Parenting styles and student achievement in normal and mental health populations : a reliability and validity study of the home environment profile

The primary purpose of this study was to assess the reliability and validity of the Home Environment Profile (HEP) and to determine the most effective use of items and scales in predicting school achievement. The HEP is a 69-item test that measures nine parenting styles. Most of the items used in the HEP were selected from actions that research on parent training had shown to have treatment validity. Items reflect a learning theory paradigm. Items were grouped by judges into 9 scales: (a) Modeling Attitudes and Behavior, (b) Monitoring Social Behavior, (c) Monitoring Academic Behavior, (d) Rewarding School Work and Behavior, (e) Disciplining, (f) Problem Solving and Communicating, (g) Nurturing, (h) Self-Managing, and (i) Teaching and Motivating. Parents completed the untimed instrument using a 5-point rating scale for each item. Student grades were rated on a 4-point scale. Initially, the subjects (N= 196) in this study consisted of three groi5)s of parents: (a) parents of high-achieving students making at least 75% As and B+s (n = 127), (b) parents of low-achieving students making at least 75% Cs, Ds, and Fs (n = 69), and (c) a group of parents whose children were being served by mental health facilities for emotional and behavioral problems (n = 24). Due to insufficient sample size, the Mental Health group was combined with the high and low groups for a total sample of 196. Items of the HEP were judged by two independent raters to be in 1 of 9 parenting scales. Rater agreement was 93% across all items, with judges agreeing on the placement of 65 of 69 items. Test-retest reliability for the HEP was r = .77, with item coefficients ranging from .03 to .98 (two-week interval for a sample of 30). Scale reliability was also determined by test-retest, with correlation coefficients ranging from .44 to .93. To assess the validity of the HEP, all items were then correlated to school achievement. Forty-five items correlated (Spearman\u27s Rho) significantly with ranks of grades. Scales formed from rater judgments were then used to determine the degree of association between scales and grades. All but one scale (Problem Solving and Communicating) were found to correlate (Spearman\u27s Rho) at a statistically significant level with student grades. Logistic regression analyses were then performed to predict parent membership of the High Achievement (As and B+s) and Low Achievement (Cs, Ds, and Fs) groups. Of the 8 HEP scales having at least 3 items, 3 scales (Monitoring Academic Behavior, Rewarding School Work and Behavior, and Nurturing) increased the prediction rate above the base rate of 63.84%. Using only these 3 scales increased the prediction rate to 83.05%. No other scales contributed to the improvement in the prediction of group membership

Structural Diversity of Ultralong CDRH3s in Seven Bovine Antibody Heavy Chains

Antigen recognition by mammalian antibodies represents the most diverse setting for protein-protein interactions, because antibody variable regions contain exceptionally diverse variable gene repertoires of DNA sequences containing combinatorial, non-templated junctional mutational diversity. Some animals use additional strategies to achieve structural complexity in the antibody combining site, and one of the most interesting of these is the formation of ultralong heavy chain complementarity determining region 3 loops in cattle. Repertoire sequencing studies of bovine antibody heavy chain variable sequences revealed that bovine antibodies can contain heavy chain complementarity determining region 3 (CDRH3) loops with 60 or more amino acids, with complex structures stabilized by multiple disulfide bonds. It is clear that bovine antibodies can achieve long, peculiarly structured CDR3s, but the range of diversity and complexity of those structures is poorly understood. We determined the atomic resolution structure of seven ultralong bovine CDRH3 loops. The studies, combined with five previous structures, reveal a large diversity of cysteine pairing variations, and highly diverse globular domains

Capturing the Spectrum of Interaction Effects in Genetic Association Studies by Simulated Evaporative Cooling Network Analysis

Evidence from human genetic studies of several disorders suggests that interactions between alleles at multiple genes play an important role in influencing phenotypic expression. Analytical methods for identifying Mendelian disease genes are not appropriate when applied to common multigenic diseases, because such methods investigate association with the phenotype only one genetic locus at a time. New strategies are needed that can capture the spectrum of genetic effects, from Mendelian to multifactorial epistasis. Random Forests (RF) and Relief-F are two powerful machine-learning methods that have been studied as filters for genetic case-control data due to their ability to account for the context of alleles at multiple genes when scoring the relevance of individual genetic variants to the phenotype. However, when variants interact strongly, the independence assumption of RF in the tree node-splitting criterion leads to diminished importance scores for relevant variants. Relief-F, on the other hand, was designed to detect strong interactions but is sensitive to large backgrounds of variants that are irrelevant to classification of the phenotype, which is an acute problem in genome-wide association studies. To overcome the weaknesses of these data mining approaches, we develop Evaporative Cooling (EC) feature selection, a flexible machine learning method that can integrate multiple importance scores while removing irrelevant genetic variants. To characterize detailed interactions, we construct a genetic-association interaction network (GAIN), whose edges quantify the synergy between variants with respect to the phenotype. We use simulation analysis to show that EC is able to identify a wide range of interaction effects in genetic association data. We apply the EC filter to a smallpox vaccine cohort study of single nucleotide polymorphisms (SNPs) and infer a GAIN for a collection of SNPs associated with adverse events. Our results suggest an important role for hubs in SNP disease susceptibility networks. The software is available at http://sites.google.com/site/McKinneyLab/software

Human monoclonal antibodies against NS1 protein protect against lethal West Nile virus infection

Envelope protein-targeted vaccines for flaviviruses are limited by concerns of antibody-dependent enhancement (ADE) of infections. Nonstructural protein 1 (NS1) provides an alternative vaccine target that avoids this risk since this protein is absent from the virion. Beyond its intracellular role in virus replication, extracellular forms of NS1 function in immune modulation and are recognized by host-derived antibodies. The rational design of NS1-based vaccines requires an extensive understanding of the antigenic sites on NS1, especially those targeted by protective antibodies. Here, we isolated human monoclonal antibodies (MAbs) from individuals previously naturally infected with WNV, mapped their epitopes using structure-guided mutagenesis, and evaluated their efficac

A human antibody against Zika virus crosslinks the E protein to prevent infection

The recent Zika virus (ZIKV) epidemic has been linked to unusual and severe clinical manifestations including microcephaly in fetuses of infected pregnant women and Guillian-Barré syndrome in adults. Neutralizing antibodies present a possible therapeutic approach to prevent and control ZIKV infection. Here we present a 6.2 Å resolution three-dimensional cryo-electron microscopy (cryoEM) structure of an infectious ZIKV (strain H/PF/2013, French Polynesia) in complex with the Fab fragment of a highly therapeutic and neutralizing human monoclonal antibody, ZIKV-117. The antibody had been shown to prevent fetal infection and demise in mice. The structure shows that ZIKV-117 Fabs cross-link the monomers within the surface E glycoprotein dimers as well as between neighbouring dimers, thus preventing the reorganization of E protein monomers into fusogenic trimers in the acidic environment of endosomes

A cross-reactive antibody protects against Ross River virus musculoskeletal disease despite rapid neutralization escape in mice

Arthritogenic alphaviruses cause debilitating musculoskeletal disease and historically have circulated in distinct regions. With the global spread of chikungunya virus (CHIKV), there now is more geographic overlap, which could result in heterologous immunity affecting natural infection or vaccination. Here, we evaluated the capacity of a cross-reactive anti-CHIKV monoclonal antibody (CHK-265) to protect against disease caused by the distantly related alphavirus, Ross River virus (RRV). Although CHK-265 only moderately neutralizes RRV infection in cell culture, it limited clinical disease in mice independently of Fc effector function activity. Despite this protective phenotype, RRV escaped from CHK-265 neutralization in vivo, with resistant variants retaining pathogenic potential. Near the inoculation site, CHK-265 reduced viral burden in a type I interferon signaling-dependent manner and limited immune cell infiltration into musculoskeletal tissue. In a parallel set of experiments, purified human CHIKV immune IgG also weakly neutralized RRV, yet when transferred to mice, resulted in improved clinical outcome during RRV infection despite the emergence of resistant viruses. Overall, this study suggests that weakly cross-neutralizing antibodies can protect against heterologous alphavirus disease, even if neutralization escape occurs, through an early viral control program that tempers inflammation