bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of Caribbean Precipitation by the Madden–Julian Oscillation
Authors: Martin Elinor R. , Schumacher Courtney
Published: October 2010

Based on 12 years of daily satellite precipitation data and reanalysis winds, intraseasonal (30–90 days) variability in Caribbean precipitation is linked to phases of the Madden–Julian oscillation (MJO). Intraseasonal variability is largest during September–November (SON), but some modulation of precipitation by the MJO appears throughout all seasons. Precipitation anomalies up to 50% above (below) the annual mean are observed in phases 1 and 2 (5 and 6) of the MJO. The changes in Caribbean precipitation associated with the MJO are shown to be related to changes in the low-level (925 hPa) winds. When precipitation anomalies are above (below) average in phases 1 and 2 (5 and 6), wind anomalies act to decrease (increase) the strength of the prevailing easterly trade winds. The changes in the low-level winds are most apparent in the region of the Caribbean low-level jet (CLLJ), and divergence anomalies associated with the entrance and exit regions of the CLLJ precede the precipitation anomalies. The CLLJ itself is also shown to be subject to intraseasonal variability, and its magnitude varies with the phase of the MJO. Again, intraseasonal variability in the CLLJ associated with the MJO is observed in all seasons and shows a significant coherence with intraseasonal variability in the precipitation. Extreme rainfall events over islands in the Caribbean show a strong relationship with the MJO phase, with extreme events being most common in phases 1 and 2 of an MJO event. This relationship between the MJO and extreme events has important implications for the predictability of precipitation extremes in the Caribbean.
Characteristics of Large-Scale Orographic Precipitation in a Linear Perspective
Authors: Kunz Michael
Published: October 2010

Simulations of orographic precipitation over the low mountain ranges of southwestern Germany and eastern France with two different physics-based linear precipitation models are presented. Both models are based on 3D airflow dynamics from linear theory and consider advection of condensed water and leeside drying. Sensitivity studies for idealized conditions and a real case study show that the amount and spatial distribution of orographic precipitation is strongly controlled by characteristic time scales for cloud and hydrometeor advection and background precipitation due to large-scale lifting. These parameters are estimated by adjusting the model results on a 2.5-km grid to observed precipitation patterns for a sample of 40 representative orography-dominated stratiform events (24 h) during a calibration period (1971–80). In general, the best results in terms of lowest rmse and bias are obtained for characteristic time scales of 1600 s and background precipitation of 0.4 mm h−1. Model simulations of a sample of 84 events during an application period (1981–2000) with fixed parameters demonstrate that both models are able to reproduce quantitatively precipitation patterns obtained from observations and reanalyses from a numerical model [Consortium for Small-scale Modeling (COSMO)]. Combining model results with observation data shows that heavy precipitations over mountains are restricted to situations with strong atmospheric forcings in terms of synoptic-scale lifting, horizontal wind speed, and moisture content.
Warm Season Afternoon Thunderstorm Characteristics under Weak Synoptic-Scale Forcing over Taiwan Island
Authors: Lin Pin-Fang , Chang Pao-Liang , Jou Ben Jong-Dao , Wilson James W. , Roberts Rita D.
Published: October 2010

The spatial and temporal characteristics and distributions of thunderstorms in Taiwan during the warm season (May–October) from 2005 to 2008 and under weak synoptic-scale forcing are documented using radar reflectivity, lightning, radiosonde, and surface data. Average hourly rainfall amounts peaked in midafternoon (1500–1600 local solar time, LST). The maximum frequency of rain was located in a narrow strip, parallel to the orientation of the mountains, along the lower slopes of the mountains. Significant diurnal variations were found in surface wind, temperature, and dewpoint temperature between days with and without afternoon thunderstorms (TSA and non-TSA days). Before thunderstorms occurred, on TSA days, the surface temperature was warmer (about 0.5°–1.5°C) and the surface dewpoint temperature was moister (about 0.5°–2°C) than on non-TSA days. Sounding observations from northern Taiwan also showed warmer and higher moisture conditions on TSA days relative to non-TSA days. The largest average difference was in the 750–550-hPa layer where the non-TSA days averaged 2.5°–3.5°C drier. These preconvective factors associated with the occurrences of afternoon thunderstorms could be integrated into nowcasting tools to enhance warning systems and decision-making capabilities in real-time operations.
TGF-β1 and FAK Regulate Periostin Expression in PDL Fibroblasts
Authors: Wen W. , Chau E. , Jackson-Boeters L. , Elliott C. , Daley T.D. , Hamilton D.W.
Published: October 2010

Recently identified as a key component of the murine periodontal ligament (PDL), periostin has been implicated in the regulation of collagen fibrillogenesis and fibroblast differentiation. We investigated whether periostin protein is expressed in the human PDL in situ and the mechanisms regulating periostin expression in PDL fibroblasts in vitro. With immunohistochemistry, periostin protein was identified in the PDL, with expression lower in teeth with reduced occlusal loading. In vitro application of uniaxial cyclic strain to PDL fibroblasts elevated periostin mRNA levels, depending on the age of the patient. Treatment with transforming growth factor-beta1 (TGF-β1) also significantly increased periostin mRNA levels, an effect attenuated by focal adhesion kinase (FAK) inhibition. FAK-null fibroblasts contained no detectable periostin mRNA, even after stimulation with cyclic strain. In conclusion, periostin protein is strongly expressed in the human PDL. In vitro, periostin mRNA levels are modulated by cyclic strain as well as TGF-β1 via FAK-dependent pathways.
Rechargeable Infection-responsive Antifungal Denture Materials
Authors: Cao Z. , Sun X. , Yeh C.-K. , Sun Y.
Published: October 2010

Candida-associated denture stomatitis (CADS) is a significant clinical concern. We developed rechargeable infection-responsive antifungal denture materials for potentially managing the disease. Polymethacrylic acid (PMAA) was covalently bound onto diurethane dimethacrylate denture resins in the curing step. The PMAA resins bound cationic antifungal drugs such as miconazole and chlorhexidine digluconate (CG) through ionic interactions. The anticandidal activities of the drug-containing PMAA-resin discs were sustained for a prolonged period of time (weeks and months). Drug release was much faster at acidic conditions (pH 5) than at pH 7. Drugs bound to the denture materials could be “washed out” by treatment with EDTA, and the drug-depleted resins could be recharged with the same or a different class of anticandidal drugs. These results suggest clinical potential of the newly developed antifungal denture materials in the management of CADS and other infectious conditions.
Involvement of Autoimmunity in the Pathogenesis of Aggressive Periodontitis
Authors: Hendler A. , Mulli T.K. , Hughes F.J. , Perrett D. , Bombardieri M. , Houri-Haddad Y. , Weiss E.I. , Nissim A.
Published: October 2010

The aim of this study was to investigate the involvement of autoimmune reactions to native and post-translationally modified extracellular matrix components in the pathogenesis of periodontitis. Sera from individuals with aggressive periodontitis (AgP, n = 25), chronic periodontitis (CP, n = 14), and gingivitis (G, n = 18) were tested for the presence of autoantibodies against: (a) native collagen type I (CI) and collagen type III (CIII); (b) CI and CIII post-translationally modified by reactive oxygen species (ROS) of the type present during inflammation; and (c) citrullinated filaggrin-derived peptides (CCP). Autoantibodies to native and ROS-modified CI and CIII as well as autoantibodies to CCP were observed exclusively in patients with AgP and not in those with CP or G. In conclusion, autoimmune reactions to native and post-translationally modified self-antigens may play a role specifically in the pathogenesis of AgP.
Nanoleakage Inhibition Within Hybrid Layer Using New Protective Chemicals and Their Effect on Adhesion
Authors: Dündar M. , Özcan M. , Çömlekoğlu M.E. , Şen B.H.
Published: October 2010

Hybrid-layer degradation occurs because of acidic properties of currently used adhesive systems. Titanium tetrafluoride couples with tooth surface, and titanium compounds are not substituted. Caffeic acid phenethyl esther inhibits endogenous matrix metalloproteinases that cause hybrid-layer degradation. It was hypothesized that titanium tetrafluoride and caffeic acid phenethyl esther application on exposed dentine surfaces before adhesive applications would inhibit nanoleakage and hybrid-layer degradation without compromising the bond strength of the adhesives. In ultracut thin sections, human dentine–chemical agent–adhesive composite interfaces were observed under transmission electron microscope with complementary scanning electron microscopy. Microtensile bond strength tests were also accomplished. Titanium tetrafluoride and titanium tetrafluoride + caffeic acid phenethyl esther applications decreased bond strength values. Caffeic acid phenethyl esther showed decreased silver nitrate penetration for cements based on Bisphenol glycydilmethacrylate and methyl methacrylate, whereas cement based on 4-methacryloyloxyethyl trimellitate anhydride methyl methacrylate showed almost no infiltration. Caffeic acid phenethyl esther application before cementation could inhibit nanoleakage and biodegradation of the hybrid layer.
Irradiation Modes’ Impact on Radical Entrapment in Photoactive Resins
Authors: Leprince J.G. , Lamblin G. , Devaux J. , Dewaele M. , Mestdagh M. , Palin W.M. , Gallez B. , Leloup G.
Published: October 2010

Different irradiation protocols are proposed to polymerize dental resins, and discordances remain concerning their impact on the material. To improve this knowledge, we studied entrapment of free radicals in unfilled Bis-GMA/TEGDMA (50:50 wt%) resin after light cure. The tested hypothesis was that various irradiation parameters (curing time, irradiance, and radiant exposure) and different irradiation modes (continuous and pulse-delay) led to different amounts of trapped free radicals. The analysis of cured samples (n = 3) by electron paramagnetic resonance (EPR) revealed that the concentrations of trapped free radicals significantly differed according to the curing protocol. When continuous modes with similar radiant exposure were compared, higher concentrations of trapped free radicals were measured for longer times with lower irradiance. Concerning pulse modes, the delay had no influence on trapped radical concentration. These results give new insights into the understanding of the photopolymerization process and highlight the relevance of using EPR when studying polymerization of dimethacrylate-based materials.
The Discovery of Surgical Anesthesia
Authors: López-Valverde A. , Montero J. , Albaladejo A. , Gómez de Diego R.
Published: October 2010

The suppression of pain during surgical interventions has been a major achievement for humankind. Chronologically, in 1842, William E. Clarke, a chemist in Rochester (NY), provided Elijah Pope with ether for the purposes of tooth extraction. In 1844, in Boston, G.Q. Colton and the dentist Horace Wells used nitrous oxide as an anesthetic for tooth extraction. On the 16th of October, 1846, the American dentist William T.G. Morton became a pioneer within the medical community with respect to anesthesia by inhalation when he used ether as an anesthetic at the Massachusetts General Hospital. In 1847, the Scot James Young Simpson began to use chloroform as an anesthetic for obstetrics in Edinburgh. These events gave rise to several disputes among their users (who are not very well-known today), who strove to claim that they had been the discoverers of surgical anesthesia, with a view to obtaining a series of patents and state sinecures. This article attempts to clarify certain discrepancies about the authorship of surgical anesthesia. The evidence suggests that surgical anesthesia first began to be applied in the field of dentistry.
Asymmetric Information, Entrepreneurial Activity, and the Scope of Fiscal Policy in an Open Regional Economy
Authors: Batabyal Amitrajeet A. , Nijkamp Peter
Published: October 2010

The authors analyze two hitherto little studied but salient questions concerning the trinity of asymmetric information, entrepreneurial activity, and the scope of fiscal policy in an open regional economy. First, the authors use a two-period model to analyze the contractual relationship between entrepreneurs and venture capitalists when the latter are located outside the region. Because there is moral hazard, venture capitalists do not offer entrepreneurs the first best investment contract and entrepreneurial activity is suboptimal. Second, they analyze a two-period model with venture capitalists who are now located inside the regional economy. They show that despite the existence of a credit market imperfection, because, inter alia, the regional authority (RA) does not have an informational advantage over the private sector, it is not possible for this RA to use fiscal policy to make a Pareto improving intervention in which some agents are better off and others are no worse off.
Thyroid functions in paints production workers and the mechanism of oxidative-antioxidants status
Authors: Saad-Hussein Amal , Hamdy Hanaa , Aziz Hisham M , Mahdy-Abdallah Heba
Published: October 2010

Assessment of occupational exposure to paints production chemicals mainly organic solvents in production of thyroid dysfunction and the mechanism of oxidative-antioxidant imbalance. Triiodothyronine (T3), thyroxine (T4), malondialdehyde (MDA), nitric oxide (NO) and total antioxidants was measured in 36 workers and 40 controls. T3 and T4 were elevated in 18.8% and 44.4% of the workers, respectively. T3, T4, MDA and NO levels were significantly higher in workers compared to controls. Total antioxidants was significantly lower in workers than in controls. T3 and T4 were significantly correlated with duration of exposure, while, total antioxidants was inversely correlated. In workers, T3 was significantly correlated with MDA and inversely correlated with total antioxidants levels. MDA and NO were significantly higher in workers with abnormal T 4 than normal workers. Workers exposed to organic solvents proved to be at risk for hyperthyroidism. Oxidative-antioxidant imbalance was found to have a significant role in development of hyperthyroidism with increasing duration of exposure.
Toward a Mentalistic Account of Early Psychological Reasoning
Authors: Luo Yuyan , Baillargeon Renée
Published: October 2010

Recent investigations of early psychological understanding have revealed three key findings. First, young infants attribute goals and dispositions to any entity they perceive as an agent, whether human or nonhuman. Second, when interpreting an agent’s actions in a scene, young infants take into account the agent’s representation of the scene, even if this representation is less complete than their own. Third, at least by the second year of life, infants recognize that agents can hold false beliefs about a scene. Together, these findings support a system-based, mentalistic account of early psychological reasoning.
Antecedents of Failure for Newly Chartered Banks in the U.S. Banking Industry
Authors: DeVaughn Michael L. , Leary Myleen M.
Published: October 2010

In the United States, newly chartered banks are subject to increased regulatory scrutiny during their early years of operation to ensure their long-term viability. As the record number of bank failures in 2009 has shown, this additional regulation does not guarantee success. To better understand the internal factors in this environment that result in organizational distress, an antecedent failure state, the authors focus on the group-level characteristics of the banks’ founding teams, specifically ownership concentration and four explicit types of founding experience. Using a sample of 129 banks based in Florida, they find that increased ownership concentration, prior industry experience, heterogeneous occupational experience and joint prior founding experience and prior shared experience decreases organizational distress. Their results provide direction on characteristics that may help firms avoid organizational distress.
The Institutional Mobility of Minority Members of Congress
Authors: Rocca Michael S. , Sanchez Gabriel R. , Morin Jason L.
Published: October 2010

This article examines the extent to which race and ethnicity affect mobility to leadership positions within Congress. The authors utilize survival analysis to examine the rate at which legislators attained committee leadership positions between the 101st and 108th Congresses. The results show that black legislators attain leadership positions faster than white legislators. This may be because of the tendency for black members of Congress (MCs) to sit on less prestigious committees than white MCs, which creates greater opportunity for institutional promotion. Ethnicity, on the other hand, does not matter to mobility as Latinos acquire leadership positions at the same rate as non-Latino legislators.
Impact of excitation signal upon the acceleration harmonic distortion of an electro-hydraulic shaking table
Authors: Yao Jian-Jun , Hu Sheng-Hai , Wei Fu  , Han Jun-Wei
Published: October 2010

The shaking table is an important experimental apparatus for mechanical environment tests. This work is focused on an electro-hydraulic shaking table, which has a single degree of freedom. Its configuration and working principle are described. A three-variable controller composed of feed-forward and feedback is applied to achieve iso-acceleration control. The acceleration excitation signal is filtered by an input filter to obtain input variables for the three-variable controller. From the sinusoidal shaking results, harmonic distortion exists in the acceleration response. The frequencies of harmonics are integer multiples of the fundamental frequency. Different harmonic distortion and harmonic distribution occur in the acceleration response excited by different acceleration excitation signals. The acceleration harmonic distortion is decreased as the amplitude and frequency of the excitation signal are increased.
Dynamic behavior of cable-stayed beam with localized damage
Authors: Zhu J. , Ye GR , Xiang YQ , Chen WQ
Published: October 2010

An elastic continuous model is presented for the inclined cable with damage which is described as reduction of the axial stiffness. The damage effect on the static configuration of the cable under self-weight is investigated through a numerical solution. Hamilton’s principle is then employed to derive the governing equations for the in-plane dynamic motion of the cable-stayed beam with cable damage. The linear eigenmodes are obtained via the method of reverberation-ray matrix after a standard condensation procedure. A single-degree-of-freedom nonlinear model is obtained by the single-mode discretization. The homotopy analysis method is then successfully applied to get the frequency-amplitude relationship, which enables the influence of cable damage on the nonlinear dynamic behavior of the system to be characterized.
Financing democracy in Japan: The allocation and consequences of government subsidies to political parties
Authors: Carlson Matthew
Published: October 2010

In 1994, the Japanese Diet implemented a system of public assistance for political parties which many hoped would encourage party-centred rather than candidate-centred campaigns. This study examines some of the consequences of this system for party organizations and politicians. Using data culled from official subsidy and campaign finance reports, two empirical questions are addressed: first, how has the advent of the subsidy affected the funds available to national party organizations and to individual politicians? Second, what are the factors that shape the allocation of the subsidy from national party organizations to party branches? It is argued that the subsidy has made it easier for party organizations to access funds but that the amounts of subsidies received by individual politicians are generally too small to alleviate much of their fund-raising pressures. In addition, party leaders have allocated the subsidy largely by following a principle of equality.
The Appreciation of the Spiritual in Mental Illness: A Qualitative Study of Beliefs Among Clergy in the UK
Authors: Leavey Gerard
Published: October 2010

Clergy in the UK continue to provide health and social care services. However, collaboration between mental health services and clergy may be problematic, particularly in the resolution of conflicting beliefs and therapeutic modalities. For example, belief in demonic possession and other supernatural causes of mental illness, which are contentious among secular medical practitioners, remain prevalent in many ethnoreligious communities. Thus, interpretations of illness by clergy within health systems may be crucial to appropriate intervention for people with mental illness. However, clergy conceptualizations of suffering also reveal something about the secularization within religious institutions through the despiritualization of particular phenomena. This paper on Christian clergy beliefs and attitudes to supernatural explanations, describes how the negotiation of such beliefs are complex and often equivocal among mainstream clergy but integral to the Pentecostal churches and evangelical clergy in the mainstream, institutional churches. These beliefs and their implications for collaboration with psychiatry are discussed in the context of a rapidly changing religious and cultural landscape.
Value-Sensitive Psychiatric Rehabilitation
Authors: Greenberg David , Kalian Moshe , Witztum Eliezer
Published: October 2010

Psychiatric rehabilitation contains value-laden concepts that may be unacceptable to certain cultures and many individuals. The concepts of independence and work are examined in a clash between mental health professionals in charge of national policies in psychiatric rehabilitation in Israel and a rehabilitation center for the severely mentally ill within the ultra-orthodox Jewish community. The government professionals considered that having the living quarters and work site in the same building deemed it unsuitable for rehabilitation, and too few progressed to independent living and working. As such, they ordered the center to be closed. Clients’ families turned to the Supreme Court and the claims and counter claims reveal value-laden positions. The bases for misunderstanding and lack of cooperation between the government professionals and the rehabilitation center are explained in the context of everyday life and values in the ultra-orthodox Jewish community and attitudes in the general population. Fruitful cooperation is based on appreciating core values, identifying and working with the community’s figures of authority, and accepting that the role of the mental health professional is to advise the community, within which the professional has no status.
Portrayal of the Slow Food movement in the Australian print media
Authors: Germov John , Williams Lauren , Freij Maria
Published: October 2010

The Slow Food movement promotes itself as supporting ethical modes of food production and consumption. This article reports on research that investigated the representations of the movement in the Australian print media, exploring the discourses relating to Slow Food and examining whether the media exposure is positively or negatively framed. A content and discourse analysis was undertaken of articles on Slow Food over a three-month period. The analysis aimed to provide a contextual basis for how Slow Food is perceived, the messages it conveys, and the activities it undertakes. Major themes arising from the data were ‘conviviality’ (social pleasures of sharing ‘good food’), ‘localism’ (social, health and environmental benefits of local produce), and ‘romanticism’ (of idyllic rural lifestyles as an antidote to the time-poverty of urban life). The findings shed light on the role played by the print media in reproducing and creating public understandings of the Slow Food movement.
Mapping the road to fun: Natural video game controllers, presence, and game enjoyment
Authors: Skalski Paul , Tamborini Ron , Shelton Ashleigh , Buncher Michael , Lindmark Pete
Published: October 2010

This investigation examines how video game interactivity can affect presence and game enjoyment. Interactivity in the form of natural mapping has been advocated as a possible contributor to presence experiences, yet few studies to date have investigated this potential. The present work formulates a preliminary typology of natural mapping and addresses how several types of mapping impact the experience of a video game, with the expectation that more natural mapping leads to increased spatial presence affecting enjoyment. Two studies were conducted. In the first study, 48 participants played a golfing video game using one of two controller types (Nintendo Wiimote or gamepad). In the second, 78 participants played a driving video game using an even more natural controller (steering wheel) or one of three other controller types. Participants then completed measures of perceived naturalness, presence, and enjoyment. Results of both studies were generally consistent with expectations.
The limits of peer production: Some reminders from Max Weber for the network society
Authors: Kreiss Daniel , Finn Megan , Turner Fred
Published: October 2010

In the last few years, a powerful consensus has emerged among scholars of digitally enabled peer production. In this view, digital technologies and social production processes are driving a dramatic democratization of culture and society. Moreover, leading scholars now suggest that these new, hyper-mediated modes of living and working are specifically challenging the hierarchical structures and concentrated power of bureaucracies. This paper first maps the assumptions underlying the new consensus on peer production so as to reveal the sources of its coherence. It then revisits Max Weber’s account of bureaucracy. With Weber in mind, the paper aims to expose analytical weaknesses in the consensus view and offer a new perspective from which to study contemporary digital media.
Stories of a public: Journalism and the validity of citizens’ testimonies
Authors: Kunelius Risto , Renvall Mika
Published: October 2010

One of the recurrent findings of journalism research has been that access to the news and public discussion is severely structurally limited. Elite speakers tend to appear as ‘primary definers’ while ordinary people play the subordinate role of ‘symbol people’. Less attention has been paid to how ‘ordinary people’ could be represented differently. This article offers a close reading of two journalistic experiments in which journalists tried to break this deadlock by allowing ordinary people to tell stories about their own experiences. In this way the ordinary people were able to participate seriously in a public debate. Habermas’ theory of communicative action is used in the article in order to show why this was possible.
Confusion, Cost, and Emotion Research
Authors: Landreth Anthony
Published: October 2010

The inferences that can be drawn from Izard’s article are unclear. Izard (2010) suggests that his data raise questions concerning inconsistencies, confusion, and costs in emotion research. I suggest that his data do not speak to the issues of confusion and costs, and that the choice of distinguished scientists may have been inappropriate to meet the goals of Izard’s study. Of course, questions concerning the efficiency of research in emotion studies are interesting. I describe more appropriate ways of addressing such issues.
Mantle cell lymphoma: biology, pathogenesis, and the molecular basis of treatment in the genomic era
Authors: Pérez-Galán Patricia , Dreyling Martin , Wiestner Adrian
Published: October 2010

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma of which at least a subset arises from antigen-experienced B cells. However, what role antigen stimulation plays in its pathogenesis remains ill defined. The genetic hallmark is the chromosomal translocation t(11;14) resulting in aberrant expression of cyclin D1. Secondary genetic events increase the oncogenic potential of cyclin D1 and frequently inactivate DNA damage response pathways. In combination these changes drive cell-cycle progression and give rise to pronounced genetic instability. Several signaling pathways contribute to MCL pathogenesis, including the often constitutively activated PI3K/AKT/mTOR pathway, which promotes tumor proliferation and survival. WNT, Hedgehog, and NF-κB pathways also appear to be important. Although MCL typically responds to frontline chemotherapy, it remains incurable with standard approaches. Proteasome inhibitors (bortezomib), mTOR inhibitors (temsirolimus), and immunomodulatory drugs (lenalidomide) have recently been added to the treatment options in MCL. The molecular basis for the antitumor activity of these agents is an area of intense study that hopefully will lead to further improvements in the near future. Given its unique biology, relative rarity, and the difficulty in achieving long-lasting remissions with conventional approaches, patients with MCL should be encouraged to participate in clinical trials.
A tick salivary protein targets cathepsin G and chymase and inhibits host inflammation and platelet aggregation
Authors: Chmelar Jindrich , Oliveira Carlo J. , Rezacova Pavlina , Francischetti Ivo M. B. , Kovarova Zuzana , Pejler Gunnar , Kopacek Peter , Ribeiro José M. C. , Mares Michael , Kopecky Jan , Kotsyfakis Michail
Published: October 2010

Platelet aggregation and acute inflammation are key processes in vertebrate defense to a skin injury. Recent studies uncovered the mediation of 2 serine proteases, cathepsin G and chymase, in both mechanisms. Working with a mouse model of acute inflammation, we revealed that an exogenous salivary protein of Ixodes ricinus, the vector of Lyme disease pathogens in Europe, extensively inhibits edema formation and influx of neutrophils in the inflamed tissue. We named this tick salivary gland secreted effector as I ricinus serpin-2 (IRS-2), and we show that it primarily inhibits cathepsin G and chymase, while in higher molar excess, it affects thrombin activity as well. The inhibitory specificity was explained using the crystal structure, determined at a resolution of 1.8 Å. Moreover, we disclosed the ability of IRS-2 to inhibit cathepsin G-induced and thrombin-induced platelet aggregation. For the first time, an ectoparasite protein is shown to exhibit such pharmacological effects and target specificity. The stringent specificity and biological activities of IRS-2 combined with the knowledge of its structure can be the basis for the development of future pharmaceutical applications.
Examination of the relationship between essential genes in PPI network and hub proteins in reverse nearest neighbor topology
Authors: Ning Kang , Ng Hoong Kee , Srihari Sriganesh , Leong Hon Wai , Nesvizhskii Alexey I
Published: October 2010

Background

In many protein-protein interaction (PPI) networks, densely connected hub proteins are more likely to be essential proteins. This is referred to as the "centrality-lethality rule", which indicates that the topological placement of a protein in PPI network is connected with its biological essentiality. Though such connections are observed in many PPI networks, the underlying topological properties for these connections are not yet clearly understood. Some suggested putative connections are the involvement of essential proteins in the maintenance of overall network connections, or that they play a role in essential protein clusters. In this work, we have attempted to examine the placement of essential proteins and the network topology from a different perspective by determining the correlation of protein essentiality and reverse nearest neighbor topology (RNN).

Results

The RNN topology is a weighted directed graph derived from PPI network, and it is a natural representation of the topological dependences between proteins within the PPI network. Similar to the original PPI network, we have observed that essential proteins tend to be hub proteins in RNN topology. Additionally, essential genes are enriched in clusters containing many hub proteins in RNN topology (RNN protein clusters). Based on these two properties of essential genes in RNN topology, we have proposed a new measure; the RNN cluster centrality. Results from a variety of PPI networks demonstrate that RNN cluster centrality outperforms other centrality measures with regard to the proportion of selected proteins that are essential proteins. We also investigated the biological importance of RNN clusters.

Conclusions

This study reveals that RNN cluster centrality provides the best correlation of protein essentiality and placement of proteins in PPI network. Additionally, merged RNN clusters were found to be topologically important in that essential proteins are significantly enriched in RNN clusters, and biologically important because they play an important role in many Gene Ontology (GO) processes.
Geoseq: a tool for dissecting deep-sequencing datasets
Authors: Gurtowski James , Cancio Anthony , Shah Hardik , Levovitz Chaya , George Ajish , Homann Robert , Sachidanandam Ravi
Published: October 2010

Background

Datasets generated on deep-sequencing platforms have been deposited in various public repositories such as the Gene Expression Omnibus (GEO), Sequence Read Archive (SRA) hosted by the NCBI, or the DNA Data Bank of Japan (ddbj). Despite being rich data sources, they have not been used much due to the difficulty in locating and analyzing datasets of interest.

Results

Geoseq http://geoseq.mssm.edu provides a new method of analyzing short reads from deep sequencing experiments. Instead of mapping the reads to reference genomes or sequences, Geoseq maps a reference sequence against the sequencing data. It is web-based, and holds pre-computed data from public libraries. The analysis reduces the input sequence to tiles and measures the coverage of each tile in a sequence library through the use of suffix arrays. The user can upload custom target sequences or use gene/miRNA names for the search and get back results as plots and spreadsheet files. Geoseq organizes the public sequencing data using a controlled vocabulary, allowing identification of relevant libraries by organism, tissue and type of experiment.

Conclusions

Analysis of small sets of sequences against deep-sequencing datasets, as well as identification of public datasets of interest, is simplified by Geoseq. We applied Geoseq to, a) identify differential isoform expression in mRNA-seq datasets, b) identify miRNAs (microRNAs) in libraries, and identify mature and star sequences in miRNAS and c) to identify potentially mis-annotated miRNAs. The ease of using Geoseq for these analyses suggests its utility and uniqueness as an analysis tool.
The evolution of vertebrate tetraspanins: gene loss, retention, and massive positive selection after whole genome duplications
Authors: Huang Shengfeng , Tian Haozheng , Chen Zelin , Yu Ting , Xu Anlong
Published: October 2010

Background

The vertebrate tetraspanin family has many features which make it suitable for preserving the imprint of ancient sequence evolution and amenable for phylogenomic analysis. So we believe that an in-depth analysis of the tetraspanin evolution not only provides more complete understanding of tetraspanin biology, but offers new insights into the influence of the two rounds of whole genome duplication (2R-WGD) at the origin of vertebrates.

Results

A detailed phylogeny of vertebrate tetraspanins was constructed by using multiple lines of information, including sequence-based phylogenetics, key structural features, intron configuration and genomic synteny. In particular, a total of 38 modern tetraspanin ortholog lineages in bony vertebrates have been identified and subsequently classified into 17 ancestral lineages existing before 2R-WGD. Based on this phylogeny, we found that the ohnolog retention rate of tetraspanins after 2R-WGD was three times as the average (a rate similar to those of transcription factors and protein kinases). This high rate didn't increase the tetrapanin family size, but changed the family composition, possibly by displacing vertebrate-specific gene lineages with the lineages conserved across deuterostomes. We also found that the period from 2R-WGD to recent time is controlled by gene losses. Meanwhile, positive selection has been detected on 80% of the branches right after 2R-WGDs, which declines significantly on both magnitude and extensity on the following speciation branches. Notably, the loss of mammalian RDS2 is accompanied by strong positive selection on mammalian ROM1, possibly due to gene loss-induced compensatory evolution.

Conclusions

First, different from transcription factors and kinases, high duplicate retention rate after 2R-WGD didn't increase the tetraspanin family size but just reshaped the family composition. Second, the evolution of tetraspanins right after 2R-WGD had been impacted by a massive wave of gene loss and positive selection on coding sequences. Third, the lingering effect of 2R-WGD on tetraspanin gene loss and positive selection might last for 300-400 million years.
Clostridium sticklandii, a specialist in amino acid degradation:revisiting its metabolism through its genome sequence
Authors: Fonknechten Nuria , Chaussonnerie Sébastien , Tricot Sabine , Lajus Aurélie , Andreesen Jan R , Perchat Nadia , Pelletier Eric , Gouyvenoux Michel , Barbe Valérie , Salanoubat Marcel , Le Paslier Denis , Weissenbach Jean , Cohen Georges N , Kreimeyer Annett
Published: October 2010

Background

Clostridium sticklandii belongs to a cluster of non-pathogenic proteolytic clostridia which utilize amino acids as carbon and energy sources. Isolated by T.C. Stadtman in 1954, it has been generally regarded as a "gold mine" for novel biochemical reactions and is used as a model organism for studying metabolic aspects such as the Stickland reaction, coenzyme-B12- and selenium-dependent reactions of amino acids. With the goal of revisiting its carbon, nitrogen, and energy metabolism, and comparing studies with other clostridia, its genome has been sequenced and analyzed.

Results

C. sticklandii is one of the best biochemically studied proteolytic clostridial species. Useful additional information has been obtained from the sequencing and annotation of its genome, which is presented in this paper. Besides, experimental procedures reveal that C. sticklandii degrades amino acids in a preferential and sequential way. The organism prefers threonine, arginine, serine, cysteine, proline, and glycine, whereas glutamate, aspartate and alanine are excreted. Energy conservation is primarily obtained by substrate-level phosphorylation in fermentative pathways. The reactions catalyzed by different ferredoxin oxidoreductases and the exergonic NADH-dependent reduction of crotonyl-CoA point to a possible chemiosmotic energy conservation via the Rnf complex. C. sticklandii possesses both the F-type and V-type ATPases. The discovery of an as yet unrecognized selenoprotein in the D-proline reductase operon suggests a more detailed mechanism for NADH-dependent D-proline reduction. A rather unusual metabolic feature is the presence of genes for all the enzymes involved in two different CO2-fixation pathways: C. sticklandii harbours both the glycine synthase/glycine reductase and the Wood-Ljungdahl pathways. This unusual pathway combination has retrospectively been observed in only four other sequenced microorganisms.

Conclusions

Analysis of the C. sticklandii genome and additional experimental procedures have improved our understanding of anaerobic amino acid degradation. Several specific metabolic features have been detected, some of which are very unusual for anaerobic fermenting bacteria. Comparative genomics has provided the opportunity to study the lifestyle of pathogenic and non-pathogenic clostridial species as well as to elucidate the difference in metabolic features between clostridia and other anaerobes.
Genome-wide expression patterns in physiological cardiac hypertrophy
Authors: Drozdov Ignat , Tsoka Sophia , Ouzounis Christos A , Shah Ajay M
Published: October 2010

Background

Physiological left ventricular hypertrophy (LVH) involves complex cardiac remodeling that occurs as an adaptive response to chronic exercise. A stark clinical contrast exists between physiological LVH and pathological cardiac remodeling in response to diseases such as hypertension, but little is known about the precise molecular mechanisms driving physiological adaptation.

Results

In this study, the first large-scale analysis of publicly available genome-wide expression data of several in vivo murine models of physiological LVH was carried out using network analysis. On evaluating 3 million gene co-expression patterns across 141 relevant microarray experiments, it was found that physiological adaptation is an evolutionarily conserved processes involving preservation of the function of cytochrome c oxidase, induction of autophagy compatible with cell survival, and coordinated regulation of angiogenesis.

Conclusion

This analysis not only identifies known biological pathways involved in physiological LVH, but also offers novel insights into the molecular basis of this phenotype by identifying key networks of co-expressed genes, as well as their topological and functional properties, using relevant high-quality microarray experiments and network inference.
Light intensity affects RNA silencing of a transgene in Nicotiana benthamianaplants
Authors: Kotakis Christos , Vrettos Nicholas , Kotsis Dimitrios , Tsagris Mina , Kotzabasis Kiriakos , Kalantidis Kriton
Published: October 2010

Background

Expression of exogenous sequences in plants is often suppressed through one of the earliest described RNA silencing pathways, sense post-transcriptional gene silencing (S-PTGS). This type of suppression has made significant contributions to our knowledge of the biology of RNA silencing pathways and has important consequences in plant transgenesis applications. Although significant progress has been made in recent years, factors affecting the stability of transgene expression are still not well understood. It has been shown before that the efficiency of RNA silencing in plants is influenced by various environmental factors.

Results

Here we report that a major environmental factor, light intensity, significantly affects the induction and systemic spread of S-PTGS. Moreover, we show that photoadaptation to high or low light intensity conditions differentially affects mRNA levels of major components of the RNA silencing machinery.

Conclusions

Light intensity is one of the previously unknown factors that affect transgene stability at the post-transcriptional level. Our findings demonstrate an example of how environmental conditions could affect RNA silencing.
Peroxiredoxin 2: a potential biomarker for early diagnosis of Hepatitis B Virus related liver fibrosis identified by proteomic analysis of the plasma
Authors: Lu Ye , Liu Jie , Lin Chengzhao , Wang Haijian , Jiang Ying , Wang Jiyao , Yang Pengyuan , He Fuchu
Published: October 2010

Background

Liver fibrosis is a middle stage in the course of chronic Hepatitis B virus (HBV) infection, which will develop into cirrhosis and eventually hepatocellular carcinoma (HCC) if not treated at the early stage. Considering the limitations and patients' reluctance to undergo liver biopsy, a reliable, noninvasive diagnostic system to predict and assess treatment and prognosis of liver fibrosis is needed. The aim of this study was to identify biomarkers for early diagnosis of HBV related liver fibrosis.

Method

Plasma samples from 7 healthy volunteers and 27 HBV infected patients with different stages of fibrosis were selected for 2-DIGE proteomic screening. One-way ANOVA analysis was used to assess differences in protein expression among all groups. The alteration was further confirmed by western blotting. Plasma levels of 25 serological variables in 42 healthy volunteers and 68 patients were measured to establish a decision tree for the detection of various stages fibrosis.

Result

The up-regulated proteins along with fibrosis progress included fibrinogen, collagen, macroglobulin, hemopexin, antitrypsin, prealbumin and thioredoxin peroxidase. The down-regulated proteins included haptoglobin, serotransferrin, CD5 antigen like protein, clusterin, apolipoprotein and leucine-rich alpha-2-glycoprotein. For the discrimination of milder stage fibrosis, the area under curve for Prx II was the highest. Four variables (PT, Pre, HA and Prx II) were selected from the 25 variables to construct the decision tree. In a training group, the correct prediction percentage for normal control, milder fibrosis, significant fibrosis and early cirrhosis was 100%, 88.9%, 95.2% and 100%, respectively, with an overall correct percent of 95.9%.

Conclusion

This study showed that 2-D DIGE-based proteomic analysis of the plasma was helpful in screening for new plasma biomarkers for liver disease. The significant up-expression of Prx II could be used in the early diagnosis of HBV related liver fibrosis.
Suggestive evidence of associations between liver X receptor β polymorphisms with type 2 diabetes mellitus and obesity in three cohort studies: HUNT2 (Norway), MONICA (France) and HELENA (Europe)
Authors: Solaas Karianne , Legry Vanessa , Retterstol Kjetil , Berg Paul R , Holven Kirsten B , Ferrières Jean , Amouyel Philippe , Lien Sigbjorn , Romeo Javier , Valtueña Jara , Widhalm Kurt , Ruiz Jonatan R , Dallongeville Jean , Tonstad Serena , Rootwelt Helge , Halvorsen Bente , Nenseter Marit S , Birkeland Kare I , Thorsby Per M , Meirhaeghe Aline , Nebb Hilde I
Published: October 2010

Background

The liver X receptors (LXR) α and β regulate lipid and carbohydrate homeostasis and inflammation. Lxrβ

-/-
mice are glucose intolerant and at the same time lean. We aimed to assess the associations between single nucleotide polymorphisms (SNPs) in LXRβ and risk of type 2 diabetes mellitus (T2DM), obesity and related traits in 3 separate cohort studies.

Methods

Twenty LXRβ SNPs were identified by sequencing and genotyped in the HUNT2 adult nested case-control study for T2DM (n = 835 cases/1986 controls). Five tag-SNPs (rs17373080, rs2695121, rs56151148, rs2303044 and rs3219281), covering 99.3% of the entire common genetic variability of the LXRβ gene were identified and genotyped in the French MONICA adult study (n = 2318) and the European adolescent HELENA cross-sectional study (n = 1144). In silico and in vitro functionality studies were performed.

Results

We identified suggestive or significant associations between rs17373080 and the risk of (i) T2DM in HUNT2 (OR = 0.82, p = 0.03), (ii) obesity in MONICA (OR = 1.26, p = 0.05) and (iii) overweight/obesity in HELENA (OR = 1.59, p = 0.002). An intron 4 SNP (rs28514894, a perfect proxy for rs17373080) could potentially create binding sites for hepatic nuclear factor 4 alpha (HNF4α) and nuclear factor 1 (NF1). The C allele of rs28514894 was associated with ~1.25-fold higher human LXRβ basal promoter activity in vitro. However, no differences between alleles in terms of DNA binding and reporter gene transactivation by HNF4α or NF1 were observed.

Conclusions

Our results suggest that rs17373080 in LXRβ is associated with T2DM and obesity, maybe via altered LXRβ expression.