During healing of the skin, the cytoskeleton of keratinocytes and their matrix adhesions, including focal adhesions (FAs), undergo reorganization. These changes are coordinated by small GTPases and their regulators, including the guanine nucleotide exchange factor β-PIX (also known as ARHGEF7). In fibroblasts, β-PIX activates small GTPases, thereby enhancing migration. In keratinocytes in vitro, β-PIX localizes to FAs. To study β-PIX functions, we generated β-PIX knockdown keratinocytes. During wound closure of β-PIX knockdown cell monolayers, disassembly of FAs is impaired, and their number and size are increased. In addition, in the β-PIX knockdown cells, phosphorylated myosin light chain (MLC; also known as MYL2) is present not only in the leading edge of cells at the wound front, but also in the cells following the front, while p21-activated kinase 2 (PAK2), a regulator of MLC kinase (MYLK), is mislocalized. Inhibition or depletion of MYLK restores FA distribution in β-PIX knockdown cells. Traction forces generated by β-PIX knockdown cells are increased relative to those in control cells, a result consistent with an unexpected enhancement in the migration of single β-PIX knockdown cells and monolayers of such cells. We propose that targeting β-PIX might be a means of promoting epithelialization of wounds in vivo.
Branching morphogenesis of epithelia involves division of cells into leader (tip) and follower (stalk) cells. Published work on cell lines in culture has suggested that symmetry‐breaking takes place via a secreted autocrine inhibitor of motility, the inhibitor accumulating more in concave regions of the culture boundary, slowing advance of cells there, and less in convex areas, allowing advance and a further exaggeration of the concave/convex difference. Here we test this hypothesis using a two‐dimensional culture system that includes strong flow conditions to remove accumulating diffusible secretions. We find that, while motility does indeed follow boundary curvature in this system, flow makes no difference: this challenges the hypothesis of control by a diffusible secreted autocrine inhibitor.
BackgroundObstructive Sleep Apnea (OSA) is prevalent throughout the world. However, there are currently limited data concerning the prevalence of OSA in populations that originate from developing countries; the prevalence of OSA is expected to rise in these countries. OSA is poorly characterized amongst Ethiopians, and our study is the first to describe clinical characteristics of OSA among Ethiopians.MethodsWe conducted a retrospective study of primarily Ethiopian patients at an internal medicine clinic in Rockville, Maryland. All patients (n=24) were evaluated for daytime sleepiness using the Epworth Sleepiness Scale (ESS) and received physical examinations and polysomnograms (PSG) by either portable monitoring (Itamar WatchPAT 200 device) or in-lab. Statistical analyses were performed in R.ResultsLinear regression model of Body-Mass Index (BMI) and Apnea-Hypopnea Index (AHI) indicated that for every 1-unit increase in BMI, there was a 0.8657-unit increase in AHI (p<0.05). Pearson's correlation coefficient indicateda positive linear relationship between BMI and AHI (0.47) (p<0.05). Adjusted linear regression model for AHI and oxygen saturation indicated that for every 1-unit increase of AHI, there was a 0.8452-unit decrease in nocturnal oxygen saturation (p<0.05). Pearson's correlation coefficient did not demonstrate significance between AHI and oxygen desaturation (p=0.062). Patients received either continuous positive airway pressure (CPAP) (n=15) or oral appliance therapy (n=3).ConclusionAll patients who complied with therapy reported improved sleep quality, snoring resolution, and improved daytime alertness. Practitioners in developing countries should suspect OSA in the right clinical setting and offer diagnostic and therapeutic services when available.
A 69-year-old Caucasian woman presented with chronic lymphocytic leukaemia (CLL; stage 1-Rai System), significant oropharyngeal lymphoid enlargement, snoring and fatigue. Overnight polysomnography revealed moderately severe obstructive sleep apnoea (OSA), which was managed successfully with oral appliance therapy with resolution of snoring and daytime fatigue. Structural abnormalities of the upper airways are known to cause OSA. Airway narrowing can result from bony structural abnormalities, nasopharyngeal growth, soft tissue redundancy, macroglossia, malignant and benign growth of the upper aero-digestive tract, and adenotonsilar enlargement. Clinicians should be encouraged to consider a diagnosis of OSA in patients with CLL when they present with symptoms of worsening fatigue.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.