High-density sub-100-nm peptide-gold nanoparticle complexes improve vaccine presentation by dendritic cells in vitro.

Nanocarriers have been explored to improve the delivery of tumor antigens to dendritic cells (DCs). Gold nanoparticles are attractive nanocarriers because they are inert, non-toxic, and can be readily endocytosed by DCs. Here, we designed novel gold-based nanovaccines (AuNVs) using a simple self-assembling bottom-up conjugation method to generate high-peptide density delivery and effective immune responses with limited toxicity. AuNVs were synthesized using a self-assembling conjugation method and optimized using DC-to-splenocyte interferon-γ enzyme-linked immunosorbent spot assays. The AuNV design has shown successful peptide conjugation with approximately 90% yield while remaining smaller than 80 nm in diameter. DCs uptake AuNVs with minimal toxicity and are able to process the vaccine peptides on the particles to stimulate cytotoxic T lymphocytes (CTLs). These high-peptide density AuNVs can stimulate CTLs better than free peptides and have great potential as carriers for various vaccine types.

Amygdala activation during emotion processing of neutral faces in children with severe mood dysregulation versus ADHD or bipolar disorder.

OBJECTIVE: To understand disorder-unique and common pathophysiology, studies in multiple patient groups with overlapping symptoms are needed. Deficits in emotion processing and hyperarousal symptoms are prominent features of bipolar disorder, attention deficit hyperactivity disorder (ADHD), and severe mood dysregulation. The authors compared amygdala response during emotional and nonemotional ratings of neutral faces in youths with these disorders as well as a group of healthy comparison youths. METHOD: Blood-oxygen-level-dependent (BOLD) signal in the amygdala was examined in children with bipolar disorder (N=43), ADHD (N=18), and severe mood dysregulation (N=29) and healthy comparison subjects (N=37). During functional magnetic resonance imaging (fMRI), participants attended to emotional and nonemotional aspects of neutral faces. RESULTS: While rating subjective fear of neutral faces, youths with ADHD demonstrated left amygdala hyperactivity relative to the other three groups, whereas youths with severe mood dysregulation demonstrated hypoactivity. CONCLUSIONS: These findings support the role of unique neural correlates in face-emotion processing among youths with bipolar disorder, ADHD, and severe mood dysregulation.

Practitioner review: the assessment of bipolar disorder in children and adolescents.

BACKGROUND: An increasing number of youth are being diagnosed with, and treated for, bipolar disorder (BD). Controversy exists about whether youth with non-episodic irritability and symptoms of attention deficit hyperactivity disorder (ADHD) should be considered to have a developmental presentation of mania. METHOD: A selective review of the literature related to this question, along with recommendations to guide clinical assessment. RESULTS: Data indicate differences between youth with episodic mania and those with non-episodic irritability in longitudinal diagnostic associations, family history, and pathophysiology. In youth with episodic mania, elation and irritability are both common during manic episodes. CONCLUSIONS: In diagnosing mania in youth, clinicians should focus on the presence of episodes that consist of a distinct change in mood accompanied by concurrent changes in cognition and behavior. BD should not be diagnosed in the absence of such episodes. In youth with ADHD, symptoms such as distractibility and agitation should be counted as manic symptoms only if they are markedly increased over the youth's baseline symptoms at the same time that there is a distinct change in mood and the occurrence of other associated symptoms of mania. Although different techniques for diagnosing comorbid illnesses have not been compared systematically, it appears most rational to diagnose co-occurring illnesses such as ADHD only if the symptoms of the co-occurring illness are present when the youth is euthymic.

A streamlined method for rapid and sensitive chromatin immunoprecipitation.

We report a streamlined procedure to efficiently carry samples from chromatin to qPCR-compatible DNA in as little as 4 h. We use this streamlined ChIP to quantify histone H3 modifications at active (cad) and repressed (T early alpha) promoters in a Rag1-deficient pro-T cell line after 1-2 h IP. We further show that the protocol readily quantified histone modifications in chromatin from 10(4) Rag-deficient DN thymocytes. Taken together, these data outline a simple, cost-effective procedure for efficient ChIP analysis.