The integrin alpha 6 beta 4 is a laminin receptor

In this study, the putative laminin receptor function of the alpha 6 beta 4 integrin was assessed. For this purpose, we used a human cell line, referred to as clone A, that was derived from a highly invasive, colon adenocarcinoma. This cell line, which expresses the alpha 6 beta 4 integrin, adheres to the E8 and not to the P1 fragment of laminin. The adhesion of clone A cells to laminin is extremely rapid with half-maximal adhesion observed at 5 min after plating. Adhesion to laminin is blocked by GoH3, and alpha 6 specific antibody (60% inhibition), as well as by A9, a beta 4 specific antibody (30% inhibition). Most importantly, we demonstrate that alpha 6 beta 4 binds specifically to laminin-Sepharose columns in the presence of either Mg2+ or Mn2+ and it is eluted from these columns with EDTA but not with NaCl. The alpha 6 beta 4 integrin does not bind to collagen-Sepharose, but the alpha 2 beta 1 integrin does bind. Clone A cells do not express alpha 6 beta 1 as evidenced by the following observations: (a) no beta 1 integrin is detected in beta 1 immunoblots of GoH3 immunoprecipitates; and (b) no alpha 6 beta 1 integrin is seen in GoH3 immunoprecipitates of clone A extracts that had been immunodepleted of all beta 4 containing integrin using the A9 antibody. These data establish that laminin is a ligand for the alpha 6 beta 4 integrin and that this integrin can function as a laminin receptor independently of alpha 6 beta 1

Uncertainty analysis of diffuse-gray radiation enclosure problems: A hypersensitive case study

An uncertainty analysis of diffuse-gray enclosure problems is presented. The genesis was a diffuse-gray enclosure problem which proved to be hypersensitive to the specification of view factors. This genesis is discussed in some detail. The uncertainty analysis is presented for the general diffuse-gray enclosure problem and applied to the hypersensitive case study. It was found that the hypersensitivity could be greatly reduced by enforcing both closure and reciprocity for the view factors. The effects of uncertainties in the surface emissivities and temperatures are also investigated

The significance of attachment security for children’s social competence with peers: a meta-analytic study

This meta-analytic review examines the association between attachment during the early life course and social competence with peers during childhood, and compares the strength of this association with those for externalizing and internalizing symptomatology. Based on eighty independent samples (N = 4,441), the association between security and peer competence was significant (d = 0.39, CI 0.32; 0.47) and not moderated by the age at which peer competence was assessed. Avoidance (d = 0.17, CI 0.05; 0.30), resistance (d = 0.29, CI 0.09; 0.48), and disorganization (d = 0.25, CI 0.10; 0.40) were significantly associated with lower peer competence. Attachment security was significantly more strongly associated with peer competence than internalizing (but not externalizing) symptomatology. Discussion focuses on the significance of early attachment for the development of peer competence versus externalizing and internalizing psychopathology

Configurations of mother–child and father–child attachment relationships as predictors of child language competence: An individual participant data meta‐analysis

An individual participant data meta-analysis was conducted to test pre-registered hypotheses about how the configuration of attachment relationships to mothers and fathers predicts children's language competence. Data from seven studies (published between 1985 and 2014) including 719 children (Mage: 19.84months; 51% female; 87% White) were included in the linear mixed effects analyses. Mean language competence scores exceeded the population average across children with different attachment configurations. Children with two secure attachment relationships had higher language competence scores compared to those with one or no secure attachment relationships (d=.26). Children with two organized attachment relationships had higher language competence scores compared to those with one organized attachment relationship (d=.23), and this difference was observed in older versus younger children in exploratory analyses. Mother– child and father–child attachment quality did not differentially predict language competence, supporting the comparable importance of attachment to both parents in predicting developmental outcomes.info:eu-repo/semantics/publishedVersio

The parenting experience of those with borderline personality disorder traits: practitioner and parent perspectives

Background: Borderline Personality Disorder (BPD) is associated with challenges around emotional intensity and interpersonal difficulties. The children of parents with BPD are at risk of poorer outcomes in terms of their own mental health, educational outcomes and wellbeing. The challenges of being a parent can also exacerbate the symptoms of those with BPD traits. There is a pressing need to understand the experience of these parents and to determine what support would be appropriate and useful. Aim: To explore and compare the experiences and support needs of parents with BPD traits with the experiences and understanding of practitioners who work with them. Methods: Interviews with 12 parents with BPD traits and 21 practitioners with experience of working with individuals with BPD. The two strands of interviews were analyzed independently using a thematic framework approach, after which the superordinate and subordinate themes were subject to comparison. Results: Parents with BPD traits represent themselves as experiencing considerable challenges in their role as a parent. These included the impact of emotional intensity, social isolation and lack of a positive parenting models to draw upon. Practitioners demonstrated a strong degree of shared understanding into these difficulties. Both groups highlighted a lack of appropriate support for these parents. Conclusion: This research highlights the clinical need for parenting-focused support for individuals with BPD traits. Preliminary suggestions for format and content are given

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN