Epithelial-Mesenchymal Transition (EMT) is a dynamic process through which epithelial cells transdifferentiate from an epithelial phenotype into a mesenchymal phenotype. Previous studies have also demonstrated that both mechanical signaling and soluble growth factor signaling facilitate this process. One possible point of integration for mechanical and growth factor signaling is the extracellular matrix. Here we investigate the role of the extracellular matrix (ECM) protein fibronectin (FN) in this process. We demonstrate that inhibition of FN fibrillogenesis blocks activation of the Transforming Growth Factor-Beta (TGF-β) signaling pathway via Smad2 signaling, decreases cell migration and ultimately leads to inhibition of EMT. Results show that soluble FN, FN fibrils, or increased contractile forces are insufficient to independently induce EMT. We further demonstrate that inhibition of latent TGF-β1 binding to FN fibrils via either a monoclonal blocking antibody against the growth factor binding domain of FN or through use of a FN deletion mutant that lacks the growth factor binding domains of FN blocks EMT progression, indicating a novel role for FN in EMT in which the assembly of FN fibrils serves to localize TGF-β1 signaling to drive EMT.

Abstract

The rapid growth in opioid therapy for non-cancer pain has occurred without an adequate appreciation of the consequences of this growth. Few studies provide patient-centered evidence that can be used to inform the current proposed standards for efficacious (safe and effective) opioid prescribing in non-cancer pain. Furthermore, different terms may be used interchangeably in the literature to refer to opioid-taking behaviors, resulting in imprecise or vague interpretation of existing evidence. We therefore sought to explore patterns of opioid-taking behavior and their biopsychosocial-spiritual determinants in African-American adults with sickle cell disease (SCD). METHODS: We conducted a multi-phase mixed methods study which included quantitative and semi-structured qualitative interviews. A grounded theory approach was used to analyze the data. RESULTS: The final sample consisted of 11 men and 10 women, average age 36 years. Qualitative thematic analysis uncovered several patterns of opioid-taking behavior and several related biopsychosocial-spiritual phenomena, some hypothesized and some not. These patterns and phenomena portrayed a new six-domain conceptual framework that addresses the complex individual, relational, environmental, cultural, and system issues surrounding opioid taking-behavior in SCD, and provides a roadmap for future research: 1) Pain and its consequences; 2) Prescribed opioidtaking behaviors and their biopsychosocial consequences; 3) Effects of biopsychosocial determinants on opioid-taking behaviors; 4) Aberrant behavior; 5) Physician prescribing behaviors and attitudes; and 6) Hypothetical targets for interventions to improve prescribing and opioid taking-behaviors. Further, the data portrayed explanatory factors that could be classified into various levels or domains based on models proposed in prior research. Factors included withinpatient (biological, spiritual, psychological), and social and environmental (social support, provider relationships, institutional norms, culture, legal and governmental policy) domains. CONCLUSIONS: The explored domains offer rich guidance toward understanding multi-level explanatory effect of pain, its pharmacotherapy, and medication taking behaviors on SCD individual's health that simultaneously bridges all health care domains.

, under review). Recent studies have conclusively indicated the results can potentially provide very useful avenues both for theoretical and experimental setting to understand fundamental molecular bond breaking process by implementing single molecule force and torque spectroscopy to complement the theoretical predictions here. In this work we will present our most recent results on Binol system as its unique structure has been found to be an excellent molecule for the proof of concepts here. Besides results from several semi-quantum techniques, we will outline proposed experimentations and also further ab initio based results on the system and also proposed logical extension to large biomacromolecular cases.

The rapid growth in opioid therapy for non-cancer pain has occurred without an adequate appreciation of the consequences of this growth. Few studies provide patient-centered evidence that can be used to inform the current proposed standards for efficacious (safe and effective) opioid prescribing in non-cancer pain. Furthermore, different terms may be used interchangeably in the literature to refer to opioid-taking behaviors, resulting in imprecise or vague interpretation of existing evidence. We therefore sought to explore patterns of opioid-taking behavior and their biopsychosocial-spiritual determinants in African-American adults with sickle cell disease (SCD). METHODS: We conducted a multi-phase mixed methods study which included quantitative and semi-structured qualitative interviews. A grounded theory approach was used to analyze the data. RESULTS: The final sample consisted of 11 men and 10 women, average age 36 years. Qualitative thematic analysis uncovered several patterns of opioid-taking behavior and several related biopsychosocial-spiritual phenomena, some hypothesized and some not. These patterns and phenomena portrayed a new six-domain conceptual framework that addresses the complex individual, relational, environmental, cultural, and system issues surrounding opioid taking-behavior in SCD, and provides a roadmap for future research: 1) Pain and its consequences; 2) Prescribed opioidtaking behaviors and their biopsychosocial consequences; 3) Effects of biopsychosocial determinants on opioid-taking behaviors; 4) Aberrant behavior; 5) Physician prescribing behaviors and attitudes; and 6) Hypothetical targets for interventions to improve prescribing and opioid taking-behaviors. Further, the data portrayed explanatory factors that could be classified into various levels or domains based on models proposed in prior research. Factors included withinpatient (biological, spiritual, psychological), and social and environmental (social support, provider relationships, institutional norms, culture, legal and governmental policy) domains. CONCLUSIONS: The explored domains offer rich guidance toward understanding multi-level explanatory effect of pain, its pharmacotherapy, and medication taking behaviors on SCD individual's health that simultaneously bridges all health care domains.