Ablation of Bscl2/Seipin in hepatocytes does not cause metabolic dysfunction in congenital generalised lipodystrophy

Funding Work was supported by the Medical Research Council (GDM/JJR; MR/L002620/1, MC/PC/15077), the Biotechnology and Biological Sciences Research Council (JJR; BB/K017772/1), Diabetes UK (GDM/JJR; 18/0005884), the British Heart Foundation (MD;PG/14/43/30889) and the Wellcome Trust and the University of Aberdeen ISSF Fund (GDM; ISSF Fellowship Support Fund).Peer reviewedPublisher PD

Gene therapy restores adipose tissue and metabolic health in a pre-clinical mouse model of lipodystrophy

The authors are extremely grateful to Dr Donna MacCallum (University of Aberdeen) for assistance with AAV vector i.v. tail vein injections and Pat Bain (University of Aberdeen) for design and generation of the graphical abstract. The authors would also like to thank the staff at the University of Aberdeen’s Microscopy and Histology Core Facility and the Medical Research Facility for support with animal breeding and maintenance. This research was supported by funding from the EFSD/Lilly Young Investigator Research Award Programme, Wellcome Trust ISSF Fellowship Support Fund, and Diabetes UK RD Lawrence Fellowship (21/0006280) awarded to G.D.M. and Diabetes UK (18/0005884) awarded to J.J.R.Peer reviewedPublisher PD

The coupling of valence shell and particle-hole degrees of freedom in a partial random phase approximation

It is well known that the random phase approximation breaks down in the absence of a substantial energy gap between occupied and unoccupied single-particle states. Particle-hole excitations are then inevitably accompanied by substantial rearrangements of the particles in the neighbourhood of the Fermi surface. To accommodate this situation, a partial RPA is introduced which corresponds to replacing only the particle-hole degrees of freedom by bosons but leaving the valence space degrees of freedom intact. The PRPA is therefore a mapping of the many-fermion dynamics into the dynamics of a coupled boson-valence space. In application of the PRPA, algebraic methods, of either a fermionic or Lie algebra type, can be introduced, if desired, to facilitate the treatment of the valence space degrees of freedom. Results of applications are presented in which the valence space particles are treated in the rotational and SU(3) models, and are coupled strongly to giant dipole and quadrupole resonances.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26774/1/0000326.pd

Ordered growth of vanadyl phthalocyanine (VOPc) on an iron phthalocyanine (FePc) monolayer

The growth and characterisation of a non-planar phthalocyanine (Vanadyl Phthalocyanine, VOPc) on a complete monolayer (ML) of a planar phthalocyanine (Iron (II) Phthalocyanine, FePc) on an Au (111) surface, has been investigated using ultra-high vacuum (UHV) scanning tunnelling microscopy (STM) and low energy electron diffraction (LEED). The surface mesh of the initial FePc monolayer has been determined and shown to correspond to an incommensurate overlayer, not commensurate as previously reported. Ordered islands of VOPc, with (1x1) epitaxy, grow on the FePc layer at submonolayer coverages. The individual VOPc molecules occupy sites directly atop the underlying FePc molecules, indicating that significant intermolecular bonding must occur. It is proposed that this interaction implies that the V=O points down into the surface, allowing a Fe-O bond to form. The detailed appearance of the STM images of the VOPc molecules is consistent with previous studies in other VOPc growth studies in which this molecular orientation has been proposed

Bscl2 Deficiency Does Not Directly Impair the Innate Immune Response in a Murine Model of Generalized Lipodystrophy

Funding: Work was supported by Diabetes UK (JJR;18/0005884, MD;17/0005621) the Medical Research Council (JJR; MR/L002620/1, MC/PC/15077), the British Heart Foundation (MD; PG/14/43/30889), The Agency for Science, Technology and Research, Singapore (A*STAR) (WH), The Wellcome Trust (ISSF Funding to GDM) and the European Union’s Horizon 2020 ERC consolidator award (MB:2016-726152-TYPHI).Peer reviewedPublisher PD

Malaria and pregnancy: placental cytokine expression and its relationship to intrauterine growth retardation

Malaria infections during pregnancy can lead to the delivery of low-birth-weight infants. In this study, cytokine mRNA was measured in placentas from 23 malaria-infected and 21 uninfected primigravid women who had delivered in Mangochi, Malawi, a region with a high rate of transmission of falciparum malaria. Significantly increased expression of interleukin (IL)-1beta, IL-8, and tumor necrosis factor (TNF)-alpha and decreased expression of IL-6 and transforming growth factor-beta1 were found in malaria-infected compared with uninfected placentas. TNF-alpha and IL-8 were produced by maternally derived hemozoin-laden placental macrophages. Increased TNF-alpha expression was associated with increased placental hemozoin concentrations. Increased TNF-alpha or IL-8 expression in the placenta was associated with intrauterine growth retardation but not with preterm delivery. The results suggest that malaria infections induce a potentially harmful proinflammatory response in the placenta

Platforms to differentiate exotic pathovars of plant bacteria

Many of the EPPs that pose the biggest threat to the biosecurity of Australia’s plant industries are bacterial, but difficulties in identification to the subspecific or ‘ pathovar ’ level can seriously delay incursion management and affect market access. Pathovars are defined by host specificity so bio assays remain the definitive means of identification, but these require high level physical containment and can be slow and subjective , delaying diagnosis . Some pathovar - specific serological and molecular tests are available but better diagnostic methods are often required. This project used proteomics and metabolomics, platforms that identify functional molecules potentially associated with plant - pathogen interactions, to identify biomarkers that differentiate pathovars in species of Xanthomonas . Membrane - associated proteins from a collection of bacterial isolates were compared on 2Dimensional gels. Proteins that were found to be differentially expressed between distinct pathovars may be important modulators of host specificity so they were identified and the genes that encode them located by reference to genomic sequences . DNA - based assays targeting these genes were designed and validated for their specificity to the pathovar level . We have developed two new assays that provide levels of specificity not reported elsewhere in the literature. These assays specifically target the bacteria causing the different forms of citrus canker, but without cross - reaction to the closely - related organisms causing bacterial blight on cotton and Citrus Bacterial Spot. The molecular assays will be incorporated into the National Diagnostic Protocol for citrus canker through the SPHDS process. The metabolomics component has analysed metabolite expression in selected bacterial pathovars. Results showed separation between the different pathovars based on differential levels of expression of particular metabolites. These metabolites may be important determinants of pathogenicity. Neither proteomics nor metabolomics had been implemented before in the study of phytopathogenic bacteria and whilst both proved to be technically demanding, each delivered new biomarkers that differentiate phytopathogenic bacteria to a subspecific level . This confirmed the viability of these approaches as platforms to discover novel diagnostic targets. The new methods developed will be implemented into the national incursion response capability , improving the specificity of diagnostic testing available and reducing the possibility of false positive diagnosis . The project has fostered new collaborative partnerships both nationally (NSW, Victoria, WA) and internationally (to Thailand and the USA). The next phase of this work will provide a strong start - up project to the Plant Biosecurity Cooperative Research Centre ( PBCRC ) . This project has directly enhanced the plant bacteriology capacity of NSW and Australia trough the recruitment and training of science professionals and an undergraduate student , and supported the specialist training of a Thai scientist through allied project CRC20093

Donor–acceptor co-adsorption ratio controls the structure and electronic properties of two-dimensional alkali–organic networks on Ag(100)

P.T.P.R. and P.J.B. acknowledge financial support from Diamond Light Source and EPSRC. G.C. acknowledges financial support from the EU through the ERC Grant “VISUAL-MS” (Project ID: 308115). B.S. and R.J.M. acknowledge doctoral studentship funding from the EPSRC and the National Productivity Investment Fund (NPIF). R.J.M. acknowledges financial support via a UKRI Future Leaders Fellowship (MR/S016023/1).The results are presented of a detailed combined experimental and theoretical investigation of the influence of coadsorbed electron-donating alkali atoms and the prototypical electron acceptor molecule 7,7,8,8-tetracyanoquinodimethane (TCNQ) on the Ag(100) surface. Several coadsorption phases were characterized by scanning tunneling microscopy, low-energy electron diffraction, and soft X-ray photoelectron spectroscopy. Quantitative structural data were obtained using normal-incidence X-ray standing wave (NIXSW) measurements and compared with the results of density functional theory (DFT) calculations using several different methods of dispersion correction. Generally, good agreement between theory and experiment was achieved for the quantitative structures, albeit with the prediction of the alkali atom heights being challenging for some methods. The adsorption structures depend sensitively on the interplay of molecule–metal charge transfer and long-range dispersion forces, which are controlled by the composition ratio between alkali atoms and TCNQ. The large difference in atomic size between K and Cs has negligible effects on stability, whereas increasing the ratio of K/TCNQ from 1:4 to 1:1 leads to a weakening of molecule–metal interaction strength in favor of stronger ionic bonds within the two-dimensional alkali–organic network. A strong dependence of the work function on the alkali donor–TCNQ acceptor coadsorption ratio is predicted.Publisher PDFPeer reviewe