Removal of organic content from diesel exhaust particles alters cellular responses of primary human bronchial epithelial cells cultured at an air-liquid interface

Background Exposure to air pollutants, including diesel particulate matter, has been linked to adverse respiratory health effects. Inhaled diesel particulate matter contains adsorbed organic compounds. It is not clear whether the adsorbed organics or the residual components are more deleterious to airway cells. Using a physiologically relevant model, we investigated the role of diesel organic content on mediating cellular responses of primary human bronchial epithelial cells (HBECs) cultured at an air-liquid interface (ALI). Methods Primary HBECs were cultured and differentiated at ALI for at least 28 days. To determine which component is most harmful, we compared primary HBEC responses elicited by residual (with organics removed) diesel emissions (DE) to those elicited by neat (unmodified) DE for 30 and 60 minutes at ALI, with cigarette smoke condensate (CSC) as the positive control, and filtered air as negative control. Cell viability (WST-1 cell proliferation assay), inflammation (TNF-α, IL-6 and IL-8 ELISA) and changes in gene expression (qRT-PCR for HO-1, CYP1A1, TNF-α and IL-8 mRNA) were measured. Results Immunofluorescence and cytological staining confirmed the mucociliary phenotype of primary HBECs differentiated at ALI. Neat DE caused a comparable reduction in cell viability at 30 or 60 min exposures, whereas residual DE caused a greater reduction at 60 min. When corrected for cell viability, cytokine protein secretion for TNF-α, IL-6 and IL-8 were maximal with residual DE at 60 min. mRNA expression for HO-1, CYP1A1, TNF-α and IL-8 was not significantly different between exposures. Conclusion This study provides new insights into epithelial cell responses to diesel emissions using a physiologically relevant aerosol exposure model. Both the organic content and residual components of diesel emissions play an important role in determining bronchial epithelial cell response in vitro. Future studies should be directed at testing potentially useful interventions against the adverse health effects of air pollution exposure.

Tie-2 regulates the stemness and metastatic properties of prostate cancer cells

Ample evidence supports that prostate tumor metastasis originates from a rare population of cancer cells, known as cancer stem cells (CSCs). Unfortunately, little is known about the identity of these cells, making it difficult to target the metastatic prostate tumor. Here, for the first time, we report the identification of a rare population of prostate cancer cells that express the Tie-2 protein. We found that this Tie-2High population exists mainly in prostate cancer cell lines that are capable of metastasizing to the bone. These cells not only express a higher level of CSC markers but also demonstrate enhanced resistance to the chemotherapeutic drug Cabazitaxel. In addition, knockdown of the expression of the Tie-2 ligand angiopoietin (Ang-1) led to suppression of CSC markers, suggesting that the Ang-1/Tie-2 signaling pathway functions as an autocrine loop for the maintenance of prostate CSCs. More importantly, we found that Tie-2High prostate cancer cells are more adhesive than the Tie-2Low population to both osteoblasts and endothelial cells. Moreover, only the Tie-2High, but not the Tie-2Low cells developed tumor metastasis in vivo when injected at a low number. Taken together, our data suggest that Tie-2 may play an important role during the development of prostate tumor metastasis.

Coordinated Verb Pairs in Texts

This dissertation discusses the relation between lexis, grammar and textual organisation. The major premise adopted here is that grammatical structures are motivated both by semantic potential of words and by text-pragmatic demands. In other words, it is argued that grammatical structures form the interface between lexis and textual organisation, and that linguistic analysis should not concentrate on analysing grammatical structures in isolation, independent of context. From this point of view, grammatical structures are said to be 'well-formed' only in relation to the context they occur in. This study is based on a corpus of three million words of recent Finnish fiction from which all the occurrences of the coordinated verb pairs ([V ja V] -pairs]) containing one of the intransitive motion verbs 'lähteä' (to go), 'mennä' (to go), 'päästä' (to get into), 'nousta' (to get up), and 'laskea' (to go down), were extracted. This set of verbs was established using methods described in earlier work by Lagus & Airola (2001, and 2005). The quantitative analysis of the [V ja V] -pairs was used to carry out a qualitative analysis of individual texts. In analysing the texts, an analogy was made between musical and textual structure. The results show among others that individual verbs specialise in different functions when occurring in coordinated verb pairs. One aspect was that those verb pairs including the verb 'nousta' tend to function as markers of textual boundaries and thus reflect the organisation of narrative substance. The verb 'mennä' has weakened literal meanings, but strengthened modal meanings when occurring in [V ja V] -pairs, and, in many cases, the verb 'lähteä' in [V ja V] -pairs function as an aspectual marker rather than a pure verb of motion. That there is a gradient from the concrete sense of motion into more differentiated senses of a verb in [V ja V] -pairs alongside the structure-creating potential of the [V ja V] -pairs themselves suggest an ongoing grammaticalisation process of the patterns discussed.

Adipocytes promote prostate cancer stem cell self-renewal through amplification of the cholecystokinin autocrine loop

Obesity has long been linked with prostate cancer progression, although the underlying mechanism is still largely unknown. Here, we report that adipocytes promote the enrichment of prostate cancer stem cells (CSCs) through a vicious cycle of autocrine amplification. In the presence of adipocytes, prostate cancer cells actively secrete the peptide hormone cholecystokinin (CCK), which not only stimulates prostate CSC self-renewal, but also induces cathepsin B (CTSB) production of the adipocytes. In return, CTSB facilitates further CCK secretion by the cancer cells. More importantly, inactivation of CCK receptor not only suppresses CTSB secretion by the adipocytes, but also synergizes the inhibitory effect of CTSB inhibitor on adipocyte-promoted prostate CSC self-renewal. In summary, we have uncovered a novel mechanism underlying the mutual interplay between adipocytes and prostate CSCs, which may help explaining the role of adipocytes in prostate cancer progression and provide opportunities for effective intervention.

Cancer stem cells in oesophageal squamous cell carcinoma: Identification, prognostic and treatment perspectives

Cancer stem cells (CSCs) are a vital subpopulation of cells to target for the treatment of cancers. In oesophageal squamous cell carcinoma (ESCC), there are several markers such as CD44, ALDH, Pygo2, MAML1, Twist1, Musashi1, Side population (SP), CD271 and CD90 that have been proposed to identify the cancer stem cells in individual cancer masses. It has also been demonstrated that stem cell markers like ALDH1, HIWI, Oct3/4, ABCG2, SOX2, SALL4, BMI-1, NANOG, CD133 and podoplanin are associated with patient's prognosis, pathological stages, cancer recurrence and therapy resistance. Finding new cancer stem cell targets or designing drugs to manipulate the known molecular targets in CSCs could be useful for improvements in clinical outcomes of the disease. To conclude, data suggest that CSCs in oesophageal squamous cell carcinoma are related to resistance to therapy and poor prognosis of patients with ESCC. Therefore, innovative insights into CSC biology and CSC-targeted therapies will help to achieve more effective management of patients with oesophageal squamous cell carcinoma.

Modulatory roles of microRNAs in the regulation of different signalling pathways in large bowel cancer stem cells

There are emerging data to suggest that microRNAs (miRNAs) have significant roles in regulating the function of normal cells and cancer stem cells (CSCs). This review aims to analyse the roles of miRNAs in the regulation of colon CSCs through their interaction with various signalling pathways. Studies showed a large number of miRNAs that are reported to be deregulated in colon CSCs. However, few of the studies available were able to outline the function of miRNAs in colon CSCs and uncover their signalling pathways. From those miRNAs, which are better described, miR-21 followed by miR-34, miR-200 and miR-215 are the most reported miRNAs to have roles in colon CSC regulation. In particular, miRNAs have been reported to regulate the stemness features of colon CSCs mainly via Wnt/B-catenin and Notch signalling pathways. Additionally, miRNAs have been reported to act on processes involving CSCs through cell cycle regulation genes and epithelial-mesenchymal transition. The relative paucity of data available on the significance of miRNAs in CSCs means that new studies will be of great importance to determine their roles and to identify the signalling pathways through which they operate. Such studies may in future guide further research to target these genes for more effective cancer treatment. miRNAs were shown to regulate the function of cancer stem cells in large bowel cancer by targeting a few key signalling pathways in cells.

Lung cancer stem cells: The root of resistance

In the absence of specific treatable mutations, platinum-based chemotherapy remains the gold standard of treatment for lung cancer patients. However, 5-year survival rates remain poor due to the development of resistance and eventual relapse. Resistance to conventional cytotoxic therapies presents a significant clinical challenge in the treatment of this disease. The cancer stem cell (CSC) hypothesis suggests that tumors are arranged in a hierarchical structure, with the presence of a small subset of stem-like cells that are responsible for tumor initiation and growth. This CSC population has a number of key properties such as the ability to asymmetrically divide, differentiate and self-renew, in addition to having increased intrinsic resistance to therapy. While cytotoxic chemotherapy kills the bulk of tumor cells, CSCs are spared and have the ability to recapitulate the heterogenic tumor mass. The identification of lung CSCs and their role in tumor biology and treatment resistance may lead to innovative targeted therapies that may ultimately improve clinical outcomes in lung cancer patients. This review will focus on lung CSC markers, their role in resistance and their relevance as targets for future therapies.

Cubic Sieve Congruence of the Discrete Logarithm Problem, and fractional part sequences

The Cubic Sieve Method for solving the Discrete Logarithm Problem in prime fields requires a nontrivial solution to the Cubic Sieve Congruence (CSC) x(3) equivalent to y(2)z (mod p), where p is a given prime number. A nontrivial solution must also satisfy x(3) not equal y(2)z and 1 <= x, y, z < p(alpha), where alpha is a given real number such that 1/3 < alpha <= 1/2. The CSC problem is to find an efficient algorithm to obtain a nontrivial solution to CSC. CSC can be parametrized as x equivalent to v(2)z (mod p) and y equivalent to v(3)z (mod p). In this paper, we give a deterministic polynomial-time (O(ln(3) p) bit-operations) algorithm to determine, for a given v, a nontrivial solution to CSC, if one exists. Previously it took (O) over tilde (p(alpha)) time in the worst case to determine this. We relate the CSC problem to the gap problem of fractional part sequences, where we need to determine the non-negative integers N satisfying the fractional part inequality {theta N} < phi (theta and phi are given real numbers). The correspondence between the CSC problem and the gap problem is that determining the parameter z in the former problem corresponds to determining N in the latter problem. We also show in the alpha = 1/2 case of CSC that for a certain class of primes the CSC problem can be solved deterministically in <(O)over tilde>(p(1/3)) time compared to the previous best of (O) over tilde (p(1/2)). It is empirically observed that about one out of three primes is covered by the above class. (C) 2013 Elsevier B.V. All rights reserved.

Competing views on cancer

Despite intense research efforts that have provided enormous insight, cancer continues to be a poorly understood disease. There has been much debate over whether the cancerous state can be said to originate in a single cell or whether it is a reflection of aberrant behaviour on the part of a `society of cells'. This article presents, in the form of a debate conducted among the authors, three views of how the problem might be addressed. We do not claim that the views exhaust all possibilities. These views are (a) the tissue organization field theory (TUFT) that is based on a breakdown of tissue organization involving many cells from different embryological layers, (b) the cancer stem cell (CSC) hypothesis that focuses on genetic and epigenetic changes that take place within single cells, and (c) the proposition that rewiring of the cell's protein interaction networks mediated by intrinsically disordered proteins (IDPs) drives the tumorigenic process. The views are based on different philosophical approaches. In detail, they differ on some points and agree on others. It is left to the reader to decide whether one approach to understanding cancer appears more promising than the other.

Simvastatin Induced Neurite Outgrowth Unveils Role of Cell Surface Cholesterol and Acetyl CoA Carboxylase in SH-SY5Y Cells

Statins are known to modulate cell surface cholesterol (CSC) and AMP-activated protein kinase (AMPK) in nonneural cells; however no study demonstrates whether CSC and AMPK may regulate simvastatin induced neuritogenesis (SIN). We found that simvastatin (SIM) maintains CSC as shown by Fillipin III staining, Flotillin-2 protein expression / localization and phosphorylation of various receptor tyrosine kinases (RTKs) in the plasma membrane. Modulation of CSC revealed that SIN is critically dependent on this CSC. Simultaneously, phospho array for mitogen activated protein kinases (MAPKs) revealed PI3K / Akt as intracellular pathway which modulates lipid pathway by inhibiting AMPK activation. Though, SIM led to a transient increase in AMPK phosphorylation followed by a sudden decline; the effect was independent of PI3K. Strikingly, AMPK phosphorylation was regulated by protein phosphatase 2A (PP2A) activity which was enhanced upon SIM treatment as evidenced by increase in threonine phosphorylation. Moreover, it was observed that addition of AMP analogue and PP2A inhibitor inhibited SIN. Biocomposition of neurites shows that lipids form a major part of neurites and AMPK is known to regulate lipid metabolism majorly through acetyl CoA carboxylase (ACC). AMPK activity is negative regulator of ACC activity and we found that phosphorylation of ACC started to decrease after 6 hrs which becomes more pronounced at 12 hrs. Addition of ACC inhibitor showed that SIN is dependent on ACC activity. Simultaneously, addition of Fatty acid synthase (FAS) inhibitor confirmed that endogenous lipid pathway is important for SIN. We further investigated SREBP-1 pathway activation which controls ACC and FAS at transcriptional level. However, SIM did not affect SREBP-1 processing and transcription of its target genes likes ACC1 and FAS. In conclusion, this study highlights a distinct role of CSC and ACC in SIN which might have implication in process of neuronal differentiation induced by other agents.

Techniques for spatial analysis and visualization of benthic mapping data: final report

The mapping and geospatial analysis of benthic environments are multidisciplinary tasks that have become more accessible in recent years because of advances in technology and cost reductions in survey systems. The complex relationships that exist among physical, biological, and chemical seafloor components require advanced, integrated analysis techniques to enable scientists and others to visualize patterns and, in so doing, allow inferences to be made about benthic processes. Effective mapping, analysis, and visualization of marine habitats are particularly important because the subtidal seafloor environment is not readily viewed directly by eye. Research in benthic environments relies heavily, therefore, on remote sensing techniques to collect effective data. Because many benthic scientists are not mapping professionals, they may not adequately consider the links between data collection, data analysis, and data visualization. Projects often start with clear goals, but may be hampered by the technical details and skills required for maintaining data quality through the entire process from collection through analysis and presentation. The lack of technical understanding of the entire data handling process can represent a significant impediment to success. While many benthic mapping efforts have detailed their methodology as it relates to the overall scientific goals of a project, only a few published papers and reports focus on the analysis and visualization components (Paton et al. 1997, Weihe et al. 1999, Basu and Saxena 1999, Bruce et al. 1997). In particular, the benthic mapping literature often briefly describes data collection and analysis methods, but fails to provide sufficiently detailed explanation of particular analysis techniques or display methodologies so that others can employ them. In general, such techniques are in large part guided by the data acquisition methods, which can include both aerial and water-based remote sensing methods to map the seafloor without physical disturbance, as well as physical sampling methodologies (e.g., grab or core sampling). The terms benthic mapping and benthic habitat mapping are often used synonymously to describe seafloor mapping conducted for the purpose of benthic habitat identification. There is a subtle yet important difference, however, between general benthic mapping and benthic habitat mapping. The distinction is important because it dictates the sequential analysis and visualization techniques that are employed following data collection. In this paper general seafloor mapping for identification of regional geologic features and morphology is defined as benthic mapping. Benthic habitat mapping incorporates the regional scale geologic information but also includes higher resolution surveys and analysis of biological communities to identify the biological habitats. In addition, this paper adopts the definition of habitats established by Kostylev et al. (2001) as a “spatially defined area where the physical, chemical, and biological environment is distinctly different from the surrounding environment.” (PDF contains 31 pages)

Coral Remote Sensing Workshop: Proceedings and Recommendations, 17-18 September, Sheraton, Brickell Ave, Miami FL

Coral reefs exist in warm, clear, and relatively shallow marine waters worldwide. These complex assemblages of marine organisms are unique, in that they support highly diverse, luxuriant, and essentially self-sustaining ecosystems in otherwise nutrient-poor and unproductive waters. Coral reefs are highly valued for their great beauty and for their contribution to marine productivity. Coral reefs are favorite destinations for recreational diving and snorkeling, as well as commercial and recreational fishing activities. The Florida Keys reef tract draws an estimated 2 million tourists each year, contributing nearly $800 million to the economy. However, these reef systems represent a very delicate ecological balance, and can be easily damaged and degraded by direct or indirect human contact. Indirect impacts from human activity occurs in a number of different forms, including runoff of sediments, nutrients, and other pollutants associated with forest harvesting, agricultural practices, urbanization, coastal construction, and industrial activities. Direct impacts occur through overfishing and other destructive fishing practices, mining of corals, and overuse of many reef areas, including damage from souvenir collection, boat anchoring, and diver contact. In order to protect and manage coral reefs within U.S. territorial waters, the National Oceanic and Atmospheric Administration (NOAA) of the U.S. Department of Commerce has been directed to establish and maintain a system of national marine sanctuaries and reserves, and to monitor the condition of corals and other marine organisms within these areas. To help carry out this mandate the NOAA Coastal Services Center convened a workshop in September, 1996, to identify current and emerging sensor technologies, including satellite, airborne, and underwater systems with potential application for detecting and monitoring corals. For reef systems occurring within depths of 10 meters or less (Figure 1), mapping location and monitoring the condition of corals can be accomplished through use of aerial photography combined with diver surveys. However, corals can exist in depths greater than 90 meters (Figure 2), well below the limits of traditional optical imaging systems such as aerial or surface photography or videography. Although specialized scuba systems can allow diving to these depths, the thousands of square kilometers included within these management areas make diver surveys for deeper coral monitoring impractical. For these reasons, NOAA is investigating satellite and airborne sensor systems, as well as technologies which can facilitate the location, mapping, and monitoring of corals in deeper waters. The following systems were discussed as having potential application for detecting, mapping, and assessing the condition of corals. However, no single system is capable of accomplishing all three of these objectives under all depths and conditions within which corals exist. Systems were evaluated for their capabilities, including advantages and disadvantages, relative to their ability to detect and discriminate corals under a variety of conditions. (PDF contains 55 pages)

Pilot investigation of remote sensing for intertidal oyster mapping in coastal South Carolina: a methods comparison

South Carolina’s oyster reefs are a major component of the coastal landscape. Eastern oysters Crassostrea virginica are an important economic resource to the state and serve many essential functions in the environment, including water filtration, creek bank stabilization and habitat for other plants and animals. Effective conservation and management of oyster reefs is dependent on an understanding of their abundance, distribution, condition, and change over time. In South Carolina, over 95% of the state’s oyster habitat is intertidal. The current intertidal oyster reef database for South Carolina was developed by field assessment over several years. This database was completed in the early 1980s and is in need of an update to assess resource/habitat status and trends across the state. Anthropogenic factors such as coastal development and associated waterway usage (e.g., boat wakes) are suspected of significantly altering the extent and health of the state’s oyster resources. In 2002 the NOAA Coastal Services Center’s (Center) Coastal Remote Sensing Program (CRS) worked with the Marine Resources Division of the South Carolina Department of Natural Resources (SCDNR) to develop methods for mapping intertidal oyster reefs along the South Carolina coast using remote sensing technology. The objective of this project was to provide SCDNR with potential methodologies and approaches for assessing oyster resources in a more efficiently than could be accomplished through field digitizing. The project focused on the utility of high-resolution aerial imagery and on documenting the effectiveness of various analysis techniques for accomplishing the update. (PDF contains 32 pages)

Guidance for benthic habitat mapping: an aerial photographic approach

This document, Guidance for Benthic Habitat Mapping: An Aerial Photographic Approach, describes proven technology that can be applied in an operational manner by state-level scientists and resource managers. This information is based on the experience gained by NOAA Coastal Services Center staff and state-level cooperators in the production of a series of benthic habitat data sets in Delaware, Florida, Maine, Massachusetts, New York, Rhode Island, the Virgin Islands, and Washington, as well as during Center-sponsored workshops on coral remote sensing and seagrass and aquatic habitat assessment. (PDF contains 39 pages) The original benthic habitat document, NOAA Coastal Change Analysis Program (C-CAP): Guidance for Regional Implementation (Dobson et al.), was published by the Department of Commerce in 1995. That document summarized procedures that were to be used by scientists throughout the United States to develop consistent and reliable coastal land cover and benthic habitat information. Advances in technology and new methodologies for generating these data created the need for this updated report, which builds upon the foundation of its predecessor.

Seagrass and Aquatic Habitat Assessment Workshop Summary

Seagrass communities are among the richest and most productive, photoautotrophic coastal systems in the world. They protect and improve water quality, provide shoreline stabilization, and are important habitats for an array of fish, birds, and other wildlife. Hence, much can be gained by protecting and restoring these important living resources. Human’s impact on these vital resources from population growth, pollution, and physical damage from boating and other activities can disrupt the growth of these seagrasses communities and have devastating effects on their health and vitality. Inventory and monitoring are required to determine the dynamics of seagrasses and devise better protection and restoration for these rich resources. The purpose of this seagrass workshop, sponsored by NOAA’s CSC , USGS, and FMRI, was to move toward greater objectivity and accuracy in seagrass mapping and monitoring. This workshop helped foster interaction and communication among seagrass professionals. In order to begin the process of determining the best uniform mapping process for the biological research community. Increasing such awareness among the seagrass and management communities, it is hoped that an improved understanding of the monitoring and mapping process will lead to more effective and efficient preservation os submerged aquatic vegetation. (PDF contains 20 pages)