bluuebunny/crossref_metadata_2025 huggingface dataset:
Science Translational Medicine
Podcast: 5 May 2010
Authors: Edelman Elazer R. , Kelner Katrina L.
Published: May 2010

A conversation with
Science Translational Medicine
's Senior Scientific Advisor about the unique challenges and benefits of combining engineering and biology in translational medicine.
Insights from geodynamical modeling on possible fates of continental mantle lithosphere: collision, removal, and overturnThis article is one of a series of papers published in this Special Issue on the theme Lithoprobe — parameters, processes, and the evolution of a continent.
Authors: Pysklywec Russell N. , Gogus Oguz , Percival J. , Cruden A. R. , Beaumont C.
Published: May 2010

Geodynamic modeling demonstrates various modes of behaviour of the tectonically active continental mantle lithosphere. At continental collision, mantle lithosphere below thickening crust can be accommodated by mixed subduction-like consumption and viscous drip-like instability, depending on the material rheology, temperature, and convergence velocity. Late-stage slab steepening, dual-sided and ablative consumption, and breakoff can occur as the buoyant crust resists subduction. Removal of accreted crust by erosion can modify how even the deepest portions of the mantle lithosphere evolves during contraction. When gravitational forcing rather than plate shortening dominates, mantle lithosphere may be removed through viscous dripping-like instability or delamination. The removal induces crustal heating, modified topography, and deformation, but distinctive styles of these develop depending on whether mantle lithosphere delaminates or drips. With a modified density stratification postulated for the Archean, relatively buoyant mantle lithosphere may undergo an in-situ overturn when triggered by unstable dense eclogite and basal traction. This causes a pulse of rapid crustal heating as hot lowermost lithosphere is brought into contact with the base of the crust. As an interpretive tool, the geodynamic experiments illustrate some of the dynamically feasible modes of behaviour and controlling parameters for the continental mantle lithosphere in ancient to modern tectonic environments.
The Grenville Orogen explained? Applications and limitations of integrating numerical models with geological and geophysical dataThis article is one of a series of papers published in this Special Issue on the theme Lithoprobe — parameters, processes, and the evolution of a continent.
Authors: Jamieson R. A. , Beaumont C. , Warren C. J. , Nguyen M. H.
Published: May 2010

Numerical models offer powerful insights into tectonic processes, especially when their validity can be tested against geological and geophysical observations from natural orogenic belts. Here we explain some of the criteria for success in integrating orogenic models with data, using examples from the Grenville Orogen. Model designs must be simplified by comparison with nature to illuminate the first-order processes that control orogenic evolution, which limits the extent to which model results can reproduce geological observations. For the western Grenville Orogen, observed variations in geological properties are represented by lower crustal blocks with strength decreasing from the exterior to the interior of the model. GO-series models with this design reproduce the first-order crustal architecture of the Georgian Bay and Montréal – Val d’Or Lithoprobe transects. Both constant-convergence and stop-convergence models produce similar geometries, but only stop-convergence models produce normal-sense shear zones like those observed. EGO-series models, incorporating an initial weak zone bounded by stronger lower crustal blocks, predict exhumation of high-pressure rocks as observed in the eastern Grenville Orogen, although other aspects of these model results are not as successful. The single most important test of a geodynamic model is its ability to integrate diverse and independent observations in a self-consistent manner. Other criteria include consistency with crustal-scale geometry and structural and metamorphic histories. By these criteria, the present models account reasonably well for the syn- and post-convergent evolution of the western Grenville Orogen, but further work is required to produce a fully satisfactory model for the eastern end of the system.
ANALYTICAL STUDY OF EXTERNAL MAGNETIC FIELD EFFECT ON THE ENERGY LEVELS OF A TWO-ELECTRON QUANTUM DOT
Authors: HASSANABADI H. , HAMZAVI M. , RAJABI A. A.
Published: May 2010

We introduce an analytical method to solve the corresponding Schrödinger equation of a two-electron quantum dot in the presence of harmonic plus linear terms as well as a term related to spin interaction. Next, we calculate the energy eigenstates in the presence of an external magnetic field. The obtained results are comparable to those of [Formula: see text] expansion and WKB methods.
ON THE DECIDABILITY OF MEMBERSHIP IN THE GLOBAL OF A MONOID PSEUDOVARIETY
Authors: AUINGER K.
Published: May 2010

It is proved that the global operator g : V ↦ gV does not preserve decidability of membership. More specifically, some of Kad'ourek's results on the locality of the pseudovariety DG in combination with a construction by Steinberg and the author are used to find a pseudovariety H of groups, with decidable membership, for which membership in the category pseudovariety gDH is undecidable. This answers a question raised by Rhodes and Steinberg. As a consequence, the operator V ↦ V * D = V * LI does not preserve decidability of membership either — this refutes an old conjecture by Straubing.
PERIODIC ELEMENTS OF THE FREE IDEMPOTENT GENERATED SEMIGROUP ON A BIORDERED SET
Authors: EASDOWN D. , SAPIR M. V. , VOLKOV M. V.
Published: May 2010

We show that every periodic element of the free idempotent generated semigroup on an arbitrary biordered set belongs to a subgroup of the semigroup.
MODULES
Authors: TILSON BRET
Published: May 2010

This paper introduces the notion of a module over a graph and defines the wreath product and derived module of a relational morphism in this context.
FPQRNA: HARDWARE-ACCELERATED QRNA PACKAGE FOR NONCODING RNA GENE DETECTING ON FPGA
Authors: XIA FEI , DOU YONG , LEI GUO-QING
Published: May 2010

Noncoding RNAs (ncRNAs) have important functional roles in biological processes and have become a central research interest in modern molecular biology. However, how to find ncRNA attracts much more attention since ncRNA gene sequences do not have strong statistical signals, unlike protein coding genes. QRNA is a powerful program and has been widely used as an efficient analysis tool to detect ncRNA gene at present. Unfortunately, the O(L3) computing requirements and complicated data dependency greatly limit the usefulness of QRNA package with the explosion in gene database. In this paper, we present a fine-grained parallel QRNA prototype system, FPQRNA, for accelerating ncRNA gene detection application on FPGA chip. We propose a systolic-like array architecture with multiple PEs (Processing Elements). We partition the tasks by columns and assign tasks to PEs for load balance. We exploit data reuse schemes to reduce the need to load matrices from external memory. The experimental results show a speedup factor of more than 18× over the QRNA - 2.0.3c software running on a PC platform with AMD Phenom 9650 Quad CPU for pairwise sequence alignment with 996 residues, however the power consumption of our FPGA accelerator is only about 30% of that of the general-purpose microprocessors.
Synthesis and spectral property study of porphyrin-anthraquinone dyads bonded through azo
Authors: Tao Minli , Liu Dongzhi , Zhang Minghua , Zhou Xueqin , Li Luhai
Published: May 2010

To determine if the dihedral angle between the phenyl group and the porphyrin ring in the meso-phenyl porphyrin (H2TPP) could be adjusted by selective substitution of the naphthyl group for phenyl groups, novel dyads with a free-base porphyrin donor and anthraquinone acceptor linked by a rigid azo bond were synthesized and their spectral properties were investigated in detail. The Soret absorption band of dyads with meso-naphthyl groups in porphyrin shows 5–7 nm red shift as compared to the corresponding raw materials due to the introduction of the anthraquinone moiety. Fluorescence from the porphyrin moiety was found to be intensely quenched with the addition of anthraquinone moiety in the dyads; the highest quenching rate was observed to be 95% in the dyad prepared by meso-tetranaphthyl porphyrin. This indicates that the efficiency of the intramolecular photoinduced electron transfer in porphyrin-anthraquinone dyads could be changed by substituting the meso-phenyl group in porphyrin for the meso-naphthyl group.
The elimination of molecular chlorine catalyzed by BCl3: an aspect of chloroboron subphthalocyanine formation
Authors: Nohr Ronald S. , McCallum Charles M. , Schuchmann Heinz-Peter
Published: May 2010

This study is focused on the final stage of the formation mechanism of chloroboron subphthalocyanine from boron trichloride and phthalonitrile, in the context of recent work on the earlier stages of this reaction. The results of extensive quantum-chemical energetic, structural, and charge-distribution computations show that a catalytic effect of boron trichloride is most probably essential to explain the fact that molecular chlorine is liberated in the formation of chloroboron subphthalocyanine (reaction 2). This process turns out to be closely concerted (reactions 2a and 2b).
O-H insertion and tandem N-H insertion/cyclization reactions using an iron porphyrin as catalyst with diazo compounds as carbene sources
Authors: Mbuvi Harun M. , Klobukowski Erik R. , Roberts Gina M. , Woo L. Keith
Published: May 2010

Iron(III) tetraphenylporphyrin chloride, Fe(TPP)Cl , efficiently catalyzed the insertion of carbenes derived from methyl 2-phenyldiazoacetates into O-H bonds of aliphatic and aromatic alcohols, with yields generally above 80%. Although the analogous N-H insertions are rapid at room temperature, the O-H insertion reactions are slower and required heating in refluxing methylene chloride for about 8 hours using 1.0 mol.% catalyst. Fe(TPP)Cl was also found to be effective for tandem N-H insertion/cyclization reactions when 1,2-diamines and 1,2-alcoholamines were treated with diazo reagents to give piperazinones and morpholinones and related analogs such as quinoxalinones and benzoxazin-2-ones. This approach provides a new one-pot route for synthesizing these classes of heterocyclic compounds.
The Rise and Routinization of Social Capital, 1988–2008
Authors: Woolcock Michael
Published: May 2010

Social capital has not merely risen as a social scientific term in the scholarly literature; it has become routinized into everyday conversation and policy discourse across an extraordinarily diverse set of disciplines and substantive domains in countries around the world. It currently enjoys citation counts some 100 times larger than it did just 20 years ago and its popularity continues apace, despite numerous trenchant criticisms. Some of the reasons for the rise and routinization of social capital are explored, especially as they pertain to issues of primary concern to political science, namely collective action, economic development, and democratic governance (issues made especially salient by Putnam 1993 ). While ongoing debate is to be welcomed and rigor from individual scholars required, social capital must continue to do double duty: providing for diverse audiences a simple and intuitively appealing way of highlighting the intrinsic and instrumental importance of social relationships, while also yielding at the appropriate time to more precise terms appropriate for particular specialist audiences. Social capital is another “essentially contested concept” ( Gallie 1956 ) whose utility to social science (and beyond) rests less on its capacity to forge an inherently elusive scholarly or policy consensus on complex issues than its capacity to facilitate constructive dialogue about agreements and disagreements between groups who would otherwise rarely (if ever) interact.
What Political Science Can Learn from the New Political History
Authors: Zelizer Julian E.
Published: May 2010

This essay explores how three components of the new political history—research on the motivations behind the rise of conservatism, the discovery of the nineteenth-century state, and arguments about the particularities of public policy—can offer useful analytical tools for political scientists.
Indigenous Peoples' Politics in Latin America
Authors: Van Cott Donna Lee
Published: May 2010

Political science research on indigenous peoples' politics in Latin America is methodologically diverse and interdisciplinary. It has produced significant insights about citizenship, reform of the state, and the causes and consequences of the emergence and success of identity-based social movements and political parties. In order to expand and deepen our knowledge, future research should pursue three goals. First, scholars should explore a wider selection of cases, including countries where indigenous populations are small and where dramatic events have not occurred, in order to better explain more common types of indigenous political mobilization in the region. Second, they should better connect the study of indigenous politics to that of Afro-descendent movements and gender and, thus, expand our understanding of racial and gender politics. Third, they should be more critical of the democratic performance of indigenous organizations and politicians, especially when they hold public office.
The Politics of Effective Foreign Aid
Authors: Wright Joseph , Winters Matthew
Published: May 2010

There is little consensus on whether foreign aid can reliably increase economic growth in recipient countries. We review the literature on aid allocation and provide new evidence suggesting that since 1990 aid donors reward political contestation but not political inclusiveness. Then we examine some challenges in analyzing cross-national data on the aid/growth relationship. Finally, we discuss the causal mechanisms through which foreign aid might affect growth and argue that politics can be viewed as both (a) an exogenous constraint that conditions the causal process linking aid to growth and (b) an endogenous factor that is affected by foreign aid and in turn impacts economic growth.
The Immutability of Categories and the Reshaping of Southern Politics
Authors: Kousser J. Morgan
Published: May 2010

How did the no-party, extremely-low-turnout, fragmented political system that V.O. Key, Jr. described in his 1949 book Southern Politics get transformed into the Republican-dominant, average-turnout, highly-organized political structure that propelled Georgia Republican Newt Gingrich into the House Speakership in 1995? After a long series of analytical narratives that focused on racial explanations for the shifts in white voting behavior, several of the most recent works have emphasized class and economic development. I suggest that both explanations are misleading because they treat race, class, and party as stable phenomena, when it is the changes in these phenomena and in their interactions that ought to be the focus of explanations for the reshaping of southern politics. A comprehensive successor to Key's masterwork will have to blend religion and ideology (which have also undergone dramatic changes in the six decades of southern history since Key wrote) with race and class, and it will have to describe and explain changes in governance, as well.
Legislative Obstructionism
Authors: Wawro Gregory J. , Schickler Eric
Published: May 2010

We review debates concerning the evolution and impact of parliamentary obstruction in the U.S. Senate, focusing on path dependency versus remote majoritarian perspectives. We consider the viability of circumventing supermajority requirements for rules changes by using rulings from the chair to establish precedents. Because the viability of this approach depends, at least in part, on the anticipated reaction of the public, we conduct a preliminary analysis of public opinion data from the 1940s through the 1960s and from the showdown over the obstruction of judicial nominees in 2005. We contend that the balance of the evidence favors the position that senators have generally supported the maintenance of the filibuster and have been able to make procedural adjustments when obstruction threatened a committed majority's top priorities, although we offer some important refinements required in comparing the historical operation of obstruction to its impact in today's Senate.
The Politics of Inequality in America: A Political Economy Framework
Authors: Jacobs Lawrence R. , Soss Joe
Published: May 2010

Theories of political economy offer rich intellectual resources for scholars today who hope to explain some of the most striking real-world changes of contemporary American politics, including the dramatic widening of economic inequality since the 1970s, the financial and economic breakdowns since 2008, and the government policies that contributed to these developments. Yet few scholars in American politics have been making use of these resources. This article reviews research on the politics of inequality within the United States and situates it more explicitly within an intellectual framework for the study of political economy. The article traces the decline of political economy research within mainstream scholarship on American politics and reviews the upsurge of interest in the politics of inequality. It develops a typology of distinct frameworks for analyzing the American political economy and for bringing greater intellectual organization to a growing but disparate body of research.
Political Theory of Empire and Imperialism
Authors: Pitts Jennifer
Published: May 2010

The past decade has seen a spate of new work on empire in political theory and the history of political thought. Much of this work has focused on the place of empire in the thought of many canonical thinkers and in the formation of modern liberalism and related arenas, such as postcolonial settler societies and the discipline of international law. Political theory's turn to empire has been belated in comparison to other fields, such as history, literature, and anthropology, which had been grappling with the histories and legacies of modern European empires since the 1970s. Despite intense attention to the question of American imperialism during the Bush administration, political theory arguably continues to fail to deal adequately with the imperial features of the current global order, including the substantial responsibility on the part of the great powers for conditions such as extreme poverty, ecological crisis, civil conflict, and tyranny around the world.
Christian Democracy
Authors: Kalyvas Stathis N. , van Kersbergen Kees
Published: May 2010

Despite its centrality in European politics, Christian democracy came to be the object of systematic research only recently. We review the research that has emerged since the mid-1990s and pinpoint its contributions in specifying the origins, evolution, and broader impact of Christian democratic parties. We begin with a discussion of the origins of Christian democracy and show that it is a distinctive political movement; we review the state of contemporary Christian democratic politics, describe the impact of Christian democracy on the process of European integration, evaluate the content of the Christian democratic welfare regime, and explore whether the European Christian democratic experience travels outside Europe and Christianity, especially in the world of political Islam. We conclude with an overview of the future outlook of this political movement.
Origins and Persistence of Economic Inequality
Authors: Boix Carles
Published: May 2010

After reviewing the current literature on the causes of economic inequality, the article models the historical emergence of inequality as the result of a key technological change (i.e., the adoption of agriculture) that widened income differentials and led to the construction of state institutions, which shaped (depending on their particular nature, more or less authoritarian) the final distribution of economic assets within and across different societies. The article then explores the evolution of inequality in societies already endowed with state structures: A stream of biased technological shocks happens randomly and the “decisive” voter (who differs across political regimes) accepts or blocks them as a function of their effect on her net income. The decisive voter's response determines the overall distribution of income. The model is employed to give a coherent account of some broad historical trends in the evolution of income inequality.
Treaty Compliance and Violation
Authors: Simmons Beth
Published: May 2010

International law has enjoyed a recent renaissance as an important subfield of study within international relations. Two trends are evident in the recent literature. First, the obsession with theoretical labels is on the decline. Second, empirical, especially quantitative, work is burgeoning. This article reviews the literature in four issues areas—security, war, and peace; international trade; protection of the environment; and human rights—and concludes we have a much stronger basis for assessing claims about compliance and violation now than was the case only a few years ago. Still, the literature suffers from a few weaknesses, including problems of selection and endogeneity of treaties themselves and an enduring state-centric focus, despite the fact that researchers recognize that nonstate and substate actors influence treaty behavior. Nonetheless, the quality and quantity of new work demonstrates that international law has regained an important place in the study of international politics.
Oxidation of intramyocellular lipids is dependent on mitochondrial function and the availability of extracellular fatty acids
Authors: Corpeleijn Eva , Hessvik Nina P. , Bakke Siril S. , Levin Klaus , Blaak Ellen E. , Thoresen G. Hege , Gaster Michael , Rustan Arild C.
Published: May 2010

Obesity and insulin resistance are related to both enlarged intramyocellular triacylglycerol stores and accumulation of lipid intermediates. We investigated how lipid overflow can change the oxidation of intramyocellular lipids (ICLOX) and intramyocellular lipid storage (ICL). These experiments were extended by comparing these processes in primary cultured myotubes established from healthy lean and obese type 2 diabetic (T2D) individuals, two extremes in a range of metabolic phenotypes. ICLs were prelabeled for 2 days with 100 μM [14C]oleic acid (OA). ICLOX was studied using a 14CO2 trapping system and measured under various conditions of extracellular OA (5 or 100 μM) and glucose (0.1 or 5.0 mM) and the absence or presence of mitochondrial uncoupling [carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP)]. First, increased extracellular OA availability (5 vs. 100 μM) reduced ICLOX by 37%. No differences in total lipolysis were observed between low and high OA availability. Uncoupling with FCCP restored ICLOX to basal levels during high OA availability. Mitochondrial mass was positively related to ICLOX, but only in myotubes from lean individuals. In all, a lower mitochondrial mass and lower ICLOX were related to a higher cell-associated OA accumulation. Second, myotubes established from obese T2D individuals showed reduced ICLOX. ICLOX remained lower during uncoupling ( P < 0.001), even with comparable mitochondrial mass, suggesting decreased mitochondrial function. Furthermore, the variation in ICLOX in vitro was significantly related to the in vivo fasting respiratory quotient of all subjects ( P < 0.02). In conclusion, the rate of ICLOX is dependent on the availability of extracellular fatty acids and mitochondrial function rather than mitochondrial mass.
Changes in S1 Neural Responses During Tactile Discrimination Learning
Authors: Wiest Michael C. , Thomson Eric , Pantoja Janaina , Nicolelis Miguel A. L.
Published: May 2010

In freely moving rats that are actively performing a discrimination task, single-unit responses in primary somatosensory cortex (S1) are strikingly different from responses to comparable tactile stimuli in immobile rats. For example, in the active discrimination context prestimulus response modulations are common, responses are longer in duration and more likely to be inhibited. To determine whether these differences emerge as rats learned a whisker-dependent discrimination task, we recorded single-unit S1 activity while rats learned to discriminate aperture-widths using their whiskers. Even before discrimination training began, S1 responses in freely moving rats showed many of the signatures of active responses, such as increased duration of response and prestimulus response modulations. As rats subsequently learned the discrimination task, single unit responses changed: more cortical units responded to the stimuli, neuronal sensory responses grew in duration, and individual neurons better predicted aperture-width. In summary, the operant behavioral context changes S1 tactile responses even in the absence of tactile discrimination, whereas subsequent width discrimination learning refines the S1 representation of aperture-width.
A Dynamic Role for GABA Receptors on the Firing Pattern of Midbrain Dopaminergic Neurons
Authors: Lobb Collin J. , Wilson Charles J. , Paladini Carlos A.
Published: May 2010

Dopaminergic neurons are subject to a significant background GABAergic input in vivo. The presence of this GABAergic background might be expected to inhibit dopaminergic neuron firing. However, dopaminergic neurons are not all silent but instead fire in single-spiking and burst firing modes. Here we present evidence that phasic changes in the tonic activity of GABAergic afferents are a potential extrinsic mechanism that triggers bursts and pauses in dopaminergic neurons. We find that spontaneous single-spiking is more sensitive to activation of GABA receptors than phasic N-methyl-d-aspartate (NMDA)-mediated burst firing in rat slices (P15–P31). Because tonic activation of GABAA receptors has previously been shown to suppress burst firing in vivo, our results suggest that the activity patterns seen in vivo are the result of a balance between excitatory and inhibitory conductances that interact with the intrinsic pacemaking currents observed in slices. Using the dynamic clamp technique, we applied balanced, constant NMDA and GABAA receptor conductances into dopaminergic neurons in slices. Bursts could be produced by disinhibition (phasic removal of the GABAA receptor conductance), and these bursts had a higher frequency than bursts produced by the same NMDA receptor conductance alone. Phasic increases in the GABAA receptor conductance evoked pauses in firing. In contrast to NMDA receptor, application of constant AMPA and GABAA receptor conductances caused the cell to go into depolarization block. These results support a bidirectional mechanism by which GABAergic inputs, in balance with NMDA receptor–mediated excitatory inputs, control the firing pattern of dopaminergic neurons.
Rank Signals in Four Areas of Macaque Frontal Cortex During Selection of Actions and Objects in Serial Order
Authors: Berdyyeva Tamara K. , Olson Carl R.
Published: May 2010

Neurons in several areas of monkey frontal cortex exhibit ordinal position (rank) selectivity during the performance of serial order tasks. It has been unclear whether rank selectivity or the dependence of rank selectivity on task context varies across the areas of frontal cortex. To resolve this issue, we recorded from neurons in the supplementary motor area (SMA), presupplementary motor area (pre-SMA), supplementary eye field (SEF), and dorsolateral prefrontal cortex (dlPFC) as monkeys performed two oculomotor tasks, one requiring the selection of three actions in sequence and the other requiring the selection of three objects in sequence. We found that neurons representing all ranks were present in all areas. Only to a moderate degree did the prevalence and nature of rank selectivity vary from area to area. The two most prominent inter-area differences involved a lower prevalence of rank selectivity in the dlPFC than in the other areas and a higher proportion of neurons preferring late ranks in the SMA and SEF than in the other areas. Neurons in all four areas are rank generalists in the sense of favoring the same rank in both the serial action task and the serial object task.
Response Competition in the Primary Motor Cortex: Corticospinal Excitability Reflects Response Replacement During Simple Decisions
Authors: Michelet Thomas , Duncan Gary H. , Cisek Paul
Published: May 2010

It has been suggested that, during decisions about actions, multiple options are initially specified in parallel and then gradually eliminated in a competition for overt execution. To further test this hypothesis, we studied the modulation of human corticospinal excitability during the reaction time of the Eriksen flanker task. In the task, subjects responded with finger flexion or extension to a central arrow while ignoring congruent or incongruent flanker arrows. Single-pulse transcranial magnetic stimulation (TMS) was applied over primary motor cortex (M1) at one of five different latencies after stimulus onset, and motor-evoked potentials (MEPs) were measured in the contralateral index finger. During the control (no flankers) and congruent conditions, MEP size in the agonist increased gradually over the course of reaction time, indicating an increase in corticospinal excitability. Conversely, when the same muscle acted as an antagonist, MEP size decreased, suggesting inhibition. Critically, in the incongruent condition, MEPs briefly increased in the muscle corresponding to an initial default response to the flanker arrows and were later replaced by MEPs corresponding to the correct response to the central arrow. Finally, we found that the gradually growing MEPs for the three conditions reached a constant maximum level just before movement initiation. We propose that this dynamic modulation in corticospinal excitability reflects the competition process, leading to the selection of one response and the rejection of the other. Our results suggest that response competition influences activity in primary motor cortex and that its timing directly influences motor output latency.
Genomic analysis of miRNAs in an extreme mammalian hibernator, the Arctic ground squirrel
Authors: Liu Yuting , Hu Wenchao , Wang Haifang , Lu Minghua , Shao Chunxuan , Menzel Corinna , Yan Zheng , Li Ying , Zhao Sen , Khaitovich Philipp , Liu Mofang , Chen Wei , Barnes Brian M. , Yan Jun
Published: May 2010

MicroRNAs (miRNAs) are 19- to 25-nucleotide-long small and noncoding RNAs now well-known for their regulatory roles in gene expression through posttranscriptional and translational controls. Mammalian hibernation is a physiological process involving profound changes in set-points for food consumption, body mass and growth, body temperature, and metabolic rate in which miRNAs may play important regulatory roles. In an initial study, we analyzed miRNAs in the liver of an extreme hibernating species, the Arctic ground squirrel ( Spermophilus parryii ), using massively parallel Illumina sequencing technology. We identified >200 ground squirrel miRNAs, including 18 novel miRNAs specific to ground squirrel and mir-506 that is fast evolving in the ground squirrel lineage. Comparing animals sampled after at least 8 days of continuous torpor (late torpid), within 5 h of a spontaneous arousal episode (early aroused), and 1–2 mo after hibernation had ended (nonhibernating), we identified differentially expressed miRNAs during hibernation, which are also compared with the results from two other miRNA profiling methods: Agilent miRNA microarray and real-time PCR. Among the most significant miRNAs, miR-320 and miR-378 were significantly underexpressed during both stages of hibernation compared with nonhibernating animals, whereas miR-486 and miR-451 were overexpressed in late torpor but returned in early arousal to the levels similar to those in nonhibernating animals. Analyses of their putative target genes suggest that these miRNAs could play an important role in suppressing tumor progression and cell growth during hibernation. High-throughput sequencing data and microarray data have been submitted to GEO database with accession: GSE19808 .
Impact of asymptomatic nodavirus carrier state and intraperitoneal viral mimic injection on brain transcript expression in Atlantic cod (Gadus morhua)
Authors: Rise Matthew L. , Hall Jennifer R. , Rise Marlies , Hori Tiago S. , Browne Mitchell J. , Gamperl A. Kurt , Hubert Sophie , Kimball Jennifer , Bowman Sharen , Johnson Stewart C.
Published: May 2010

Nodaviruses and other RNA viruses have a profoundly negative impact on the global aquaculture industry. Nodaviruses target nervous tissue causing viral nervous necrosis, a disease characterized by neurological damage, swimming abnormalities, and morbidity. This study used functional genomic techniques to study the Atlantic cod ( Gadus morhua ) brain transcript expression responses to asymptomatic high nodavirus carrier state and intraperitoneal injection of polyriboinosinic polyribocytidylic acid (pIC). Reciprocal suppression subtractive hybridization (SSH) cDNA libraries enriched for virus-responsive brain transcripts were constructed and characterized. We generated 1,938 expressed sequence tags (ESTs) from a forward brain SSH library (enriched for transcripts upregulated by nodavirus and/or pIC) and 1,980 ESTs from a reverse brain SSH library (enriched for transcripts downregulated by nodavirus and/or pIC). To examine the effect of nodavirus carrier state on individual brain gene expression in asymptomatic cod, 27 transcripts of interest were selected for quantitative reverse transcription-polymerase chain reaction (QPCR) studies. Transcripts found to be >10-fold upregulated in individuals with a high nodavirus carrier state relative to those in a no/low nodavirus carrier state were identified as ISG15, IL8, DHX58 (alias LGP2), ZNFX1, RSAD2 (alias viperin), and SACS (sacsin, alias spastic ataxia of Charlevoix-Saguenay). These and other SSH-identified transcripts were also found by QPCR to be significantly ( P < 0.05) upregulated by pIC compared with saline-injected controls within 72 h of injection. Several transcripts identified in the reverse SSH library, including two putative ubiquitination pathway members (HERC4 and SUMO2), were found to be significantly ( P < 0.05) downregulated in individuals with a high nodavirus carrier state. Our data shows that Atlantic cod brains have a strong interferon pathway response to asymptomatic high nodavirus carrier state and that many interferon pathway and other immune relevant transcripts are significantly induced in brain by both nodavirus and pIC.
The Association between Childhood Overweight and Reflux Esophagitis
Authors: Patel Nirav R. , Ward Mary J. , Beneck Debra , Cunningham-Rundles Susanna , Moon Aeri
Published: May 2010

Background. In adults, it has been shown that obesity is associated with gastroesophageal reflux disease (GERD) and GERD-related complications. There are sparse pediatric data demonstrating associations between childhood overweight and GERD.Objective. To investigate the association between childhood overweight and RE.Methods. We performed a retrospective chart review of 230 children (M :  : 116) who underwent esophagogastroduodenoscopy (EGD) with biopsies between January 2000 and April 2006. Patient demographics, weight, height, clinical indications for the procedure, the prevalence of BMI classification groups, the prevalence of RE and usage of anti-reflux medications were reviewed. For these analyses, the overweight group was defined to include subjects with 85th percentile. The normal weight group was defined to include subjects with BMI 5th to 85th percentile.Results. Among the 230 subjects, 67 (29.1%) had BMI percentiles above the 85th percentile for age and gender. The prevalence of RE in the overweight group did not differ significantly from that in the normal weight group (23.9% versus 24.5%, resp.). Overweight subjects taking anti-reflux medications clearly demonstrated a higher prevalence of biopsy-proven RE compared to overweight subjects not taking anti-reflux medications (34.1% versus 7.7%, ).Conclusions. There was no significant difference in the prevalence of biopsy-proven RE in the overweight group compared to the normal weight group. However, the prevalence of RE was significantly higher in overweight subjects on anti-reflux medications compared to overweight subjects not taking anti-reflux medications. This finding emphasizes the importance of early recognition and treatment of GERD for the overweight pediatric patients with symptoms in conjunction with weight loss program for this population to reduce long-term morbidities associated with GERD.
Physiological and Histopathological Investigations on the Effects of-Lipoic Acid in Rats Exposed to Malathion
Authors: Al-Attar Atef M.
Published: May 2010

The present study was designed to evaluate the influence of -lipoic acid treatment in rats exposed to malathion. Forty adult male rats were used in this study and distributed into four groups. Animals of group 1 were untreated and served as control. Rats of group 2 were orally given malathion at a dose level of 100 mg/kg body weight (BW) for a period of one month. Experimental animals of group 3 were orally given -lipoic acid at a dose level of 20 mg/kg BW and after 3 hours exposed to malathion at the same dose given to group 2. Rats of group 4 were supplemented with -lipoic acid at the same dose given to group 3. The activities of serum glutamic oxaloacetic acid transaminase (GOT), glutamic pyruvic acid transaminase (GPT), alkaline phosphatase (ALP), and acid phosphatase (ACP), and the values of creatinine, urea, and uric acid were statistically increased, while the values of total protein and total albumin were significantly decreased in rats exposed to malathion. Moreover, administration of malathion for one month resulted in damage of liver and kidney structures. Administration of -lipoic acid before malathion exposure to rat can prevent severe alterations of hematobiochemical parameters and disruptions of liver and kidney structures. In conclusion, this study obviously demonstrated that pretreatment with -lipoic acid significantly attenuated the physiological and histopathological alterations induced by malathion. Also, the present study identifies new areas of research for development of better therapeutic agents for liver, kidney, and other organs' dysfunctions and diseases.
A New Perspective on Intercalated Disc Organization: Implications for Heart Disease
Authors: Li Jifen , Radice Glenn L.
Published: May 2010

Adherens junctions and desmosomes are intercellular adhesive junctions and essential for the morphogenesis, differentiation, and maintenance of tissues that are subjected to high mechanical stress, including heart and skin. The different junction complexes are organized at the termini of the cardiomyocyte called the intercalated disc. Disruption of adhesive integrity via mutations in genes encoding desmosomal proteins causes an inherited heart disease, arrhythmogenic right ventricular cardiomyopathy (ARVC). Besides plakoglobin, which is shared by adherens junctions and desmosomes, other desmosomal components, desmoglein‐2, desmocollin‐2, plakophilin‐2, and desmoplakin are also present in ultrastructurally defined fascia adherens junctions of heart muscle, but not other tissues. This mixed‐type of junctional structure is termed hybrid adhering junction or area composita. Desmosomal plakophilin‐2 directly interacts with adherens junction protein alphaT‐catenin, providing a new molecular link between the cadherin‐catenin complex and desmosome. The area composita only exists in the cardiac intercalated disc of mammalian species suggesting that it evolved to strengthen mechanical coupling in the heart of higher vertebrates. The cross‐talk among different junctions and their implication in the pathogenesis of ARVC are discussed in this review.
Epoetin Delta Reduces Oxidative Stress in Primary Human Renal Tubular Cells
Authors: De Beuf Annelies , Hou Xiang-hua , D'Haese Patrick C. , Verhulst Anja
Published: May 2010

Erythropoietin (EPO) exerts (renal) tissue protective effects. Since it is unclear whether this is a direct effect of EPO on the kidney or not, we investigated whether EPO is able to protect human renal tubular epithelial cells (hTECs) from oxidative stress and if so which pathways are involved. EPO (epoetin delta) could protect hTECs against oxidative stress by a dose-dependent inhibition of reactive oxygen species formation. This protective effect is possibly related to the membranous expression of the EPO receptor (EPOR) since our data point to the membranous EPOR expression as a prerequisite for this protective effect. Oxidative stress reduction went along with the upregulation of renoprotective genes. Whilst three of these, heme oxygenase-1 (HO-1), aquaporin-1 (AQP-1), and B-cell CLL/lymphoma 2 (Bcl-2) have already been associated with EPO-induced renoprotection, this study for the first time suggests carboxypeptidase M (CPM), dipeptidyl peptidase IV (DPPIV), and cytoglobin (Cygb) to play a role in this process.
Venous Doppler in the Evaluation of Fetal Hydrops
Authors: Hofstaetter C. , Gudmundsson S.
Published: May 2010

Objective. To examine venous blood flow velocity in different types of fetal hydrops and its value in the prediction of outcome of pregnancies. Methods. Venous Doppler sonography was performed in 100 hydropic fetuses from 15 to 37 weeks of gestation. Blood velocity was recorded in the right hepatic vein (HV), the ductus venosus (DV) and in the intra‐abdominal part of the umbilical vein (UV). Blood velocity indices were calculated and pulsations in the umbilical vein noted and grouped into a single, double or triple flow pattern. Blood velocity was related to cause of hydrops. Results. Mortality was noted in 51 cases of which 19 were by termination of pregnancy. Mortality in the 30 with normal venous blood velocity was 35%, but 58% in cases of abnormal Doppler. Abnormal HV and DV blood velocities were recorded in 39 and 34 cases, respectively and were strongly related to mortality (P < .04 and P < .003, resp.). UV pulsations were noted in 49 fetuses and were significantly related to mortality (P < .04). Mortality and abnormal venous velocities were most frequent in the low‐output hydrops group (79% and 75%, resp.). Conclusions. Abnormal venous blood velocity is related to mortality in pregnancies complicated by fetal hydrops. Venous Doppler sonography should be a part of the routine work‐up of pregnancies complicated by fetal hydrops.
Peritoneal Adipocytes and Their Role in Inflammation during Peritoneal Dialysis
Authors: Lai Kar Neng , Leung Joseph C. K.
Published: May 2010

Adipose tissue is a major site of chronic inflammation associated with peritoneal dialysis (PD) frequently complicating peritonitis. Adiposity-associated inflammation plays a significant contributory role in the development of chronic inflammation in patients undergoing maintenance PD. However, the molecular and cellular mechanisms of this link remain uncertain. Adipose tissue synthesizes different adipokines and cytokines that orchestrate and regulate inflammation, insulin action, and glucose metabolism locally and systemically. In return, inflammation retards adipocyte differentiation and further exacerbates adipose dysfunction and inflammation. An understanding of the inflammatory roles played by adipose tissue during PD and the healing mechanism of injured mesothelium will help to devise new therapeutic approach to slow the progression of peritoneal damage during peritoneal dialysis. This article reviews the roles of peritoneal adipose tissue in chronic peritoneal inflammation under PD and in serosal repair during PD.
Application of Adoptive T-Cell Therapy Using Tumor Antigen-Specific T-Cell Receptor Gene Transfer for the Treatment of Human Leukemia
Authors: Ochi Toshiki , Fujiwara Hiroshi , Yasukawa Masaki
Published: May 2010

The last decade has seen great strides in the field of cancer immunotherapy, especially the treatment of melanoma. Beginning with the identification of cancer antigens, followed by the clinical application of anti-cancer peptide vaccination, it has now been proven that adoptive T-cell therapy (ACT) using cancer antigen-specific T cells is the most effective option. Despite the apparent clinical efficacy of ACT, the timely preparation of a sufficient number of cancer antigen-specific T cells for each patient has been recognized as its biggest limitation. Currently, therefore, attention is being focused on ACT with engineered T cells produced using cancer antigen-specific T-cell receptor (TCR) gene transfer. With regard to human leukemia, ACT using engineered T cells bearing the leukemia antigen-specific TCR gene still remains in its infancy. However, several reports have provided preclinical data on TCR gene transfer using Wilms' tumor gene product 1 (WT1), and also preclinical and clinical data on TCR gene transfer involving minor histocompatibility antigen, both of which have been suggested to provide additional clinical benefit. In this review, we examine the current status of anti-leukemia ACT with engineered T cells carrying the leukemia antigen-specific TCR gene, and discuss the existing barriers to progress in this area.
The Zn‐ or Cu‐Thionein Character of a Metallothionein Determines Its Metal Load When Synthesized in Physiological (Metal‐Unsupplemented) Conditions
Authors: Capdevila Mercè , Palacios Òscar , Atrian Sílvia
Published: May 2010

The present work comprises the recombinant synthesis of four metallothioneins (MTs) in metal‐unsupplemented cultures and the characterization of the recovered metal complexes by means of analytical and spectrometric techniques. The four MTs are two Drosophila (MtnA and MtnB), one yeast (Crs5), and one mouse (mMT1) metallothionein isoforms. These four MTs exhibit distinct metal binding preferences, from a clear Cu‐thionein character to a definite Zn‐thionein nature, respectively. Although in all cases, the only metal ion present in the purified complexes is Zn2+, our results highlight an inherently different behaviour of those two types of MTs, in conditions that would mimic their synthesis in physiological environments. Therefore, intrinsically different roles can be hypothesized for the constitutively‐produced MT peptides in the absence of any metal overload, depending on their Zn‐ or Cu‐thionein character.
Antheraea pernyiSilk Fiber: A Potential Resource for Artificially Biospinning Spider Dragline Silk
Authors: Zhang Yaopeng , Yang Hongxia , Shao Huili , Hu Xuechao
Published: May 2010

The outstanding properties of spider dragline silk are likely to be determined by a combination of the primary sequences and the secondary structure of the silk proteins.Antheraea pernyisilk has more similar sequences to spider dragline silk than the silk from its domestic counterpart,Bombyx mori. This makes it much potential as a resource for biospinning spider dragline silk. This paper further verified its possibility as the resource from the mechanical properties and the structures of theA. pernyisilks prepared by forcible reeling. It is surprising that the stress-strain curves of theA. pernyifibers show similar sigmoidal shape to those of spider dragline silk. Under a controlled reeling speed of 95 mm/s, the breaking energy was1.04×105 J/kg, the tensile strength was 639 MPa and the initial modulus was 9.9 GPa. It should be noted that this breaking energy of theA. pernyisilk approaches that of spider dragline silk. The tensile properties, the optical orientation and theβ-sheet structure contents of the silk fibers are remarkably increased by raising the spinning speeds up to 95 mm/s.