The Hippo signaling pathway is required for salivary gland development and its dysregulation is associated with Sjogren's-like disease

Sjogren's syndrome (SS) is a complex autoimmune disease that primarily affects salivary and lacrimal glands and is associated with high morbidity. Although the prevailing dogma is that immune system pathology drives SS, increasing evidence points to structural defects, including defective E-cadherin adhesion, to be involved in its etiology. We have shown that E-cadherin plays pivotal roles in the development of the mouse salivary submandibular gland (SMG) by organizing apical-basal polarity in acinar and ductal progenitors and by signaling survival for differentiating duct cells. Recently, E-cadherin junctions have been shown to interact with effectors of the Hippo signaling pathway, a core pathway regulating organ size, cell proliferation and differentiation. We now show that Hippo signaling is required for SMG branching morphogenesis and is involved in the pathophysiology of SS. During SMG development, a Hippo pathway effector, TAZ, becomes increasingly phosphorylated and associated with E-cadherin and α-catenin, consistent with the activation of Hippo signaling. Inhibition of Lats2, an upstream kinase that promotes TAZ phosphorylation, results in dysmorphogenesis of the SMG and impaired duct formation. SMGs from NOD mice, a mouse model for SS, phenocopy the Lats2-inhibited SMGs and exhibit a reduction in E-cadherin junctional components, including TAZ. Importantly, labial specimens from human SS patients display mislocalization of TAZ from junctional regions to the nucleus, coincident with accumulation of extracellular matrix components, fibronectin and CTGF, known downstream targets of TAZ. Our studies show that Hippo signaling plays a crucial role in SMG branching morphogenesis and provide evidence that defects in this pathway are associated with SS in humans

Angiotensin-(1-7) activates a tyrosine phosphatase and inhibits glucose-induced signalling in proximal tubular cells

<b>Background.</b> In the diabetic kidney, stimulation of mitogen-activated protein kinases (MAPKs) leads to extracellular matrix protein synthesis. In the proximal tubule, angiotensin-(1–7) [Ang-(1–7)] blocks activation of MAPKs by angiotensin II. We studied the effect of Ang-(1–7) on signalling responses in LLC-PK1 cells in normal (5 mM) or high (25 mM) glucose.<p></p> <b>Methods.</b> The p38 MAPK was assayed by immunoblot, Src homology 2-containing protein-tyrosine phosphatase-1 (SHP-1) activity was measured after immunoprecipitation, cell protein synthesis was determined by [3H]-leucine incorporation and transforming growth factor-β1 (TGF-β1), fibronectin and collagen IV were assayed by immunoblots and/or ELISA.<p></p> <b>Results.</b> High glucose stimulated p38 MAPK. This response was inhibited by Ang-(1–7) in a concentration-dependent fashion, an effect reversed by the receptor Mas antagonist A-779. Ang-(1–7) increased SHP-1 activity, via the receptor Mas. An inhibitor of tyrosine phosphatase, phenylarsine oxide, reversed the inhibitory effect of Ang-(1–7) on high glucose-stimulated p38 MAPK. Ang-(1–7) inhibited high glucose-stimulated protein synthesis, and blocked the stimulatory effect of glucose on TGF-β1. Conversely, Ang-(1–7) had no effect on glucose-stimulated synthesis of fibronectin or collagen IV.<p></p> <b>Conclusions.</b> These data indicate that in proximal tubular cells, binding of Ang-(1–7) to the receptor Mas stimulates SHP-1, associated with the inhibition of glucose-stimulated p38 MAPK. Ang-(1–7) selectively inhibits glucose-stimulated protein synthesis and TGF-β1. In diabetic nephropathy, Ang-(1–7) may partly counteract the profibrotic effects of high glucose

Laser abrading of carbon fibre reinforced composite for improving paint adhesion

Surface contaminations (originating from manufacturing processes), smooth surface, and poor wettability of carbon fiber reinforced polymer (CFRP) composite impair its successful paint adhesion. Surface pretreatment of composite materials is often required. Previous approaches of using manual sand-papering result in non-uniform surface conditions and occasional damages to the fibres. Furthermore, the process is labour intensive, slow and can be hazardous to the workers if protections are not appropriate. This paper reports an investigation into a new surface treatment method based on laser multi-tasking surface abrading and surface cleaning/texturing for the improvement of paint adhesion. A KrF Excimer laser with a wavelength of 248 nm is used as the laser source. Significant improvement in paint adhesion has been demonstrated compared with as-received and sand-papered samples. This improvement is achieved by eliminating surface contaminants, minimizing chain scission and increasing in surface active functional groups as well as increasing in surface roughness. The former two play dominant roles

Control: A perspective

Feedback is an ancient idea, but feedback control is a young field. Nature long ago discovered feedback since it is essential for homeostasis and life. It was the key for harnessing power in the industrial revolution and is today found everywhere around us. Its development as a field involved contributions from engineers, mathematicians, economists and physicists. It is the first systems discipline; it represented a paradigm shift because it cut across the traditional engineering disciplines of aeronautical, chemical, civil, electrical and mechanical engineering, as well as economics and operations research. The scope of control makes it the quintessential multidisciplinary field. Its complex story of evolution is fascinating, and a perspective on its growth is presented in this paper. The interplay of industry, applications, technology, theory and research is discussed