bluuebunny/crossref_metadata_2025 huggingface dataset:
Chasing Science at Sea: Racing Hurricanes, Stalking Sharks, and Living Undersea With Ocean Experts
Authors: Lee Cindy
Published: December 2008

Ellen Prager's new book, Chasing Science at Sea, is a personal account of why fieldwork is so important in many areas of ocean science, and how exciting that fieldwork can be. Prager has interwoven her own story of studying carbonates at the interface between biology and geology with stories from friends and colleagues. Storm stories and up‐close‐and‐personal encounters with ocean creatures such as reef squid, marine iguanas, and whales abound. Throughout the book, she emphasizes the idea that the combination of observations and serendipity plays a critical role in science, and she gives examples of where this combination has led to especially important discoveries (e.g., that of hydrothermal vent organisms).
Cassak and Cully Receive 2008 F. L. Scarf Award
Authors: Anonymous
Published: December 2008

Paul Adam Cassak and Christopher M. Cully have been awarded the F. L. Scarf Award, given annually to recent Ph.D. recipients for outstanding dissertation research that contributes directly to solarplanetary sciences.

They will be formally presented with the award at the SPA Section Dinner during the 2008 AGU Fall Meeting, which will be held 15–19 December in San Francisco, Calif.
Rypina Receives 2008 Donald L. Turcotte Award
Authors: Anonymous
Published: December 2008

Irina Rypina has been awarded the Donald L. Turcotte Award, given annually to recent Ph.D. recipients for outstanding dissertation research that contributes directly to the field of non linear geophysics. Rypina's thesis is entitled “Lagrangian coherent structures and transport in two‐dimensional incompressible flows with oceano graphic and atmospheric applications.” She will be formally presented with the award at the Nonlinear Geophysics Focus Group Reception during the 2008 AGU Fall Meeting, which will be held 15–19 December in San Francisco, Calif.
Travel Grants Benefit 120 Students
Authors: Anonymous
Published: December 2008

AGU is pleased to announce that 120 students from 21 countries will travel to the AGU Fall Meeting in San Francisco to present their research. The travel grants are made possible through the generosity of Exxon Mobil, Northrup Grumman, Elsevier, Sequoia Scientific, Li‐Cor Biogeosciences, Cassidy Associates, Decagon Devices, RBR Ltd., Springer, Jamie A. Austin Jr., the Max Hammond Student Travel Endowment, and 157 AGU members.
Tracking provenance change during the late Miocene in the eastern Mediterranean using geochemical and environmental magnetic parameters
Authors: Köhler C. M. , Heslop D. , Dekkers M. J. , Krijgsman W. , van Hinsbergen D. J. J. , von Dobeneck T.
Published: December 2008

Marls of the Metochia section (Gavdos, Greece) have been analyzed using geochemistry, environmental magnetism, and diffuse reflectance spectrometry to study late Miocene paleoenvironmental changes in the eastern Mediterranean region. Fuzzy c‐means cluster analysis (FCM), combined with nonlinear mapping (NLM), has been performed on a multiparameter data set to identify and characterize terrigenous source areas from North Africa and the Aegean margin. The parameters included in the FCM were selected on the basis of their univariate characteristics and their ability to trace input changes from regional source areas. The hard isothermal remanent magnetization (HIRM), calculated on a carbonate‐free basis, and the Ti/Al ratio are used to distinguish aeolian dust and transport mechanisms of material originating from North Africa. Mass accumulation rates of Al and Ni are employed to represent the input of terrigenous material originating from the Aegean region. CaCO3, calculated from Ca abundance, provides information concerning marine productivity and Mn/Al is used to trace reductive diagenesis in the marls. After performing the FCM and NLM analysis, a four‐cluster solution has the greatest stability and describes paleoenvironmental changes in both the African and European source areas. The cluster solution clearly reveals the change from input dominated by terrigenous material in the lower parts of the Metochia section to marine input at the top of the section but also reveals changes in paleoenvironmental conditions in North Africa from arid to more humid conditions at ∼8.2 Ma.
Periodic tilting of Saturn's plasma sheet
Authors: Carbary J. F. , Mitchell D. G. , Brandt P. , Roelof E. C. , Krimigis S. M.
Published: December 2008

From the vantage of the dawn sector, the INCA instrument on Cassini imaged neutral hydrogen atoms (20–50 keV) emitted from the center of the Saturn's plasma sheet for five days during late 2004. Points along the center of the plasma sheet were found from contoured images projected onto the noon‐midnight plane; points within 20 RS of Saturn were fitted to straight lines, and the slopes of these lines were examined as a function of time at one hour resolution. The slopes vary between ∼17° and ∼24° with a period of 10.80 hours, the same as that of Saturn kilometric radiation (SKR). This periodic tilting of the plasma sheet is in phase with SKR radiation in the sense that the maximum tilt angle occurs when the maximum in the SKR power occurs, and the tilt angle periodicity has a phase angle of ∼47° in SLS‐3 longitude.
Modeling a force‐free flux transfer event probed by multiple Time History of Events and Macroscale Interactions during Substorms (THEMIS) spacecraft
Authors: Zhang H. , Khurana K. K. , Kivelson M. G. , Angelopoulos V. , Pu Z. Y. , Zong Q.‐G. , Liu J. , Zhou X.‐Z.
Published: December 2008

A flux transfer event (FTE) was encountered by all five Time History of Events and Macroscale Interactions during Substorms (THEMIS) spacecraft just outside the dusk magnetopause on 20 May 2007. In the present paper, we fit the magnetic field observations from multiple satellites to a flux rope model in order to obtain the critical geometric parameters of this FTE. The model used includes both electromagnetic force and pressure gradient force and reduces to a force‐free model when the magnetic tension is balanced mainly by the magnetic pressure gradient. The cross‐sectional scales of the FTE were estimated to be 0.6 × 1.3 RE. The core field direction is found to differ only slightly from the results of the minimum variance analysis and the Grad‐Shafranov technique. The maximum electric current density within the FTE was ∼100 nA/m2 and the total current was 0.3 MA, which is comparable with the current per RE flowing on the local magnetopause. The magnetic flux inside the FTE was ∼4 × 105 Wb. Magnetic field data and plasma data show that this FTE was fully embedded in the boundary region between the magnetosheath and the magnetosphere. The magnetic configuration and the flow distribution around the FTE suggest that X lines were present both ahead of and behind the FTE, but we cannot determine whether these X lines formed synchronously. Our observations favor the conclusion that multiple X line models are the candidate mechanisms for the generation of this FTE, and some of the FTE's features cannot be understood in the frame of any single X line FTE model.
Adaptive octree‐based finite element analysis of two‐ and three‐dimensional indentation problems
Authors: Thieulot C. , Fullsack P. , Braun J.
Published: December 2008

In recent years, much has been done to develop numerical tools to study the three‐dimensional nature of the Earth's lithosphere deformation. DOUAR is one of them: it is a new ALE Finite Element code that is based on an adaptive grid, a key feature in the capture of localized deformation. In order to illustrate this, various simulations of punch experiments have been performed on rigid plastic materials with von Mises and Drucker‐Prager type of rheologies. We present the grid refinement algorithm based on strain rate measurements and rederive the plane strain punch analytical solution which allows us to test the accuracy of our results. Various 3‐D strip punches experiments with different aspect ratios show DOUAR's ability to capture complex fault patterns. We also discuss the degree to which the incompressibility and rigid plasticity constraints are satisfied. Finally, we show the results of a crustal‐scale deformation experiment demonstrating the potential of the octree‐based mesh refinement algorithm to solve complex three‐dimensional geodynamical problems with great efficiency and accuracy.
Bayesian data fusion applied to water table spatial mapping
Authors: Fasbender D. , Peeters L. , Bogaert P. , Dassargues A.
Published: December 2008

Water table elevations are usually sampled in space using piezometric measurements that are unfortunately expensive to obtain and are thus scarce over space. Most of the time, piezometric data are sparsely distributed over large areas, thus providing limited direct information about the level of the corresponding water table. As a consequence, there is a real need for approaches that are able at the same time to (1) provide spatial predictions at unsampled locations and (2) enable the user to account for all potentially available secondary information sources that are in some way related to water table elevations. In this paper, a recently developed Bayesian data fusion (BDF) framework is applied to the problem of water table spatial mapping. After a brief presentation of the underlying theory, specific assumptions are made and discussed to account for a digital elevation model and for the geometry of a corresponding river network. On the basis of a data set for the Dijle basin in the north part of Belgium, the suggested model is then implemented and results are compared to those of standard techniques such as ordinary kriging and cokriging. Respective accuracies and precisions of these estimators are finally evaluated using a “leave‐one‐out” cross‐validation procedure. Although the BDF methodology was illustrated here for the integration of only two secondary information sources (namely, a digital elevation model and the geometry of a river network), the method can be applied for incorporating an arbitrary number of secondary information sources, thus opening new avenues for the important topic of data integration in a spatial mapping context.
The Policy Requirements of Gene-Environment Research
Authors: Wise Paul
Published: December 2008

Dr. Paul Wise began with a brief overview of policy formation, specifically that related to child development. He then delved into the changing taxonomy of disease and its implications for policy. He concluded by stressing the need for frameworks for collective action to reframe policy in terms of gene-environment interactions.To watch Dr. Wise’s presentation, please see the Panel 4 "Google Video posting.":http://video.google.com/videoplay?docid=-1375553372274016362&hl=en Panel 4 also features presentations by Dr. Richard Sharp of the Cleveland Clinic on "Disease Advocacy and Contested Environments" and by Professor Sara Shostak of Brandeis University on "Sealing Complexity: Genetics, Social Structure and Policy Environments."To view more of the Capturing Complexity Symposium, please see the Panel 5 "Google Video posting,":http://video.google.com/videoplay?docid=2359679706574224441&hl=en featuring Drs. Marc Feldman and Paul Ehrlich of Stanford University and Sir Michael Rutter of the Institute of Psychiatry, London. Dr. Feldman explored the lack of consideration of environmental influences in recent genome-wide association studies. Dr. Ehrlich also stressed the importance of the environment, and Sir Rutter concluded by responding to evocative topics brought up earlier in the Symposium such as personalized insurance policies, causation models and translational research.To view the final deliberative discussion, involving all panelists and moderated by Professor Hank Greely, JD, please see the Panel 6 "Google Video posting.":http://video.google.com/videoplay?docid=-7026328789822465424&hl=en
History and Philosophy of Gene Environment Interaction
Authors: Schaffner Kenneth
Published: December 2008

Dr. Kenneth Schaffner gave a brief introduction to the symposium topics. He began with a history of the thinking on gene-environment interactions and described the ensuing controversies. He cited the lack of a consensus theory of the environment and then described some methodological and technological advances in the studies of gene-environment interactions.To watch Dr. Schaffner’s presentation, please see the Panel 1 "Google Video posting.":http://video.google.com/videoplay?docid=-3097337289947323438&hl=en
The compositional simulation and seismic monitoring of CO2 EOR and sequestration in new gas condensate reservoir
Authors: Yuan Chengwu , Jin Long
Published: December 2008

While mature oil reservoir and aquifers are good candidates for CO2 sequestration, we proposed and investigated the alternative approach which, at the very start of production, combines CO2 sequestration and CO2 EOR in gas condensate reservoir. Firstly, we conducted compositional reservoir simulation and synthetic seismic simulation in a five-spot well pattern to investigate whether seismic data can monitor of CO2 front and gas condensate bank. The simulated results and the seismic simulation results are compared with each other. Although the density contrast among reservoir gas, injected CO2 and condensate is smaller than the density contrast in the case of CO2 sequestration in aquifer, the seismic signal can capture this smaller difference and monitor the CO2 injection front and locate the condensate zone. When there is no adequate data available for reservoir characterization at early period of production, this direct measurement is very valuable for reservoir characterization and for any stimulation of condensate block. Secondly, we compare the production by natural depletion and production combined CO2 EOR and storage at the very beginning. The latter will speed up the recovery process, increase the recovery rate while simultaneously store CO2 in reservoir. The extra benefit in gas condensate reservoir is that injection of CO2 will increase the pressure and postpone and decrease liquid dropout and relieve the condensate blocking.
How mitochondria produce reactive oxygen species
Authors: Murphy Michael P.
Published: December 2008

The production of ROS (reactive oxygen species) by mammalian mitochondria is important because it underlies oxidative damage in many pathologies and contributes to retrograde redox signalling from the organelle to the cytosol and nucleus. Superoxide (O2•−) is the proximal mitochondrial ROS, and in the present review I outline the principles that govern O2•− production within the matrix of mammalian mitochondria. The flux of O2•− is related to the concentration of potential electron donors, the local concentration of O2 and the second-order rate constants for the reactions between them. Two modes of operation by isolated mitochondria result in significant O2•− production, predominantly from complex I: (i) when the mitochondria are not making ATP and consequently have a high Δp (protonmotive force) and a reduced CoQ (coenzyme Q) pool; and (ii) when there is a high NADH/NAD+ ratio in the mitochondrial matrix. For mitochondria that are actively making ATP, and consequently have a lower Δp and NADH/NAD+ ratio, the extent of O2•− production is far lower. The generation of O2•− within the mitochondrial matrix depends critically on Δp, the NADH/NAD+ and CoQH2/CoQ ratios and the local O2 concentration, which are all highly variable and difficult to measure in vivo. Consequently, it is not possible to estimate O2•− generation by mitochondria in vivo from O2•−-production rates by isolated mitochondria, and such extrapolations in the literature are misleading. Even so, the description outlined here facilitates the understanding of factors that favour mitochondrial ROS production. There is a clear need to develop better methods to measure mitochondrial O2•− and H2O2 formation in vivo, as uncertainty about these values hampers studies on the role of mitochondrial ROS in pathological oxidative damage and redox signalling.
New insights into the roles of phosphoinositides and inositol polyphosphates in yeast
Authors: Michell R.H. , Perera N.M. , Dove S.K.
Published: December 2008

During the past half century, we have progressed from simply viewing myo-inositol-containing glycerophospholipids as quantitatively minor membrane constituents to the present, very striking, situation in which more and more important cellular functions are being assigned to a plethora of phosphorylated derivatives of inositol and phosphatidylinositol. Two such examples are discussed briefly: the activation by environmental stresses of the single phosphoinositidase C of yeast, which is related to the phospholipase C δs of other eukaryotes, and the involvement of PtdIns(3,5)P2 in endomembrane trafficking.
Structure and activation of muscarinic acetylcholine receptors
Authors: Hulme E.C. , Lu Z.L. , Saldanha J.W. , Bee M.S.
Published: December 2008

A homology model of the M1 muscarinic acetylcholine receptor, based on the X-ray structure of bovine rhodopsin, has been used to interpret the results of scanning and point mutagenesis studies on the receptor's transmembrane (TM) domain. Potential intramolecular interactions that are important for the stability of the protein fold have been identified. The residues contributing to the binding site for the antagonist, N-methyl scopolamine, and the agonist, acetylcholine, have been mapped. The positively charged headgroups of these ligands probably bind in a charge-stabilized aromatic cage formed by amino acid side chains in TM helices TM3, TM6 and TM7, while residues in TM4 may participate as part of a peripheral docking site. Closure of the cage around the headgroup of acetylcholine may be part of the mechanism for transducing binding energy into receptor activation, probably by disrupting a set of Van der Waals interactions between residues lying beneath the binding site that help to constrain the receptor to the inactive state, in the absence of agonist. This may trigger the reorganization of a hydrogen-bonding network between highly conserved residues in the core of the receptor, whose integrity is crucial for achievement of the activated state.
Neural differentiation of mouse embryonic stem cells
Authors: Stavridis M.P. , Smith A.G.
Published: December 2008

Pluripotent embryonic stem cells can give rise to neuroectodermal derivatives in culture. This potential could be harnessed to generate neurons and glia for cell-replacement therapies in the central nervous system and for use in drug discovery. However, current methods of neural differentiation are empirical and relatively innefficient. Here, we review these methodologies and present new tools for quantification, analysis and manipulation of embryonic stem cell neural determination.
Neuron–glia interactions during axon guidance in Drosophila
Authors: Hidalgo A.
Published: December 2008

Axons navigate to trace stereotypic trajectories over an environment often rich in glial cells. Once axonal trajectories are defined, their structuring proceeds through multiple fasciculation and defasciculation events, to finally establish the mature bundles. Fasciculation and ensheathment also proceed in close association between axons and glial cells, and ultimately require glia. The cross-talk between axons and glia during axon guidance is manifested in: (i) axonal fasciculation and bundling, promoted by glia; (ii) growth cone guidance, as glia function as guidepost cells at choice points; (iii) glial migration patterns, which are influenced by neurons; (iv) cell survival control, which constrains position and number of both cell types; and (iv) connectivity, where an axon contacts its final target aided by glial cells. Understanding the reciprocal interactions between neurons and glia during guidance and fasciculation is absolutely necessary to implement repair of axonal trajectories upon damage. Drosophila can be used as a model system for these purposes.
Structure and mechanism of the oestrogen receptor
Authors: Kong E.H. , Pike A.C.W. , Hubbard R.E.
Published: December 2008

We have determined the structures of the oestrogen receptor ligand-binding domain in complex with a range of ligands and with fragments of co-regulator proteins. These structures provide insights into the structural mechanisms underlying the receptor's complex pharmacological properties and how the conformation of the receptor modulates its ability to recruit co-regulators that are necessary for transcriptional activation.
Route of steroid-activated macromolecules through nuclear pores imaged with atomic force microscopy
Authors: Oberleithner H. , Schäfer C. , Shahin V. , Albermann L.
Published: December 2008

In eukaryotic cells, two concentric membranes, the nuclear envelope (NE), separate the nucleus from the cytoplasm. The NE is punctured by nuclear pore complexes (NPCs; molecular mass 120 MDa) that serve as regulated pathways for macromolecules entering and leaving the nuclear compartment. Transport across NPCs occurs through central channels. Such import and export of macromolecules through individual NPCs can be elicited in the Xenopus laevis oocyte by injecting the mineralocorticoid aldosterone and can be visualized with atomic force microscopy. The electrical NE resistance in intact cell nuclei can be measured in parallel. Resistance increases when macromolecules are engaged with the NPC. This article describe six observations made from these experiments and the conclusions that can be drawn from them. (i) A homogeneous population of macromolecules (approx. 100 kDa) attaches to the cytoplasmic face of the NPC 2 min after aldosterone injection. They are most likely to be aldosterone receptors. After a few minutes, they have disappeared. (ii) Large plugs (approx. molecular mass 1 MDa) appear in the central channels 20 min after hormone injection. They are most likely to be ribonucleoproteins exiting the nucleus. (iii) Electrical resistance measurements in isolated nuclei reveal transient electrical NE resistance peaks: an early (2 min) peak and a late (20 min) peak. Electrical peaks reflect macromolecule interaction with the NPC. (iv) Spironolactone blocks both the early and late peaks. This indicates that classic aldosterone receptors are involved in the pregenomic (early) and post-genomic (late) responses. (v) Actinomycin D and, independently, RNase A block the late electrical peak, confirming that plugs are genomic in nature. (vi) Intracellular calcium chelation blocks both early and late electrical peaks. Thus, the release of calcium from internal stores, which is known to be the first intracellular signal in response to aldosterone, is a prerequisite for the late genomic response.
Calcium signalling in and around the nuclear envelope
Authors: Gerasimenko J. , Maruyama Y. , Tepikin A. , Petersen O.H. , Gerasimenko O.
Published: December 2008

We have compared calcium mobilization by Ins(1,4,5)P3(IP3), cADP-ribose (cADPR) and nicotinic acid–adenosine dinucleotide phosphate (NAADP) from the envelope of isolated nuclei with the calcium signalling in intact isolated pancreatic acinar cells. Ca2+ uptake and release were studied with calcium-sensitive fluorescent probes. In the present study, we have shown that all calcium messengers induce Ca2+ release from the nuclear envelope. Pre-treatment of nuclei with thapsigargin completely abolished the responses to the calcium messengers, indicating that Ca2+ stores in isolated nuclei are thapsigargin-sensitive. Using different pharmacological tools, we show that Ca2+ release from pancreatic nuclei is unlikely to occur from stores other than those with endoplasmic reticulum characteristics. We conclude that all three calcium messengers can release Ca2+ from pancreatic acinar nuclear stores, as previously shown for IP3 and cADPR. It would appear that NAADP releases Ca2+ from the same IP3- and cADPR-sensitive stores with endoplasmic reticulum characteristics.
Regulation, secretion and activity of type III-secreted proteins of enterohaemorrhagic Escherichia coli O157
Authors: Roe A.J. , Hoey D.E.E. , Gally D.L.
Published: December 2008

Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 causes gastrointestinal disease with the potential for life-threatening sequelae. Although Shiga-like toxins are responsible for much of the serious pathology in humans, the bacterium also possesses a type III protein secretion system that is responsible for intimate attachment to host intestinal mucosa. This sophisticated interaction requires co-ordination that is governed by environmental and genetic factors. Ongoing research supports the following model for how EHEC enables and controls this process: (i) specific environmental cues that are present in the host result in the expression of a number of adhesins, including fimbriae, which allow the initial binding to the mucosal surface. The same conditions support the expression of the basal type III secretion apparatus; (ii) targeting and assembly of the translocon requires both an mRNA signal and chaperones, with coupled translation and secretion of translocon proteins, EspA, B and D; (iii) opening up of a conduit between the bacterium and host cell releases a cytoplasmic pool of effector proteins. A consequence of this is increased expression of particular effector proteins. Potentially, different proteins could be released into the cell at different times or have activities modulated with time; (iv) intimate contact between the translocated intimin receptor (Tir) and the bacterial surface factor intimin requires translocon expression to be down-regulated and translocon filaments to be lost. Fluorescent protein fusions allow contact-mediated regulation and protein targeting through the type III secretion system to be studied in detail.
Arthropod semiochemicals: mosquitoes, midges and sealice
Authors: Mordue Luntz A.J.
Published: December 2008

Signalling chemicals play an essential role in arthropod life cycles. They provide the means whereby mates, host and oviposition sites are located and recognized. The identification of such semiochemicals (sex pheromones, host location and habitat-related cues) in mosquitoes, midgesand sealice of farmed salmon is revealing ways in which such devastating pests may be monitored and controlled by behavioural means using push–pull strategies to manipulate the pests away from hosts and into traps.
A molecular approach to the concerted action of kinases involved in energy homoeostasis
Authors: Neumann D. , Schlattner U. , Wallimann T.
Published: December 2008

One of the most important duties of a cell is energy homoeostasis. Several kinases, including AMP-activated protein kinase (AMPK), creatine kinase and adenylate kinase, are involved in the immediate response to stress, resulting in energy depletion. Here, we present our view of events preceding the downstream processes mediated by AMPK and leading to reduced energy expenditure and increased energy production. Unfortunately, AMPK is very poorly defined at the molecular level. Thus a procedure for production of AMPK in milligram amounts is presented which will greatly facilitate the functional and structural characterization of this protein kinase.
AMP-activated protein kinase regulation and action in skeletal muscle during exercise
Authors: Musi N. , Yu H. , Goodyear L.J.
Published: December 2008

Physical exercise increases muscle glucose uptake, enhances insulin sensitivity and leads to fatty acid oxidation in muscle. The AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that is strongly activated during muscle contraction due to acute decreases in ATP/AMP and phosphocreatine/creatine ratios. Accumulating evidence suggests that AMPK plays an important role in mediating these metabolic processes. Furthermore, AMPK has been implicated in regulating gene transcription and therefore may play a role in some of the cellular adaptations to training exercise. There is also evidence that changes in AMPK activity result in altered cellular glycogen content, suggesting that this enzyme regulates glycogen metabolism. Recent studies have shown that the magnitude of AMPK activation and associated metabolic responses are affected by factors such as glycogen content, exercise training and fibre type. In summary, AMPK regulates several metabolic pathways during acute exercise and modifies the expression of many genes involved in the adaptive changes to exercise training.
Malonyl-CoA and AMP-activated protein kinase (AMPK): possible links between insulin resistance in muscle and early endothelial cell damage in diabetes
Authors: Ruderman N.B. , Cacicedo J.M. , Itani S. , Yagihashi N. , Saha A.K. , Ye J.M. , Chen K. , Zou M. , Carling D. , Boden G. , Cohen R.A. , Keaney J. , Kraegen E.W. , Ido Y.
Published: December 2008

Based on available evidence, we would propose the following. (i) Excesses of glucose and free fatty acids cause insulin resistance in skeletal muscle and damage to the endothelial cell by a similar mechanism. (ii) Key pathogenetic events in this mechanism very likely include increased fatty acid esterification, protein kinase C activation, an increase in oxidative stress (demonstrated to date in endothelium) and alterations in the inhibitor κB kinase/nuclear factor κB system. (iii) Activation of AMP-activated protein kinase (AMPK) inhibits all of these events and enhances insulin signalling in the endothelial cell. It also enhances insulin action in muscle; however, the mechanism by which it does so has not been well studied. (iv) The reported beneficial effects of exercise and metformin on cardiovascular disease and insulin resistance in humans could be related to the fact that they activate AMPK. (v) The comparative roles of AMPK in regulating metabolism, signalling and gene expression in muscle and endothelial cells warrant further study.
AMP-activated protein kinase regulation of fatty acid oxidation in the ischaemic heart
Authors: Hopkins T.A. , Dyck J.R.B. , Lopaschuk G.D.
Published: December 2008

The heart relies predominantly on a balance between fatty acids and glucose to generate its energy supply. There is an important interaction between the metabolic pathways of these two substrates in the heart. When circulating levels of fatty acids are high, fatty acid oxidation can dominate over glucose oxidation as a source of energy through feedback inhibition of the glucose oxidation pathway. Following an ischaemic episode, fatty acid oxidation rates increase further, resulting in an uncoupling between glycolysis and glucose oxidation. This uncoupling results in an increased proton production, which worsens ischaemic damage. Since high rates of fatty acid oxidation can contribute to ischaemic damage by inhibiting glucose oxidation, it is important to maintain proper control of fatty acid oxidation both during and following ischaemia. An important molecule that controls myocardial fatty acid oxidation is malonyl-CoA, which inhibits uptake of fatty acids into the mitochondria. The levels of malonyl-CoA in the heart are controlled both by its synthesis and degradation. Three enzymes, namely AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC) and malonyl-CoA decarboxylase (MCD), appear to be extremely important in this process. AMPK causes phosphorylation and inhibition of ACC, which reduces the production of malonyl-CoA. In addition, it is suggested that AMPK also phosphorylates and activates MCD, promoting degradation of malonyl-CoA levels. As a result malonyl-CoA levels can be dramatically altered by activation of AMPK. In ischaemia, AMPK is rapidly activated and inhibits ACC, subsequently decreasing malonyl-CoA levels and increasing fatty acid oxidation rates. The consequence of this is a decrease in glucose oxidation rates. In addition to altering malonyl-CoA levels, AMPK can also increase glycolytic rates, resulting in an increased uncoupling of glycolysis from glucose oxidation and an enhanced production of protons and lactate. This decreases cardiac efficiency and contributes to the severity of ischaemic damage. Decreasing the ischaemic-induced activation of AMPK or preventing the downstream decrease in malonyl-CoA levels may be a therapeutic approach to treating ischaemic heart disease.
Glycogen storage disease as a unifying mechanism of disease in the PRKAG2 cardiac syndrome
Authors: Gollob M.H.
Published: December 2008

The AMP-activated protein kinase (AMPK) system was first discovered 30 years ago. Since that time, knowledge of the diverse physiological functions of AMPK has grown rapidly and continues to evolve. Most recently, the observation that spontaneously occurring genetic mutations in the γ regulatory subunits of AMPK give rise to a skeletal and cardiac muscle disease emphasizes the critical importance of AMPK in the maintenance of health and disease. The cardiac phenotype observed in humans harbouring genetic mutations in the γ2 regulatory subunit (PRKAG2) of AMPK is consistent with abnormal glycogen accumulation in the heart. The perturbation of AMPK activity induced by genetic mutations in PRKAG2 and the resultant effect on muscle cell glucose metabolism may be relevant to the issue of targeting AMPK in drug development for insulin-resistant diabetes mellitus.
Protein–protein interactions during mammalian DNA single-strand break repair
Authors: Caldecott K.W.
Published: December 2008

The genetic stability of living cells is continually threatened by endogenous reactive oxygen species and other genotoxic molecules. Of particular threat are the thousands of single-strand breaks that arise in each cell every day. If left unrepaired, such breaks can give rise to potentially clastogenic or lethal chromosomal double-strand breaks. This article summarizes our current understanding of how mammalian cells detect and repair single strand breaks, and provides insights into novel polypeptide components of this process.
Regulation of eukaryotic DNA replication at the initiation step
Authors: Pollok S. , Stoepel J. , Bauerschmidt C. , Kremmer E. , Nasheuer H.-P.
Published: December 2008

The studies of cell growth and division have remained at the centre of biomedical research for more than 100 years. The combination of genetic, biochemical, molecular and cell biological techniques recently yielded a burst in what is known of the molecular control of cell growth processes. The initiation of DNA replication is crucial for the stability of the genetic information of a cell. Two factors, Cdc45p (cell division cycle 45p) and DNA polymerase α-primase, are necessary in this process. Depending on growth signals, Cdc45p is expressed as a late protein. New phosphorylation-specific antibodies specifically recognize the phosphorylated subunit, p68, of the four subunit DNA polymerase α-primase and show that the phosphorylated polypeptide is exclusively nuclear.
PI3K-signalling in B- and T-cells: insights from gene-targeted mice
Authors: Okkenhaug K. , Vanhaesebroeck B.
Published: December 2008

Phosphoinositide 3-kinases (PI3Ks) are important signalling enzymes in most cell types. Recent gene targeting studies have shed light on the importance of this family of lipid kinases in the immune system, and the complex mechanisms by which these kinases are regulated in vivo. We have recently reported a phenotype of mice in which the p110 Δ PI3K catalytic subunit was inactivated by point mutation. In the present paper, we compare and contrast the phenotypes of p110 Δ mutant mice with those of mice that lack p85α or p110γ, and discuss these in the context of PI3K signalling in B- and T-cells.
FcγRIIB activation leads to inhibition of signalling by independently ligated receptors
Authors: Brauweiler A.M. , Cambier J.C.
Published: December 2008

The inhibitory IgG receptor, FcγRIIB, blocks signalling by co-aggregated antigen receptors on mature and activated B-cells. FcγRIIB is also expressed by immature B-cells; however, its function on these cells has not been defined. In the present paper, we demonstrate that immature B-cells are highly sensitive to inhibitory signalling mediated by FcγRIIB. Co-aggregation of FcγRIIB with the B-cell antigen receptor (BCR) on immature B-cells leads to near ablation of late phase calcium mobilization. Concomitant with enhanced inhibitory signalling, we found that Src-homology-2-domain-containing inositol 5′-phosphatase (SHIP) is expressed at much higher levels in immature B-cells than in mature B-cells. Perhaps most importantly, we report that SHIP activated by BCR–FcγRIIB co-aggregation inhibits independently ligated receptors whose signalling requires PtdIns(3,4,5)P3. We found that stromal-derived factor 1 (SDF-1)-induced cell migration is impaired by prior activation of FcγRIIB. This inhibition is reduced in SHIP-deficient B-cells. Therefore receptor-mediated signalling responses that are dependent on PtdIns(3,4,5)P3 are subject to both direct and indirect inhibition by FcγRIIB-activated SHIP.
Role of Src homology 2-containing-inositol 5′-phosphatase (SHIP) in mast cells and macrophages
Authors: Rauh M.J. , Kalesnikoff J. , Hughes M. , Sly L. , Lam V. , Krystal G.
Published: December 2008

The haemopoietic-restricted Src homology 2-containing inositol 5´-phosphatase (SHIP) acts as a negative regulator of myeloid cell proliferation, survival and end-cell activation. It does so, at least in part, by hydrolysing the phosphoinositide 3-kinase (PI3K)-generated second messenger, PtdIns(3,4,5)P3 (PI-3,4,5-P3) to PtdIns(3,4)P2. As a result, the myeloid progenitors in SHIP-knockout mice display enhanced survival and proliferation and the mice have increased numbers of neutrophils and monocytes/macrophages. Interestingly, although SHIP is not required for mast cell or macrophage development, it restrains their differentiation since progenitors from SHIP−/− mice differentiate into mature mast cells and macrophages significantly faster than their wild-type counterparts. This could suggest that elevated PI-3,4,5-P3 levels accelerate myeloid differentiation. In bone-marrow-derived mast cells, SHIP prevents degranulation by IgE alone, restrains IgE–antigen-induced degranulation and limits the production of inflammatory cytokines. On the other hand, in peritoneal macrophages, SHIP is a positive regulator of NO production, since SHIP−/− peritoneal macrophages produce 5–10-fold less NO than their wild-type counterparts, even though they show greater lipopolysaccharide/interferon-γ-induced nuclear factor κB activation and more rapid inducible NO synthase (iNOS) generation. This is a result of 10-fold higher levels of arginase I in the SHIP−/− macrophages, which redirects the iNOS substrate, l-arginine, from NO to ornithine production. This suggests that the chronically elevated PI-3,4,5-P3 levels in SHIP−/− mice may convert M1 (killing) macrophages, which produce NO to kill micro-organisms and tumour cells, into M2 (healing) macrophages, which produce ornithine to promote host cell growth and fibrosis.
High-density lipoproteins, inflammation and oxidative stress
Authors: Tabet Fatiha , Rye Kerry-Anne
Published: December 2008

Plasma levels of HDL (high-density lipoprotein)-cholesterol are strongly and inversely correlated with atherosclerotic cardiovascular disease. Both clinical and epidemiological studies have reported an inverse and independent association between serum HDL-cholesterol levels and CHD (coronary heart disease) risk. The cardioprotective effects of HDLs have been attributed to several mechanisms, including their involvement in the reverse cholesterol transport pathway. HDLs also have antioxidant, anti-inflammatory and antithrombotic properties and promote endothelial repair, all of which are likely to contribute to their ability to prevent CHD. The first part of this review summarizes what is known about the origins and metabolism of HDL. We then focus on the anti-inflammatory and antioxidant properties of HDL and discuss why these characteristics are cardioprotective.
Open Yourself Up to the Possibilities: “Communicating” With People With Dementia
Authors: Burke Grace M.
Published: December 2008

What would it be like to lose your “words,” to be unable to remember a phrase or the name of your children? When will you learn your last “new word” and struggle to even recall the ones that you learned very early in your life? What if losing these words was just the tip of the proverbial iceberg? What about when you eventually can't understand what others are saying to you or when the stories they tell are too hard to follow, words are too complex, the environment too overwhelming, and you can't listen for more than a few seconds? What about when words no longer come for important needs like a drink, a sweet, or a walk in the sun?

Difficulty with communication is often one of the first noticeable symptoms of people who have Alzheimer's disease and other dementias and is listed as one of the 10 Warning Signs of Alzheimer's (Alzheimer's Association, n.d.).
Mathematical foundation of quantum annealing
Authors: Morita Satoshi , Nishimori Hidetoshi
Published: December 2008

Quantum annealing is a generic name of quantum algorithms that use quantum-mechanical fluctuations to search for the solution of an optimization problem. It shares the basic idea with quantum adiabatic evolution studied actively in quantum computation. The present paper reviews the mathematical and theoretical foundations of quantum annealing. In particular, theorems are presented for convergence conditions of quantum annealing to the target optimal state after an infinite-time evolution following the Schrödinger or stochastic (Monte Carlo) dynamics. It is proved that the same asymptotic behavior of the control parameter guarantees convergence for both the Schrödinger dynamics and the stochastic dynamics in spite of the essential difference of these two types of dynamics. Also described are the prescriptions to reduce errors in the final approximate solution obtained after a long but finite dynamical evolution of quantum annealing. It is shown there that we can reduce errors significantly by an ingenious choice of annealing schedule (time dependence of the control parameter) without compromising computational complexity qualitatively. A review is given on the derivation of the convergence condition for classical simulated annealing from the view point of quantum adiabaticity using a classical-quantum mapping.
Nonuniform temperature dependence of the reactivity of disordered VOx/κ-Al2O3(001) surfaces: A density functional theory based Monte Carlo study
Authors: Fortrie Rémy , Todorova Tanya K. , Ganduglia-Pirovano M. Verónica , Sauer Joachim
Published: December 2008

Periodic density functional theory (DFT) calculations concerning VOx/κ-Al2O3(001) surfaces are used for parametrizing Monte Carlo simulations performed on a mesoscopic scale surface sample (41.95×48.80 nm2). New structural and chemical information are then obtained that are not accessible from DFT calculations: segregation, short- and long-range ordering, and the effect of the temperature on the reducibility. The reducibility of the surface is investigated for locating chemical potential regions where the catalyst is especially reactive for oxidation reactions. Comparison with the V2O5(001) surface at catalytic conditions (800 K, 1 bar) is performed. The reducibility exhibits an unexpectedly strong temperature dependence.
Charge-transport-mediated recruitment of DNA repair enzymes
Authors: Fok Pak-Wing , Guo Chin-Lin , Chou Tom
Published: December 2008

Damaged or mismatched bases in DNA can be repaired by base excision repair enzymes (BER) that replace the defective base. Although the detailed molecular structures of many BER enzymes are known, how they colocalize to lesions remains unclear. One hypothesis involves charge transport (CT) along DNA [Yavin et al., Proc. Natl. Acad. Sci. U.S.A. 102, 3546 (2005)]. In this CT mechanism, electrons are released by recently adsorbed BER enzymes and travel along the DNA. The electrons can scatter (by heterogeneities along the DNA) back to the enzyme, destabilizing and knocking it off the DNA, or they can be absorbed by nearby lesions and guanine radicals. We develop a stochastic model to describe the electron dynamics and compute probabilities of electron capture by guanine radicals and repair enzymes. We also calculate first passage times of electron return and ensemble average these results over guanine radical distributions. Our statistical results provide the rules that enable us to perform implicit-electron Monte Carlo simulations of repair enzyme binding and redistribution near lesions. When lesions are electron absorbing, we show that the CT mechanism suppresses wasteful buildup of enzymes along intact portions of the DNA, maximizing enzyme concentration near lesions.
Advances in the criteria for dividing thin superconducting films into narrow and wide films
Authors: Dmitriev V. M. , Zolochevskiĭ I. V. , Bezuglyĭ E. V.
Published: December 2008

The results of experimental investigations of the critical currents and certain nonequilibrium phenomena in thin tin films of different width w are analyzed. Ordinarily, thin superconducting films are divided into two groups: narrow channels w<λ⊥ and wide films w>λ⊥. A wide transitional region where the condition w>λ⊥ holds with a large margin and at the same time cannot be explained from the standpoint of the theory of the appearance of a vortex state has been found. This shows that the generally accepted criterion w∼λ⊥ for dividing films into wide and narrow does not work. The transition into a wide-film regime, described by the existing theory of the vortex state, is fully completed only for w∕λ⊥(T)>10–20.
Magnon relaxation in a spin nematic
Authors: Butrim V. I. , Ivanov B. A. , Kuznetsov A. S. , Khymyn R. S.
Published: December 2008

Magnon relaxation processes in the nematic phase of a magnet with spin S=1 are investigated for a general form of the isotropic exchange interaction, including bilinear and biquadratic interactions in respect to the site spin operators. The temperature dependence and momentum dependence of the magnetic decrement are found in the long-wavelength approximation. It is shown that the elementary excitations in a spin nematic (magnons) have all the properties of Goldstone excitations; in the limit of small wave vectors they have a linear dispersion law, while the damping is quadratic in the wave vector. The similarity of magnon behavior in a spin nematic to that in an antiferromagnet is noted.
Schottky anomaly of linear birefringence of light in the antiferromagnetic crystal LiCoPO4
Authors: Kharchenko N. F. , Kharchenko Yu. N. , Miloslavskaya O. V.
Published: December 2008

Anomalous behavior of the birefringence of linearly polarized light has been observed in the antiferromagnetic magnetoelectric crystal LiCoPO4 at temperatures approaching the Néel temperature. Arguments are present in support of the assumption that the observed nonmonotonic change of the birefringence of light is due to the interplay of two anomalies—a magnetic anomaly, associated with the intensification of the contribution of correlated spin fluctuations, and the Schottky anomaly, due to the changing occupations of the ground and lowest excited electronic states of Co2+ ions. The estimate of the energy splitting from the excited state (45–55K) agrees satisfactorily with the position of the weakly dispersing branch in the energy spectrum of this crystal, observed in an investigation of the inelastic scattering of neutrons, as well as with the energies of the low-energy bands in the Raman scattering spectrum.
Observation of the coexistence of crystalline and liquid-like states in krypton-doped argon clusters
Authors: Danil’chenko A. G. , Kovalenko S. I. , Samovarov V. N.
Published: December 2008

Superposition of narrow diffraction peaks and wide bands of the halo type has been observed for large, mixed Ar–Kr clusters (N=(6–9)⋅104 atoms/cluster). Such a superposition shows that a crystalline solution and a phase component with short-range order (liquid-like) coexist. The effect has not been previously observed either for atomic macrosystems or for large atomic clusters. The result obtained could indicate nonclassical properties of large argon clusters doped with krypton.