bluuebunny/crossref_metadata_2025 huggingface dataset:
Left ventricular pacing site in cardiac resynchronization therapy: Clinical follow‐up and predictors of failed lateral implant
Authors: Macías Alfonso , Gavira Juan‐José , Castaño Sara , Alegría Eduardo , García‐Bolao Ignacio
Published: April 2008

The effects of the left ventricular (LV) pacing site on the clinical results of resynchronization therapy (CRT) are not well characterized. The aim of this study was to define the effect of LV lead location on clinical response and LV remodelling, and to identify predictors of failure to implant the LV lead in a lateral location.

One hundred and seventy two consecutive patients were evaluated at baseline and 6 months after CRT. In 128 patients, the LV lead was implanted in the lateral region (Group 1), while 44 received an anterior implant due to anatomical or electrical factors (Group 2). Group 1 was associated with a significantly better functional outcome assessed both by NYHA class (p < 0.001) and by the six‐minute‐walk test (p = 0.01) compared with group 2. LV ejection fraction and volumes, and inter‐ and intraventricular dyssynchrony only improved significantly (p < 0.01) in group 1. The only independent predictor of a failed lateral implant was the presence of ischaemic cardiomyopathy (OR 3.29, 95% CI 2.2–13.7; p = 0.02).

In conclusion, a lateral lead location results in a better functional outcome and greater reverse LV remodelling compared with anterior locations. The presence of ischaemic cardiomyopathy is a risk factor for a failed lateral LV implant.
The Lhcb protein and xanthophyll composition of the light harvesting antenna controls the ΔpH‐dependency of non‐photochemical quenching in Arabidopsis thaliana
Authors: Pérez-Bueno Maria L. , Johnson Matthew P. , Zia Ahmad , Ruban Alexander V. , Horton Peter
Published: April 2008

Nonphotochemical quenching (NPQ) is the photoprotective dissipation of energy in photosynthetic membranes. The hypothesis that the ΔpH‐dependent component of NPQ (qE) component of non‐photochemical quenching is controlled allosterically by the xanthophyll cycle has been tested using Arabidopsis mutants with different xanthophyll content and composition of Lhcb proteins. The titration curves of qE against ΔpH were different in chloroplasts containing zeaxanthin or violaxanthin, proving their roles as allosteric activator and inhibitor, respectively. The curves differed in mutants deficient in lutein and specific Lhcb proteins. The results show that qE is determined by xanthophyll occupancy and the structural interactions within the antenna that govern allostericity.
A comparison of the effects of kaempferol and quercetin on cytokine-induced pro-inflammatory status of cultured human endothelial cells
Authors: Crespo Irene , García-Mediavilla María V. , Gutiérrez Belén , Sánchez-Campos Sonia , Tuñón María J. , González-Gallego Javier
Published: April 2008

We investigated the effects of the flavonols kaempferol and quercetin on the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), endothelial cell selectin (E-selectin), inducible NO synthase (iNOS) and cyclo-oxygenase-2 (COX-2), and on the activation of the signalling molecules NF-κB and activator protein-1 (AP-1), induced by a cytokine mixture in cultured human umbilical vein endothelial cells. Inhibition of reactive oxygen and nitrogen species generation did not differ among both flavonols at 1 μmol/l but was significantly stronger for kaempferol at 5–50 μmol/l. Supplementation with increasing concentrations of kaempferol substantially attenuated the increase induced by the cytokine mixture in VCAM-1 (10–50 μmol/l), ICAM-1 (50 μmol/l) and E-selectin (5–50 μmol/l) expression. A significantly inhibitory effect of quercetin on VCAM-1 (10–50 μmol/l), ICAM-1 (50 μmol/l) and E-selectin (50 μmol/l) expression was also observed. Expression of adhesion molecules was always more strongly inhibited in kaempferol-treated than in quercetin-treated cells. The inhibitory effect on iNOS and COX-2 protein level was stronger for quercetin at 5–50 μmol/l. The effect of kaempferol on NF-κB and AP-1 binding activity was weaker at high concentrations (50 μmol/l) as compared with quercetin. The present study indicates that differences exist in the modulation of pro-inflammatory genes and in the blockade of NF-κB and AP-1 by kaempferol and quercetin. The minor structural differences between both flavonols determine differences in their anti-inflammatory properties and in their efficiency in inhibiting signalling molecules.
Impact of treatment with praziquantel, silymarin and/or β-glucan on pathophysiological markers of liver damage and fibrosis in mice infected withMesocestoides vogae(Cestoda) tetrathyridia
Authors: Velebný S. , Hrčkova G. , Kogan G.
Published: April 2008

Mesocestoides vogaetetrathyridia infection in mice causes hepatocyte injury, hepatic granulomatous inflammmation, liver fibrosis and chronic peritonitis manifested with portal hypertension. To reduce the detrimental effect of parasites on the host liver, the effect of the anthelmintic drug praziquantel (PZQ) in combination with natural products silymarin (an antioxidant) and β-glucan (an immunomodulator) was investigated. The therapeutic effect of drugs was assessed by means of aminotransferase (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) activities, content of albumin, total proteins and hyaluronic acid (HA) in sera of ICR mice infected withM. vogaelarvae. Animals were treated with PZQ suspended in oil emulsion (Group 1), PZQ combined with silymarin incorporated into lipid microspheres (LMS) (Group 2), PZQ combined with β-glucan incorporated into liposomes (LG) (Group 3), PZQ co-administered with LMS and LG (Group 4). Untreated animals (Group 5) served as the control. Treatment of animals started at the early chronic phase of infection (day 14 p.i.) and lasted 10 days; serum samples were collected on days 0, 7, 14, 25, 28, 31, 35 and 45 p.i. ALT and AST activities were significantly (P < 0.05) decreased in Groups 2, 3 and 4. HA content was significantly (P < 0.05 and 0.01) lower in Groups 2 and 4. Albumin levels were decreased in Groups 2 and 4, total protein concentration decreased in Groups 1 and 3 (P < 0.05 and 0.01). These results showed that combined treatment of PZQ with silymarin and/or β-glucan was able to ameliorate or suppress fibrogenesis in the liver, protect liver cells from oxidative damage and, possibly, stimulate regeneration of the parenchyma.
Insights from the colour category controversy
Authors: Belpaeme Tony
Published: April 2008

There are striking parallels between the basic tastes debate and the debate on human colour categorisation. Colour categories show a remarkable cross-cultural similarity, but at the same the time exhibit seemingly inexplicable large interpersonal variations. Recent results suggest that colour categories are the result of cultural learning constrained by the neural substrate of colour perception.
Synthesizing complex sensations from simple components
Authors: Warren Richard M.
Published: April 2008

The target article suggests that taste is not based on the traditional four basic tastes, but rather is a continuum subserved by cross-fiber integration. This commentary describes evidence indicating that the traditional concept is valid, and that with suitable precautions, it is possible to match natural substances using mixtures representing fundamental tastes.
Buoyant melting instabilities beneath extending lithosphere: 1. Numerical models
Authors: Hernlund John W. , Tackley Paul J. , Stevenson David J.
Published: April 2008

Buoyant decompression melting instabilities in regions of partially molten upper mantle have been proposed to be an important process that might account for some characteristics of intraplate volcanism on Earth and other terrestrial planets. The instability is driven by variations in the melting rate within a partially molten layer whenever a relative decrease in density accompanies decompression melting of ascending mantle. Here, the development of buoyant decompression melting instabilities in a plane layer of passively upwelling and partially melting mantle beneath diffusely extending lithosphere is studied using numerical convection models covering a wide range of physical parameters. We find that the occurrence and nature of these instabilities in such a scenario is strongly affected by the rate of extension and melt percolation, as well as depth distribution of solid density variations arising from melt depletion. In some cases, instabilities do not occur during extension, but only develop after extension has slowed or stopped completely. This behavior creates two pulses of magma generation due to passive upwelling accompanying extension followed by the subsequent instability and is favored by a faster rate of extension, higher mantle viscosity, higher rate of melt percolation, and smaller amount of solid residuum depletion‐derived buoyancy. Larger degrees of solid density changes accompanying melt depletion can enhance the instability of partially molten mantle during extension but decrease the cumulative volume of generated melt. This kind of behavior modifies the conventional expectation of spatially and temporally correlated volcanism and extension and may lend insight into the observed increase in localized volcanic activity following Miocene Basin and Range extension in the western United States.
Equatorial Pacific chemical and biological variability, 1997–2003
Authors: Strutton Peter G. , Evans Wiley , Chavez Francisco P.
Published: April 2008

Using a database of roughly 300 basin‐wide conductivity‐temperature‐depth (CTD) stations per year from 1997 to 2003, we examined interannual and seasonal variability of nutrients and chlorophyll across the equatorial Pacific. During this period, chlorophyll concentrations exceeded the range of previous measurements for this region. Nitrate, silicic acid, and phosphate also varied widely but not necessarily coherently with each other or with chlorophyll. Across the La Niña to El Niño continuum there was nonmonotonic variability in chlorophyll, particulate backscatter (a proxy for phytoplankton carbon), and large size fraction (diatom) chlorophyll. In general, while El Niño was associated with decreased phytoplankton biomass, there was no corresponding increase in phytoplankton or diatoms during La Niña. However, there were increases in macronutrients in response to La Niña. We suggest that the lack of a biological response to these nutrient increases is due to their decoupling from iron supply. Multiple linear regression analysis of the physical factors responsible for vertical nutrient fluxes emphasized the importance of winds in the central and western Pacific, and thermocline depth in the east. We suggest that the role of the winds is not limited to enhancement of upwelling, but perhaps more importantly to increased vertical mixing of nutrients. Seasonal patterns were weak but consistent with previous work which has suggested that enhanced productivity in the second half of the calendar year causes reduced surface pCO2. Enhanced coverage of nutrient sensors on the tropical atmosphere ocean (TAO) array would help to quantify seasonal signals associated with processes such as tropical instability waves and lead to a better understanding of the links between productivity, carbon export, and air‐sea CO2 exchange.
New acoustic velocity measurements on CaO‐MgO‐Al2O3‐SiO2 liquids: Reevaluation of the volume and compressibility of CaMgSi2O6‐CaAl2Si2O8 liquids to 25 GPa
Authors: Ai Yuhui , Lange Rebecca A.
Published: April 2008

Relaxed sound speed measurements on 12 liquids in the CaO‐MgO‐Al2O3‐SiO2 (CMAS) system have been performed from 1410 to 1620°C at 1 bar with a frequency sweep acoustic interferometer. In all liquids, the sound speeds either decrease or remain constant with increasing temperature. These data are combined with those in the literature to calibrate models for βT and (∂V/∂P)T as a function of composition and temperature for CMAS liquids. CaO is the only oxide component that contributes to the temperature dependence of compressibility. The new compressibility models permit the bulk modulus (KT,0) of CaMgSi2O6 (Di), CaAl2Si2O8 (An), and the Di64‐An36 eutectic liquid to be directly obtained. These results are used to uniquely constrain values for the pressure dependence of the bulk modulus (K0′ = dK0/dP) in a third‐order Birch‐Murnaghan equation of state (EOS) for these three liquids from shock wave data in the literature. The revised K0′ value is 6.8 (versus 6.9) for CaMgSi2O6 liquid, 4.7 (versus 5.3) for CaAl2Si2O8 liquid, and 5.6 (versus 4.85) for Di64‐An36 liquid. Information on both KT,0 and K0′ allows the density and compressibility for each of these three liquids to be calculated as a function of pressure to 25 GPa. Both the molar volume and isothermal compressibility of CaMgSi2O6‐CaAl2Si2O8 liquids mix ideally between 0 and 25 GPa. The dominant mechanism of compression at low pressure (0–5 GPa) for all three liquids (CaMgSi2O6, CaAl2Si2O8, and the Di64‐An36 eutectic) is topological, whereas gradual Al/Si coordination change plays an increasingly important role at higher pressure as topological mechanisms of compression are diminished.
Women's Organizing and the Conflict in Iraq since 2003
Authors: Al-Ali Nadje , Pratt Nicola
Published: April 2008

This article examines the development of a women's movement in Iraq since the invasion in 2003. It describes the types of activities and the strategies of different women activists, as well as highlighting the main divisions among them. The article also discusses the various ways in which the ongoing occupation and escalating violence in Iraq has shaped women's activism and the object of their struggles. Communal and sectarian tensions had been fostered by the previous regime as well as by the political opposition in exile prior to 2003, but the systematic destruction of national institutions, such as the army and the police, by the occupation forces, has led to a flare-up of the sectarian conflict. The article concludes by evaluating women's activism in terms of its contributions to conflict on the one hand and national reconciliation on the other.
Quantum dynamics study of the K+HF(v=–2,j=)→KF+H reaction and comparison with quasiclassical trajectory results
Authors: Mayneris Jordi , Martínez Rodrigo , Hernando Jordi , Gray Stephen K. , González Miguel
Published: April 2008

Extensive quantum real wave packet calculations within the helicity decoupling approximation are used to analyze the influence of the HF vibrational excitation on the K+HF(v=0–2,j=0)→KF+H reaction. Quantum reaction probabilities P and reaction cross sections σ are compared with corresponding quasiclassical trajectory (QCT) results. Disregarding threshold regions for v=0 and 1 (v=2 has no threshold), both approaches lead to remarkably similar results, particularly for σ, validating the use of the QCT method for this system. When moving from v=0 to v=1 there is a large increase in P and σ, as expected for a late barrier system. For v=2 the reaction becomes exoergic and P≈0.95 (with the exception of large total angular momenta where centrifugal barriers play a role). While substantial vibrational enhancement of the reactivity is thus seen, it is still quite less than that inferred from experimental data in the intermediate and high collision energy ranges. The origin of this discrepancy is unclear.
Effects of crystalline morphology on the tensile properties of electrospun polymer nanofibers
Authors: Lim C. T. , Tan E. P. S. , Ng S. Y.
Published: April 2008

Crystalline morphology of electrospun polymeric nanofibers strongly influences the mechanical properties. In this study, electrospun polycaprolactone nanofibers with smaller diameters that are produced from dilute polymer solutions have a higher degree of molecular orientation, crystallinity, stiffness, and strength, but lower ductility. Nanofiber diameter and the resulting crystalline morphology is influenced by whether complete crystallization of polymer chains took place before or after the electrospinning jet has reached the collector. The former would result in the formation of smaller fibers with fibrillar structure and aligned lamellae, whereas, the latter would result in the formation of a misaligned lamellar structure.
The electron affinity of gallium nitride (GaN) and digallium nitride (GaNGa): The importance of the basis set superposition error in strongly bound systems
Authors: Tzeli Demeter , Tsekouras Athanassios A.
Published: April 2008

The electron affinity of GaN and Ga2N as well as the geometries and the dissociation energies of the ground states of gallium nitrides GaN, GaN−, Ga2N, and Ga2N− were systematically studied by employing the coupled cluster method, RCCSD(T), in conjunction with a series of basis sets, (aug-)cc-pVxZ(-PP), x=D, T, Q, and 5 and cc-pwCVxZ(-PP), x=D, T, and Q. The calculated dissociation energy and the electron affinity of GaN are 2.12 and 1.84eV, respectively, and those of Ga2N are 6.31 and 2.53eV. The last value is in excellent agreement with a recent experimental value for the electron affinity of Ga2N of 2.506±0.008eV. For such quality in the results to be achieved, the Ga 3d electrons had to be included in the correlation space. Moreover, when a basis set is used, which has not been developed for the number of the electrons which are correlated in a calculation, the quantities calculated need to be corrected for the basis set superposition error.
Multilayer magnetic antidot arrays from block copolymer templates
Authors: Chuang V. P. , Jung W. , Ross C. A. , Cheng J. Y. , Park Oun-Ho , Kim Ho-Cheol
Published: April 2008

Antidot arrays (films with periodic arrays of holes) with periodicity of 26 or 40nm have been prepared from Co and Co∕Cu∕NiFe films using a block copolymer templating method. The magnetic properties of the antidot arrays differ from those of continuous films. The holes raise the coercivity of single-layer Co films and in the multilayers lead to an antiparallel alignment of the moments in the Co and NiFe layers at remanence, as a result of the strong magnetostatic interactions between the layers. These results are confirmed by micromagnetic modeling and the trend in coercivity is explained in terms of the interactions between the nanoscale holes and the domain walls in the films.
Use of the cage formation probability for obtaining approximate phase diagrams
Authors: Kraemer Atahualpa S. , Naumis Gerardo G.
Published: April 2008

In this work, we introduce the idea of cage formation probability, defined by considering the angular space needed by a particle in order to leave a cage given an average distance to its neighbors. Considering extreme fluctuations, two phases appear as a function of the number of neighbors and their distances to a central one: Solid and fluid. This allows us to construct an approximated phase diagram based on a geometrical approach. As an example, we apply this probability concept to hard disks in two dimensions and hard spheres in three dimensions. The results are compared with numerical simulations using a Monte Carlo method.
Self-adaptive enhanced sampling in the energy and trajectory spaces: Accelerated thermodynamics and kinetic calculations
Authors: Gao Yi Qin
Published: April 2008

Here, we introduce a simple self-adaptive computational method to enhance the sampling in energy, configuration, and trajectory spaces. The method makes use of two strategies. It first uses a non-Boltzmann distribution method to enhance the sampling in the phase space, in particular, in the configuration space. The application of this method leads to a broad energy distribution in a large energy range and a quickly converged sampling of molecular configurations. In the second stage of simulations, the configuration space of the system is divided into a number of small regions according to preselected collective coordinates. An enhanced sampling of reactive transition paths is then performed in a self-adaptive fashion to accelerate kinetics calculations.
Optical constants of evaporated gold films measured by surface plasmon resonance at telecommunication wavelengths
Authors: Lee Wook-Jae , Kim Jae-Eun , Park Hae Yong , Park Suntak , Kim Min-su , Kim Jin Tae , Ju Jung Jin
Published: April 2008

We report the first measurement of the optical constants of evaporated gold films by using the surface plasmon resonance curve fitting method with an attenuated total reflection device from 16 to 70 nm thickness at telecommunication wavelengths. The results that were obtained by surface plasmon resonance measurement are in good agreement with those obtained by ellipsometry. Until now, optical constants of thin metal films are known to change according to the thickness due to the variation of the electrical resistivity. This phenomenon is also verified in this study by a simple surface plasmon resonance measurement. It is observed that for the gold films of thicknesses of less than 20 nm, the real part of the refractive index increases and the imaginary part decreases with decreasing film thickness.
A z-component magnetoresistive sensor
Authors: da Silva F. C. S. , Halloran S. T. , Yuan L. , Pappas D. P.
Published: April 2008

A thin-film sensor bridge that measures the component of the magnetic field perpendicular to the plane of the substrate (also called the z-component field) is described. The sensor is fabricated on anisotropically etched, V-shaped groves on Si(100) substrates. The anisotropic magnetoresistive effect was used to measure the z component of the magnetic field with a 40dB rejection of other components. The device can be integrated with standard in-plane x- and y-component sensors to form a system with a footprint of 100×100μm2 and a noise floor of 20nT at 1Hz.
Pulsating electrospray modes at the liquid-liquid interface
Authors: Alexander Matthew S.
Published: April 2008

Unforced liquid-liquid electrosprays have been demonstrated for water/heptane and ethylene glycol/heptane couples which exhibit stable high frequency current oscillations in the kilohertz range. Using in-line flow sensor measurements, the controlled ejection of subpicoliter volumes into an immiscible liquid phase was shown possible.
DNA looping can enhance lysogenic CI transcription in phage lambda
Authors: Anderson L. Meadow , Yang Haw
Published: April 2008

The lysogenic state of bacteriophage lambda is maintained by CI repressor, which negatively regulates two promoters to block lytic gene expression. Expression of CI is itself controlled by positive and negative feedback as CI binds to
O
R
to regulate the
P
RM
promoter. In addition to direct interactions with operator DNA, CI tetramers bound at
O
L
and
O
R
can come together to form an octamer, looping the DNA that lies between them and allowing
O
L
to assist with negative regulation of
P
RM
. We used a fluorescent reporter protein to measure the CI concentration for a set of constructs that differ in their ability to assume various forms of the looped structure. Based on the observed steady-state fluorescence for these constructs, the presence of
O
L
increases
P
RM
activation unless both operators can be fully occupied. By calculating the probabilities for the underlying operator configurations present in each construct, two different models for the mechanism of enhanced activation allow us to predict that when the DNA is looped,
P
RM
activation can be 2- to 4-fold higher than is possible for unlooped DNA. Based on our results, transcriptional regulation for lambda's lysogenic/lytic switch includes both activation and repression due to DNA looping.
Rare steroid receptor-negative basal-like tumorigenic cells in luminal subtype human breast cancer xenografts
Authors: Horwitz Kathryn B. , Dye Wendy W. , Harrell Joshua Chuck , Kabos Peter , Sartorius Carol A.
Published: April 2008

There are two major subtypes of human breast cancers: the luminal, estrogen, and progesterone receptor-positive, cytokeratin 18-positive (ER
+
PR
+
CK18
+
) subtype, and the basal ER
−
PR
−
CK18
−
CK5
+
subtype. Tumor-initiating cells (CD44
+
) have been described for human breast cancers; whether these are common to the two subtypes is unknown. We have identified a rare population of cells that are both CD44
+
and ER
−
PR
−
CK5
+
in luminal-like ER
+
PR
+
T47D human breast tumor xenografts. The tumor-isolated CD44
+
cell fraction was highly enriched for clonogenic (
in vitro
culture) and tumorigenic (
in vivo
reimplantation) cells compared with the CD44
−
cell fraction. Rare ER
−
PR
−
CK5
+
cells were present within CD44
+
-derived colonies. Tumor-isolated cells placed in minimal media also contained rare ER
−
PR
−
CK5
+
cells at early time points (<10 cells); however, this population did not expand with increasing colony size. The number of ER
+
PR
+
CK5
−
cells, conversely, increased linearly with colony growth. Similary, tumors originating
in vivo
from CD44
+
cells contained a rare static ER
−
PR
−
CK5
+
population, an intermediate ER
−
PR
−
CK5
−
population, and an expanding ER
+
PR
+
CK5
−
population. Putative ER
+
PR
+
CK5
+
transitional cells could be seen only in colonies or tumors treated with a progestin. We propose that luminal ER
+
PR
+
breast tumors contain a minor ER
−
PR
−
CK5
+
population that has the capacity to generate the majority of ER
+
PR
+
CK18
+
CK5
−
cells. Luminal breast cancers are treated with endocrine therapies that target ER. The rare ER
−
PR
−
CK5
+
progenitor cells would escape such treatments and survive to repopulate the tumor.
Tlx3 exerts context-dependent transcriptional regulation and promotes neuronal differentiation from embryonic stem cells
Authors: Kondo Takako , Sheets Patrick L. , Zopf David A. , Aloor Heather L. , Cummins Theodore R. , Chan Rebecca J. , Hashino Eri
Published: April 2008

The T cell leukemia 3 (
Tlx3
) gene has been implicated in specification of glutamatergic sensory neurons in the spinal cord. In cranial sensory ganglia,
Tlx3
is highly expressed in differentiating neurons during early embryogenesis. To study a role of
Tlx3
during neural differentiation, mouse embryonic stem (ES) cells were transfected with a
Tlx3
expression vector. ES cells stably expressing
Tlx3
were grown in the presence or absence of a neural induction medium. In undifferentiated ES cells, there was no significant difference in gene expression in the presence or absence of
Tlx3
, even after ES cells were cultured for an extensive time period. In contrast, expression levels of
Mash1
,
Ngn1
, and
NeuroD
were significantly higher in
Tlx3
-expressing cells after neural induction for 4 days compared with those in cells expressing the control vector. At 7 days after neural induction, whereas expression of the proneural genes was down-regulated,
VGLUT2
,
GluR2
, and
GluR4
were significantly increased in ES cell-derived neurons expressing
Tlx3
. The sequential and coordinated expression of the proneural and neuronal subtype-specific genes identifies
Tlx3
as a selector gene in ES cells undergoing neural differentiation. In addition, the differential effects of
Tlx3
overexpression in undifferentiated ES cells compared with ES cell-derived neurons suggest that
Tlx3
exerts context-dependent transcriptional signals on its downstream target genes. The context-dependent function of
Tlx3
as a selector gene may be used to establish a novel strategy to conditionally generate excitatory glutamatergic neurons from ES cells to cure various types of neurodegenerative disorders.
Identification of a potent synthetic FXR agonist with an unexpected mode of binding and activation
Authors: Soisson Stephen M. , Parthasarathy Gopalakrishnan , Adams Alan D. , Sahoo Soumya , Sitlani Ayesha , Sparrow Carl , Cui Jisong , Becker Joseph W.
Published: April 2008

The farnesoid X receptor (FXR), a member of the nuclear hormone receptor family, plays important roles in the regulation of bile acid and cholesterol homeostasis, glucose metabolism, and insulin sensitivity. There is intense interest in understanding the mechanisms of FXR regulation and in developing pharmaceutically suitable synthetic FXR ligands that might be used to treat metabolic syndrome. We report here the identification of a potent FXR agonist (MFA-1) and the elucidation of the structure of this ligand in ternary complex with the human receptor and a coactivator peptide fragment using x-ray crystallography at 1.9-Å resolution. The steroid ring system of MFA-1 binds with its D ring-facing helix 12 (AF-2) in a manner reminiscent of hormone binding to classical steroid hormone receptors and the reverse of the pose adopted by naturally occurring bile acids when bound to FXR. This binding mode appears to be driven by the presence of a carboxylate on MFA-1 that is situated to make a salt-bridge interaction with an arginine residue in the FXR-binding pocket that is normally used to neutralize bound bile acids. Receptor activation by MFA-1 differs from that by bile acids in that it relies on direct interactions between the ligand and residues in helices 11 and 12 and only indirectly involves a protonated histidine that is part of the activation trigger. The structure of the FXR:MFA-1 complex differs significantly from that of the complex with a structurally distinct agonist, fexaramine, highlighting the inherent plasticity of the receptor.
An insulin-like peptide regulates egg maturation and metabolism in the mosquito
Aedes aegypti
Authors: Brown Mark R. , Clark Kevin D. , Gulia Monika , Zhao Zhangwu , Garczynski Stephen F. , Crim Joe W. , Suderman Richard J. , Strand Michael R.
Published: April 2008

Ingestion of vertebrate blood is essential for egg maturation and transmission of disease-causing parasites by female mosquitoes. Prior studies with the yellow fever mosquito,
Aedes aegypti
, indicated blood feeding stimulates egg production by triggering the release of hormones from medial neurosecretory cells in the mosquito brain. The ability of bovine insulin to stimulate a similar response further suggested this trigger is an endogenous insulin-like peptide (ILP).
A. aegypti
encodes eight predicted ILPs. Here, we report that synthetic ILP3 dose-dependently stimulated yolk uptake by oocytes and ecdysteroid production by the ovaries at lower concentrations than bovine insulin. ILP3 also exhibited metabolic activity by elevating carbohydrate and lipid storage. Binding studies using ovary membranes indicated that ILP3 had an IC
50
value of 5.9 nM that was poorly competed by bovine insulin. Autoradiography and immunoblotting studies suggested that ILP3 binds the mosquito insulin receptor (MIR), whereas loss-of-function experiments showed that ILP3 activity requires MIR expression. Overall, our results identify ILP3 as a critical regulator of egg production by
A. aegypti
.
MicroRNA-repressed mRNAs contain 40S but not 60S components
Authors: Wang Bingbing , Yanez Adrienne , Novina Carl D.
Published: April 2008

MicroRNAs (miRNAs) are small noncoding RNAs that may target more than one-third of human genes, yet the mechanisms used by miRNAs to repress translation of target mRNAs are obscure. Using a recently described cell-free assay of miRNA function, we observe that miRNA-targeted mRNAs are enriched for 40S but not 60S ribosome components. Additionally, toeprinting analysis of miRNA-targeted mRNAs demonstrates that ≈18 nt 3′ relative to the initiating AUG are protected, consistent with 40S ribosome subunits positioned at the AUG codon. Our results suggest that miRNAs repress translation initiation by preventing 60S subunit joining to miRNA-targeted mRNAs.
MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins
Authors: Sengupta Srikumar , den Boon Johan A. , Chen I-How , Newton Michael A. , Stanhope Stephen A. , Cheng Yu-Juen , Chen Chien-Jen , Hildesheim Allan , Sugden Bill , Ahlquist Paul
Published: April 2008

Using highly sensitive microarray-based procedures, we identified eight microRNAs (miRNAs) showing robust differential expression between 31 laser-capture-microdissected nasopharyngeal carcinomas (NPCs) and 10 normal healthy nasopharyngeal epithelial samples. In particular, miRNA
mir-29c
was expressed at one-fifth the levels in tumors as in normal epithelium. In NPC tumors, the lower
mir-29c
levels correlated with higher levels of multiple mRNAs whose 3′ UTRs can bind
mir-29c
at target sequences conserved across many vertebrates. In cultured cells, introduction of
mir-29c
down-regulated these genes at the level of mRNA and inhibited expression of luciferase encoded by vectors having the 3′ UTRs of these genes. Moreover, for each of several genes tested, mutating the
mir-29c
target sites in the 3′ UTR abrogated
mir-29c
-induced inhibition of luciferase expression. Most of the
mir-29c
-targeted genes identified encode extracellular matrix proteins, including multiple collagens and laminin γ1, that are associated with tumor cell invasiveness and metastatic potential, prominent characteristics of NPC. Thus, we identify eight miRNAs differentially expressed in NPC and demonstrate the involvement of one in regulating genes involved in metastasis.
Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category
Authors: Luger Dror , Silver Phyllis B. , Tang Jun , Cua Daniel , Chen Zoe , Iwakura Yoichiro , Bowman Edward P. , Sgambellone Nicole M. , Chan Chi-Chao , Caspi Rachel R.
Published: April 2008

Experimental autoimmune uveitis (EAU) represents autoimmune uveitis in humans. We examined the role of the interleukin (IL)-23–IL-17 and IL-12–T helper cell (Th)1 pathways in the pathogenesis of EAU. IL–23 but not IL-12 was necessary to elicit disease by immunization with the retinal antigen (Ag) interphotoreceptor retinoid-binding protein (IRBP) in complete Freund's adjuvant. IL-17 played a dominant role in this model; its neutralization prevented or reversed disease, and Th17 effector cells induced EAU in the absence of interferon (IFN)-γ. In a transfer model, however, a polarized Th1 line could induce severe EAU independently of host IL-17. Furthermore, induction of EAU with IRBP-pulsed mature dendritic cells required generation of an IFN-γ–producing effector response, and an IL-17 response by itself was insufficient to elicit pathology. Finally, genetic deficiency of IL-17 did not abrogate EAU susceptibility. Thus, autoimmune pathology can develop in the context of either a Th17 or a Th1 effector response depending on the model. The data suggest that the dominant effector phenotype may be determined at least in part by conditions present during initial exposure to Ag, including the quality/quantity of Toll-like receptor stimulation and/or type of Ag-presenting cells. These data also raise the possibility that the nonredundant requirement for IL-23 in EAU may extend beyond its role in promoting the Th17 effector response and help provide a balance in the current Th1 versus Th17 paradigm.
Approximate solutions to the neutrino oscillation problem in matter
Authors: Aquino Veríssimo M de , Oliveira J S S de
Published: April 2008

In this paper, we present approximate solutions to the neutrino evolution equation, calculated by different methods. In a two-neutrino framework, we compute the transition probability by using numerical methods, series solutions, and by taking the neutrino evolution operator as a product of ordered partial operators. This procedure is applied to linearly and sinusoidally varying matter densities just as illustrative examples, using the physical parameters, which produce the main effects on neutrino oscillations from νeto other flavors forL≃3000 Km andE≃1 GeV. The evolution operator as a product of partial operators in the three-neutrino case is obtained. We compare the results and discuss the extension to an arbitrary density profile.
Caveat Emptor: Abolishing Public Measurements, Standardizing Quantities, and Enhancing Market Transparency in the London Coal Trade c1830
Authors: Velkar Aashish
Published: April 2008

This article evaluates efforts to standardize quantities in the London coal trade c1830, and traces the end of the public measurement system first introduced in the fourteenth century. Increasing traffic in coal, reduction of taxes on the commodity, inefficient public meters, etc., contributed to the demise of public measurements. This outcome was the result of extensive negotiations between merchants, the various levels of state bureaucracy, and the parliament. Switching measurement standards was difficult, if not costly, to coordinate. Abolishing public measurements and switching from volume to weight measurements was part of the efforts to strengthen governance along the commodity chain, secure property rights by making quantities predictable and alter a mechanism that powerful merchants considered had become inappropriate.
Strategies and Boundaries: Subcontracting and the London Trades in the Long Eighteenth Century
Authors: Riello Giorgio
Published: April 2008

In the eighteenth century subcontracting was an important way of organising production in sectors producing as different commodities as clocks, coaches, footwear, furniture and scientific instruments. This article argues that subcontracting was not simply a form of cost reduction in labour-intensive and technologically unsophisticated sectors. Subcontracting could be seen as a way to respond to profound changes in the way commodities were produced, exchanged and consumed in an eighteenth-century metropolis like London. The expansion in size and complexity of the metropolitan market, the appearance of new commodities classified as semi-luxuries and fashion items, and the consequent re-assessment of traditional social structures and norms of production, made subcontracting a tool of organisational flexibility.
Delphinid spatial distribution and abundance estimates over the shelf of the Bay of Biscay
Authors: Certain G. , Ridoux V. , van Canneyt O. , Bretagnolle V.
Published: April 2008

Certain, G., Ridoux, V., van Canneyt, O., and Bretagnolle, V. 2008. Delphinid spatial distribution and abundance estimates over the shelf of the Bay of Biscay. – ICES Journal of Marine Science, 65: 656–666. The small delphinid community (bottlenose Tursiops truncatus, common Delphinus delphis, and striped Stenella coeruleoalba dolphins) of the Bay of Biscay (100 000 km2 of continental shelf along the French Atlantic coast) has been studied here by combining strip-transect aerial surveys conducted between 2001 and 2004 and ship-based surveys conducted between 2003 and 2006. Distribution was modelled spatially in relation to several large-scale descriptors of the environment. Highest densities of small delphinids were associated with the shelf break, in particular in two hotspots located in the north and the south of the bay. Using ship-based data, we found strong spatial segregation between common and bottlenose dolphins in spring, with common dolphins associated with coastal areas (and especially river plumes) and bottlenose dolphins on the outer shelf and the shelf break. Assuming a detection probability of 1, a strip-transect abundance estimate for the small delphinid community was obtained in August 2002 with 56 500 (95% CI 29 100–90 400), but relative abundance varied across months.
What do pelagic freezer-trawlers discard?
Authors: Borges Lisa , van Keeken Olvin A. , van Helmond Aloysius T. M. , Couperus Bram , Dickey-Collas Mark
Published: April 2008

Borges, L., van Keeken, O. A., van Helmond, A. T. M., Couperus, B., and Dickey-Collas, M. 2008. What do pelagic freezer-trawlers discard? – ICES Journal of Marine Science, 65: 605–611. Estimates of discards by the Dutch pelagic freezer-trawler fleet were derived based on data from observers on board commercial vessels. In all, 27 fishing trips of duration 2–5 weeks each were sampled between 2002 and 2005, covering the North Sea and the western waters of the British Isles. Different methods to estimate discards were compared, and raising these estimates by number of trips or by total landings did not greatly influence the annual estimates of total discards. Some 30 000 t of fish were discarded annually by the fleet, the commercial target species mackerel, herring, and horse mackerel being discarded most, with 41%, 19%, and 15% of the total discards by weight, respectively. The most commonly discarded non-commercial species was boarfish, accounting for 5% of total discards. Slippage accounts for 10% of all discards, and the most common species slipped is herring. There is extensive discarding of juvenile mackerel in the horse mackerel fishery, and to a lesser extent highgrading of mackerel in the same fishery.
David Tabor. 23 October 1913 — 26 November 2005
Authors: Field John
Published: April 2008

David Tabor died in Cambridge on 26 November 2005. At the time of his death he was Emeritus Professor of Physics and an EmeritusFellow of Gonville and Caius College, Cambridge. He was a humane and gentle man, yet despite his modesty he was a formidable and respectedscientist. With Philip Bowden (FRS 1948), he laid the foundation for understanding friction and lubrication and the way in which contactingsurfaces interact. Both Bowden and Tabor had great physical insight and were empiricists who favoured the most direct and simple approach toproblems. They built up a research group that was interdisciplinary and motivated to basic research but with a flair to see the practical advantages of their research to industry. As individuals they would both have achieved much, but the way in which they integrated produced anexceptional ‘team’. There are many examples of the benefits of their collaboration. Their research started in Cambridge; during theWorld War II period they ran a laboratory in Melbourne, Australia, with both returning to Cambridge after the war. Initially, they were part ofthe Chemistry Department but left Physical Chemistry to become part of the Department of Physics in 1957, when Nevill Mott FRS was Head of Department. After Bowden's death in 1968, Tabor became Head of the Physics and Chemistry of Solids (PCS) Group as it was called, and remained Head until he retired in 1981. Tabor continued as an Emeritus Professor and researcher. In 1992, a new group (Polymers and Colloids) was founded and worked in the ‘Tabor Laboratory’. A visiting Professorship at Imperial College, London, continued and papers were produced up to 1998. He was, indeed, a scientist of great originality and versatility.
Frank Stuart Spring. 5 September 1907 — 2 March 1997
Authors: Mitchell Vivien , Spring John
Published: April 2008

Frank Spring was an organic chemist who made important contributions to our knowledge of the naturally occurring sterols, triterpenes and heterocyclic compounds. He investigated the structure of a large number of complex molecules, and proved his conclusions by synthesis. In the 1950s he was one of many researchers who contributed to the long series of transformations required for the synthesis of cortisone, his contribution being the evolution of mechanisms for the introduction of an oxygen atom at the 11–position of the steroid nucleus,and the development of routes for the synthesis of cortisone from ergosterol as a more convenient starting point than the bile acids previously used.
Large-scale analysis of gene clustering in bacteria
Authors: Yang Qingwu , Sze Sing-Hoi
Published: April 2008

An important strategy to study operons and their evolution is to investigate clustering of related genes across multiple bacterial genomes. Although existing algorithms are available that can identify gene clusters across two or more genomes, very few algorithms are efficient enough to study gene clusters across hundreds of genomes. We observe that a querying strategy can be used to analyze gene clusters across a large number of genomes and develop an efficient algorithm to identify all related clusters on a genome from a given query cluster. We use this algorithm to study gene clustering in 400 bacterial genomes by starting from a well-characterized list of operons in Escherichia coli K12 and perform comparative analysis of operon occurrences, gene orientations, and rearrangements both within and across clusters. We show that important biological insights can be obtained by comparing results across these categories. A software program implementing the algorithm (GCQuery) and supplementary data containing detailed results are available at http://faculty.cs.tamu.edu/shsze/gcquery.
AtOSA1, a Member of the Abc1-Like Family, as a New Factor in Cadmium and Oxidative Stress Response
Authors: Jasinski Michal , Sudre Damien , Schansker Gert , Schellenberg Maya , Constant Signarbieux , Martinoia Enrico , Bovet Lucien
Published: April 2008

The analysis of gene expression in Arabidopsis (Arabidopsis thaliana) using cDNA microarrays and reverse transcription-polymerase chain reaction showed that AtOSA1 (A. thaliana oxidative stress-related Abc1-like protein) transcript levels are influenced by Cd2+ treatment. The comparison of protein sequences revealed that AtOSA1 belongs to the family of Abc1 proteins. Up to now, Abc1-like proteins have been identified in prokaryotes and in the mitochondria of eukaryotes. AtOSA1 is the first member of this family to be localized in the chloroplasts. However, despite sharing homology to the mitochondrial ABC1 of Saccharomyces cerevisiae, AtOSA1 was not able to complement yeast strains deleted in the endogenous ABC1 gene, thereby suggesting different function between AtOSA1 and the yeast ABC1. The atosa1-1 and atosa1-2 T-DNA insertion mutants were more affected than wild-type plants by Cd2+ and revealed an increased sensitivity toward oxidative stress (hydrogen peroxide) and high light. The mutants exhibited higher superoxide dismutase activities and differences in the expression of genes involved in the antioxidant pathway. In addition to the conserved Abc1 region in the AtOSA1 protein sequence, putative kinase domains were found. Protein kinase assays in gelo using myelin basic protein as a kinase substrate revealed that chloroplast envelope membrane fractions from the AtOSA1 mutant lacked a 70-kD phosphorylated protein compared to the wild type. Our data suggest that the chloroplast AtOSA1 protein is a new factor playing a role in the balance of oxidative stress.
LEUNIG_HOMOLOGandLEUNIGPerform Partially Redundant Functions during Arabidopsis Embryo and Floral Development
Authors: Sitaraman Jayashree , Bui Minh , Liu Zhongchi
Published: April 2008

Transcription corepressors play important roles in animal and plant development. In Arabidopsis (Arabidopsis thaliana), LEUNIG (LUG) and LEUNIG_HOMOLOG (LUH) encode two highly homologous proteins that are similar to the animal and fungal Gro/Tup1-type corepressors. LUG was previously shown to form a putative corepressor complex with another protein, SEUSS (SEU), and to repress the transcription of AGAMOUS in floral organ identity specification. However, the function of LUH is completely unknown. Here, we show that single luh loss-of-function mutants develop normal flowers, but lug; luh double mutants are embryo lethal, uncovering a previously unknown function of LUG and LUH in embryonic development. In addition, luh/+ enhances the floral phenotype of lug, revealing a minor role of LUH in flower development. Functional diversification between LUH and LUG is evidenced by the inability of 35S∷LUH overexpression to rescue lug mutants and by the opposite expression trends of LUG and LUH in response to biotic and abiotic stresses. The luh-1 mutation does not enhance the defect of seu in flower development, but LUH could directly interact with SEU in yeast. We propose a model that explains the complex relationships among LUH, LUG, and SEU. As most eukaryotes have undergone at least one round of whole-genome duplication during evolution, gene duplication and functional diversification are important issues to consider in uncovering gene function. Our study provides important insights into the complexity in the relationship between two highly homologous paralogous genes.