D1 Structures Research Articles

Structure of human phospholipase D3, a single-strand exonuclease associated with Alzheimer's disease.

Phospholipase D3 (PLD3) has emerged as an important 5'-exonuclease in charge of removing single-stranded DNA in lysosomes. Rare genetic variants of the gene encoding PLD3 have been implicated in late-onset Alzheimer's disease (AD). Ishii etal. have produced the soluble domain of human PLD3 with the aim of determining its three-dimensional structure using X-ray crystallography. The high-resolution structure (2.3 Å) provides new insights into the biochemical properties of the enzyme and paves the way to a deeper understanding of amino acid replacements affecting the stability and activity of the enzyme.

Late Paleozoic to Mesozoic tectonic evolution of the Qinling Orogenic Belt: Structural and geochronological constraints from the Devonian Liuling Group, eastern Qinling area, China

The Late Paleozoic to Mesozoic tectonic evolution of the Qinling Orogenic Belt is not fully understood. To address this, structural analysis and rutile U-Pb dating were performed on the Middle–Late Devonian Liuling Group located along the northern margin of the South Qinling Belt (SQB). Detailed structural analysis reveals that the Liuling Group experienced four main deformation events (D1–D4). Initial D1 deformation is characterized by intrafolial folds (F1) and a regional penetrative foliation (S1). Subsequent D2 is marked by SW-vergent asymmetric, overturned folds and related crenulation lineation (L2). D3 and D4 are represented by, respectively, nearly E-W trending open folds and NNE-SSW trending centimeter-scale kink folds, both of which slightly modify D1 and D2 structures. Taking into account published chronological data, we propose that D1 and D2 occurred at 363–349 Ma and 332–318 Ma, respectively, and were associated with NE-SW oriented shortening during continental subduction of the SQB. Our new rutile U-Pb ages of 243–240 Ma provide a lower age limit for D3 deformation, which was related to N-S oriented shortening triggered by continental collision between the South China Block (SCB) and SQB along the Mianlue Suture Zone (MLSZ). Finally, D4 deformation was associated with the far-field effects of Late Jurassic subduction of the Paleo-Pacific Plate, which generated a WNW-ESE oriented shortening. Our findings suggest that continental subduction of the SQB continued until the earliest Late Carboniferous. Subsequently, the northern margin of the SQB experienced a Triassic metamorphic overprint triggered by collision between the SCB and SQB.

Crystal structure of Alzheimer's disease phospholipase D3 provides a molecular basis for understanding its normal and pathological functions.

Human 5'-3' exonuclease PLD3, a member of the phospholipase D family of enzymes, has been validated as a therapeutic target for treating Alzheimer's disease. Here, we have determined the crystal structure of the luminal domain of the enzyme at 2.3 Å resolution, revealing a bilobal structure with a catalytic site located between the lobes. We then compared the structure with published crystal structures of other human PLD family members which revealed that a number of catalytic and lipid recognition residues, previously shown to be key for phospholipase activity, are not conserved or, are absent. This led us to test whether the enzyme is actually a phospholipase. We could not measure any phospholipase activity but the enzyme shows robust nuclease activity. Finally, we have mapped key single nucleotide polymorphisms onto the structure which reveals plausible reasons as to why they have an impact on Alzheimer's disease.

Gold concentration during polyphase deformation: Insights from Boulanger Project, French Guiana

The Boulanger gold deposit is hosted within the Rhyacian greenstone belts from the Guiana shield located within the North Guiana Through, French Guiana. The Boulanger deposit is characterized by a complex polyphase deformation and mineralization history involving a coaxial shortening phase, D1, followed by a transcurrent deformation event, D2. The main ore bodies consist of a series of quartz-tourmaline-pyrite-carbonate extension and shear veins in response to NNE-SSW shortening event (D1), and adjacent altered host-rocks. The proximal alteration bordering the vein system is characterized by pyrite-tourmaline (main ore assemblage). This shortening event is followed by transcurrent deformation, D2. Locally, D2 is expressed by the formation of N020-030 narrow zones (F2 axial trace) along which D1 structures are reoriented. The structural analysis performed on both S1/0 foliation and on geophysical data interpretation highlights the presence of Type-1 interference patterns. These zones are associated with significant gold enrichment and the presence of a new ore assemblage dominated by pyrrhotite-pyrite. Quantitative structural analysis approach, based on measured foliations (S1/0) and gold grade demonstrates that D2-related folding is associated with important gold endowment. These findings suggest that the characterization of the exact fold interference pattern is fundamental for the targeting of favorable enriched zones at the deposit scale.

Quaternary functional semiconductor devices

Al/(Zn:Cd:Ni:TiO2)/p-Si diodes with (4:2:2:2), (5:2:2:1) and (6:4:4:0) ratios were named as D1, D2, D3, and Al/(CdO:ZnO:NiO:Ti)/p-Si diodes with of (4:2:2:2), (5:2:2:1) and (6:4:4:0) ratios were named as D4, D5 and D6, respectively. The functional interlayer was deposited via sol-gel spin coating method to develop new diodes/structures. Whereas the Ln(I)–V plot shows two linear sections for D1, D2, D3, and D5 structures, D2 and D6 revealed only one linear section in the forward-bias voltages. Therefore, D1, D2, D3, and D5 structures were found to exhibit two-exponential or two-parallel diode behavior in literature. The main electric parameters such as zero-bias barrier height, BH, (Φbo), ideality factor (n), reverse saturation-current (Is or Io)), rectification ratio at ±4.5 V, series resistance (Rs) and shunt resistance (Rsh) were extracted from the current-voltage (I-V) measurements. The number of surface sates (Nss) and their energy distribution were obtained using forward-bias I-V data by considering the voltage dependence of n and Φbo for each diode. The capacitance/conductance-voltage (C/G–V) plots at 1 MHz were used for extracting some of the other basic electrical parameters. The comparison of all the experimental results suggests that D1 and D3 structures have good performance in terms of lower leakage current, Nss and higher RR and so could be successfully used instead of conventional metal/insulator/semiconductor (MIS) structures.

Structural Evolution, Exhumation Rates, and Rheology of the European Crust During Alpine Collision: Constraints From the Rotondo Granite—Gotthard Nappe

AbstractThe rheology of crystalline units controls the large‐scale deformation geometry and dynamics of collisional orogens. Defining a time‐constrained rheological evolution of such units may help unravel the details of collisional dynamics. Here, we integrate field analysis, pseudosection calculations and in situ garnet U–Pb and mica Rb–Sr geochronology to define the structural and rheological evolution of the Rotondo granite (Gotthard nappe, Central Alps). We identify a sequence of four (D1–D4) deformation stages. Pre‐collisional D1 brittle faults developed before Alpine peak metamorphism, which occurred at 34–20 Ma (U–Pb garnet ages) at 590 ± 25°C and 0.9 ± 0.1 GPa. The reactivation of D1 structures controlled the rheological evolution, from D2 reverse mylonitic shearing at amphibolite facies (520 ± 40°C and 0.8 ± 0.1 GPa) at 18–20 Ma (white mica Rb–Sr ages), to strike‐slip, brittle‐ductile shearing at greenschist‐facies D3 (395 ± 25°C and 0.4 ± 0.1 GPa) at 14–15 Ma (white mica and biotite Rb–Sr ages), and then to D4 strike‐slip faulting at shallow conditions. Although highly misoriented for the Alpine collisional stress orientation, D1 brittle structures controlled the localization of D2 ductile mylonites accommodating fast (∼3 mm/yr) exhumation rates due to their weak shear strength (<10 MPa). This structural and rheological evolution is common across External Crystalline Massifs (e.g., Aar, Mont Blanc), suggesting that the European upper crust was extremely weak during Alpine collision, its strength controlled by weak ductile shear zones localized on pre‐collisional deformation structures, that in turn controlled localized exhumation at the scale of the orogen.

Multiscalar 3D temporal structural characterisation of Smøla island, mid-Norwegian passive margin: an analogue for unravelling the tectonic history of offshore basement highs

Abstract. Smøla island, situated within the mid-Norwegian passive margin, contains crystalline-basement-hosted intricate fracture and fault arrays formed during a polyphase brittle tectonic evolution. Its detailed study may strengthen correlation attempts between the well-exposed onshore domain and the inaccessible offshore domain, further the understanding of the passive margin evolution, and provide useful constraints on petrophysical properties of fractured basement blocks. A combination of geophysical and remote sensing lineament analysis, field mapping, high-resolution drill hole logging, 3D modelling, petrographic and microstructural studies, and fault gouge K–Ar geochronology made it possible to define five deformation episodes (D1 to D5). These episodes occurred between the post-Caledonian evolution of the regional-scale Møre–Trøndelag Fault Complex (MTFC) and the Late Cretaceous and younger crustal extension preceding the final stages of Greenland–Norway break-up. Each reconstructed deformation stage is associated with different structural features, fault and fracture geometries, and kinematic patterns. Synkinematic mineralisations evolved progressively from epidote–prehnite, sericite–chlorite–calcite, chlorite–hematite, hematite–zeolite–calcite, to quartz–calcite. K–Ar geochronology constrains brittle deformation to discrete localisation events spanning from the Carboniferous to the Late Cretaceous. Multiscalar geometrical modelling at scales of 100, 10, and 1 m helps constrain the extent and size of the deformation zones of each deformation episode, with D2 structures exhibiting the greatest strike continuity and D1 features the most localised. Overall, the approach highlighted here is of great utility for unravelling complex brittle tectonic histories within basement volumes. It is also a prerequisite to constrain the dynamic evolution of the petrophysical properties of basement blocks.

2730–2670 Ma rifting triggers sagduction prior to the onset of orogenesis at ca 2650 Ma: implications for gold mineralisation, Eastern Goldfields, Western Australia

The dominant structural fabric in the Eastern Goldfields is the steep north- to north-northwest-trending S2 foliation that is axial planar to upright F2 folds, developed during intense horizontal east–west shortening (D2–4 event). These structures consistently overprint D1 structures, which comprise layer-parallel S1 foliation, extensional shears, thrusts and recumbent F1 folds. The D1 event represents a separate and distinct episode of deformation with a markedly different stress regime (dominant vertical σ1), compared with the stress regime during the D2–4 events (horizontal east–west oriented σ1). There is little evidence for pre-2670 Ma ductile deformation in the Eastern Goldfields, as: (1) the ca 2730–2670 Ma greenstone sequences are deposited conformably on the older ca 2800 Ma greenstone sequences, with the first significant angular unconformities observed at the base of the post greenstone late basins; (2) a lack of schist or gneiss clasts in the late basins suggests that the surrounding uplifted sequence was largely undeformed; (3) the layer-parallel S1 foliation is observed throughout the 2720–2670 Ma greenstone sequence; and (4) the dominant low north- and south-plunges of F2 folds suggest that the sequence was predominantly flat-lying prior to strong east–west shortening (D2–4 events). The ca 2670–2655 Ma D1 event represents a period of sagduction that occurred immediately after cessation of rifting as a result of gravitational instability from deposition of dense, cold, greenstone sequences onto thinned, light, hot felsic crust. Late basins represent depocentres on the sinking greenstones during sagduction. Marked contrasts in the structural style of gold deposits, metallogeny and fluid sources, typically attributed to progressive deformation during orogenesis, could instead reflect temporally distinct mineralising events during changing tectonic regimes. In the East Yilgarn, an early plumbing system dominated by north-northwest-trending basin-controlling structures was likely established during rifting and focused fluids during multiple hydrothermal circulation events.

Investigation of dielectric and electric modulus properties of Al/p-Si structures with pure, 3%, and 5% (graphene:PVA) by impedance spectroscopy

The Z–V measurements were performed in wide-range voltage (± 6 V), and then the real/imaginary parts of ε* (ε′, ε″), M* (M′, M″), Z* (Z′, Z″), tanδ, and σac values of the Al/p-Si structure with pure polyvinyl alcohol (PVA) (D1), 3% (D2), and 5% (D3) graphene-doped PVA interfacial-layer were calculated at four frequencies (1, 10, 100, and 1000 kHz). When the frequency in D2 and D3 structures was increased from 1 kHz to 1 MHz, the dielectric constant value changed from 32.47 to 5.12 and from 26.26 to 1.00, respectively. They have a strong frequency dependence due to the presence of interface traps (Nit), polarization types, and organic interlayers at low frequencies. The observed anomalous peak in the ε′ and ε″ versus voltage curves in the depletion zone is the result of re-structure/re-ordering molecules in these traps under voltage/electric-field, and Nit measured frequency (f = 1/T). As a result, the ε′ and ε″ will be given an excess value to their real-value at lower frequencies. Because Nit and dipoles do not have enough time to spin themselves in the direction of the electric field and follow the ac signal at high frequencies, they cannot contribute the true value of them. In general, series resistance (Rs) and the interfacial layer are effective in the accumulation zone, while Nit is effective in the depletion region. These findings demonstrate that pure and (Gr:PVA) polymer-films at the M/S interface can be employed successfully in place of standard oxide materials. According to the comparison of dielectric constants, electrical modulus, impedance, and ac conductivity of all three structures at 100 kHz and 1 MHz frequencies, 3% Gr doping to PVA increases interfacial characteristics.

Kinematic and tectonic implications of crenulation cleavage, kink bands, and mesoscopic folds in the Baraboo Syncline, Wisconsin (∼1.45 Ga Picuris Orogen)

The Baraboo Syncline of Wisconsin is a south-verging, regional-scale fold that formed during the ∼1.45 Ga Picuris Orogeny. It involves Mesoproterozoic quartzite and phyllite of the Baraboo Quartzite. Phyllite layers preserve two deformational assemblages. D1 includes the regional-scale flexural-slip to flexural-flow syncline and associated mesoscopic parasitic folds. It also includes spaced cleavage in quartzite layers and north-dipping phyllitic cleavage in phyllite layers. On the gently north-dipping south limb of the regional syncline, parasitic folds verge south (out-of-the-hinge). On this limb, D2 includes north-verging monoclinal kink bands as well as south-dipping asymmetric crenulation cleavage; kink bands have not been found on the north limb. Crenulation growth micro-folded phyllitic cleavage domains into asymmetric sigmoids that are shaped like an ‘S' on the Baraboo Syncline's south limb and like a ‘Z' on the fold's north limb (as viewed looking east). The origin of D2 structures has long been controversial. Some authors attribute them to a post-syncline phase of extensional tectonism on north-dipping shear zones, whereas others consider them to be a consequence of progressive crustal shortening that continued after D1 fabrics had developed. Our structural analysis supports the second hypothesis and therefore implies that the manifestation of the Picuris Orogeny in southern Wisconsin did not include a post-syncline extensional phase. This interpretation is compatible with a tectonic model in which the Baraboo Syncline formed during inversion of a rift or pull-apart basin during north-south crustal shortening. Specifically, we found no north-dipping normal-sense shear zones, and we demonstrate that the kink bands and asymmetric crenulation of the south limb accommodated a component of north-south shortening in the plane of phyllitic cleavage. Published analog models show that the north-verging kink bands of the south limb could have developed in the same deformation regime as did south-verging parasitic folds. The geometry of crenulation in the north limb indicates that it could be an extensional crenulation accommodating stretching of the limb once it was steep. Late-stage flattening at a high angle to bedding on the south limb locally rotated the crenulation cleavage domains to a sub-horizontal dip. Outcrops in the Baraboo Syncline emphasize that asymmetric crenulation is a fungible fabric, in that examples with similar appearance can accommodate different strains and displacements depending on local context.

Pacific-Gondwana Permo-Triassic Orogenic Belt with Lesser Overprinted Cenozoic Deformation, Eastern Bird Head Peninsula, West Papua, Indonesia

The Paleozoic to Early Mesozoic Pacific-facing active margin of East Gondwana has been shown to extend into the Kemum Block of northern Bird Head Peninsula (western New Guinea), and was associated with Mid Paleozoic orogenic deformation and Devonian to Triassic silicic magmatism and foreland basin deposition. In the Mawi Bay area of the eastern Bird Head Peninsula, the (?) Permian Mawi Complex is a multiply-deformed unit with a pre-Late Triassic D1 deformation formed in an Andean back-arc setting associated with active margin tectonism. The D1 deformation is characterized by recumbent, isoclinal to tight, north-northeast facing folds with an axial planar S1 cleavage formed at a low metamorphic grade, and predated the unconformably overlying Upper Triassic - Middle Jurassic Tipuma Formation. South of the Mawi Complex, the Mesozoic-Paleogene succession of the northern Lengguru Fold Belt is affected by north-northwest trending folds, cleavage, and most of the succession dips moderately to gently to the west-southwest. This deformation is reflected in the underlying Mawi Complex by northwest-trending D2 structures that have folded the D1 folds, and have steeply inclined open to gentle folds, some polyclinal folds, and fault-related folds. The structures in the northern Lengguru Fold Belt may have influenced The Pliocene to Quaternary Central Bird Head Monocline associated with the Kemum Block uplifting in the northern Bird Head Peninsula

40Ar/39Ar dates controlled by white mica deformation and strain localization: Insights from comparing in situ laser ablation and single‐grain fusion techniques

AbstractIn situ laser ablation and single‐grain fusion 40Ar/39Ar geochronological techniques were directly compared using white mica from nine metasedimentary rocks from the Vaimok Lens of the Seve Nappe Complex (SNC) in the Scandinavian Caledonides. Seven of the rocks are from the eclogite‐bearing Grapesvare nappe within the lens that is defined by D2 structures (S2 and F2), which were formed during exhumation following late Cambrian/Early Ordovician ultra‐high pressure metamorphism. Two other rocks were obtained from ‘Scandian’ shear zones that delimit the nappes within the lens. The shear zones were active during terminal collision of Baltica and Laurentia in the Silurian to Devonian. The rocks exhibit variable deformation intensities and degrees of strain localization, expressed in particular by white mica. The in situ laser ablation and single‐grain fusion 40Ar/39Ar dates both span from the late Cambrian to Middle Devonian. Results of both techniques generally show decreasing dates with increasing bulk deformation intensity and successive structural generations (i.e., D2 then Scandian structures). Furthermore, several discrepancies are evident when comparing the results of the two techniques for the same rocks, indicating the 40Ar/39Ar dates are not solely governed by bulk deformation intensities and structural generations. Instead, the discrepancies demonstrate the additional influence of white mica strain localization, which is illuminated by the different analytical volumes of the techniques. Thus, the 40Ar/39Ar datasets are altogether deciphered as a function of bulk deformation intensity and degree of strain localization that affected the overall white mica volume. The former controls the gross 40Ar loss from the overall volume and the latter dictates the variability of 40Ar loss within the volume. Exploiting the interplay of these two phenomena for the Vaimok Lens rocks with in situ laser ablation allows for the broad span of 40Ar/39Ar dates to be contextualized into a sequence of tectonic events: (1) cooling at 474 ± 3 Ma, (2) pre‐collision deformation at 447 ± 2 Ma and (3) activation of crustal‐scale shear zones in the SNC related to continental collision at 431 ± 3 Ma and 411 ± 3 Ma.

Intraplate records of a transform margin formation: Brittle deformation in the basement of the basins from the northeastern extremity of the Brazilian equatorial margin

The diachronous rifting of the Pangea supercontinent, with the dispersion of the continental masses, resulted in the formation of numerous rift systems, which primarily evolved into passive margins, such as the Brazilian Equatorial Margin (BEM). In the South American counterpart, basement structures serve as the primary markers for direct analysis of the nucleation and development of the BEM since much of the rift record occurs in the subsurface. The geodynamic models that explain the evolution of this margin are largely based on geophysical and numerical modeling data. In this paper, we carried out an onshore, multitool, and multiscale structural analysis of the brittle deformation overprinted on the Precambrian basement of the Potiguar and Ceará basins, which led to the proposition of four superimposed events. The D1 event (Late-Brasiliano) is mainly represented by the NE-SW (dextral) stepped fracture systems and the unfilled and quartz- or chalcedony-filled NE-SW to E-W-trending extensional joints. This event is related to NE-SW intraplate transpression, associated with the progressive exhumation of the Brasiliano-Pan African orogenic belt. The D2 event (Jurassic to early Aptian) represents the intracontinental deformation related to the initial rupture of the Pangea. The brasiliano-age ductile shear zones were reactivated (brittle) along with the development of NE-SW normal faults, NNE-SSW en échelon fractures, NE-SW joints, as well as the emplacement of the basic dykes (NE-SW and E-W) related to the Rio Ceará-Mirim magmatism. This event is associated with the NW-SE extension responsible for the origin of the Cariri-Potiguar trend basins. At the beginning of the installation of the equatorial proto-margin, a significant cataclastic process took place, marking the D3 event (post-early Aptian). This enabled the nucleation of hybrid (WNW-ESE, E-W, and NW-SE), shear fractures (WNW-ESE, NNW-SSE, E-W, NNE-SSW, and ENE-WSW), and NW-SE unfilled or filled (chalcedony, iron oxide and hydroxide, and calcite) dilatational joints, which express an E-W dextral transtensional regime related to this event. E-W and NW-SE pull-apart dilatational jogs are characteristic of this event and may be analog to the E-W Messejana and Jacaúna transtensional grabens (western part of the Potiguar Basin). The younger event (D4) is characterized by N–S normal faults and joints, and dry or filled (calcite and iron oxide/hydroxide) NNW-SSE hybrid shear fractures. A clockwise rotation of the South American plate with respect to the African plate and the paleostress field change to N–S compression and E-W extension, are responsible for the formation of D4 structures. The brittle structures developed in the crystalline basement of the Potiguar and Ceará basins represent the intracontinental record of the deformation related to the formation of the Atlantic equatorial margin under a dextral transtensional regime.

Paleozoic Gondwanan structure along the Maule river valley between Toconey and Constitución (35.4°S, Chilean Pacific Coast)

During the late Carboniferous–middle Permian, the basement of the Chilean Coastal Cordillera was deformed by the Gondwanan Orogeny, developed by the subduction of the Paleo-Pacific plate under Gondwana from the early Carboniferous. In the Maule sector (35.4°S), the following metamorphic rock units are distinguished: (i) Western Series, formed by metapelites, metabasites, metacherts, metaconglomerates, and marbles, mixed in a subduction channel, with probably ages between the Cambrian and the Carboniferous; (ii) Eastern Series, consisting of metasediments of a fore-arc basin, Carboniferous in age. In the Eastern Series two units are recognized in terms of lithology and deformation style: the Eastern Pelitic Series and the Eastern Sandy Series. Three Gondwanan deformation episodes have been distinguished, affecting both series unequaly. In the Western Series, D1 structures consist of a foliation (S1) developed under high-pressure and low-temperature conditions, while in the Eastern Series it comprise tight east-verging folds, with the associated S1 developed under low PT metamorphic conditions (greenschist facies). D2 structures are only present in the Western Series and Eastern Pelitic Series and represent the exhumation of the accretionary prism and its emplacement to the east over the fore-arc basin, with the development of east-verging recumbent folds and a thick shear-zone. Difficulties in the propagation of the deformation by the presence of the Coastal Batholith to the east led to the development of the D3 deformation event, only well developed in the Eastern Sandy Series, and represented by the Los Tablones Back-thrust and associated folds, as well as N–S open right folds formed under low PT metamorphic conditions.

Structural Study of the Precambrian Basement of Kaele (Far North Cameroon): Contribution of Remote Sensing (Application of Landsat 8 OLI/TIRS Images) and Field Data

The Kaele is located in the northern domain of the Pan-African fold belt of Central Africa in Cameroon, north of Mayo- Kébbi domain. The structural study carried out in this area is based on Landsat 8 OLI/ TIRS image processing techniques and traditional geological prospection methods. The objective is to evaluate the contribution of landsat 8 OLI/TIRS image processing and field data in the structural mapping of the Kaélé region. The application of the 7×7 directional filters of the Sobel type in the N-S, E-W, NE-SW and NW-SE directions, to the ETM+3 channels gives better results. The rose diagram of the lineament map (obtained from image processing) shows a major E-W direction (N100E) and a secondary direction N-S (N10E). The studied area is affected by a polyphase deformation D1 to D4. The first phase of deformation (D1) is tangential and has set up the sub-horizontal dipping S1 schistosity which bears a composite L1 lineation (stretching, mineral). The D2 phase is constrictional and responsible for the establishment of the subvertical S2 axial plane foliation of the P2 folds, carrying the composite L2 lineation (stretching, mineral) and the B2 boudinage. The dextral-moving C2 shear cuts the S1 foliation, the P2 folds are asymmetrical isopach and anisopach. The third phase D3 is a constriction and set up the S3 schistosity which appears in syn -tectonic granite and highlight the C3 shear planes. The C3 shear is dextral and the P3 folds are isopach, anisopach, intrafolial and sheath fold. The last phase of deformation D4 is brittle and has set up faults and joints. There exist similarities between orientation of lineament from image processing and direction of D2, D3 and D4 deformational phases structures.

Highly potent, naturally acquired human monoclonal antibodies against Pfs48/45 block Plasmodium falciparum transmission to mosquitoes

Malaria transmission-blocking vaccines (TBVs) aim to induce antibodies that interrupt malaria parasite development in the mosquito, thereby blocking onward transmission, and provide a much-needed tool for malaria control and elimination. The parasite surface protein Pfs48/45 is a leading TBV candidate. Here, we isolated and characterized a panel of 81 human Pfs48/45-specific monoclonal antibodies (mAbs) from donors naturally exposed to Plasmodium parasites. Genetically diverse mAbs against each of the three domains (D1-D3) of Pfs48/45 were identified. The most potent mAbs targeted D1 and D3 and achieved >80% transmission-reducing activity in standard membrane-feeding assays, at 10 and 2μg/mL, respectively. Co-crystal structures of D3 in complex with four different mAbs delineated two conserved protective epitopes. Altogether, these Pfs48/45-specific human mAbs provide important insight into protective and non-protective epitopes that can further our understanding of transmission and inform the design of refined malaria transmission-blocking vaccine candidates.

The atypical Gaoligong orocline: Its geodynamic origin and evolution

Various orocline systems around the India–Eurasia collision zone have long been recognized and studied. Different portions of the India–Eurasia boundaries represent various scales and models of orocline-forming processes, such as the Baluchistan orocline formed by multiple deformation events and the Himalayan orocline formed by a mixture of complex structural mechanisms. The curvature from the eastern Himalayan syntaxis through east Burma to west Yunnan showed a unique convex curvature toward the mantle wedge. This is different from the concave Baluchistan orocline and the Himalayan orocline. The unique geometry of the Gaoligong orocline shows an N-S trend for the northern section and a NE-SW trend for the southern section. This curvature also marks the boundary between the Tengchong and Baoshan blocks along the Santaishan suture in western Yunnan, China. Our structural reconstruction identified five deformation events: 1) D1 is km-scale upright folding, which only affected the Neoproterozoic meta-sedimentary unit, 2) D2 recumbent folding, which only developed in the southern section of the Gaoligong orocline, 3) D3 large-scale gently westward-inclined thrust folding, 4) D4 right-lateral shear belt, and 5) the D5 normal faults. Since the D3 structure is the earliest event that shows penetrative foliation development along the orocline, we consider D1 and D2 as pre-orocline-forming events. The geometry of the Gaoligong orocline is controlled by the distribution of the Ordovician basement between the Tengchong and Baoshan blocks. Both north and south sections experienced the same structural evolution since D3 (a fault-propagation fold system occurred between 40 Ma and 28 Ma), D4 (steep right-lateral shear belt occurred between 28 Ma and 15 Ma), and D5 (normal faults after 15 Ma). The curvature first developed as a shovel-like top-to-the-NE thrust plane (S3) that formed under amphibolite-facies conditions between 40 Ma and 28 Ma. The following deformation events (D4 and D5) show orocline parallel foliation development under lower metamorphic conditions, indicating that the curvature of the Gaoligong orocline is not generated by additional rotation along multiple deformation events. However, due to the lack of orocline parallel foliation development for S3, and the lack of a proper position of the indenter, the Gaoligong orocline cannot be classified as a primary orocline nor a rotational orocline. The curved geometry is an interference pattern of topography relief to the shovel-like thrust plane that developed during D3. Our new reconstructed structural evolution concludes that the Gaoligong orocline is an “atypical” orocline.

Polyphase deformation-controlled giant Renli Nb–Ta deposit, South China: Constraints from systematic structural analysis

The Early Cretaceous Renli Nb–Ta deposit was recently discovered near the southern margin of the Late Jurassic–Early Cretaceous Mufushan composite granitic batholith, central Jiangnan Orogenic Belt, and represents the largest known rare metal deposit in South China. Substantial breakthroughs have been made in prospecting the pegmatite-dike-type of Nb–Ta mineralization in the deposit, especially from the perspective of geochemical exploration. However, there is still a lack of systematic structural studies in this area which has seriously hindered the in-depth understanding of the emplacement of pegmatite dikes and the distribution patterns of Nb–Ta ore bodies. In order to shed new light on this key issue, this study presents new and detailed structural data from the Mufushan region. The results indicate that the Renli and adjacent areas have experienced several deformational events, including D1 Neoproterozoic NE–SW contraction and upright-folding, D2 latest Late Jurassic to Early Cretaceous regional extension accompanied by granitic magma intrusion, and D3 Early Cretaceous brittle normal faulting and fracturing with granitic magma emplacement and Nb–Ta mineralization. The D1 event, corresponding to the Jiangnan Orogeny, formed regional-scale NW–SE-striking upright folds with ubiquitous subvertical S1 cleavages and subhorizontal L1 crenulation lineations. The D2 event represented orogenic exhumation and produced a domal structure cored primarily by gneissic/mylonitic rocks and granites and mantled by schists, which dominated the bulk structural architecture of the Mufushan area. This was followed by the D3 event which controlled the formation of numerous extension fractures in the study area. The Nb–Ta-bearing magmatic-hydrothermal fluids migrated along the pre-existing D2 shear zone and subsequently filled in the widespread D3 extension fractures to form pegmatite dikes. The D2 to D3 phases can be considered as a progressive exhumation event from plastic to brittle regimes. The D2 and D3 structures dictate the spatial distribution of Nb–Ta ore bodies.

Deformation history and processes during accretion of seamounts in subduction zones: The example of the Durkan Complex (Makran, SE Iran)

The Durkan Complex is a tectonic element of the Makran Accretionary Prism (SE Iran) that includes fragments of Late Cretaceous seamounts. In this paper, the results of map- to micro-scale structural studies of the western Durkan Complex are presented with the aim to describe its structural and tectono-metamorphic evolution. The Durkan Complex consists of several tectonic units bordered by mainly NNW-striking thrusts. Three main deformation phases (D1, D2, and D3) are distinguished and likely occurred from the Late Cretaceous to the Miocene–Pliocene. D1 is characterized by sub-isoclinal to close and W-verging folds associated with an axial plane foliation and shear zone along the fold limbs. This phase records the accretion of fragments of the seamount within the Makran at blueschist facies metamorphic conditions (160–300 °C and 0.6 – 1.2 GPa). D2 is characterized by open to close folds with sub-horizontal axial plane that likely developed during the exhumation of previously accreted seamount fragments. An upper Paleocene – Eocene siliciclastic succession unconformably sealed the D1 and D2 structures and is, in turn, deformed by W-verging thrust faults typical of D3. The latter likely testifies for a Miocene – Pliocene tectonic reworking of the accreted seamount fragments with the activation of out of sequence thrusts. Our results shed light on the mechanism of accretion of seamount materials in the accretionary prisms, suggesting that seamount slope successions favour the localization and propagation of the basal décollement. This study further confirms that the physiography of the subducting plates plays a significant role in the tectonic evolution of the subduction complexes.

Crystal structure of active CDK4-cyclin D and mechanistic basis for abemaciclib efficacy

Despite the biological and therapeutic relevance of CDK4/6 for the treatment of HR+, HER2- advanced breast cancer, the detailed mode of action of CDK4/6 inhibitors is not completely understood. Of particular interest, phosphorylation of CDK4 at T172 (pT172) is critical for generating the active conformation, yet no such crystal structure has been reported to date. We describe here the x-ray structure of active CDK4-cyclin D3 bound to the CDK4/6 inhibitor abemaciclib and discuss the key aspects of the catalytically-competent complex. Furthermore, the effect of CDK4/6 inhibitors on CDK4 T172 phosphorylation has not been explored, despite its role as a potential biomarker of CDK4/6 inhibitor response. We show mechanistically that CDK4/6i stabilize primed (pT172) CDK4-cyclin D complex and selectively displace p21 in responsive tumor cells. Stabilization of active CDK4-cyclin D1 complex can lead to pathway reactivation following alternate dosing regimen. Consequently, sustained binding of abemaciclib to CDK4 leads to potent cell cycle inhibition in breast cancer cell lines and prevents rebound activation of downstream signaling. Overall, our study provides key insights demonstrating that prolonged treatment with CDK4/6 inhibitors and composition of the CDK4/6-cyclin D complex are both critical determinants of abemaciclib efficacy, with implications for this class of anticancer therapy.