Coordinate expression of secretory phospholipase A(2) and cyclooxygenase-2 in activated human keratinocytes

PGE₂ levels are altered in human epidermisafter in vivo wounding; however, mechanisms modulatingPGE₂ production in activated keratinocytes are unclear. Inprevious studies, we showed that PGE₂ is a growth-promotingautacoid in human primary keratinocyte cultures, and its production ismodulated by plating density, suggesting that regulatedPGE₂ synthesis is an important component of wound healing.Here, we examine the role of phospholipase A₂ (PLA₂) and cyclooxygenase (COX) enzymes in modulation ofPGE₂ production. We report that the increasedPGE₂ production that occurs in keratinocytes grown innonconfluent conditions is also observed after in vitro wounding,indicating that similar mechanisms are involved. This increase wasassociated with coordinate upregulation of both COX-2 and secretoryPLA₂ (sPLA₂) proteins. IncreasedsPLA₂ activity was also observed. By RT-PCR, we identifiedthe presence of type IIA and type V sPLA₂, along with theM-type sPLA₂ receptor. Thus the coordinate expression ofsPLA₂ and COX-2 may be responsible for the increasedprostaglandin synthesis in activated keratinocytes during wound repair.

     

Network Diversity and Affect Dynamics: The Role of Personality Traits

People divide their time unequally among their social contacts due to time constraints and varying strength of relationships. It was found that high diversity of social communication, dividing time more evenly among social contacts, is correlated with economic well-being both at macro and micro levels. Besides economic well-being, it is not clear how the diversity of social communication is also associated with the two components of individuals’ subjective well-being, positive and negative affect. Specifically, positive affect and negative affect are two independent dimensions representing the experience (feeling) of emotions. In this paper, we investigate the relationship between the daily diversity of social communication and dynamic affect states that people experience in their daily lives. We collected two high-resolution datasets that capture affect scores via daily experience sampling surveys and social interaction through wearable sensing technologies: sociometric badges for face-to-face interaction and smart phones for mobile phone calls. We found that communication diversity correlates with desirable affect states–e.g. an increase in the positive affect state or a decrease in the negative affect state–for some personality types, but correlates with undesirable affect states for others. For example, diversity in phone calls is experienced as good by introverts, but bad by extroverts; diversity in face-to-face interaction is experienced as good by people who tend to be positive by nature (trait) but bad for people who tend to be not positive by nature. More broadly, the moderating effect of personality type on the relationship between diversity and affect was detected without any knowledge of the type of social tie or the content of communication. This provides further support for the power of unobtrusive sensing in understanding social dynamics, and in measuring the effect of potential interventions designed to improve well-being.     

Trace elements in cerebrospinal fluid in motor neurone disease.

Concentrations of sodium, chlorine, potassium, chromium, iron, cobalt, zinc, rubidium, silver, caesium, and selenium in cerebrospinal fluid from 14 control subjects and 20 patients with motor neurone disease were measured by in vitro neutron activation analysis. No statistically significant correlation was found between the concentrations of any two elements other than sodium and chlorine in either the patient or control group (r = 0.9905; p less than 0.001). The mean cobalt concentration was significantly lower in the patients (p = 0.0015). No other statistically significant difference was shown. The relevance of this finding was examined in relation to current concepts of the pathogenesis of motor neurone disease and the role of cobalt in cellular metabolism.     

Modulation of proliferation in epidermal keratinocyte cultures by lowered oxygen tension

The modulation of proliferation and differentiation in primary epidermal keratinocyte cultures by lowered gas phase oxygen tensions was studied. Neonatal mouse epidermal keratinocyte cultures were grown in an Heraeus type B 5060 EK/O2 incubator in oxygen tensions between 5% and 15% (within the physiologic range); the oxygen tension of ambient air being 21%. Cell morphology was studied using histochemical stains and electron microscopy. Differentiation was assessed using autoradiography of SDS PAGE gels of six serially extracted cell protein fractions with [3H]leucine as a marker. Autoradiographs using [14C]glucosamine and 32Pi as markers were also assessed as a measure of other cell functions. Proliferation was studied using autoradiography of [3H]thymidine ([3H]TdR) pulse-labeled cultures and [3H]TdR incorporation into isolated DNA fractions. The results of these studies showed that lowering the oxygen tension in the gas phase reversibly inhibited cell proliferation. There was a direct arithmetic relationship between the proliferative rate of the cultures and the oxygen tension. No change in differentiation as defined by [3H]leucine indexing of protein synthesis was seen. Other markers of cell function, such as [14C]glucosamine glycosylation and [32P] phosphorylation of proteins were also unchanged. These results suggest that oxygen tension regulates only proliferation in epidermal keratinocytes. This epidermal response is well adapted to its role in the healing wound, and is an example of a tissue-specific modification of a regulatory function.     

Effects of PGF2alpha on human melanocytes and regulation of the FP receptor by ultraviolet radiation

Prostaglandins are potent lipid hormones that activate multiple signaling pathways resulting in regulation of cellular growth, differentiation, and apoptosis. In the skin, prostaglandins are rapidly released by keratinocytes following ultraviolet radiation and are chronically present in inflammatory skin lesions. We have shown previously that melanocytes, which provide photoprotection to keratinocytes through the production of melanin, express several receptors for prostaglandins, including the PGE2 receptors EP1 and EP3 and the PGF2alpha receptor FP, and that PGF2alpha stimulates melanocyte dendricity. We now show that PGF2alpha stimulates the activity and expression of tyrosinase, the rate-limiting enzyme in melanin synthesis. Analysis of FP receptor regulation showed that the FP receptor is regulated by ultraviolet radiation in melanocytes in vitro and in human skin in vivo. We also show that ultraviolet irradiation stimulates production of PGF2alpha by melanocytes. These results show that PGF2alpha binding to the FP receptor activates signals that stimulate a differentiated phenotype (dendricity and pigmentation) in melanocytes. The regulation of the FP receptor and the stimulation of production of PGF2alpha in melanocytes in response to ultraviolet radiation suggest that PGF2alpha could act as an autocrine factor for melanocyte differentiation.     

Change in BMI Accurately Predicted by Social Exposure to Acquaintances

Research has mostly focused on obesity and not on processes of BMI change more generally, although these may be key factors that lead to obesity. Studies have suggested that obesity is affected by social ties. However these studies used survey based data collection techniques that may be biased toward select only close friends and relatives. In this study, mobile phone sensing techniques were used to routinely capture social interaction data in an undergraduate dorm. By automating the capture of social interaction data, the limitations of self-reported social exposure data are avoided. This study attempts to understand and develop a model that best describes the change in BMI using social interaction data.We evaluated a cohort of 42 college students in a co-located university dorm, automatically captured via mobile phones and survey based health-related information. We determined the most predictive variables for change in BMI using the least absolute shrinkage and selection operator (LASSO) method. The selected variables, with gender, healthy diet category, and ability to manage stress, were used to build multiple linear regression models that estimate the effect of exposure and individual factors on change in BMI. We identified the best model using Akaike Information Criterion (AIC) and R².This study found a model that explains 68% (p<0.0001) of the variation in change in BMI. The model combined social interaction data, especially from acquaintances, and personal health-related information to explain change in BMI.This is the first study taking into account both interactions with different levels of social interaction and personal health-related information. Social interactions with acquaintances accounted for more than half the variation in change in BMI. This suggests the importance of not only individual health information but also the significance of social interactions with people we are exposed to, even people we may not consider as close friends.