| 1. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 2. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 3. |
- Ao, Y., et al.
(författare)
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Deep Submillimeter and Radio Observations in the SSA22 Field. I. Powering Sources and the Ly alpha Escape Fraction of Ly alpha Blobs
- 2017
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 850:2
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Tidskriftsartikel (refereegranskat)abstract
- We study the heating mechanisms and Ly alpha escape fractions of 35 Ly alpha blobs (LABs) at z approximate to 3.1 in the SSA22 field. Dust continuum sources have been identified in 11 of the 35 LABs, all with star formation rates (SFRs) above 100M(circle dot) yr(-1). Likely radio counterparts are detected in 9 out of 29 investigated LABs. The detection of submillimeter dust emission is more linked to the physical size of the Ly alpha emission than to the Ly alpha luminosities of the LABs. A radio excess in the submillimeter/ radio-detected LABs is common, hinting at the presence of active galactic nuclei. Most radio sources without X-ray counterparts are located at the centers of the LABs. However, all X-ray counterparts avoid the central regions. This may be explained by absorption due to exceptionally large column densities along the line-of-sight or by LAB morphologies, which are highly orientation dependent. The median Lya escape fraction is about 3% among the submillimeter-detected LABs, which is lower than a lower limit of 11% for the submillimeter-undetected LABs. We suspect that the large difference is due to the high dust attenuation supported by the large SFRs, the dense large-scale environment as well as large uncertainties in the extinction corrections required to apply when interpreting optical data.
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| 4. |
- Wiedorn, Max O., et al.
(författare)
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Megahertz serial crystallography
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The new European X-ray Free-Electron Laser is the first X-ray free-electron laser capable of delivering X-ray pulses with a megahertz inter-pulse spacing, more than four orders of magnitude higher than previously possible. However, to date, it has been unclear whether it would indeed be possible to measure high-quality diffraction data at megahertz pulse repetition rates. Here, we show that high-quality structures can indeed be obtained using currently available operating conditions at the European XFEL. We present two complete data sets, one from the well-known model system lysozyme and the other from a so far unknown complex of a beta-lactamase from K. pneumoniae involved in antibiotic resistance. This result opens up megahertz serial femtosecond crystallography (SFX) as a tool for reliable structure determination, substrate screening and the efficient measurement of the evolution and dynamics of molecular structures using megahertz repetition rate pulses available at this new class of X-ray laser source.
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| 5. |
- Chorell, Erik, et al.
(författare)
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Bacterial Chaperones CsgE and CsgC Differentially Modulate Human α-Synuclein Amyloid Formation via Transient Contacts.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 10:10, s. e0140194-
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid formation is historically associated with cytotoxicity, but many organisms produce functional amyloid fibers (e.g., curli) as a normal part of cell biology. Two E. coli genes in the curli operon encode the chaperone-like proteins CsgC and CsgE that both can reduce in vitro amyloid formation by CsgA. CsgC was also found to arrest amyloid formation of the human amyloidogenic protein α-synuclein, which is involved in Parkinson's disease. Here, we report that the inhibitory effects of CsgC arise due to transient interactions that promote the formation of spherical α-synuclein oligomers. We find that CsgE also modulates α-synuclein amyloid formation through transient contacts but, in contrast to CsgC, CsgE accelerates α-synuclein amyloid formation. Our results demonstrate the significance of transient protein interactions in amyloid regulation and emphasize that the same protein may inhibit one type of amyloid while accelerating another.
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| 6. |
- Evans, Margery L, et al.
(författare)
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The bacterial curli system possesses a potent and selective inhibitor of amyloid formation
- 2015
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Ingår i: Molecular Cell. - : Elsevier BV. - 1097-4164 .- 1097-2765. ; 57:3, s. 445-455
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Tidskriftsartikel (refereegranskat)abstract
- Curli are extracellular functional amyloids that are assembled by enteric bacteria during biofilm formation and host colonization. An efficient secretion system and chaperone network ensures that the major curli fiber subunit, CsgA, does not form intracellular amyloid aggregates. We discovered that the periplasmic protein CsgC was a highly effective inhibitor of CsgA amyloid formation. In the absence of CsgC, CsgA formed toxic intracellular aggregates. In vitro, CsgC inhibited CsgA amyloid formation at substoichiometric concentrations and maintained CsgA in a non-β-sheet-rich conformation. Interestingly, CsgC inhibited amyloid assembly of human α-synuclein, but not Aβ42, in vitro. We identified a common D-Q-Φ-X0,1-G-K-N-ζ-E motif in CsgC client proteins that is not found in Aβ42. CsgC is therefore both an efficient and selective amyloid inhibitor. Dedicated functional amyloid inhibitors may be a key feature that distinguishes functional amyloids from disease-associated amyloids.
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| 7. |
- Geach, J. E., et al.
(författare)
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ALMA OBSERVATIONS OF Ly alpha BLOB 1 : HALO SUBSTRUCTURE ILLUMINATED FROM WITHIN
- 2016
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 832:1
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Tidskriftsartikel (refereegranskat)abstract
- We present new Atacama Large Millimeter/Submillimeter Array (ALMA) 850 mu m continuum observations of the original Ly alpha Blob (LAB) in the SSA22 field at z = 3.1 (SSA22-LAB01). The ALMA map resolves the previously identified submillimeter source into three components with a total flux density of S-850 = 1.68 +/- 0.06 mJy, corresponding to a star-formation rate of similar to 150M(circle dot) yr(-1). The submillimeter sources are associated with several faint (m approximate to 27 mag) rest-frame ultraviolet sources identified in Hubble Space Telescope Imaging Spectrograph (STIS) clear filter imaging (lambda approximate to 5850 angstrom). One of these companions is spectroscopically confirmed with the Keck Multi-Object Spectrometer For Infra-Red Exploration to lie within 20 projected kpc and 250 km s(-1) of one of the ALMA components. We postulate that some of these STIS sources represent a population of low-mass star-forming satellites surrounding the central submillimeter sources, potentially contributing to their growth and activity through accretion. Using a high-resolution cosmological zoom simulation of a 10(13)M(circle dot) halo at z = 3, including stellar, dust, and Ly alpha radiative transfer, we can model the ALMA + STIS observations and demonstrate that Ly alpha photons escaping from the central submillimeter sources are expected to resonantly scatter in neutral hydrogen, the majority of which is predicted to be associated with halo substructure. We show how this process gives rise to extended Ly alpha emission with similar surface brightness and morphology to observed giant LABs.
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| 8. |
- Jain, Neha, et al.
(författare)
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Inhibition of curli assembly and Escherichia coli biofilm formation by the human systemic amyloid precursor transthyretin
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 114:46, s. 12184-12189
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Tidskriftsartikel (refereegranskat)abstract
- During biofilm formation, Escherichia coli and other Enterobacteriaceae produce an extracellular matrix consisting of curli amyloid fibers and cellulose. The precursor of curli fibers is the amyloidogenic protein CsgA. The human systemic amyloid precursor protein transthyretin (TTR) is known to inhibit amyloid-β (Aβ) aggregation in vitro and suppress the Alzheimer’s-like phenotypes in a transgenic mouse model of Aβ deposition. We hypothesized that TTR might have broad antiamyloid activity because the biophysical properties of amyloids are largely conserved across species and kingdoms. Here, we report that both human WT tetrameric TTR (WT-TTR) and its engineered nontetramer-forming monomer (M-TTR, F87M/L110M) inhibit CsgA amyloid formation in vitro, with M-TTR being the more efficient inhibitor. Preincubation of WT-TTR with small molecules that occupy the T4 binding site eliminated the inhibitory capacity of the tetramer; however, they did not significantly compromise the ability of M-TTR to inhibit CsgA amyloidogenesis. TTR also inhibited amyloid-dependent biofilm formation in two different bacterial species with no apparent bactericidal or bacteriostatic effects. These discoveries suggest that TTR is an effective antibiofilm agent that could potentiate antibiotic efficacy in infections associated with significant biofilm formation.
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| 9. |
- Simons, Matthew C., et al.
(författare)
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Structure, Dynamics, and Reactivity for Light Alkane Oxidation of Fe(II) Sites Situated in the Nodes of a Metal–Organic Framework
- 2019
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 141:45, s. 18142-18151
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Tidskriftsartikel (refereegranskat)abstract
- Metal organic frameworks (MOFs), with their crystalline, porous structures, can be synthesized to incorporate a wide range of catalytically active metals in tailored surroundings. These materials have potential as catalysts for conversion of light alkanes, feedstocks available in large quantities from shale gas that are changing the economics of manufacturing commodity chemicals. Mononuclear high-spin (S = 2) Fe(II) sites situated in the nodes of the MOF MIL-100(Fe) convert propane via dehydrogenation, hydroxylation, and overoxidation pathways in reactions with the atomic oxidant N2O. Pair distribution function analysis, N-2 adsorption isotherms, X-ray diffraction patterns, and infrared and Raman spectra confirm the single-phase crystallinity and stability of MIL-100(Fe) under reaction conditions (523 K in vacuo, 378-408 K C3H8 + N2O). Density functional theory (DFT) calculations illustrate a reaction mechanism for the formation of 2-propanol, propylene, and 1-propanol involving the oxidation of Fe(II) to Fe(III) via a high-spin Fe(IV)=O intermediate. The speciation of Fe(II) and Fe(III) in the nodes and their dynamic interchange was characterized by in situ X-ray absorption spectroscopy and ex situ Mossbauer spectroscopy. The catalytic relevance of Fe(II) sites and the number of such sites were determined using in situ chemical titrations with NO. N-2 and C3H6 production rates were found to be first-order in N2O partial pressure and zero-order in C3H8 partial pressure, consistent with DFT calculations that predict the reaction of Fe(II) with N2O to be rate determining. DFT calculations using a broken symmetry method show that Fe-trimer nodes affecting reaction contain antiferromagnetically coupled iron species, and highlight the importance of stabilizing high-spin (S = 2) Fe(II) species for effecting alkane oxidation at low temperatures (<408 K).
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| 10. |
- Umehata, Hideki, et al.
(författare)
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ALMA Reveals Strong [C II] Emission in a Galaxy Embedded in a Giant Ly alpha Blob at z=3.1
- 2017
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 834:2
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Tidskriftsartikel (refereegranskat)abstract
- We report the result from observations conducted with the Atacama Large Millimeter/submillimeter Array (ALMA) to detect [C II] 158 mu m fine structure line emission from galaxies embedded in one of the most spectacular Ly alpha blobs (LABs) at z = 3.1, SSA22-LAB1. Of three dusty star-forming galaxies previously discovered by ALMA 860 mu m dust continuum survey toward SSA22-LAB1, we detected the [C II] line from one, LAB1-ALMA3 at z = 3.0993 +/- 0.0004. No line emission was detected, associated with the other ALMA continuum sources or from three rest-frame UV/optical selected z(spec) similar or equal to 3.1 galaxies within the field of view. For LAB1-ALMA3, we find relatively bright [C II] emission compared to the infrared luminosity (L-[C II]/LIR approximate to 0.01) and an extremely high [C II] 158 mu m and [N II] 205 mu m emission line ratio (L[C II]/L[N II] > 55). The relatively strong [C II] emission may be caused by abundant photodissociation regions and sub-solar metallicity, or by shock heating. The origin of the unusually strong [C II] emission could be causally related to the location within the giant LAB, although the relationship between extended Ly alpha emission and interstellar medium conditions of associated galaxies is yet to be understand.
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