Resolving the genetic heterogeneity of prelingual hearing loss within one family: Performance comparison and application of two targeted next generation sequencing approaches.

published_or_final_versio

Human Metapneumovirus Inhibits IFN-β Signaling by Downregulating Jak1 and Tyk2 Cellular Levels

Human metapneumovirus (hMPV), a leading cause of respiratory tract infections in infants, inhibits type I interferon (IFN) signaling by an unidentified mechanism. In this study, we showed that infection of airway epithelial cells with hMPV decreased cellular level of Janus tyrosine kinase (Jak1) and tyrosine kinase 2 (Tyk2), due to enhanced proteosomal degradation and reduced gene transcription. In addition, hMPV infection also reduced the surface expression of type I IFN receptor (IFNAR). These inhibitory mechanisms are different from the ones employed by respiratory syncytial virus (RSV), which does not affect Jak1, Tyk2 or IFNAR expression, but degrades downstream signal transducer and activator of transcription proteins 2 (STAT2), although both viruses are pneumoviruses belonging to the Paramyxoviridae family. Our study identifies a novel mechanism by which hMPV inhibits STAT1 and 2 activation, ultimately leading to viral evasion of host IFN responses

Expansion of CCR4+ activated T cells is associated with memory B cell reduction in DOCK8-deficient patients.

Hyper-IgE syndrome (HIES) is a genetic disorder characterized by elevated IgE serum levels, mostly due to mutations in STAT3 or DOCK8. Despite clinical heterogeneity between the two forms of the disease, clinical manifestations may not be conclusive for diagnosis and immunological differences are still unclear. Herein, we performed a detailed characterization of the T- and B-cell compartments by flow cytometry in seven HIES patients with homozygous DOCK8 mutations and six patients presenting heterozygous STAT3 mutations. We observed that DOCK8-deficient patients showed a marked reduction of naive and recent thymic emigrant (RTE) T lymphocytes together with a relative increase of activated T cells, most of which co-expressed the chemokine receptor CCR4, a marker of Th2 polarization. Moreover, an extreme reduction of memory B cells was detected, despite a normal/increased proportion of immunoglobulin-secreting cells. These observations indicate that DOCK8-deficient patients display a distinctive immunophenotype which is characteristic of this form of HIES

Exome sequencing reveals a pallidin mutation in a Hermansky-Pudlak-like primary immunodeficiency syndrome.

No abstract availabl

Effectiveness of Group Positive Parenting Program (Triple P) in changing child behavior, parenting style, and parental adjustment: An intervention study in Japan

The purpose of this study is to investigate the effectiveness of a group-based family intervention program known as the Group Positive Parenting Program (Triple P), with families in Japan. Reductions in children's behavioral problems, changes in dysfunctional parenting practices, and affects on parenting adjustment were examined. Participants of both the intervention and control groups (N = 91 and N = 24, respectively) were recruited from mothers visiting health clinics in Kawasaki City, Kanagawa. Intervention and control groups were assessed in terms of child behavior (Strength and Difficulty Questionnaire, SDQ), parenting style (Parenting Scale, PS), and parenting adjustment (Depression-Anxiety-Stress Scale, DASS; and Parenting Experience Survey, PES), both pre- and postintervention. A repeated measures multivariate analysis of variance was used to determine the intervention's effects. The SDQ score for the conduct problems subscale indicated a significant intervention effect. In addition, the postintervention scores for all subscales of the PS, the DASS depression subscale and total scores, as well as ratings for perceived difficulty of parenting in the PES, were significantly reduced in the intervention group alone. The PES also revealed that confidence in parenting significantly increased only in the intervention group. Group Triple P is effective in decreasing child conduct problems, dysfunctional parenting practices, depression, anxiety, stress, and the perceived level of parenting difficulty, as well as in improving parenting confidence, among Japanese families