasks, and to determine if emotional tasks elicited even greater activation than nonemotional tasks. Methods:, We performed functional magnetic resonance imaging scans while alcoholic patients and nonalcoholic controls viewed pictures from the International Affective Picture System. In 3 separate runs, participants viewed the images without making a judgment, determined whether the images were indoor or outdoor scenes, or decided if they liked or disliked the images. Results:, There was little difference in brain activation between alcoholics and controls when no judgment was required. When participants made judgments about either the location or whether they liked or disliked an image, however, we observed significantly increased activation in frontal, limbic, and temporal regions in the patients relative to the controls. Increases were particularly robust in the frontal lobe and in areas of the brain associated with language. When we compared the emotional to the nonemotional judgment, the alcoholics, but not the controls, showed greater activation in the ventral mesial frontal cortex. Conclusions:, Alcoholic patients appear to use brain language areas more than nonalcoholics while making judgments about the setting or liking of emotionally arousing visual images. This increased activation may reflect a compensatory recruitment of brain regions to perform simple decision-making tasks. [source] Hyperfrontality in patients with schizophrenia during saccade and antisaccade tasks: A study with fMRIPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 2 2009Mai Fukumoto-Motoshita mms Aims:, Antisaccadic eye movements, requiring inhibition of a saccade toward a briefly appearing peripheral target, are known to be impaired in schizophrenia. Previous neuroimaging studies have indicated that patients with schizophrenia show diminished activations in the frontal cortex and basal ganglia. These studies used target fixation as a baseline condition. However, if the levels of brain activities at baseline are not compatible between patients and healthy subjects, between-group comparison on antisaccade-related activations is consequently invalidated. One possibility is that patients with schizophrenia may present with greater activation during fixation than healthy subjects. In order to examine this possibility, here we investigated brain activities associated with antisaccade in the two groups without using target fixation at baseline. Methods:, Functional brain images were acquired during prosaccades and antisaccades in 18 healthy subjects and 18 schizophrenia patients using a box-car functional magnetic resonance imaging design. Eye movements were measured during scanning. Results:, In the patient group, the elevated activities in the dorsolateral prefrontal cortex (DLPFC) and thalamus, normally seen in antisaccade tasks relative to saccade tasks, were no longer observed. Moreover, in normal subjects, activities in the DLPFC and thalamus were greater during the antisaccade task than during the saccade task. In patients, no such difference was observed between the two tasks, suggesting that these brain regions are likely to be highly activated even by a simple task such as fixation. In particular, the DLPFC and thalamus in patients were not activated at a level commensurate with the difficulty of the tasks presented. Conclusions:, From these results, it is suggested that schizophrenia entails dysfunctions in the fronto-striato-thalamo-cortical network associated with motor function control. [source] Stroop performance in bipolar disorder: further evidence for abnormalities in the ventral prefrontal cortexBIPOLAR DISORDERS, Issue 1 2006Dina M Kronhaus Objectives:, Bipolar patients are impaired in Stroop task performance, a measure of selective attention. Structural and functional abnormalities in task-associated regions, in particular the prefrontal cortex (PFC), have been reported in this population. We aimed to examine the relationship between functional abnormalities, impaired task performance and the severity of depressive symptoms in bipolar patients. Methods:, Remitted bipolar patients (n = 10; all medicated), either euthymic or with subsyndromal depression, and age-matched control subjects (n = 11) viewed 10 alternating blocks of incongruent Stroop and control stimuli, naming the colour of the ink. Neural response was measured using functional magnetic resonance imaging. We computed between-group differences in neural response and within-group correlations with mood and anxiety. Results:, There were no significant between-group differences in task performance. During the Stroop condition, controls demonstrated greater activation of visual and dorsolateral and ventrolateral prefrontal cortical areas; bipolar patients demonstrated relative deactivation within orbital and medial prefrontal cortices. Depression scores showed a trend towards a negative correlation with the magnitude of orbitofrontal cortex deactivation in bipolar patients, whereas state anxiety correlated positively with activation of dorsolateral PFC and precuneus in controls. Conclusions:, Our findings confirm previous reports of decreased ventral prefrontal activity during Stroop task performance in bipolar patients, and suggest a possible negative correlation between this and depression severity in bipolar patients. These findings further highlight the ventromedial PFC as a potential candidate for illness related dysfunction in bipolar disorder. [source] An unusual class of PITX2 mutations in Axenfeld-Rieger syndromeBIRTH DEFECTS RESEARCH, Issue 3 2006Irfan Saadi Abstract BACKGROUND Mutations in the PITX2 homeobox gene are known to contribute to Axenfeld-Rieger syndrome (ARS), an autosomal-dominant developmental disorder. Although most mutations are in the homeodomain and result in a loss of function, there is a growing subset in the C-terminal domain that has not yet been characterized. These mutations are of particular interest because the C-terminus has both inhibitory and stimulatory activities. METHODS In this study we used a combination of in vitro DNA binding and transfection reporter assays to investigate the fundamental issue of whether C-terminal mutations result in gain or loss of function at a cellular level. RESULTS We report a new frameshift mutation in the PITX2 allele that predicts a truncated protein lacking most of the C-terminal domain (D122FS). This newly reported mutant and another ARS C-terminal mutant (W133Stop) both have greater binding than wild-type to the bicoid element. Of interest, the mutants yielded ,5-fold greater activation of the prolactin promoter in CHO cells, even though the truncated proteins were expressed at lower levels than the wild-type protein. The truncated proteins also had greater than wild-type activity in 2 other cell lines, including the LS8 oral epithelial line that expresses the endogenous Pitx2 gene. CONCLUSIONS The results indicate that the PITX2 C-terminal domain has inhibitory activity and support the notion that ARS may also be caused by gain-of-function mutations. Birth Defects Research (Part A), 2006. © 2006 Wiley-Liss, Inc. [source] | |||||||||||||