A role for fibroblasts in mediating the effects of tobacco-induced epithelial cell growth and invasion

Cigarette smoke and smokeless tobacco extracts contain multiple carcinogenic compounds, but little is known about the mechanisms by which tumors develop and progress upon chronic exposure to carcinogens such as those present in tobacco products. Here, we examine the effects of smokeless tobacco extracts on human oral fibroblasts. We show that smokeless tobacco extracts elevated the levels of intracellular reactive oxygen, oxidative DNA damage, and DNA double-strand breaks in a dose-dependent manner. Extended exposure to extracts induced fibroblasts to undergo a senescence-like growth arrest, with striking accompanying changes in the secretory phenotype. Using cocultures of smokeless tobacco extracts-exposed fibroblasts and immortalized but nontumorigenic keratinocytes, we further show that factors secreted by extracts-modified fibroblasts increase the proliferation and invasiveness of partially transformed epithelial cells, but not their normal counterparts. In addition, smokeless tobacco extracts-exposed fibroblasts caused partially transformed keratinocytes to lose the expression of E-cadherin and ZO-1, as well as involucrin, changes that are indicative of compromised epithelial function and commonly associated with malignant progression. Together, our results suggest that fibroblasts may contribute to tumorigenesis indirectly by increasing epithelial cell aggressiveness. Thus, tobacco may not only initiate mutagenic changes in epithelial cells but also promote the growth and invasion of mutant cells by creating a procarcinogenic stromal environment.     

Modification of kidney barrier function by the urokinase receptor

Podocyte dysfunction, represented by foot process effacement and proteinuria, is often the starting point for progressive kidney disease. Therapies aimed at the cellular level of the disease are currently not available. Here we show that induction of urokinase receptor (uPAR) signaling in podocytes leads to foot process effacement and urinary protein loss via a mechanism that includes lipid-dependent activation of alphavbeta3 integrin. Mice lacking uPAR (Plaur-/-) are protected from lipopolysaccharide (LPS)-mediated proteinuria but develop disease after expression of a constitutively active beta3 integrin. Gene transfer studies reveal a prerequisite for uPAR expression in podocytes, but not in endothelial cells, for the development of LPS-mediated proteinuria. Mechanistically, uPAR is required to activate alphavbeta3 integrin in podocytes, promoting cell motility and activation of the small GTPases Cdc42 and Rac1. Blockade of alphavbeta3 integrin reduces podocyte motility in vitro and lowers proteinuria in mice. Our findings show a physiological role for uPAR signaling in the regulation of kidney permeability.     

A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology

Genomic data allow the large-scale manual or semi-automated assembly of metabolic network reconstructions, which provide highly curated organism-specific knowledge bases. Although several genome-scale network reconstructions describe Saccharomyces cerevisiae metabolism, they differ in scope and content, and use different terminologies to describe the same chemical entities. This makes comparisons between them difficult and underscores the desirability of a consolidated metabolic network that collects and formalizes the 'community knowledge' of yeast metabolism. We describe how we have produced a consensus metabolic network reconstruction for S. cerevisiae. In drafting it, we placed special emphasis on referencing molecules to persistent databases or using database-independent forms, such as SMILES or InChI strings, as this permits their chemical structure to be represented unambiguously and in a manner that permits automated reasoning. The reconstruction is readily available via a publicly accessible database and in the Systems Biology Markup Language (http://www.comp-sys-bio.org/yeastnet). It can be maintained as a resource that serves as a common denominator for studying the systems biology of yeast. Similar strategies should benefit communities studying genome-scale metabolic networks of other organisms.     

Preparation and characteristics of moulded biodegradable cellulose fibers/MPU-20 composites (CFMCs) by steam injection technology

In this work, the moulded cellulose fibers/MPU-20 composites (CFMCs) with apparent specific gravity lower than 100 kg/m³ and thickness of 20–200 mm have been successfully manufactured using a new design of steam injection technology and equipment. It was found that the CFMCs have good cushioning properties, with a cushion factor lower than 4. Two yield deformation stages were observed in the compressive process. Compressive stress–strain and cushion factor-stain curves were measured as a function of steam injection pressure, transmission time, holding time, MPU-20 resin dosage and apparent specific gravity. Chemical groups, crystallinity, and thermal properties of samples were studied through the use of FTIR spectroscopy, X-ray diffraction (XRD), and DTA–TGA. In addition, the microstructure and morphology were investigated by scanning electron microscope (SEM) and atomic force microscope (AFM).     

Effects of nitrogen deposition on forest biodiversity

Humans have altered global and regional cycles of nitrogen (N) more than any other elements. Increasing N emissions to the atmosphere from accelerating industrialization and production and use of fertilizer N now make N deposition significant not only in densely populated regions of Europe and North America, but also in other parts of the world (e.g., Asia and Latin America). Increased atmospheric N deposition is known to be able to reduce biodiversity in natural and semi-natural ecosystems. It is suggested that N deposition will be the third greatest driver of biodiversity loss on the global scale in this century, after land use and climate change. Based on published study results, we reviewed the impacts of N deposition on forest biodiversity by emphasizing 3 aspects: (1) plant diversity, including arborous plants, understory plants and cryptogam plants; (2) soil microorganism diversity; (3) animal diversity, including underground soil fauna and aboveground herbivores. In general, it was found that N deposition could alter species diversity, and excessive N could reduce species diversity, such as richness and abundance, and even lose special species. We also identified specific mechanisms on how excessive N deposition affected forest biodiversity. Finally, we summarized the current status of research on N deposition in China and in other countries, and proposed potential research activities and recommendations.     

Pro‐apoptotic Noxa is involved in ablative focal irradiation‐induced lung injury

Although lung injury including fibrosis is a well‐documented side effect of lung irradiation, the mechanisms underlying its pathology are poorly understood. X‐rays are known to cause apoptosis in the alveolar epithelial cells of irradiated lungs, which results in fibrosis due to the proliferation and differentiation of fibroblasts and the deposition of collagen. Apoptosis and BH3‐only pro‐apoptotic proteins have been implicated in the pathogenesis of pulmonary fibrosis. Recently, we have established a clinically analogous experimental model that reflects focal high‐dose irradiation of the ipsilateral lung. The goal of this study was to elucidate the mechanism underlying radiation‐induced lung injury based on this model. A radiation dose of 90 Gy was focally delivered to the left lung of C57BL/6 mice for 14 days. About 9 days after irradiation, the mice began to show increased levels of the pro‐apoptotic protein Noxa in the irradiated lung alongside increased apoptosis and fibrosis. Suppression of Noxa expression by small interfering RNA protected cells from radiation‐induced cell death and decreased expression of fibrogenic markers. Furthermore, we showed that reactive oxygen species participate in Noxa‐mediated, radiation‐induced cell death. Taken together, our results show that Noxa is involved in X‐ray‐induced lung injury.     

The adsorption of NO,NH<Subscript>3</Subscript>, N<Subscript>2</Subscript> on carbon surface: a density functional theory study

To explore the adsorption mechanism of NO, NH₃, N₂ on a carbon surface, and the effect of basic and acidic functional groups, density functional theory was employed to investigate the interactions between these molecules and carbon surfaces. Molecular electrostatic potential, Mulliken population analyses, reduced density gradient, and Mayer bond order analyses were used to clarify the adsorption mechanism. The results indicate that van der Waals interactions are responsible for N₂ physisorption, and N₂ is the least likely to adsorb on a carbon surface. Modification of carbon materials to decorate basic or acidic functional groups could enhance the NH₃ physisorption because of hydrogen bonding or electrostatic interactions, however, NO physisorption on a carbon surface is poor. Zig-zag sites are more reactive than armchair sites when these gas molecules absorb on the edge sites of carbon surface.

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Graphical abstract NH₃, N₂, NO adsortion on carbon surface

     

<Emphasis Type="Italic">ALDH2</Emphasis> genes are negatively correlated with natural deastringency in Chinese PCNA persimmon (<Emphasis Type="Italic">Diospyros kaki</Emphasis> Thunb.)

Chinese pollination-constant and non-astringent persimmon (C-PCNA) has important application values in the genetic improvement of PCNA for its trait of natural deastringency controlled by a single dominant gene. However, the key genes and the regulatory networks are still not fully understood. The process of C-PCNA natural deastringency may be associated with the acetaldehyde-mediated coagulation of soluble tannins, but the functions of ALDH2 genes related to the metabolism of acetaldehyde are not clear. In this work, three types of persimmon cultivars, ‘Eshi 1’ and ‘Luotian Tianshi’ (C-PCNA type), ‘Youhou’ (J-PCNA type), and ‘Mopanshi’ (non-PCNA type), were sampled. Two members of ALDH2 family genes, DkALDH2a and DkALDH2b, were isolated from ‘Eshi 1’ persimmon fruit. Gene expression patterns indicated that they may be involved in “coagulation effect”, which leads to natural deastringency in C-PCNA persimmon fruit. Transient expression in ‘Eshi 1’ leaves further demonstrated that their expression can reduce the consumption of soluble tannins and inhibit the astringency removal process. Therefore, DkALDH2a and DkALDH2b are negatively correlated with natural deastringency in C-PCNA persimmon.