Inhibition of tyrosine kinase activity decreases expression of surfactant protein A in a human lung adenocarcinoma cell line independent of epidermal growth factor receptor

AbstractEpidermal growth factor (EGF) enhances fetal lung development in vivo and in vitro. Ligand binding to the EGF receptor stimulates an intrinsic receptor tyrosine kinase initiating a signal transduction cascade. We hypothesized that blocking EGF receptor function with tyrosine kinase inhibitors would decrease the expression of surfactant protein A in human pulmonary epithelial cells. Human pulmonary adenocarcinoma cells (NCI-H441) were exposed to genistein (a broad range inhibitor of tyrosine kinases) and tyrphostin AG1478 (a specific inhibitor of EGF receptor tyrosine kinase). Genistein significantly decreased surfactant protein A (SP-A) and SP-A mRNA levels in H441 cells without affecting cell viability. The inhibitory effect of genistein on SP-A content was reversible. In contrast, tyrphostin AG1478 had no effect on SP-A levels despite a greater inhibitory effect than genistein on EGF receptor tyrosine autophosphorylation. Furthermore, treatment of H441 cells with exogenous EGF did not increase SP-A content or mRNA levels beyond baseline. We conclude that inhibition of tyrosine kinase activity other than the EGF receptor decreases the expression of surfactant protein A at a pretranslational level in human pulmonary adenocarcinoma cells. These results suggest the importance of tyrosine kinases in modulating human SP-A synthesis

Human Metapneumovirus, Peru

We retrospectively studied 420 pharyngeal swab specimens collected from Peruvian and Argentinean patients with influenzalike illness in 2002 and 2003 for evidence of human metapneumovirus (HMPV). Twelve specimens (2.3%) were positive by multiple assays. Six specimens yielded HMPV isolates. Four of the 6 isolates were of the uncommon B1 genotype

The Palomar/Keck Adaptive Optics Survey of Young Solar Analogs: Evidence for a Universal Companion Mass Function

We present results from an adaptive optics survey for substellar and stellar companions to Sun-like stars. The survey targeted 266 F5-K5 stars in the 3Myr to 3Gyr age range with distances of 10-190pc. Results from the survey include the discovery of two brown dwarf companions (HD49197B and HD203030B), 24 new stellar binaries, and a triple system. We infer that the frequency of 0.012-0.072Msun brown dwarfs in 28-1590AU orbits around young solar analogs is 3.2% (+3.1%,-2.7%; 2sigma limits). The result demonstrates that the deficiency of substellar companions at wide orbital separations from Sun-like stars is less pronounced than in the radial velocity "brown dwarf desert." We infer that the mass distribution of companions in 28-1590AU orbits around solar-mass stars follows a continuous dN/dM_2 ~ M_2^(-0.4) relation over the 0.01-1.0Msun secondary mass range. While this functional form is similar to that for <0.1Msun isolated objects, over the entire 0.01-1.0Msun range the mass functions of companions and of isolated objects differ significantly. Based on this conclusion and on similar results from other direct imaging and radial velocity companion surveys in the literature, we argue that the companion mass function follows the same universal form over the entire range between 0-1590AU in orbital semi-major axis and 0.01-20Msun in companion mass. In this context, the relative dearth of substellar versus stellar secondaries at all orbital separations arises naturally from the inferred form of the companion mass function.Comment: Final version accepted by ApJ Supplements. 50 pages, including 12 tables + 16 figures. Version with full tables available at http://www.astro.sunysb.edu/metchev/PUBLICATIONS/cmf.pd

Nurses' experiences of recruitment and migration from developing countries: a phenomenological approach

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Muscle Fiber Type-Dependent Differences in the Regulation of Protein Synthesis

This study examined fiber type-dependent differences in the regulation of protein synthesis in individual muscle fibers found within the same whole muscle. Specifically, the in vivo SUrface SEnsing of Translation (SUnSET) methodology was used to measure protein synthesis in type 1, 2A, 2X and 2B fibers of the mouse plantaris muscle, in response to food deprivation (FD), and mechanical overload induced by synergist ablation (SA). The results show that 48 h of FD induced a greater decrease in protein synthesis in type 2X and 2B fibers compared to type 1 and 2A fibers. Type 2X and 2B fibers also had the largest FD-induced decrease in total S6 protein and Ser240/244 S6 phosphorylation, respectively. Moreover, only type 2X and 2B fibers displayed a FD-induced decrease in cross-sectional area (CSA). Ten days of SA also induced fiber type-dependent responses, with type 2B fibers having the smallest SA-induced increases in protein synthesis, CSA and Ser240/244 S6 phosphorylation, but the largest increase in total S6 protein. Embryonic myosin heavy chain (MHCEmb) positive fibers were also found in SA muscles and the protein synthesis rates, levels of S6 Ser240/244 phosphorylation, and total S6 protein content, were 3.6-, 6.1- and 2.9-fold greater than that found in fibers from control muscles, respectively. Overall, these results reveal differential responses in the regulation of protein synthesis and fiber size between fiber types found within the same whole muscle. Moreover, these findings demonstrate that changes found at the whole muscle level do not necessarily reflect changes in individual fiber types

Hedge Funds, Financial Intermediation, and Systemic Risk

Hedge funds are significant players in the U.S. capital markets, but differ from other market participants in important ways such as their use of a wide range of complex trading strategies and instruments, leverage, opacity to outsiders, and their compensation structure. The traditional bulwark against financial market disruptions with potential systemic consequences has been the set of counterparty credit risk management (CCRM) practices by the core of regulated institutions. The characteristics of hedge funds make CCRM more difficult as they exacerbate market failures linked to agency problems, externalities, and moral hazard. While various market failures may make CCRM imperfect, it remains the best line of defense against systemic risk

Plasticity of the Muscle Stem Cell Microenvironment

Satellite cells (SCs) are adult muscle stem cells capable of repairing damaged and creating new muscle tissue throughout life. Their functionality is tightly controlled by a microenvironment composed of a wide variety of factors, such as numerous secreted molecules and different cell types, including blood vessels, oxygen, hormones, motor neurons, immune cells, cytokines, fibroblasts, growth factors, myofibers, myofiber metabolism, the extracellular matrix and tissue stiffness. This complex niche controls SC biology-quiescence, activation, proliferation, differentiation or renewal and return to quiescence. In this review, we attempt to give a brief overview of the most important players in the niche and their mutual interaction with SCs. We address the importance of the niche to SC behavior under physiological and pathological conditions, and finally survey the significance of an artificial niche both for basic and translational research purposes

Genotype Prevalence and Risk Factors for Severe Clinical Adenovirus Infection, United States 2004-2006

Recently, epidemiological and clinical data have revealed important changes with regard to clinical adenovirus infection, including alterations in antigenic presentation, geographical distribution, and virulence of the virus

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead