Context-dependent changes in maritime traffic activity during the first year of the COVID-19 pandemic

This article is a contribution of the COVID-19 Bio-Logging Initiative, which is funded in part by the Gordon and Betty Moore Foundation (GBMF9881) and the National Geographic Society (NGS-82515R-20) (both grants to C.R.), and endorsed by the United Nations Decade of Ocean Science for Sustainable Development. Specifically, A.L.’s, R.P.’s and B.R.’s postdoctoral positions were funded by the Gordon and Betty Moore Foundation (GBMF9881), and J.S.’s contributions were funded by the National Geographic Society (NGS-82515R-20). D.W.S. was supported by a Marine Biological Association Senior Research Fellowship with additional support from the Natural Environment Research Council (Discovery Science NE/R00997/X/1) and the European Research Council (Advanced Grant 883583 OCEAN DEOXYFISH).Rapid implementation of human mobility restrictions during the COVID-19 pandemic dramatically reduced maritime activity in early 2020. But where and when activity rebounded, or remained low, during the full extent of 2020 restrictions remains unclear. Using global high-resolution datasets, we reveal a surprising degree of complexity in maritime activity patterns during 2020, yielding a more nuanced picture of how restrictions affected activity. Overall, shipping activity in Exclusive Economic Zones decreased (1.35 %), as expected, however high-seas activity increased (0.28 %). While these annual changes appear modest, there were striking spatially and temporally asynchronous variations in different vessel types’ activity in the second half of 2020, ranging from an > 80 % sustained reduction in passenger vessel activity to a 150 % increase in fishing activity. Results suggest systems-level responses were highly context-dependent, pinpointing areas that experienced significant reductions and spikes in activity, and providing hitherto missing details of COVID-19 impacts on economic and environmental sustainability.Publisher PDFPeer reviewe

The gene-rich genome of the scallop Pecten maximus.

BACKGROUND: The king scallop, Pecten maximus, is distributed in shallow waters along the Atlantic coast of Europe. It forms the basis of a valuable commercial fishery and plays a key role in coastal ecosystems and food webs. Like other filter feeding bivalves it can accumulate potent phytotoxins, to which it has evolved some immunity. The molecular origins of this immunity are of interest to evolutionary biologists, pharmaceutical companies, and fisheries management. FINDINGS: Here we report the genome assembly of this species, conducted as part of the Wellcome Sanger 25 Genomes Project. This genome was assembled from PacBio reads and scaffolded with 10X Chromium and Hi-C data. Its 3,983 scaffolds have an N50 of 44.8 Mb (longest scaffold 60.1 Mb), with 92% of the assembly sequence contained in 19 scaffolds, corresponding to the 19 chromosomes found in this species. The total assembly spans 918.3 Mb and is the best-scaffolded marine bivalve genome published to date, exhibiting 95.5% recovery of the metazoan BUSCO set. Gene annotation resulted in 67,741 gene models. Analysis of gene content revealed large numbers of gene duplicates, as previously seen in bivalves, with little gene loss, in comparison with the sequenced genomes of other marine bivalve species. CONCLUSIONS: The genome assembly of P. maximus and its annotated gene set provide a high-quality platform for studies on such disparate topics as shell biomineralization, pigmentation, vision, and resistance to algal toxins. As a result of our findings we highlight the sodium channel gene Nav1, known to confer resistance to saxitoxin and tetrodotoxin, as a candidate for further studies investigating immunity to domoic acid

The synthetic TRPML1 agonist ML-SA1 rescues Alzheimer-related alterations of the endosomal-autophagic-lysosomal system

Abnormalities in the endosomal-autophagic-lysosomal (EAL) system are an early event in Alzheimer's disease (AD) pathogenesis. However, the mechanisms underlying these abnormalities are unclear. The transient receptor potential channel mucolipin 1(TRPML1, also known as MCOLN1), a vital endosomal-lysosomal Ca2+ channel whose loss of function leads to neurodegeneration, has not been investigated with respect to EAL pathogenesis in late-onset AD (LOAD). Here, we identify pathological hallmarks of TRPML1 dysregulation in LOAD neurons, including increased perinuclear clustering and vacuolation of endolysosomes. We reveal that induced pluripotent stem cell (iPSC)-derived human cortical neurons expressing APOE ε4, the strongest genetic risk factor for LOAD, have significantly diminished TRPML1-induced endolysosomal Ca2+ release. Furthermore, we found that blocking TRPML1 function in primary neurons by depleting the TRPML1 agonist PI(3,5)P2 via PIKfyve inhibition, recreated multiple features of EAL neuropathology evident in LOAD. This included increased endolysosomal Ca2+ content, enlargement and perinuclear clustering of endolysosomes, autophagic vesicle accumulation and early endosomal enlargement. Strikingly, these AD-like neuronal EAL defects were rescued by TRPML1 reactivation using its synthetic agonist ML-SA1. These findings implicate defects in TRPML1 in LOAD EAL pathogenesis and present TRPML1 as a potential therapeutic target

Synoviocyte-targeted therapy synergizes with TNF inhibition in arthritis reversal

Fibroblast-like synoviocytes (FLS) are joint-lining cells that promote rheumatoid arthritis (RA) pathology. Current disease-modifying antirheumatic agents (DMARDs) operate through systemic immunosuppression. FLS-targeted approaches could potentially be combined with DMARDs to improve control of RA without increasing immunosuppression. Here, we assessed the potential of immunoglobulin-like domains 1 and 2 (Ig1&2), a decoy protein that activates the receptor tyrosine phosphatase sigma (PTPRS) on FLS, for RA therapy. We report that PTPRS expression is enriched in synovial lining RA FLS and that Ig1&2 reduces migration of RA but not osteoarthritis FLS. Administration of an Fc-fusion Ig1&2 attenuated arthritis in mice without affecting innate or adaptive immunity. Furthermore, PTPRS was down-regulated in FLS by tumor necrosis factor (TNF) via a phosphatidylinositol 3-kinase–mediated pathway, and TNF inhibition enhanced PTPRS expression in arthritic joints. Combination of ineffective doses of TNF inhibitor and Fc-Ig1&2 reversed arthritis in mice, providing an example of synergy between FLS-targeted and immunosuppressive DMARD therapies.publishedVersio

Dynamic changes in gene expression in vivo predict prognosis of tamoxifen-treated patients with breast cancer

Introduction: Tamoxifen is the most widely prescribed anti-estrogen treatment for patients with estrogen receptor (ER)-positive breast cancer. However, there is still a need for biomarkers that reliably predict endocrine sensitivity in breast cancers and these may well be expressed in a dynamic manner. Methods: In this study we assessed gene expression changes at multiple time points (days 1, 2, 4, 7, 14) after tamoxifen treatment in the ER-positive ZR-75-1 xenograft model that displays significant changes in apoptosis, proliferation and angiogenesis within 2 days of therapy. Results: Hierarchical clustering identified six time-related gene expression patterns, which separated into three groups: two with early/transient responses, two with continuous/late responses and two with variable response patterns. The early/transient response represented reductions in many genes that are involved in cell cycle and proliferation (e.g. BUB1B, CCNA2, CDKN3, MKI67, UBE2C), whereas the continuous/late changed genes represented the more classical estrogen response genes (e.g. TFF1, TFF3, IGFBP5). Genes and the proteins they encode were confirmed to have similar temporal patterns of expression in vitro and in vivo and correlated with reduction in tumour volume in primary breast cancer. The profiles of genes that were most differentially expressed on days 2, 4 and 7 following treatment were able to predict prognosis, whereas those most changed on days 1 and 14 were not, in four tamoxifen treated datasets representing a total of 404 patients. Conclusions: Both early/transient/proliferation response genes and continuous/late/estrogen-response genes are able to predict prognosis of primary breast tumours in a dynamic manner. Temporal expression of therapy-response genes is clearly an important factor in characterising the response to endocrine therapy in breast tumours which has significant implications for the timing of biopsies in neoadjuvant biomarker studies.Publisher PDFPeer reviewe

Improved Outcome Prediction Using CT Angiography in Addition to Standard Ischemic Stroke Assessment: Results from the STOPStroke Study

Purpose: To improve ischemic stroke outcome prediction using imaging information from a prospective cohort who received admission CT angiography (CTA). Methods: In a prospectively designed study, 649 stroke patients diagnosed with acute ischemic stroke had admission NIH stroke scale scores, noncontrast CT (NCCT), CTA, and 6-month outcome assessed using the modified Rankin scale (mRS) scores. Poor outcome was defined as mRS.2. Strokes were classified as ‘‘major’ ’ by the (1) Alberta Stroke Program Early CT Score (ASPECTS+) if NCCT ASPECTS was#7; (2) Boston Acute Stroke Imaging Scale (BASIS+) if they were ASPECTS+ or CTA showed occlusion of the distal internal carotid, proximal middle cerebral, or basilar arteries; and (3) NIHSS for scores.10. Results: Of 649 patients, 253 (39.0%) had poor outcomes. NIHSS, BASIS, and age, but not ASPECTS, were independent predictors of outcome. BASIS and NIHSS had similar sensitivities, both superior to ASPECTS (p,0.0001). Combining NIHSS with BASIS was highly predictive: 77.6 % (114/147) classified as NIHSS.10/BASIS+ had poor outcomes, versus 21.5 % (77/358) with NIHSS#10/BASIS2 (p,0.0001), regardless of treatment. The odds ratios for poor outcome is 12.6 (95 % CI: 7.9 to 20.0

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Reproductive Schedules in Southern Bluefin Tuna: Are Current Assumptions Appropriate?

Southern bluefin tuna (SBT) appear to comprise a single stock that is assumed to be both mixed across its distribution and having reproductive adults that are obligate, annual spawners. The putative annual migration cycle of mature SBT consists of dispersed foraging at temperate latitudes with migration to a single spawning ground in the tropical eastern Indian Ocean. Spawning migrations have been assumed to target two peaks in spawning activity; one in September-October and a second in February-March. SBT of sizes comparable to that of individuals observed on the spawning ground were satellite tagged in the Tasman Sea region (2003–2008) and demonstrated both migrations to the spawning grounds and residency in the Tasman Sea region throughout the whole year. All individuals undertaking apparent spawning migrations timed their movements to coincide with the second recognised spawning peak or even later. These observations suggest that SBT may demonstrate substantial flexibility in the scheduling of reproductive events and may even not spawn annually as currently assumed. Further, the population on the spawning grounds may be temporally structured in association with foraging regions. These findings provide new perspectives on bluefin population and spatial dynamics and warrant further investigation and consideration of reproductive schedules in this species

Mechanical Analysis of Feeding Behavior in the Extinct “Terror Bird” Andalgalornis steulleti (Gruiformes: Phorusrhacidae)

The South American phorusrhacid bird radiation comprised at least 18 species of small to gigantic terrestrial predators for which there are no close modern analogs. Here we perform functional analyses of the skull of the medium-sized (∼40 kg) patagornithine phorusrhacid Andalgalornis steulleti (upper Miocene–lower Pliocene, Andalgalá Formation, Catamarca, Argentina) to assess its mechanical performance in a comparative context. Based on computed tomographic (CT) scanning and morphological analysis, the skull of Andalgalornis steulleti is interpreted as showing features reflecting loss of intracranial immobility. Discrete anatomical attributes permitting such cranial kinesis are widespread phorusrhacids outgroups, but this is the first clear evidence of loss of cranial kinesis in a gruiform bird and may be among the best documented cases among all birds. This apomorphic loss is interpreted as an adaptation for enhanced craniofacial rigidity, particularly with regard to sagittal loading. We apply a Finite Element approach to a three-dimensional (3D) model of the skull. Based on regression analysis we estimate the bite force of Andalgalornis at the bill tip to be 133 N. Relative to results obtained from Finite Element Analysis of one of its closest living relatives (seriema) and a large predatory bird (eagle), the phorusrhacid's skull shows relatively high stress under lateral loadings, but low stress where force is applied dorsoventrally (sagittally) and in “pullback” simulations. Given the relative weakness of the skull mediolaterally, it seems unlikely that Andalgalornis engaged in potentially risky behaviors that involved subduing large, struggling prey with its beak. We suggest that it either consumed smaller prey that could be killed and consumed more safely (e.g., swallowed whole) or that it used multiple well-targeted sagittal strikes with the beak in a repetitive attack-and-retreat strategy