bluuebunny/crossref_metadata_2025 huggingface dataset:
Paleoenvironmental evolution of the Guercif basin (south Rifain corridor, northern morocco). Implications for the Messinian salinity crisis
Authors: Dayja Driss , Bignot Gérard
Published: June 2005

Foraminiferal biostratigraphic and paleoenvironmental results from the MDS1 borehole of the Guercif basin reveal the detailed history of its paleogeographic evolution during the late Neogene.

Four biostratigraphic events are recognised based on the study of planktonic foraminifera. In addition to the placement of the Tortonian-Messinian boundary at 798 m depth, they also allow correlation of the MSD1 borehole with other late Miocene sections in the Mediterranean area.

The diversity of benthic foraminifera is significant in the studied borehole. 111 species assigned to 55 genera, were identified.

Three successive assemblages of benthic foraminifera were recognised, each one conveying a different paleoenvironmental information. They thus recorded a number of fundamental changes in the environmental and water mass characteristics of the Guercif basin.

Following the oldest upper Tortonian transgressive marine deposits found at the bottom of the borehole, marls accumulated at lower epibathyal to upper mesobathyal depths (~400 to ~800 m). They recorded sea-floor dysoxia and associated stratification of the water column for the time interval between ~7.5 and ~7.3 Ma. During the latest Tortonian-early Messinian the basin experienced a rapid shallowing, first from the previously bathyal environments to deep neritic (~100 to ~200 m), and to shallow neritic afterwards (0 to ~30 m). The total absence of any foraminifera in the conglomerates situated at the top of the study borehole suggests that these sediments were deposited in subaerial environments. At this time the connection between the Atlantic Ocean and the Mediterranean Sea through the South Rifain Corridor was stopped. This local event contributed to the establishment of the particular conditions of the Messinian salinity crisis.
The very high alluvial formation of early Pleistocene age in the Creuse River Valley at Eguzon (Indre) : cryoturbation patterns, prehistoric occupation sites and absolute dating
Authors: Despriée Jackie , Gageonnet Robert
Published: June 2005

Around twenty prehistoric sites of the very early Palaeolithic were discovered on the northern edge of the Massif Central, in the Creuse Valley between Crozant and the Paris Basin, and on the Aigurande crystalline plateau that borders it. Concentrated more particularly around Eguzon, the sites are all closely linked to fluviatile formations, whose study, despite difficult exploration conditions, revealed many remnants of alluvial deposits. Those of the very high formation, some up to 15 m thick, were the best preserved.

The most significant site, at “Pont-de-Lavaud”, is in a thin bed of gravel made up mainly of quartz pebbles and debris with small, interbedded sand lenses. Tilted 6 to 7° in a small depression in the weathered foliated crystalline basement, the bed is at mid-slope of an interfluve between the Creuse River and one of its small tributaries. Excavation done between 1983 and 1995 uncovered many prehistoric artefacts carved out of quartz in the upper part of the sediment and, below this, various cryoturbation patterns (sorted circles, polygons, inclusions in the alluvium of alterite from the bedrock) and scattered, less abundant artefacts of the same type. Due to the outstanding state of conservation of these findings, they could be studied in a particularly detailed manner and, when coupled with the study of the alluvial formations, enabled us to :

– place them at the base of the very high terrace, located 90–110 m above the river’s present-day low water level – attribute the unusual position of the outcrop to the tilting of a block of bedrock by new displacement of an old fault, thus confirming the role of recent tectonics in the regional morphology ;

Absolute age dating by Electron Spin Resonance (ESR) of the best conserved outcrops of the very high alluvial formation gave an age of 1 to 1.2 million years, thus placing them at the end of the early Pleistocene. However, dating of alluvial remains near the site and of the site itself, gave ages between 0,9 and 1 million years. Differences are attributed to the role that greater erosion and pedogenic weathering might have played. Therefore, the “Pont-de-Lavaud” occupation sites are among the oldest presently known in Europe.
Diversity of radiolarian families through time
Authors: De Wever Patrick , O’dogherty Luis , Caridroit Martial , Dumitrica Paulian , Guex Jean , Nigrini Catherine , Caulet Jean-Pierre
Published: June 2005

The examination of radiolarian biodiversity at the family level through Phanerozoic time reveals some general trends known in other groups of organisms, especially among plankton, while some other trends seem to be quite peculiar. The Permian /Triassic crisis that is one of the most important in the evolution of marine organisms, is marked in radiolarian assemblages by the extinction of two orders (Albaillellaria and Latentifistularia) towards the end of the Permian, and mostly by the tremendous diversification of Spumellaria and Nassellaria in the early-mid Triassic. Radiolarian diversity increased from Cambrian to Jurassic, remained quite stable during the Cretaceous and has decreased slightly since then.
Syn-folding remagnetization events in the French-Belgium Variscan thrust front as markers of the fold-and-thrust belt kinematics
Authors: Szaniawski Rafal , Lewandowski Marek , Mansy Jean-Louis , Averbuch Olivier , Lacquement Frederic
Published: June 2005

New paleomagnetic studies have been carried out within the Ardennes segment of the N France - S Belgium Variscan fold-and-thrust belt to set constraints on the fold-thrust belt kinematics and reveal the casual relationships between vertical-axis rotations and major strike deviated zones localised along the general trend of the belt. Magnetite-bearing Devonian and Carboniferous limestones yielded two characteristic, secondary components of the natural remanent magnetization : a low temperature component recorded most probably during the late stages of folding and a high temperature component, acquired during incipient stages of deformation. Both post- and synfolding magnetizations were identified in the Lower Devonian hematite bearing sandstones. Ages of magnetization, inferred from the analysis of characteristic remanence inclinations compared to the reference curves for the stable parts of the Old Red Sandstones Continent (ORC), suggest the previous remagnetization event to be due to the burial of sedimentary rocks under the thick molassic foreland basin of Namurian-Westphalian age and the second to the final out-of-sequence activation of the thrust front in Stephanian times. Irrespective of the age of the magnetizations, orientations of paleomagnetic directions are dominantly governed by second-order structural trends. Clockwise rotations are observed in relatively narrow zones featuring deviated orientations of fold axes, other sites show paleomagnetic directions akin to those known from the ORC. We interpret this feature as a result of local transpressive deformations and related rotations, which occurred at lateral borders of propagating thrust-sheets. The latter deformation zones are suggested to be controlled by deep-seated discontinuities inherited from the Devonian Rheno-hercynian basin development. The Ardennes thrust belt was thus not rotated as a whole unit with respect to the ORC after the Namurian, preserving the initial orientation of the continental margin.
Ontogeny and covariation in the Toarcian genus Osperleioceras (Ammonoidea)
Authors: Morard Alain , Guex Jean
Published: June 2005

Starting from embryonic (protoconch-ammonitella) and early juvenile shells, which are indistinguishable at the species level, growth curves of Osperleioceras from the Reynesi Subzone (Upper Toarcian) of the Causses Basin (Aveyron, France) show a continuous radiating range of correlated variation in dimensional and ornamental characters, such as involution, whorl compression, rib strength and rib density. This covariation pattern can be observed among single-horizon assemblages, as well as during individual ontogenetic development.

The existence of a continuous intergradational series of shells, ranging from stout coarsely ribbed to smooth suboxycone morphologies, rules out functional or ecological selectivity to explain this non-random variability pattern. The complex interdependence of shape and sculpture can be simulated by a model in which sculpture intensity depends on mantle curvature [Guex, 1999].

The expression of covariation in subadult specimens since the base of Upper Toarcian reveals a rise in variability, concomitant with a size decrease, both contemporaneous with environmental instability. It developed in successive bursts from a fairly long low variability period spanning the whole Middle Toarcian.
Successive shearing tectonics during the Hercynian collisional evolution of the southwestern French Massif Central
Authors: Duguet Manuel , Faure Michel
Published: June 2005

In the French Massif Central, the Devonian-Carboniferous tectonic evolution of the Rouergue-Albigeois area is characterized by three phases of low-angle ductile shearing. The first event D1, which occurred probably in the Lower Devonian, is responsible for the south-westward thrusting of the high metamorphic Lévézou nappe which belongs to the Upper Gneiss Unit above the Lower Gneiss Unit overlying itself the Para-autochthonous Unit, (locally called the St-Serninsur-Rance nappe). In the late Devonian-early Carboniferous, this stack of nappes is reworked by a second event, D2, characterized by a top-to-the-NW shearing of the Para-autochthonous Unit upon the Lower Gneiss Unit developed under medium pressure/medium temperature metamorphism. The contact between the Lower Gneiss Unit and the Para-autochthonous Unit is a top-to-the NW low-angle fault that progressively evolues into a dextral strike-slip fault from west to east. The D2 event is followed by a top-to-the south D3 thrusting dated around 330–340 Ma. The main feature of the D3 compressional stage is the emplacement of the whole stack of nappes previously structured by D1 and D2 events upon the Albigeois series. The D3 event produced south-verging recumbent folds in the Albigeois, Mont-de-Lacaune and Montagne Noire. The significance of the D2 event either as thrusting or normal faulting is discussed.
A tectonic inversion by steps during the Cenozoic : the Dover Strait
Authors: Van Vliet-Lanoë Brigitte , Mansy Jean-Louis , Henriet Jean-Pierre , Laurent Michel , Vidier Jean-Pierre
Published: June 2005

The Boulonnais is a dome incised by a former marine gulf inset into a zone of tectonic inversion from the Middle Eocene, which was already partly excavated at least at the Upper Eocene. New sedimentological and paleopedological data obtained within the Boulonnais, completed with old seismic profiles, allow a better understanding of the inversion process which developed step by step. The initial breaching probably took place in the late Eocene. The Dover Strait was probably opened during the Lutetian, a part of the Oligocene and the late Neogene. Oligocene and Pliocene faunal assemblages are identical on both sides of the Strait. It was closed again for tectonic and eustatic reasons in the early Quaternary and reopen subsequently just before the Last Interglacial. The opening is related to the evolution of the Western Channel and of its paleovalley system. The inversion of the Variscan front accommodates most of the shortening induced by the Pyrenean Orogen on the western border of the European plate. The inversion of the Dover Strait region is almost synchronous with those of other basins of the Channel and North Sea areas. Tectonic, geomorphologic and climatic implications of this dynamic are discussed within the western European context.
Indication for counterclockwise declination deviation in the Cretaceous of the North Paris Basin
Authors: Márton Emó , Csontos László , Mansy Jean-Louis , Bergerat Françoise
Published: June 2005

Paleomagnetic sampling was carried out in Mesozoic exposures of Northwest France and Southeast Belgium. Cretaceous localities in Hainaut, Boulonnais and Normandie yielded statistically well defined paleomagnetic directions. These localities fall into two groups. Hainaut and Boulonnais are characterized by declinations suggesting 30° counterclockwise (CCW) angular deviation of declination with respect to the present North, while Normandie exhibits moderate (12°) clockwise (CW) angular deviation with respect to the present North. In Normandie, we also observed occasionally very weak signals of a CCW deviated component, which, however, could not be treated statistically. Fold test suggests that both groups of samples were remagnetized during deformation. The overall mean paleomagnetic declination of the first group is westernly, that of the second group practically coincides with post-Eocene European reference directions, From assessing structural inversion and relevant paleostress-directions in Normandie, remagnetization may be connected to tectonic inversion in late Eocene-Oligocene times.

While the statistically meaningful paleomagnetic result for the second group fit the synthetic stable European apparent polar wander path (APWP) at about 30 Ma, the overall mean paleomagnetic direction of the first group (based on 5 localities, representing 42 samples) defines a pole which is significantly offset from it, at any time following the deposition of the studied sediments. One explanation of this offset could be intraplate rotation on a small (Brabant Massif) scale. However, the angle of deviation in declination seems to be too large for a tectonic solution. Furthermore the data obtained from the Paleozoic do not show such declination deviation. It seems, therefore, that we need to increase considerably the direct stable European paleomagnetic database for the late Cretaceous-Tertiary, in order to further improve the late Cretaceous-Paleogene segment of the European APWP.
Fluid palaeo-circulation generated by the Pyrenean orogeny and its potential role in the formation of lead-zinc deposits in the Cévennes region: a modelling approach
Authors: Jost Anne , Violette Sophie , Macquar Jean-Claude , Dromart Gilles
Published: June 2005

Recent studies of the host rock palaeomagnetism of the lead-zinc deposits on the Cévennes margins pointed towards regional fluid circulation from the early to middle Eocene. The hypothesis has therefore been put forward that mineralising fluids might have migrated as a consequence of the Pyrenean uplift. Based on this assumption, a digital model was developed to describe this palaeo-circulation along two reconstituted cross-sections, in early Eocene times. One of them extends from the Gulf of Lion to the Les Malines deposits at the southern end of the Cévennes mountains; the other one connects the Montagne Noire to Les Malines in order to test the hypothesis of a more localised fluid circulation. The modelling of heat and fluid circulation along these cross-sections is constrained mainly by fluid-temperature data, derived from analyses of fluid inclusions. The maximum recorded temperatures are about 150°C. The METIS code (Ecole des Mines, Paris) was used to test the transport scenarios while prescribing hydrodynamic characteristics in the series that would allow fluid flow. Gravity-driven flow is initiated at a high point, either the Montagne Noire or the Pyrenees. Drainage occurs at depth. The permeable formations concerned are: Cambrian dolomite in the cross-section beginning in the Montagne Noire, and Triassic and Liassic carbonate or sandstone formations in the other one. The fluids converge at the deposit site through faults on the margins of the Cévennes horst. The highest temperatures reproduced by the digital simulations in a steady-state regime are in the order of 80°C at the deposit site for each pathway. A sensitivity test showed that higher temperatures, in the order of 150°C, could only be reached with a heat flux of 120 mW.m−2 and by optimising such parameters as permeability, aquifer geometry and thermal conductivity. However, such a parameter set does not seem geologically feasible. The modelling demonstrates that circulation must have occurred at greater depths in the case of gravity-driven fluid flow. The most probable explanation is that the fluid migrated in the deep crustal basement and that, during its ascent along the faults bordering the Cévennes heights, it mixed with basinal brines migrating through shallower aquifers.
Evidence of magmatic flow by 2-D image analysis of 3-D shape preferred orientation distributions
Authors: Launeau Patrick
Published: June 2005

The 3-D Shape Preferred Orientation (SPO) ellipsoid can be obtained by image analysis on a minimum of three perpendicular sections, when the 2-D measurements can be assimilated to ellipses. As numerous phenomenons can modify the SPO in magma (boundary condition effects, crystal interactions, joint migrations, etc.), the ellipsoid calculation is first tested on a set of digital models of simple shear flow. Those models, made of scattered shape ratio distribution, show that a suspension of crystals in a simple shear flow of the magma produces SPO parallel to the shear direction with an intensity given by the average shape ratio of the crystals, without any link with the amount of shear flow. This steady state SPO along the flow direction is particularly useful to study magma emplacement even if it is also shown that a critical shear rate γ between 4 and 8, for crystal shape ratio between 2 and 5 respectively, is sufficient to completely reorient a SPO. Therefore the SPO does not record magmatic strain as may do an enclave, which is an interface between two magmas with low viscosity contrast, that can record the whole strain of the magma by its passive deformation along the flow. An infinite strain is necessary here to parallelize the enclave on the shear flow direction. The application to a natural case (gabbronorite of the Bushveld, South Africa) shows that we must take care of the mineral chosen to describe a flow in a magma and that a careful classical study of the structures observed in thin sections is always required. To allow anyone to test the quality of the 2-D/3-D conversions, a web site is associated to this publication with a free access to all the image analysis and ellipsoid programs presented below.
Ammonites phylogenetic analysis: state of the art and new prospects
Authors: Rouget Isabelle , Neigeet Pascal , Dommergues Jean-Louis
Published: June 2005

Two main types of data are available to resolve phylogenies using fossils data: (1) stratigraphic ordering of taxa, and (2) morphological characters. In most phylogenetic studies dealing with ammonites, authors have given priority to the stratigraphic distribution of taxa. This practice is classically justified by the fact that the ammonite fossil record is frequently outstandingly good. In practice, the level of integration of stratigraphic and morphologic information in a single analysis depends on the confidence that authors have in the quality of data. Besides, many evolutionary concepts, which could differ over time and between authors (e.g. anagenesis, cladogenesis, iterative evolution), are added to these data to help infer phylogenetic relationships. As a result, phylogenetic hypotheses are based on eclectic methods which depend on the relative weight given to stratigraphic and morphologic information as well as on evolutionary concepts used. The validity of relationships proposed by previous authors is not dealt with in this paper. Instead, our goal is to draw attention to problems that these eclectic methods may cause, that is to say: (1) ammonites systematics is poorly formalised and (2) phylogenetic hypotheses as they are classically constructed are not rigorously testable. During the last 10 years, cladistic analysis has been applied to ammonites but is still unpopular among ammonitologists. However, studies have consistently shown that cladistics is not as unsuited a tool for ammonites phylogenetic reconstruction as is widely believed. Moreover, classical works open new questions about ammonite phylogeny and in particular, help to reappraise our view on the definition of morphological characters and their phylogenetic significance.
A new species of Hippopotamidae (Mammalia, Artiodactyla) from the Sagantole Formation, Middle Awash, Ethiopia
Authors: Boisserie Jean-Renaud
Published: June 2005

A new species of Hippopotamidae, Hexaprotodon dulu nov. sp., was discovered in the Middle Awash valley, Afar, Ethiopia. It was found in the Sagantole Formation, within volcaniclastic beds aged between 5.2 Ma and 4.9 Ma (40Ar/39Ar). It is therefore the oldest hippo species described as yet from Ethiopia. This hexaprotodont hippo exhibits a general morphology that is primitive, close in that respect to other Mio-Pliocene forms. However, its cranium and dentition display a distinctive association of measurements and features. This new species increases the hippo fossil record in East Africa. It also reinforces the hypothesis of hippo endemism in each African basin as early as the basal Pliocene.
Reconstitution of dune morphologies and palaeowind regimes in the Proto-Namib since the Miocene
Authors: Segalen Loïc , Rognon Pierre , Pickford Martin , Senut Brigitte , Emmanuel Laurent , Renard Maurice , Ward John
Published: June 2005

In the Namib Desert, indurated fossil dunes are found between the active sands. Establishment of a biostratigraphic scale based on associated mammal faunas and ratite eggshells allows the study of palaeowind fluctuations that have controlled these palaeodunes since the Middle Miocene with a temporal resolution of between 1 and 3 Ma. In the southern Namib, the Proto-Namib aeolian systems consist of crescent dunes (barkhan type). In the eastern part of the Namib Desert, the aeolianite cross-bedding corresponds to longitudinal or pyramidal dunes. These aeolian structures are also controlled by local winds, resulting from high relief and the southern trade winds : this regime is identical to that which currently sweeps, through the Namib Desert, and is related to the presence of anticyclonic conditions in the Atlantic Ocean. A regime of seasonal winds from the northeastern sector is also recorded starting in the late Miocene.
Stochastic Modeling of Diffuse Pesticide Losses from a Small Agricultural Catchment
Authors: Lindahl Anna M. L. , Kreuger Jenny , Stenström John , Gärdenäs Annemieke I. , Alavi Ghasem , Roulier Stéphanie , Jarvis Nicholas J.
Published: June 2005

The objective of this study was to identify the main sources of variation in pesticide losses at field and catchment scales using the dual permeability model MACRO. Stochastic simulations of the leaching of the herbicide MCPA (4‐chloro‐2‐methylphenoxyacetic acid) were compared with seven years of measured concentrations in a stream draining a small agricultural catchment and one year of measured concentrations at the outlet of a field located within the catchment. MACRO was parameterized from measured probability distributions accounting for spatial variability of soil properties and local pedotransfer functions derived from information gathered in field‐ and catchment‐scale soil surveys. At the field scale, a single deterministic simulation using the means of the input distributions was also performed. The deterministic run failed to reproduce the summer outflows when most leaching occurred, and greatly underestimated pesticide leaching. In contrast, the stochastic simulations successfully predicted the hydrologic response of the field and catchment and there was a good resemblance between the simulations and measured MCPA concentrations at the field outlet. At the catchment scale, the stochastic approach underestimated the concentrations of MCPA in the stream, probably mostly due to point sources, but perhaps also because the distributions used for the input variables did not accurately reflect conditions in the catchment. Sensitivity analyses showed that the most important factors affecting MACRO modeled diffuse MCPA losses from this catchment were soil properties controlling macropore flow, precipitation following application, and organic carbon content.
Phosphorus Concentrations in Overland Flow from Diverse Locations on a New York Dairy Farm
Authors: Hively W. Dean , Bryant Ray B. , Fahey Timothy J.
Published: June 2005

The National Phosphorus Project rainfall simulator was used to quantify overland flow and P transport from nine sites distributed throughout the watershed of a New York City Watershed Agriculture Program collaborating dairy farm. Observed concentrations of total dissolved phosphorus (TDP) were low (0.007–0.12 mg L−1) in flow from deciduous forest, extensively managed pasture, and hillside seeps; moderate (0.18–0.64 mg L−1) in flow from intensively managed pastures, a hayfield, and a cow path; and extremely high (11.6 mg L−1) in flow from a manured barnyard. Concentrations of TDP from sites without fresh manure were strongly correlated with soil test P (TDP [mg L−1] = 0.0056 + 0.0180 × Morgan's soil test phosphorus [STP, mg kg−1]; R2 = 84%). Observed concentrations of suspended solids were low (16–137 mg L−1) in flow from vegetated sites, but were higher (375–615 mg L−1) in flow from sites with little ground cover (barnyard, cow path, plowed field). Under dry summer conditions the time to observed overland flow was shorter (<18 min) for nonfield areas (seeps, barnyard, cow path) than for field and forest areas (27–93 min), indicating that hydrologically active nonfield areas of minor spatial extent but with high soil P (e.g., cow paths and barnyards) can play a significant role in summertime P loading. When soils started from field capacity (second‐day) time to overland flow was uniformly less than 23 min, indicating that under wet watershed conditions low‐P source areas can dilute overland flow from concentrated sources.
Analysis of Temperature Effects on Tension Infiltrometry of Low Permeability Materials
Authors: Castiglione Paolo , Shouse Peter J. , Mohanty Binayak P. , van Genuchten Martinus Th.
Published: June 2005

Tension infiltrometers have become popular for in situ measurement of the near‐saturated hydraulic conductivity as a function of the soil water pressure head. Unfortunately, fluctuating ambient temperatures can cause dramatic pressure variations due to the presence of confined air inside the infiltrometer, thereby affecting the intended pressure head to be applied to the soil surface and hence also the measured infiltration rate. This is especially true for low infiltration rates and long equilibration times typical of low permeability materials, including unsaturated fractured rock. We developed a model to analyze the effects of temperature changes on the static pressure of the confined air volume within tension infiltrometers. The model was tested using several prototype infiltrometer designs in a computer‐controlled variable‐temperature room. Experimental results confirmed the model simulations. For example, predicted and measured changes in the pressure head in one experiment were 11.2 and 12.5 cm following a change of 18.5°C in the temperature. Using the model, we were able to optimize several infiltrometer designs that significantly reduced the undesired effects of temperature on tension infiltration results.
Numerical Analysis to Investigate the Effects of the Design and Installation of Equilibrium Tension Plate Lysimeters on Leachate Volume
Authors: Mertens J. , Barkle G. F. , Stenger R.
Published: June 2005

The composition and quantity of leachate as it moves down through the vadose zone is seldom measured directly because sampling in this unsaturated zone at the depths required has proven to be extremely difficult. A promising technique is the use of large porous plates known as equilibrium tension plate lysimeters (ETPLs), which have a controlled suction exerted on them that mimics the soil matric potential measured in the surrounding undisturbed soil profile. In the design phase for the installation of 15 ETPLs at five different depths (three replicates) around a central access chamber in the vadose zone in the Lake Taupo catchment of New Zealand, questions arose regarding the effects of the design and installation layout of the ETPLs on the measured leachate fluxes. To investigate the important design criteria and the spacing of the ETPLs, a numerical investigation using the HYDRUS‐2D software was conducted. This analysis showed that the distance between the tension plate and the base (lower boundary) of the ETPL needs to be large enough to ensure that the effect of the dry zone (rain shadow effect) created below the ETPL on the soil zone being sampled above the plate is minimized. The boundary condition between the ETPL and the central access chamber was also shown to be critical, requiring a free‐drainage condition in this location. The sampling efficiency of the ETPLs increases when the horizontal distance between adjacent ETPLs increases. Less obvious was the result that the sampling efficiency decreases with increasing vertical distance. This work demonstrates that the design and installation configuration of the ETPLs can significantly impact sampling efficiency. The relationships demonstrated in this work must be recognized and implemented in the design process, particularly when multiple ETPLs are installed at various depths through the vadose zone at other locations.
Reciprocal Mutations in TM2/TM3 in a D2 Dopamine Receptor Background Confirms the Importance of this Microdomain as a Selective Determinant of Para‐Halogenated 1,4‐Disubstituted Aromatic Piperazines
Authors: Floresca Christina Z. , Chen Shiuhwei , Kortagere Sandhya , Schetz John A.
Published: June 2005

We recently demonstrated that in the D4 dopamine receptor the aromatic microdomain that spans the interface of the second and third transmembrane (TM) domains influences the high affinity interactions of extremely D4‐selective ligands possessing a 1,4‐disubstituted aromatic piperazine/piperidine (1,4‐DAP) structure. On the basis of their substructural features and patterns of sensitivity to mutations constructed in a D4 receptor background, the D4‐selective 1,4‐DAPs were categorized as having two distinct modes of binding that we named mode‐1 and mode‐3 [1]. Here we extend these findings of the ligand‐receptor structure‐affinity relationships for some of these highly D4‐selective 1,4‐DAPs by measuring the effect of the corresponding reciprocal TM2/TM3 mutations constructed in a D2 dopamine receptor background on the binding affinity of the para‐halogenated mode‐1 ligands L750,667 and FAUC213. The results indicate that the D2‐V2.61F+FV3.28‐3.29LM mutant binds L750,667 and FAUC213 with significantly increased affinity, i.e., its binding profile becomes more D4‐like. These findings further support the assignment of the TM2/TM3 aromatic microdomain encompassing positions 2.61 and 3.28‐3.29 as a 1,4‐DAP D4‐selectivity microdomain and highlights the importance of the precise emplacement of aromatics in this microdomain as key to the selective molecular recognition of L750,667 and FAUC213.
Chirospecific and Subtype Selective Dopamine Receptor Binding of Heterocyclic Methoxynaphthamide Analogs
Authors: Bettinetti Laura , Hübner Harald , Gmeiner Peter
Published: June 2005

Employing the D3 and D4 selective methoxynaphthalines nafadotride and FAUC 182, respectively, as lead compounds, the pyrazolo[1,5‐a]pyridine‐3‐carboxamides of type 1a and 2a as well as their 2‐substituted regioisomers 1b and 2b were synthesized when following an ex‐chiral pool approach. Dopamine receptor binding studies involving the target compounds (1a,b, 2a,b) and the respective optical antipodes ent‐1a,b and ent‐2a,b revealed the heterocyclic carboxamide 2a as a strong and selective D4 ligand (Ki = 8.6 nM). According to a mitogenesis assay, 2a shows D4 partial agonist effects (29%, EC50 = 6.7 nM) and, thus, might be of interest for the treatment of sexual dysfunction.
Delineation of Receptor‐Ligand Interactions at the Human Histamine H1 Receptor by a Combined Approach of Site‐Directed Mutagenesis and Computational Techniques – or – How to Bind the H1 Receptor
Authors: Jongejan Aldo , Leurs Rob
Published: June 2005

Histamine H1 antagonists or “antihistamines” are one of the most prescribed drug families in Western countries. They exert their effect by binding to the histamine H1 receptor, a receptor belonging to the class of rhodopsin‐like G protein‐coupled receptors (GPCRs). In this review, the binding of ligands to the human histamine H1 receptor with respect to site‐directed mutagenesis studies and molecular modeling techniques is described. The ligands described include agonists (histamine and histapro difens), a stereoselective partial agonist (lisuride), and selected inverse agonists (mepyramine, acrivastine and triprolidine).
Postnatal development of rat pups after maternal exposure to diethanolamine
Authors: Price Catherine J. , Marr Melissa C. , Myers Christina B. , Jahnke Gloria D.
Published: June 2005

BACKGROUND: Diethanolamine (DEA), a widely used surfactant, was administered to pregnant mice at the oral LD10 resulting in failure of pups to grow and thrive through postnatal day (PND) 3 [National Toxicology Program, 1987; York et al., Teratology 37:503–504, 1988]. The toxicity profile for DEA differs among rodent species. This study investigated DEA‐induced postnatal toxicity in a second species. METHODS: Timed‐mated Sprague‐Dawley rats were dosed (0, 50, 125, 200, 250, or 300 mg DEA/kg/day, p.o.) on gestational days (GD) 6–19. Dams and pups were monitored for body weight, feed/water intake, clinical signs, litter size, and sex ratio. At necropsy (PND 21), maternal liver and kidney weights and number of uterine implantation sites were recorded. RESULTS: The high‐dose group was terminated early due to excessive toxicity. The estimated maternal LD10 was 218 mg/kg/day. Maternal effects included decreased body weight and relative feed intake (≥200 mg/kg/day), transiently reduced relative water intake (125 and 250 mg/kg/day), and increased absolute kidney weight (≥125 mg/kg/day). Postimplantation loss (PND 0) and pup mortality (PND 0–4) were increased (≥200 and ≥125 mg/kg/day, respectively). Pup body weight was reduced (≥200 mg/kg/day) as late as PND 21. CONCLUSIONS: This study demonstrates reduced postnatal growth and survival in a second species after gestational exposure to DEA, persistence of toxic effects through the end of lactation, possibly due to long elimination half‐life, and maternal and developmental toxicity no‐observed‐adverse‐effect level (NOAELs) (50 mg/kg/day) and lowest‐observed‐adverse‐effect level (LOAELs) (125 mg/kg/day) for oral DEA exposure during embryo/fetal development in the rat. Birth Defects Res B 74:243–254, 2005. © 2005 Wiley‐Liss, Inc.
Prior exposure to indole‐3‐carbinol decreases the incidence of specific cyclophosphamide‐induced developmental defects in mice
Authors: Bailey Melissa M. , Sawyer Robert D. , Behling Jeremy E. , Boohaker Jonathan G. , Hicks Justin G. , O'Donnell Molly A. , Stringer Kelli R. , Rasco Jane F. , Hood Ronald D.
Published: June 2005

BACKGROUND: Indole‐3‐carbinol (I3C) is a product of the hydrolysis of glucobrassicin that is found in cruciferous vegetables. I3C can intervene in toxic processes that are mediated by oxidative mechanisms because it possesses the chemical and pharmacokinetic properties necessary to provide a free radical trap. Cyclophosphamide (CP) is a bifunctional alkylating agent known to produce DNA damage and to cause developmental toxicity, including malformations, in laboratory animals. METHODS: Pregnant CD‐1 mice were given a 100 mg/kg dose of I3C 24 or 48 hr before administration of 20 mg/kg CP on gestation day 10 (GD 10). Controls were given the vehicle (DMSO), I3C, or CP. This regimen was carried out to determine if I3C could protect against the developmental toxicity of alkylating agents, such as CP. Dams were sacrificed on GD 17 and their litters were examined for adverse effects. RESULTS: Treatment with I3C 48 hr before CP administration was associated with decreased fetal limb and tail malformations. Limb malformation incidences were reduced from 42% litters affected in the CP control to 16% in the I3C/CP 48‐hr treatment group, and tail malformations were reduced from 45% in the CP control to 16% in the I3C/CP 48‐hr treatment group, indicating a protective effect of prior exposure to I3C. I3C given 24 hr before CP had no significant protective effect, while having an apparently adverse consequence with regard to the incidence of talipes. CONCLUSIONS: Exposure of a developing mammal to indole‐3‐carbinol before exposure to cyclophosphamide during organogenesis can influence the teratogenicity of cyclophosphamide. Birth Defects Res B. 74:261–267, 2005. © 2005 Wiley‐Liss, Inc.
Effects of hyperthermia and boric acid on skeletal development in rat embryos
Authors: Harrouk Wafa A. , Wheeler Kellylynn E. , Kimmel Gary L. , Hogan Karen A. , Kimmel Carole A.
Published: June 2005

BACKGROUND: The individual effects of boric acid (BA) and hyperthermia on the development of the axial skeleton have been reported previously. Both cause an increased incidence of axial skeletal defects including a decrease in the total number of ribs and vertebrae. Because of the similarity in the effects of the two agents, we examined their interaction when given in combination to pregnant rats on gestational day (GD) 10. METHODS: Dams were treated on GD 10 with BA (0, 250, or 500 mg/kg) and hyperthermia (37, 41, or 42°C) and allowed to deliver their pups. Doses of BA were based on results from a dose‐finding study. Litters were evaluated on postnatal days (PND) 1 and 3 for number, gender, and weight of pups. On PND3, pups were examined externally and viscerally, and double‐stained for skeletal evaluation. RESULTS: A dose‐dependent, statistically significant increase in fetal skeletal defects was seen on PND 3 with BA or hyperthermia alone with even greater effects when given in combination. Defects included rib and vertebral fusions, split vertebral centra in the thoracic and lumbar areas, and a decrease in the total number of ribs and vertebrae. CONCLUSIONS: The increased incidence of skeletal defects resulting from combined exposure to hyperthermia and BA was additive for segmentation defects and synergistic for the reduction in numbers of vertebrae. Birth Defects Res B 74:268–276, 2005. Published 2005 Wiley‐Liss, Inc.
Cartilage formation in growth plate and arteries: from physiology to pathology
Authors: Magne D. , Julien M. , Vinatier C. , Merhi‐Soussi F. , Weiss P. , Guicheux J.
Published: June 2005

Vascular calcifications are the consequence of several pathological conditions such as atherosclerosis, diabetes, hypercholesterolemia and chronic renal insufficiency. They are associated with risks of amputation, ischemic heart disease, stroke and increased mortality. A growing body of evidence indicates that vascular smooth muscle cells (VSMCs) undergo chondrogenic commitment eventually leading to vascular calcification, by mechanisms similar to those governing ossification in the cartilage growth plate. Our knowledge of the formation of cartilage growth plate can therefore help us to understand why and how arteries calcify and, consequently, develop new therapeutic strategies. Reciprocally, thorough consideration of the events leading to ectopic chondrocyte differentiation appears crucial to further increase our understanding of growth plate formation. In this context, we will review the effects of known or suspected factors that promote chondrogenic differentiation in growth plate and arteries. BioEssays 27:708–716, 2005. © 2005 Wiley Periodicals, Inc.
Chromosome chains and platypus sex: kinky connections
Authors: Ashley Terry
Published: June 2005

Mammal sex determination depends on an XY chromosome system, a gene for testis development and a means of activating the X chromosome. The duckbill platypus challenges these dogmas.1,2 Gutzner et al.1 find no recognizable SRY sequence and question whether the mammalian X was even the original sex chromosome in the platypus. Instead they suggest that the original platypus sex chromosomes were derived from the ZW chromosome system of birds and reptiles. Unraveling the puzzles of sex determination and dosage compensation in the platypus has been complicated by the fact that it has a surplus of sex chromosomes. Rather than a single X and Y chromosome, the male platypus has five Xs and five Ys. BioEssays 27:681–684, 2005. © 2005 Wiley Periodicals, Inc.
Cover Picture: Artificial Metalloenzymes for Enantioselective Catalysis Based on the Noncovalent Incorporation of Organometallic Moieties in a Host Protein (Chem. Eur. J. 13/2005)
Authors: Ward Thomas R.
Published: June 2005

Enzymatic and homogeneous catalysis offer complementary means to produce enantiopure products. Incorporation of achiral, biotinylated aminodiphosphine–rhodium complexes in (strept)avidin, which fit to each other as a hand in a glove, affords enantioselective hydrogenation catalysts. A combined chemogenetic procedure that allows the optimization of the activity and the selectivity of such artificial metalloenzymes is described in the Concept article by T. R. Ward on page 3798 ff.
Does a delay in external beam radiation therapy after tissue diagnosis affect outcome for men with prostate carcinoma?
Authors: Andrews Stephen F. , Horwitz Eric M. , Feigenberg Steven J. , Eisenberg Debra F. , Hanlon Alexandra L. , Uzzo Robert G. , Pollack Alan
Published: June 2005

BACKGROUND

Physicians involved in the care of men diagnosed with prostate carcinoma must assess the urgency of treatment. For those men who choose external beam radiation therapy (EBRT), the delay from the time of biopsy to treatment may be stressful. There are limited data on the consequences of radiation treatment delay. The purpose of the current study was to evaluate the effect of time to treatment (TTT) on outcomes.

METHODS

The authors of the current study analyzed 1322 patients who were treated with EBRT alone. Overall survival (OS), cause specific survival (CSS), distant metastasis (DM), and freedom from biochemical failure (FFBF) were calculated. TTT was first analyzed at 4 intervals: < 3, 3–6, 6–9 and > 9 months, and at the median TTT. Cox multivariate analysis (MVA) was then performed with 2002 American Joint Commission on Cancer T‐stage, Gleason score, prostate specific antigen (PSA), radiation dose, and TTT as covariates.

RESULTS

There were no statistical differences in OS, CSS, DM, or FFBF among men whose EBRT began < 3, 3–6, 6–9, or > 9 months after diagnosis. This was also true at the median TTT of 3.1 months. A subgroup analysis was performed in which patients were stratified into low‐, intermediate‐ and high‐risk groups based on pretreatment PSA, Gleason score and AJCC T‐stage. FFBF, and DM were calculated above and below the median TTT of 3.1 months. In this analysis, there was no statistically significant difference in FFBF or DM within the risk groups.

CONCLUSIONS

Within the limits of the current study, data indicate that a treatment delay, even in high‐risk patients, has little effect on clinical or biochemical outcome. Cancer 2005. © 2005 American Cancer Society.
Investigation of Ethylene Dimerization over Faujasite Zeolite by the ONIOM Method
Authors: Namuangruk Supawadee , Pantu Piboon , Limtrakul Jumras
Published: June 2005

Ethylene dimerization was investigated by using an 84T cluster of faujasite zeolite modeled by the ONIOM3(MP2/6‐311++G(d,p):HF/6‐31G(d):UFF) method. Concerted and stepwise mechanisms were evaluated. In the stepwise mechanism, the reaction proceeds by protonation of ethylene to form the surface ethoxide and then CC bond formation between the ethoxide and the second ethylene molecule to give the butoxide product. The first step is rate‐determining and has an activation barrier of 30.06 kcal mol−1. The ethoxide intermediate is rather reactive and readily reacts with another ethylene molecule with a smaller activation energy of 28.87 kcal mol−1. In the concerted mechanism, the reaction occurs in one step of simultaneous protonation and CC bond formation. The activation barrier is calculated to be 38.08 kcal mol−1. Therefore, the stepwise mechanism should dominate in ethylene dimerization.
A New, Expeditious Entry to the Benzophenanthrofuran Framework by a Pd‐Catalyzed C‐ and O‐Arylation/PIFA‐Mediated Oxidative Coupling Sequence
Authors: Churruca Fátima , SanMartin Raul , Tellitu Imanol , Domínguez Esther
Published: June 2005

The synthesis of a series of 2,3‐diarylbenzo[b]furans starting from 1,2‐diarylethanones and 1,2‐dibromoarenes proceeds by means of both homogeneous and polymer‐anchored palladium catalysts. This tandem process can be effectively halted at the C‐arylation step, thus providing key o‐bromoarylated deoxybenzoin intermediates in good yields. The efficient oxidative coupling leading to benzo[b]phenanthro[9,10‐d]furans is carried out using the safer hypervalent iodine reagent PIFA. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
The Formation of Silylated β‐Lactams from Silylketenes through Lewis Acid Promoted [2+2] Cycloaddition: A Combined Theoretical and Experimental Study
Authors: Pelotier Béatrice , Rajzmann Michel , Pons Jean‐Marc , Campomanes Pablo , López Ramón , Sordo Tomás L.
Published: June 2005

The stereoselective formation of silylated cis‐β‐lactams from (trimethylsilyl)ketene and an α‐imino ester by Lewis acid catalysis is described. Theoretical results suggest that the reaction between (trimethylsilyl)ketene and trans‐(methoxycarbonyl)‐N‐methylformaldimine would proceed most favourably with the BF3 catalyst coordinated to the ketene. Moreover, the calculated energy barriers account for the cis:trans ratio found experimentally. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Monatin, Its Stereoisomers and Derivatives: Modeling the Sweet Taste Chemoreception Mechanism
Authors: Bassoli Angela , Borgonovo Gigliola , Busnelli Gilberto , Morini Gabriella , Merlini Lucio
Published: June 2005

The sweet natural compound monatin 1 has two stereogenic centers, and the 2S,4S absolute configuration has been attributed previously to the natural isomer. Among the four stereoisomers of monatin, three of them, particularly the 2R,4R isomer, tastes intensely sweet. The conformations of the four compounds have been studied by means of molecular modelling techniques. Both the diastereoisomeric forms show strong intramolecular hydrogen bonds which involve different functional groups and give rise to two different minimum energy conformations. The tertiary alcohol group in monatin seems to be indirectly involved in the generation of the taste, acting as an important contraint in generating the active conformation. The most important glucophores have been identified in the terminal –NH3+ and –COO– groups and in the indole ring by comparison with known topological models of sweet compounds and through the synthesis of appropriate derivatives in which some of these groups are lacking or modified. The relative affinity of each stereoisomer for its putative sweet taste receptor has been estimated semiquantitatively with the pseudoreceptor modelling technique. The predicted activity calculated with this technique is in good agreement with the experimental data and explains why the 2R,4R isomer (and not the natural 2S,4S isomer) is the sweetest of the series. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Dihydroaromatic Boronic Esters as Building Blocks for the Synthesis of Phenanthrenes and Phenanthridines
Authors: Hilt Gerhard , Hess Wilfried , Schmidt Frank
Published: June 2005

Alkenyl‐substituted dihydroaromatic boronic esters, generated by neutral cobalt(I)‐catalysed Diels–Alder reactions, reacted under palladium catalysis conditions with diiodobenzene, bromoiodobenzene and iodoaniline derivatives for the synthesis of regioselectively substituted phenanthrene and phenanthridine derivatives. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)