U–Pb (LA–ICP-MS) dating of detrital zircons from Cambrian clastic rocks in Avalonia: erosion of a Neoproterozoic arc along the northern Gondwanan margin

Most Neoproterozoic and Early Palaeozoic tectonic syntheses place Avalonia and related peri-Gondwanan terranes facing an open ocean along the northern margin of Gondwana, thereby providing important constraints for palaeocontinental reconstructions during that time interval. However, the precise location of Avalonia along the margin and its position relative to other peri-Gondwanan terranes is controversial. We present laser ablation–inductively coupled plasma mass spectrometry U–Pb data for detrital zircons from Cambrian clastic rocks in two localities in Avalonia: the Antigonish Highlands of Nova Scotia (62 analyses) and the British Midlands (55 analyses). The data from both samples are very similar, and taken together indicate an overwhelming dominance of Neoproterozoic (c. 580–680 Ma) or Early Cambrian source rocks with minor older Neoproterozoic clusters at c. 710 Ma or of Mesoproterozoic age, three Palaeoproterozoic zircons and one Archaean zircon. The zircons can all be derived from local Avalonian sources. The Neoproterozoic zircons are attributed to erosion of the underlying Avalonian arc. Mesoproterozoic and Palaeoproterozoic zircons of similar ages are also found in Avalonian Neoproterozoic clastic rocks and their presence in the Cambrian clastic rocks could represent recycling of Neoproterozoic strata and do not necessarily imply the presence of Mesoproterozoic or Palaeoproterozoic basement rocks within their respective drainage basins. Comparison with the data from the Neoproterozoic arc-related clastic sequences suggests significant differences between their respective drainage systems. Whereas the Neoproterozoic data require extensive drainage systems, the Cambrian data can be attributed to localized drainage systems. The change in drainage patterns could reflect rifting and isolation of Avalonia from Amazonia between c. 585 and 540 Ma. Alternatively, it might reflect the creation of topographical barriers along the northern Gondwanan margin, in a manner analogous to the Cenozoic rise of the Andes or the creation of the Basin-and-Range topography in the Western USA

Overprinting orogenic events, ductile extrusion and strain partitioning during Caledonian transpression, NW Mainland Shetland

A 3.6 km thick stack of mid-crustal deformed Precambrian rocks is associated with the North Roe Nappe (NRN) and Walls Boundary Fault in the northernmost Scottish Caledonides on NW Mainland Shetland. The greenschist- to amphibolite-facies rocks display unusually complex and heterogeneous combinations of coaxial and non-coaxial transpressional deformation. Previously published isotopic dating, together with new detailed field mapping and microstructural characterisation show that the NRN preserves a record of Neoarchaean, Neoproterozoic (Knoydartian) and Ordovician-Silurian (Caledonian) overprinting deformation and metamorphism. Neoarchaean events in the Uyea Gneiss Complex located in its footwall are reworked by younger events in the overlying nappe pile. The main ductile fabrics were formed during Caledonian top-to-the W/NW thrusting and top-to-the N sinistral shearing, with subordinate regions of top- to-the E extensional and NNE-SSW dextral shearing. In lower parts of the NRN, these different kinematic domains are texturally indistinguishable and overprinting relationships are absent. At higher levels, top-to-the-W/NW thrust-related fabrics are consistently overprinted by top-to-the-N/NE sinistral shearing. The highly partitioned transpressional deformation shows similarities with equivalent rocks of the Moine Nappe in NW Scotland

Tectonic Transport Directions, Shear Senses and Deformation Temperatures Indicated by Quartz c‐Axis Fabrics and Microstructures in a NW‐SE Transect across the Moine and Sgurr Beag Thrust Sheets, Caledonian Orogen of Northern Scotland

Moine metasedimentary rocks of northern Scotland are characterized by arcuate map patterns of mineral lineations that swing progressively clockwise from orogen‐perpendicular E‐trend-ing lineations in greenschist facies mylonites above the Moine thrust on the foreland edge of the Caledonian Orogen, to S‐trending lineations at higher structural levels and metamorphic grades in the hinterland. Quartz c‐axis fabrics measured on a west to east coast transect demonstrate that the lineations developed parallel to the maximum principal extension direction and therefore track the local tectonic transport direction. Microstructures and c‐axis fabrics document a progressive change from top to the N shearing in the hinterland to top to the W shearing on the foreland edge. Field relationships indicate that the domain of top to the N shearing was at least 55 km wide before later horizontal shortening on km‐scale W‐vergent folds that detach on the underlying Moine thrust. Previously published data from the Moine thrust mylonites demonstrate that top to the W shearing had largely ceased by 430 Ma, while preliminary isotopic age data suggest top to the N shearing occurred at ~470–450 Ma. In addition, data from the east coast end of our transect indicate normal-sense top down‐SE shearing at close to peak temperatures at ~420 Ma that may be related to the closing stages of Scandian deformation, metamorphism and cooling/exhumation

Tectonic Plates Come Apart at the Seams

Around the time that the first birds evolved from their reptilian ancestors, between 100 million and 200 million years ago, the Atlantic Ocean was being born. Its creation marked the destruction of the supercontinent Pangea, in which all the land on Earth formed a gigantic, unbroken island surrounded by a worldwide sea

Origin of the Rheic Ocean: Rifting along a Neoproterozoic suture?

The Rheic Ocean is widely believed to have formed in the Late Cambrian–Early Ordovician as a result of the drift of peri-Gondwanan terranes, such as Avalonia and Carolina, from the northern margin of Gondwana, and to have been consumed in the Devonian Carboniferous by continent-continent collision during the formation of Pangea. Other peri-Gondwanan terranes (e.g., Armorica, Ossa-Morena, northwest Iberia, Saxo-Thuringia, Moldanubia) remained along the Gondwanan margin at the time of Rheic Ocean formation. Differences in the Neoproterozoic histories of these peri-Gondwanan terranes suggest the location of the Rheic Ocean rift may have been inherited from Neoproterozoic lithospheric structures formed by the accretion and dispersal of peri-Gondwanan terranes along the northern Gondwanan margin prior to Rheic Ocean opening. Avalonia and Carolina have Sm-Nd isotopic characteristics indicative of recycling of a juvenile ca. 1 Ga source, and they were accreted to the northern Gondwanan margin prior to voluminous late Neoproterozoic arc magmatism. In contrast, Sm-Nd isotopic characteristics of most other peri-Gondwanan terranes closely match those of Eburnian basement, suggesting they reflect recycling of ancient (2 Ga) West African crust. The basements of terranes initially rifted from Gondwana to form the Rheic Ocean were those that had previously accreted during Neoproterozoic orogenesis, suggesting the rift was located near the suture between the accreted terranes and cratonic northern Gondwana. Opening of the Rheic Ocean coincided with the onset of subduction beneath the Laurentian margin in its predecessor, the Iapetus Ocean, suggesting geodynamic linkages between the destruction of the Iapetus Ocean and the creation of the Rheic Ocean

Integrated community case management in a peri-urban setting: a qualitative evaluation in Wakiso District, Uganda.

Integrated community case management (iCCM) strategies aim to reach poor communities by providing timely access to treatment for malaria, pneumonia and diarrhoea for children under 5 years of age. Community health workers, known as Village Health Teams (VHTs) in Uganda, have been shown to be effective in hard-to-reach, underserved areas, but there is little evidence to support iCCM as an appropriate strategy in non-rural contexts. This study aimed to inform future iCCM implementation by exploring caregiver and VHT member perceptions of the value and effectiveness of iCCM in peri-urban settings in Uganda.A qualitative evaluation was conducted in seven villages in Wakiso district, a rapidly urbanising area in central Uganda. Villages were purposively selected, spanning a range of peri-urban settlements experiencing rapid population change. In each village, rapid appraisal activities were undertaken separately with purposively selected caregivers (n = 85) and all iCCM-trained VHT members (n = 14), providing platforms for group discussions. Fifteen key informant interviews were also conducted with community leaders and VHT members. Thematic analysis was based on the 'Health Access Livelihoods Framework'.iCCM was perceived to facilitate timely treatment access and improve child health in peri-urban settings, often supplanting private clinics and traditional healers as first point of care. Relative to other health service providers, caregivers valued VHTs' free, proximal services, caring attitudes, perceived treatment quality, perceived competency and protocol use, and follow-up and referral services. VHT effectiveness was perceived to be restricted by inadequate diagnostics, limited newborn care, drug stockouts and VHT member absence - factors which drove utilisation of alternative providers. Low community engagement in VHT selection, lack of referral transport and poor availability of referral services also diminished perceived effectiveness. The iCCM strategy was widely perceived to result in economic savings and other livelihood benefits.In peri-urban areas, iCCM was perceived as an effective, well-utilised strategy, reflecting both VHT attributes and gaps in existing health services. Depending on health system resources and organisation, iCCM may be a useful transitional service delivery approach. Implementation in peri-urban areas should consider tailored community engagement strategies, adapted selection criteria, and assessment of population density to ensure sufficient coverage

Challenges in quantifying changes in the global water cycle

Human influences have likely already impacted the large-scale water cycle but natural variability and observational uncertainty are substantial. It is essential to maintain and improve observational capabilities to better characterize changes. Understanding observed changes to the global water cycle is key to predicting future climate changes and their impacts. While many datasets document crucial variables such as precipitation, ocean salinity, runoff, and humidity, most are uncertain for determining long-term changes. In situ networks provide long time-series over land but are sparse in many regions, particularly the tropics. Satellite and reanalysis datasets provide global coverage, but their long-term stability is lacking. However, comparisons of changes among related variables can give insights into the robustness of observed changes. For example, ocean salinity, interpreted with an understanding of ocean processes, can help cross-validate precipitation. Observational evidence for human influences on the water cycle is emerging, but uncertainties resulting from internal variability and observational errors are too large to determine whether the observed and simulated changes are consistent. Improvements to the in situ and satellite observing networks that monitor the changing water cycle are required, yet continued data coverage is threatened by funding reductions. Uncertainty both in the role of anthropogenic aerosols, and due to large climate variability presently limits confidence in attribution of observed changes

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Linking collisional and accretionary orogens during Rodinia assembly and breakup: Implications for models of supercontinent cycles

Periodic assembly and dispersal of continental fragments has been a characteristic of the solid Earth for much of its history. Geodynamic drivers of this cyclic activity are inferred to be either top-down processes related to near surface lithospheric stresses at plate boundaries or bottom-up processes related to mantle convection and, in particular, mantle plumes, or some combination of the two. Analysis of the geological history of Rodinian crustal blocks suggests that internal rifting and breakup of the supercontinent were linked to the initiation of subduction and development of accretionary orogens around its periphery. Thus, breakup was a top-down instigated process. The locus of convergence was initially around north-eastern and northern Laurentia in the early Neoproterozoic before extending to outboard of Amazonia and Africa, including Avalonia–Cadomia, and arcs outboard of Siberia and eastern to northern Baltica in the mid-Neoproterozoic (~760 Ma). The duration of subduction around the periphery of Rodinia coincides with the interval of lithospheric extension within the supercontinent, including the opening of the proto-Pacific at ca. 760 Ma and the commencement of rifting in east Laurentia. Final development of passive margin successions around Laurentia, Baltica and Siberia was not completed until the late Neoproterozoic to early Paleozoic (ca. 570–530 Ma), which corresponds with the termination of convergent plate interactions that gave rise to Gondwana and the consequent relocation of subduction zones to the periphery of this supercontinent. The temporal link between external subduction and internal extension suggests that breakup was initiated by a top-down process driven by accretionary tectonics along the periphery of the supercontinent. Plume-related magmatism may be present at specific times and in specific places during breakup but is not the prime driving force. Comparison of the Rodinia record of continental assembly and dispersal with that for Nuna, Gondwana and Pangea suggests grouping into two supercycles in which Nuna and Gondwana underwent only partial or no break-up phase prior to their incorporation into Rodinia and Pangea respectively. It was only after this final phase of assembly that the supercontinents then underwent full dispersal

Spatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function

The glycocalyx component and sialomucin podocalyxin (PODXL) is required for normal tissue development by promoting apical membranes to form between cells, triggering lumen formation. Elevated PODXL expression is also associated with metastasis and poor clinical outcome in multiple tumor types. How PODXL presents this duality in effect remains unknown. We identify an unexpected function of PODXL as a decoy receptor for galectin-3 (GAL3), whereby the PODXL-GAL3 interaction releases GAL3 repression of integrin-based invasion. Differential cortical targeting of PODXL, regulated by ubiquitination, is the molecular mechanism controlling alternate fates. Both PODXL high and low surface levels occur in parallel subpopulations within cancer cells. Orthotopic intraprostatic xenograft of PODXL-manipulated cells or those with different surface levels of PODXL define that this axis controls metastasis in vivo. Clinically, interplay between PODXL-GAL3 stratifies prostate cancer patients with poor outcome. Our studies define the molecular mechanisms and context in which PODXL promotes invasion and metastasis