bluuebunny/crossref_metadata_2025 huggingface dataset:
Rho directs widespread termination of intragenic and stable RNA transcription
Authors: Peters Jason M. , Mooney Rachel A. , Kuan Pei Fen , Rowland Jennifer L. , Keleş Sündüz , Landick Robert
Published: August 2009

The transcription termination factor Rho is a global regulator of RNA polymerase (RNAP). Although individual Rho-dependent terminators have been studied extensively, less is known about the sites of RNAP regulation by Rho on a genome-wide scale. Using chromatin immunoprecipitation and microarrays (ChIP-chip), we examined changes in the distribution of
Escherichia coli
RNAP in response to the Rho-specific inhibitor bicyclomycin (BCM). We found ≈200 Rho-terminated loci that were divided evenly into 2 classes: intergenic (at the ends of genes) and intragenic (within genes). The intergenic class contained noncoding RNAs such as small RNAs (sRNAs) and transfer RNAs (tRNAs), establishing a previously unappreciated role of Rho in termination of stable RNA synthesis. The intragenic class of terminators included a previously uncharacterized set of short antisense transcripts, as judged by a shift in the distribution of RNAP in BCM-treated cells that was opposite to the direction of the corresponding gene. These Rho-terminated antisense transcripts point to a role of noncoding transcription in
E. coli
gene regulation that may resemble the ubiquitous noncoding transcription recently found to play myriad roles in eukaryotic gene regulation.
Regulation of endosomal membrane traffic by a Gadkin/AP-1/kinesin KIF5 complex
Authors: Schmidt Michael R. , Maritzen Tanja , Kukhtina Viktoria , Higman Victoria A. , Doglio Laura , Barak Naomi N. , Strauss Holger , Oschkinat Hartmut , Dotti Carlos G. , Haucke Volker
Published: August 2009

Endosomes and endosomal vesicles (EVs) rapidly move along cytoskeletal filaments allowing them to exchange proteins and lipids between different endosomal compartments, lysosomes, the trans-Golgi network (TGN), and the plasma membrane. The precise mechanisms that connect membrane traffic between the TGN and perinuclear endosomal compartments with motor-protein driven transport have largely remained elusive. Here we show that Gadkin (also termed γ-BAR), a peripheral membrane protein localized to the TGN and to TGN-derived EVs, directly associates with the clathrin adaptor AP-1 and with the motor protein kinesin KIF5, thereby potentially regulating EV dynamics. Gadkin overexpression induced the dispersion of transferrin (Tf)- and Rab4-positive EVs to the cell periphery, whereas KIF5B-depleted cells displayed a perinuclear concentration. Functional experiments suggest that the role of Gadkin as a regulator of endosomal membrane traffic critically depends on complex formation with both AP-1 and KIF5. Our data thus provide a direct molecular link between TGN-derived EVs and the microtubule-based cytoskeleton.
Glut9 is a major regulator of urate homeostasis and its genetic inactivation induces hyperuricosuria and urate nephropathy
Authors: Preitner Frédéric , Bonny Olivier , Laverrière Alexandra , Rotman Samuel , Firsov Dmitri , Da Costa Anabela , Metref Salima , Thorens Bernard
Published: August 2009

Elevated plasma urate levels are associated with metabolic, cardiovascular, and renal diseases. Urate may also form crystals, which can be deposited in joints causing gout and in kidney tubules inducing nephrolithiasis. In mice, plasma urate levels are controlled by hepatic breakdown, as well as, by incompletely understood renal processes of reabsorption and secretion. Here, we investigated the role of the recently identified urate transporter, Glut9, in the physiological control of urate homeostasis using mice with systemic or liver-specific inactivation of the
Glut9
gene. We show that Glut9 is expressed in the basolateral membrane of hepatocytes and in both apical and basolateral membranes of the distal nephron. Mice with systemic knockout of
Glut9
display moderate hyperuricemia, massive hyperuricosuria, and an early-onset nephropathy, characterized by obstructive lithiasis, tubulointerstitial inflammation, and progressive inflammatory fibrosis of the cortex, as well as, mild renal insufficiency. In contrast, liver-specific inactivation of the
Glut9
gene in adult mice leads to severe hyperuricemia and hyperuricosuria, in the absence of urate nephropathy or any structural abnormality of the kidney. Together, our data show that Glut9 plays a major role in urate homeostasis by its dual role in urate handling in the kidney and uptake in the liver.
Evolutionary limits ameliorate the negative impact of an invasive plant
Authors: Lankau Richard A. , Nuzzo Victoria , Spyreas Greg , Davis Adam S.
Published: August 2009

Invasive species can quickly transform biological communities due to their high abundance and strong impacts on native species, in part because they can be released from the ecological forces that limit native populations. However, little is known about the long-term dynamics of invasions; do invaders maintain their dominant status over long time spans, or do new ecological and evolutionary forces eventually develop to limit their populations?Alliaria petiolatais a Eurasian species that aggressively invades North American forest understories, in part due to the production of toxic phytochemicals. Here we document a marked decline in its phytotoxin production and a consequent decline in their impact on three native species, across a 50+ year chronosequence ofAlliaria petiolatainvasion. Genetic evidence suggests that these patterns result from natural selection for decreased phytotoxin production rather than founder effects during introduction and spread. These patterns are consistent with the finding of slowingA. petiolatapopulation growth and rebounding native species abundance across a separate chronosequence in Illinois, U.S. These results suggest that this invader is developing evolutionary limits in its introduced range and highlight the importance of understanding the long-term processes that shape species invasions and their impacts.
STIM1 and calmodulin interact with Orai1 to induce Ca
2+
-dependent inactivation of CRAC channels
Authors: Mullins Franklin M. , Park Chan Young , Dolmetsch Ricardo E. , Lewis Richard S.
Published: August 2009

Ca
2+
-dependent inactivation (CDI) is a key regulator and hallmark of the Ca
2+
release-activated Ca
2+
(CRAC) channel, a prototypic store-operated Ca
2+
channel. Although the roles of the endoplasmic reticulum Ca
2+
sensor STIM1 and the channel subunit Orai1 in CRAC channel activation are becoming well understood, the molecular basis of CDI remains unclear. Recently, we defined a minimal CRAC activation domain (CAD; residues 342–448) that binds directly to Orai1 to activate the channel. Surprisingly, CAD-induced CRAC currents lack fast inactivation, revealing a critical role for STIM1 in this gating process. Through truncations of full-length STIM1, we identified a short domain (residues 470–491) C-terminal to CAD that is required for CDI. This domain contains a cluster of 7 acidic amino acids between residues 475 and 483. Neutralization of aspartate or glutamate pairs in this region either reduced or enhanced CDI, whereas the combined neutralization of six acidic residues eliminated inactivation entirely. Based on bioinformatics predictions of a calmodulin (CaM) binding site on Orai1, we also investigated a role for CaM in CDI. We identified a membrane-proximal N-terminal domain of Orai1 (residues 68–91) that binds CaM in a Ca
2+
-dependent manner and mutations that eliminate CaM binding abrogate CDI. These studies identify novel structural elements of STIM1 and Orai1 that are required for CDI and support a model in which CaM acts in concert with STIM1 and the N terminus of Orai1 to evoke rapid CRAC channel inactivation.
Honey bee aggression supports a link between gene regulation and behavioral evolution
Authors: Alaux Cédric , Sinha Saurabh , Hasadsri Linda , Hunt Greg J. , Guzmán-Novoa Ernesto , DeGrandi-Hoffman Gloria , Uribe-Rubio José Luis , Southey Bruce R. , Rodriguez-Zas Sandra , Robinson Gene E.
Published: August 2009

A prominent theory states that animal phenotypes arise by evolutionary changes in gene regulation, but the extent to which this theory holds true for behavioral evolution is not known. Because “nature and nurture” are now understood to involve hereditary and environmental influences on gene expression, we studied whether environmental influences on a behavioral phenotype, i.e., aggression, could have evolved into inherited differences via changes in gene expression. Here, with microarray analysis of honey bees, we show that aggression-related genes with inherited patterns of brain expression are also environmentally regulated. There were expression differences in the brain for hundreds of genes between the highly aggressive Africanized honey bee compared with European honey bee (EHB) subspecies. Similar results were obtained for EHB in response to exposure to alarm pheromone (which provokes aggression) and when comparing old and young bees (aggressive tendencies increase with age). There was significant overlap of the gene lists generated from these three microarray experiments. Moreover, there was statistical enrichment of several of the same
cis
regulatory motifs in promoters of genes on all three gene lists. Aggression shows a remarkably robust brain molecular signature regardless of whether it occurs because of inherited, age-related, or environmental (social) factors. It appears that one element in the evolution of different degrees of aggressive behavior in honey bees involved changes in regulation of genes that mediate the response to alarm pheromone.
The inverse and direct Hofmeister series for lysozyme
Authors: Zhang Yanjie , Cremer Paul S.
Published: August 2009

Anion effects on the cloud-point temperature for the liquid−liquid phase transition of lysozyme were investigated by temperature gradient microfluidics under a dark field microscope. It was found that protein aggregation in salt solutions followed 2 distinct Hofmeister series depending on salt concentration. Namely, under low salt conditions the association of anions with the positively charged lysozyme surface dominated the process and the phase transition temperature followed an inverse Hofmeister series. This inverse series could be directly correlated to the size and hydration thermodynamics of the anions. At higher salt concentrations, the liquid–liquid phase transition displayed a direct Hofmeister series that correlated with the polarizability of the anions. A simple model was derived to take both charge screening and surface tension effects into account at the protein/water interface. Fitting the thermodynamic data to this model equation demonstrated its validity in both the high and low salt regimes. These results suggest that in general positively charged macromolecular systems should show inverse Hofmeister behavior only at relatively low salt concentrations, but revert to a direct Hofmeister series as the salt concentration is increased.
The Transnational Ethnic Activism of Vojvodina Hungarians
Authors: Hagan Margaret Darin
Published: August 2009

Serbia's ethnic Hungarian minority, concentrated in the northern province of Vojvodina, is little known compared to other ethnic minorities in the Balkans. Unlike Kosovo Albanians, Bosnian Muslims, Bosnian Serbs, and Croatian Serbs, the Vojvodina Hungarians were not involved in violent conflict during Yugoslavia's disintegration of the 1990s. The Hungarian minority is not without its grievances or its political demands, however. Over the past two decades, Vojvodina Hungarians have organized a campaign for greater cultural accommodation and political autonomy for their community. They argue that the province as a whole has lost most of its meaningful autonomous powers, that the Hungarian minority does not have adequate political representation and cultural institutions, and that the state does not fully protect the minority from growing threats of ethnic violence and discrimination. The minority's campaign directs most of its appeals to the Belgrade authorities, but increasingly it looks beyond Serbia's borders for support as well. Especially when the Serbian government appears hostile or indifferent to their appeals, the Vojvodina Hungarians look to make alliances with foreign actors, including the Hungarian government, the US government, EU institutions, and assorted other media outlets and NGOs. The minority leaders expect that by sending these foreign actors accounts of the human rights abuses that Vojvodina Hungarians suffer, they will ally themselves with the campaign and pressure the Serbian authorities to compromise with its demands.
“Thugs with Guns”: Disaggregating “Ethnic Violence” in the Russian Federation
Authors: Arnold Richard
Published: August 2009

How can one understand the phenomenon known as “ethnic violence?” Does subsuming events under the category “ethnic violence” assist our understanding or does it obscure it? Are there lessons that theformethnic violence takes can teach us? These questions are important not only for anyone interested in the causes and prevention of ethnic violence but also for those who wish to understand group behavior more generally. I explore this question more fully through analysis of the case of the Russian Federation. Russia is a country where in recent times skinhead violence against ethnic minorities has become an important issue. According to Tarasov, Russia contains between 60,000 and 65,000 skinheads active in at least 85 different cities. These skinheads daily commit appalling acts of violence against members of ethnic minorities and human rights activists. Three instances of violence all from the year 2006 help to illustrate some of their activities.
Narratives of Victims and Villains in Kosovo
Authors: Zdravković-Zonta Helena
Published: August 2009

This article uses ideological criticism to examine how and why victimage, identity and nationalism are produced through everyday discursive practices of Serbs and Albanians in Kosovo. Wander contends that the ideological turn in criticism confronts and studies what is professed and obscure, and Greene argues that part of this criticism involves unmasking forms of domination. Examining cultural or rhetorical narratives is part of ideological criticism. The narratives in this study can be regarded as competing vernacular memories representative of Serbs and Albanians in Kosovo. The participants invoke personal and collective memories with official national histories to explain contemporary victimization as a continuance of historical victimage. This use of the past can serve to legitimize their national and political claims, as well as to justify violence against the other group, since historical victimage provides a rationale for hating the other group and perpetuating a vicious cycle of violence.
The Role of Networks in Tajikistan's Civil War: Network Activation and Violence Specialists*
Authors: Kılavuz İdil Tunçer
Published: August 2009

This article identifies the dynamics which shaped the eruption of civil war in Tajikistan. It argues that the mechanisms of network activation by the elites, together with the establishment of local militias and their involvement in the war through the activation of violence specialists, were important factors in bringing about the eruption of violence. This article is not about the causes of the civil war. Its aim is not to answer the question of why, but the question of how: what mechanisms led Tajikistan into civil war, how networks were activated from the top down, how mobilization was achieved at the micro level in the villages. This article stresses both macro- and micro-level mechanisms, and argues that there is a connection between the two—a look at both is necessary to understand the dynamics of the war.
Liver vessel enhancement by gd-bopta and gd-eob-dtpa: a comparison in healthy volunteers
Authors: Brismar T. B. , Dahlström N. , Edsborg N. , Persson A. , Smedby Ö. , Albiin N.
Published: August 2009

Background: A thorough understanding of magnetic resonance (MR) contrast media dynamics makes it possible to choose the optimal contrast media for each investigation. Differences in visualizing hepatobiliary function between Gd-BOPTA and Gd-EOB-DTPA have previously been demonstrated, but less has been published regarding differences in liver vessel visualization.

Purpose: To compare the liver vessel and liver parenchymal enhancement dynamics of Gd-BOPTA (MultiHance) and Gd-EOB-DTPA (Primovist).

Material and Methods: The signal intensity of the liver parenchyma, the common hepatic artery, the middle hepatic vein, and a segmental branch of the right portal vein was obtained in 10 healthy volunteers before contrast media administration, during arterial and portal venous phases, and 10, 20, 30, 40, and 130 min after intravenous contrast medium injection, but, due to scanner limitations, not during the hepatic venous phase. The doses of contrast media were 0.1 mmol/kg for Gd-BOPTA and 0.025 mmol/kg for Gd-EOB-DTPA.

Results: Maximum enhancement of liver parenchyma was observed from the portal venous phase until 130 min after Gd-BOPTA administration and from 10 min to 40 min after Gd-EOB-DTPA. There was no difference in maximum enhancement of liver parenchyma between the two contrast media. When using Gd-BOPTA, the vascular contrast enhancement was still apparent 40 min after injection, but had vanished 10 min after Gd-EOB-DTPA injection. The maximum difference in signal intensity between the vessels and the liver parenchyma was significantly greater with Gd-BOPTA than with Gd-EOB-DTPA ( P<0.0001).

Conclusion: At the dosage used in this study, Gd-BOPTA yields higher maximum enhancement of the hepatic artery, portal vein, and middle hepatic vein during the arterial and the portal venous phase and during the delayed phases than Gd-EOB-DTPA does, whereas there is no difference in liver parenchymal enhancement between the two contrast agents.
The Competitive Process in the Age of the Internet
Authors: Earl Peter E. , Mandeville Tom
Published: August 2009

This paper examines some of the impacts of the widespread adoption and use of the Internet in advanced countries on business, consumers and the media. It is argued that while capital costs of entry into Internet‐based businesses may be very low, this does not guarantee that markets in which such firms operate will necessarily be hotly contested, for success may require substantial sunk costs to be incurred in development. It explores the changing nature of market institutions associated with the rise of e‐commerce (including the advent of what are labelled ‘portal’ firms) and associated changes in the division of labour between buyers, sellers and intermediaries. The authors provide behavioural, evolutionary, and information theoretic perspectives on these dynamic issues.
Top‐Down e‐Infrastructure Meets Bottom‐Up Research Innovation: The Social Shaping of e‐Research
Authors: Meyer Eric T. , Dutton William H.
Published: August 2009

Are advances in ICTs enabling positive transformations in academic research practices? This paper explores key themes emerging from a 2008 survey of researchers aimed at identifying use and non‐use of advanced ICTs for research. Deterministic perspectives on e‐Research suggest that new e‐infrastructures will reshape research in predictable ways, such as by fostering more collaboration. In contrast, social shaping perspectives lead to the expectation that existing practices and institutions will shape the ways in which e‐Research is employed. This exploratory study found that individual variations across researchers cluster into identifiable groupings of research practices, which help to illuminate involvement in e‐Research, and differences in methods and research software used across the disciplines. In line with a social shaping perspective, the findings suggest that, in the social sciences, top‐down visions of e‐infrastructure development need to be tied to the realities of bottom‐up patterns of innovation in approaches to e‐Research.
A Socio‐cognitive Perspective of Industry Innovation Initiatives
Authors: Sneddon Joanne , Soutar Geoffrey , Mazzarol Tim
Published: August 2009

This article contributes to the emerging theory of industry belief systems and the social construction of innovation by examining how industry actors conceptualise and negotiate industry transformation through the development and diffusion of new technologies. In a qualitative study of innovation in the Australian wool industry, we found that the social construction of industry belief systems and new technologies was an evolutionary process of social sensemaking in which there was reciprocity between individual and collective meaning‐making that reflected conflict, consensus and compliance between industry actors about new technologies and industry beliefs.
Identifying the History and Logic of Negative, Ambivalent, and Positive Responses to Literature: A Case-Study Analysis of Cultural Models
Authors: Thein Amanda Haertling
Published: August 2009

This paper begins with the assumption that the interpretive practices people acquire in social worlds often transfer to their stances toward and interpretations of worlds encountered in literature (Beach, Thein, & Parks, 2007). The goal of this paper is to identify the history and logic behind one student's negative, ambivalent, and positive responses to classroom texts. This paper joins socio-cultural theories of response to literature (Galda & Beach, 2001) with theories of identity (Holland, Lachicotte, Skinner, & Cain, 2002) and cultural models (Gee, 1999) to understand the social and cultural history that this student, Molly, drew upon in her interpretations of texts. More specifically, this paper examines Molly's interpretations of her lived-worlds and the worlds of texts that she read outside of class as locations for investigating social and cultural practices that were relevant to her. This paper develops a case study that looks closely at the cultural models (Gee, 1996, 1999, 2004) that Molly drew upon in her interpretations of her lived-worlds and worlds of texts she read outside of class in order to better understand how social and cultural practices and beliefs mediated her responses to classroom literature. Findings from this study suggest that teaching students to identify, acknowledge, and value the stances that they bring with them to the classroom, while at the same time teaching them to understand the usefulness of other theories for interpreting texts, has the potential to engage students in more critical and thorough interpretations of literature.
Profiles of Reading Motivation among African American and Caucasian Students
Authors: Guthrie John T. , Coddington Cassandra S. , Wigfield Allan
Published: August 2009

Previous research has investigated motivations for reading by examining positive or affirming motivations, including intrinsic motivation and self-efficacy. Related to them, we examined two negative, or undermining, motivations consisting of avoidance and perceived difficulty. We proposed that the motivations of intrinsic motivation and avoidance are relatively independent and thus can be combined to form meaningful profiles consisting of avid, ambivalent, apathetic, and averse readers. With Grade 5 students we found that these motivations were relatively independent for both Caucasian and African American students. The two motivations uniquely explained a significant proportion of variance in reading comprehension and other cognitive reading variables. Although intrinsic motivation correlated higher with achievement than avoidance for Caucasians, avoidance correlated higher with achievement than intrinsic motivation for African Americans. For both groups, the profile of avid readers showed higher reading achievement than the other profiles.
Applying Social Marketing in the Development of a Volunteer Program
Authors: Boehm Amnon
Published: August 2009

This article asserts that social marketing may be effective in programs that are concerned with volunteering. A short review of the central elements of the social marketing approach and discussion of their application in the area of volunteering is followed by a description of a program based on this approach for recruiting volunteers. The results of the program, which was implemented in Israel, support the development of additional programs for marketing volunteering. The article discusses the main contributions of the social marketing approach in this area, related dilemmas, and the administrative measures necessary for designing a marketing approach specifically for volunteer recruitment.
“Get Firefighters Moving”: Marketing a Physical Fitness Intervention to Reduce Sudden Cardiac Death Risk in Full-Time Firefighters
Authors: Staley John A.
Published: August 2009

Firefighters as an occupational group are at increased risk for a cardiac-related injury, with the largest proportion (44%) of firefighter on-duty mortality due to sudden cardiac death. As poor physical fitness behaviors are a contributing factor to this risk, a social marketing approach was used to design and market a competitive team-sports intervention to improve physical fitness and reduce cardiac risk factors in a group of full-time firefighters. This article describes how social marketing principles were used in the design and implementation of the “Get Firefighters Moving” physical fitness intervention. This includes strategic development of the marketing plan, with discussion of audience segmentation and the marketing mix used to implement the intervention. Preliminary findings are also presented, as they suggest improvement in cardiac risk factors including blood pressure, cardiovascular class, flexibility, and percent body fat.
Strategic Social Marketing in Canada: Ten Phases to Planning and Implementing Cancer Prevention and Cancer Screening Campaigns
Authors: Dooley Jennifer Allyson , Jones Sandra C. , Desmarais Kendra
Published: August 2009

Social marketing has gained prominence among researchers and practitioners working in social issues. Campaigns labelled as social marketing are implemented worldwide by governments, nonprofit organizations, and private industry. However, there is evidence that the concepts and processes associated with these campaigns are misunderstood and not consistently applied. This article describes social marketing benchmark criteria and follows with an overview of a strategic process for social marketing, specifically: planning, research, campaign development, implementation, monitoring, and evaluation. The main focus is the social marketing development process undertaken by the Alberta Health Services to plan and implement cancer prevention and cancer screening campaigns. Unique to this process is an internationally recognized panel of social marketing experts to review and provide consultation. Improvements in planning and implementing campaigns are outlined, including stakeholder engagement, use of audience-centred strategies, and endorsement of campaigns by management. The primary outcome of bringing together a clear and organized social marketing tool for cancer prevention and cancer screening in Alberta is the development, implementation, and evaluation of campaigns that follow a systematic best-practice process. The learnings from this process will have important implications provincially in Alberta, nationally in Canada, and worldwide for the advancement of the social marketing discipline.
Implementing a Community-Based Social Marketing Program to Increase Recycling
Authors: Haldeman Tracey , Turner Jeanine Warisse
Published: August 2009

This article examines the effectiveness of implementing a community-based social marketing program to increase recycling. Researchers went door-to-door in a 200-home community distributing recycling containers, securing commitments to recycle, and increasing knowledge of what, why, how, and when to recycle. We analyzed the effect of the program by weighing recycling collected immediately after program implementation and then analyzing the weight of recycling collected a number of months later to measure sustainability. We found that automatic curbside distribution of recycling containers and face-to-face contact have a sizable, and partially sustainable, positive effect on the rate of recycling. Based on the results, we propose practical implications for motivating increased recycling.
Can Environmental Promotion Backfire? Evidence from the Vehicle Market
Authors: Teisl Mario F. , Noblet Caroline L. , Rubin Jonathan
Published: August 2009

Several studies document the potential for eco-labeling and marketing programs; however, they focused on inexpensive, frequently purchased items. We identify whether such programs can be effective with more expensive, durable goods. We isolate the impact of the program on consumers by analyzing responses to a survey administered before and after the program to independent samples of individuals residing in and out of the marketing area. We used both multivariate analysis of variance and regression approaches in the analyses. Few vehicle dealers participated in the eco-labeling portion and we find the eco-marketing component of the program led to only one positive outcome; individuals exposed to the marketing are less likely to think all vehicles pollute about the same when driven. This was one of the key misperceptions that the Maine Clean Car Campaign attempted to correct. However, we also found three negative impacts of the Campaign. Individuals exposed to the marketing viewed vehicle emissions as being a smaller contributor to Maine's air quality problems and had an increased perception that greener vehicles suffered from poor performance and were more expensive.

[Supplementary materials are available for this article. Go to the publisher's online edition of Social Marketing Quarterly for the following free supplemental resources: results of data analyses.]
A boosting approach to structure learning of graphs with and without prior knowledge
Authors: Anjum Shahzia , Doucet Arnaud , Holmes Chris C.
Published: August 2009

Motivation: Identifying the network structure through which genes and their products interact can help to elucidate normal cell physiology as well as the genetic architecture of pathological phenotypes. Recently, a number of gene network inference tools have appeared based on Gaussian graphical model representations. Following this, we introduce a novel Boosting approach to learn the structure of a high-dimensional Gaussian graphical model motivated by the applications in genomics. A particular emphasis is paid to the inclusion of partial prior knowledge on the structure of the graph. With the increasing availability of pathway information and large-scale gene expression datasets, we believe that conditioning on prior knowledge will be an important aspect in raising the statistical power of structural learning algorithms to infer true conditional dependencies.

Results: Our Boosting approach, termed BoostiGraph, is conceptually and algorithmically simple. It complements recent work on the network inference problem based on Lasso-type approaches. BoostiGraph is computationally cheap and is applicable to very high-dimensional graphs. For example, on graphs of order 5000 nodes, it is able to map out paths for the conditional independence structure in few minutes. Using computer simulations, we investigate the ability of our method with and without prior information to infer Gaussian graphical models from artificial as well as actual microarray datasets. The experimental results demonstrate that, using our method, it is possible to recover the true network topology with relatively high accuracy.

Availability: This method and all other associated files are freely available from http://www.stats.ox.ac.uk/∼anjum/.

Contact:  s.anjum@har.mrc.ac.uk; cholmes@stats.ox.ac.uk

Supplementary information:  Supplementary data are available at Bioinfomatics online.
GRIMP: a web- and grid-based tool for high-speed analysis of large-scale genome-wide association using imputed data
Authors: Estrada Karol , Abuseiris Anis , Grosveld Frank G. , Uitterlinden André G. , Knoch Tobias A. , Rivadeneira Fernando
Published: August 2009

Summary: The current fast growth of genome-wide association studies (GWAS) combined with now common computationally expensive imputation requires the online access of large user groups to high-performance computing resources capable of analyzing rapidly and efficiently millions of genetic markers for ten thousands of individuals. Here, we present a web-based interface—called GRIMP—to run publicly available genetic software for extremely large GWAS on scalable super-computing grid infrastructures. This is of major importance for the enlargement of GWAS with the availability of whole-genome sequence data from the 1000 Genomes Project and for future whole-population efforts.

Contact:  ta.knoch@taknoch.org; f.rivadeneira@erasmusmc.nl
Metabolite and reaction inference based on enzyme specificities
Authors: de Groot M. J. L. , van Berlo R. J. P. , van Winden W. A. , Verheijen P. J. T. , Reinders M. J. T. , de Ridder D.
Published: August 2009

Motivation: Many enzymes are not absolutely specific, or even promiscuous: they can catalyze transformations of more compounds than the traditional ones as listed in, e.g. KEGG. This information is currently only available in databases, such as the BRENDA enzyme activity database. In this article, we propose to model enzyme aspecificity by predicting whether an input compound is likely to be transformed by a certain enzyme. Such a predictor has many applications, for example, to complete reconstructed metabolic networks, to aid in metabolic engineering or to help identify unknown peaks in mass spectra.

Results: We have developed a system for metabolite and reaction inference based on enzyme specificities (MaRIboES). It employs structural and stereochemistry similarity measures and molecular fingerprints to generalize enzymatic reactions based on data available in BRENDA. Leave-one-out cross-validation shows that 80% of known reactions are predicted well. Application to the yeast glycolytic and pentose phosphate pathways predicts a large number of known and new reactions, often leading to the formation of novel compounds, as well as a number of interesting bypasses and cross-links.

Availability: Matlab and C++ code is freely available at https://gforge.nbic.nl/projects/mariboes/

Contact:  d.deridder@tudelft.nl

Supplementary information:  Supplementary data are available at Bioinformatics online.
ShotgunFunctionalizeR: an R-package for functional comparison of metagenomes
Authors: Kristiansson Erik , Hugenholtz Philip , Dalevi Daniel
Published: August 2009

Summary: Microorganisms are ubiquitous in nature and constitute intrinsic parts of almost every ecosystem. A culture-independent and powerful way to study microbial communities is metagenomics. In such studies, functional analysis is performed on fragmented genetic material from multiple species in the community. The recent advances in high-throughput sequencing have greatly increased the amount of data in metagenomic projects. At present, there is an urgent need for efficient statistical tools to analyse these data. We have created ShotgunFunctionalizeR, an R-package for functional comparison of metagenomes. The package contains tools for importing, annotating and visualizing metagenomic data produced by shotgun high-throughput sequencing. ShotgunFunctionalizeR contains several statistical procedures for assessing functional differences between samples, both for individual genes and for entire pathways. In addition to standard and previously published methods, we have developed and implemented a novel approach based on a Poisson model. This procedure is highly flexible and thus applicable to a wide range of different experimental designs. We demonstrate the potential of ShotgunFunctionalizeR by performing a regression analysis on metagenomes sampled at multiple depths in the Pacific Ocean.

Availability:  http://shotgun.zool.gu.se

Contact:  dalevi@chalmers.se; erik.kristiansson@zool.gu.se

Supplementary information:  supplementary data are available at Bioinformatics online.
PiSQRD: a web server for decomposing proteins into quasi-rigid dynamical domains
Authors: Aleksiev T. , Potestio R. , Pontiggia F. , Cozzini S. , Micheletti C.
Published: August 2009

Summary: The PiSQRD web resource can be used to subdivide protein structures in quasi-rigid dynamical domains. The latter are groups of amino acids behaving as approximately rigid units in the course of protein equilibrium fluctuations. The PiSQRD server takes as input a biomolecular structure and the desired fraction of protein internal fluctuations that must be accounted for by the relative rigid-body motion of the dynamical domains. Next, the lowest energy modes of fluctuation of the protein (optionally provided by the user) are calculated and used to identify the rigid subunits. The resulting optimal subdivision is returned through a web page containing both interactive graphics and detailed data output.

Availability: The PiSQRD web server, which requires Java, is available free of charge for academic users at http://pisqrd.escience-lab.org.

Contact:  potestio@sissa.it
Ganoderma lucidum Polysaccharides Induce Macrophage‐Like Differentiation in Human Leukemia THP‐1 Cells via Caspase and p53 Activation
Authors: Hsu Jia-Wei , Huang Hsuan-Cheng , Chen Shui-Tein , Wong Chi-Huey , Juan Hsueh-Fen
Published: August 2009

Differentiation therapy by induction of tumor cells is an important method in the treatment of hematological cancers such as leukemia. Tumor cell differentiation ends cancer cells′ immortality, thus stopping cell growth and proliferation. In our previous study, we found that fucose‐containing polysaccharide fraction F3 extracted from Ganoderma lucidum can bring about cytokine secretion and cell death in human leukemia THP‐1 cells. This prompted us to further investigate on how F3 induces the differentiation in human leukemia cells. We integrated time‐course microarray analysis and network modeling to study the F3‐induced effects on THP‐1 cells. In addition, we determined the differentiation effect using Liu′s staining, nitroblue tetrazolium (NBT) reduction assay, flow cytometer, western blotting and Q‐PCR. We also examined the modulation and regulation by F3 during the differentiation process. Dynamic gene expression profiles showed that cell differentiation was induced in F3‐treated THP‐1 cells. Furthermore, F3‐treated THP‐1 cells exhibited enhanced macrophage differentiation, as demonstrated by changes in cell adherence, cell cycle arrest, NBT reduction and expression of differentiation markers including CD11b, CD14, CD68, matrix metalloproteinase‐9 and myeloperoxidase. In addition, caspase cleavage and p53 activation were found to be significantly enhanced in F3‐treated THP‐1 cells. We unraveled the role of caspases and p53 in F3‐induced THP‐1 cells differentiation into macrophages. Our results provide a molecular explanation for the differentiation effect of F3 on human leukemia THP‐1 cells and offer a prospect for a potential leukemia differentiation therapy.
Comment on: Williams et al. (2009) “Australia's deep-water reserve network: implications of false homogeneity for classifying abiotic surrogates of biodiversity”. ICES Journal of Marine Science, 66: 214–224
Authors: Harris Peter T. , Heap Andrew D. , Anderson Tara J. , Brooke Brendan
Published: August 2009

Harris, P. T., Heap, A. D., Anderson, T. J., and Brooke, B. 2009. Comment on: Williams et al. (2009) “Australia's deep-water reserve network: implications of false homogeneity for classifying abiotic surrogates of biodiversity”. ICES Journal of Marine Science, 66: 214–224. – ICES Journal of Marine Science, 66: 2082–2085. Williams et al. (2009) report on new multibeam sonar bathymetry and underwater video data collected from submarine canyons and seamounts on Australia's southeast continental margin to “investigate the degree to which geomorphic features act as surrogates for benthic megafaunal biodiversity” (p. 214). The authors describe what they view as deficiencies in the design of the Marine Protected Areas (MPAs) in the southeast region of Australia, in which geomorphology information was employed as a surrogate to infer regional-scale patterns of benthic biodiversity. This comment is designed to support and underscore the importance of evaluating MPA designs and the validity of using abiotic surrogates such as geomorphology to infer biodiversity patterns, and also seeks to clarify some of the discrepancies in geomorphic terminologies and approaches used between the original study and the Williams et al. (2009) evaluation. It is our opinion that the MPA design criteria used by the Australian Government are incorrectly reported by Williams et al. (2009). In particular, we emphasize the necessity for consistent terminology and approaches when undertaking comparative analyses of geomorphic features. We show that the MPA selection criteria used by the Australian Government addressed the issues of false homogeneity described by Williams et al. (2009), but that final placement of MPAs was based on additional stakeholder considerations. Finally, we argue that although the Williams et al. (2009) study provides valuable information on biological distributions within seamounts and canyons, the hypothesis that geomorphic features (particularly seamounts and submarine canyons) are surrogates for benthic biodiversity is not tested explicitly by their study.
Hierarchical analysis of a remote, Arctic, artisanal longline fishery
Authors: Dennard Susan T. , MacNeil M. Aaron , Treble Margaret A. , Campana Steven , Fisk Aaron T.
Published: August 2009

Dennard, S. T., MacNeil, M. A., Treble, M. A., Campana, S., and Fisk, A. T. 2010. Hierarchical analysis of a remote, Arctic, artisanal longline fishery. – ICES Journal of Marine Science, 67: 41–51. This is the first paper to explore trends in catch per unit effort (cpue) through time of a Greenland halibut Reinhardtius hippoglossoides stock targeted by an artisanal, winter fishery in Cumberland Sound on southern Baffin Island, Canada. We modelled cpue data from 1987 to 2003, looking at two questions: what factors have driven cpue trends, and is cpue an accurate index of a stock's abundance? In the context of limited data availability, we used generalized linear models (GLMs) and hierarchical models to assess important predictors of cpue. Hierarchical models with multiple fixed environmental effects contained fishing location or individual fisher as random effects. A month effect showed greatest catch rates during February and March; the monthly North Atlantic Oscillation index was positively associated with catch rates; and a change from decreasing to increasing cpue after 1996 was linked to reduced fishery participation following a large storm. The best Akaike's information criterion-ranked GLM identified a negative relationship of cpue with shark bycatch. Although data limitations precluded conventional stock assessment, our models implicated the environment and fisher behaviour as drivers of cpue trends. Additionally, using multiple hierarchical models to predict cpue provided a more informative analysis for understanding trends in cpue than a GLM alone.
Galactic spiral structure
Authors: Francis Charles , Anderson Erik
Published: August 2009

We describe the structure and composition of six major stellar streams in a population of 20 574 local stars in the New Hipparcos Reduction with known radial velocities. We find that, once fast moving stars are excluded, almost all stars belong to one of these streams. The results of our investigation have led us to re-examine the hydrogen maps of the Milky Way, from which we identify the possibility of a symmetric two-armed spiral with half the conventionally accepted pitch angle. We describe a model of spiral arm motions that matches the observed velocities and compositions of the six major streams, as well as the observed velocities of the Hyades and Praesepe clusters at the extreme of the Hyades stream. We model stellar orbits as perturbed ellipses aligned at a focus in coordinates rotating at the rate of precession of apocentre. Stars join a spiral arm just before apocentre, follow the arm for more than half an orbit, and leave the arm soon after pericentre. Spiral pattern speed equals the mean rate of precession of apocentre. Spiral arms are shown to be stable configurations of stellar orbits, up to the formation of a bar and/or ring. Pitch angle is directly related to the distribution of orbital eccentricities in a given spiral galaxy. We show how spiral galaxies can evolve to form bars and rings. We show that orbits of gas clouds are stable only in bisymmetric spirals. We conclude that spiral galaxies evolve toward grand design two-armed spirals. We infer from the velocity distributions that the Milky Way evolved into this form about 9 billion years ago (Ga).
Green’s functions in non-local three-dimensional linear elasticity
Authors: Weckner Olaf , Brunk Gerd , Epton Michael A. , Silling Stewart A. , Askari Ebrahim
Published: August 2009

In this paper, we compare small deformations in an infinite linear elastic body due to the presence of point loads within the classical, local formulation to the corresponding deformations in the peridynamic, non-local formulation. Owing to the linearity of the problem, the response to a point load can be used to obtain the response to general body force loading functions by superposition. Using Laplace and Fourier transforms, we thus obtain an integral representation for the three-dimensional peridynamic solution with the help of Green’s functions. We illustrate this new theoretical result by dynamic and static examples in one and three dimensions. In addition to this main result, we also derive the non-local three-dimensional jump conditions, as well as the weak formulation of peridynamics together with the associated finite element discretization.
Senescence impairs successful reprogramming to pluripotent stem cells
Authors: Banito Ana , Rashid Sheikh T. , Acosta Juan Carlos , Li SiDe , Pereira Carlos F. , Geti Imbisaat , Pinho Sandra , Silva Jose C. , Azuara Veronique , Walsh Martin , Vallier Ludovic , Gil Jesús
Published: August 2009

Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by overexpressing combinations of factors such as Oct4, Sox2, Klf4, and c-Myc. Reprogramming is slow and stochastic, suggesting the existence of barriers limiting its efficiency. Here we identify senescence as one such barrier. Expression of the four reprogramming factors triggers senescence by up-regulating p53, p16INK4a, and p21CIP1. Induction of DNA damage response and chromatin remodeling of the INK4a/ARF locus are two of the mechanisms behind senescence induction. Crucially, ablation of different senescence effectors improves the efficiency of reprogramming, suggesting novel strategies for maximizing the generation of iPS cells.