New insights into the rift to drift transition across the northeastern Nova Scotian margin from wide-angle seismic waveform inversion and reflection imaging

Author Posting. © American Geophysical Union, 2021. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Solid Earth 126(12), (2021): e2021JB022201, https://doi.org/10.1029/2021JB022201.Sparse wide-angle seismic profiling supported by coincident reflection imaging has been instrumental for advancing our knowledge about rifted margins. Nevertheless, features of critical importance for understanding rifting processes have been poorly resolved. We derive a high-resolution velocity model by applying full waveform inversion to the dense OETR-2009 wide-angle seismic profile crossing the northeastern Nova Scotian margin. We then create a coincident reflection image by prestack depth migrating the multichannel seismic data. This allows for the first detailed interpretation of the structures related to the final stages of continental breakup and incipient oceanic accretion at the Eastern North America Margin. Our interpretation includes a hyperextended continental domain overlying partially serpentinized mantle, followed by a 10-km-wide domain consisting of a continental block surrounded by layered and bright reflectors indicative of magmatic extrusions. A major fault, representing the continent-ocean boundary, marks a sharp seaward transition to a 16-km-wide domain characterized by smoother basement with chaotic reflectors, where no continental materials are present and a 3-km-thick embryonic oceanic crust overlying partially serpentinized mantle is created by the breakup magmatism. Further seaward, thin oceanic crust overlies the serpentinized mantle suggesting magma-poor oceanic spreading with variable magma supply as determined from variable basement topography, 2–4 km thick volcanic layer, and magnetic anomalies. Our results demonstrate that magmatism played an important role in the lithospheric breakup of the area crossed by the OETR-2009 profile. Considering that the northeastern Nova Scotian margin has been classified as amagmatic, large margin-parallel variations in magma supply likely characterize a single rift segment.H. Jian was supported by the Ocean Frontier Institute International Postdoctoral Fellowship at Dalhousie University and NSF grant OCE-2001012

Crustal structure across the Grand Banks–Newfoundland Basin Continental Margin – II. Results from a seismic reflection profile

Author Posting. © Blackwell, 2006. This is the author's version of the work. It is posted here by permission of Blackwell for personal use, not for redistribution. The definitive version was published in Geophysical Journal International 167 (2006): 157-170, doi:10.1111/j.1365-246X.2006.02989.x.New multi-channel seismic (MCS) reflection data were collected over a 565km transect covering the non-volcanic rifted margin of the central eastern Grand Banks and the Newfoundland Basin in the northwestern Atlantic. Three major crustal zones are interpreted from west to east over the seaward 350-km of the profile: (1) continental crust; (2) transitional basement; (3) oceanic crust. Continental crust thins over a wide zone (~160 km) by forming a large rift basin (Carson Basin) and seaward fault block, together with a series of smaller fault blocks eastward beneath the Salar and Newfoundland basins. Analysis of selected previous reflection profiles (Lithoprobe 85-4, 85-2 and Conrad NB-1) indicates that prominent landward-dipping reflections observed under the continental slope are a regional phenomenon. They define the landward edge of a deep serpentinized mantle layer, which underlies both extended continental crust and transitional basement. The 80-km-wide transitional basement is defined landward by a basement high that may consist of serpentinized peridotite and seaward by a pair of basement highs of unknown crustal origin. Flat and unreflective transitional basement most likely is exhumed, serpentinized mantle, although our results do not exclude the possibility of anomalously thinned oceanic crust. A Moho reflection below interpreted oceanic crust is first observed landward of magnetic anomaly M4, 230 km from the shelf break. Extrapolation of ages from chron M0 to the edge of interpreted oceanic crust suggests that the onset of seafloor spreading was ~138Ma (Valanginian) in the south (southern Newfoundland Basin) to ~125Ma (Barremian-Aptian boundary) in the north (Flemish Cap), comparable to those proposed for the conjugate margins.This work was funded by NSF grants OCE-9819053 and OCE-0326714 to Woods Hole Oceanographic Institution, NSERC (Canada) and the Danish Research Council. B. Tucholke also acknowledges support from the Henry Bryant Bigelow Chair in Oceanography at Woods Hole Oceanographic Institution

Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells

Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator

Crustal structure across the Grand Banks–Newfoundland Basin Continental Margin – I. Results from a seismic refraction profile

Author Posting. © Blackwell, 2006. This is the author's version of the work. It is posted here by permission of Blackwell for personal use, not for redistribution. The definitive version was published in Geophysical Journal International 167 (2006): 127-156, doi:10.1111/j.1365-246X.2006.02988.x.A P-wave velocity model along a 565-km-long profile across the Grand Banks/Newfoundland basin rifted margin is presented. Continental crust ~36-kmthick beneath the Grand Banks is divided into upper (5.8-6.25 km/s), middle (6.3- 6.53 km/s) and lower crust (6.77-6.9 km/s), consistent with velocity structure of Avalon zone Appalachian crust. Syn-rift sediment sequences 6-7-km thick occur in two primary layers within the Jeanne d’Arc and the Carson basins (~3 km/s in upper layer; ~5 km/s in lower layer). Abrupt crustal thinning (Moho dip ~ 35º) beneath the Carson basin and more gradual thinning seaward forms a 170-km-wide zone of rifted continental crust. Within this zone, lower and middle continental crust thin preferentially seaward until they are completely removed, while very thin (<3 km) upper crust continues ~60 km farther seaward. Adjacent to the continental crust, high velocity gradients (0.5-1.5 s-1) define an 80-km-wide zone of transitional basement that can be interpreted as exhumed, serpentinized mantle or anomalously thin oceanic crust, based on its velocity model alone. We prefer the exhumed-mantle interpretation after considering the non-reflective character of the basement and the low amplitude of associated magnetic anomalies, which are atypical of oceanic crust. Beneath both the transitional basement and thin (<6 km) continental crust, a 200-kmwide zone with reduced mantle velocities (7.6-7.9 km/s) is observed, which is interpreted as partially (<10%) serpentinized mantle. Seaward of the transitional basement, 2- to 6-km-thick crust with layer 2 (4.5-6.3 km/s) and layer 3 (6.3-7.2 km/s) velocities is interpreted as oceanic crust. Comparison of our crustal model with profile IAM-9 across the Iberia Abyssal Plain on the conjugate Iberia margin suggests asymmetrical continental breakup in which a wider zone of extended continental crust has been left on the Newfoundland side.This research was supported by National Science Foundation (NSF) grants OCE-9819053 and OCE-0326714, by the National Sciences and Engineering Research Council of Canada (NSERC), and by the Danish National Research Foundation. B. Tucholke also acknowledges support from the Henry Bryant Bigelow Chair in Oceanography from Woods Hole Oceanographic Institution

A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome

Attention bias to emotional faces varies by IQ and anxiety in Williams syndrome

Individuals with Williams syndrome (WS) often experience significant anxiety. A promising approach to anxiety intervention has emerged from cognitive studies of attention bias to threat. To investigate the utility of this intervention in WS, this study examined attention bias to happy and angry faces in individuals with WS (N=46). Results showed a significant difference in attention bias patterns as a function of IQ and anxiety. Individuals with higher IQ or higher anxiety showed a significant bias toward angry, but not happy faces, whereas individuals with lower IQ or lower anxiety showed the opposite pattern. These results suggest that attention bias interventions to modify a threat bias may be most effectively targeted to anxious individuals with WS with relatively high IQ

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

The First Post-Kepler Brightness Dips of KIC 8462852

We present a photometric detection of the first brightness dips of the unique variable star KIC 8462852 since the end of the Kepler space mission in 2013 May. Our regular photometric surveillance started in October 2015, and a sequence of dipping began in 2017 May continuing on through the end of 2017, when the star was no longer visible from Earth. We distinguish four main 1-2.5% dips, named "Elsie," "Celeste," "Skara Brae," and "Angkor", which persist on timescales from several days to weeks. Our main results so far are: (i) there are no apparent changes of the stellar spectrum or polarization during the dips; (ii) the multiband photometry of the dips shows differential reddening favoring non-grey extinction. Therefore, our data are inconsistent with dip models that invoke optically thick material, but rather they are in-line with predictions for an occulter consisting primarily of ordinary dust, where much of the material must be optically thin with a size scale <<1um, and may also be consistent with models invoking variations intrinsic to the stellar photosphere. Notably, our data do not place constraints on the color of the longer-term "secular" dimming, which may be caused by independent processes, or probe different regimes of a single process