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In F. graminearum, the transcriptional regulator Tri6 is encoded within the trichothecene gene cluster and regulates genes involved in the biosynthesis of the secondary metabolite deoxynivalenol (DON). The Tri6 protein with its Cys₂His₂ zinc-finger may also conform to the class of global transcription regulators. This class of global transcriptional regulators mediate various environmental cues and generally responds to the demands of cellular metabolism. To address this issue directly, we sought to find gene targets of Tri6 in F. graminearum grown in optimal nutrient conditions. Chromatin immunoprecipitation followed by Illumina sequencing (ChIP-Seq) revealed that in addition to identifying six genes within the trichothecene gene cluster, Tri1, Tri3, Tri6, Tri7, Tri12 and Tri14, the ChIP-Seq also identified 192 additional targets potentially regulated by Tri6. Functional classification revealed that, among the annotated genes, ∼40% are associated with cellular metabolism and transport and the rest of the target genes fall into the category of signal transduction and gene expression regulation. ChIP-Seq data also revealed Tri6 has the highest affinity toward its own promoter, suggesting that this gene could be subject to self-regulation. Electro mobility shift assays (EMSA) performed on the promoter of Tri6 with purified Tri6 protein identified a minimum binding motif of GTGA repeats as a consensus sequence. Finally, expression profiling of F. graminearum grown under nitrogen-limiting conditions revealed that 49 out of 198 target genes are differentially regulated by Tri6. The identification of potential new targets together with deciphering novel binding sites for Tri6, casts new light into the role of this transcriptional regulator in the overall growth and development of F. graminearum.

Understanding how a subset of expressed genes dictates cellular phenotype is a considerable challenge owing to the large numbers of molecules involved, their combinatorics and the plethora of cellular behaviours that they determine 1 , 2 . Here we reduced this complexity by focusing on cellular organization—a key readout and driver of cell behaviour 3 , 4 —at the level of major cellular structures that represent distinct organelles and functional machines, and generated the WTC-11 hiPSC Single-Cell Image Dataset v1, which contains more than 200,000 live cells in 3D, spanning 25 key cellular structures. The scale and quality of this dataset permitted the creation of a generalizable analysis framework to convert raw image data of cells and their structures into dimensionally reduced, quantitative measurements that can be interpreted by humans, and to facilitate data exploration. This framework embraces the vast cell-to-cell variability that is observed within a normal population, facilitates the integration of cell-by-cell structural data and allows quantitative analyses of distinct, separable aspects of organization within and across different cell populations. We found that the integrated intracellular organization of interphase cells was robust to the wide range of variation in cell shape in the population; that the average locations of some structures became polarized in cells at the edges of colonies while maintaining the ‘wiring’ of their interactions with other structures; and that, by contrast, changes in the location of structures during early mitotic reorganization were accompanied by changes in their wiring. A dataset of 3D images from more than 200,000 human induced pluripotent stem cells is used to develop a framework to analyse cell shape and the location and organization of major intracellular structures.

Cognitive impairments in schizophrenia are well documented and correlated with functional disability. Although some patients demonstrate normal neuropsychological (NP) functioning, little is known about their functional disability. We examined the cross-sectional functional implications of NP normality and symptomatic remission in older outpatients diagnosed with schizophrenia or schizoaffective disorder, who were administered a NP battery and performance-based measures of functional and social competence, with their real-world functioning rated by case managers. NP status was classified by the General Deficit Score (GDS) and remission status was based on the Positive and Negative Syndrome Scale (PANSS), yielding four subsamples of patients: NP normal-remitted (n = 21), NP normal-symptomatic (n = 22), NP impaired-remitted (n = 90), and NP impaired-symptomatic (n = 97). NP normal patients demonstrated better functional and social competence and better ratings of real world functioning, after controlling for premorbid abilities. However, compared to normative date, NP normal patients manifested disability in several real-world domains, including residential status. These results suggest that NP status is a better predictor of functional outcome then symptom status or the interaction of the two factors. The disability seen in NP normal cases indicates that factors other than cognitive impairments may determine aspects of everyday outcomes in schizophrenia. (JINS, 2008, 14, 479–488.)

Language impairment is a primary characteristic of children with autism; however, findings on the language deficits of these children have been inconclusive, and even less is known about the language profiles of Chinese-speaking children with autism. The present study examined the verbal expression—comprehension abilities of 46 Chinese children at ages 5 to 6. The children with autism were further classified into high- or low-functioning groups based on their nonverbal intelligence. Results showed that 63% of the children with autism demonstrated language impairment. Specifically, 42% were impaired in both verbal expression and comprehension abilities, and 21% demonstrated impaired expression skills. General intelligence did not seem to explain this heterogeneity, as variability was also observed among the high-functioning children with autism. The results also suggested that a test of expressive language is more sensitive than a test of comprehension in differentiating Chinese children with autism from their age-matched counterparts at early childhood.

There has been increasing empirical evidence for the enhancing effects of Dejian Mind-Body Intervention (DMBI), a traditional Chinese Shaolin healing approach, on human frontal brain activity/functions, including patients with autism who are well documented to have frontal lobe problems. This study aims to compare the effects of DMBI with a conventional behavioural/cognitive intervention (CI) on enhancing the executive functions and memory of a nine-year-old boy with low-functioning autism (KY) and to explore possible underlying neural mechanism using EEG theta cordance. At post-one-month DMBI, KY's inhibitory control, cognitive flexibility, and memory functioning have significantly improved from “severely-to-moderately impaired” to “within-normal” range. This improvement was not observed from previous 12-month CI. Furthermore, KY showed increased cordance gradually extending from the anterior to the posterior brain region, suggesting possible neural mechanism underlying his cognitive improvement. These findings have implicated potential applicability of DMBI as a rehabilitation program for patients with severe frontal lobe and/or memory disorders.

The present study examined the neuro-electrophysiological activity of the brain associated with the application of a herbal remedy developed by a Shaolin monk based upon the Chan healing principle of clearing the orifices (i.e., the nasal cavities). A repeated-measures design was used. Fourteen normal adults were administered herbal remedy and saline solution intranasally on separate sessions. Two intervals of eyes-closed resting EEG data were obtained individually before and after each administration. Results showed that only the herbal remedy but not the saline solution induced elevation in cordance, an index correlated with cerebral perfusion, in the anterior brain region. In addition, the activity of the anterior cingulate cortex (ACC), as examined by the LORETA analysis, was also increased after the application of the herbal remedy but not saline solution. The present study provided some preliminary evidence suggesting that the herbal nasal drop enhanced the activity of the frontal lobe and ACC. Implications for the potential clinical application of the herbal remedy to treat patients with frontal lobe disorders were discussed.

A functional polymorphism of the gene coding for Catechol-O-methyltrasferase (COMT), an enzyme responsible for the degradation of the catecholamine dopamine (DA), epinephrine, and norepinephrine, is associated with cognitive deficits. However, previous studies have not examined the effects of COMT on context processing, as measured by the AX-CPT, a task hypothesized to be maximally relevant to DA function. 32 individuals who were either healthy, with schizotypal personality disorder, or non-cluster A, personality disorder (OPD) were genotyped at the COMT Val158Met locus. Met/Met (n = 6), Val/Met (n = 10), Val/Val (n = 16) individuals were administered a neuropsychological battery, including the AX-CPT and the N-back working memory test. For the AX-CPT, Met/Met demonstrated more AY errors (reflecting good maintenance of context) than the other genotypes, who showed equivalent error rates. Val/Val demonstrated disproportionately greater deterioration with increased task difficulty from 0-back to 1-back working memory demands as compared to Met/Met, while Val/Met did not differ from either genotypes. No differences were found on processing speed or verbal working memory. Both context processing and working memory appear related to COMT genotype and the AX-CPT and N-back may be most sensitive to the effects of COMT variation.

Cognitive impairments in schizophrenia are well documented and correlated with functional disability. Although some patients demonstrate normal neuropsychological (NP) functioning, little is known about their functional disability. We examined the cross-sectional functional implications of NP normality and symptomatic remission in older outpatients with schizophrenia or schizoaffective disorder, who were administered a NP battery and performance-based measures of functional and social competence, with their real-world functioning rated by case managers. NP status was classified by the General Deficit Score (GDS) and remission status was based on the Positive and Negative Syndrome Scale (PANSS), yielding four subsamples of patients: NP normal-remitted (n=21), NP normal-symptomatic (n=22), NP impaired-remitted (n=90), and NP impaired-symptomatic (n=97). NP normal patients demonstrated better functional and social competence and better ratings of real-world functioning, after controlling for premorbid abilities. However, compared to normative date, NP normal patients manifested disability in several real-world domains, including residential status. These results suggest that NP status is a better predictor of functional outcome then symptom status or the interaction of the two factors. The disability seen in NP normal cases indicates that factors other than cognitive impairments may determine aspects of everyday outcomes in schizophrenia.

Winnie W Leung1, Margaret M McClure1, Larry J Siever1,2, Deanna M Barch3, Philip D Harvey1,21Department of Veterans Affairs, VISN 3 Mental Illness Research, Education, and Clinical Center (MIRECC), Bronx, NY, USA; 2Department of Psychiatry, Mt. Sinai School of Medicine, New York, NY, USA; 3Departments of Psychology and Psychiatry, Washington University, St. Louis, MO, USAAbstract: A functional polymorphism of the gene coding for Catechol-O-methyltrasferase (COMT), an enzyme responsible for the degradation of the catecholamine dopamine (DA), epinephrine, and norepinephrine, is associated with cognitive deficits. However, previous studies have not examined the effects of COMT on context processing, as measured by the AX-CPT, a task hypothesized to be maximally relevant to DA function. 32 individuals who were either healthy, with schizotypal personality disorder, or non-cluster A, personality disorder (OPD) were genotyped at the COMT Val158Met locus. Met/Met (n = 6), Val/Met (n = 10), Val/Val (n = 16) individuals were administered a neuropsychological battery, including the AX-CPT and the N-back working memory test. For the AX-CPT, Met/Met demonstrated more AY errors (reflecting good maintenance of context) than the other genotypes, who showed equivalent error rates. Val/Val demonstrated disproportionately greater deterioration with increased task difficulty from 0-back to 1-back working memory demands as compared to Met/Met, while Val/Met did not differ from either genotypes. No differences were found on processing speed or verbal working memory. Both context processing and working memory appear related to COMT genotype and the AX-CPT and N-back may be most sensitive to the effects of COMT variation.Keywords: COMT, dopamine, context processing, working memory, schizotypal personality disorder

Social anhedonia is an important feature of schizophrenia and it is a promising indicator of schizotypy. Although social anhedonia is defined as an affective construct (less pleasure derived from social encounters), little is actually known about the affective correlates of social anhedonia. Prior laboratory research is limited in that no prior study has used affiliative social stimuli in examining affective reactions associated with anhedonia. This study sought to extend prior research through an examination of the expression and experience of emotion in social anhedonics by using a novel social affiliative film stimulus. After screening a large sample of female undergraduate students (N = 1,085), a cohort of psychometrically identified social anhedonics (n = 34) and normally hedonic controls (n = 45) participated in laboratory assessments involving trait affectivity, self-reported dispositional emotional expressiveness, and the expression and experience of emotion in response to neutral, non-affiliative (i.e., comedy) and affiliative film clips. Results showed that social anhedonics have lower trait positive affect compared to controls, but there were no group differences in trait negative affect. At baseline, social anhedonics reported lower state positive affect and less warmth and affection compared to controls, but there were no group differences in state negative affect. Social anhedonics also reported the disposition to be less expressive. Consistent with their reports of attenuated emotional experience and expression outside of the laboratory, social anhedonics reported less positive affect and displayed less facial expressions in response to affect eliciting films in the laboratory. Social anhedonics, however, did not report less warmth and affection across the films as compared to controls. Additionally, social anhedonics did not report less positive emotions or warmth and affection in response to the affiliative film, as compared to the non-affiliative (i.e., comedy) film. Implications and study limitations are discussed.