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Disclosure following stressful events produces physical and psychological benefits. This study was designed to compare the benefits following disclosure through face-to-face versus instant messaging. Eighty female undergraduates were asked to view a dramatized rape scene. Following this viewing, participants in the disclosure groups were asked to discuss their thoughts and feelings about the video with trained female confederates through face-to-face or instant messaging interactions. The nondisclosure groups discussed a neutral topic through the same two modes of communication. Positive and negative affect, pulse rate, and galvanic skin response were assessed at baseline, following the acute stressor, and following the conversation. The disclosure groups experienced a greater reduction in physiological stress symptoms than the nondisclosure groups, although self-report of negative affect improved significantly more for those that did not disclose. The face-to-face disclosure group showed greater physiological improvement than the instant messaging disclosure group, with no differences in affect. Social interaction modality impacts physiological coping following stressful events. [ABSTRACT FROM AUTHOR]

Abstract: The Internet Paradox refers to findings that demonstrated that the increase in communications brought about by Internet usage actually had negative effects on user’s psychological well-being and social involvement. This study proposes that face-to-face contact promotes the development of rapport and thereby individuals that use the internet excessively will lack these necessary social skills. Specifically, we investigate whether, through use of telephone communications, average users ratings of likeability and rapport would differ when speaking to excessive internet users. This experiment utilized previously unacquainted individuals who conversed by telephone while discussing both, a cooperative and an adversarial task. Results indicate that excessive users were more likely to be depressed and socially inhibited, and also were rated as having a lower level of rapport and likeability. Further research is required in order to explain the role of personality in excessive internet usage. [Copyright &y& Elsevier]

Apert syndrome is an autosomal dominant disorder characterized by malformations of the skull, limbs and viscera. Two-thirds of affected individuals have a S252W mutation in fibroblast growth factor receptor 2 (FGFR2). To study the pathogenesis of this condition, we generated a knock-in mouse model with this mutation. The Fgfr2+/S252W mutant mice have abnormalities of the skeleton, as well as of other organs including the brain, thymus, lungs, heart and intestines. In the mutant neurocranium, we found a midline sutural defect and craniosynostosis with abnormal osteoblastic proliferation and differentiation. We noted ectopic cartilage at the midline sagittal suture, and cartilage abnormalities in the basicranium, nasal turbinates and trachea. In addition, from the mutant long bones, in vitro cell cultures grown in osteogenic medium revealed chondrocytes, which were absent in the controls. Our results suggest that altered cartilage and bone development play a significant role in the pathogenesis of the Apert syndrome phenotype. [ABSTRACT FROM AUTHOR]

Patients with lung cancer with activating mutations in the EGF receptor (EGFR) kinase, who are treated longterm with tyrosine kinase inhibitors (TKI), often develop secondary mutations in EGFR associated with resistance. Mice engineered to develop lung adenocarcinomas driven by the human EGFR T790M resistance mutation are similarly resistant to the EGFR TKI erlotinib. By tumor volume endpoint analysis, these mouse tumors respond to BIBW 2992 (an irreversible EGFR/HER2 TKI) and rapamycin combination therapy. To correlate EGFR-driven changes in the lung with response to drug treatment, we conducted an integrative analysis of global transcriptome and metabolite profiling compared with quantitative imaging and histopathology at several time points during tumor progression and treatment. Responses to single-drug treatments were temporary, whereas combination therapy elicited a sustained response. During tumor development, metabolomic signatures indicated a shift to high anabolic activity and suppression of antitumor programs with 11 metabolites consistently present in both lung tissue and blood. Combination drug treatment reversed many of the molecular changes found in tumored lung. Data integration linking cancer signaling networks with metabolic activity identified key pathways such as glutamine and glutathione metabolism that signified response to single or dual treatments. Results from combination drug treatment suggest that metabolic transcriptional control through C-MYC and SREBP, as well as ELK1, NRF1, and NRF2, depends on both EGFR and mTORC1 signaling. Our findings establish the importance of kinetic therapeutic studies in preclinical assessment and provide in vivo evidence that TKI-mediated antiproliferative effects also manifest in specific metabolic regulation. [ABSTRACT FROM AUTHOR]

Members of the highly conserved homeobox (HOX) gene family encode transcription factors that confer cellular and tissue identities along the antero-posterior axis of mice and humans. We have identified a founder homozygous missense mutation in HOXB1 in two families from a conservative German American population. The resulting phenotype includes bilateral facial palsy, hearing loss, and strabismus and correlates extensively with the previously reported Hoxb1 −/− mouse phenotype. The missense variant is predicted to result in the substitution of a cysteine for an arginine at amino acid residue 207 (Arg207Cys), which corresponds to the highly conserved Arg5 of the homeodomain. Arg5 interacts with thymine in the minor groove of DNA through hydrogen bonding and electrostatic attraction. Molecular modeling and an in vitro DNA-protein binding assay predict that the mutation would disrupt these interactions, destabilize the HOXB1:PBX1:DNA complex, and alter HOXB1 transcriptional activity. [Copyright &y& Elsevier]