Programmable promoter editing for precise control of transgene expression.

Subtle changes in gene expression direct cells to distinct cellular states. Identifying and controlling dose-dependent transgenes require tools for precisely titrating expression. To this end, we developed a highly modular, extensible framework called DIAL for building editable promoters that allow for fine-scale, heritable changes in transgene expression.

Incorporation of noncanonical base Z yields modified mRNA with minimal immunogenicity and improved translational capacity in mammalian cells.

Chemically modified mRNAs hold great potential for therapeutic applications . Currently, the base modification scheme largely preserves the canonical Watson-Crick base pairing, thus missing one mode of mRNA modulation by altering its secondary structure. Here we report the incorporation of base Z (2-aminoadenine) into mRNA to create Z-mRNA with improved translational capacity, decreased cytotoxicity, and drastically reduced immunogenicity compared to the unmodified mRNA in mammalian cells.

SHIELD: a platform for high-throughput screening of barrier-type DNA elements in human cells.

Chromatin boundary elements contribute to the partitioning of mammalian genomes into topological domains to regulate gene expression. Certain boundary elements are adopted as DNA insulators for safe and stable transgene expression in mammalian cells. These elements, however, are ill-defined and less characterized in the non-coding genome, partially due to the lack of a platform to readily evaluate boundary-associated activities of putative DNA sequences.

Replicable differences in preferred circadian phase between bipolar disorder patients and control individuals.

Morningness/eveningness (M/E) is a stable, quantifiable measure reflecting preferred circadian phase. Two prior studies suggest that bipolar I disorder (BP1) cases are more likely to have lower M/E scores, i.e.

Lifetime psychiatric disorders in school-aged offspring of parents with bipolar disorder: the Pittsburgh Bipolar Offspring study.

Context: Whether offspring of parents with bipolar disorder (BP) are at specifically high risk to develop BP and other psychiatric disorders has not been adequately studied.

Objective: To evaluate lifetime prevalence and specificity of psychiatric disorders in offspring of parents with BP-I and BP-II.

Design: Offspring aged 6 to 18 years who have parents with BP and community control subjects were interviewed with standardized instruments.

Schedule for affective disorders and schizophrenia for school-age children (K-SADS-PL) for the assessment of preschool children--a preliminary psychometric study.

Objective: To assess the psychometrics of the schedule for affective disorders and schizophrenia for school-age children present and lifetime version (K-SADS-PL) in diagnosing DSM-IV psychiatric disorders and subsyndromal symptomatology in preschool children.

Method: Parents were interviewed about their children using the K-SADS-PL, and they completed the early childhood inventory-4 (ECI-4) and child behavior checklist for ages 1(1/2)-5 years (CBCL). Discriminant, divergent, and convergent validity of the K-SADS-PL were evaluated in 204 offspring ages 2-5 years old of parents from an ongoing study.

Mentoring increases connectedness and knowledge: a cross-sectional evaluation of two programs in child and adolescent psychiatry.

Objective: The authors assess changes in knowledge and feeling connected to the field of child and adolescent psychiatry (CAP) after participation in a brief mentoring program held at two CAP conferences.

Methods: Similar mentorship programs were implemented at two CAP conferences, one national (N=119 participants), one international (N=53). The 4-day programs were part of larger travel awards, and included daily small group meetings consisting of a mode of two mentors and six participants.

Mother-child interactions in depressed children and children at high risk and low risk for future depression.

Objective: To compare mother-child interactions and parenting styles in families of children with major depressive disorder, youths at high risk for depression, and healthy controls.

Method: Currently depressed (n = 43), high-risk (n = 28), and healthy control (n = 41) youths and their mothers engaged in a standardized videotaped problem-solving interaction. Measures of affect and behavior for both mothers and children were obtained, in addition to global measures of parenting.

Aggression, hostility, and irritability in children at risk for bipolar disorder.

Objectives: To assess aggression, irritability and hostility in children at risk for bipolar disorder (BP).

Methods: Using the parent and the child versions of the Children's Hostility Inventory (CHI), we assessed aggression, hostility, and irritability in 300 offspring aged 6-18 years old of BP parents and 169 children of community controls.

Results: Children of BP parents have significantly higher scores on the total CHI and its subscales than do children of control parents.

Fluoxetine for the treatment of childhood anxiety disorders: open-label, long-term extension to a controlled trial.

Objective: To assess the efficacy of fluoxetine for the long-term treatment of children and adolescents with anxiety disorders, including generalized anxiety disorder, separation anxiety disorder, and/or social phobia.

Method: Children and adolescents (7-17 years old) with anxiety disorders were studied in open treatment for 1 year after they completed a randomized, controlled trial (RCT) comparing fluoxetine and placebo. The follow-up phase assessments included clinician, parent, and child ratings with measures of global severity, global improvement, and anxiety symptoms.

Citalopram treatment of pediatric recurrent abdominal pain and comorbid internalizing disorders: an exploratory study.

Objective: To assess the potential efficacy, tolerability, and safety of citalopram in the treatment of functional pediatric recurrent abdominal pain and comorbid internalizing disorders.

Method: Twenty-five clinically referred children and adolescents with recurrent abdominal pain aged 7 to 18 years, inclusive, participated in a 12-week, flexible-dose, open-label trial of citalopram. Primary outcome measure was the Clinical Global Impression Scale-Improvement, with responders defined by ratings of 1 (very much improved) or 2 (much improved).

Recurrent abdominal pain, anxiety, and depression in primary care.

Objective: The prevalence of psychiatric disorder in children and adolescents with functional recurrent abdominal pain (RAP) is unknown. Our aim was to determine whether RAP is associated with psychiatric symptoms and disorders, anxious temperament, and functional impairment in pediatric primary care.

Methods: Children and adolescents who were 8 to 15 years of age, inclusive, and presented with RAP (N = 42) or for routine care in the absence of recurrent pain (N = 38) were identified by a screening procedure in pediatric primary care office waiting rooms and recruited to participate in a case-control study.

Fluoxetine for the treatment of childhood anxiety disorders.

Objective: To assess the efficacy and tolerability of fluoxetine for the acute treatment of children and adolescents with generalized anxiety disorder, separation anxiety disorder, and/or social phobia.

Method: Anxious youths (7-17 years old) who had significant functional impairment were randomized to fluoxetine (20 mg/day) (n = 37) or placebo (n = 37) for 12 weeks.

Results: Fluoxetine was effective in reducing the anxiety symptoms and improving functioning in all measures.

Is bipolar disorder specifically associated with panic disorder in youths?

Objective: To replicate previous findings of high rates of bipolar disorder (BPD) in patients with panic disorder (PD) and determine if youths with both PD and BPD have more severe illness.

Method: 2025 youths aged 5 to 19 years seen at a mood and anxiety specialty clinic were assessed using the Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present Episode, 4th Revision. Diagnoses were made using DSM-III and DSM-III-R criteria and then updated to conform to DSM-IV criteria.