Thrombin-mediated Proteoglycan Synthesis Utilizes Both Protein-tyrosine Kinase and Serine/Threonine Kinase Receptor Transactivation in Vascular Smooth Muscle Cells

G protein-coupled receptor signaling is mediated by three main mechanisms of action; these are the classical pathway, β-arrestin scaffold signaling, and the transactivation of protein-tyrosine kinase receptors such as those for EGF and PDGF. Recently, it has been demonstrated that G protein-coupled receptors can also mediate signals via transactivation of serine/threonine kinase receptors, most notably the transforming growth factor-β receptor family. Atherosclerosis is characterized by the development of lipid-laden plaques in blood vessel walls. Initiation of plaque development occurs via low density lipoprotein retention in the neointima of vessels due to binding with modified proteoglycans secreted by vascular smooth muscle cells. Here we show that transactivation of protein-tyrosine kinase receptors is mediated by matrix metalloproteinase triple membrane bypass signaling. In contrast, serine/threonine kinase receptor transactivation is mediated by a cytoskeletal rearrangement-Rho kinase-integrin system, and both protein-tyrosine kinase and serine/threonine kinase receptor transactivation concomitantly account for the total proteoglycan synthesis stimulated by thrombin in vascular smooth muscle. This work provides evidence of thrombin-mediated proteoglycan synthesis and paves the way for a potential therapeutic target for plaque development and atherosclerosis.     

Alkaline Water Electrolysis at 25 A cm−2 with a Microfibrous Flow‐through Electrode

The generation of renewable electricity is variable, leading to periodic oversupply. Excess power can be converted to H₂ via water electrolysis, but the conversion cost is currently too high. One way to decrease the cost of electrolysis is to increase the maximum productivity of electrolyzers. This study investigates how nano‐ and microstructured porous electrodes can improve the productivity of H₂ generation in a zero‐gap, flow‐through alkaline water electrolyzer. Three nickel electrodes—foam, microfiber felt, and nanowire felt—are studied to examine the tradeoff between surface area and pore structure on the performance of alkaline electrolyzers. Although the nanowire felt with the highest surface area initially provides the highest performance, this performance quickly decreases as gas bubbles are trapped within the electrode. The open structure of the foam facilitates bubble removal, but its small surface area limits its maximum performance. The microfiber felt exhibits the best performance because it balances high surface area with the ability to remove bubbles. The microfiber felt maintains a maximum current density of 25 000 mA cm^?2 over 100 h without degradation, which corresponds to a hydrogen production rate 12.5‐ and 50‐times greater than conventional proton‐exchange membrane and alkaline electrolyzers, respectively.     

c-MET Regulates Myoblast Motility and Myocyte Fusion during Adult Skeletal Muscle Regeneration

Adult muscle stem cells, satellite cells (SCs), endow skeletal muscle with tremendous regenerative capacity. Upon injury, SCs activate, proliferate, and migrate as myoblasts to the injury site where they become myocytes that fuse to form new muscle. How migration is regulated, though, remains largely unknown. Additionally, how migration and fusion, which both require dynamic rearrangement of the cytoskeleton, might be related is not well understood. c-MET, a receptor tyrosine kinase, is required for myogenic precursor cell migration into the limb for muscle development during embryogenesis. Using a genetic system to eliminate c-MET function specifically in adult mouse SCs, we found that c-MET was required for muscle regeneration in response to acute muscle injury. c-MET mutant myoblasts were defective in lamellipodia formation, had shorter ranges of migration, and migrated slower compared to control myoblasts. Surprisingly, c-MET was also required for efficient myocyte fusion, implicating c-MET in dual functions of regulating myoblast migration and myocyte fusion.     

Design and evaluation of novel 8-oxo-pyridopyrimidine Jak1/2 inhibitors

A highly ligand efficient, novel 8-oxo-pyridopyrimidine containing inhibitor of Jak1 and Jak2 isoforms with a pyridone moiety as the hinge-binding motif was discovered. Structure-based design strategies were applied to significantly improve enzyme potency and the polarity of the molecule was adjusted to gain cellular activity. The crystal structures of two representative inhibitors bound to Jak1 were obtained to enable SAR exploration.     

DNA barcoding and species delimitation of butterflies (Lepidoptera) from Nigeria

Molecular Biology Reports - Accurate identification of species is a prerequisite for successful biodiversity management and further genetic studies. Species identification techniques often require...     

Patient-specific prediction of intrinsic mechanical loadings on sub-muscular pectoral pacemaker implants based on an inter-species transfer function

With the steady technological development enabling reduced device dimensions and new patient populations, detailed data on mechanical in vivo loads become increasingly important to ensure reliability of implantable medical devices. Based on an intra-species correlation of in-line and transverse force of the Pectoralis major established previously for the Chacma baboon (de Vaal et al., 2010a), a simplified physiological model and a mechanical equivalent model were developed for a sub-muscular pectoral device implant considering Pectoralis major, Pectoralis minor and rib cage. By assessing the morphometric and mechanical parameters of these musculo-skeletal structures and the associated model parameters, the intra-species correlation was shown to exhibit (a) robustness for a larger intra-species subject population and (b) linear scale variance allowing application for humans under consideration of the inter-species difference of the attachment angles of Pectoralis major. The transfer function provides a basis for the prediction of patient-specific maximum mechanical loadings on a sub-muscular pectoral cardiac pacemaker implant through non- or minimal invasive measurements on the patient.     

Ultrastructural comparison of Aplysia and Dolabrifera ink glands suggests cellular sites of anti-predator protein production and algal pigment processing

Ultrastructural comparison between the ink gland of a sea harespecies that produces copious purple ink (Aplysia californica)and one that produces none (Dolabrifera dolabrifera), suggeststhat the rough endoplasmic reticulum rich cell and not the inkvesicle cell is the site for synthesis of A. californica's anti-predatorink protein, escapin. Dolabrifera dolabrifera were found tohave vestigial ink glands incapable of producing ink or itsassociated anti-predator proteins regardless of diet. This studyalso suggests that the granulate cells serve only as a storagesite for excess ink pigment acquired during periods of luxuryfeeding on red algae. Slit dimensions in sieve areas of granulatecells are also significantly different between the two species.These slit sizes are larger than those of rhogocytes, a relatedcell type commonly found in connective tissue of gastropod molluscs.Several traits of granulate cells suggest that they are distinctfrom rhogocytes and are a special cell type in the ink glandof sea hares. (Received 1 July 2005; accepted 1 April 2006)     

Exhaustive exercise, animal stress, and environmental hypercapnia on motility of sperm of steelhead trout (Oncorhynchus mykiss)

Motility of salmonid sperm is inhibited by the presence of carbon dioxide (CO2) in vitro; however, whether this occurs in response to challenges to the adult in vivo is not known. To determine whether CO2 negatively impacts sperm function in vivo, mature males were exposed to exhaustive exercise as well as to acute stress, chronic stress, tricaine anesthesia and environmental hypercapnia and sperm motility and semen CO2 tensions and pH values assessed. Semen CO2 rose and pH decreased significantly only in response to exhaustive exercise and environmental hypercapnia (13 kPa CO2). These changes in semen CO2 and pH were associated with reductions in numbers of sperm becoming motile upon water activation. Chronic and acute stress and tricaine anesthesia were without effect on sperm motility or on semen CO2 or pH. The time course of CO2 inhibition and recovery was evaluated in vitro. At least 50 min was required to note 50% of the inhibitory effect of low CO2 tensions on motility when sperm were exposed to 1.6-3.1 kPa CO2. At higher CO2 levels sperm motility displayed 50% of the inhibitory effect of these tensions within about 30 min. Sperm recovered maximal motility within 1 h of being placed in a nominally CO2-free environment. This study demonstrates sperm vulnerability to not only in vitro CO2 exposure but also in vivo exposure during exhaustive exercise and as result of environmental hypercapnia.