bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular taphonomy of arthropod and plant cuticles from the Carboniferous of North America: implications for the origin of kerogen
Authors: STANKIEWICZ B. A. , SCOTT A. C. , COLLINSON M. E. , FINCH P. , MÖSLE B. , BRIGGS D. E. G. , EVERSHED R. P.
Published: December 2007

Analyses of identifiable organic fossil remains of animals and plants have considerable potential to resolve conflicting models of organic matter diagenesis and kerogen formation (e.g. selective preservation versus random polymerization). Fossil cuticles of arthropods (scorpion, eurypterid) and plants (cordaite, pteridosperm) from Upper Carboniferous strata of Lone Star Lake, Kansas, USA and Joggins, Nova Scotia, Canada were analysed by pyrolysis–gas chromatography/mass spectrometry and examined by electron microscopy. Recent
Pandinus
(scorpion) and
Araucaria
(conifer) provided a basis for comparison. Pyrolysis of Recent dewaxed scorpion cuticle yielded products derived from chitin and proteins. These products were absent in the fossil arthropod cuticles, however, which yielded an homologous series of alkanes and alkenes, together with phenolic and other aromatic constituents. Recent dewaxed plant cuticle yielded fatty acids, phenols and carbohydrate-derived compounds indicative of cutin polyester and associated lignocellulose. The pyrolysates of the fossil plant cuticles, on the other hand, were dominated by alkane–alkene doublets, with minor phenolic and other benzenoid components. There is no evidence that the preservation of these cuticles as particulate organic matter in kerogen is simply a result of selective preservation. Nonetheless, the chemistry and morphology remain characteristic of a particular taxon, thereby eliminating the possibility of incorporation of randomly repolymerized materials or the transfer of material between plant and animal residues. The aliphatic moieties in the fossil cuticles are thought to be the result of polymerization of the associated epicuticular, cuticular and/or tissue lipids during diagenesis.
Volcanic plume monitoring using atmospheric electric potential gradients
Authors: JAMES M. R. , LANE S. J. , GILBERT J. S.
Published: December 2007

By monitoring perturbations of the natural atmospheric electric potential gradient, it is possible to detect and track particle laden volcanic plumes. The perturbations are produced by electrical charge that resides on the solid particles and liquid droplets of the plume, and the ions within it. A network of potential gradient monitoring stations around a volcano can provide data on eruption time, magnitude, plume dispersion direction and areas of ashfall. Our laboratory experiments have produced electrically charged ash by fragmenting pumice. These results support the theory that charging is due to the magma fragmentation process and should therefore be ubiquitous in all particulate volcanic plumes.
The structural setting and U–Pb geochronology of Knoydartian pegmatites in W Inverness-shire: evidence for Neoproterozoic tectonothermal events in the Moineof NW Scotland
Authors: ROGERS G. , HYSLOP E. K. , STRACHAN R. A. , PATERSON B. A. , HOLDSWORTH R. E.
Published: December 2007

U–Pb monazite data for the Ardnish and Sgurr Breac pegmatites in the SW Moine block give Knoydartian ages of 827±2 and 784±1 Ma respectively. Structural and metamorphic studies of the pegmatites and the local Moinian metasediments suggest that pegmatite generation was a consequence of localized high-temperature shearing and metamorphism within the pelitic horizons. Petrographic evidence from the sheared pelites is interpreted as indicating that the local garnet-grade metamorphism was contemporaneous with the shearing and pegmatite generation, and was, therefore, Knoydartian in age. Chemical zoning profiles in garnets are consistent with their growth during prograde regional metamor-phic increases in
P
and
T
. The
c.
45 Ma difference between the pegmatite ages implies that the Knoydartian tectonothermal event was diachronous, being either a prolonged or episodic event. The metamorphic and geochronological data are consistent with the presence of Neoproterozoic orogenic events in the SW Moine.
Processes of Late Cretaceous to Late Miocene episodic thrust-sheet translation in the Lycian Taurides, SW Turkey
Authors: COLLINS ALAN S. , ROBERTSON ALASTAIR H. F.
Published: December 2007

The Lycian Taurides of SW Turkey consist of an allochthonous Mesozoic passive margin succession that was episodically detached from its autochthon and translated southeastwards between latest Cretaceous to Late Miocene times. A combination of structural analysis, sedimentology, palaeontology and geochemistry allows subdivision of this orogenic event into: (1) latest Cretaceous trench–passive margin collision causing ophiolite obduction and detachment of the Köyceđiz Thrust Sheet; (2) Mid–Late Eocene continent–continent collision renewing southeastwards thrusting and causing detachment of the Teke Dere Thrust Sheet and Yavus Thrust Sheets; (3) Miocene extensional collapse of the orogen with southeastwards translation of the allochthon coeval with rift-basin formation in the hinterland.
Geochemical constraints on kaolinization in the St Austell Granite, Cornwall, England
Authors: PSYRILLOS AGAMEMNON , MANNING DAVID A. C. , BURLEY STUART D.
Published: December 2007

The St Austell Granite contains important kaolin deposits, the formation of which is chronologically the last identifiable mineralization episode in the pluton. Field evidence demonstrates that kaolinization is spatially associated with hydrothermal quartz veins and progressed through the migration of alteration fronts away from reactivated pre-existing hydrothermal vein structures. Kaolin veins, sometimes with a quartz core, also occur. Kaolinization results in the formation of a kaolin+smectite assemblage, with no precipitation of quartz. Geochemical models of kaolinization at 25–100 °C show that appropriate mineral assemblages are produced from parent granite by reaction with meteoric water at these temperatures, and with high salinity brine at 75 and 100°C. The aolin+smectite mineral assemblage does not reflect conditions of equilibrium, but reflects elevation of fluid silica activities in excess of quartz saturation as a consequence of feldspar dissolution. Quartz fails to nucleate because of slow precipitation kinetics at the temperatures of kaolinization (<100
°
C). Kaolinization of the granites was a dynamic process, controlled by feldspar dissolution kinetics, the precipitation kinetics of silica minerals and the initial log a (K
+
/H
+
) of the fluids that interacted with the granites.
Transtensive synsedimentary tectonics associated with ocean opening: the Essaouira–Agadir segment of the Moroccan Atlantic margin
Authors: PIQUÉ A. , LE ROY P. , AMRHAR M.
Published: December 2007

The Mesozoic–Cenozoic sedimentary sequences of the Agadir–Essaouira region were studied by field observations in the onshore basin and offshore by seismic profiles and borehole data. During the Late Jurassic and the Early Cretaceous, they were frequently disturbed by repeated synsedimentary tectonic instability, extensively demonstrated by structures such as slumps, breccias, faults, etc. Regionally, these movements led to the initiation of ridges, in some cases diapiric, as well as depocentres. These are mainly N 70°E to E–W trending. Contemporaneously with a slight tectonic inversion of some of the offshore half grabens, the Late Jurassic–Cretaceous regional deformation converted the synsedimentary ridges to anticlines, and the depocentres to synclines, before the latest ‘Atlasic’ orogenic uplift, during the Cenozoic. This structural evolution distinguishes the Agadir–Essaouira segment from other parts of the Atlantic margin of Morocco. It results from an interference between the N20°E-oriented passive margin of Morocco and the N70°E-oriented Atlasic zone. The latter acted as a transform zone during Late Jurassic–Early Cretaceous times and then suffered a N–S compression during the Atlasic orogeny.
Origin, sedimentary processes and depositional evolution of the Agadir turbidite system, central eastern Atlantic
Authors: ERCILLA G. , ALONSO B. , PEREZ-BELZUZ F. , ESTRADA F. , BARAZA J. , FARRAN M. , CANALS M. , MASSON D.
Published: December 2007

The Oligocene to Recent Agadir turbidite system occurs in the Agadir Basin, abutting against the continental margin off South Morocco (central eastern Atlantic). This system is part of the submarine drainage system linking back to the Anti- and High Atlas mountains through the Agadir Canyon, and its sedimentary evolution is shown to comprise lateral shifts of canyon, channel, overbank and lobe deposits, governed by local topography (draped palaeorelief, seamounts, and a contourite ridge) and channel avulsions. In addition, the turbidite system shows an overall retrogradational stacking (migrating about 60 km upslope). This probably reflects a decrease in gradient on the continental margin, gradual basin filling, and/or a progressive decrease in energy and load of the sediment gravity flows that fed the system. The latter change in sediment flux could result from the interplay between the progressive denudation of the source areas, together with the climatic change which led to the present arid/desertic conditions in the hinterland. The seismic features observed with new ultra-high resolution seismic tools allow the recognition of the present-day sedimentary activity within the Agadir turbidite system, and this is related, among other factors, to the active seismicity of the area.
Genesis of the Middle Miocene stratabound sulphur deposits of northern Iraq
Authors: JASSIM S. Z. , RAISWELL R. , BOTTRELL S. H.
Published: December 2007

Stratabound sulphur deposits of northern Iraq occur in folded Middle Miocene evaporites overlying Lower Miocene hydrocarbon reservoirs. Rocks hosting sulphur mainly comprise gypsum, dolomitic marl, carbonate mudstones and bioclastic dolomitized limestones, whereas the mineralized rocks are mainly composed of calcite and sulphur. Sulphur was formed by the oxidation of H
2
S produced from gypsum dissolution followed by sulphate reduction in the presence of hydrocarbons. Sulphate reduction occurred in a partially closed to closed system as reflected by the sulphur δ
34
S values of +7‰ to +20‰ (original gypsum +21‰). Host rock carbonates were calcitized by the dissolved carbonate formed by oxidation of the hydrocarbons, which produced low δ
13
C values ( – 14 to – 32‰). Periodic invasion by meteoric water and elevated temperatures produced
18
O-depleted compositions for the newly-formed calcite (down to – 9‰) and dolomite (down to – 7‰), and oxidized the H
2
S produced during sulphate reduction.

These sulphur deposits formed through the favourable stratigraphic juxtaposition of gypsum sulphate, brines and hydrocarbons. Tectonically produced fracture permeability in carbonates allowed rising brines from the underlying hydrocarbon reservoirs to mix with laterally migrating and descending, sulphate-bearing meteoric waters and produced the oscillating redox conditions needed for the bacterial reduction of sulphate and the oxidation of sulphide.
Treatment of faults in production simulation models
Authors: Fisher Q. J. , Jolley S. J.
Published: December 2007

This paper describes basic ‘rules-of-thumb’ that offer an indication of common uncertainties and pitfalls, as well as the analytical methods, data requirements and work elements required to replicate the impact of faults on fluid flow in production simulation models successfully. The first, and most important, stage in this modelling process is to ensure that an accurate structural interpretation is incorporated into the simulation model. In particular, that all fault linkages and cross-fault juxtapositions are taken from the seismic interpretation into the simulation grid. Fault rocks sometimes reduce the rate of cross-fault flow in which case it is important to account for this reduction in flow within simulation models. This is best achieved if databases of fault rock properties, measured from the field of interest or nearby similar reservoirs, are up-scaled to calculate fault transmissibility multipliers. It is sometimes necessary to consider not just the single-phase permeability but also the capillary pressure and relative permeability characteristics of the fault rocks present. Finally, all the relevant static and dynamic data must be appraised critically. However, the interpretation of such data is usually non-unique and misinterpretations can create errors in the production-related fault seal analysis. Where these basic guidelines are followed, it has been our experience that the project time required to achieve a history match of production data is dramatically reduced. In addition, as the history match is more geologically reasonable, the model is often more reliable for predicting the long-term behaviour of the reservoir. This gives confidence in the model's forecast to guide development planning and day-to-day field management decisions.
Definition of a fault permeability predictor from outcrop studies of a faulted turbidite sequence, Taranaki, New Zealand
Authors: Childs C. , Walsh J. J. , Manzocchi T. , Strand J. , Nicol A. , Tomasso M. , Schöpfer M. P. J. , Aplin A. C.
Published: December 2007

Post-depositional normal faults within the turbidite sequence of the Late Miocene Mount Messenger Formation of the Taranaki Basin, New Zealand are characterized by granulation and cataclasis of sands and by the smearing of clay beds. Clay smears maintain continuity for high ratios of fault throw to clay source bed thickness (
c
. 8), but are highly variable in thickness, and gaps occur at any point between the clay source bed cut-offs at higher ratios. Although cataclastic fault rock permeabilities may be appreciably lower (
c
. two orders of magnitude) than host rock sandstone permeabilities, the occurrence of continuous clay smears, combined with low clay permeabilities (10s to 100s nD) means that the primary control on fault rock permeability is clay smear continuity. A new permeability predictor, the Probabilistic Shale Smear Factor (PSSF), is developed which incorporates the main characteristics of clay smearing from the Taranaki Basin. The PSSF method calculates fault permeabilities from a simple model of multiple clay smears within fault zones, predicting a more heterogeneous and realistic fault rock structure than other approaches (e.g. Shale Gouge Ratio, SGR). Nevertheless, its averaging effects at higher ratios of fault throw to bed thickness provide a rationale for the application of other fault rock mixing models, e.g. SGR, at appropriate scales.
Mechanics of fault and expulsion rollover systems developed on passive margins detached on salt: insights from analogue modelling and optical strain monitoring
Authors: Krézsek C. , Adam J. , Grujic D.
Published: December 2007

Scaled analogue experiments with layered brittle and ductile materials have been used to simulate the development of listric growth-fault and expulsion rollover systems during gravitational spreading of a passive margin sedimentary wedge detached on salt. The experiments were performed with varying sedimentation patterns and rates to simulate different depositional scenarios. Deformation monitoring with 3D optical image correlation techniques was used to quantify the 3D surface evolution and strain history of model structures. Our results indicate that rollover structure kinematics is strongly coupled to sedimentation patterns and rates. Whereas differential loading governs the margin-scale state of stress and extensional spreading in the experiments, more localized feedback between the dynamic depositional systems, fault-controlled subsidence, and salt mobilization control the strain history of local fault structures. This is reflected in the characteristic succession of extensional structures that evolve from symmetrical grabens through early, mature and late (collapsed) basinward listric growth-fault and rollover systems into landward listric growth-fault and rollover systems. A lack of sedimentation enhances reactive diapir rise and passive diapirism, whereas low sedimentation rates favour development of long-lived basinward listric growth-fault or expulsion rollover systems. Conversely, high sedimentation rates lead to the development of landward listric growth-fault and rollover systems.
Uterine artery myosin phosphatase isoform switching and increased sensitivity to SNP in a rat l-NAME model of hypertension of pregnancy
Authors: Lu Yuan , Zhang Haiying , Gokina Natalia , Mandala Maurizio , Sato Osamu , Ikebe Mitsuo , Osol George , Fisher Steven A.
Published: December 2007

Dramatic and vascular bed-specific hemodynamic changes occur in pregnancy and hypertension of pregnancy (HtP). Because myosin phosphatase (MP) is the primary effector of smooth muscle relaxation and a key target of signaling pathways that regulate vascular tone, we hypothesized that MP expression would be altered in these conditions. The abundance of the targeting/regulatory subunit of MP (MYPT1) mRNA and protein was increased 1.7- to 2.0-fold specifically in the uterine arteries (UAs) of late-pregnant rats without isoform switching. In a model of HtP in which nitric oxide (NO) synthesis is blocked by the chronic administration of Nω-nitro-l-arginine methyl ester, MYPT1 was downregulated and switched to the splice variant isoform that codes for the COOH-terminal leucine zipper motif. This was associated with increased sensitivity of the main UA and its subbranches to the vasorelaxant effects of the NO donor drug sodium nitroprusside. This difference was abolished by pretreatment with the phosphatase inhibitor tautomycetin. The sensitivity of relaxation to the NO second messenger cGMP was also increased under calcium-clamp conditions in permeabilized UAs, indicating heightened activation of MP. The changes in MP expression in HtP were largely prevented by treatment with the antihypertensive medicine hydralazine. We propose that MYPT1 isoform switching is an adaptive response to reduce vascular resistance and maintain uterine blood flow in the setting of hypertension-triggered inward remodeling of the UAs in hypertension of pregnancy.
Passive leg movement enhances interstitial VEGF protein, endothelial cell proliferation, and eNOS mRNA content in human skeletal muscle
Authors: Hellsten Ylva , Rufener Nora , Nielsen Jens J. , Høier Birgitte , Krustrup Peter , Bangsbo Jens
Published: December 2007

The present study used passive limb movement as an experimental model to study the effect of increased blood flow and passive stretch, without enhanced metabolic demand, in young healthy male subjects. The model used was 90 min of passive movement of the leg leading to a 2.8-fold increase ( P < 0.05) in blood flow without a significant enhancement in oxygen uptake. Muscle interstitial fluid was sampled with microdialysis technique and analyzed for vascular endothelial growth factor (VEGF) protein and for the effect on endothelial cell proliferation. Biopsies obtained from the musculus vastus lateralis were analyzed for mRNA content of VEGF, endothelial nitric oxide synthase (eNOS), and matrix metalloproteinase-2 (MMP-2). The passive leg movement caused an increase ( P < 0.05) in interstitial VEGF protein concentration above rest (73 ± 21 vs. 344 ± 83 pg/ml). Addition of muscle dialysate to cultured endothelial cells revealed that dialysate obtained during leg movement induced a 3.2-fold higher proliferation rate ( P < 0.05) than dialysate obtained at rest. Passive movement also enhanced ( P < 0.05) the eNOS mRNA level fourfold above resting levels. VEGF mRNA and MMP-2 mRNA levels were unaffected. The results show that a session of passive leg movement, elevating blood flow and causing passive stretch, augments the interstitial concentrations of VEGF, the proliferative effect of interstitial fluid, and eNOS mRNA content in muscle tissue. We propose that enhanced blood flow and passive stretch are positive physiological stimulators of factors associated with capillary growth in human muscle.
Upregulation of cortical COX-2 in salt-sensitive hypertension: role of angiotensin II and reactive oxygen species
Authors: Jaimes Edgar A. , Zhou Ming-Sheng , Pearse Damien D. , Puzis Leopold , Raij Leopoldo
Published: December 2007

Salt-sensitive (SS) hypertension is a vascular diathesis characterized by reduced cardiovascular and renal nitric oxide bioavailability and local upregulation of ANG II. We have demonstrated that rats infused with ANG II manifest increased cortical cyclooxygenase (COX)-2 expression and activity via NADPH oxidase-derived reactive oxygen species (ROS). In the present studies we used Dahl salt-sensitive (DS) rats to test the hypothesis that hypertensive SS rats have increased cortical COX-2 upregulation, which is mediated by ANG II and ROS. DS rats were placed on either a normal-salt diet (0.5% NaCl) or a high-salt diet (4% NaCl) for 6 wk and treated with either the ANG II type 1 (AT1) receptor blocker candesartan (Can, 10 mg·kg−1·day−1) or the SOD mimetic tempol (1 mmol/l). Hypertensive SS rats had a twofold increase in the cortical expression of COX-2 as assessed by Western blot. These changes in COX-2 expression were accompanied by a 10-fold increase in COX-2 mRNA expression and a 2-fold increase in the urinary excretion of PGE2. Treatment with either the AT1receptor blocker Can or the SOD mimetic tempol did not reduce blood pressure but resulted in significant reductions in the cortical expression of COX-2 and the urinary excretion of PGE2. In conclusion, we have demonstrated that local activation of the renin-angiotensin system, via increased ROS generation, mediates COX-2 upregulation in hypertensive SS rats. These studies unveil novel mechanistic pathways that may play a role in the pathogenesis of hypertensive renal injury.
Shared Computational Mechanism for Tilt Compensation Accounts for Biased Verticality Percepts in Motion and Pattern Vision
Authors: De Vrijer M. , Medendorp W. P. , Van Gisbergen J.A.M.
Published: December 2007

To determine the direction of object motion in external space, the brain must combine retinal motion signals and information about the orientation of the eyes in space. We assessed the accuracy of this process in eight laterally tilted subjects who aligned the motion direction of a random-dot pattern (30% coherence, moving at 6°/s) with their perceived direction of gravity (motion vertical) in otherwise complete darkness. For comparison, we also tested the ability to align an adjustable visual line (12° diameter) to the direction of gravity (line vertical). For small head tilts (<40°), systematic errors in either task were almost negligible. In contrast, tilts >60° revealed a pattern of large systematic errors (often >30°) that was virtually identical in both tasks. Regression analysis confirmed that mean errors in the two tasks were closely related, with slopes close to 1.0 and correlations >0.89. Control experiments ruled out that motion settings were based on processing of individual single-dot paths. We conclude that the conversion of both motion direction and line orientation on the retina into a spatial frame of reference involves a shared computational strategy. Simulations with two spatial-orientation models suggest that the pattern of systematic errors may be the downside of an optimal strategy for dealing with imperfections in the tilt signal that is implemented before the reference-frame transformation.
D2-Like Dopamine Receptors Modulate SKCaChannel Function in Subthalamic Nucleus Neurons Through Inhibition of Cav2.2 Channels
Authors: Ramanathan Sankari , Tkatch Tatiana , Atherton Jeremy F. , Wilson Charles J. , Bevan Mark D.
Published: December 2007

The activity patterns of subthalamic nucleus (STN) neurons are intimately related to motor function/dysfunction and modulated directly by dopaminergic neurons that degenerate in Parkinson's disease (PD). To understand how dopamine and dopamine depletion influence the activity of the STN, the functions/signaling pathways/substrates of D2-like dopamine receptors were studied using patch-clamp recording. In rat brain slices, D2-like dopamine receptor activation depolarized STN neurons, increased the frequency/irregularity of their autonomous activity, and linearized/enhanced their firing in response to current injection. Activation of D2-like receptors in acutely isolated neurons reduced transient outward currents evoked by suprathreshold voltage steps. Modulation was inhibited by a D2-like receptor antagonist and occluded by voltage-dependent Ca2+(Cav) channel or small-conductance Ca2+-dependent K+(SKCa) channel blockers or Ca2+-free media. Because Cavchannels are targets of Gi/o-linked receptors, actions on step- and action potential waveform-evoked Cavchannel currents were studied. D2-like receptor activation reduced the conductance of Cav2.2 but not Cav1 channels. Modulation was mediated, in part, by direct binding of Gβγ subunits because it was attenuated by brief depolarization. D2and/or D3dopamine receptors may mediate modulation because a D4-selective agonist was ineffective and mRNA encoding D2and D3but not D4dopamine receptors was detectable. Brain slice recordings confirmed that SKCachannel-mediated action potential afterhyperpolarization was attenuated by D2-like dopamine receptor activation. Together, these data suggest that D2-like dopamine receptors potently modulate the negative feedback control of firing that is mediated by the functional coupling of Cav2.2 and SKCachannels in STN neurons.
Olfactory Representations byDrosophilaMushroom Body Neurons
Authors: Turner Glenn C. , Bazhenov Maxim , Laurent Gilles
Published: December 2007

Learning and memory has been studied extensively in Drosophila using behavioral, molecular, and genetic approaches. These studies have identified the mushroom body as essential for the formation and retrieval of olfactory memories. We investigated odor responses of the principal neurons of the mushroom body, the Kenyon cells (KCs), in Drosophila using whole cell recordings in vivo. KC responses to odors were highly selective and, thus sparse, compared with those of their direct inputs, the antennal lobe projection neurons (PNs). We examined the mechanisms that might underlie this transformation and identified at least three contributing factors: excitatory synaptic potentials (from PNs) decay rapidly, curtailing temporal integration, PN convergence onto individual KCs is low (∼10 PNs per KC on average), and KC firing thresholds are high. Sparse activity is thought to be useful in structures involved in memory in part because sparseness tends to reduce representation overlaps. By comparing activity patterns evoked by the same odors across olfactory receptor neurons and across KCs, we show that representations of different odors do indeed become less correlated as they progress through the olfactory system.
A Novel Polymorphism in the Promoter Region ofERBB4Is Associated with Breast and Colorectal Cancer Risk
Authors: Rokavec Matjaž , Justenhoven Christina , Schroth Werner , Istrate Monica Adina , Haas Susanne , Fischer Hans-Peter , Vollmert Caren , Illig Thomas , Hamann Ute , Ko Yon-Dschun , Glavač Damjan , Brauch Hiltrud
Published: December 2007

Purpose: The receptor tyrosine kinase ERBB4/HER4 plays a role in cell division, migration, differentiation, as well as apoptosis, and is frequently overexpressed in breast and colorectal tumors. To understand the role of genetic variations in the regulation of ERBB4 expression, we identified new polymorphisms and investigated their functional implication and risk association with breast and colorectal cancer.

Experimental Design: We screened colorectal tumors from 92 patients for genetic variants at the ERBB4 ATG −1000 bp 5′-regulatory region by denaturing high-performance liquid chromatography and sequencing. Variants were subjected to DNA-protein interaction analyses (electrophoretic mobility shift assay), reporter gene assays in breast cancer cell lines MDA134 and MDA157, and immunohistochemical analyses of breast tumors. We established genotype frequencies within a breast cancer case-control collection (1,021 cases, 1,015 population-based controls) and a colorectal cancer case-control collection (459 cases, 569 blood donors) using matrix-assisted laser desorption ionization/time of flight mass spectrometry. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were assessed by multivariate logistic regression.

Results: We identified five new germ line variants −815 A>T, −782 G>T, −638 insTC, −267 C>G, and −219 del10bp. Two variants showed in vitro functional effects. The −782T allele showed lower protein binding affinity and lower promoter activity compared with the −782G allele, however, the −815T allele showed higher protein binding affinity and higher promoter activity. The −782T variant was identified as a risk allele for breast and colorectal cancer (OR, 1.59; 95% CI, 1.06-2.34 and OR, 2.21; 95% CI, 1.22-3.99, respectively).

Conclusion: The ERBB4 −782 G>T polymorphism, by virtue of its in vitro functional implication and incidence, is a risk factor for breast and colorectal cancer.
Input of DNA Microarrays to Identify Novel Mechanisms in Multiple Myeloma Biology and Therapeutic Applications
Authors: Mahtouk Karène , Hose Dirk , De Vos John , Moreaux Jérôme , Jourdan Michel , Rossi Jean François , Rème Thierry , Goldschmidt Harmut , Klein Bernard
Published: December 2007

Multiple myeloma is a B-cell neoplasia characterized by the proliferation of a clone of malignant plasma cells in the bone marrow. We review here the input of gene expression profiling of myeloma cells and of their tumor microenvironment to develop new tumor classifiers, to better understand the biology of myeloma cells, to identify some mechanisms of drug sensitivity and resistance, to identify new myeloma growth factors, and to depict the complex interactions between tumor cells and their microenvironment. We discuss how these findings may improve the clinical outcome of this still incurable disease.
The Challenge of Drugging Undruggable Targets in Cancer: Lessons Learned from Targeting BCL-2 Family Members
Authors: Verdine Gregory L. , Walensky Loren D.
Published: December 2007

The genomic and proteomic revolutions have provided us with an ever-increasing number of mechanistic insights into cancer pathogenesis. Mutated genes and pathologic protein products have emerged as the basis for modern anticancer drug development. With the increasing realization of the importance of disrupting oncogenic protein-protein interaction, new challenges have emerged for classical small molecule and protein-based drug modalities, i.e., the critical need to target flat and extended protein surfaces. Here, we highlight two distinct technologies that are being used to bridge the pharmacologic gap between small molecules and protein therapeutics. With the BCL-2 family of survival proteins as their substrate for intracellular targeting, we conclude that peptide stapling and fragment-based drug discovery show promise to traverse the critical surface features of proteins that drive human cancer.
Eupsychia Revisited: the Role of Spiritual Leaders
Authors: Rego Arménio , Pina E Cunha Miguel , Oliveira Miguel
Published: December 2007

This study builds on the workplace spirituality and spiritual leadership literatures to revisit the Maslowian notion of eupsychian management, showing that leaders' behavior has an impact on how people perceive the organization at the higher levels of self-actualization: the spiritual ones. A total of 105 employees reported 175 critical incidents, 120 antieupsychian events, and 55 eupsychian ones. The most frequent antieupsychian behaviors were power abuse and bossiness, ruthlessness or unkindness, disrespect for personal and inner life of employees, and laziness and cowardice. The more frequent reactions to those behaviors were expressing protest and/or disapproval against leader behavior, negative emotions and feelings, neglect and passivity, retaliation or disobedience, and performance decrease. The most cited eupsychian behaviors were the promotion of self-determination, employee personal development, and respect for the personal and inner life of employees. The most frequent reactions to these behaviors were higher levels of psychological well-being, higher commitment, and stronger sense of calling.
Partnership Governance and Democratic Effectiveness
Authors: Munro Hugh A.D. , Roberts Mark , Skelcher Chris
Published: December 2007

The design and evaluation of partnerships delivering public policy goals should consider questions of democratic performance as much as matters of service delivery. The flexibility afforded to partnership working places a premium on managerial action loosely coupled to political oversight. Yet the goals of partnerships are inherently political choices in which the public interest should be represented. This article examines the way in which community leaders and public managers impact on the democratic performance of partnerships. We conceptualize community leaders and public managers as `dual intermediaries' between the formal institutional design of partnership governance and its wider political constituency of citizens, service users and stakeholders. We build on three partnership design archetypes — club, agency and polity — identified in previous research, and theorize how these might be expected to shape the roles of community leaders and public managers. The article concludes by drawing out implications for the theory and practice of partnership working.
Anxiety, Methylphenidate Response, and Working Memory in Children With ADHD
Authors: Bedard Anne-Claude , Tannock Rosemary
Published: December 2007

Objective: To investigate the effects of methylphenidate (MPH) on components of working memory (WM) in children with ADHD and determine whether MPH produces differential effects on WM in children with comorbid anxiety (ANX). Method: Participants were a clinical sample of 130 children with ADHD, aged 6 to 12 years old (32% comorbid ANX). Each child participated in an acute randomized, double-blind, placebo-controlled, crossover trial with single challenges of three MPH doses. Four WM measures were used that varied in processing demands (storage versus manipulation of information) and modality (auditory—verbal; visual—spatial). Results: MPH improved auditory—verbal manipulation but only in the non-ANX children with ADHD. It had no effect on auditory—verbal storage of information. Also, MPH improved the ability to manipulate visual—spatial information in both ADHD groups, but beneficial effects on visual—spatial storage were evident only in children without comorbid ANX. Conclusions: Findings provide insight into potential mechanisms underlying individual differences in treatment response in ADHD, which may facilitate more targeted treatments. (J. of Att. Dis. 2008; 11(5) 546-557)
High corrosion resistance multilayer nickel coatings on AZ91D magnesium alloys
Authors: Song Y. W. , Shan D. Y. , Han E. H.
Published: December 2007

The multilayer coatings consisting of electroless Ni–P, Ni–P–ZrO2 and electroplating Ni coatings were investigated. The surface and cross-section morphologies of coatings were observed with SEM. The microstructures were analysed by XRD. The corrosion resistance was evaluated by potentiodynamic polarisation curves and salt spray tests. The results showed that the electroplating Ni coating was crystal structure, whereas the electroless Ni–P and Ni–P–ZrO2 coatings displayed amorphous characteristic. The electroplating Ni coating exhibited more positive corrosion potential Ecorr and lower corrosion current density Icorr than that of electroless Ni–P and Ni–P–ZrO2 coatings. The samples covered with multilayer coatings of Ni–P–ZrO2/Ni/Ni–P (from substrate to surface) indicated the best corrosion resistance among six samples, and the salt spray tests were carried out for more than 1000 h. According to the analysis of corrosion mechanism, the upper Ni–P layer served as sacrificial protection anode due to its more negative corrosion potential Ecorr in comparison with the middle electroplating Ni layer. When the upper Ni–P layer was consumed, the middle Ni layer went to prevent from corroding. Until the corrosion pits penetrated all of the protective coatings, the substrate of magnesium alloys was destroyed completely.
Pseudomonas aeruginosain the home environment of newly infected cystic fibrosis patients
Authors: Schelstraete P. , Van daele S. , De Boeck K. , Proesmans M. , Lebecque P. , Leclercq-Foucart J. , Malfroot A. , Vaneechoutte M. , De Baets F.
Published: December 2007

The source of acquisition ofPseudomonas aeruginosain cystic fibrosis (CF) patients remains unknown. Patient-to-patient transmission has been well documented but the role of the environment as a source of initial infection is as yet unclear.

In the present study, the origin of the firstP. aeruginosaisolate in CF patients was investigated by comparing theP. aeruginosagenotype(s) from newly infected patients with genotypes ofP. aeruginosaisolates from the home environment and from other patients from the same CF centre.

A total of 50 newly infected patients were studied.P. aeruginosacould be cultured from 5.9% of the environmental samples, corresponding to 18 patients. For nine of these, the genotype of the environmentalP. aeruginosaisolate was identical to the patient's isolate. In total, 72% of the environmentalP. aeruginosaisolates were encountered in the bathroom. Patient-to-patient transmission within the CF centre could not be ruled out for three patients.

In summary, a low prevalence ofPseudomonas aeruginosawas found in the home environment of the newly infected cystic fibrosis patients. The bathroom should be targeted in any preventive cleaning procedures. An environmental source of the new infection could not be ruled out in nine patients.
Proximal visceral endoderm and extraembryonic ectoderm regulate the formation of primordial germ cell precursors
Authors: de Sousa Lopes Susana M Chuva , Hayashi Katsuhiko , Surani M Azim
Published: December 2007

Background

The extraembryonic tissues, visceral endoderm (VE) and extraembryonic ectoderm (ExE) are known to be important for the induction of primordial germ cells (PGCs) in mice via activation of the bone morphogenetic protein (BMP) signalling pathway. We investigated whether the VE and ExE have a direct role in the specification of PGCs, or in an earlier event, namely the induction of the PGC precursors in the proximal posterior epiblast cells.

Results

We cultured embryonic day (E) 5.75 to E7.0 mouse embryos in an explant-assay with or without extraembryonic tissues. The reconstituted pieces of embryonic and extraembryonic tissues were assessed for the formation of both PGC precursors and specified PGCs. For this, Blimp1:gfp and Stella:gfp transgenic mouse lines were used to distinguish between PGC precursors and specified PGC, respectively. We observed that the VE regulates formation of an appropriate number of PGC precursors between E6.25–E7.25, but it is not essential for the subsequent specification of PGCs from the precursor cells. Furthermore, we show that the ExE has a different role from that of the VE, which is to restrict localization of PGC precursors to the posterior part of the embryo.

Conclusion

We show that the VE and ExE have distinct roles in the induction of PGC precursors, namely the formation of a normal number of PGC precursors, and their appropriate localization during early development. However, these tissues do not have a direct role during the final stages of specification of the founder population of PGCs.
A phase III trial comparing an anionic phospholipid-based cream and aloe vera-based gel in the prevention of radiation dermatitis in pediatric patients
Authors: Merchant Thomas E , Bosley Christina , Smith Julie , Baratti Pam , Pritchard David , Davis Tina , Li Chenghong , Xiong Xiaoping
Published: December 2007

Purpose

Radiation dermatitis is a common side effect of radiation therapy (RT). In severe cases, RT must be interrupted until the skin heals, which can compromise treatment. The purpose of the study was to compare an anionic polar phospholipid (APP)-based cream and an aloe vera-based gel to determine their effectiveness in preventing and treating radiation dermatitis.

Patients and methods

Forty-five pediatric patients (median age, 11 years) with various diagnoses who received at least 23.4 Gy participated. APP cream and aloe vera gel were symmetrically applied within the irradiated field after each treatment. Three measures were collected before, during and after completion of treatment: subject's skin comfort, dermatologic assessment, and common toxicity criteria (CTC).

Results

Significant differences in specific variables favoring APP cream use were noted in some patients including skin comfort variables, dry (p = 0.002), soft (p = 0.057), feels good (p = 0.002), rough (p = 0.065), smooth (p = 0.012) and dermatologic variables, dryness (p = 0.013), erythema (p = 0.002) and peely (p = 0.008). Grouped CTC scores were supportive of APP cream (p = 0.004). In comparing the first and last assessments, two dermatologic variables, dryness (p = 0.035) and peely (p = 0.016), favored APP cream.

Conclusion

APP cream is more effective than aloe vera-based gel for prevention and treatment of radiation dermatitis.
Cytoplasmic location of factor-inhibiting hypoxia-inducible factor is associated with an enhanced hypoxic response and a shorter survival in invasive breast cancer
Authors: Tan Ern Yu , Campo Leticia , Han Cheng , Turley Helen , Pezzella Francesco , Gatter Kevin C , Harris Adrian L , Fox Stephen B
Published: December 2007

Introduction

Hypoxia-inducible factor (HIF)-1α levels in invasive breast carcinoma have been shown to be an adverse prognostic indicator. Cellular HIF-1α activity is regulated by factor-inhibiting hypoxia-inducible factor 1 (FIH-1). In hypoxia, FIH-1 hydroxylation of Asn803 within the C-terminal transactivation domain does not occur and HIF-1α forms a fully active transcriptional complex. The present study investigates the role of FIH-1 in invasive breast carcinoma and its correlation with hypoxia.

Methods

Microarrayed tissue cores from 295 invasive carcinomas were stained for FIH-1, for HIF-1α and for carbonic anhydrase 9. FIH-1 expression was correlated with standard clinicopathological parameters and with the expression of the surrogate hypoxic markers HIF-1α and carbonic anhydrase 9.

Results

FIH-1 was positive in 239/295 (81%) tumours, 42/295 (14%) exclusively in the nucleus and 54/295 (18%) exclusively in the cytoplasm. Exclusive nuclear FIH-1 expression was significantly inversely associated with tumour grade (P = 0.02) and risk of recurrence (P = 0.04), whereas exclusive cytoplasmic FIH-1 was significantly positively associated with tumour grade (P = 0.004) and carbonic anhydrase 9 expression (P = 0.02). Patients with tumours that excluded FIH-1 from the nucleus had a significantly shorter survival compared with those with exclusive nuclear expression (P = 0.02). Cytoplasmic FIH-1 expression was also an independent poor prognostic factor for disease-free survival.

Conclusion

FIH-1 is widely expressed in invasive breast carcinoma. As with other HIF regulators, its association between cellular compartmentalization and the hypoxic response and survival suggests that tumour regulation of FIH-1 is an additional important mechanism for HIF pathway activation.
TheGata5target,TGIF2, defines the pancreatic region by modulating BMP signals within the endoderm
Authors: Spagnoli Francesca M. , Brivanlou Ali H.
Published: December 2007

Mechanisms underlying regional specification of distinct organ precursors within the endoderm, including the liver and pancreas, are still poorly understood. This is particularly true for stages between endoderm formation and the initiation of organogenesis. In this report, we have investigated these intermediate steps downstream of the early endodermal factor Gata5, which progressively lead to the induction of pancreatic fate. We have identified TGIF2 as a novel Gata5 target and demonstrate its function in the establishment of the pancreatic region within dorsal endoderm in Xenopus. TGIF2 acts primarily by restricting BMP signaling in the endoderm to allow pancreatic formation. Consistently, we found that blocking BMP signaling by independent means also perturbs the establishment of pancreatic identity in the endoderm. Previous findings demonstrated a crucial role for BMP signaling in determining dorsal/ventral fates in ectoderm and mesoderm. Our results now extend this trend to the endoderm and identify TGIF2 as the molecular link between dorsoventral patterning of the endoderm and pancreatic specification.
Six3inactivation causes progressive caudalization and aberrant patterning of the mammalian diencephalon
Authors: Lavado Alfonso , Lagutin Oleg V. , Oliver Guillermo
Published: December 2007

The homeobox gene Six3 represses Wnt1 transcription. It is also required in the anterior neural plate for the development of the mammalian rostral forebrain. We have now determined that at the 15- to 17-somite stage, the prospective diencephalon is the most-anterior structure in the Six3-null brain, and Wnt1 expression is anteriorly expanded. Consequently, the brain caudalizes, and at the 22- to 24-somite stage, the prospective thalamic territory is the most-anterior structure. At around E11.0, the pretectum replaces this structure. Analysis of Six3;Wnt1 double-null mice revealed that Six3-mediated repression of Wnt1 is necessary for the formation of the rostral diencephalon and that Six3 activity is required for the formation of the telencephalon. These results provide insight into the mechanisms that establish anteroposterior identity in the developing mammalian brain.
FGF signaling regulates mesenchymal differentiation and skeletal patterning along the limb bud proximodistal axis
Authors: Yu Kai , Ornitz David M.
Published: December 2007

Fibroblast growth factors (FGFs) are signals from the apical ectodermal ridge (AER) that are essential for limb pattern formation along the proximodistal (PD) axis. However, how patterning along the PD axis is regulated by AER-FGF signals remains controversial. To further explore the molecular mechanism of FGF functions during limb development, we conditionally inactivated fgf receptor 2 (Fgfr2) in the mouse AER to terminate all AER functions; for comparison, we inactivated both Fgfr1 and Fgfr2 in limb mesenchyme to block mesenchymal AER-FGF signaling. We also re-examined published data in which Fgf4 and Fgf8 were inactivated in the AER. We conclude that limb skeletal phenotypes resulting from loss of AER-FGF signals cannot simply be a consequence of excessive mesenchymal cell death, as suggested by previous studies, but also must be a consequence of reduced mesenchymal proliferation and a failure of mesenchymal differentiation, which occur following loss of both Fgf4 and Fgf8. We further conclude that chondrogenic primordia formation,marked by initial Sox9 expression in limb mesenchyme, is an essential component of the PD patterning process and that a key role for AER-FGF signaling is to facilitate SOX9 function and to ensure progressive establishment of chondrogenic primordia along the PD axis.