Effects of commuting and mode of transportation on performance, affect, cardiovascular activity, and frustration tolerance

It was hypothesized that making a commute elevates blood pressure, causes negative affect, reduces frustration tolerance, and impairs performance on simple and complex cognitive tasks. This hypothesis was tested by varying choice and type of commute in an experiment in which 168 volunteers were randomly assigned to one of six experimental conditions. The behavior of subjects who drove 30 miles or rode on a bus for the same distance were compared with the reactions of students who did not commute. Multivariate analyses of variance indicated that subjects who made the commute showed lower frustration tolerance and deficits on complex cognitive task performance. Commuting also raised pulse and systolic blood pressure. Multivariate analyses of covariance (MANCOVA) were performed in an effort to identify physiological and emotional reactions that may mediate these relations. No mediational relationships were uncovered. ^

Flanerie: A post -reflexive mode of urban research inquiry

Urban ethnographic studies in social science usually proceed from within a pre-figured research framework that guides field activity and filters what is considered see-worthy and study-worthy to those phenomena which are in some way necessary for the fulfillment of specific research agendas. Reliance on formalized ethnographic research methods to explore the city, and the reflex to intellectualize that which is observed by using them, frequently leads to the neglect of much of what comprises the ethnographic richness of city-life through an overly-contemplative intellectuocentrism. ^ Flânerie, an avocational, proto-sociological ethnographic mode of urban exploration and observation originating in early-nineteenth-century Paris, is representative of an alternate approach to exploration and study of the city—one less subject to a compressed horizon of ethnographic experience. It affords insight into a broad range of phenomena taking place in interstitial urban space and time which often escape the instrumentally overly-determined gaze of professionalist research inquiry. ^ The present work addressed the fact that the concept of flânerie , though occasionally invoked in discussions of methodology in urban sociology and cultural studies, had not been subjected to a systematic attempt to relate it to the research methods of these disciplines. Though as a typological figure the flâneur is thought to have disappeared long ago, practices represented by the concept continue to be engaged in by persons inside and outside of academia who approach city life and social science with a perspective somewhat transcending the reified dichotomies of private-professional and art-and-science. This study transferred aspects of the experience of the city embodied in the flâneur to the realm of ethnographic urban studies and the building of grounded social theory, finding flânerie to be crucial to the development of a refined knowledge of urban life, and an important means by which previously overlooked social phenomena and silenced avenues of research inquiry might be exposed. ^ The conclusions reached found a “flâneuristic” approach to the city as being beneficial to research practice and the vitalization of urban ethnographic inquiry, by affording opportunities for exposure to, and immersion within, an expanded range of quotidian social phenomena that have frequently escaped the academicist gaze. ^

Novel insights into the mechanisms of regulation of tyrosine kinase receptors by Ras Interference 1

Receptor-tyrosine kinases (RTKs) are membrane bound receptors characterized by their intrinsic kinase activity. RTK activities play an essential role in several human diseases, including cancer, diabetes and neurodegenerative diseases. RTK activities have been regulated by the expression or silencing of several genes as well as by the utilization of small molecules. Ras Interference 1 (Rin1) is a multifunctional protein that becomes associated with activated RTKs upon ligand stimulation. Rin1 plays a key role in receptor internalization and in signal transduction via activation of Rab5 and association with active form of Ras. This study has two main objectives: (1) It determines the role of Rin1 in the regulation of several RTKs focusing on insulin receptor. This was accomplished by studying the Rin1-insulin receptor interaction using a variety of biochemical and morphological assays. This study shows a novel interaction between the insulin receptor and Rin1 through the Vps9 domain. Two more RTKs (epidermal growth factor receptor and nerve growth factor receptor) also interacted with the SH2 domain of Rin1. The effect of the Rin1-RTK interaction on the activation of both Rab5 and Ras was also studied during receptor internalization and intracellular signaling. Finally, the role of Rin1 was examined in two differentiation processes (adipogenesis and neurogenesis). Rin1 showed a strong inhibitory effect on 3T3-L1 preadipocyte differentiation but it seems to show a modest effect in PC12 neurite outgrowth. These data indicate a selective function and specific interaction of Rin1 toward RTKs. (2) It examines the role of the small molecule Dehydroleucodine (DhL) on several key signaling molecules during adipogenesis. This was accomplished by studying the differentiation of 3T3-L1 preadipocytes exposed to different concentrations of DhL in different days of the adipocyte formation process. The results indicate that DhL selectively blocked adipocyte formation, as well as the expression of PPARγ, and C/EBP&agr;. However, DhL treatment did not affect Rin1 or Rab5 expression and their activities. Taken together, the data indicate a potential molecular mechanism by which proteins or small molecules regulate selective and specific RTK intracellular membrane trafficking and signaling during cell growth and differentiation in normal and pathological conditions.

4-hydroxy estradiol-induced oxidant-mediated signaling is involved in the development of breast cancer

Breast cancer is a disease associated with excess exposures to estrogens. While the mode of cancer causation is unknown, others have shown that oxidative stress induced by prolonged exposure to estrogens mediates renal, liver, endometrial and mammary tumorigenesis though the mechanism(s) underling this process is unknown. In this study, we show that 4-hydroxyl 17β-estradiol (4-OHE2), a catechol metabolite of estrogen, induces mammary tumorigenesis in a redox dependent manner. We found that the mechanism of tumorigenesis involves redox activations of nuclear respiratory factor-1 (NRF1); a transcriptions factor associated with regulation of mitochondria biogenesis and oxidative phosphorylation (OXPHOS), as well as mediation of cell survival and growth of cells during periods of oxidative stress. Key findings from our study are as follows: (i) Prolonged treatments of normal mammary epithelial cells with 4-OHE2, increased the formation of intracellular reactive oxygen species (ROS). (ii) Estrogen-induced ROS activates redox sensitive transcription factors NRF1. (iii) 4-OHE2 through activation of serine-threonine kinase and histone acetyl transferase, phosphorylates and acetylate NRF1 respectively. (iv) Redox mediated epigenetic modifications of NRF1 facilitates mammary tumorigenesis and invasive phenotypes of breast cancer cells via modulations of genes involved in proliferation, growth and metastasis of exposed cells. (v) Animal engraftment of transformed clones formed invasive tumors. (vi) Treatment of cells or tumors with biological or chemical antioxidants, as well as silencing of NRF1 expressions, prevented 4-OHE2 induced mammary tumorigenesis and invasive phenotypes of MCF-10A cells. Based on these observations, we hypothesize that 4-OHE2 induced ROS epigenetically activate NRF1 through its phosphorylation and acylation. This, in turn, through NRF1-mediated transcriptional activation of the cell cycle genes, controls 4-OHE2 induced cell transformation and tumorigenesis.^