The Drosophila DmGluRA is required for social interaction and memory

Metabotropic glutamate receptors (mGluRs) have well-established roles in cognition and social behavior in mammals. Whether or not these roles have been conserved throughout evolution from invertebrate species is less clear. Mammals have eight mGluRs whereas Drosophila has a single DmGluRA, which has both Gi and Gq coupled signaling activity. We have utilized Drosophila to examine the role of DmGluRA in social behavior and various phases of memory. We have found that flies that are homozygous or heterozygous for loss of function mutations of DmGluRA have impaired social behavior in male Drosophila. Futhermore, flies that are heterozygous for loss of function mutations of DmGluRA have impaired learning during training, immediate-recall memory, short-term memory, and long-term memory as young adults. This work demonstrates a role for mGluR activity in both social behavior and memory in Drosophila

PDE-4 inhibition rescues aberrant synaptic plasticity in Drosophila and mouse models of fragile X syndrome.

Fragile X syndrome (FXS) is the leading cause of both intellectual disability and autism resulting from a single gene mutation. Previously, we characterized cognitive impairments and brain structural defects in a Drosophila model of FXS and demonstrated that these impairments were rescued by treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium. A well-documented biochemical defect observed in fly and mouse FXS models and FXS patients is low cAMP levels. cAMP levels can be regulated by mGluR signaling. Herein, we demonstrate PDE-4 inhibition as a therapeutic strategy to ameliorate memory impairments and brain structural defects in the Drosophila model of fragile X. Furthermore, we examine the effects of PDE-4 inhibition by pharmacologic treatment in the fragile X mouse model. We demonstrate that acute inhibition of PDE-4 by pharmacologic treatment in hippocampal slices rescues the enhanced mGluR-dependent LTD phenotype observed in FXS mice. Additionally, we find that chronic treatment of FXS model mice, in adulthood, also restores the level of mGluR-dependent LTD to that observed in wild-type animals. Translating the findings of successful pharmacologic intervention from the Drosophila model into the mouse model of FXS is an important advance, in that this identifies and validates PDE-4 inhibition as potential therapeutic intervention for the treatment of individuals afflicted with FXS

The Anatoki fault and structure of the adjacent Buller and Takaka terrane rocks, northwest Nelson, New Zealand

The Early Paleozoic rocks exposed in the northwest of the South Island, New Zealand, can be grouped into two terranes. An Ordovician deep water passive margin assemblage makes up the Buller terrane. A Cambrian arc assemblage and an Ordovician to Silurian mainly shallow water passive margin assemblage make up the Takaka terrane. The two terranes are cut by Late Paleozoic and Early Cretaceous plutonic rocks. The terrane boundary is the Anatoki Fault, which is a north-south striking, east dipping structure that steepens southwards. This thesis is a study of the movement history of the Anatoki Fault and a study of structures and microstructures in the flanking lithologies of the Buller and Takaka terranes. The study area is divided into seven areal domains, each containing structural evidence that can be related on an inter-domainal scale. In the study area, three major deformation events can be recognised in both the Buller and Takaka terrane rocks. Each consecutive deformation event recognised in one of the terranes has structures that can be matched in style, orientation, and timing of development with that in the adjacent terrane. D, is represented by upright to overturned towards the west, N-S trending, large scale folds with an axial planar slaty cleavage. D, structures are observed in all domains and relate to other N-S trending structures seen in both terranes. Based principally on constraints outside the study area, D, is thought to be Early-Middle Devonian in age. A well-developed foliation, which obliterates D, structures in close to the Anatoki Fault, represents D2• The foliation expresses a zone of non-coaxial ductile deformation observed in the north of the study area. Rb-Sr geochronology, and the relationship between the foliation and the adjacent ~lllMa Mt Olympus Pluton, suggest D2 formed in the Early Cretaceous (soon after ~ IllMa). D3 is represented mainly by mesoscale folds with an axial planar crenulation cleavage. D3 structures crenulate and refold both D, and D2 structures and are mid-Cretaceous in age. Two deformations are recognised in the Balloon Melange of the Takaka terrane. The first deformation is responsible for the melanging when the protolith was in an unlithified state. This deformation occurred in the Late Cambrian. The second deformation is expressed by a slaty fabric when the melange was lithified and is thought to be related to D,. The contact between the Balloon Melange and other units in the Takaka terrane is thought to be tectonic but locally intrusive. Most structures in Northwest Nelson can be correlated with D" D2, and D3 of the study area. However, some N-S trending folds in the Cambrian arc assemblage are thought to be older than D, and are here thought to relate to pre-D, Late Cambrian deformation recognised in the Balloon Melange. The Anatoki Fault records a complex history of both ductile and brittle movement, a history which differs in various segments of the fault. Thus, tectonites from central segments of the study area record ductile east over west reverse-slip associated with D" and represent an early stage in its movement history; D2 tectonites from the northernmost studied segment record Early Cretaceous ductile dextral-slip reactivation; tectonites from the southernmost segment records ductilelbrittle dextral normal-slip reactivation that postdates the intrusion of the ~137Ma Crow Granite. The post-137Ma movement, and brittle/ductile movement of unknown age recorded in the remaining segments, may be related to D2• The Anatoki Fault has also undergone Late Cenozoic brittle reactivation. A plate tectonic model is developed to explain the earlier structures of the study area and the general structure of Northwest Nelson. It is proposed that an accretionary wedge/fore-arc setting related to a Cambrian island arc subduction zone provides the environment in which pre-D, structures formed, and that in the Early-Middle Devonian, the two terranes amalgamated as a result of a convergent strike-slip plate boundary. Much of the Takaka terrane was truncated by the strike-slip movement which dominated the early stages of Devonian deformation whereas convergence related thin-skinned tectonics dominated the latter stages of deformation, and resulted in formation of the D, structures. In this model, the Central Belt of the Takaka terrane, which consists primarily of the Cambrian arc assemblage, is interpreted as an uplifted tectonic wedge in which the Anatoki Fault is a back-thrust. D2 and D3 relate to an extremely active and changing tectonic period of New Zealand in the Early to mid-Cretaceous. Twinning in ankerite porphyroblasts in D2 tectonites was examined to investigate the twin laws and their usefulness as a paleostress indicator. Results show that the twin laws are the same as those in dolomite and that twinning occurs at temperatures above ~250°C. Paleostress axes derived from the analysis provide evidence of microscale strain partitioning in which the porphyroblasts have accommodated a pure shear component. The c-axes preferred orientations in dynamically recrystallised calcite tectonites, from the Anatoki Fault zone, most closely resemble those produced in the grain-boundary migration regime of experimental studies. As such, the preferred orientations cannot be used to indicate shear-sense

Investigation of an Arthur Marble brecciated sheet, upper Takaka, northwest Nelson

A deeply eroded brecciated Arthur Marble sheet rests discordantly on late Tertiary sediments. The sheet extends as a "tongue" from the adjacent Pikikiruna fault controlled Scarp, Upper Takaka, Northwest Nelson. The sheet can be divided into a proximal and distal deposit (in relation to the Pikikiruna Scarp). The proximal deposit is a marble breccia with equidimensional clasts. The distal deposit is a relatively intact, bedded, and fractured marble invaded by numerous sheet-like breccia zones and breccia pockets. Closely spaced bedding planes and fractures are accentuated by open fissures, and often appear as a three dimensional jigsaw puzzle. The base of the sheet is characterised by fine marble breccia underlain by a thin continuous clay band. Clay-rich dikes intrude the overlying marble sheet. The parent material of the clay appears to be a carbonaceous mudstone associated with the Tertiary Waitui Sandstone. From observations in the field and comparison of similar deposits recorded elsewhere, it is inferred that the brecciated sheet represents a rapid mass-movement deposit. A hypothesis for the sheet's emplacement involves: failure of the Pikikiruna Scarp front principally along bedding planes; the detached slab initially slides, then transforms into a two layer composite flow upon interaction with water saturated Tertiary sediments. The volume of the initial brecciated deposit is estimated to be at least two and a half times more than the present volume, and covered much of the Upper Takaka valley. The suggested age of the emplacement event is late Pliocene or early Pleistocene

The Supergiant, High-Grade, Paleoproterozoic Metasedimentary Rock- and Shear Vein-Hosted Obuasi (Ashanti) Gold Deposit, Ghana, West Africa

Obuasi, with a total mineral resource plus past production of 70 Moz, is the largest gold deposit in West Africa, and one of the largest in the world. It is hosted by ~2135 Ma siliciclastic rocks of the Eburnean Kumasi Basin, which were obliquely shortened along an inverted boundary with the older Eoeburnean Ashanti belt to the east. Greenschist facies metamorphism was coeval with mineralization and related alteration at ~2095 Ma. The steeply dipping, ENE-plunging lodes extend over an 8-km strike length and to depths of >2.5 km. They include paragenetically complex gold-rich quartz veins surrounded by refractory auriferous arsenopyrite and closely associated carbonate-muscovite alteration halos in deformed carbonaceous phyllites and subordinate metaigneous host rocks. Gold and arsenic were initially precipitated during deformation-assisted interaction with reduced host rocks at ~350°C and 100 to 200 MPa. The mineralizing fluids were derived primarily from deeper, As-rich metasedimentary sources by basinal fluid expulsion and metamorphic devolatilization triggered by inversion and shortening, followed by transpression. Continued fluid injection during and after the metamorphic peak produced changes in gold fineness, sulfide assemblages, repeated dissolution (stylolites) and reprecipitation of mineralized veins, and a change from early deformed shear-related, sulfide-rich lodes to later quartz-rich lodes that plunge down or across the axes of younger transpressional folds. Channelized fluid flow due to reactivation of basin-edge transfer structures, and/or irregularly distributed gold source rocks, may explain the variation in gold endowment along the former basin boundary

Rapid Formation of Porphyry and Skarn Copper-Gold Mineralization in a Postsubduction Environment: Re-Os and U-Pb Geochronology of the Ok Tedi Mine, Papua New Guinea

The Ok Tedi copper-gold mine in Western Province, Papua New Guinea, is situated in the western part of the Ok Tedi Complex where monzodiorite to quartz monzonite intrusions are associated with porphyry- and skarn-style copper-gold mineralization. The Pleistocene age of the intrusive rocks and mineralization provides an opportunity to study the longevity of the magmatic and hydrothermal evolution at Ok Tedi through U-Pb dating of zircon and high-precision Re-Os dating of molybdenite. Six main phases of intrusive rocks can be recognized within the mine area, with the sequence of intrusion indicated by contact relationships. Each has been dated by the SHRIMP U-Pb technique with correction for Th-U disequilibrium based on the U and Th content of each sample. In order of intrusion from oldest to youngest these include: Sydney Monzodiorite (1.368 ± 0.045 Ma), Warsaw Monzodiorite (1.269 ± 0.039 Ma), Kalgoorlie Monzodiorite (1.261 ± 0.050 Ma), Ningi Quartz Monzonite Porphyry (QMP)(1.229 ± 0.051 Ma), Bonn Quartz Monzonite (1.219 ± 0.040 Ma), and Fubilan QMP (1.213 ± 0.049 Ma). The intrusions are alkaline, high K to shoshonitic rocks with high Sr/Y ratios typical of Cu-fertile arc magmas. Chondrite-normalized REE patterns have minor or no negative Eu anomalies and downward sloping to listric-shaped HREE patterns typical of arc magmas in which high water contents supress plagioclase fractionation in favor of an evolution by hornblende ± garnet ± titanite fractionation. Cu-Au mineralization at Ok Tedi can be divided into four main stages based on crosscutting relationships: (1) skarn-endoskarn and associated vein-style mineralization in the Darai Limestone, Ieru siltstone, and Sydney Monzodiorite; (2) porphyry-style veins and breccias within the Ningi QMP and older intrusions, and at Siltstone Ridge: (3) porphyry-style veins and breccias in the Fubilan QMP and older intrusions: and (4) skarn-style mineralization in the lower part of the Darai Limestone along the Taranaki thrust. High-precision Re-Os dating of molybdenite has enabled a chronology to be established for the first three stages. Molybdenite from a quartz-mushketovite-epidote-carbonate-pyrite-chalcopyrite-molybdenite vein in clinopyroxene- and garnet-altered Sydney Monzodiorite has an age of 1.3206 ± 0.0020 Ma, and this dates the formation of the Gold Coast and Berlin skarns. Molybdenite from a quartz-pyrite-chalcopyrite-molybdenite vein in the sericite-altered Sydney Monzodiorite yields an age of 1.3166 ± 0.0043 Ma, and a quartz-pyrite-chalcopyrite-molybdenite vein with K-feldspar alteration selvages hosted in Ieru siltstone beneath the Gold Coast skarn has an age of 1.3031 ± 0.0015 Ma. Samples of molybdenite from quartz-sulfide veins from Siltstone Ridge have ages of 1.2116 ± 0.0029 and 1.2078 ± 0.0031 Ma. Molybdenite from a quartz-K-feldspar-pyrite-molybdenite vein, which overprints propylitic alteration in the Sydney Monzodiorite, has an age of 1.2120 ± 0.0024 Ma. These samples date porphyry-style mineralization in and around the Ningi QMP and at Siltstone Ridge. A sample of molybdenite from the matrix of hydrothermal intrusive breccia in the Fubilan QMP has an age of 1.2146 ± 0.0020 Ma, similar to the age of the adjacent Siltstone Ridge mineralization, and is interpreted to have been mechanically incorporated into the breccia during its formation. Several samples have been dated from the Fubilan porphyry system, including molybdenite from the matrix of a hydrothermal intrusive breccia (1.1648 ± 0.0020 Ma) and three samples from veins which postdate the breccias: a vuggy quartz-sulfide vein (1.1532 ± 0.0027 Ma), chalcopyrite-pyrite-molybdenite vein (1.1446 ± 0.0028 Ma), and duplicate analyses of a molybdenite-only vein (1.1326 ± 0.0034 and 1.1297 ± 0.0026 Ma) in agreement at 2σ. Molybdenite from a quartz-K-feldspar-biotite-magnetite-pyrite-chalcopyrite-molybdenite vein in endoskarn-altered Sydney Monzodiorite (beneath the Gold Coast skarn) has an age of 1.1459 ± 0.0012 Ma, and a similar vein without magnetite hosted in Warsaw Monzodiorite has an age of 1.1438 ± 0.0042 Ma, both within error of the chalcopyrite-pyrite-molybdenite vein in Fubilan QMP. Intrusive rocks in the Ok Tedi mine were emplaced over a period of approximately 200,000 years, with Cu-Au mineralization formed in discrete episodes of much shorter duration. The Gold Coast skarn and associated porphyry-style veins in Sydney Monzodiorite and Ieru siltstone formed in 14,000 to 21,000 years (n = 3), the Siltstone Ridge porphyry system in 2,000 to 12,000 years (n = 4), and the Fubilan porphyry system in 31,000 to 40,000 years (n = 6). The Taranaki skarn has not been dated in the mine area due to a lack of molybdenite, but geologic relationships indicate it is younger than the Fubilan QMP

Remote sensing data types and techniques for lahar path detection: a case study at Mt Ruapehu, New Zealand

Mt Ruapehu is New Zealand's most active onshore volcano. In 2007, the volcano produced a large lahar following a break-out from the summit Crater Lake. Here, satellite and airborne remote sensing and image processing is used to extract the path of the lahar using ASTER and SPOT5 visible and near infra-red imagery, ALOS-PALSAR L-band synthetic aperture RADAR data, and airborne LiDAR. The results obtained from each of these datasets were compared to the lahar deposit manually digitized from aerial photography. SPOT5 imagery produced the most accurate map of the lahar deposit (77% correct), even though these data were acquired a year after the event. This is attributed to the spatial resolution of the data. The ALOS-PALSAR coherence mapping calculated from images acquired 2 months before and nine months after the lahar was not as accurate as that obtained using the optical imagery (43% correct), but this was still considered an important tool for acquiring data during cloudy periods. LiDAR topographic data, collected to constrain geomorphic changes caused by the lahar, was the least accurate in terms of mapping the lahar path (28% correct). No single technique was deemed to be the most accurate under all circumstances, and a combination of data types would produce the best results. By combining the satellite and LiDAR data, it was possible to accurately classify 92% of the lahar path

PDE-4 Inhibition Rescues Aberrant Synaptic Plasticity in Drosophila and Mouse Models of Fragile X Syndrome

Fragile X syndrome (FXS) is the leading cause of both intellectual disability and autism resulting from a single gene mutation. Previously, we characterized cognitive impairments and brain structural defects in a Drosophila model of FXS and demonstrated that these impairments were rescued by treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium. A well-documented biochemical defect observed in fly and mouse FXS models and FXS patients is low cAMP levels. cAMP levels can be regulated by mGluR signaling. Herein, we demonstrate PDE-4 inhibition as a therapeutic strategy to ameliorate memory impairments and brain structural defects in the Drosophila model of fragile X. Furthermore, we examine the effects of PDE-4 inhibition by pharmacologic treatment in the fragile X mouse model. We demonstrate that acute inhibition of PDE-4 by pharmacologic treatment in hippocampal slices rescues the enhanced mGluR-dependent LTD phenotype observed in FXS mice. Additionally, we find that chronic treatment of FXS model mice, in adulthood, also restores the level of mGluR-dependent LTD to that observed in wild-type animals. Translating the findings of successful pharmacologic intervention from the Drosophila model into the mouse model of FXS is an important advance, in that this identifies and validates PDE-4 inhibition as potential therapeutic intervention for the treatment of individuals afflicted with FXS