2'-5'-Oligoadenylate synthetase-like protein inhibits intracellular M. tuberculosis replication and promotes proinflammatory cytokine secretion

CITATION: Leisching, G. et al. 2020. 2'-5'-Oligoadenylate synthetase-like protein inhibits intracellular M. tuberculosis replication and promotes proinflammatory cytokine secretion. Molecular Immunology, 118:73–78, doi:0.1016/j.molimm.2019.12.004.The original publication is available at https://www.sciencedirect.comHost cytoplasmic surveillance pathways are known to elicit type I interferon (IFN) responses which are crucial to antimicrobial defense mechanisms. Oligoadenylate synthetase-like (OASL) protein has been extensively characterized as a part of the anti-viral mechanism, however a number of transcriptomic studies reveal its upregulation in response to infection with a wide variety of intracellular bacterial pathogens. To date, there is no evidence documenting the role (if any) of OASL during mycobacterium tuberculosis infection. Using two pathogenic strains differing in virulence only, as well as the non-pathogenic M. bovis BCG strain, we observed that pathogenicity and virulence strongly induced OASL expression after 24 h of infection. Further, we observed that OASL knock down led to a significant increase in M. tb CFU counts 96 h post-infection in comparison to the respective controls. Luminex revealed that OASL silencing significantly decreased IL-1β, TNF-α and MCP-1 secretion in THP-1 cells and had no effect on IL-10 secretion. We therefore postulate that OASL regulates pro-inflammatory mediators such as cytokines and chemokines which suppress intracellular mycobacterial growth and survival.South African Medical Research CouncilNational Research Foundation of South AfricaPublisher's versio

Dynamic and approximate pattern matching in 2D

International audienc

Critical animal and media studies: Expanding the understanding of oppression in communication research

Critical and communication studies have traditionally neglected the oppression conducted by humans towards other animals. However, our (mis)treatment of other animals is the result of public consent supported by a morally speciesist-anthropocentric system of values. Speciesism or anthroparchy, as much as any other mainstream ideologies, feeds the media and at the same time is perpetuated by them. The goal of this article is to remedy this neglect by introducing the subdiscipline of Critical Animal and Media Studies. Critical Animal and Media Studies takes inspiration both from critical animal studies – which is so far the most consolidated critical field of research in the social sciences addressing our exploitation of other animals – and from the normative-moral stance rooted in the cornerstones of traditional critical media studies. The authors argue that the Critical Animal and Media Studies approach is an unavoidable step forward for critical media and communication studies to engage with the expanded circle of concerns of contemporary ethical thinking

Diversity within the adenovirus fiber knob hypervariable loops influences primary receptor interactions

Adenovirus based vectors are of increasing importance for wide ranging therapeutic applications. As vaccines, vectors derived from human adenovirus species D serotypes 26 and 48 (HAdV-D26/48) are demonstrating promising efficacy as protective platforms against infectious diseases. Significant clinical progress has been made, yet definitive studies underpinning mechanisms of entry, infection, and receptor usage are currently lacking. Here, we perform structural and biological analysis of the receptor binding fiber-knob protein of HAdV-D26/48, reporting crystal structures, and modelling putative interactions with two previously suggested attachment receptors, CD46 and Coxsackie and Adenovirus Receptor (CAR). We provide evidence of a low affinity interaction with CAR, with modelling suggesting affinity is attenuated through extended, semi-flexible loop structures, providing steric hindrance. Conversely, in silico and in vitro experiments are unable to provide evidence of interaction between HAdV-D26/48 fiber-knob with CD46, or with Desmoglein 2. Our findings provide insight into the cell-virus interactions of HAdV-D26/48, with important implications for the design and engineering of optimised Ad-based therapeutics

Galaxy morphology and evolution from SWAN Adaptive Optics imaging

We present the results from adaptive optics (AO) assisted imaging in the Ks band of an area of 15 arcmin^2 for SWAN (Survey of a Wide Area with NACO). We derive the high resolution near-IR morphology of ~400 galaxies up to Ks~23.5 in the first 21 SWAN fields around bright guide stars, carefully taking into account the survey selection effects and using an accurate treatment of the anisoplanatic AO PSF. The detected galaxies are sorted into two morphological classes according to their Sersic index. The extracted morphological properties and number counts of the galaxies are compared with the predictions of different galaxy formation and evolution models, both for the whole galaxy population and separately for late-type and early-type galaxies. This is one of the first times such a comparison has been done in the near-IR, as AO observations and accurate PSF modeling are needed to obtain reliable morphological classification of faint field galaxies at these wavelengths. For early-type galaxies we find that a pure luminosity evolution model, without evidence for relevant number and size evolution, better reproduces the observed properties of our Ks-selected sample than current semi-analytic models based on the hierarchical picture of galaxy formation. In particular, we find that the observed flattening of elliptical galaxy counts at Ks~20 is quantitatively in good agreement with the prediction of the pure luminosity evolution model that was calculated prior to the observation. For late-type galaxies, while both models are able to reproduce the number counts, we find some hints of a possible size growth. These results demonstrate the unique power of AO observations to derive high resolution details of faint galaxies' morphology in the near-IR and drive studies of galaxy evolution.Comment: 15 pages, 10 figures. A&A, in press. Final version with corrected typo

Applying support-vector machine learning algorithms toward predicting host-guest interactions with cucurbit[7]uril.

Machine learning is a valuable tool in the development of chemical technologies but its applications into supramolecular chemistry have been limited. Here, the utility of kernel-based support vector machine learning using density functional theory calculations as training data is evaluated when used to predict equilibrium binding coefficients of small molecules with cucurbit[7]uril (CB[7]). We find that utilising SVMs may confer some predictive ability. This algorithm was then used to predict the binding of drugs TAK-580 and selumetinib. The algorithm did predict strong binding for TAK-580 and poor binding for selumetinib, and these results were experimentally validated. It was discovered that the larger homologue cucurbit[8]uril (CB[8]) is partial to selumetinib, suggesting an opportunity for tunable release by introducing different concentrations of CB[7] or CB[8] into a hydrogel depot. We qualitatively demonstrated that these drugs may have utility in combination against gliomas. Finally, mass transfer simulations show CB[7] can independently tune the release of TAK-580 without affecting selumetinib. This work gives specific evidence that a machine learning approach to recognition of small molecules by macrocycles has merit and reinforces the view that machine learning may prove valuable in the development of drug delivery systems and supramolecular chemistry more broadly.A.T. and M.P.S. thank The Winston Churchill Foundation of the United States. A.T. thanks the National Science Foundation graduate research fellowship, the MIT Chemical Engineering first year fellowship, and the Churchill College post-graduate grant program. G.W. thanks the Leverhulme Trust (project: ‘Natural material innovation for sustainable living’). V.K.R. thanks the Swiss National Science Foundation (P2EZP2_168784). O.A.S. acknowledges EPSRC Programme grant Nano-Optics to controlled Nano- Chemistry (NOtCH, EP/L027151/1) for funding

Sustaining the Digital Humanities in the UK

The Sustaining Digital Humanities in the UK report is timely for the UK Digital Humanities (DH) landscape. The establishment of UK Research and Innovation (UKRI) has created an opportune moment for the strategic planning of research infrastructure between and across all the research areas. Led by Giles Bergel and Pip Willcox, this report is based on the findings of a workshop held at the University of Oxford’s e-Research Centre (OeRC) on 21 June 2018 and sponsored by the Software Sustainability Institute. The workshop was led by an advisory board of Digital Humanities practitioners, representing a range of career stages, roles, and disciplines. The workshop’s organisers and advisory board are the joint authors of this report, with contributions from workshop participants. The mission of the Software Sustainability Institute (SSI) is to cultivate better, more sustainable, research software to enable world-class research. Currently celebrating its 10th year, the SSI has achieved broadening engagement across academic communities including humanities – for example as a longstanding supporter of the Digital Humanities at Oxford Summer School (DHOxSS), and with SSI Fellows in the arts and humanities areas. This report was commissioned by the SSI with the aim of advancing its mission within the humanities. Digital Humanities, a broad intersection of models, methods, tools, materials, career paths and affiliations, in both established and novel disciplines was identified as the area within the humanities that most closely aligns with the SSI’s role

Transcriptomic analysis of field-droughted sorghum from seedling to maturity reveals biotic and metabolic responses.

Drought is the most important environmental stress limiting crop yields. The C4 cereal sorghum [Sorghum bicolor (L.) Moench] is a critical food, forage, and emerging bioenergy crop that is notably drought-tolerant. We conducted a large-scale field experiment, imposing preflowering and postflowering drought stress on 2 genotypes of sorghum across a tightly resolved time series, from plant emergence to postanthesis, resulting in a dataset of nearly 400 transcriptomes. We observed a fast and global transcriptomic response in leaf and root tissues with clear temporal patterns, including modulation of well-known drought pathways. We also identified genotypic differences in core photosynthesis and reactive oxygen species scavenging pathways, highlighting possible mechanisms of drought tolerance and of the delayed senescence, characteristic of the stay-green phenotype. Finally, we discovered a large-scale depletion in the expression of genes critical to arbuscular mycorrhizal (AM) symbiosis, with a corresponding drop in AM fungal mass in the plants' roots

Longitudinal-Transverse Separations of Structure Functions at Low Q2Q^{2} for Hydrogen and Deuterium

We report on a study of the longitudinal to transverse cross section ratio, $R=\sigma_L/\sigma_T$, at low values of $x$ and $Q^{2}$, as determined from inclusive inelastic electron-hydrogen and electron-deuterium scattering data from Jefferson Lab Hall C spanning the four-momentum transfer range 0.06 $< Q^{2} < 2.8$ GeV$^{2}$. Even at the lowest values of $Q^{2}$, $R$ remains nearly constant and does not disappear with decreasing $Q^{2}$, as expected. We find a nearly identical behaviour for hydrogen and deuterium.Comment: 4 pages, 2 gigure