Despite their rarity, massive stars dominate the ecology of galaxies via their strong, radiatively-driven winds throughout their lives and as supernovae in their deaths. However, their evolution and ...subsequent impact on their environment can be significantly affected by the presence of a magnetic field. While recent studies indicate that about 7% of OB stars in the Milky Way host strong, stable, organised (fossil) magnetic fields at their surfaces, little is known about the fields of very massive stars, nor the magnetic properties of stars outside our Galaxy. We aim to continue searching for strong magnetic fields in a diverse set of massive and very massive stars (VMS) in the Large and Small Magellanic Clouds (LMC/SMC), and we evaluate the overall capability of FORS2 to usefully search for and detect stellar magnetic fields in extra-galactic environments. We have obtained FORS2 spectropolarimetry of a sample of 41 stars, which principally consist of spectral types B, O, Of/WN, WNh, and classical WR stars in the LMC and SMC. Four of our targets are Of?p stars; one of them was just recently discovered. Each spectrum was analysed to infer the longitudinal magnetic field. No magnetic fields were formally detected in our study, although Bayesian statistical considerations suggest that the Of?p star SMC 159-2 is magnetic with a dipolar field of the order of 2.4–4.4 kG. In addition, our first constraints of magnetic fields in VMS provide interesting insights into the formation of the most massive stars in the Universe.
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FMFMET, NUK, UL, UM, UPUK
Abstract
The removal of RNA primers is essential for mitochondrial DNA (mtDNA) replication. Several nucleases have been implicated in RNA primer removal in human mitochondria, however, no conclusive ...mechanism has been elucidated. Here, we reconstituted minimal in vitro system capable of processing RNA primers into ligatable DNA ends. We show that human 5′-3′ exonuclease, EXOG, plays a fundamental role in removal of the RNA primer. EXOG cleaves short and long RNA-containing flaps but also in cooperation with RNase H1, processes non-flap RNA-containing intermediates. Our data indicate that the enzymatic activity of both enzymes is necessary to process non-flap RNA-containing intermediates and that regardless of the pathway, EXOG-mediated RNA cleavage is necessary prior to ligation by DNA Ligase III. We also show that upregulation of EXOG levels in mitochondria increases ligation efficiency of RNA-containing substrates and discover physical interactions, both in vitro and in cellulo, between RNase H1 and EXOG, Pol γA, Pol γB and Lig III but not FEN1, which we demonstrate to be absent from mitochondria of human lung epithelial cells. Together, using human mtDNA replication enzymes, we reconstitute for the first time RNA primer removal reaction and propose a novel model for RNA primer processing in human mitochondria.
Underlying the architectural complexity of plants are diverse cell types that, under the microscope, easily reveal relationships between cell structure and specialized functions. Much less obvious ...are the mechanisms by which the cellular growth machinery and mechanical properties of the cell interact to dictate cell shape. The recent combined use of mutants, genomic analyses, sophisticated spectroscopies, and live cell imaging is providing new insight into how cytoskeletal systems and cell wall biosynthetic activities are integrated during morphogenesis. The purpose of this review is to discuss the unique geometric properties and physical processes that regulate plant cell expansion, then to overlay on this mechanical system some of the recent discoveries about the protein machines and cellular polymers that regulate cell shape. In the end, we hope to make clear that there are many interesting opportunities to develop testable mathematical models that improve our understanding of how subcellular structures, protein motors, and extracellular polymers can exert effects at spatial scales that span cells, tissues, and organs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cancer treatment suffers from limitations that have a major impact on the patient’s quality of life and survival. In the case of chemotherapy, the systemic distribution of cytotoxic drugs reduces ...their efficacy and causes severe side effects due to nonselective toxicity. Photopharmacology allows a novel approach to address these problems because it employs external, local activation of chemotherapeutic agents by using light. The development of photoswitchable histone deacetylase (HDAC) inhibitors as potential antitumor agents is reported herein. Analogues of the clinically used chemotherapeutic agents vorinostat, panobinostat, and belinostat were designed with a photoswitchable azobenzene moiety incorporated into their structure. The most promising compound exhibits high inhibitory potency in the thermodynamically less stable cis form and a significantly lower activity for the trans form, both in terms of HDAC activity and proliferation of HeLa cells. This approach offers a clear prospect towards local photoactivation of HDAC inhibition to avoid severe side effects in chemotherapy.
Bright therapy: Chemotherapeutic histone deacetylase (HDAC) inhibitors with photocontrolled activity are presented. On HDAC2, the best compound shows high potency (similar to the clinically used parent hydroxamic acid; see figure) in the thermodynamically less stable state and 40× lower potency in the resting state. This approach offers prospects towards local photoactivation of HDAC inhibition to avoid severe side effects in chemotherapy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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Machine learning (ML) has become a valuable tool to assist and improve materials characterization, enabling automated interpretation of experimental results with techniques such as X-ray ...diffraction (XRD) and electron microscopy. Because ML models are fast once trained, there is a key opportunity to bring interpretation in-line with experiments and make on-the-fly decisions to achieve optimal measurement effectiveness, which creates broad opportunities for rapid learning and information extraction from experiments. Here, we demonstrate such a capability with the development of autonomous and adaptive XRD. By coupling an ML algorithm with a physical diffractometer, this method integrates diffraction and analysis such that early experimental information is leveraged to steer measurements toward features that improve the confidence of a model trained to identify crystalline phases. We validate the effectiveness of an adaptive approach by showing that ML-driven XRD can accurately detect trace amounts of materials in multi-phase mixtures with short measurement times. The improved speed of phase detection also enables in situ identification of short-lived intermediate phases formed during solid-state reactions using a standard in-house diffractometer. Our findings showcase the advantages of in-line ML for materials characterization and point to the possibility of more general approaches for adaptive experimentation.
A facile method has been developed to prepare aqueous dispersions of encapsulated conjugated polymer nanoparticles exhibiting high fluorescence brightness. Salient features of the nanoparticles ...include their small diameter and spherical morphology. Encapsulation of the nanoparticles with a silica shell reduces the rate of photooxidation and allows facile attachment of functional groups for subsequent bioconjugation and nanoparticle assembly. Functionalization of the nanoparticle with amine groups followed by the addition of Au nanoparticles resulted in the formation of nanoparticle assemblies, as evidenced by the efficient quenching of the conjugated polymer fluorescence by the Au nanoparticles.
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IJS, KILJ, NUK, PNG, UL, UM
To develop a reliable and valid clinical scale measuring the severity of ataxia.
The authors devised the Scale for the Assessment and Rating of Ataxia (SARA) and tested it in two trials of 167 and ...119 patients with spinocerebellar ataxia.
The mean time to administer SARA in patients was 14.2 +/- 7.5 minutes (range 5 to 40). Interrater reliability was high, with an intraclass coefficient (ICC) of 0.98. Test-retest reliability was high with an ICC of 0.90. Internal consistency was high as indicated by Cronbach's alpha of 0.94. Factorial analysis revealed that the rating results were determined by a single factor. SARA ratings showed a linear relation to global assessments using a visual analogue scale, suggesting linearity of the scale (p < 0.0001, r(2) = 0.98). SARA score increased with the disease stage (p < 0.001) and was closely correlated with the Barthel Index (r = -0.80, p < 0.001) and part IV (functional assessment) of the Unified Huntington's Disease Rating Scale (UHDRS-IV) (r = -0.89, p < 0.0001), whereas it had only a weak correlation with disease duration (r = 0.34, p < 0.0002).
The Scale for the Assessment and Rating of Ataxia is a reliable and valid measure of ataxia, making it an appropriate primary outcome measure for clinical trials.
Delafossite structured ternary nitrides, ABN 2 , have been of recent experimental investigation for applications such as tandem solar and photoelectrochemical cells. We present a thorough first ...principles computational investigation of their stability, electronic structure, and optical properties. Nine compounds, where A = Cu, Ag, Au and B = V, Nb, Ta, were studied. For three of these compounds, CuTaN 2 , CuNbN 2 , and AgTaN 2 , our computations agree well with experimental results. Optimized lattice parameters, formation energies, and mechanical properties have been computed using the generalized gradient approximation (GGA). Phonon density of states computed at zero-temperature shows that all compounds are dynamically unstable at low temperatures. Including finite-temperature anharmonic effects stabilizes all compounds at 300 K, with the exception of AgVN 2 . Analysis of Crystal Orbital Hamiltonian Populations (COHP) provides insight into the bonding and antibonding characters of A–N and B–N pairs. Instability at low temperatures can be attributed to strong A–N antibonding character near the Fermi energy. B–N bonding is found to be crucial in maintaining stability of the structure. AgVN 2 is the only compound to display significant B–N antibonding below the Fermi energy, as well as the strongest degree of A–N antibonding, both of which provide explanation for the sustained instability of this compound up to 900 K. Hybrid functional calculations of electronic and optical properties show that real static dielectric constants in the semiconductors are related to corresponding band gaps through the Moss relation. CuTaN 2 , CuNbN 2 , AgTaN 2 , AgNbN 2 , AgVN 2 , AuTaN 2 , and AuNbN 2 exhibit indirect electronic band gaps while CuVN 2 and AuVN 2 are metallic. Imaginary parts of the dielectric function are characterized by d–d interband transitions in the semiconductors and d–d intraband transitions in the metals. Four compounds, CuTaN 2 , CuNbN 2 , AgTaN 2 , and AgNbN 2 , are predicted to exhibit large light absorption in the range of 1.0 to 1.7 eV, therefore making these materials good candidates for solar-energy conversion applications. Two compounds, AuTaN 2 and AuNbN 2 , have band gaps and absorption onsets near the ideal range for obtaining high solar-cell conversion efficiency, suggesting that these compounds could become potential candidates as absorber materials in tandem solar cells or for band-gap engineering by alloying.
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