135 research outputs found

    A Structural View on the Stereospecificity of Plant Borneol‐Type Dehydrogenases

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    The development of sustainable processes for the valorization of byproducts and other waste streams remains an ongoing challenge in the field of catalysis. Racemic borneol, isoborneol and camphor are currently produced from alpha-pinene, a side product from the production of cellulose. The pure enantiomers of these monoterpenoids have numerous applications in cosmetics and act as reagents for asymmetric synthesis, making an enzymatic route for their separation into optically pure enantiomers a desirable goal. Known short-chain borneol-type dehydrogenases (BDHs) from plants and bacteria lack the required specificity, stability or activity for industrial utilization. Prompted by reports on the presence of pure (-)-borneol and (-)-camphor in essential oils from rosemary, we set out to investigate dehydrogenases from the genus Salvia and discovered a dehydrogenase with high specificity (E>120) and high specific activity (>0.02 U mg(-1)) for borneol and isoborneol. Compared to other specific dehydrogenases, the one reported here shows remarkably higher stability, which was exploited to obtain the first three-dimensional structure of an enantiospecific borneol-type short-chain dehydrogenase. This, together with docking studies, led to the identification of a hydrophobic pocket in the enzyme that plays a crucial role in the stereo discrimination of bornane-type monoterpenoids. The kinetic resolution of borneol and isoborneol can be easily integrated into the existing synthetic route from alpha-pinene to camphor thereby allowing the facile synthesis of optically pure monoterpenols from an abundant renewable source

    Water in the terrestrial planet-forming zone of the PDS 70 disk

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    Terrestrial and sub-Neptune planets are expected to form in the inner (<10 <10~AU) regions of protoplanetary disks. Water plays a key role in their formation, although it is yet unclear whether water molecules are formed in-situ or transported from the outer disk. So far Spitzer Space Telescope observations have only provided water luminosity upper limits for dust-depleted inner disks, similar to PDS 70, the first system with direct confirmation of protoplanet presence. Here we report JWST observations of PDS 70, a benchmark target to search for water in a disk hosting a large (54 \sim54~AU) planet-carved gap separating an inner and outer disk. Our findings show water in the inner disk of PDS 70. This implies that potential terrestrial planets forming therein have access to a water reservoir. The column densities of water vapour suggest in-situ formation via a reaction sequence involving O, H2_2, and/or OH, and survival through water self-shielding. This is also supported by the presence of CO2_2 emission, another molecule sensitive to UV photodissociation. Dust shielding, and replenishment of both gas and small dust from the outer disk, may also play a role in sustaining the water reservoir. Our observations also reveal a strong variability of the mid-infrared spectral energy distribution, pointing to a change of inner disk geometry.Comment: To appear in Nature on 24 July 2023. 21 pages, 10 figures; includes extended data. Part of the JWST MINDS Guaranteed Time Observations program's science enabling products. Spectra downloadable on Zenodo at https://zenodo.org/record/799102

    Role of Position 627 of PB2 and the Multibasic Cleavage Site of the Hemagglutinin in the Virulence of H5N1 Avian Influenza Virus in Chickens and Ducks

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    Highly pathogenic H5N1 avian influenza viruses have caused major disease outbreaks in domestic and free-living birds with transmission to humans resulting in 59% mortality amongst 564 cases. The mutation of the amino acid at position 627 of the viral polymerase basic-2 protein (PB2) from glutamic acid (E) in avian isolates to lysine (K) in human isolates is frequently found, but it is not known if this change affects the fitness and pathogenicity of the virus in birds. We show here that horizontal transmission of A/Vietnam/1203/2004 H5N1 (VN/1203) virus in chickens and ducks was not affected by the change of K to E at PB2-627. All chickens died between 21 to 48 hours post infection (pi), while 70% of the ducks survived infection. Virus replication was detected in chickens within 12 hours pi and reached peak titers in spleen, lung and brain between 18 to 24 hours for both viruses. Viral antigen in chickens was predominantly in the endothelium, while in ducks it was present in multiple cell types, including neurons, myocardium, skeletal muscle and connective tissues. Virus replicated to a high titer in chicken thrombocytes and caused upregulation of TLR3 and several cell adhesion molecules, which may explain the rapid virus dissemination and location of viral antigen in endothelium. Virus replication in ducks reached peak values between 2 and 4 days pi in spleen, lung and brain tissues and in contrast to infection in chickens, thrombocytes were not involved. In addition, infection of chickens with low pathogenic VN/1203 caused neuropathology, with E at position PB2-627 causing significantly higher infection rates than K, indicating that it enhances virulence in chickens

    Circumstellar disks and planets. Science cases for next-generation optical/infrared long-baseline interferometers

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    We present a review of the interplay between the evolution of circumstellar disks and the formation of planets, both from the perspective of theoretical models and dedicated observations. Based on this, we identify and discuss fundamental questions concerning the formation and evolution of circumstellar disks and planets which can be addressed in the near future with optical and infrared long-baseline interferometers. Furthermore, the importance of complementary observations with long-baseline (sub)millimeter interferometers and high-sensitivity infrared observatories is outlined.Comment: 83 pages; Accepted for publication in "Astronomy and Astrophysics Review"; The final publication is available at http://www.springerlink.co

    Probing the cold magnetised Universe with SPICA-POL (B-BOP)

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    Space Infrared Telescope for Cosmology and Astrophysics (SPICA), the cryogenic infrared space telescope recently pre-selected for a 'Phase A' concept study as one of the three remaining candidates for European Space Agency (ESA's) fifth medium class (M5) mission, is foreseen to include a far-infrared polarimetric imager [SPICA-POL, now called B-fields with BOlometers and Polarizers (B-BOP)], which would offer a unique opportunity to resolve major issues in our understanding of the nearby, cold magnetised Universe. This paper presents an overview of the main science drivers for B-BOP, including high dynamic range polarimetric imaging of the cold interstellar medium (ISM) in both our Milky Way and nearby galaxies. Thanks to a cooled telescope, B-BOP will deliver wide-field 100-350 μm images of linearly polarised dust emission in Stokes Q and U with a resolution, signal-to-noise ratio, and both intensity and spatial dynamic ranges comparable to those achieved by Herschel images of the cold ISM in total intensity (Stokes I). The B-BOP 200 μm images will also have a factor ∼30 higher resolution than Planck polarisation data. This will make B-BOP a unique tool for characterising the statistical properties of the magnetised ISM and probing the role of magnetic fields in the formation and evolution of the interstellar web of dusty molecular filaments giving birth to most stars in our Galaxy. B-BOP will also be a powerful instrument for studying the magnetism of nearby galaxies and testing Galactic dynamo models, constraining the physics of dust grain alignment, informing the problem of the interaction of cosmic rays with molecular clouds, tracing magnetic fields in the inner layers of protoplanetary disks, and monitoring accretion bursts in embedded protostars

    HST/ACS Multiband Coronagraphic Imaging of the Debris Disk around Beta Pictoris

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    (Abridged.) We present F435W (B), F606W (Broad V), and F814W (Broad I) coronagraphic images of the debris disk around Beta Pictoris obtained with HST's Advanced Camera for Surveys. We confirm that the previously reported warp in the inner disk is a distinct secondary disk inclined by ~5 deg from the main disk. The main disk's northeast extension is linear from 80 to 250 AU, but the southwest extension is distinctly bowed with an amplitude of ~1 AU over the same region. Both extensions of the secondary disk appear linear, but not collinear, from 80 to 150 AU. Within ~120 AU of the star, the main disk is ~50% thinner than previously reported. The surface-brightness profiles along the spine of the main disk are fitted with four distinct radial power laws between 40 and 250 AU, while those of the secondary disk between 80 and 150 AU are fitted with single power laws. These discrepancies suggest that the two disks have different grain compositions or size distributions. The F606W/F435W and F814W/F435W flux ratios of the composite disk are nonuniform and asymmetric about both projected axes of the disk. Within ~120 AU, the m_F435W-m_F606W and m_F435W-m_F814W colors along the spine of the main disk are ~10% and ~20% redder, respectively, than those of Beta Pic. These colors increasingly redden beyond ~120 AU, becoming 25% and 40% redder, respectively, than the star at 250 AU. We compare the observed red colors within ~120 AU with the simulated colors of non-icy grains having a radial number density ~r^-3 and different compositions, porosities, and minimum grain sizes. The observed colors are consistent with those of compact or moderately porous grains of astronomical silicate and/or graphite with sizes >0.15-0.20 um, but the colors are inconsistent with the blue colors expected from grains with porosities >90%.Comment: 38 pages (including 21 figures and 4 tables) in EmulateApJ format, accepted for publication in The Astronomical Journal. Full-resolution figures and fully processed FITS images (with error maps) are available at http://acs.pha.jhu.edu/~dag/betapic Version 2: Added 4 references and some clarifying text. Basic facts and conclusions are unchange

    Status of the mid-IR ELT imager and spectrograph (METIS)

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    The Mid-Infrared ELT Imager and Spectrograph (METIS) is one of three first light instruments on the ELT. It will provide high-contrast imaging and medium resolution, slit-spectroscopy from 3 - 19um, as well as high resolution (R ∼ 100,000) integral field spectroscopy from 2.9-5.3μm. All modes observe at the diffraction limit of the ELT, by means of adaptive optics, yielding angular resolutions of a few tens of milliarcseconds. The range of METIS science is broad, from Solar System objects to active galactic nuclei (AGN). We will present an update on the main science drivers for METIS: circum-stellar disks and exoplanets. The METIS project is now in full steam, approaching its preliminary design review (PDR) in 2018. In this paper we will present the current status of its optical, mechanical and thermal design as well as operational aspects. We will also discuss the challenges of building an instrument for the ELT, and the required technologies. © 2018 SPIE

    Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation

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    Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a life-saving procedure used for the treatment of selected hematological malignancies, inborn errors of metabolism, and bone marrow failures. The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection. However, recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions. Accordingly, neutrophils are emerging as highly versatile cells that are able to acquire different, often opposite, functional capacities depending on the microenvironment and their differentiation status. Herein, we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT, from the hematopoietic stem cell (HSC) mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion. We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versus-host disease (GVHD) prophylaxis. Finally, the potential involvement of neutrophils in alloHSCT-related complications, such as transplant-associated thrombotic microangiopathy (TA-TMA), acute and chronic GVHD, and cytomegalovirus (CMV) reactivation, is also discussed. Based on the data reviewed herein, the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role. However, much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT
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