D1 Structures Research Articles

Variscan structure in the eastern part of the Pallaresa massif, Axial Zone of the Pyrenees (NW Andorra). Tectonic implications

AbstractThe Variscan structures of the Axial Zone of the Pyrenees are traditionally separated into the “infrastructure” and the “suprastructure” domains. Three deformation events have been recognized within Cambro-Ordovician rocks in the eastern part of the Pallaresa massif. D1 consists of a slaty cleavage (S1), and no folds have been found associated with it. The D2 event is characterized by E-W trending and north-verging recumbent folds with an associated foliation (S2) that can be observed at all scales. The S2 foliation has a horizontal orientation, and is the main foliation in the northern and central parts of the study area. The D3 deformation event is distinguished by development of E-W trending, upright folds, of centimetric to metric scale. These folds are associated with a steep and rough crenulation cleavage (S3) in the southern part of the study area. Subvertical faults trending E-W are associated with D3 folds. Most of the structures recognized in the eastern part of the Pallaresa massif have developed under low metamorphic grade conditions, although close to the Aston and Hospitalet domes, in the vicinity of some igneous intrusions, the metamorphism is coeval with S2 foliation and may reach high grade conditions. A gradual transition can be observed from zones characterized by structures of type D2 to zones exhibiting a better development of D3 structures. This transition can be explained by a décollement level located in the Cambro-Ordovician succession. This level can be related to faults and D3 folds observed in the eastern part of the Pallaresa massif. Most of the structures can be explained in a contractional geological setting. In addition the relationships between the different Variscan structures of the eastern part of the Pallaresa massif are better described. The different models recently presented by some authors about the Variscan structure of the Pyrenees are discussed in the light of these new results.

Crystallographic Insights into the Autocatalytic Assembly Mechanism of a Bacteriophage Tail Spike

The tailed bacteriophage phi29 has 12 "appendages" (gene product 12, gp12) attached to its neck region that participate in host cell recognition and entry. In the cell, monomeric gp12 undergoes proteolytic processing that releases the C-terminal domain during assembly into trimers. We report here crystal structures of the protein before and after catalytic processing and show that the C-terminal domain of gp12 is an "autochaperone" that aids trimerization. We also show that autocleavage of the C-terminal domain is a posttrimerization event that is followed by a unique ATP-dependent release. The posttranslationally modified N-terminal part has three domains that function to attach the appendages to the phage, digest the cell wall teichoic acids, and bind irreversibly to the host, respectively. Structural and sequence comparisons suggest that some eukaryotic and bacterial viruses as well as bacterial adhesins might have a similar maturation mechanism as is performed by phi29 gp12 for Bacillus subtilis.

The Lüliang Massif: a key area for the understanding of the Palaeoproterozoic Trans-North China Belt, North China Craton

Abstract This paper documents the first detailed structural analysis of the Lüliang Massif in the Trans-North China Belt, North China Craton. A nappe, made up of a Terrigeneous and Mafic Unit (TMU) derived from an oceanic basin thrust over gneisses and volcanic-sedimentary rocks, is interpreted as a magmatic arc deposited upon a TTG basement. The nappe is rooted to the west in the Trans-North China Suture that separates the Fuping Block from the Western Block. Nappe stacking, coeval with a top-to-the-SE synmetamorphic D 1 event, is dated around 1890–1870 Ma using chemical U–Th/Pb EPMA datings on monazite and U–Pb LA-ICP-MS dating on zircon. A second D 2 ductile event, characterized by SE-verging folds, reworks the D 1 structures. D 2 is the first event recorded in the late-orogenic sedimentary series that unconformably covers the metamorphic units formed during D 1 . These lithological, structural and geochronological results are correlated with those described in the eastern massifs of Hengshan, Wutaishan and Fuping. The Trans-North China Belt resulted from the collision of the Fuping Block and the Western Block after a westward-directed subduction and subsequent closure of an oceanic basin where the TMU was deposited.

Structural and tectonic evolution of the Jabal Sumeini – Al Ain – Buraimi region, northern Oman and eastern United Arab Emirates

ABSTRACT Four main Late Cretaceous and Tertiary phases of crustal shortening and thrust-related deformation are recognised in the northern Oman Mountains, each phase ending with a regional unconformity throughout the Oman Mountains and the UAE foreland. The earliest is the major thrust emplacement of the Semail Ophiolite, and underlying Haybi, Hawasina and Sumeini duplexes from NE to SW onto the depressed northeastern continental margin of the Arabian Plate during the Cenomanian to Campanian-early Maastrichtian (D1). A prominent widespread unconformity that places Maastrichtian Qahlah Formation laterite, sandstones and conglomerates and Simsima Formation rudist - Acteonellid gastropod limestones over all underlying allochthonous units is recognised throughout the Oman Mountains. SW-verging folds and thrusts in Triassic to Cretaceous carbonate slope facies rocks exposed in Jabal Sumeini (Sumeini Group and Hamrat Duru Group) have been emplaced over uppermost Cretaceous Juweiza Formation conglomerates at the highest level of the Aruma foreland basin. These Sumeini D1 structures are abruptly truncated by an unconformity, above which are Middle Maastrichtian beds showing up to 95% ‘death assemblage’ rudists and gastropods just below the Cretaceous – Tertiary boundary (top of Simsima Formation). A second deformation event (D2) affected the Simsima Formation and underlying Sumeini Group, Hamrat Duru complex and Semail Ophiolite rocks. This phase shows gentle folding about NW-SE fold axes (e.g. Jabal Rawdah), along a similar trend to the Late Cretaceous D1 event. This trend is also parallel to a regional set of NW-SE aligned fractures in the UAE foreland. A major angular unconformity occurs beneath the Upper Palaeocene – Eocene shallow-marine limestones (Umm Er Radhuma, Rus and Dammam formations). Many foreland jabals in eastern Abu Dhabi (Jabals Qatar, Malaqet, Mundasa) show gentle post-Eocene folding formed during the third stage of crustal shortening (D3). The large pericline of Jabal Hafit is a double-plunging, east-verging box fold that formed after deposition of the Oligocene Asmari Formation limestones and Miocene Fars Formation gypsum and clays, the youngest beds affected by the fold. This Late Miocene – Pliocene phase of crustal shortening (D4) is the youngest phase of deformation in the eastern Al Ain-Buraimi region.

Assessing uncertainty in the integration of aeromagnetic data and structural observations in the Deering Hills region of the Musgrave Province

Integrated aeromagnetic and field-based structural analysis provides a method for establishing a constrained regional-scale tectonic model where insufficient outcrop, remoteness or restricted access precludes widespread structural mapping. In this method the different scales of observation lead to uncertainty in integrating the observations. An integrated analysis of the Deering Hills region of the Musgrave Province shows that this uncertainty is largely dependent on the magnetic data resolution, the scale of deformation, and mineralogy. In the Deering Hills, four deformation events are defined, each with different structural character. These differences in character result in different levels of uncertainty in integrating these observations with aeromagnetic data. D1 was only evident at small scales in outcrop, and therefore any correlation with aeromagnetic data is inherently uncertain. However, well-defined relative timing to D2, and the parallel nature of an S1 foliation and regional D1 structures identified in the aeromagnetic data permitted the derivation of a moderately reliable regional model indicating northwest to southeast directed shortening at a deep crustal level during the Musgravian Orogeny. This resulted in a pervasive gneissic foliation, and a regional array of northeast-trending reverse-shear zones and tight to isoclinal upright folds. A higher confidence regional model was derived for the second deformation event (D2), which was identified at the regional scale in outcrop and could be directly correlated with features in the aeromagnetic data. North–south-directed crustal shortening, either in the late Musgravian Orogeny or during deformation ca 1060 Ma resulting in east-southeast- and southeast-trending reverse- and dextral-reverse shear zones and southeast-trending recumbent isoclinal nappes. For the third and fourth deformation events, links could not be made between field observations and aeromagnetic data, and the regional models for these events are low in confidence. The regional setting of D3 is not defined, and D4 is interpreted to represent the development of shear zones during north–south compression in the Petermann Orogeny.

Geologic and Structural Setting of Gold Mineralization in the Kirkland Lake-Larder Lake Gold Belt, Ontario

The Kirkland Lake-Larder Lake gold belt includes the giant Kirkland Lake and world-class Kerr-Addison-Chesterville gold deposits, along with several smaller deposits and occurrences. It corresponds to an east-trending band of Timiskaming clastic and volcanic rocks that unconformably overlie older volcanic assemblages in the southern Abitibi greenstone belt of the Archean Superior province. The gold belt is bounded to the south by the Larder Lake-Cadillac deformation zone, which roughly follows the contact between the younger Timiskaming rocks and the older volcanic units. Three generations of fabrics formed during post-Timiskaming regional deformation (D2, D3, and D4) of the belt. North-south shortening during D2 produced a penetrative, generally east-striking, steeply dipping, S2 foliation, and an east-plunging, L2 stretching lineation. S2 is most intense within the syn-D2 Larder Lake-Cadillac deformation zone and its northeast-trending splay, the Upper Canada deformation zone. The D2 structures are overprinted by a north-trending crenulation cleavage S3, which formed during east-west D3 shortening across the belt. A northeast-trending regional S4 foliation associated with Z-shaped F4 folds and overprinting both S2 and S3 formed during northwest-southeast D4 shortening. Gold mineralization is localized along the Larder Lake-Cadillac deformation zone (Anoki and McBean deposits), the Upper Canada deformation zone (Upper Canada deposit), and the brittle Kirkland Lake fault and ‘04 Break (Kirkland Lake deposit). The Upper Canada, McBean, and Anoki deposits formed during D2, and, along with Kerr-Addison-Chesterville, Omega, and Cheminis deposits, are probably related to a regionally extensive hydrothermal system associated with the Larder Lake-Cadillac deformation zone. The sulfide-poor gold- and telluride-bearing quartz veins of the Kirkland Lake deposit are interpreted to have been emplaced during D4, synchronous with reverse-dextral movement along the ore-controlling brittle Kirkland Lake fault. The Kirkland Lake mineralization has a distinct metal signature (Te>Au, Mo, Pb, Ag, high Au/Ag, low As) and probably represents a separate hydrothermal system linked to a deep magmatic (alkalic) fluid source and unrelated to mineralization along the syn-D2 deformation zones.

Theoretical Characterization of the Lowest Triplet Excited States of the Tris-(1,4,5,8-tetraazaphenanthrene) Ruthenium Dication Complex

We present a theoretical study of the ground and the lowest triplet excited states of the tris-(1,4,5,8-tetraazaphenanthrene) ruthenium complex [Ru(tap)3]2+. Density functional theory (DFT) was used to obtain the relaxed geometries and emission energies (Delta-SCF), whereas time-dependent DFT (TD-DFT) was used to compute the absorption spectrum. Our calculations have revealed the presence of three low-lying excited-state minima, which may be relevant in the photophysical/photochemical properties of this complex. Two minima with similar energies correspond to the MLCT 3A2 and MLCT 3B metal-to-ligand charge-transfer states, the first one corresponding to a D3 structure, whereas the second is a slightly localized C2 species. The third and lowest one corresponds to the metal-centered MC 3A state and displays a pronounced C2 distortion. We have examined for the first time the localized character of the excitation in the computed MLCT states. In particular, we have evaluated the pseudorotation barrier between the Jahn-Teller C2 MLCT 3B minima in the moat around the D3 conical intersection. We have shown that the complex should be viewed as a delocalized [Ru3+(tap(-1/3))3]2+ complex in the lowest MLCT states, in agreement with subpicosecond interligand electron transfer observed by femtosecond transient absorption anisotropy study. Upper-bound estimates of the MLCT-->MC (3 kcal/mol) and MC-->MLCT (10 kcal/mol) activation energy barriers obtained from potential energy profiles in vacuum corroborate the high photoinstability of the MLCT states of the [Ru(tap)3]2+complex.

Crystal structure of archaeal tRNA(m1G37)methyltransferase aTrm5

Methylation of the N1 atom of guanosine at position 37 in tRNA, the position 3'-adjacent to the anticodon, generates the modified nucleoside m(1)G37. In archaea and eukaryotes, m(1)G37 synthesis is catalyzed by tRNA(m(1)G37)methyltransferase (archaeal or eukaryotic Trm5, a/eTrm5). Here we report the crystal structure of archaeal Trm5 (aTrm5) from Methanocaldococcus jannaschii (formerly known as Methanococcus jannaschii) in complex with the methyl donor analogue at 2.2 A resolution. The crystal structure revealed that the entire protein is composed of three structural domains, D1, D2, and D3. In the a/eTrm5 primary structures, D2 and D3 are highly conserved, while D1 is not conserved. The D3 structure is the Rossmann fold, which is the hallmark of the canonical class-I methyltransferases. The a/eTrm5-defining domain, D2, exhibits structural similarity to some class-I methyltransferases. In contrast, a DALI search with the D1 structure yielded no structural homologues. In the crystal structure, D3 contacts both D1 and D2. The residues involved in the D1:D3 interactions are not conserved, while those participating in the D2:D3 interactions are well conserved. D1 and D2 do not contact each other, and the linker between them is disordered. aTrm5 fragments corresponding to the D1 and D2-D3 regions were prepared in a soluble form. The NMR analysis of the D1 fragment revealed that D1 is well folded by itself, and it did not interact with either the D2-D3 fragment or the tRNA. The NMR analysis of the D2-D3 fragment revealed that it is well folded, independently of D1, and that it interacts with tRNA. Furthermore, the D2-D3 fragment was as active as the full-length enzyme for tRNA methylation. The positive charges on the surface of D2-D3 may be involved in tRNA binding. Therefore, these findings suggest that the interaction between D1 and D3 is not persistent, and that the D2-D3 region plays the major role in tRNA methylation.

Caracterização tectonoestrutural do Campo de Xaréu (Sub-Bacia de Mundaú, Bacia do Ceará -NE do Brasil): abordagem multiescala e pluriferramental

The Xaréu Oil Field, located in the centralsouthern portion of Mundaú Sub-Basin (eastern Ceará Basin), is characterized by an array of NW-trending and NE-dipping normal faults. Those faults constitute an extensional listric fan rooted along a detachment surface which corresponds to the Mundaú Fault, located at the southwestern border of Mundaú Sub-Basin. The main carbonatic unit in the oil field, the Trairí Member (Paracuru Formation, Early Aptian to Early Albian), contains the largest oil volume in the area, which is concentrated in structurally controlled accumulations. The structural analysis carried out by drill cores and image profiles studies of the Trairí Member identified two generations of meso- to microscale structures: (i) the earliest D1 structures partially present a typical hydroplastic character, characterized by bedding-parallel and oblique shear zones, besides late brittle structures; and (ii) the D2 structures present a typical brittle character, encompassing normal faults and recrystallized argillaceous slickenlines. Although the macrofaults observed in the Xaréu Oil Field (and, consequently, in the Mundaú Sub-Basin) are classically referred as dip-slip normal faults, the kinematic analysis of the D1 structures indicates that such faults are, actually, oblique-slip structures, presenting tectonic transport towards ENE. Those oblique movements might be the response to the onset of a transtractive context in the Mundaú Sub-Basin, which is, ultimately, the result of a strike-slip tectonics that took place during the origin of the Atlantic Equatorial Margin.

Grenville Front zone, Gagnon terrane, southwestern Labrador: Configuration of a midcrustal foreland fold‐thrust belt

Evolution of a metamorphic fold‐thrust belt in Archean and Proterozoic rocks in the Gagnon terrane, northwestern Grenville province, involved underthrusting beneath a crustal‐scale, orogenic wedge and metamorphism ranging from upper greenschist facies (∼600 ± 100 MPa/450 ± 50°C) to upper amphibolite facies (∼1100 ± 100 MPa/750 ± 50°C) during the terminal stages of the Grenvillian Orogeny. Structural and metamorphic data indicate that D1 structures formed at peak pressures during basal accretion to the overriding orogenic wedge, whereas D2 structures developed within the wedge during its displacement toward the foreland in a sinistral transpressive setting. The fold‐thrust belt developed sequentially on two levels: a thin‐skinned, cover‐dominated thrust system preceded and overlies a thick‐skinned, basement‐dominated system. The D3 cross‐folds postdated normal faulting at the top of the wedge and formed during gravitational collapse. On the basis of this study, characteristic features of midcrustal, metamorphic, thrust wedges include growth by basal accretion, polyphase ductile deformation and noncoaxial strain, dual‐level development, extensive basement involvement, and terminal gravitational collapse associated with cross‐folding.

Distinct Taconic, Salinic, and Acadian deformation along the Iapetus suture zone, Newfoundland Appalachians

Structural mapping in central Newfoundland has identified seven distinct phases of deformation (D1 to D7), the most significant of which are D1, D2, and D4. D1 involved the formation of a Middle and Late Ordovician south-southeast-directed thrust belt and concomitant development of mylonite and phyllonite. A Late Ordovician to Early Silurian D2 thrust and fold belt overprints D1 mylonitic deformation and is the most distinctive deformation event in the study area. Late Silurian to Devonian D4 is responsible for folds and north-northwest-directed dextral thrust and reverse faults that overprint D1 to D3 structures. D4 structures in central Newfoundland include the Exploits–Gander boundary. Subsequent deformation is generally of local significance only. The arc–back-arc complexes making up the various terranes in central Newfoundland are predominantly juxtaposed along D1 shear zones, which include the Red Indian Line. Our data indicate that terrane boundaries initiated during D1 may have protracted deformation histories spanning several deformation events. This has important implications for the interpretation of terrane boundaries in Newfoundland, as D1 terrane boundaries may be interpreted as D2 or D4 shear zones depending on the intensity of overprinting or reactivation. The deformation history proposed in this paper corresponds closely to that of established Appalachian orogenic cycles. D1 is correlated with the Ordovician Taconic orogeny and involved accretion of arc–back-arc complexes to the Laurentian margin. D2 and D4 are correlated with the Ordovician–Silurian Salinic and Silurian–Devonian Acadian orogenies, which involved the subsequent accretion of the Ganderia and Avalonia microcontinents to the Laurentian margin, respectively.

Köli nappes in the north-central Swedish Caledonides – new views on stratigraphy and structural evolution

The Köli Nappes of the Scandinavian Caledonides are composed of oceanic and island-arc terranes of Cambro–Silurian age and represent the upper part of the major Caledonian Upper Allochthon. Field, structural, microscopic, geophysical and geochemical data, together with a review of published information show new aspects on stratigraphy, structural evolution, nappe geometry and late Ordovician greywacke provenance in the Köli Nappes of southwestern Västerbotten and northern Jämtland counties, Sweden. It is proposed here to divide the lower part of the Köli succession of this area, i.e. the correlative of the Seima Formation, into three formations, the Kvemoen Mica Schist, the Ankarede Volcanite, and the Gilliks Formations. Trace element geochemistry of Ordovician Gilliks Formation greywackes indicates a provenance from a continental magmatic arc. New data also show that the overlying quartzite and limestone succession interpreted as the Vojtja and Slätdal Formations here is representing the top of the Stikke Nappe succession, which thus now reaches up into the highest Ordovician. The early repetition and inversion of the stratigraphy is an effect of D1-D2 deformation. The subsequent D3 episode comprises thrusting of, for example, the Middle Köli Nappe over the Lower Köli Nappe. A new aspect is that fault bends in D3 thrusts may give rise to fault-bend folds in overlying units, which are also D3 structures. The D3 episode also includes movement of the Köli units relative to the underlying Seve Nappes with top-to-the-west-directed shearing at the Seve-Köli boundary. It is succeeded by D4 regional-scale folds, related to nappe stacking in the underlying allochthons. The east-dipping limbs of these folds are thus locked for later, top-to-the-west shear deformation. Therefore, at least these parts of the Seve-Köli boundary cannot be regarded as re-activated during late (D5) and post-Caledonian gravitational deformation. Further work will have to show, whether the observed latest stage deformation represents late Caledonian tectonics or is related to subsequent extensional tectonics.

Intramolecular rearrangements of β-diketonates of metals. A non-emprical study of the structure of Y(MDA)3 and La(MDA)3 complexes

The structure of tris-complexes of yttrium and lanthanum with malonic dialdehyde (MDA = C3O2H3) is studied by a non-empirical Hartree-Fock method and also with taking into account the electron correlation by the second order Moller-Plesset perturbation theory using the effective pseudo-potentials to describe the atomic cores and two-exponent valence basis sets supplemented with polarization functions. Three most probable geometrical configurations of the D3, D3h, and C2 nuclei symmetry are considered for each molecule. The D3 structure corresponds to the minimum on the potential energy surface. The D3h and C2v configurations correspond to the transition states on the path of two most energetically favorable intramolecular rearrangements. Using the results of our previous calculations for the Sc(MDA)3 molecule, regularities in the change in molecular parameter values of the series Sc(MDA)3→Y(MDA)3→La(MDA)3 are analyzed. The theoretical and experimental structural and spectral data available in the literature are compared.

Late structural evolution in an accretionary wedge: insights from the Voltri Massif (Ligurian Alps, Italy)

The Voltri Massif underwent a polyphasic tectono-metamorphic evolution that records both the Alpine and part of the Apennine deformation events. So this is a key-area to investigate the relationships between Alpine and Apennine deformation events. This paper focus on the upper crustal deformations (UCD) that characterize the last stages of the tectonics of the Voltri Massif. In the Voltri Massif UCD are characterized by the superpositions of ductile, brittle-ductile and brittle structures that can be attributed to three main tectonic events (from D3 to D5). The oldest UCD event (D3) developed folds and reverse shear zones under ductile to brittle-ductile conditions. Main compressive NW-SE oriented regime characterized D3 event. Brittle-ductile to brittle reverse shear zones and important strike-slip/transpressive systems overprinted D3 structures. This D4 event was significant at the regional scale and occurred under main transpressive, NE-SW oriented, regime. The latest normal and transtensional brittle structures, that formed during UCD D5 event, locally reactivated the older structures.

The tectono-metamorphic evolution of the central part of the Neoproterozoic Allaqi–Heiani suture, south Eastern Desert of Egypt

The Precambrian basement of the Um El Tuyor area represents the central part of the ca. 750–720 Ma Allaqi–Heiani suture in the extreme south of the Egyptian Eastern Desert. It is composed of allochtonous ophiolitic thrust slices and detached sheets, island arc metavolcanic–volcanoclastic and metasedimentary assemblages, and syn- to post-orogenic granitoid intrusions. These rocks are collectively referred to as a fold-and-thrust belt in view of their deformational styles, and as ophiolites and their lithologic association are concerned. Structural analysis reveals three major deformation events, namely: (a) D1: an early thrust-and-fold system, through which overturned to recumbent folds and major thrusts were developed and later overprinted by a sinistral transpression, (b) D2: a NE–SW-compressional regime that deformed the D1 structures by major folds (F 2) and penetrative axial planar NW–SE foliations (S 2) and associated major NW–SE sinistral faults and shear zone, and (c) D3: a late ENE–WSW compressional strain increment expressed by a series of NNW–SSE striking folds and crenulations (F3). Related right-lateral NNW–SSE strike slip faults and discrete brittle–ductile shear zones indicate a later transcurrent shear which is best developed in the metasedimentary successions. Mineral associations and porphyroblast-matrix fabrics in the pelitic metasediments indicate three phases of regional metamorphism (M1 → M3), syn-kinematic with D1, D2 and D3 respectively. Based on the petrographic and microprobe data, the peak metamorphic conditions were attained at 534°–561 °C/5.26–6.20 kbar, under which garnet, staurolite and sillimanite coexisted during D2. Although associated with the most significant metamorphic event, D2 corresponds roughly to a late collisional stage (650–620 Ma) during which the accreted Pan-African terrains attached to the East Saharan Craton. This is further confirmed by the D2-related sinistral strike slip faults that affiliate to the ca. 630–540 Ma Najd strike slip fault system in the Arabian–Nubian Shield. Criteria including an anticipated fold–thrust vergence generally to northwesterly directions, discrete mesoscopic duplexes, shear bands, and minor folds and thrust zones all indicate that the ophiolites were emplaced roughly from northwest to southeast. However, deformation of the ophiolite basal contacts and associated fabrics argue that the northwestward rooting of the ophiolitic massif in the study area cannot be considered as a criterion for the original direction of tectonic transport, which was likely from north to south if the entire Allaqi–Heiani belt is considered. Such deviation is best attributed to rotation through deformation by the N–S Hamisana shear zone. This principally agrees with the tectonic evolution of the Arabian–Nubian Shield in south Egypt proposed previously, which includes an early N–S arc–arc collision followed by a stage of E–W crustal shortening.

Further Synthetic and Biological Studies on Vitamin D Hormone Antagonists Based on C24-Alkylation and C2α-Functionalization of 25-Dehydro-1α-hydroxyvitamin D3-26,23-lactones

An efficient synthesis and the biological evaluation of 80 novel analogs of 25-dehydro-1alpha-hydroxyvitamin D3-26,23S-lactone 2 (TEI-9647) and its 23R epimer (3) in which the lactone ring was systematically functionalized by introduction of a C1 to C4 primary alkyl group at the C24 position (5 sets of 4 diastereomers), together with their C2alpha-methyl, 3-hydroxypropyl, and 3-hydroxypropoxy-substituted derivatives were described. The triene structure of the vitamin D3 was constructed using palladium-catalyzed alkenylative cyclization of the A-ring precursor enyne with the CD-ring counterpart bromoolefin having the C24-alkylated lactone moiety on the side chain. The CD-ring precursors having 23,24-cis lactones were prepared by using a chromium-mediated syn-selective allylation-lactonization process, and the 23,24-trans lactone derivatives were derived from these via inversion of the C23 stereochemistry. The biological evaluation revealed that both binding affinity for chick vitamin D hormone receptor and antagonistic activity (inhibition of vitamin D hormone induced HL-60 cell differentiation) were affected by the orientation and chain-length of the primary alkyl group on the lactone ring. Furthermore, the C2alpha-functionalization of the C24-alkylated vitamin D3 lactones dramatically enhanced their biological activities. The most potent compound to emerge, (23S,24S)-2alpha-(3-hydroxypropoxy)-24-propyl exhibited almost 1000-fold stronger antagonistic activity (IC50=7.4 pM) than 2 (IC50=6.3 nM).

Multiple deformation episodes at Myra Falls volcanic-hosted massive sulfide camp, central Vancouver Island, British Columbia, Canada

A detailed deformation history for central Vancouver Island was determined at Myra Falls volcanic-hosted massive sulfide camp with early ductile deformation overprinted by several distinct episodes of brittle deformation. Brittle structures were subdivided into separate groups based on their morphology, geometry, kinematics, and crosscutting relations. The central location of this study provides a link between previous deformation studies in northern and southern Vancouver Island. Late Paleozoic northeast–southwest compression (D1) produced open upright folds with variably developed north-northwest-striking axial planar cleavage zones (S1) and subhorizontal stretching lineations (L1) subparallel to F1 fold axes. Renewed northeast–southwest compression during the collision of Wrangellia and North America produced a second foliation (S2) in localized shear zones, slightly oblique to the dominant S1 foliation. These two events are recorded throughout Vancouver Island wherever the basement is exposed. Mid-Cretaceous northeast–southwest compression during D3 produced early steep conjugate strike-slip faults (D3a), overprinted by northeast- and southwest-dipping thrust faults and bedding-parallel shears (D3b). D3 structures have been previously recognized in northern Vancouver Island but not as far south as Myra Falls. North–south extension (D4) produced east, north, and east–southeast-striking normal faults. These faults consistently crosscut earlier D1–D3 structures and reactivate steep D3a faults. Normal faulting is correlated with the development of the Upper Cretaceous Nanaimo Basin, but no faults of this age have previous been reported from onshore studies. The youngest structures at Myra Falls are large northwest-striking, northeast-dipping thrust faults and steep west- to west-northwest-striking sinistral strike-slip faults formed during the D5 event. These faults are gouge-rich, wavy anastomosing structures, with cleaved wall-rock zones up to several metres wide. The D5 faults are correlated with Eocene deformation caused by the accretion of the Pacific Rim and Crescent Terranes along the southwestern margin of Vancouver Island. Myra Falls is the northernmost location to have been reported, at which the structures formed as part of the Cowichan fold and thrust belt.

N-Glycosylation of Fibroblast Growth Factor Receptor 1 Regulates Ligand and Heparan Sulfate Co-receptor Binding

The regulation of cell function by fibroblast growth factors (FGF) occurs through a dual receptor system consisting of a receptor-tyrosine kinase, FGFR and the glycosaminoglycan heparan sulfate (HS). Mutations of some potential N-glycosylation sites in human fgfr lead to phenotypes characteristic of receptor overactivation. To establish how N-glycosylation may affect FGFR function, soluble- and membrane-bound recombinant receptors corresponding to the extracellular ligand binding domain of FGFR1-IIIc were produced in Chinese Hamster Ovary cells. Both forms of FGFR1-IIIc were observed to be heavily N-glycosylated and migrated on SDS-PAGE as a series of multiple bands between 50 and 75 kDa, whereas the deglycosylated receptors migrated at 32 kDa, corresponding to the expected molecular weight of the polypeptides. Optical biosensor and quartz crystal microbalance-dissipation binding assays show that the removal of the N-glycans from FGFR1-IIIc caused an increase in the binding of the receptor to FGF-2 and to heparin-derived oligosaccharides, a proxy for cellular HS. This effect is mediated by N-glycosylation reducing the association rate constant of the receptor for FGF-2 and heparin oligosaccharides. N-Glycans were analyzed by mass spectrometry, which demonstrates a predominance of bi- and tri-antennary core-fucosylated complex type structures carrying one, two, and/or three sialic acids. Modeling of such glycan structures on the receptor protein suggests that at least some may be strategically positioned to interfere with interactions of the receptor with FGF ligand and/or the HS co-receptor. Thus, the N-glycans of the receptor represent an additional pathway for the regulation of the activity of FGFs.

Polyorogenic deformation history recognized at very shallow structural levels: the case of the Antola Unit (Northern Apennine, Italy)

The Antola Unit is a Ligurian Unit occurring at the top of the nappe pile of the Northern Apennines (Italy). Structural analysis indicates that the Antola Unit has been involved in a complex polyphase deformation history developed at a shallow structural level. The successive deformation phases belong to both the Alpine and Apenninic orogenic cycles. Therefore the Antola Unit is a good example of a polyorogenic tectonic unit deformed at a very shallow structural level. The older part of the structural evolution is assigned to the Meso-Alpine tectonic stage and consists of two deformation phases (D1 and D2) characterized by opposite tectonic transport directions. The D1 and D2 structures were sealed by the middle Eocene-Miocene deposits of the Tertiary Piedmont Basin. The younger part of the deformation history instead can be referred to the Northern Apennines tectonics, and consists of two phases (D3 and D4) both involving the Tertiary Piedmont Basin succession. The structural data indicate that the D1 deformations developed in mostly unlithified rocks, and that these structures can be related to the westward emplacement of the Antola Unit in the Alpine orogenic wedge. The D2 phase is characterized by folds and low-angle extensional faults, and is referable to a gravity-driven deformation. Both the D3 and D4 phases, characterized by folds and thrusts, are due to the compressive regime related to the development of the Northern Apennines.

Structural Motif-Based Homology Modeling of CYP27A1 and Site-Directed Mutational Analyses Affecting Vitamin D Hydroxylation

Human CYP27A1 is a mitochondrial cytochrome P450, which is principally found in the liver and plays important roles in the biological activation of vitamin D3 and in the biosynthesis of bile acids. We have applied a systematic analysis of hydrogen bonding patterns in 11 prokaryotic and mammalian CYP crystal structures to construct a homology-based model of CYP27A1. Docking of vitamin D3 structures into the active site of this model identified potential substrate contact residues in the F-helix, the β-3 sheet, and the β-5 sheet. Site-directed mutagenesis and expression in COS-1 cells confirmed that these positions affect enzymatic activity, in some cases shifting metabolism of 1α-hydroxyvitamin D3 to favor 25- or 27-hydroxylation. The results suggest that conserved hydrophobic residues in the β-5 hairpin help define the shape of the substrate binding cavity and that this structure interacts with Phe-248 in the F-helix. Mutations directed toward the β-3a strand suggested a possible heme-binding interaction centered on Asn-403 and a structural role for substrate contact residues Thr-402 and Ser-404.