Epidermal growth factor induction of front-rear polarity and migration in keratinocytes is mediated by integrin-linked kinase and ELMO2

Epidermal growth factor (EGF) is a potent chemotactic and mitogenic factor for epidermal keratinocytes, and these properties are central for normal epidermal regeneration after injury. The involvement of mitogen-activated protein kinases as mediators of the proliferative effects of EGF is well established. However, the molecular mechanisms that mediate motogenic responses to this growth factor are not clearly understood. An obligatory step for forward cell migration is the development of front-rear polarity and formation of lamellipodia at the leading edge. We show that stimulation of epidermal keratinocytes with EGF, but not with other growth factors, induces development of front-rear polarity and directional migration through a pathway that requires integrin-linked kinase (ILK), Engulfment and Cell Motility-2 (ELMO2), integrin β1, and Rac1. Furthermore, EGF induction of front-rear polarity and chemotaxis require the tyrosine kinase activity of the EGF receptor and are mediated by complexes containing active RhoG, ELMO2, and ILK. Our findings reveal a novel link between EGF receptor stimulation, ILK-containing complexes, and activation of small Rho GTPases necessary for acquisition of front-rear polarity and forward movement. © 2012 Ho and Dagnino

Emerging role of ILK and ELMO2 in the integration of adhesion and migration pathways

Integrins and their associated proteins are essential components of the cellular machinery that modulates adhesion and migration. In particular, integrinlinked kinase (ILK), which binds to the cytoplasmic tail of β1 integrins, is required for migration in a variety of cell types. We previously identified engulfment and motility 2 (ELMO2) as an ILK-binding protein in epidermal keratinocytes. Recently, we investigated the biological role of the ILK/ELMO2 complexes, and found that they exist in the cytoplasm. ILK/ELMO2 species are recruited by active RhoG to the plasma membrane, where they induce Rac1 activation and formation of lamellipodia at the leading edge of migrating cells. A large number of growth factors and cytokines induce keratinocyte migration. However, we found that formation of RhoG/ELMO2/ILK complexes occurs selectively upon stimulation by epidermal growth factor, but not by transforming growth factor-β1 or keratinocyte growth factor. Herein we discuss the relevance of these complexes to our understanding of the molecular mechanisms involved in cell migration, as well as their potential functions in morphogenesis and tissue regeneration following injury. © 2012 Landes Bioscience

Correlations between anthropometric measurements, biochemical indicators, dietary intake and Dialysis Malnutrition Score among haemodialysis patients in Sibu, Sarawak

Introduction: Malnutrition is a common problem associated with increased risk of morbidity and mortality among haemodialysis (HD) patients. Methods: This study determined the correlation between anthropometric measurements, biochemical indicators, dietary intake and dialysis malnutrition score among HD patients in Sibu, Sarawak. A total of 55 patients were recruited by purposive sampling and their biochemical parameters were retrieved from dialysis records. Anthropometric measurements and dietary intake were determined using standardised protocols while Dialysis Malnutrition Score (DMS) was computed to determine patients’ nutritional status. Results: Mean age of the patients was 53.0±12.2 years. Mean DMS was low, indicating low tendency of malnutrition among the patients. Approximately one-third of the patients had high interdialytic weight gain (IDWG), indicating a poor adherence on fluid recommendation. Mean intakes of dietary energy (DEI) and protein (DPI) were low, with only approximately 15% achieving the recommendations according to Kidney Disease Outcomes Quality Initiative (K/ DOQI). Increase in age (r=0.337, p=0.012) and dialysis vintage (r=0.403, p=0.002) were associated with poorer nutritional status while higher BMI, MUAC, and serum albumin were associated with better nutritional status. Conclusion: This study revealed a high proportion of the HD patients with poor adherence on fluid intake, and the prevalence of inadequate DEI and DPI, indicating the importance of regular dietary counselling for HD patients. In view of their non-invasive nature and close relationship with nutritional status, body mass index, mid-upper arm circumference, and serum albumin should be included as part of the comprehensive periodic nutrition assessment of HD patients

Integrin-linked kinase and ELMO2 modulate recycling endosomes in keratinocytes

The formation of tight cell-cell junctions is essential in the epidermis for its barrier properties. In this tissue, keratinocytes follow a differentiation program tightly associated with their movement from the innermost basal to the outer suprabasal layers, and with changes in their cell-cell adhesion profile. Intercellular adhesion in keratinocytes is mediated through cell-cell contacts, including E-cadherin-based adherens junctions. Although the mechanisms that mediate E-cadherin delivery to the plasma membrane have been widely studied in simple epithelia, this process is less well understood in the stratified epidermis. In this study, we have investigated the role of Engulfment and Cell Motility 2 (ELMO2) and integrin-linked kinase (ILK) in the positioning of E-cadherin-containing recycling endosomes during establishment of cell-cell contacts in differentiating keratinocytes. We now show that induction of keratinocyte differentiation by Ca2 + is accompanied by localization of ELMO2 and ILK to Rab4- and Rab11a-containing recycling endosomes. The positioning of long-loop Rab11a-positive endosomes at areas adjacent to cell-cell contacts is disrupted in ELMO2- or ILK-deficient keratinocytes, and is associated with impaired localization of E-cadherin to cell borders. Our studies show a previously unrecognized role for ELMO2 and ILK in modulation of endosomal positioning, which may play key roles in epidermal sheet maintenance and permeability barrier function

Epithelial Migration and Non-adhesive Periderm Are Required for Digit Separation during Mammalian Development.

The fusion of digits or toes, syndactyly, can be part of complex syndromes, including van der Woude syndrome. A subset of van der Woude cases is caused by dominant-negative mutations in the epithelial transcription factor Grainyhead like-3 (GRHL3), and Grhl3-/-mice have soft-tissue syndactyly. Although impaired interdigital cell death of mesenchymal cells causes syndactyly in multiple genetic mutants, Grhl3-/- embryos had normal interdigital cell death, suggesting alternative mechanisms for syndactyly. We found that in digit separation, the overlying epidermis forms a migrating interdigital epithelial tongue (IET) when the epithelium invaginates to separate the digits. Normally, the non-adhesive surface periderm allows the IET to bifurcate as the digits separate. In contrast, in Grhl3-/- embryos, the IET moves normally between the digits but fails to bifurcate because of abnormal adhesion of the periderm. Our study identifies epidermal developmental processes required for digit separation

Personality, Social Support, and Quality Of Life as Determinants of Coping Behaviour amoung Visually Impaired Individuals

This study examined personality, social support, and quality of life as determinant of coping behaviour among the visually impaired individuals. Fifty (50) visually impaired individuals drawn from Benin City participated in the study. Four hypotheses were stated and tested using independent t. test and regression analysis. The results confirmed three out of the four hypotheses stated. High social support was found to significantly determine high coping behaviour (t = 3.261, df 48, P < 0.05), high quality of life significantly determine high coping behaviour (t = 5.136, df 48, P < 0.05), and that personality, social support, and quality of life jointly predict coping behaviour among visually impaired individuals (R =0.647, R2 = 42%, F(34.626) =; P < 0.001). Based on the findings of this study, it is recommended that parents/guardians, teachers/counselors of visually impaired individuals should not relent in supporting them. Also relevant authorities should facilitate programmes that will enhance quality of life of individuals with visual impairment to enable them cope better

Serum potassium and handgrip strength as predictors of sleep qualtiy among hemodialysis patients in Malaysia

Background and Objectives:Poor sleep quality is prevalent among hemodialysis (HD) patients and leads to adverse health outcomes. This study investigated the association of nutritional parameters with sleep quality among Malaysian HD patients. Methods and Study Design:A cross-sectional study was conducted among 184 Malaysian HD patients. Anthropometric measurements and handgrip strength (HGS) were obtained using standardized protocols. Relevant biochemical indicators were retrieved from patients’ medical records. Nutritional status was assessed using the dialysis malnutrition score. The sleep quality of patients was determined using the Pittsburgh Sleep Quality Index questionnaire on both dialysis and non-dialysis days. Results: Slightly more than half of the HD patients were poor sleepers, with approximately two-third of them having a sleep duration of <7 hours per day. Sleep latency (1.5±1.2) had the highest sleep component score, whereas sleep medicine use (0.1±0.6) had the lowest score. Significantly longer sleep latency and shorter sleep duration were observed in the poor sleepers, regardless of whether it was a dialysis day or not (p<0.001). Poor sleep quality was associated with male sex, old age, small triceps skinfold, hypoproteinemia, hyperkalemia, hyperphosphatemia, and poorer nutritional status. In a multivariate analysis model, serum potassium (β=1.41,p=0.010), male sex (β=2.15, p=0.003), and HGS (β=−0.088, p=0.021) were found as independent predictors of sleep quality.Conclusions: Poor sleep quality was evident among the HD patients in Malaysia. The sleep quality of the HD patients was associated with nutritional parameters. Routine assessment of sleep quality and nutritional parameters indicated that poor sleepers have a risk of malnutrition and may benefit from appropriate interventions

Theoretical and Experimental Studies of Schottky Diodes That Use Aligned Arrays of Single Walled Carbon Nanotubes

We present theoretical and experimental studies of Schottky diodes that use aligned arrays of single walled carbon nanotubes. A simple physical model, taking into account the basic physics of current rectification, can adequately describe the single-tube and array devices. We show that for as grown array diodes, the rectification ratio, defined by the maximum-to-minimum-current-ratio, is low due to the presence of m-SWNT shunts. These tubes can be eliminated in a single voltage sweep resulting in a high rectification array device. Further analysis also shows that the channel resistance, and not the intrinsic nanotube diode properties, limits the rectification in devices with channel length up to ten micrometer.Comment: Nano Research, 2010, accepte