Activation of High and Low Affinity Dopamine Receptors Generates a Closed Loop that Maintains a Conductance Ratio and its Activity Correlate

Neuromodulators alter network output and have the potential to destabilize a circuit. The mechanisms maintaining stability in the face of neuromodulation are not well described. Using the pyloric network in the crustacean stomatogastric nervous system, we show that dopamine (DA) does not simply alter circuit output, but activates a closed loop in which DA-induced alterations in circuit output consequently drive a change in an ionic conductance to preserve a conductance ratio and its activity correlate. DA acted at low affinity type 1 receptors (D1Rs) to induce an immediate modulatory decrease in the transient potassium current (I A ) of a pyloric neuron. This, in turn, advanced the activity phase of that component neuron, which disrupted its network function and thereby destabilized the circuit. DA simultaneously acted at high affinity D1Rs on the same neuron to confer activity-dependence upon the hyperpolarization activated current (I h ) such that the DA- induced changes in activity subsequently reduced I h . This DA-enabled, activity-dependent, intrinsic plasticity exactly compensated for the modulatory decrease in I A to restore the I A :I h ratio and neuronal activity phase, thereby closing an open loop created by the modulator. Activation of closed loops to preserve conductance ratios may represent a fundamental operating principle neuromodulatory systems use to ensure stability in their target networks

Induction of a protective capsular polysaccharide antibody response to a multiepitope DNA vaccine encoding a peptide mimic of meningococcal serogroup C capsular polysaccharide

Systemic infection by encapsulated organisms, such as Neisseria meningitidis, is a major cause of morbidity and mortality worldwide, especially in individuals less than 2 years of age. Antibodies directed at the capsular polysaccharide are shown to be protective against disease by inducing complement-dependent bactericidal activity. The current polysaccharide vaccine has been shown to be poorly immunogenic in high-risk groups and this is probably related to its T-independent properties. An alternative approach to eliciting a T-dependent serum immunoglobulin G (IgG) antibody response to encapsulated pathogens is DNA vaccination. We assessed the immunogenicity of a multiepitope DNA vaccine encoding a T-cell helper epitope and a peptide mimic of N. meningitidis serogroup C. The DNA construct induced a significant anti-polysaccharide antibody response that was bactericidal. Mice immunized with the DNA construct were subsequently protected against challenge with a lethal dose of N. meningitidis serogroup C

Shifting Childrearing to Single Mothers: Results from 17 Western Countries

We investigate how recent changes in the Western family have affected childhood living arrangements. For 17 developed countries, we use multistate life table techniques to estimate childhood trajectories of coresi-dence with biological fathers versus other maternal partners. In all countries childhood exposure to single parenting is more often caused by parental separation than out-of-partnership childbearing. Both exposure to single parenting and expectancy of childhood spent with a single non-cohabiting mother vary widely across countries, with the United States exhibiting the highest levels of each at early 1990s rates. The greatest international variations concern parental cohabitation-its prevalence, durability, and the degree to which its increase has compensated for a decrease in the expectancy of childhood spent with married parents. Overall, we find little evidence of international convergence in childrearing arrangements, except that in countries where parental marriage has declined over time, childrearing has predominantly shifted to single mothers. Copyright 2003 by The Population Council, Inc..

Distilling Common History and Practice Elements to Inform Dissemination: Hanf-Model BPT Programs as an Example

There is a shift in evidence-based practice toward an understanding of the treatment elements that characterize empirically-supported interventions in general and the core components of specific approaches in particular. The evidence-base for Behavioral Parent Training (BPT), the standard of care for early-onset disruptive behavior disorders (Oppositional Defiant Disorder and Conduct Disorder), which frequently co-occur with Attention Deficit Hyperactivity Disorder, is well-established; yet, an ahistorical, program-specific lens tells little regarding how leaders, including Constance Hanf at the University of Oregon, shaped the common practice elements of contemporary evidence-based BPT. Accordingly, this review summarizes the formative work of Hanf, as well as the core elements, evolution, and extensions of her work, represented in Community Parent Education (COPE; Cunningham, Bremner, & Boyle, 1995; Cunningham, Bremner, Secord, & Harrison, 2009), Defiant Children (DC; Barkley 1987; Barkley, 2013), Helping the Noncompliant Child (HNC; Forehand & McMahon, 1981; McMahon & Forehand, 2003), Parent-Child Interaction Therapy (PCIT; Eyberg, & Robinson, 1982; Eyberg, 1988; Eyberg & Funderburk, 2011), and the Incredible Years (IY; Webster-Stratton, 1981; 1982; 2008). Our goal is not to provide an exhaustive review of the evidence-base for the Hanf-Model programs; rather, our intention is to provide a template of sorts from which agencies and clinicians can make informed choices about how and why they are using one program versus another, as well as how to make inform flexible use one program or combination of practice elements across programs, to best meet the needs of child clients and their families. Clinical implications and directions for future work are discussed