scispace - formally typeset
Search or ask a question

Showing papers by "University of Kansas published in 2010"


Journal ArticleDOI
TL;DR: This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features.
Abstract: Objective The 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classifi cation criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classifi cation criteria for RA. Methods A joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated infl ammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/ or erosive disease—this being the appropriate current paradigm underlying the disease construct ‘RA’. Results In the new criteria set, classifi cation as ‘defi nite RA’ is based on the confi rmed presence of synovitis in at least one joint, absence of an alternative diagnosis better explaining the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in four domains: number and site of involved joints (range 0–5), serological abnormality (range 0–3), elevated acute-phase response (range 0–1) and symptom duration (two levels; range 0–1). Conclusion This new classifi cation system redefi nes the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defi ning the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimise the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct ‘RA’.

7,120 citations


Journal ArticleDOI
TL;DR: The iterative threading assembly refinement (I-TASSER) server is an integrated platform for automated protein structure and function prediction based on the sequence- to-structure-to-function paradigm.
Abstract: The iterative threading assembly refinement (I-TASSER) server is an integrated platform for automated protein structure and function prediction based on the sequence-to-structure-to-function paradigm. Starting from an amino acid sequence, I-TASSER first generates three-dimensional (3D) atomic models from multiple threading alignments and iterative structural assembly simulations. The function of the protein is then inferred by structurally matching the 3D models with other known proteins. The output from a typical server run contains full-length secondary and tertiary structure predictions, and functional annotations on ligand-binding sites, Enzyme Commission numbers and Gene Ontology terms. An estimate of accuracy of the predictions is provided based on the confidence score of the modeling. This protocol provides new insights and guidelines for designing of online server systems for the state-of-the-art protein structure and function predictions. The server is available at http://zhanglab.ccmb.med.umich.edu/I-TASSER.

5,792 citations


Journal ArticleDOI
TL;DR: To develop simple, practical criteria for clinical diagnosis of fibromyalgia that are suitable for use in primary and specialty care and that do not require a tender point examination, and to provide a severity scale for characteristic fibromyalgic symptoms.
Abstract: Objective To develop simple, practical criteria for clinical diagnosis of fibromyalgia that are suitable for use in primary and specialty care and that do not require a tender point examination, and to provide a severity scale for characteristic fibromyalgia symptoms. Methods We performed a multicenter study of 829 previously diagnosed fibromyalgia patients and controls using physician physical and interview examinations, including a widespread pain index (WPI), a measure of the number of painful body regions. Random forest and recursive partitioning analyses were used to guide the development of a case definition of fibromyalgia, to develop criteria, and to construct a symptom severity (SS) scale. Results Approximately 25% of fibromyalgia patients did not satisfy the American College of Rheumatology (ACR) 1990 classification criteria at the time of the study. The most important diagnostic variables were WPI and categorical scales for cognitive symptoms, unrefreshed sleep, fatigue, and number of somatic symptoms. The categorical scales were summed to create an SS scale. We combined the SS scale and the WPI to recommend a new case definition of fibromyalgia: (WPI > or =7 AND SS > or =5) OR (WPI 3-6 AND SS > or =9). Conclusion This simple clinical case definition of fibromyalgia correctly classifies 88.1% of cases classified by the ACR classification criteria, and does not require a physical or tender point examination. The SS scale enables assessment of fibromyalgia symptom severity in persons with current or previous fibromyalgia, and in those to whom the criteria have not been applied. It will be especially useful in the longitudinal evaluation of patients with marked symptom variability.

3,192 citations


Journal ArticleDOI
TL;DR: This work presents an integrative 2-level MSEM mathematical framework that subsumes new and existing multilevel mediation approaches as special cases and uses several applied examples to illustrate the flexibility of this framework.
Abstract: Several methods for testing mediation hypotheses with 2-level nested data have been proposed by researchers using a multilevel modeling (MLM) paradigm. However, these MLM approaches do not accommodate mediation pathways with Level-2 outcomes and may produce conflated estimates of between- and within-level components of indirect effects. Moreover, these methods have each appeared in isolation, so a unified framework that integrates the existing methods, as well as new multilevel mediation models, is lacking. Here we show that a multilevel structural equation modeling (MSEM) paradigm can overcome these 2 limitations of mediation analysis with MLM. We present an integrative 2-level MSEM mathematical framework that subsumes new and existing multilevel mediation approaches as special cases. We use several applied examples and accompanying software code to illustrate the flexibility of this framework and to show that different substantive conclusions can be drawn using MSEM versus MLM.

2,595 citations


Journal ArticleDOI
TL;DR: DendroPy uses a splits-hash mapping to perform rapid calculations of tree distances, similarities and shape under various metrics, and contains rich simulation routines to generate trees under a number of different phylogenetic and coalescent models.
Abstract: Summary: DendroPy is a cross-platform library for the Python programming language that provides for object-oriented reading, writing, simulation and manipulation of phylogenetic data, with an emphasis on phylogenetic tree operations. DendroPy uses a splits-hash mapping to perform rapid calculations of tree distances, similarities and shape under various metrics. It contains rich simulation routines to generate trees under a number of different phylogenetic and coalescent models. DendroPy’s data simulation and manipulation facilities, in conjunction with its support of a broad range of phylogenetic data formats (NEXUS, Newick, PHYLIP, FASTA, NeXML, etc.), allow it to serve a useful role in various phyloinformatics and phylogeographic pipelines. Availability: The stable release of the library is available for download and automated installation through the Python Package Index site (http://pypi.python.org/pypi/DendroPy), while the active development source code repository is available to the public from GitHub (http://github.com/jeetsukumaran/DendroPy).

1,462 citations


Journal ArticleDOI
Robert S. Fisher1, Vicenta Salanova2, Thomas C. Witt2, Robert M. Worth2, Thomas R. Henry3, Robert E. Gross3, Kalarickal J. Oommen4, Ivan Osorio5, Jules M. Nazzaro5, Douglas Labar6, Michael G. Kaplitt6, Michael R. Sperling7, Evan Sandok8, John H. Neal8, Adrian Handforth9, John M. Stern10, Antonio DeSalles9, Steve Chung11, Andrew G. Shetter11, Donna Bergen12, Roy A.E. Bakay12, Jaimie M. Henderson1, Jacqueline A. French13, Gordon H. Baltuch13, William E. Rosenfeld, Andrew Youkilis, William J. Marks14, Paul A. Garcia14, Nicolas Barbaro14, Nathan B. Fountain15, Carl W. Bazil16, Robert R. Goodman16, Guy M. McKhann16, K. Babu Krishnamurthy17, Steven Papavassiliou17, Charles M. Epstein3, John R. Pollard13, Lisa Tonder18, Joan Grebin18, Robert J. Coffey18, Nina M. Graves18, Marc A. Dichter, William Elias, Paul Francel, Robert C. Frysinger, Kevin Graber, John Grant, Gary Heit, Susan T. Herman, Padmaja Kandula, Andres M. Kanner, Jeanne Ann King, Eric Kobylarz, Karen Lapp, Suzette M. LaRoche, Susan Lippmann, Rama Maganti, Timothy Mapstone, Dragos Sabau, Lara M. Schrader, Ashwini Sharan, Mike Smith, David M. Treiman, Steve Wilkinson, Steven Wong, Andro Zangaladze, Shelley Adderley, Brian Bridges, Mimi Callanan, Dawn Cordero, Cecelia Fields, Megan Johnson, MaryAnn Kavalir, Patsy Kretschmar, Carol Macpherson, Kathy Mancl, Marsha Manley, Stephanie Marsh, Jean Montgomery, Pam Mundt, Phani Priya Nekkalapu, Bill Nikolov, Bruce Palmer, Linda Perdue, Alison Randall, David Smith, Linda Smith, Kristen Strybing, Leigh Stott, Robin Taylor, Stacy Thompson, Zornitza Timenova, Bree Vogelsong, Virginia Balbona, Donna K. Broshek, Deborah A. Cahn-Weiner, Lisa Clift, Mary Davidson, Evan Drake, Sally Frutiger, Lynette Featherstone, Chris Grote, Dan Han, Dianne Henry, Jessica Horsfall, Andrea Hovick, Jennifer Gray, David Kareken, Kristin Kirlin, Debbie Livingood, Michele Meyer, Nancy Minniti, Jeannine Morrone Strupinsky, William Schultz, James Scott, Joseph I. Tracy, Stuart Waltonen, Penelope Ziefert, Carla Van Amburg, Mark E Burdelle, Sandra Clements, Robert Cox, Raeleen Dolin, Michelle Fulk, Harinder R. Kaur, Lawrence J. Hirsch, Thomas J. Hoeppner, Andrea Hurt, Mary Komosa, Scott E. Krahl, Laura Ponticello, Mark Quigg, Helene Quinn, Marvin A. Rossi, Patty Schaefer, Christopher Skidmore, Diane Sundstrom, Patricia Trudeau, Monica Volz, Norman C. Wang, Lynette Will, Carol Young 
TL;DR: A multicenter, double‐blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization‐related epilepsy is reported.
Abstract: Summary Purpose: We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy Methods: Participants were adults with medically refractory partial seizures, including secondarily generalized seizures Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation Results: One hundred ten participants were randomized Baseline monthly median seizure frequency was 195 In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0002) Unadjusted median declines at the end of the blinded phase were 145% in the control group and 404% in the stimulated group Complex partial and “most severe” seizures were significantly reduced by stimulation By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months Five deaths occurred and none were from implantation or stimulation No participant had symptomatic hemorrhage or brain infection Two participants had acute, transient stimulation-associated seizures Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events Discussion: Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures Benefit persisted for 2 years of study Complication rates were modest Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures

1,444 citations


Journal ArticleDOI
TL;DR: Patients with Parkinson's disease had similar improvement in motor function after either pallidal or subthalamic stimulation, and nonmotor factors may reasonably be included in the selection of surgical target for deep-brain stimulation.
Abstract: Background Deep-brain stimulation is the surgical procedure of choice for patients with advanced Parkinson's disease. The globus pallidus interna and the subthalamic nucleus are accepted targets for this procedure. We compared 24-month outcomes for patients who had undergone bilateral stimulation of the globus pallidus interna (pallidal stimulation) or subthalamic nucleus (subthalamic stimulation). Methods At seven Veterans Affairs and six university hospitals, we randomly assigned 299 patients with idiopathic Parkinson's disease to undergo either pallidal stimulation (152 patients) or subthalamic stimulation (147 patients). The primary outcome was the change in motor function, as blindly assessed on the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III), while patients were receiving stimulation but not receiving antiparkinsonian medication. Secondary outcomes included self-reported function, quality of life, neurocognitive function, and adverse events. Results Mean changes in the primary out...

1,158 citations


Journal ArticleDOI
TL;DR: In this article, the authors examine how employees' innovative behavior is explained by expectations for such behavior to affect job performance (expected positive performance outcomes) and image inside their organizations (expected image risks and expected image gains).
Abstract: Why do employees engage in innovative behavior at their workplaces? We examine how employees' innovative behavior is explained by expectations for such behavior to affect job performance (expected positive performance outcomes) and image inside their organizations (expected image risks and expected image gains). We found significant effects of all three outcome expectations on innovative behavior. These outcome expectations, as intermediate psychological processes, were shaped by contextual and individual difference factors, including perceived organization support for innovation, supervisor relationship quality, job requirement for innovativeness, employee reputation as innovative, and individual dissatisfaction with the status quo.

1,125 citations


Journal ArticleDOI
TL;DR: The EXPLORER trial enrolled patients with moderately-to-severely active SLE and used aggressive background treatment and sensitive cutoffs for nonresponse, and no differences were noted between placebo and rituximab in the primary and secondary end points.
Abstract: Objective B cells are likely to contribute to the pathogenesis of systemic lupus erythematosus (SLE), and rituximab induces depletion of B cells. The Exploratory Phase II/III SLE Evaluation of Rituximab (EXPLORER) trial tested the efficacy and safety of rituximab versus placebo in patients with moderately-to-severely active extrarenal SLE.

1,117 citations


Journal ArticleDOI
TL;DR: In this article, the authors study the growth of massive galaxies from z = 2 to the present using data from the NOAO/Yale NewFIRM Medium Band Survey.
Abstract: We study the growth of massive galaxies from z = 2 to the present using data from the NOAO/Yale NEWFIRM Medium Band Survey. The sample is selected at a constant number density of n = 2 × 10–4 Mpc–3, so that galaxies at different epochs can be compared in a meaningful way. We show that the stellar mass of galaxies at this number density has increased by a factor of 2 since z = 2, following the relation log Mn (z) = 11.45 – 0.15z. In order to determine at what physical radii this mass growth occurred, we construct very deep stacked rest-frame R-band images of galaxies with masses near Mn (z), at redshifts z = 0.6, 1.1, 1.6, and 2.0. These image stacks of typically 70-80 galaxies enable us to characterize the stellar distribution to surface brightness limits of ~28.5 mag arcsec–2. We find that massive galaxies gradually built up their outer regions over the past 10 Gyr. The mass within a radius of r = 5 kpc is nearly constant with redshift, whereas the mass at 5 kpc < r < 75 kpc has increased by a factor of ~4 since z = 2. Parameterizing the surface brightness profiles, we find that the effective radius and Sersic n parameter evolve as re α (1 + z)–1.3 and n α (1 + z)–1.0, respectively. The data demonstrate that massive galaxies have grown mostly inside-out, assembling their extended stellar halos around compact, dense cores with possibly exponential radial density distributions. Comparing the observed mass evolution to the average star formation rates of the galaxies we find that the growth is likely dominated by mergers, as in situ star formation can only account for ~20% of the mass buildup from z = 2 to z = 0. A direct consequence of these results is that massive galaxies do not evolve in a self-similar way: their structural profiles change as a function of redshift, complicating analyses which (often implicitly) assume self-similarity. The main uncertainties in this study are possible redshift-dependent systematic errors in the total stellar masses and the conversion from light-weighted to mass-weighted radial profiles.

880 citations


Journal ArticleDOI
TL;DR: In this review, the currently known molecular and cellular factors that contribute to SNV to OS are summarized and include high intrinsic OS, high demand for ROS/RNS-based signaling, low ATP production, mitochondrial dysfunction, and high inflammatory response in vulnerable neurons.
Abstract: Oxidative stress (OS), caused by the imbalance between the generation and detoxification of reactive oxygen and nitrogen species (ROS/RNS), plays an important role in brain aging, neurodegenerative diseases, and other related adverse conditions, such as ischemia. While ROS/RNS serve as signaling molecules at physiological levels, an excessive amount of these molecules leads to oxidative modification and, therefore, dysfunction of proteins, nucleic acids, and lipids. The response of neurons to this pervasive stress, however, is not uniform in the brain. While many brain neurons can cope with a rise in OS, there are select populations of neurons in the brain that are vulnerable. Because of their selective vulnerability, these neurons are usually the first to exhibit functional decline and cell death during normal aging, or in age-associated neurodegenerative diseases, such as Alzheimer's disease. Understanding the molecular and cellular mechanisms of selective neuronal vulnerability (SNV) to OS is important in the development of future intervention approaches to protect such vulnerable neurons from the stresses of the aging process and the pathological states that lead to neurodegeneration. In this review, the currently known molecular and cellular factors that contribute to SNV to OS are summarized. Included among the major underlying factors are high intrinsic OS, high demand for ROS/RNS-based signaling, low ATP production, mitochondrial dysfunction, and high inflammatory response in vulnerable neurons. The contribution to the selective vulnerability of neurons to OS by other intrinsic or extrinsic factors, such as deficient DNA damage repair, low calcium-buffering capacity, and glutamate excitotoxicity, are also discussed.

Journal ArticleDOI
TL;DR: A method first introduced by Stolzenberg (1980) for estimating indirect effects in models of mediators and outcomes that are nonlinear functions but linear in their parameters is described and extended.
Abstract: Most treatments of indirect effects and mediation in the statistical methods literature and the corresponding methods used by behavioral scientists have assumed linear relationships between variables in the causal system. Here we describe and extend a method first introduced by Stolzenberg (1980) for estimating indirect effects in models of mediators and outcomes that are nonlinear functions but linear in their parameters. We introduce the concept of the instantaneous indirect effect of X on Y through M and illustrate its computation and describe a bootstrapping procedure for inference. Mplus code as well as SPSS and SAS macros are provided to facilitate the adoption of this approach and ease the computational burden on the researcher.

Journal ArticleDOI
Jarrod Chapman1, Ewen F. Kirkness2, Oleg Simakov3, Oleg Simakov4, Steven E. Hampson5, Therese Mitros3, Thomas Weinmaier6, Thomas Rattei6, Prakash G. Balasubramanian4, Jon Borman2, Dana A. Busam2, Kathryn Disbennett2, Cynthia Pfannkoch2, Nadezhda Sumin2, Granger G. Sutton2, Lakshmi D. Viswanathan2, Brian P. Walenz2, David Goodstein1, Uffe Hellsten1, Takeshi Kawashima3, Simon E. Prochnik1, Nicholas H. Putnam3, Nicholas H. Putnam7, Nicholas H. Putnam1, Shengquiang Shu1, Bruce Blumberg5, Catherine E. Dana5, Lydia Gee5, Dennis F. Kibler5, Lee Law5, Dirk Lindgens5, Daniel E. Martínez8, Jisong Peng5, Philip A. Wigge9, Philip A. Wigge7, Bianca Bertulat4, Corina Guder4, Yukio Nakamura4, Suat Özbek4, Hiroshi Watanabe4, Konstantin Khalturin10, Georg Hemmrich10, Andre Franke10, René Augustin10, Sebastian Fraune10, Eisuke Hayakawa11, Shiho Hayakawa11, Mamiko Hirose11, Jung Shan Hwang11, Kazuho Ikeo11, Chiemi Nishimiya-Fujisawa11, Atshushi Ogura7, Atshushi Ogura11, Toshio Takahashi, Patrick R. H. Steinmetz12, Xiaoming Zhang13, Roland Aufschnaiter14, Marie Kristin Eder14, Anne Kathrin Gorny7, Anne Kathrin Gorny14, Willi Salvenmoser14, Alysha M. Heimberg15, Benjamin M. Wheeler16, Kevin J. Peterson15, Angelika Böttger17, Patrick Tischler6, Alexander Wolf17, Takashi Gojobori11, Karin A. Remington2, Karin A. Remington7, Robert L. Strausberg2, J. Craig Venter2, Ulrich Technau12, Bert Hobmayer14, Thomas C. G. Bosch10, Thomas W. Holstein4, Toshitaka Fujisawa11, Hans R. Bode5, Charles N. David17, Daniel S. Rokhsar1, Daniel S. Rokhsar3, Robert Steele5 
25 Mar 2010-Nature
TL;DR: Comparisons of the Hydra genome to the genomes of other animals shed light on the evolution of epithelia, contractile tissues, developmentally regulated transcription factors, the Spemann–Mangold organizer, pluripotency genes and the neuromuscular junction.
Abstract: The freshwater cnidarian Hydra was first described in 17021 and has been the object of study for 300 years. Experimental studies of Hydra between 1736 and 1744 culminated in the discovery of asexual reproduction of an animal by budding, the first description of regeneration in an animal, and successful transplantation of tissue between animals2. Today, Hydra is an important model for studies of axial patterning3, stem cell biology4 and regeneration5. Here we report the genome of Hydra magnipapillata and compare it to the genomes of the anthozoan Nematostella vectensis6 and other animals. The Hydra genome has been shaped by bursts of transposable element expansion, horizontal gene transfer, trans-splicing, and simplification of gene structure and gene content that parallel simplification of the Hydra life cycle. We also report the sequence of the genome of a novel bacterium stably associated with H. magnipapillata. Comparisons of the Hydra genome to the genomes of other animals shed light on the evolution of epithelia, contractile tissues, developmentally regulated transcription factors, the Spemann–Mangold organizer, pluripotency genes and the neuromuscular junction.

Journal ArticleDOI
Leming Shi1, Gregory Campbell1, Wendell D. Jones, Fabien Campagne2  +198 moreInstitutions (55)
TL;DR: P predictive models for classifying a sample with respect to one of 13 endpoints indicative of lung or liver toxicity in rodents, or of breast cancer, multiple myeloma or neuroblastoma in humans are generated.
Abstract: Gene expression data from microarrays are being applied to predict preclinical and clinical endpoints, but the reliability of these predictions has not been established. In the MAQC-II project, 36 independent teams analyzed six microarray data sets to generate predictive models for classifying a sample with respect to one of 13 endpoints indicative of lung or liver toxicity in rodents, or of breast cancer, multiple myeloma or neuroblastoma in humans. In total, >30,000 models were built using many combinations of analytical methods. The teams generated predictive models without knowing the biological meaning of some of the endpoints and, to mimic clinical reality, tested the models on data that had not been used for training. We found that model performance depended largely on the endpoint and team proficiency and that different approaches generated models of similar performance. The conclusions and recommendations from MAQC-II should be useful for regulatory agencies, study committees and independent investigators that evaluate methods for global gene expression analysis.

Journal ArticleDOI
11 Feb 2010-Nature
TL;DR: This genome sequence of an ancient human obtained from ∼4,000-year-old permafrost-preserved hair provides evidence for a migration from Siberia into the New World some 5,500 years ago, independent of that giving rise to the modern Native Americans and Inuit.
Abstract: We report here the genome sequence of an ancient human. Obtained from approximately 4,000-year-old permafrost-preserved hair, the genome represents a male individual from the first known culture to settle in Greenland. Sequenced to an average depth of 20x, we recover 79% of the diploid genome, an amount close to the practical limit of current sequencing technologies. We identify 353,151 high-confidence single-nucleotide polymorphisms (SNPs), of which 6.8% have not been reported previously. We estimate raw read contamination to be no higher than 0.8%. We use functional SNP assessment to assign possible phenotypic characteristics of the individual that belonged to a culture whose location has yielded only trace human remains. We compare the high-confidence SNPs to those of contemporary populations to find the populations most closely related to the individual. This provides evidence for a migration from Siberia into the New World some 5,500 years ago, independent of that giving rise to the modern Native Americans and Inuit.

Journal ArticleDOI
TL;DR: Reviewing the relevance of standards and standardization in diverse theoretical traditions and sociological subfields, it is called for careful empirical analysis of the specific and unintended consequences of different sorts of standards operating in distinct social domains.
Abstract: Standards and standardization aim to render the world equivalent across cultures, time, and geography. Standards are ubiquitous but underappreciated tools for regulating and organizing social life in modernity, and they lurk in the background of many sociological works. Reviewing the relevance of standards and standardization in diverse theoretical traditions and sociological subfields, we point to the emergence and institutionalization of standards, the difficulties of making standards work, resistance to standardization, and the multiple outcomes of standards. Rather than associating standardization with totalizing narratives of globalization or dehumanization, we call for careful empirical analysis of the specific and unintended consequences of different sorts of standards operating in distinct social domains.

Journal ArticleDOI
TL;DR: The pre-print version of the Published Article can be accessed from the link below - Copyright @ 2010 Springer Verlag as discussed by the authors, which can be viewed as a preprint of the published article.
Abstract: This is the pre-print version of the Published Article, which can be accessed from the link below - Copyright @ 2010 Springer Verlag

Journal ArticleDOI
TL;DR: A comprehensive overview of transporters of the solute carrier family (SLC) is provided with regard to tissue distribution, subcellular localization, and substrate preferences.
Abstract: Transporters influence the disposition of chemicals within the body by participating in absorption, distribution, and elimination. Transporters of the solute carrier family (SLC) comprise a variety of proteins, including organic cation transporters (OCT) 1 to 3, organic cation/carnitine transporters (OCTN) 1 to 3, organic anion transporters (OAT) 1 to 7, various organic anion transporting polypeptide isoforms, sodium taurocholate cotransporting polypeptide, apical sodium-dependent bile acid transporter, peptide transporters (PEPT) 1 and 2, concentrative nucleoside transporters (CNT) 1 to 3, equilibrative nucleoside transporter (ENT) 1 to 3, and multidrug and toxin extrusion transporters (MATE) 1 and 2, which mediate the uptake (except MATEs) of organic anions and cations as well as peptides and nucleosides. Efflux transporters of the ATP-binding cassette superfamily, such as ATP-binding cassette transporter A1 (ABCA1), multidrug resistance proteins (MDR) 1 and 2, bile salt export pump, multidrug resistance-associated proteins (MRP) 1 to 9, breast cancer resistance protein, and ATP-binding cassette subfamily G members 5 and 8, are responsible for the unidirectional export of endogenous and exogenous substances. Other efflux transporters [ATPase copper-transporting β polypeptide (ATP7B) and ATPase class I type 8B member 1 (ATP8B1) as well as organic solute transporters (OST) α and β] also play major roles in the transport of some endogenous chemicals across biological membranes. This review article provides a comprehensive overview of these transporters (both rodent and human) with regard to tissue distribution, subcellular localization, and substrate preferences. Because uptake and efflux transporters are expressed in multiple cell types, the roles of transporters in a variety of tissues, including the liver, kidneys, intestine, brain, heart, placenta, mammary glands, immune cells, and testes are discussed. Attention is also placed upon a variety of regulatory factors that influence transporter expression and function, including transcriptional activation and post-translational modifications as well as subcellular trafficking. Sex differences, ontogeny, and pharmacological and toxicological regulation of transporters are also addressed. Transporters are important transmembrane proteins that mediate the cellular entry and exit of a wide range of substrates throughout the body and thereby play important roles in human physiology, pharmacology, pathology, and toxicology.

Journal ArticleDOI
TL;DR: An architectural framework for resilience and survivability in communication networks is provided and a survey of the disciplines that resilience encompasses is provided, along with significant past failures of the network infrastructure.

Journal ArticleDOI
TL;DR: The authors developed and evaluated a measure called the Dimensional Obsessive-Compulsive Scale (DOCS) to address limitations of existing OC symptom measures and hold promise as a measure of OC symptoms in clinical and research settings.
Abstract: Although several measures of obsessive-compulsive (OC) symptoms exist, most are limited in that they are not consistent with the most recent empirical findings on the nature and dimensional structure of obsessions and compulsions. In the present research, the authors developed and evaluated a measure called the Dimensional Obsessive-Compulsive Scale (DOCS) to address limitations of existing OC symptom measures. The DOCS is a 20-item measure that assesses the four dimensions of OC symptoms most reliably replicated in previous structural research. Factorial validity of the DOCS was supported by exploratory and confirmatory factor analyses of 3 samples, including individuals with OC disorder, those with other anxiety disorders, and nonclinical individuals. Scores on the DOCS displayed good performance on indices of reliability and validity, as well as sensitivity to treatment and diagnostic sensitivity, and hold promise as a measure of OC symptoms in clinical and research settings.

Journal ArticleDOI
TL;DR: This work proposes that social cognition can and should be enriched by an explicit recognition that conceptual metaphor is a unique cognitive mechanism that shapes social thought and attitudes, and introduces the metaphoric transfer strategy as a means of empirically assessing whether metaphors influence social information processing in ways that are distinct from the operation of schemas alone.
Abstract: Social cognition is the scientific study of the cognitive events underlying social thought and attitudes. Currently, the field’s prevailing theoretical perspectives are the traditional schema view and embodied cognition theories. Despite important differences, these perspectives share the seemingly uncontroversial notion that people interpret and evaluate a given social stimulus using knowledge about similar stimuli. However, research in cognitive linguistics (e.g., Lakoff & Johnson, 1980) suggests that people construe the world in large part through conceptual metaphors, which enable them to understand abstract concepts using knowledge of superficially dissimilar, typically more concrete concepts. Drawing on these perspectives, we propose that social cognition can and should be enriched by an explicit recognition that conceptual metaphor is a unique cognitive mechanism that shapes social thought and attitudes. To advance this metaphor-enriched perspective, we introduce the metaphoric transfer strategy as a means of empirically assessing whether metaphors influence social information processing in ways that are distinct from the operation of schemas alone. We then distinguish conceptual metaphor from embodied simulation—the mechanism posited by embodied cognition theories—and introduce the alternate source strategy as a means of empirically teasing apart these mechanisms. Throughout, we buttress our claims with empirical evidence of the influence of metaphors on a wide range of social psychological phenomena. We outline directions for future research on the strength and direction of metaphor use in social information processing. Finally, we mention specific benefits of a metaphor-enriched perspective for integrating and generating social cognitive research and for bridging social cognition with neighboring fields.

Journal ArticleDOI
06 Oct 2010-Neuron
TL;DR: It is concluded that empathy-related insula activation can motivate costly helping, whereas an antagonistic signal in nucleus accumbens reduces the propensity to help.

Journal ArticleDOI
22 Jul 2010-Nature
TL;DR: It is demonstrated how earlier emergence from hibernation and earlier weaning of young has led to a longer growing season and larger body masses before hibernation, and this helps explain how a shift in phenology can cause simultaneous phenotypic and demographic changes.
Abstract: Environmental change has altered the phenology, morphological traits and population dynamics of many species. However, the links underlying these joint responses remain largely unknown owing to a paucity of long-term data and the lack of an appropriate analytical framework. Here we investigate the link between phenotypic and demographic responses to environmental change using a new methodology and a long-term (1976-2008) data set from a hibernating mammal (the yellow-bellied marmot) inhabiting a dynamic subalpine habitat. We demonstrate how earlier emergence from hibernation and earlier weaning of young has led to a longer growing season and larger body masses before hibernation. The resulting shift in both the phenotype and the relationship between phenotype and fitness components led to a decline in adult mortality, which in turn triggered an abrupt increase in population size in recent years. Direct and trait-mediated effects of environmental change made comparable contributions to the observed marked increase in population growth. Our results help explain how a shift in phenology can cause simultaneous phenotypic and demographic changes, and highlight the need for a theory integrating ecological and evolutionary dynamics in stochastic environments.

Journal ArticleDOI
TL;DR: Results indicate that Andropogon ecotypes adapt to their local soil and indigenous AM fungal communities such that mycorrhizal exchange of the most limiting resource is maximized.
Abstract: Symbioses may be important mechanisms of plant adaptation to their environment. We conducted a reciprocal inoculation experiment to test the hypothesis that soil fertility is a key driver of local adaptation in arbuscular mycorrhizal (AM) symbioses. Ecotypes of Andropogon gerardii from phosphorus-limited and nitrogen-limited grasslands were grown with all possible “home and away” combinations of soils and AM fungal communities. Our results indicate that Andropogon ecotypes adapt to their local soil and indigenous AM fungal communities such that mycorrhizal exchange of the most limiting resource is maximized. Grasses grown in home soil and inoculated with home AM fungi produced more arbuscules (symbiotic exchange structures) in their roots than those grown in away combinations. Also, regardless of the host ecotype, AM fungi produced more extraradical hyphae in their home soil, and locally adapted AM fungi were, therefore, able to sequester more carbon compared with nonlocal fungi. Locally adapted mycorrhizal associations were more mutualistic in the two phosphorus-limited sites and less parasitic at the nitrogen-limited site compared with novel combinations of plants, fungi, and soils. To our knowledge, these findings provide the strongest evidence to date that resource availability generates evolved geographic structure in symbioses among plants and soil organisms. Thus, edaphic origin of AM fungi should be considered when managing for their benefits in agriculture, ecosystem restoration, and soil-carbon sequestration.

Proceedings ArticleDOI
04 Nov 2010
TL;DR: A distributed incremental data aggregation approach, in which data aggregation is performed at all smart meters involved in routing the data from the source meter to the collector unit, which is especially suitable for smart grids with repetitive routine data aggregation tasks.
Abstract: In this paper, we present a distributed incremental data aggregation approach, in which data aggregation is performed at all smart meters involved in routing the data from the source meter to the collector unit. With a carefully constructed aggregation tree, the aggregation route covers the entire local neighborhood or any arbitrary set of designated nodes with minimum overhead. To protect user privacy, homomorphic encryption is used to secure the data en route. Therefore, all the meters participate in the aggregation, without seeing any intermediate or final result. In this way, our approach supports efficient data aggregation in smart grids, while fully protecting user privacy. This approach is especially suitable for smart grids with repetitive routine data aggregation tasks.

Journal ArticleDOI
11 Nov 2010-Nature
TL;DR: It is shown, using quantitative mass spectrometry-based proteomics and phenotypic profiling, that levels of protein expression in aneuploid yeast strains largely scale with chromosome copy numbers, following the same trend as that observed for the transcriptome, and that aneuPLoidy confers diverse phenotypes.
Abstract: Aneuploidy, referring here to genome contents characterized by abnormal numbers of chromosomes, has been associated with developmental defects, cancer and adaptive evolution in experimental organisms. However, it remains unresolved how aneuploidy impacts gene expression and whether aneuploidy could directly bring about phenotypic variation and improved fitness over that of euploid counterparts. Here we show, using quantitative mass spectrometry-based proteomics and phenotypic profiling, that levels of protein expression in aneuploid yeast strains largely scale with chromosome copy numbers, following the same trend as that observed for the transcriptome, and that aneuploidy confers diverse phenotypes. We designed a novel scheme to generate, through random meiotic segregation, 38 stable and fully isogenic aneuploid yeast strains with distinct karyotypes and genome contents between 1N and 3N without involving any genetic selection. Through quantitative growth assays under various conditions or in the presence of a panel of chemotherapeutic or antifungal drugs, we found that some aneuploid strains grew significantly better than euploid control strains under conditions suboptimal for the latter. These results provide strong evidence that aneuploidy directly affects gene expression at both the transcriptome and proteome levels and can generate significant phenotypic variation that could bring about fitness gains under diverse conditions. Our findings suggest that the fitness ranking between euploid and aneuploid cells is dependent on context and karyotype, providing the basis for the notion that aneuploidy can directly underlie phenotypic evolution and cellular adaptation.

Journal ArticleDOI
TL;DR: This work distinguished the molecular events responsible for the different phases of mitophagy and placed Nix upstream of the events, finding that Nix was required for the autophagy induction.

Journal ArticleDOI
TL;DR: Knockdown of AFF4 in leukemic cells shows reduction in MLL chimera target gene expression, suggesting that AFF 4/SEC could be a key regulator in the pathogenesis of leukemia through many of the MLL partners.

Journal ArticleDOI
TL;DR: A meta-analysis of 22 studies involving 27 plant species shows a significant reduction in the proportion of seeds outcrossed in response to anthropogenic habitat modifications, and whether reproductive assurance through selfing effectively compensates for reduced outcrossing is discussed.
Abstract: There is increasing evidence that human disturbance can negatively impact plant–pollinator interactions such as outcross pollination. We present a meta-analysis of 22 studies involving 27 plant species showing a significant reduction in the proportion of seeds outcrossed in response to anthropogenic habitat modifications. We discuss the evolutionary consequences of disturbance on plant mating systems, and in particular whether reproductive assurance through selfing effectively compensates for reduced outcrossing. The extent to which disturbance reduces pollinator versus mate availability could generate diverse selective forces on reproductive traits. Investigating how anthropogenic change influences plant mating will lead to new opportunities for better understanding of how mating systems evolve, as well as of the ecological and evolutionary consequences of human activities and how to mitigate them.

Journal ArticleDOI
TL;DR: In this article, the authors measured the transverse momentum and pseudorapidity distributions in proton-proton collisions at root s = 7 TeV with the inner tracking system of the CMS detector at the LHC.
Abstract: Charged-hadron transverse-momentum and pseudorapidity distributions in proton-proton collisions at root s = 7 TeV are measured with the inner tracking system of the CMS detector at the LHC. The charged-hadron yield is obtained by counting the number of reconstructed hits, hit pairs, and fully reconstructed charged-particle tracks. The combination of the three methods gives a charged-particle multiplicity per unit of pseudorapidity dN(ch)/d eta vertical bar(vertical bar eta vertical bar<0.5) = 5.78 +/- 0.01(stat) +/- 0.23(stat) for non-single-diffractive events, higher than predicted by commonly used models. The relative increase in charged-particle multiplicity from root s = 0.9 to 7 TeV is [66.1 +/- 1.0(stat) +/- 4.2(syst)]%. The mean transverse momentum is measured to be 0.545 +/- 0.005(stat) +/- 0.015(syst) GeV/c. The results are compared with similar measurements at lower energies.