Transcriptome-Wide Binding Sites for Components of the Saccharomyces cerevisiae Non-Poly(A) Termination Pathway: Nrd1, Nab3, and Sen1

RNA polymerase II synthesizes a diverse set of transcripts including both protein-coding and non-coding RNAs. One major difference between these two classes of transcripts is the mechanism of termination. Messenger RNA transcripts terminate downstream of the coding region in a process that is coupled to cleavage and polyadenylation reactions. Non-coding transcripts like Saccharomyces cerevisiae snoRNAs terminate in a process that requires the RNA–binding proteins Nrd1, Nab3, and Sen1. We report here the transcriptome-wide distribution of these termination factors. These data sets derived from in vivo protein–RNA cross-linking provide high-resolution definition of non-poly(A) terminators, identify novel genes regulated by attenuation of nascent transcripts close to the promoter, and demonstrate the widespread occurrence of Nrd1-bound 3′ antisense transcripts on genes that are poorly expressed. In addition, we show that Sen1 does not cross-link efficiently to many expected non-coding RNAs but does cross-link to the 3′ end of most pre–mRNA transcripts, suggesting an extensive role in mRNA 3′ end formation and/or termination

Effects of Background Anger, Provocation, and Methylphenidate on Emotional Arousal and Aggressive Responding in Attention-Deficit Hyperactivity Disordered Boys with and without Concurrent Aggressiveness

We investigated the effects of background anger, provocation, and methylphenidate on emotional, physiological, and behavioral responding in children with attentiondeficit hyperactivity disorder (ADHD) with and without concurrent aggression. Our study revealed that ADHD boys showed more emotional and physiological distress when exposed to an interaction in which an administrator chastised each boy\u27\u27s favorite counselor, compared to a friendly interaction between the two adults. The background anger manipulation did not affect the aggressive behavior of the boys against an opponent in an aggressive game. High-aggressive (HA) ADHD boys were more likely to respond to provocation with aggression than low-aggressive (LA) ADHD boys, but only LA boys showed increased physiological reactivity with increasing provocation. Methylphenidate resulted in increased heart rates under all conditions and did not interact with any of the other findings

Effects of Background Anger, Provocation, and Methylphenidate on Emotional Arousal and Aggressive Responding in Attention-Deficit Hyperactivity Disordered Boys with and without Concurrent Aggressiveness

We investigated the effects of background anger, provocation, and methylphenidate on emotional, physiological, and behavioral responding in children with attentiondeficit hyperactivity disorder (ADHD) with and without concurrent aggression. Our study revealed that ADHD boys showed more emotional and physiological distress when exposed to an interaction in which an administrator chastised each boy\u27\u27s favorite counselor, compared to a friendly interaction between the two adults. The background anger manipulation did not affect the aggressive behavior of the boys against an opponent in an aggressive game. High-aggressive (HA) ADHD boys were more likely to respond to provocation with aggression than low-aggressive (LA) ADHD boys, but only LA boys showed increased physiological reactivity with increasing provocation. Methylphenidate resulted in increased heart rates under all conditions and did not interact with any of the other findings

Self-Report of ADHD Symptoms in University Students: Cross-Gender and Cross-National Prevalence

Little research has examined the structure and prevalence of attention-deficit/hyperactivity disorder (ADHD) symptoms in university students, including whether symptom structure conforms to the bidimensional (i.e., inattention and hyperactivity-impulsivity) conceptualization of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) and whether self-reported symptoms vary across gender and country. A sample of 1,209 university students from three countries (Italy, New Zealand, and the United States) completed a 24-item self-report measure (the Young Adult Rating Scale) tapping ADHD symptomatology. Factor analyses within the U.S. and New Zealand samples supported a bidimensional symptom structure, whereas weaker support for this conceptualization was provided by the Italian sample. Participants did not vary significantly by gender in symptom report; however, Italian students reported significantly more inattention and hyperactivity-impulsivity symptoms than students from the United States. The prevalence of self-reported ADHD symptoms beyond DSM-IV thresholds for diagnosis ranged from 0% (Italian women) to 8.1% (New Zealand men). The implications of these results for the use of DSM-IV criteria is identifying university students with ADHD are discussed

IFN-gamma AU-rich element removal promotes chronic IFN-gamma expression and autoimmunity in mice

We generated a mouse model with a 162 nt AU-rich element (ARE) region deletion in the 3\u27 untranslated region (3\u27UTR) of the interferon-gamma (IFN-γ) gene that results in chronic circulating serum IFN-γ levels. Mice homozygous for the ARE deletion (ARE-Del) (-/-) present both serologic and cellular abnormalities typical of patients with systemic lupus erythematosus (SLE). ARE-Del(-/-) mice display increased numbers of pDCs in bone marrow and spleen. Addition of IFN-γ to Flt3-ligand (Flt3L) treated in vitro bone marrow cultures results in a 2-fold increase in pDCs with concurrent increases in IRF8 expression. Marginal zone B (MZB) cells and marginal zone macrophages (MZMs) are absent in ARE-Del(-/-) mice. ARE-Del(+/-) mice retain both MZB cells and MZMs and develop no or mild autoimmunity. However, low dose clodronate treatment in ARE-Del(+/-) mice specifically eliminates MZMs and promotes anti-DNA antibody development and glomerulonephritis. Our findings demonstrate the consequences of a chronic IFN-γ milieu on B220(+) cell types and in particular the impact of MZB cell loss on MZM function in autoimmunity. Furthermore, similarities between disease states in ARE-Del(-/-) mice and SLE patients suggest that IFN-γ may not only be a product of SLE but may be critical for disease onset and progression