bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficiency of monolaurin in mitigating ruminal methanogenesis and modifying C-isotope fractionation when incubating diets composed of either C3or C4plants in a rumen simulation technique (Rusitec) system
Authors: Klevenhusen Fenja , Bernasconi Stefano M. , Hofstetter Thomas B. , Bolotin Jakov , Kunz Carmen , Soliva Carla R.
Published: June 2009

Mitigation of methanogenesis in ruminants has been an important goal for several decades. Free lauric acid, known to suppress ruminal methanogenesis, has a low palatability; therefore, in the present study the aim was to evaluate the mitigation efficacy of its esterified form (monolaurin). Further,13C-isotope abundance (δ13C) and13C–12C fractionation during methanogenesis and fermentation were determined to evaluate possible microbial C-isotope preferences. Using the rumen simulation technique, four basal diets, characterised either by the C3plants grass (hay) and wheat (straw and grain), or the C4plant (13C excess compared with C3plants) maize (straw and grain), and a mixture of the latter two, were incubated with and without monolaurin (50 g/kg dietary DM). Added to hay, monolaurin did not significantly affect methanogenesis. When added to the other diets (P < 0·05 for the wheat-based diet) methane formation was lowered. Monolaurin decreased fibre disappearance (least effect with the hay diet), acetate:propionate ratio, and protozoal counts. Feed residues and SCFA showed the same δ13C as the diets. Methane was depleted in13C while CO2was enriched in13C compared with the diets. Monolaurin addition resulted in13C depletion of CO2and enrichment in CH4(the latter only in the hay diet). In conclusion, monolaurin proved to effectively decrease methanogenesis in the straw–grain diets although this effect might partly be explained by the concomitantly reduced fibre disappearance. The influence on13C-isotope abundance and fractionation supports the hypothesis that ruminal microbes seem to differentiate to some extent between C-isotopes during methanogenesis and fermentation.
Erythrocyte fatty acid profiles can predict acute non-fatal myocardial infarction
Authors: Park Yongsoon , Lim Jeehyun , Lee Jaeung , Kim Soon-gil
Published: June 2009

The risk of CHD has been linked to n-3 and trans-fatty acids. The purpose of the present study was to evaluate the hypothesis that lower n-3 fatty acids and higher trans-fatty acids in erythrocytes are associated with an increased risk of acute non-fatal myocardial infarction (MI), and that fatty acid profiles can discriminate MI cases from controls. Fifty cases with acute non-fatal MI and fifty age- and sex-matched controls without MI were recruited. The Omega-3 Index (the sum of EPA and DHA in erythrocytes) was significantly lower in cases than controls (9·57 (sem 0·28) v. 11·81 (sem 0·35) %; P < 0·001), while total trans-fatty acids were significantly higher (1·01 (sem 0·04) v. 0·56 (sem 0·03) %; P < 0·001). The Omega-3 Index was associated with decreased risk of MI (OR 0·08 (95 % CI 0·02, 0·38); P = 0·001), while total trans-fatty acids were associated with an increased risk of MI (OR 72·67 (95 % CI 6·68, 790·74); P < 0·001). The area under the receiver operating characteristic curve of fatty acid profiles was larger than that for traditional risk factors, suggesting that fatty acid profiles make a higher contribution to the discrimination of MI cases from controls compared with modified Framingham risk factors. In conclusion, a higher Omega-3 Index and lower trans-fatty acids in erythrocytes are associated with a decreased risk of MI. Furthermore, fatty acid profiles improve discrimination of acute non-fatal MI compared with established risk factors.
A method for stereo-vision-based tracking for robotic applications
Authors: Pathirana Pubudu N. , Bishop Adrian N. , Savkin Andrey V. , Ekanayake Samitha W. , Black Timothy J.
Published: June 2009

Vision-based tracking of an object using perspective projection inherently results in non-linear measurement equations in the Cartesian coordinates. The underlying object kinematics can be modelled by a linear system. In this paper we introduce a measurement conversion technique that analytically transforms the non-linear measurement equations obtained from a stereo-vision system into a system of linear measurement equations. We then design a robust linear filter around the converted measurement system. The state estimation error of the proposed filter is bounded and we provide a rigorous theoretical analysis of this result. The performance of the robust filter developed in this paper is demonstrated via computer simulation and via practical experimentation using a robotic manipulator as a target. The proposed filter is shown to outperform the extended Kalman filter (EKF).
History of the international societies in health technology assessment: International Society for Technology Assessment in Health Care and Health Technology Assessment International
Authors: Banta David , Jonsson Egon , Childs Paul
Published: June 2009

The International Society for Technology Assessment in Health Care (ISTAHC) was formed in 1985. It grew out of the increasing awareness of the international dimensions of health technology assessment (HTA) and the need for new communication methods at the international level. The main function of ISTAHC was to present an annual conference, which gradually grew in size, and also to generally improve in quality from to year. ISTAHC overextended itself financially early in the first decade of the 2000s and had to cease its existence. A new society, Health Technology Assessment international (HTAi), based on many of the same ideas and people, grew up beginning in the year 2003. The two societies have played a large role in making the field of HTA visible to people around the world and providing a forum for discussion on the methods and role of HTA.
Preface
Authors: McBRIDE CONOR , UUSTALU TARMO
Published: June 2009

This special issue of the Journal of Functional Programming collects revised selected articles arising from the inaugural meeting of the Workshop on Mathematically Structured Functional Programming, MSFP 2006, held in Kuressaare, Estonia, on 2 July 2006, with support from the European Union's FP6 IST Coordination Action TYPES. This workshop raised the curtain for the Eighth International Conference on Mathematics of Program Construction, MPC 2006, but where MPC is concerned primarily with extrinsic mathematics supporting the programming process, MSFP has a complementary focus on the mathematics intrinsic to programs themselves. MSFP is about the extraction of functionality from structure.
Parameterised notions of computation
Authors: ATKEY ROBERT
Published: June 2009

Moggi's Computational Monads and Poweret al.'s equivalent notion of Freyd category have captured a large range of computational effects present in programming languages. Examples include non-termination, non-determinism, exceptions, continuations, side effects and input/output. We present generalisations of both computational monads and Freyd categories, which we callparameterisedmonads andparameterisedFreyd categories, that also capture computational effects with parameters. Examples of such are composable continuations, side effects where the type of the state varies and input/output where the range of inputs and outputs varies. By considering structured parameterisation also, we extend the range of effects to cover separated side effects and multiple independent streams of I/O. We also present two typed λ-calculi that soundly and completely model our categorical definitions – with and without symmetric monoidal parameterisation – and act as prototypical languages with parameterised effects.
The essence of the Iterator pattern
Authors: GIBBONS JEREMY , OLIVEIRA BRUNO C. d. S.
Published: June 2009

The Iterator pattern gives a clean interface for element-by-element access to a collection, independent of the collection's shape. Imperative iterations using the pattern have two simultaneous aspects: mapping and accumulating. Various existing functional models of iteration capture one or other of these aspects, but not both simultaneously. We argue that C. McBride and R. Paterson's applicative functors (Applicative programming with effects, J. Funct. Program., 18 (1): 1–13, 2008), and in particular the corresponding traverse operator, do exactly this, and therefore capture the essence of the Iterator pattern. Moreover, they do so in a way that nicely supports modular programming. We present some axioms for traversal, discuss modularity concerns and illustrate with a simple example, the wordcount problem.
Algebras for combinatorial search
Authors: SPIVEY J. MICHAEL
Published: June 2009

Combinatorial search strategies including depth-first, breadth-first and depth-bounded search are shown to be different implementations of a common algebraic specification that emphasizes the compositionality of the strategies. This specification is placed in a categorical setting that combines algebraic specifications and monads.
Outstanding Student Paper Awards
Authors: Anonymous
Published: June 2009

The following members received Outstanding Student Paper Awards at the 2008 AGU Fall Meeting in San Francisco, Calif. Awards for other sections and focus groups will be announced in a subsequent issue of Eos. See also Eos, 90(18), 159, 2009.
Planet Mars: Story of Another World
Authors: Leatherland Alex
Published: June 2009

Mars has captured the imagination of people throughout the ages, inspiring many stories. Remarkably, though, little was known about the red planet until recently. Through a great deal of exploration and theory, planetary scientists have striven to correct this situation.

Over the course of the past half century, since the first flyby of Mars by NASA's Mariner 4 spacecraft in 1967, a multitude of probes have landed on, orbited, and flown past the planet. From these missions, a great deal has been learned about Mars. Its surface has now been studied to a respectable level of detail, revealing an astonishing amount of information about volcanoes such as Olympus Mons in Mars's Tharsis region; about the gigantic Valles Marineris (Valley of Wonder), the largest known canyon in the solar system; and about lava flows, outflow channels, and the Martian regolith, among many other aspects of the planet.
Addressing Challenges for Chemical Oceanography: Unknown Knowns and Known Unknowns: Chemical Oceanography in a Changing World; Savannah, Georgia, 22–24 February 2009
Authors: Savidge William B. , Brandes Jay A.
Published: June 2009

Rapid climate change in recent decades has resulted in significant shifts in ocean chemistry. A group of more than 80 chemical oceanographers from the United States and Europe met in Savannah, Ga., to consider the challenges facing the field in upcoming decades and to reflect on what studies and resources are needed to meet these challenges. The primary focus was on carbon and related nutrient cycling and the tools, such as biomarkers, used to investigate these processes. Over the course of 2 days, a series of provocative talks and spirited discussions highlighted several challenges facing chemical oceanographers.
Mountain Weather and Climate, Third Edition
Authors: Hastenrath Stefan
Published: June 2009

For colleagues with diverse interests in the atmosphere, glaciers, radiation, landforms, water resources, vegetation, human implications, and more, Mountain Weather and Climate can be a valuable source of guidance and literature references. The book is organized into seven chapters: 1, Mountains and their climatological study; 2, Geographical controls of mountain meteorological elements; 3, Circulation systems related to orography; 4, Climatic characteristics of mountains; 5, Regional case studies; 6, Mountain bioclimatology; and 7, Changes in mountain climates. These chapters are supported by l78 diagrams and photographs, 47 tables, and some 2000 literature references. The volume has an appendix of units and energy conversion factors and a subject index, but it lacks an author index.
Budget Increases Proposed for NOAA and Energy Department
Authors: Showstack Randy
Published: June 2009

In addition to the Obama administration's proposed budget increases for NASA, the Environmental Protection Agency, and the U.S. Geological Survey (see Eos, 90(10), 83, 2009, and 90(20), 175, 2009), other federal Earth and space science agencies also would receive boosts in the proposed fiscal year (FY) 2010 budget. The proposed budget comes on top of the 2009 American Recovery and Reinvestment Act's (ARRA) US$18.3 billion in stimulus spending for research and development that can be apportioned between the FY 2009 and FY 2010 budgets. This news item focuses on the budget proposals for the National Oceanic and Atmospheric Administration (NOAA) and the Department of Energy (DOE). Next week, Eos will look at the budget proposal for the National Science Foundation.
Dynamic Planet: Mercury in the Context of Its Environment
Authors: Wood Alan
Published: June 2009

Mercury, the Sun's nearest neighbor, is tantalizingly close to the Earth yet is one of the least explored objects in our solar system. The planet's proximity to the Sun makes Earth‐based observations extremely difficult, and the harsh environment presents a significant challenge to spacecraft. Nevertheless, we are currently on the verge of a new era of exploration of this fascinating, mysterious, and largely uncharted world.

Much of our knowledge about Mercury has come from just three flybys by NASA's Mariner 10 spacecraft in the mid‐1970s. This mission sent back stunning images of about 45% of the planet's surface and made the truly puzzling discovery of a magnetic field, the source of which is still unknown. Currently, NASA's Mercury Surface, Space Environment, Geochemistry, and Ranging (MESSENGER) mission is beginning to explore Mercury and aims to answer many unresolved questions about the structure, composition, magnetic field, and history of this incredible world. To date, MESSENGER has conducted two flybys and is expected to go into orbit around Mercury in March 2011. Later, in 2013, the European Space Agency's BepiColombo mission, which uses a twin spacecraft approach, will head for the planet to understand the detail of this dynamic system.
Integrated Tsunami Data for Better Hazard Assessments
Authors: Dunbar Paula
Published: June 2009

With nearly 230,000 fatalities, the 26 December 2004 Indian Ocean tsunami was the deadliest tsunami in history, illustrating the importance of developing basin‐wide warning systems. Key to creating these systems is easy access to quality‐controlled, verified data on past tsunamis: Warning centers, emergency managers, and modelers need to know if and when similar events have occurred.

Following the 2004 tsunami, the National Oceanic and Atmospheric Administration's (NOAA) National Geophysical Data Center (NGDC) began examining all aspects of the tsunami data archive to help answer questions regarding the frequency and severity of past tsunamis. Historical databases span insufficient time to reveal a region's full tsunami hazard, so a global database of citations to articles on tsunami deposits was added to the archive. NGDC further expanded the archive to include high‐resolution tide gauge data, deep‐ocean sensor data, and digital elevation models used for propagation and inundation. NGDC continuously reviews data for accuracy, making modifications as new information is obtained.
Proposed National Science Foundation Budget on Target to Double
Authors: Showstack Randy
Published: June 2009

The Obama administration's proposed fiscal year (FY) 2010 budget for the U.S. National Science Foundation (NSF) is US$7.05 billion, $555 million (8.5%) above its FY 2009 budget, and is in addition to $3 billion in stimulus funding from the 2009 American Recovery and Reinvestment Act (ARRA). The proposed funding, which represents strong support from the administration for NSF and for science and technology, would put the foundation on track to double its budget between 2006 and 2016 (see Eos, 90(10), 83, 2009; 90(20), 175, 2009; and 90(21), 183, 2009).
Evolving Views on a Dynamic Greenhouse Earth: Climatic and Biotic Events of the Paleogene (CBEP 2009) Conference; Wellington, New Zealand, 12–15 January 2009
Authors: Hollis Chris , Huber Matthew
Published: June 2009

The Paleogene (65–24 million years ago) was a dynamic period in Earth's history in which major mammal groups became established and diversified, rapid and repeated extreme global warming events occurred, and climate began its stuttering progression from a greenhouse to an icehouse climate state. With atmospheric carbon dioxide concentrations in the range projected to occur over the next several centuries (>1000 parts per million), the Paleogene is also a window into our future (see J. C. Zachos et al., Nature, 451, 279–283, 2008).

Long‐standing interest in understanding the causes and consequences of global change in the Paleogene and the current timeliness of greenhouse climate research explain why conferences are periodically devoted to the climatic and biotic events of the Paleogene. The 2009 conference, held in New Zealand, attracted 130 participants from 20 countries. Presentations demonstrated substantial progress in new climate proxy development, new multiproxy approaches, and closer integration of paleoclimate records with climate models, consolidating around three main issues.
Wnt5 is required for notochord cell intercalation in the ascidian Halocynthia roretzi
Authors: Niwano Tomoko , Takatori Naohito , Kumano Gaku , Nishida Hiroki
Published: June 2009

Background information. In the embryos of various animals, the body elongates after gastrulation by morphogenetic movements involving convergent extension. The Wnt/PCP (planar cell polarity) pathway plays roles in this process, particularly mediolateral polarization and intercalation of the embryonic cells. In ascidians, several factors in this pathway, including Wnt5, have been identified and found to be involved in the intercalation process of notochord cells.

Results. In the present study, the role of the Wnt5 genes, Hr‐Wnt5α (Halocynthia roretzi Wnt5α) and Hr‐Wnt5β, in convergent extension was investigated in the ascidian H. roretzi by injecting antisense oligonucleotides and mRNAs into single precursor blastomeres of various tissues, including notochord, at the 64‐cell stage. Hr‐Wnt5α is expressed in developing notochord and was essential for notochord morphogenesis. Precise quantitative control of its expression level was crucial for proper cell intercalation. Overexpression of Wnt5 proteins in notochord and other tissues that surround the notochord indicated that Wnt5α plays a role within the notochord, and is unlikely to be the source of polarizing cues arising outside the notochord. Detailed mosaic analysis of the behaviour of individual notochord cells overexpressing Wnt5α indicated that a Wnt5α‐manipulated cell does not affect the behaviour of neighbouring notochord cells, suggesting that Wnt5α works in a cell‐autonomous manner. This is further supported by comparison of the results of Wnt5α and Dsh (Dishevelled) knockdown experiments. In addition, our results suggest that the Wnt/PCP pathway is also involved in mediolateral intercalation of cells of the ventral row of the nerve cord (floor plate) and the endodermal strand.

Conclusion. The present study highlights the role of the Wnt5α signal in notochord convergent extension movements in ascidian embryos. Our results raise the novel possibility that Wnt5α functions in a cell‐autonomous manner in activation of the Wnt/PCP pathway to polarize the protrusive activity that drives convergent extension.
Calcium-sensing beyond neurotransmitters: functions of synaptotagmins in neuroendocrine and endocrine secretion
Authors: Gustavsson Natalia , Han Weiping
Published: June 2009

Neurotransmitters, neuropeptides and hormones are released through the regulated exocytosis of SVs (synaptic vesicles) and LDCVs (large dense-core vesicles), a process that is controlled by calcium. Synaptotagmins are a family of type 1 membrane proteins that share a common domain structure. Most synaptotagmins are located in brain and endocrine cells, and some of these synaptotagmins bind to phospholipids and calcium at levels that trigger regulated exocytosis of SVs and LDCVs. This led to the proposed synaptotagmin–calcium-sensor paradigm, that is, members of the synaptotagmin family function as calcium sensors for the regulated exocytosis of neurotransmitters, neuropeptides and hormones. Here, we provide an overview of the synaptotagmin family, and review the recent mouse genetic studies aimed at understanding the functions of synaptotagmins in neurotransmission and endocrine-hormone secretion. Also, we discuss potential roles of synaptotagmins in non-traditional endocrine systems.
Rationale for Strength and Skill Goals in Tongue Resistance Training: A Review
Authors: Steele Catriona M. , Bailey Gemma L. , Molfenter Sonja M. , Yeates Erin M.
Published: June 2009

Recent evidence in the dysphagia literature shows that tongue resistance training can be used to improve tongue strength. In this review article, we summarize what is known about the tongue and its role in swallowing. We review the literature on tongue pressure generation capacity (strength) and response to tongue resistance exercises. Tongue skill is introduced as a possible alternate goal in tongue resistance training, based on consideration of related literature regarding neural adaptation and improvements in motor performance resulting from treatment approaches in which goal-oriented practice and performance-specific feedback are provided.
The Application of Tongue Endurance Measures to Functional Dining
Authors: Kays Stephanie , Robbins JoAnne
Published: June 2009

While tongue strength has been shown to be critical for safe swallowing, measures of tongue endurance may be more functional, given that dining requires multiple swallows performed over a period of time. Recent findings demonstrate that the act of eating a meal reduces tongue endurance in both young and older adults, but young adults tend to have higher baseline endurance measures, suggesting that older adults present with reduced reserve to safely complete a meal with minimal effort. Furthermore, observed changes in tongue endurance after dining vary with respect to anatomic tongue location, age, and gender. Evidence from studies of limb muscle endurance is utilized to discuss these findings.
REM, not incubation, improves creativity by priming associative networks
Authors: Cai Denise J. , Mednick Sarnoff A. , Harrison Elizabeth M. , Kanady Jennifer C. , Mednick Sara C.
Published: June 2009

The hypothesized role of rapid eye movement (REM) sleep, which is rich in dreams, in the formation of new associations, has remained anecdotal. We examined the role of REM on creative problem solving, with the Remote Associates Test (RAT). Using a nap paradigm, we manipulated various conditions of prior exposure to elements of a creative problem. Compared with quiet rest and non-REM sleep, REM enhanced the formation of associative networks and the integration of unassociated information. Furthermore, these REM sleep benefits were not the result of an improved memory for the primed items. This study shows that compared with quiet rest and non-REM sleep, REM enhances the integration of unassociated information for creative problem solving, a process, we hypothesize, that is facilitated by cholinergic and noradrenergic neuromodulation during REM sleep.
Implementation of National Fire Plan treatments near the wildland–urban interface in the western United States
Authors: Schoennagel Tania , Nelson Cara R. , Theobald David M. , Carnwath Gunnar C. , Chapman Teresa B.
Published: June 2009

Because of increasing concern about the effects of catastrophic wildland fires throughout the western United States, federal land managers have been engaged in efforts to restore historical fire behavior and mitigate wildfire risk. During the last 5 years (2004–2008), 44,000 fuels treatments were implemented across the western United States under the National Fire Plan (NFP). We assessed the extent to which these treatments were conducted in and near the wildland–urban interface (WUI), where they would have the greatest potential to reduce fire risk in neighboring homes and communities. Although federal policies stipulate that significant resources should be invested in the WUI, we found that only 3% of the area treated was within the WUI, and another 8% was in an additional 2.5-km buffer around the WUI, totaling 11%. Only 17% of this buffered WUI is under federal ownership, which significantly limits the ability of federal agencies to implement fire-risk reduction treatments near communities. Although treatments far from the WUI may have some fire mitigation benefits, our findings suggest that greater priority must be given to locating treatments in and near the WUI, rather than in more remote settings, to satisfy NFP goals of reducing fire risk to communities. However, this may require shifting management and policy emphasis from public to private lands.
Collective dynamics of social annotation
Authors: Cattuto Ciro , Barrat Alain , Baldassarri Andrea , Schehr Gregory , Loreto Vittorio
Published: June 2009

The enormous increase of popularity and use of the worldwide web has led in the recent years to important changes in the ways people communicate. An interesting example of this fact is provided by the now very popular social annotation systems, through which users annotate resources (such as web pages or digital photographs) with keywords known as “tags.” Understanding the rich emergent structures resulting from the uncoordinated actions of users calls for an interdisciplinary effort. In particular concepts borrowed from statistical physics, such as random walks (RWs), and complex networks theory, can effectively contribute to the mathematical modeling of social annotation systems. Here, we show that the process of social annotation can be seen as a collective but uncoordinated exploration of an underlying semantic space, pictured as a graph, through a series of RWs. This modeling framework reproduces several aspects, thus far unexplained, of social annotation, among which are the peculiar growth of the size of the vocabulary used by the community and its complex network structure that represents an externalization of semantic structures grounded in cognition and that are typically hard to access.
RETRACTED: The cytokine interleukin-33 mediates anaphylactic shock
Authors: Pushparaj Peter N. , Tay Hwee Kee , H'ng Shiau Chen , Pitman Nick , Xu Damo , McKenzie Andrew , Liew Foo Y. , Melendez Alirio J.
Published: June 2009

Anaphylactic shock is characterized by elevated immunoglobulin-E (IgE) antibodies that signal via the high affinity Fcε receptor (FcεRI) to release inflammatory mediators. Here we report that the novel cytokine interleukin-33 (IL-33) potently induces anaphylactic shock in mice and is associated with the symptom in humans. IL-33 is a new member of the IL-1 family and the ligand for the orphan receptor ST2. In humans, the levels of IL-33 are substantially elevated in the blood of atopic patients during anaphylactic shock, and in inflamed skin tissue of atopic dermatitis patients. In murine experimental atopic models, IL-33 induced antigen-independent passive cutaneous and systemic anaphylaxis, in a T cell–independent, mast cell–dependent manner.
In vitro
, IL-33 directly induced degranulation, strong eicosanoid and cytokine production in IgE-sensitized mast cells. The molecular mechanisms triggering these responses include the activation of phospholipase D1 and sphingosine kinase1 to mediate calcium mobilization, Nuclear factor–κB activation, cytokine and eicosanoid secretion, and degranulation. This report therefore reveals a hitherto unrecognized pathophysiological role of IL-33 and suggests that IL-33 may be a potential therapeutic target for anaphylaxis, a disease of considerable unmet medical need.
Lysosomal recycling terminates CD1d-mediated presentation of short and polyunsaturated variants of the NKT cell lipid antigen αGalCer
Authors: Bai Li , Sagiv Yuval , Liu Yang , Freigang Stefan , Yu Karl O. A. , Teyton Luc , Porcelli Steven A. , Savage Paul B. , Bendelac Albert
Published: June 2009

Short or polyunsaturated lipid variants of the NKT cell antigen α-galactosylceramide (αGC) exhibit decreased potency and a Th2 bias in vivo despite conserved TCR contact residues and stable binding to CD1d at neutral and acidic pH. Using reagents to directly visualize lipids in their free or CD1d-bound form, we determined that, contrary to predictions, these lipids reached the lysosome better than αGC. However, in contrast with αGC, they loaded CD1d at the cell surface and underwent immediate pH-dependent dissociation upon recycling to the lysosome. In cell-free assays, ultrafast dissociation of preformed complexes could be induced at acidic pH only when free competitor lipids were added, suggesting active lipid displacement. These findings provide a common cell biological explanation for the decreased stimulatory properties of short and polyunsaturated αGC variants. They also suggest that direct lipid displacement is a potent mechanism underlying highly dynamic lipid exchange reactions in the lysosomal compartment that shape the repertoire of lipids associated with CD1d.
Identification of a urate transporter, ABCG2, with a common functional polymorphism causing gout
Authors: Woodward Owen M. , Köttgen Anna , Coresh Josef , Boerwinkle Eric , Guggino William B. , Köttgen Michael
Published: June 2009

Genome-wide association studies (GWAS) have successfully identified common single nucleotide polymorphisms (SNPs) associated with a wide variety of complex diseases, but do not address gene function or establish causality of disease-associated SNPs. We recently used GWAS to identify SNPs in a genomic region on chromosome 4 that associate with serum urate levels and gout, a consequence of elevated urate levels. Here we show using functional assays that human ATP-binding cassette, subfamily G, 2 (ABCG2), encoded by the
ABCG2
gene contained in this region, is a hitherto unknown urate efflux transporter. We further show that native ABCG2 is located in the brush border membrane of kidney proximal tubule cells, where it mediates renal urate secretion. Introduction of the mutation Q141K encoded by the common SNP rs2231142 by site-directed mutagenesis resulted in 53% reduced urate transport rates compared to wild-type ABCG2 (
P
< 0.001). Data from a population-based study of 14,783 individuals support rs2231142 as the causal variant in the region and show highly significant associations with urate levels [whites:
P
= 10
−30
, minor allele frequency (MAF) 0.11; blacks
P
= 10
−4
, MAF 0.03] and gout (adjusted odds ratio 1.68 per risk allele, both races). Our data indicate that at least 10% of all gout cases in whites are attributable to this causal variant. With approximately 3 million US individuals suffering from often insufficiently treated gout, ABCG2 represents an attractive drug target. Our study completes the chain of evidence from association to causation and supports the common disease-common variant hypothesis in the etiology of gout.
Protein-binding elements establish in the oocyte the primary imprint of the Prader-Willi/Angelman syndromes domain
Authors: Kaufman Yotam , Heled Maya , Perk Jonathan , Razin Aharon , Shemer Ruth
Published: June 2009

Imprinting of the PWS/AS 2.4 Mb domain in the human is controlled by a paternally active imprinting center (PWS-IC). PWS-IC on the maternal allele is methylated and inactivated by an 880-bp sequence (AS-IC) located 30 kb upstream. In this communication, we report the identification of 7 cis acting elements within AS-IC. The elements: DMR, DNS, 2 OCTA sequences, SOX, E1, and E2 bind specific proteins that form at least 2 protein complexes. Using variants of an imprinted transgene, mutated at the elements each at a time, we show that (
i
) all 7 elements are involved in the methylation and inactivation of the maternal PWS-IC; (
ii
) the OCTA and SOX elements that bind a protein complex, and the E1 and E2 elements, function in establishing the primary imprint that constitutes an active and unmethylated AS-IC in the oocyte; (
iii
) DNS and DMR bind a multiprotein complex that may facilitate interaction between AS-IC and PWS-IC, mediating the inactivation in cis of PWS-IC; and (
iv
) all 7 elements participate in maintaining an unmethylated PWS-IC in the oocyte, which is essential for its maternal methylation later in development. Altogether, the above observations imply that the cis acting elements on AS-IC display diverse functions in establishing the imprints at both AS-IC and PWS-IC in the oocyte. A postulated epigenetic mark imprints the PWS-IC in the oocyte and maintains its inactive status during development before it is translated into maternal methylation.
Beyond the Fermi liquid paradigm: Hidden Fermi liquids
Authors: Jain J. K. , Anderson P. W.
Published: June 2009

An intense investigation of possible non-Fermi liquid states of matter has been inspired by two of the most intriguing phenomena discovered in the past quarter century, namely, high-temperature superconductivity and the fractional quantum Hall effect. Despite enormous conceptual strides, these two fields have developed largely along separate paths. Two widely employed theories are the resonating valence bond theory for high-temperature superconductivity and the composite fermion theory for the fractional quantum Hall effect. The goal of this perspective article is to note that they subscribe to a common underlying paradigm: They both connect these exotic quantum liquids to certain ordinary Fermi liquids residing in unphysical Hilbert spaces. Such a relation yields numerous nontrivial experimental consequences, exposing these theories to rigorous and definitive tests.
Targeting an antimicrobial effector function in insect immunity as a pest control strategy
Authors: Bulmer Mark S. , Bachelet Ido , Raman Rahul , Rosengaus Rebeca B. , Sasisekharan Ram
Published: June 2009

Insect pests such as termites cause damages to crops and man-made structures estimated at over $30 billion per year, imposing a global challenge for the human economy. Here, we report a strategy for compromising insect immunity that might lead to the development of nontoxic, sustainable pest control methods. Gram-negative bacteria binding proteins (GNBPs) are critical for sensing pathogenic infection and triggering effector responses. We report that termite GNBP-2 (tGNBP-2) shows β(
1
,
3
)-glucanase effector activity previously unknown in animal immunity and is a pleiotropic pattern recognition receptor and an antimicrobial effector protein. Termites incorporate this protein into the nest building material, where it functions as a nest-embedded sensor that cleaves and releases pathogenic components, priming termites for improved antimicrobial defense. By means of rational design, we present an inexpensive, nontoxic small molecule glycomimetic that blocks tGNBP-2, thus exposing termites in vivo to accelerated infection and death from specific and opportunistic pathogens. Such a molecule, introduced into building materials and agricultural methods, could protect valuable assets from insect pests.
Maximum leaf conductance driven by CO
2
effects on stomatal size and density over geologic time
Authors: Franks Peter J. , Beerling David J.
Published: June 2009

Stomatal pores are microscopic structures on the epidermis of leaves formed by 2 specialized guard cells that control the exchange of water vapor and CO
2
between plants and the atmosphere. Stomatal size (
S
) and density (
D
) determine maximum leaf diffusive (stomatal) conductance of CO
2
(
g

c
max

) to sites of assimilation. Although large variations in
D
observed in the fossil record have been correlated with atmospheric CO
2
, the crucial significance of similarly large variations in
S
has been overlooked. Here, we use physical diffusion theory to explain why large changes in
S
necessarily accompanied the changes in
D
and atmospheric CO
2
over the last 400 million years. In particular, we show that high densities of small stomata are the only way to attain the highest
g

c
max

values required to counter CO
2
“starvation” at low atmospheric CO
2
concentrations. This explains cycles of increasing
D
and decreasing
S
evident in the fossil history of stomata under the CO
2
impoverished atmospheres of the Permo-Carboniferous and Cenozoic glaciations. The pattern was reversed under rising atmospheric CO
2
regimes. Selection for small
S
was crucial for attaining high
g

c
max

under falling atmospheric CO
2
and, therefore, may represent a mechanism linking CO
2
and the increasing gas-exchange capacity of land plants over geologic time.
Localization of recombination proteins and Srs2 reveals anti-recombinase function in vivo
Authors: Burgess Rebecca C. , Lisby Michael , Altmannova Veronika , Krejci Lumir , Sung Patrick , Rothstein Rodney
Published: June 2009

Homologous recombination (HR), although an important DNA repair mechanism, is dangerous to the cell if improperly regulated. The Srs2 “anti-recombinase” restricts HR by disassembling the Rad51 nucleoprotein filament, an intermediate preceding the exchange of homologous DNA strands. Here, we cytologically characterize Srs2 function in vivo and describe a novel mechanism for regulating the initiation of HR. We find that Srs2 is recruited separately to replication and repair centers and identify the genetic requirements for recruitment. In the absence of Srs2 activity, Rad51 foci accumulate, and surprisingly, can form in the absence of Rad52 mediation. However, these Rad51 foci do not represent repair-proficient filaments, as determined by recombination assays. Antagonistic roles for Rad52 and Srs2 in Rad51 filament formation are also observed in vitro. Furthermore, we provide evidence that Srs2 removes Rad51 indiscriminately from DNA, while the Rad52 protein coordinates appropriate filament reformation. This constant breakdown and rebuilding of filaments may act as a stringent quality control mechanism during HR.
During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1-dependent ubiquitylation
Authors: Cohen Shenhav , Brault Jeffrey J. , Gygi Steven P. , Glass David J. , Valenzuela David M. , Gartner Carlos , Latres Esther , Goldberg Alfred L.
Published: June 2009

Loss of myofibrillar proteins is a hallmark of atrophying muscle. Expression of muscle RING-finger 1 (MuRF1), a ubiquitin ligase, is markedly induced during atrophy, and MuRF1 deletion attenuates muscle wasting. We generated mice expressing a Ring-deletion mutant MuRF1, which binds but cannot ubiquitylate substrates. Mass spectrometry of the bound proteins in denervated muscle identified many myofibrillar components. Upon denervation or fasting, atrophying muscles show a loss of myosin-binding protein C (MyBP-C) and myosin light chains 1 and 2 (MyLC1 and MyLC2) from the myofibril, before any measurable decrease in myosin heavy chain (MyHC). Their selective loss requires MuRF1. MyHC is protected from ubiquitylation in myofibrils by associated proteins, but eventually undergoes MuRF1-dependent degradation. In contrast, MuRF1 ubiquitylates MyBP-C, MyLC1, and MyLC2, even in myofibrils. Because these proteins stabilize the thick filament, their selective ubiquitylation may facilitate thick filament disassembly. However, the thin filament components decreased by a mechanism not requiring MuRF1.
Agricultural pesticide exposure and the molecular connection to lymphomagenesis
Authors: Agopian Julie , Navarro Jean-Marc , Gac Anne-Claire , Lecluse Yannick , Briand Mélanie , Grenot Pierre , Gauduchon Pascal , Ruminy Philippe , Lebailly Pierre , Nadel Bertrand , Roulland Sandrine
Published: June 2009

The t(14;18) translocation constitutes the initiating event of a causative cascade leading to follicular lymphoma (FL). t(14;18) translocations are present in blood from healthy individuals, but there is a trend of increased prevalence in farmers exposed to pesticides, a group recently associated with higher risk of t(14;18)+ non-Hodgkin's lymphoma development. A direct connection between agricultural pesticide use, t(14;18) in blood, and malignant progression, however, has not yet been demonstrated. We followed t(14;18) clonal evolution over 9 yr in a cohort of farmers exposed to pesticides. We show that exposed individuals bear particularly high t(14;18) frequencies in blood because of a dramatic clonal expansion of activated t(14;18)+ B cells. We further demonstrate that such t(14;18)+ clones recapitulate the hallmark features of developmentally blocked FL cells, with some displaying aberrant activation-induced cytidine deaminase activity linked to malignant progression. Collectively, our data establish that expanded t(14;18)+ clones constitute bona fide precursors at various stages of FL development, and provide a molecular connection between agricultural pesticide exposure, t(14;18) frequency in blood, and clonal progression.
The World Health Organization Guidelines on Hand Hygiene in Health Care and Their Consensus Recommendations
Authors: Pittet Didier , Allegranzi Benedetta , Boyce John ,   World Health Organization World Alliance for Patient Safety First Global Patient Safety Challenge Core Group of Experts
Published: June 2009

The World Health Organization's Guidelines on Hand Hygiene in Health Care have been issued by WHO Patient Safety on 5 May 2009 on the occasion of the launch of the Save Lives: Clean Your Hands initiative. The Guidelines represent the contribution of more than 100 international experts and provide a comprehensive overview of essential aspects of hand hygiene in health care, evidence- and consensus-based recommendations, and lessons learned from testing their Advanced Draft and related implementation tools.
trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses
Authors: Capella-Gutiérrez Salvador , Silla-Martínez José M. , Gabaldón Toni
Published: June 2009

Summary: Multiple sequence alignments are central to many areas of bioinformatics. It has been shown that the removal of poorly aligned regions from an alignment increases the quality of subsequent analyses. Such an alignment trimming phase is complicated in large-scale phylogenetic analyses that deal with thousands of alignments. Here, we present trimAl, a tool for automated alignment trimming, which is especially suited for large-scale phylogenetic analyses. trimAl can consider several parameters, alone or in multiple combinations, for selecting the most reliable positions in the alignment. These include the proportion of sequences with a gap, the level of amino acid similarity and, if several alignments for the same set of sequences are provided, the level of consistency across different alignments. Moreover, trimAl can automatically select the parameters to be used in each specific alignment so that the signal-to-noise ratio is optimized.

Availability: trimAl has been written in C++, it is portable to all platforms. trimAl is freely available for download (http://trimal.cgenomics.org) and can be used online through the Phylemon web server (http://phylemon2.bioinfo.cipf.es/). Supplementary Material is available at http://trimal.cgenomics.org/publications.

Contact:  tgabaldon@crg.es
Adaptive intervention in probabilistic boolean networks
Authors: Layek Ritwik , Datta Aniruddha , Pal Ranadip , Dougherty Edward R.
Published: June 2009

Motivation: A basic problem of translational systems biology is to utilize gene regulatory networks as a vehicle to design therapeutic intervention strategies to beneficially alter network and, therefore, cellular dynamics. One strain of research has this problem from the perspective of control theory via the design of optimal Markov chain decision processes, mainly in the framework of probabilistic Boolean networks (PBNs). Full optimization assumes that the network is accurately modeled and, to the extent that model inference is inaccurate, which can be expected for gene regulatory networks owing to the combination of model complexity and a paucity of time-course data, the designed intervention strategy may perform poorly. We desire intervention strategies that do not assume accurate full-model inference.

Results: This article demonstrates the feasibility of applying on-line adaptive control to improve intervention performance in genetic regulatory networks modeled by PBNs. It shows via simulations that when the network is modeled by a member of a known family of PBNs, an adaptive design can yield improved performance in terms of the average cost. Two algorithms are presented, one better suited for instantaneously random PBNs and the other better suited for context-sensitive PBNs with low switching probability between the constituent BNs.

Contact:  edward@ece.tamu.edu
Identifying the topology of protein complexes from affinity purification assays
Authors: Friedel Caroline C. , Zimmer Ralf
Published: June 2009

Motivation: Recent advances in high-throughput technologies have made it possible to investigate not only individual protein interactions, but also the association of these proteins in complexes. So far the focus has been on the prediction of complexes as sets of proteins from the experimental results. The modular substructure and the physical interactions within the protein complexes have been mostly ignored.

Results: We present an approach for identifying the direct physical interactions and the subcomponent structure of protein complexes predicted from affinity purification assays. Our algorithm calculates the union of all maximum spanning trees from scoring networks for each protein complex to extract relevant interactions. In a subsequent step this network is extended to interactions which are not accounted for by alternative indirect paths. We show that the interactions identified with this approach are more accurate in predicting experimentally derived physical interactions than baseline approaches. Based on these networks, the subcomponent structure of the complexes can be resolved more satisfactorily and subcomplexes can be identified. The usefulness of our method is illustrated on the RNA polymerases for which the modular substructure can be successfully reconstructed.

Availability: A Java implementation of the prediction methods and supplementary material are available at http://www.bio.ifi.lmu.de/Complexes/Substructures/.

Contact:  caroline.friedel@bio.ifi.lmu.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Importing ArrayExpress datasets into R/Bioconductor
Authors: Kauffmann Audrey , Rayner Tim F. , Parkinson Helen , Kapushesky Misha , Lukk Margus , Brazma Alvis , Huber Wolfgang
Published: June 2009

Summary:ArrayExpress is one of the largest public repositories of microarray datasets. R/Bioconductor provides a comprehensive suite of microarray analysis and integrative bioinformatics software. However, easy ways for importing datasets from ArrayExpress into R/Bioconductor have been lacking. Here, we present such a tool that is suitable for both interactive and automated use.

Availability: The ArrayExpress package is available from the Bioconductor project at http://www.bioconductor.org. A users guide and examples are provided with the package.

Contact:  audrey@ebi.ac.uk

Supplementary information:  Supplementary data are available Bioinformatics online.