bluuebunny/crossref_metadata_2025 huggingface dataset:
The Modern Boroughmongers? The Yorkshire Area (NUM) and Grassroots Politics
Authors: Taylor Andrew J.
Published: February 2007

Politics in Labour's heartlands—the coalfield Constituency Labour Parties—have rarely been examined. This article shows that the image of miners dominating CLPs is mistaken and since 1945 the weakness of the miners in grassroots politics has increased. The miners' role in grassroots politics is explored via three themes: the political consequences of one-party dominance, the problems encountered by the Yorkshire miners in maintaining their political influence, and the reassertion of miners' political influence since 1979.
The Use and Abuse of Political Violence
Authors: Miller David
Published: February 2007

The question addressed in this paper is whether it is permissible to use violence for political ends within the confines of a liberal democracy. After a brief defence of the liberal conception of violence, the standard liberal position on violence (which answers the above question unequivocally in the negative) is rejected as theoretically unsound. However the alternative radical view, which endorses the selective use of violence on democratic and/or humanitarian grounds, fails to come to terms with some important empirical facts about violence in democracies. The concluding section urges a more discriminating response to such violence than either the liberal or the radical view fosters.
The Protestant Work Ethic, Voting Behaviour and Attitudes to the Trade Unions
Authors: Furnham Adrian
Published: February 2007

This study set out to determine the structure and determinants of people's attitudes towards trade unions in Britain. Over two hundred subjects completed two questionnaires, the first measuring the Protestant work ethic, and the second attitudes towards the unions. Although there were few age, sex, education or trade union membership differences as regards attitudes toward the unions, subjects' beliefs in the Protestant work ethic and voting behaviour were clearly and predictably linked to their attitudes. Factor analysis of the attitude to the union scale revealed a number of interpretable factors. The results are discussed in terms of the psychology of voting and social and political attitudes in general.
Gαi3primes the G protein‐activated K+channels for activation by coexpressed Gβγ in intactXenopusoocytes
Authors: Rubinstein Moran , Peleg Sagit , Berlin Shai , Brass Dovrat , Dascal Nathan
Published: February 2007

G protein‐activated K+channels (GIRK) mediate postsynaptic inhibitory effects of neurotransmitters in the atrium and in the brain by coupling to G protein‐coupled receptors (GPCRs). In neurotransmitter‐dependent GIRK signalling, Gβγ is released from the heterotrimeric Gαβγ complex upon GPCR activation, activating the channel and attenuating its rectification. Now it becomes clear that Gα is more than a mere Gβγ donor. We have proposed that Gαi3–GDP regulates GIRK gating, keeping its basal activity low but priming (predisposing) the channel for activation by agonist in intact cells, and by Gβγ in excised patches. Here we have further investigated GIRK priming by Gαi3using a model in which the channel was activated by coexpression of Gβγ, and the currents were measured in intactXenopusoocytes using the two‐electrode voltage clamp technique. This method enables the bypass of GPCR activation during examination of the regulation of the channel in intact cells. Using this method, we further characterize the priming phenomenon. We tested and excluded the possibility that our estimates of priming are affected by artifacts caused by series resistance or large K+fluxes. We demonstrate that both Gαi3and membrane‐attached Gβγ scavenger protein, m‐phosducin, reduce the basal channel activity. However, Gαi3allows robust channel activation by coexpressed Gβγ, in sharp contrast to m‐phosducin, which causes a substantial reduction in the total Gβγ‐induced current. Furthermore, Gαi3also does not impair the Gβγ‐dependent attenuation of the channel rectification, in contrast to m‐phosducin, which prevents this Gβγ‐induced modulation. The Gαi3‐induced enhancement of direct activation of GIRK by Gβγ, demonstrated here for the first time in intact cells, strongly supports the hypothesis that Gαiregulates GIRK gating under physiological conditions.
Differential wiring of local excitatory and inhibitory synaptic inputs to islet cells in rat spinal lamina II demonstrated by laser scanning photostimulation
Authors: Kato Go , Kawasaki Yasuhiko , Ji Ru‐Rong , Strassman Andrew M.
Published: February 2007

The substantia gelatinosa (lamina II) of the spinal dorsal horn contains inhibitory and excitatory interneurons that are thought to play a critical role in the modulation of nociception. However, the organization of the intrinsic circuitry within lamina II remains poorly understood. We used glutamate uncaging by laser scanning photostimulation to map the location of neurons that give rise to local synaptic inputs to islet cells, a major class of inhibitory interneuron in lamina II. We also mapped the distribution of sites on the islet cells that exhibited direct (non‐synaptic) responses to uncaging of excitatory and inhibitory transmitters. Local synaptic inputs to islet cells arose almost entirely from within lamina II, and these local inputs included both excitatory and inhibitory components. Furthermore, there was a striking segregation in the location of sites that evoked excitatory versus inhibitory synaptic inputs, such that inhibitory presynaptic neurons were distributed more proximal to the islet cell soma. This was paralleled in part by a differential distribution of transmitter receptor sites on the islet cell, in that inhibitory sites were confined to the peri‐somatic region while excitatory sites were more widespread. This differential organization of excitatory and inhibitory inputs suggests a principle for the wiring of local circuitry within the substantia gelatinosa.
Multiquadric
Collocation Method for Time-Dependent Heat Conduction Problems With Temperature-Dependent Thermal
Properties
Authors: Chantasiriwan Somchart
Published: February 2007

The multiquadric collocation method is a meshless method that uses multiquadrics as its basis function. Problems of nonlinear time-dependent heat conduction in materials having temperature-dependent thermal properties are solved by using this method and the Kirchhoff transformation. Variable transformation is simplified by assuming that thermal properties are piecewise linear functions of temperature. The resulting nonlinear equation is solved by an iterative scheme. The multiquadric collocation method is tested by a heat conduction problem for which the exact solution is known. Results indicate satisfactory performance of the method.
On the Role of Coriolis Force in a Two-Dimensional Thermally Driven Flow in a Rotating Enclosure
Authors: Hasan Nadeem , Sanghi Sanjeev
Published: February 2007

In this work the role of Coriolis forces in the evolution of a two-dimensional thermally driven flow in a rotating enclosure of arbitrary geometry is discussed. Contrary to the claims made in some of the studies involving such class of flows that there is an active involvement of the these forces in the dynamics of the flow, it is shown that the Coriolis force does not play any role in the evolution of the velocity and temperature fields. This is theoretically demonstrated by recognizing the irrotational character of the Coriolis force in such class of flows. It is further shown that the presence of the irrotational Coriolis force affects only the pressure distribution in the rotating enclosure. The theoretical deductions apply quite generally to any geometry and thermal boundary conditions associated with the enclosure. The numerical results for the problem of two-dimensional thermally driven flow of air (Pr=0.71) in a circular rotating enclosure provide direct evidence of the theoretical deductions.
Instability of Heat Pipe Performance at Large Axial Accelerations
Authors: Asias A. , Shusser M. , Leitner A. , Nabi A. , Grossman G.
Published: February 2007

To investigate the feasibility of using heat pipes in airborne systems, heat pipe performance at large axial accelerations in the range of 3–12g was studied experimentally. The heat input chosen corresponded to the optimal heat pipe performance without acceleration. When applied against the direction of the liquid flow (unfavorable orientation) the accelerations were large enough to exceed the capillary limit, as was seen from the strong increase in the evaporator temperature. The influence of accelerations in the direction of the liquid flow (favorable orientation) was found to be more complicated. While at the acceleration of 3g the heat pipe performance improved, at higher accelerations instability developed with resulting large-amplitude oscillations of the evaporator temperature. The instability found in these experiments is thought to be related to the geyser effect observed in thermosyphons.
Effects of Gap Geometry and Gravity on Boiling Around a Constrained Bubble in 2-Propanol/Water Mixtures
Authors: Sun Chen-li , Carey Van P.
Published: February 2007

In this study, boiling experiments were conducted with 2-propanol/water mixtures in confined gap geometry under various levels of gravity. The temperature field created within the parallel plate gap resulted in evaporation over the portion of the vapor-liquid interface of the bubble near the heated surface, and condensation near the cold surface. Full boiling curves were obtained and two boiling regimes—nucleate boiling and pseudofilm boiling—and the transition condition, the critical heat flux (CHF), were identified. The observations indicated that the presence of the gap geometry pushed the nucleate boiling regime to a lower superheated temperature range, resulting in correspondingly lower heat flux. With further increases of wall superheat, the vapor generated by the boiling process was trapped in the gap to blanket the heated surface. This caused premature occurrence of CHF conditions and deterioration of heat transfer in the pseudo-film boiling regime. The influence of the confined space was particularly significant when greater Marangoni forces were present under reduced gravity conditions. The CHF value of x (molar fraction)=0.025, which corresponded to weaker Marangoni forces, was found to be greater than that of x=0.015 with a 6.4mm gap.
Nusselt Number and Friction Factor of Staggered Arrays of Low Aspect Ratio Micropin-Fins Under Cross Flow for Water as Fluid
Authors: Prasher Ravi S. , Dirner John , Chang Je-Young , Myers Alan , Chau David , He Dongming , Prstic Suzana
Published: February 2007

Experimental results of the thermal and hydraulic performances of silicon-based, low aspect ratio micropin-fin cold plates under cross flow conditions are reported. The pins were both circular and square in shape with dimensions (diameter for circular and sides for square) ranging from 50μm to 150μm. The test chip contained 20 integral 75×75μm temperature sensors which were used to determine the thermal resistance (KW−1) of the cold plates. The experiments were conducted using water, over a Reynolds number (Re) ranging from 40 to 1000. The data show that the average Nusselt number (Nu) based on the fin diameter varies as Re0.84 for Re<100 and as Re0.73 for Re>100, where Re is the Reynolds number based on maximum velocity and the fin diameter. Analysis of the Fanning friction factor (f) data shows that f varies as Re−1.35 for Re<100 and as Re−0.1 for Re>100.
Air Flow and Heat Transfer in Louver-Fin Round-Tube Heat Exchangers
Authors: Wu H. L. , Gong Y. , Zhu X.
Published: February 2007

Experimental investigations were conducted to understand the air flow and heat transfer in louver-fin round-tube two-row two-pass cross-counterflow heat exchangers. The Colburn factor j and friction factor f were obtained by using the ε-NTU approach. A three-dimensional computational fluid dynamics model was developed based on a representative unit cell with periodical and symmetric boundary conditions. Analysis of tube-side circuiting effect has been conducted and showed improvement by applying overall nonlinear tube-side fluid temperature boundary conditions. Comparison of heat transfer rate of the first and second rows showed that the first row was much more effective, achieving 68-53% of the total heat transfer rate, when air velocity changes from 1.02m∕sto2.54m∕s. A dimensionless parameter, F, was introduced to describe the louver interaction for different fin designs with various louver angles. Using j′∕f1∕3 as a criterion to evaluate the heat transfer and pressure loss performance, an optimal F was predicted around 0.62.
Experimental Verification of a New Heat and Mass Transfer Enhancement Concept in a Microchannel Falling Film Absorber
Authors: Goel Nitin , Goswami D. Yogi
Published: February 2007

This paper presents an experimental study of a new concept of using a screen mesh to enhance heat and mass transfer in a microchannel falling film absorber. Results of the experiments on the conventional and mesh-enhanced microchannel absorber designs are then reported. The experimental study shows that the absorber heat load for the mesh-enhanced design is about 17%±3.4%-26%±3.8% higher than a conventional microchannel design. The paper also presents a comparison of the experimental results with a numerical model. A finite difference scheme is used to model the heat and mass transfer processes in a falling film absorber. The numerical model agrees well with experimental results with some deviation at low temperature of coolant and high flow rate of weak solution.
Enhancement
of Convective Heat and Mass Transfer From Two Bubbles at High Reynolds
Number
Authors: Kendoush Abdullah
Abbas
Published: February 2007

Analytical solutions to the heat convection from two bubbles were obtained. These solutions were applied to the two bubbles with the flow along their line of centers and perpendicular to their line of centers. The method of images has been used to give a solution to the velocity distribution around the two bubbles. The derived solutions apply to fluid spheres. In general the derived solutions were compared well with the other available analytical and numerical results. Some avenues for further research were pointed out.
Heat Transfer in a Radially Rotating Square-Sectioned Duct With Two Opposite Walls Roughened by 45Deg Staggered Ribs at High Rotation Numbers
Authors: Chang Shyy Woei , Liou Tong-Minn , Hung Jui-Hung , Yeh Wen-Hsien
Published: February 2007

This paper describes an experimental study of heat transfer in a radially rotating square duct with two opposite walls roughened by 45deg staggered ribs. Air coolant flows radially outward in the test channel with experiments to be undertaken that match the actual engine conditions. Laboratory-scale heat transfer measurements along centerlines of two rib-roughened surfaces are performed with Reynolds number (Re), rotation number (Ro), and density ratio (Δρ∕ρ) in the ranges of 7500–15,000, 0–1.8, and 0.076–0.294. The experimental rig permits the heat transfer study with the rotation number considerably higher than those studied in other researches to date. The rotational influences on cooling performance of the rib-roughened channel due to Coriolis forces and rotating buoyancy are studied. A selection of experimental data illustrates the individual and interactive impacts of Re, Ro, and buoyancy number on local heat transfer. A number of experimental-based observations reveal that the Coriolis force and rotating buoyancy interact to modify heat transfer even if the rib induced secondary flows persist in the rotating channel. Local heat transfer ratios between rotating and static channels along the centerlines of stable and unstable rib-roughened surfaces with Ro varying from 0.1 to 1.8 are in the ranges of 0.6–1.6 and 1–2.2, respectively. Empirical correlations for periodic flow regions are developed to permit the evaluation of interactive and individual effects of ribflows, convective inertial force, Coriolis force, and rotating buoyancy on heat transfer.
Mixed Convection in a Vertical Parallel Plate Microchannel
Authors: Avcı Mete , Aydın Orhan
Published: February 2007

In this study, fully developed mixed convective heat transfer of a Newtonian fluid in an open-ended vertical parallel plate microchannel is analytically investigated by taking the velocity slip and the temperature jump at the wall into account. The effects of the mixed convection parameter, Gr/Re, the Knudsen number, Kn, and the ratio of wall temperature difference, rT, on the microchannel hydrodynamic and thermal behaviors are determined. Finally, a Nu=f(Gr∕Re,Kn,rT) expression is developed.
Thermal Conductivity and Compressive Strain of Aerogel Insulation Blankets Under Applied Hydrostatic Pressure
Authors: Bardy Erik R. , Mollendorf Joseph C. , Pendergast David R.
Published: February 2007

Aerogel is among the best solid thermal insulators. Aerogel is a silica gel formed by supercritical extraction which results in a porous open cell solid insulation with a thermal conductivity as low as 0.013W∕mK. Aerogels have a wide range of uses such as insulation for windows, vehicles, refrigerators∕freezers, etc. Usage for aerogel can be extended for use where flexibility is needed, such as apparel, by embedding it into a polyester batting blanket. These aerogel blankets, although flexible, have little resistance to compression and experience a residual strain effect upon exposure to elevated pressures. It was suggested, by Aspen Aerogels Inc., that a prototype aerogel blanket would have increased resistance to compression and minimized residual strain upon exposure to elevated pressures. Samples of prototype and normal product-line aerogel insulating blankets were acquired. These materials were separately tested for thermal conductivity and compressive strain at incremental pressure stops up to 1.2MPa. The compressive strain of the prototype aerogel blanket reached a level of 0.25mm∕mm whereas the product-line aerogel blanket compressed to 0.48mm∕mm at 1.2MPa. Before compression, the thermal conductivity of the prototype aerogel blanket was slightly higher than the product-line aerogel blanket. During compression the thermal conductivity increased 46% for the product-line aerogel blanket whereas it increased only 13% for the prototype aerogel blanket at 1.2MPa. The total thermal resistance decreased 64% for the product-line aerogel blanket at 1.2MPa and remained at that value upon decompression to atmospheric pressure. The total thermal resistance of the prototype aerogel blanket decreased 33% at 1.2MPa and returned to within 1% of its initial value upon decompression to atmospheric pressure. It was found that the prototype aerogel blanket has approximately twice as much resistance to hydrostatic compression to a pressure of 1.2MPa and also recovers to its original state upon decompression. The thermal resistance of the prototype aerogel blanket remained 37% higher than the product-line aerogel blanket at 1.2MPa. This resistance to compression and the ability to recover to its original state upon decompression from elevated pressures makes the prototype aerogel blanket suitable for applications where high insulation, resistance to compression, and recovery after a compression cycle is needed.
Crystal Structures of the Adenylate Sensor from Fission Yeast AMP-Activated Protein Kinase
Authors: Townley Robert , Shapiro Lawrence
Published: February 2007

The 5′-AMP (adenosine monophosphate)–activated protein kinase (AMPK) coordinates metabolic function with energy availability by responding to changes in intracellular ATP (adenosine triphosphate) and AMP concentrations. Here, we report crystal structures at 2.9 and 2.6 Å resolution for ATP- and AMP-bound forms of a core αβγ adenylate-binding domain from the fission yeast AMPK homolog. ATP and AMP bind competitively to a single site in the γ subunit, with their respective phosphate groups positioned near function-impairing mutants. Unexpectedly, ATP binds without counterions, amplifying its electrostatic effects on a critical regulatory region where all three subunits converge.
An Intrinsic Bond-Centered Electronic Glass with Unidirectional Domains in Underdoped Cuprates
Authors: Kohsaka Y. , Taylor C. , Fujita K. , Schmidt A. , Lupien C. , Hanaguri T. , Azuma M. , Takano M. , Eisaki H. , Takagi H. , Uchida S. , Davis J. C.
Published: February 2007

Removing electrons from the CuO
2
plane of cuprates alters the electronic correlations sufficiently to produce high-temperature superconductivity. Associated with these changes are spectral-weight transfers from the high-energy states of the insulator to low energies. In theory, these should be detectable as an imbalance between the tunneling rate for electron injection and extraction—a tunneling asymmetry. We introduce atomic-resolution tunneling-asymmetry imaging, finding virtually identical phenomena in two lightly hole-doped cuprates: Ca
1.88
Na
0.12
CuO
2
Cl
2
and Bi
2
Sr
2
Dy
0.2
Ca
0.8
Cu
2
O
8+δ
. Intense spatial variations in tunneling asymmetry occur primarily at the planar oxygen sites; their spatial arrangement forms a Cu-O-Cu bond-centered electronic pattern without long-range order but with 4
a
0
-wide unidirectional electronic domains dispersed throughout (
a
0
: the Cu-O-Cu distance). The emerging picture is then of a partial hole localization within an intrinsic electronic glass evolving, at higher hole densities, into complete delocalization and highest-temperature superconductivity.
Proteomic and Microarray Analyses of theDictyosteliumZak1-GSK-3 Signaling Pathway Reveal a Role in Early Development
Authors: Strmecki Lana , Bloomfield Gareth , Araki Tsuyoshi , Dalton Emma , Skelton Jason , Schilde Christina , Harwood Adrian , Williams Jeffrey G. , Ivens Al , Pears Catherine
Published: February 2007

GskA, theDictyosteliumGSK-3 orthologue, is modified and activated by the dual-specificity tyrosine kinase Zak1, and the two kinases form part of a signaling pathway that responds to extracellular cyclic AMP. We identify potential cellular effectors for the two kinases by analyzing the corresponding null mutants. There are proteins and mRNAs that are altered in abundance in only one or the other of the two mutants, indicating that each kinase has some unique functions. However, proteomic and microarray analyses identified a number of proteins and genes, respectively, that are similarly misregulated in both mutant strains. The positive correlation between the array data and the proteomic data is consistent with the Zak1-GskA signaling pathway's functioning by directly or indirectly regulating gene expression. The discoidin 1 genes are positively regulated by the pathway, while the abundance of the H5 protein is negatively regulated. Two of the targets, H5 and discoidin 1, are well-characterized markers for early development, indicating that the Zak1-GskA pathway plays a role in development earlier than previously observed.
Effort thrombosis of the upper extremity in a young sportsman: Paget–Schroetter syndrome
Authors: Roche-Nagle Graham , Ryan Ronan , Barry Mary , Brophy David
Published: February 2007

Paget-Schroetter syndrome is the spontaneous thrombosis of the axillary/subclavian vein. A 16-year-old male presented with acute onset of right upper limb swelling after vigorous weight training. A venogram confirmed the diagnosis of Paget–Schroetter syndrome. He was started on intravenous thrombolytics followed by oral anticoagulation therapy. His symptoms resolved and he was symptom free at six-month follow-up. Thrombolytics and anticoagulation is the most widely accepted first-line therapy for this syndrome. Defining any anatomical anomaly as the predisposing factor in this condition is essential in the selection of which patients will benefit from thoracic outlet decompression.
Reliability of MRI assessment of supraspinatus tendinopathy
Authors: Sein Mya Lay , Walton Judie , Linklater James , Harris Craig , Dugal Tej , Appleyard Richard , Kirkbride Brent , Kuah Donald , Murrell George A C
Published: February 2007

Objective:To determine the interobserver and intraobserver reliability of the interpretation of MRIs for supraspinatus tendinosis.

Methods:In the interobserver trial, the MRIs of 52 athletes’ shoulders were observed by 3 observers on one occasion within a 2-month period. All 52 images were read by the most experienced musculoskeletal radiologist on 3 different occasions on separate days without access to the previous readings for the intraobserver trial. Supraspinatus tendinosis was graded using a modified 4-point scale from grades 0 to grade 3.

Results:The grading of MRI-determined supraspinatus tendinosis was reliable, having an intraclass correlation (ICC) of 0.85 when assessed by the single well-trained observer. Interobserver reliability was only fair to good (ICC = 0.55).

Conclusions:Supraspinatus tendinosis can be accurately identified on MRI with little variation by a single well-trained observer. Interobserver reliability was only fair to good. Our data indicated that the reliability of the assessment was much greater in more experienced radiologists than in those with less experience.
REGULARITY RESULTS FOR TIME-DEPENDENT VARIATIONAL AND QUASI-VARIATIONAL INEQUALITIES AND APPLICATION TO THE CALCULATION OF DYNAMIC TRAFFIC NETWORK
Authors: BARBAGALLO ANNAMARIA
Published: February 2007

The aim of this paper is to consider time-dependent variational and quasi-variational inequalities and to study under which assumptions the continuity of solutions with respect to time can be ensured. Making an appropriate use of the set convergence in Mosco's sense, we are able to prove continuity results for strongly monotone variational and quasi-variational inequalities. The continuity results allow us to provide a discretization procedure for the calculation of solutions to the variational inequalities and, as a consequence, we can solve the time-dependent traffic network equilibrium problem.
Mechanism and Function of Formins in the Control of Actin Assembly
Authors: Goode Bruce L. , Eck Michael J.
Published: February 2007

Formins are a widely expressed family of proteins that govern cell shape, adhesion, cytokinesis, and morphogenesis by remodeling the actin and microtubule cytoskeletons. These large multidomain proteins associate with a variety of other cellular factors and directly nucleate actin polymerization through a novel mechanism. The signature formin homology 2 (FH2) domain initiates filament assembly and remains persistently associated with the fast-growing barbed end, enabling rapid insertion of actin subunits while protecting the end from capping proteins. On the basis of structural and mechanistic work, an integrated model is presented for FH2 processive motion. The adjacent FH1 domain recruits profilin-actin complexes and accelerates filament elongation. The most predominantly expressed formins in animals and fungi are autoinhibited through intramolecular interactions and appear to be activated by Rho GTPases and additional factors. Other classes of formins lack the autoinhibitory and/or Rho-binding domains and thus are likely to be controlled by alternative mechanisms.
TRP Channels
Authors: Venkatachalam Kartik , Montell Craig
Published: February 2007

The TRP (Transient Receptor Potential) superfamily of cation channels is remarkable in that it displays greater diversity in activation mechanisms and selectivities than any other group of ion channels. The domain organizations of some TRP proteins are also unusual, as they consist of linked channel and enzyme domains. A unifying theme in this group is that TRP proteins play critical roles in sensory physiology, which include contributions to vision, taste, olfaction, hearing, touch, and thermo- and osmosensation. In addition, TRP channels enable individual cells to sense changes in their local environment. Many TRP channels are activated by a variety of different stimuli and function as signal integrators. The TRP superfamily is divided into seven subfamilies: the five group 1 TRPs (TRPC, TRPV, TRPM, TRPN, and TRPA) and two group 2 subfamilies (TRPP and TRPML). TRP channels are important for human health as mutations in at least four TRP channels underlie disease.
Structure and Mechanism of Helicases and Nucleic Acid Translocases
Authors: Singleton Martin R. , Dillingham Mark S. , Wigley Dale B.
Published: February 2007

Helicases and translocases are a ubiquitous, highly diverse group of proteins that perform an extraordinary variety of functions in cells. Consequently, this review sets out to define a nomenclature for these enzymes based on current knowledge of sequence, structure, and mechanism. Using previous definitions of helicase families as a basis, we delineate six superfamilies of enzymes, with examples of crystal structures where available, and discuss these structures in the context of biochemical data to outline our present understanding of helicase and translocase activity. As a result, each superfamily is subdivided, where appropriate, on the basis of mechanistic understanding, which we hope will provide a framework for classification of new superfamily members as they are discovered and characterized.
Structures and Functions of Yeast Kinetochore Complexes
Authors: Westermann Stefan , Drubin David G. , Barnes Georjana
Published: February 2007

The kinetochore is a key cell division organelle that enables high-fidelity transmission of genetic information by coupling chromosomes to spindle microtubules during mitosis and meiosis. Despite its cytological description more than a century ago, remarkably little information is available on kinetochore function at a molecular level. Recently, important advances elucidating the overall organization of kinetochores, as well as information about the structures and molecular mechanisms of kinetochore function, have been achieved through a detailed analysis of the kinetochores of the budding yeast Saccharomyces cerevisiae. Here we review the current understanding of kinetochore function in budding yeast and draw comparisons to recent findings in other organisms.
Structural Biology of Nucleocytoplasmic Transport
Authors: Cook Atlanta , Bono Fulvia , Jinek Martin , Conti Elena
Published: February 2007

In eukaryotic cells, segregation of DNA replication and RNA biogenesis in the nucleus and protein synthesis in the cytoplasm poses the requirement of transporting thousands of macromolecules between the two cellular compartments. Transport between nucleus and cytoplasm is mediated by soluble receptors that recognize specific cargoes and carry them through the nuclear pore complex (NPC), the sole gateway between the two compartments at interphase. Nucleocytoplasmic transport is specific not only in terms of cargo recognition, but also in terms of directionality, with nuclear proteins imported into the nucleus and RNAs exported from it. How is directionality achieved? How can the receptors be both specific and versatile in recognizing a multitude of cargoes? And how can their interaction with NPCs allow fast translocation? We describe the molecular mechanisms underlying nucleocytoplasmic transport as they have been revealed by structural studies of the receptors and regulators in different steps of transport cycles.
Functions of Site-Specific Histone Acetylation and Deacetylation
Authors: Shahbazian Mona D. , Grunstein Michael
Published: February 2007

Histone acetylation regulates many cellular processes, and specific acetylation marks, either singly or in combination, produce distinct outcomes. For example, the acetylation pattern on newly synthesized histones is important for their assembly into nucleosomes by histone chaperones. Additionally, the degree of chromatin compaction and folding may be regulated by acetylation of histone H4 at lysine 16. Histone acetylation also regulates the formation of heterochromatin; deacetylation of H4 lysine 16 is important for spreading of heterochromatin components, whereas acetylation of this site serves as a barrier to this spreading. Finally, histone acetylation is critical for gene transcription, but recent results suggest that deacetylation of certain sites also plays an important role. There are many histone acetyltransferases (HATs) and deacetylases, with differing preferences for the various histone proteins and for specific sites on individual histones. Determining how these enzymes create distinct acetylation patterns and regulate the functional outcome is an important challenge.
Translocation of Proteins into Mitochondria
Authors: Neupert Walter , Herrmann Johannes M.
Published: February 2007

About 10% to 15% of the nuclear genes of eukaryotic organisms encode mitochondrial proteins. These proteins are synthesized in the cytosol and recognized by receptors on the surface of mitochondria. Translocases in the outer and inner membrane of mitochondria mediate the import and intramitochondrial sorting of these proteins; ATP and the membrane potential are used as energy sources. Chaperones and auxilliary factors assist in the folding and assembly of mitochondrial proteins into their native, three-dimensional structures. This review summarizes the present knowledge on the import and sorting of mitochondrial precursor proteins, with a special emphasis on unresolved questions and topics of current research.
Modulation of the Ryanodine Receptor and Intracellular Calcium
Authors: Zalk Ran , Lehnart Stephan E. , Marks Andrew R.
Published: February 2007

Ryanodine receptors (RyRs)/Ca2+ release channels, on the endoplasmic and sarcoplasmic reticulum of most cell types, are required for intracellular Ca2+ release involved in diverse cellular functions, including muscle contraction and neurotransmitter release. The large cytoplasmic domain of the RyR serves as a scaffold for proteins that bind to and modulate the channel's function and that comprise a macromolecular signaling complex. These proteins include calstabins [FK506-binding proteins (FKBPs)], calmodulin (CaM), phosphodiesterase, kinases, phosphatases, and their cognate targeting proteins. This review focuses on recent progress in the understanding of RyR regulation and disease mechanisms that are associated with channel dysfunction.
Structure and Function of Toll Receptors and Their Ligands
Authors: Gay Nicholas J. , Gangloff Monique
Published: February 2007

The Toll family of class I transmembrane receptors recognizes and responds to diverse structures associated with pathogenic microorganisms. These receptors mediate initial responses in innate immunity and are required for the development of the adaptive immune response. Toll receptor signaling pathways are also implicated in serious autoimmune diseases such as endotoxic shock and thus are important therapeutic targets. In this review we discuss how microbial structures as different as nucleic acids and lipoproteins can be recognized by the extracellular domains of Toll receptors. We review recent evidence that the mechanism of signal transduction is complex and involves sequential changes in the conformation of the receptor induced by binding of the ligand. Finally, we assess the emerging area of cross talk in the Toll pathways. Recent work suggests that signaling through TLR4 in response to endotoxin is modified by inputs from at least two other pathways acting through β2 integrins and protein kinase Cɛ.
Signaling Pathways Downstream of Pattern-Recognition Receptors and Their Cross Talk
Authors: Lee Myeong Sup , Kim Young-Joon
Published: February 2007

Pattern-recognition receptors (PRRs) initiate innate immunity through pathogen recognition. Serum PRRs opsonize pathogens for enhanced phagocytic clearance. Toll-like receptors (TLRs) initiate common NF-κB/AP-1 and distinct IRF3/7 pathways to coordinate innate immunity and to initiate adaptive immunity against diverse pathogens. Cytoplasmic caspase-recruiting domain (CARD) helicases, such as RIG-I/MDA5, mediate antiviral immunity by inducing the production of type I interferons via the adaptor IPS-1, whereas nucleotide-binding oligomerization domain (NOD)-like receptors mediate mainly antibacterial immunity by activating NF-κB or inflammasomes. Dectin-1 is important for antifungal immunity, promoting phagocytosis and activating NF-κB. Potentially harmful TLR signaling pathways can be negatively regulated by negative feedback mechanisms and also by anti-inflammatory factors such as TGFβ, interleukin (IL)-10, and steroids. Many combinations of TLR-TLR and TLR-NOD modulate inflammatory responses. TLRs and NALP3 interplay to produce mature IL-1β. Thus signaling pathways downstream of PRRs and their cross talk control immune responses in effective manners.
The Postsynaptic Architecture of Excitatory Synapses: A More Quantitative View
Authors: Sheng Morgan , Hoogenraad Casper C.
Published: February 2007

Excitatory (glutamatergic) synapses in the mammalian brain are usually situated on dendritic spines, a postsynaptic microcompartment that also harbors organelles involved in protein synthesis, membrane trafficking, and calcium metabolism. The postsynaptic membrane contains a high concentration of glutamate receptors, associated signaling proteins, and cytoskeletal elements, all assembled by a variety of scaffold proteins into an organized structure called the postsynaptic density (PSD). A complex machine made of hundreds of distinct proteins, the PSD dynamically changes its structure and composition during development and in response to synaptic activity. The molecular size of the PSD and the stoichiometry of many major constituents have been recently measured. The structures of some intact PSD proteins, as well as the spatial arrangement of several proteins within the PSD, have been determined at low resolution by electron microscopy. On the basis of such studies, a more quantitative and geometrically realistic view of PSD architecture is emerging.
The Magic Garden
Authors: Schatz Gottfried
Published: February 2007

For more than a century after their discovery, mitochondria were viewed almost exclusively as ATP-generating metabolic units. This view changed with the discovery of the mitochondrial genetic system and the central role of mitochondria in programmed cell death. As a result, much of the current research focuses on the complex interplay between mitochondria and the rest of the eukaryotic cell. This interplay is central to mitochondrial biogenesis. The following five reviews published in this volume summarize recent discoveries in this area: DNA Replication and Transcription in Mammalian Mitochondria, Mitochondrial-Nuclear Communications, Translocation of Proteins into Mitochondria, The Machines that Divide and Fuse Mitochondria, and Why Do We Still Have a Maternally Inherited Mitochondrial DNA? Insights from Evolutionary Medicine.
Effects of linoleic acid on sweet, sour, salty, and bitter taste thresholds and intensity ratings of adults
Authors: Mattes Richard D.
Published: February 2007

Evidence supporting a taste component for dietary fat has prompted study of plausible transduction mechanisms. One hypothesizes that long-chain, unsaturated fatty acids block selected delayed-rectifying potassium channels, resulting in a sensitization of taste receptor cells to stimulation by other taste compounds. This was tested in 17 male and 17 female adult (mean ± SE age = 23.4 ± 0.7 yr) propylthiouracil tasters with normal resting triglyceride concentrations (87.3 ± 5.6 mg/day) and body mass index (23.3 ± 0.4 kg/m2). Participants were tested during two ∼30-min test sessions per week for 8 wk. Eight stimuli were assessed in duplicate via an ascending, three-alternative, forced-choice procedure. Qualities were randomized over weeks. Stimuli were presented as room-temperature, 5-ml portions. They included 1% solutions of linoleic acid with added sodium chloride (salty), sucrose (sweet), citric acid (sour), and caffeine (bitter) as well as solutions of these taste compounds alone. Participants also rated the intensity of the five strongest concentrations using the general labeled magnitude scale. The suprathreshold samples were presented in random order with a rinse between each. Subjects made the ratings self-paced while wearing nose clips. It was hypothesized that taste thresholds would be lower and absolute intensity ratings or slopes of intensity functions would be higher for the stimuli mixed with the linoleic acid. Thresholds were compared by paired t-tests and intensity ratings by repeated measures analysis of variance. Thresholds were significantly higher (i.e., lower sensitivity) for the sodium chloride, citric acid, and caffeine solutions with added fatty acid. Sweet, sour, and salty intensity ratings were lower or unchanged by the addition of a fatty acid. The two highest concentrations of caffeine were rated as weaker in the presence of linoleic acid. These data do not support a mechanism for detecting dietary fats whereby fatty acids sensitize taste receptor cells to stimulation by taste compounds.
Importance of pH regulation and lactate/H+transport capacity for work production during supramaximal exercise in humans
Authors: Messonnier Laurent , Kristensen Michael , Juel Carsten , Denis Christian
Published: February 2007

We examine the influence of the cytosolic and membrane-bound contents of carbonic anhydrase (CA; CAII, CAIII, CAIV, and CAXIV) and the muscle content of proteins involved in lactate and proton transport [monocarboxylate transporter (MCT) 1, MCT4, and Na+/H+exchanger 1 (NHE1)] on work capacity during supramaximal exercise. Eight healthy, sedentary subjects performed exercises at 120% of the work rate corresponding to maximal oxygen uptake (Ẇmax) until exhaustion in placebo (Con) and metabolic alkalosis (Alk) conditions. The total (Wtot) and supramaximal work performed (Wsup) was measured. Muscle biopsies were obtained before and immediately after standardized exercises (se) at 120% Ẇmaxin both conditions to determine the content of the targeted proteins, the decrease in muscle pH (ΔpHm), and the muscle lactate accumulation ([Lac]m) per joule of Wsup(ΔpHm/Wsup-seand Δ[Lac]m/Wsup-se, respectively) and the dynamic buffer capacity. In Con, Wsupwas negatively correlated with ΔpHm/Wsup-se, positively correlated with Δ[Lac]m/Wsup-seand MCT1, and tended to be positively correlated with MCT4 and NHE1. CAII + CAIII were correlated positively with ΔpHm/Wsup-seand negatively with Δ[Lac]m/Wsup-se, while CAIV was positively related to Wtot. The changes in Wsupwith Alk were correlated positively with those in dynamic buffer capacity and negatively with Wsupin Con. Performance improvement with Alk was greater in subjects having a low content of proteins involved in pH regulation and lactate/proton transport. These results show the importance of pH regulating mechanisms and lactate/proton transport on work capacity and the role of the CA to delay decrease in pHmand accumulation in [Lac]mduring supramaximal exercise in humans.
IGF-II gene region polymorphisms related to exertional muscle damage
Authors: Devaney Joseph M. , Hoffman Eric P. , Gordish-Dressman Heather , Kearns Amy , Zambraski Edward , Clarkson Priscilla M.
Published: February 2007

We examined the association of a novel single-nucleotide polymorphism (SNP) in IGF-I (IGF-I −C1245T located in the promoter) and eight SNPs in the IGF-II gene region with indicators of muscle damage [strength loss, muscle soreness, and increases in circulating levels of creatine kinase (CK) and myoglobin] after eccentric exercise. We also examined two SNPs in the IGF binding protein-3 (IGFBP-3). The age, height, and body mass of the 151 subjects studied were 24.1 ± 5.2 yr, 170.8 ± 9.9 cm, and 73.3 ± 17.0 kg, respectively. There were no significant associations of phenotypes with IGF-I. IGF-II SNP (G12655A, rs3213216) and IGFBP-3 SNP (A8618T, rs6670) were not significantly associated with any variable. The most significant finding in this study was that for men, IGF-II (C13790G, rs3213221), IGF-II (ApaI, G17200A, rs680), IGF-II antisense (IGF2AS) (G11711T, rs7924316), and IGFBP-3 (−C1592A, rs2132570) were significantly associated with muscle damage indicators. We found that men who were 1) homozygous for the rare IGF-II C13790G allele and rare allele for the ApaI (G17200A) SNP demonstrated the greatest strength loss immediately after exercise, greatest soreness, and highest postexercise serum CK activity; 2) homozygous wild type for IGF2AS (G11711T, rs7924316) had the greatest strength loss and most muscle soreness; and 3) homozygous wild type for the IGF2AS G11711T SNP showed the greatest strength loss, highest muscle soreness, and greater CK and myoglobin response to exercise. In women, fewer significant associations appeared.
In vitro validation of computational fluid dynamic simulation in human proximal airways with hyperpolarized3He magnetic resonance phase-contrast velocimetry
Authors: de Rochefort Ludovic , Vial Laurence , Fodil Redouane , Maître Xavier , Louis Bruno , Isabey Daniel , Caillibotte Georges , Thiriet Marc , Bittoun Jacques , Durand Emmanuel , Sbirlea-Apiou Gabriela
Published: February 2007

Computational fluid dynamics (CFD) and magnetic resonance (MR) gas velocimetry were concurrently performed to study airflow in the same model of human proximal airways. Realistic in vivo-based human airway geometry was segmented from thoracic computed tomography. The three-dimensional numerical description of the airways was used for both generation of a physical airway model using rapid prototyping and mesh generation for CFD simulations. Steady laminar inspiratory experiments (Reynolds number Re = 770) were performed and velocity maps down to the fourth airway generation were extracted from a new velocity mapping technique based on MR velocimetry using hyperpolarized3He gas. Full two-dimensional maps of the velocity vector were measured within a few seconds. Numerical simulations were carried out with the experimental flow conditions, and the two sets of data were compared between the two modalities. Flow distributions agreed within 3%. Main and secondary flow velocity intensities were similar, as were velocity convective patterns. This work demonstrates that experimental and numerical gas velocity data can be obtained and compared in the same complex airway geometry. Experiments validated the simulation platform that integrates patient-specific airway reconstruction process from in vivo thoracic scans and velocity field calculation with CFD, hence allowing the results of this numerical tool to be used with confidence in potential clinical applications for lung characterization. Finally, this combined numerical and experimental approach of flow assessment in realistic in vivo-based human airway geometries confirmed the strong dependence of airway flow patterns on local and global geometrical factors, which could contribute to gas mixing.