Noncanonical mitochondrial unfolded protein response impairs placental oxidative phosphorylation in early-onset preeclampsia.

Preeclampsia (PE) is a dangerous complication of pregnancy, especially when it presents at <34 wk of gestation (PE < 34 wk). It is a major cause of maternal and fetal morbidity and mortality and also increases the risk of cardiometabolic diseases in later life for both mother and offspring. Placental oxidative stress induced by defective placentation sits at the epicenter of the pathophysiology. The placenta is susceptible to activation of the unfolded protein response (UPR), and we hypothesized this may affect mitochondrial function. We first examined mitochondrial respiration before investigating evidence of mitochondrial UPR (UPRmt) in placentas of PE < 34 wk patients. Reduced placental oxidative phosphorylation (OXPHOS) capacity measured in situ was observed despite no change in protein or mRNA levels of electron transport chain complexes. These results were fully recapitulated by subjecting trophoblast cells to repetitive hypoxia-reoxygenation and were associated with activation of a noncanonical UPRmt pathway; the quality-control protease CLPP, central to UPRmt signal transduction, was reduced, while the cochaperone, TID1, was increased. Transcriptional factor ATF5, which regulates expression of key UPRmt genes including HSP60 and GRP75, showed no nuclear translocation. Induction of the UPRmt with methacycline reduced OXPHOS capacity, while silencing CLPP was sufficient to reduce OXPHOS capacity, membrane potential, and promoted mitochondrial fission. CLPP was negatively regulated by the PERK-eIF2α arm of the endoplasmic reticulum UPR pathway, independent of ATF4. Similar changes in the UPRmt pathway were observed in placentas from PE < 34 wk patients. Our results identify UPRmt as a therapeutic target for restoration of placental function in early-onset preeclampsia

Urinary tract infections: resistance to fluoroquinolones in E. coli

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Erratum to: Oncoplastic Breast-Conserving Surgery for Tumors Larger than 2 Centimeters: Is it Oncologically Safe? A Matched-Cohort Analysis

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The discovery of the southernmost ultra-high-resolution Holocene paleoclimate sedimentary record in Antarctica

The response of the Antarctic ice sheet to climate warming is the main source of uncertainty regarding future global sea level rise, since little is known about its present and past dynamics. The last deglaciation is the most recent interval of large-scale climate warming, during which the Northern and Southern Hemisphere ice sheets retreated, and sea level rose globally, although at a non-uniform rate. Geologic records from the polar regions are fundamental in determining the factors that caused the major changes in ice sheets during the last deglacial under different boundary conditions. Here, we combine morpho-bathymetric and seismic data with sediment cores and oceanographic measurements to reconstruct the processes that influenced the deposition of the southernmost, most extensive, ultrahigh-resolution record of the Holocene in Edisto Inlet fjord (Ross Sea, Antarctica). We find that post-glacial sedimentation resulted in a layered diatom mud up to 110 m thick that was locally redistributed by bottom currents over confined drifts-moats in the central part of the fjord. After the Holocene climatic optimum, the fjord was not carved by ground ice, and there continued to be internal fjord water circulation associated with Ross Sea circulation. These results support a retreat of coastal glaciers by about 11 kiloyears ago (ka) from the continental shelf of North Victoria Land

Past Antarctic ice sheet dynamics (PAIS) and implications for future sea-level change

Coauthors from the PAIS community Aisling M. Dolan, University of Leeds, Leeds, UK Alan K. Cooper, U.S. Geological Survey Emeritus, Menlo Park, USA Alessandra Venuti, Istituto Nazionale di Geofisica e Vulcanologia, Rome, Italy Amy Leventer, Colgate University, Hamilton, NY, USA Andrea Bergamasco, C.N.R. (National Research Council) ISMAR, Venice, Italy Carolina Acosta Hospitaleche, CONICET, División Paleontología Vertebrados, Museo de La Plata (Facultad de Ciencias Naturales y Museo, UNLP) La Plata, Argentina Carolina Acosta Hospitaleche, CONICET – División Paleontología Vertebrados, Museo de La Plata, Facultad de Ciencias Naturales y Museo, UNLP; La Plata, Argentina Catalina Gebhardt, Alfred Wegener Institute Helmholtz Centre of Polar and Marine Research, Bremerhaven, Germany Christine S. Siddoway, Colorado College, Colorado Springs, USA Christopher C. Sorlien, Earth Research Institute, University of California, Santa Barbara, Santa Barbara, California, USA David Harwood, University of Nebraska-Lincoln, Lincoln, Nebraska, USA David Pollard, Pennsylvania State University, University Park, Pennsylvania, USA David J. Wilson, Department of Earth Sciences, University College London, London, UK Denise K. Kulhanek, Texas A&M University, College Station, TX, United States Dominic A. Hodgson, British Antarctic Survey, Cambridge, UK Edward G.W. Gasson, University of Bristol, UK Fausto Ferraccioli, NERC/British Antarctic Survey, Cambridge, UK Fernando Bohoyo, Instituto Geológico y Minero de España, Madrid, Spain Francesca Battaglia, University of Venice Cá Foscari, Italy Frank O. Nitsche, Lamont-Doherty Earth Observatory of Columbia University, Palisades, USA Georgia R. Grant, GNS Science Wellington, New Zealand Gerhard Kuhn, Alfred-Wegener-Institut Helmholtz-Zentrum für Polar- und Meeresforschung, Bremerhaven, Germany Guy J.G. Paxman, Lamont-Doherty Earth Observatory, Columbia University, New York, USA Ian D. Goodwin, Climate Change Research Centre, University of New South Wales, Sydney, Australia Isabel Sauermilch, University of Tasmania, Institute for Marine and Antarctic Studies, Australia Jamey Stutz, Antarctic Research Centre at Victoria University of Wellington, New Zealand Jan Sverre Laberg, Department of Geosciences, UiT The Arctic University of Norway, NO-9037 Tromsø, Norway Javier N. Gelfo, CONICET – UNLP, División Paleontología Vertebrados, Museo de La Plata, Argentina Johann P. Klages, Alfred Wegener Institute Helmholtz Center for Polar and Marine Research, Bremerhaven, Germany Julia S. Wellner, University of Houston, Houston, USA Karsten Gohl, Alfred Wegener Institute Helmholtz Centre for Polar and Marine Research, Bremerhaven, Germany Laura Crispini, University of Genova (DISTAV, Genova, Italy) Leanne K. Armand, Australian National University, Canberra, Australia. Marcelo A. Reguero, Instituto Antártico Argentino, B1650HMK, San Martín, Buenos Aires, Argentina Marcelo A. Reguero, Instituto Antártico Argentino, Buenos Aires, Argentina Marco Taviani, Institute of Marine Sciences (ISMAR), National Research Council (CNR), 40129, Bologna, Italy and Biology Department, Woods Hole Oceanographic Institution, 02543, Woods Hole, USA Martin J. Siegert, Imperial College London, London, UK Marvin A. Speece, Montana Technological University, Butte, USA Mathieu Casado, Alfred Wegener Institute Helmholtz Centre for Polar and Marine Research, Potsdam, Germany Michele Rebesco, OGS, Trieste, Italy Mike Weber, University of Bonn, Institute for Geosciences, Department of Geochemistry and Petrology, 53115 Bonn, Germany Minoru Ikehara, Kochi University, Japan Nicholas R. Golledge, Antarctic Research Centre Victoria University of Wellington, Wellington 6140, New Zealand Nigel Wardell, OGS, Trieste, Italy Paolo Montagna, Institute of Polar Sciences, National Research Council, Bologna, Italy Peter J. Barrett, Antarctic Research Centre, Victoria University of Wellington, Wellington, New Zealand. Peter K. Bijl, Utrecht University, Utrecht, The Netherlands Philip E. O’Brien, Macquarie University, Sydney, Australia Philip J. Bart, Louisiana State University, Baton Rouge, USA Raffaella Tolotti, University of Genoa, Genoa, Italy Reed P. Scherer, Northern Illinois University, DeKalb, IL, USA Renata G. Lucchi, National Institute of Oceanography and Applied Geophysics (OGS), Sgonico-Trieste, Italy Riccardo Geletti, National Institute of Oceanography and Applied Geophysics – OGS, Trieste, Italy Richard C.A. Hindmarsh, British Antarctic Survey & Durham University, Cambridge & Durham, United Kingdom Richard H. Levy, GNS Science and Victoria University of Wellington, Lower Hutt and Wellington, New Zealand Robert B. Dunbar, Stanford University, Stanford, California, USA Robert D. Larter, British Antarctic Survey, Cambridge, UK Robert M. Mckay, Antarctic Research Centre, Victoria University of Wellington, Wellington, New Zealand R. Selwyn Jones, Monash University (Melbourne, Australia) Sandra Passchier, Montclair State University, Montclair, USA Sean P.S. Gulick, University of Texas at Austin, Austin, Texas Sidney R. Hemming, Columbia University, New York, USA Stefanie Brachfeld, Montclair State University, New Jersey, USA Suzanne OConnell, Wesleyan University, Middletown, CT, USA Trevor Williams, International Ocean Discovery Program, Texas A&M University, College Station, USA Ursula Röhl, MARUM, University of Bremen, Bremen, Germany Yasmina M. Martos, NASA Goddard Space Flight Center, Greenbelt, MD, USA & University of Maryland College Park, MD, USAThe legacy of the Scientific Committee on Antarctic Research’s (SCAR) PAIS strategic research programme includes not only breakthrough scientific discoveries, but it is also the story of a long-standing deep collaboration amongst different multi-disciplinary researchers from many nations, to share scientific infrastructure and data, facilities, and numerical models, in order to address high priority questions regarding the evolution and behaviour of the Antarctic ice sheets (AIS). The PAIS research philosophy is based on data-data and data-model integration and intercomparison, and the development of ‘ice-to-abyss’ data transects and paleo-environmental, extending from the ice sheet interior to the deep sea. PAIS strives to improve understanding of AIS dynamics and to reduce uncertainty in model simulations of future ice loss and global sea level change, by studying warm periods of the geological past that are relevant to future climate scenarios. The multi-disciplinary approach fostered by PAIS represents its greatest strength. Eight years after the start of this programme, PAIS achievements have been high-profile and impactful, both in terms of field campaigns that collected unique data sets and samples, and in terms of scientific advances concerning past AIS dynamics, that have measurably improved understanding of ice sheet sensitivity in response to global warming. Here we provide an overview and synthesis of the new knowledge generated by the PAIS Programme and its implications for anticipating and managing the impacts of global sea-level rise.TN acknowledges support from MBIE Antarctic Science Platform contract ANTA1801

Whole mitochondrial genomes unveil the impact of domestication on goat matrilineal variability

Background: The current extensive use of the domestic goat (Capra hircus) is the result of its medium size and high adaptability as multiple breeds. The extent to which its genetic variability was influenced by early domestication practices is largely unknown. A common standard by which to analyze maternally-inherited variability of livestock species is through complete sequencing of the entire mitogenome (mitochondrial DNA, mtDNA). Results: We present the first extensive survey of goat mitogenomic variability based on 84 complete sequences selected from an initial collection of 758 samples that represent 60 different breeds of C. hircus, as well as its wild sister species, bezoar (Capra aegagrus) from Iran. Our phylogenetic analyses dated the most recent common ancestor of C. hircus to ~460,000 years (ka) ago and identified five distinctive domestic haplogroups (A, B1, C1a, D1 and G). More than 90 % of goats examined were in haplogroup A. These domestic lineages are predominantly nested within C. aegagrus branches, diverged concomitantly at the interface between the Epipaleolithic and early Neolithic periods, and underwent a dramatic expansion starting from ~12–10 ka ago. Conclusions: Domestic goat mitogenomes descended from a small number of founding haplotypes that underwent domestication after surviving the last glacial maximum in the Near Eastern refuges. All modern haplotypes A probably descended from a single (or at most a few closely related) female C. aegagrus. Zooarchaelogical data indicate that domestication first occurred in Southeastern Anatolia. Goats accompanying the first Neolithic migration waves into the Mediterranean were already characterized by two ancestral A and C variants. The ancient separation of the C branch (~130 ka ago) suggests a genetically distinct population that could have been involved in a second event of domestication. The novel diagnostic mutational motifs defined here, which distinguish wild and domestic haplogroups, could be used to understand phylogenetic relationships among modern breeds and ancient remains and to evaluate whether selection differentially affected mitochondrial genome variants during the development of economically important breeds

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M&gt;70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0&lt;e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM