Non-destructive imaging of an individual protein

The mode of action of proteins is to a large extent given by their ability to adopt different conformations. This is why imaging single biomolecules at atomic resolution is one of the ultimate goals of biophysics and structural biology. The existing protein database has emerged from X-ray crystallography, NMR or cryo-TEM investigations. However, these tools all require averaging over a large number of proteins and thus over different conformations. This of course results in the loss of structural information. Likewise it has been shown that even the emergent X-FEL technique will not get away without averaging over a large quantity of molecules. Here we report the first recordings of a protein at sub-nanometer resolution obtained from one individual ferritin by means of low-energy electron holography. One single protein could be imaged for an extended period of time without any sign of radiation damage. Since ferritin exhibits an iron core, the holographic reconstructions could also be cross-validated against TEM images of the very same molecule by imaging the iron cluster inside the molecule while the protein shell is decomposed

The geometry of a vorticity model equation

We provide rigorous evidence of the fact that the modified Constantin-Lax-Majda equation modeling vortex and quasi-geostrophic dynamics describes the geodesic flow on the subgroup of orientation-preserving diffeomorphisms fixing one point, with respect to right-invariant metric induced by the homogeneous Sobolev norm $H^{1/2}$ and show the local existence of the geodesics in the extended group of diffeomorphisms of Sobolev class $H^{k}$ with $k\ge 2$.Comment: 24 page

Adenine-Induced Nephropathy Reduces Atherosclerosis in ApoE Knockout Mice.

BACKGROUND Cardiovascular events are the main cause of death in patients with chronic kidney disease. We hypothesize that the protective effects of renal cholesterol and vitamin D3 metabolism are lost under this condition. Nephropathy was induced by adenine in Apolipoprotein E knockout mice. The atherosclerotic phenotype was compared to mice with normal renal function. METHODS Mice were fed a western diet ±0.15% adenine. Urine and feces were collected to assess renal function and fecal output. Atherosclerosis, serum lipoprotein composition and functionality, hepatic lipids, and expression of genes involved in lipid metabolism, vitamin D3 and Na+ homeostasis, were assessed. Bones were analyzed by microCT. RESULTS Mice fed with adenine showed enhanced urinary Na+, Ca2+, and Pi excretion, reduced urinary pH, UreaUrine/UreaSerum, and CreatinineUrine/CreatinineSerum ratios. They developed less atherosclerosis. Lipoproteins in serum and hepatic lipids remained unchanged. Cholesterol efflux increased. Fecal output of cholesteryl ester and triglycerides increased. In the liver, mRNA levels of Cyp27a1, Cyp7a1, and Scarb1 increased; in the kidneys, Slc9a3, Slc12a3, Vdr, and Cyp24a1 decreased. Adenine increased cholesterol efflux in vitro. Tibias were shorter. CONCLUSION Adenine induced tubular damage and was athero-protective because of enhanced cholesterol efflux and lipids elimination in feces. Bone growth was also affected

A structural evaluation of the tungsten isotopes via thermal neutron capture

Total radiative thermal neutron-capture $\gamma$-ray cross sections for the $^{182,183,184,186}$W isotopes were measured using guided neutron beams from the Budapest Research Reactor to induce prompt and delayed $\gamma$ rays from elemental and isotopically-enriched tungsten targets. These cross sections were determined from the sum of measured $\gamma$-ray cross sections feeding the ground state from low-lying levels below a cutoff energy, E$_{\rm crit}$, where the level scheme is completely known, and continuum $\gamma$ rays from levels above E$_{\rm crit}$, calculated using the Monte Carlo statistical-decay code DICEBOX. The new cross sections determined in this work for the tungsten nuclides are: $\sigma_{0}(^{182}{\rm W}) = 20.5(14)$ b and $\sigma_{11/2^{+}}(^{183}{\rm W}^{m}, 5.2 {\rm s}) = 0.177(18)$ b; $\sigma_{0}(^{183}{\rm W}) = 9.37(38)$ b and $\sigma_{5^{-}}(^{184}{\rm W}^{m}, 8.33 \mu{\rm s}) = 0.0247(55)$ b; $\sigma_{0}(^{184}{\rm W}) = 1.43(10)$ b and $\sigma_{11/2^{+}}(^{185}{\rm W}^{m}, 1.67 {\rm min}) = 0.0062(16)$ b; and, $\sigma_{0}(^{186}{\rm W}) = 33.33(62)$ b and $\sigma_{9/2^{+}}(^{187}{\rm W}^{m}, 1.38 \mu{\rm s}) = 0.400(16)$ b. These results are consistent with earlier measurements in the literature. The $^{186}$W cross section was also independently confirmed from an activation measurement, following the decay of $^{187}$W, yielding values for $\sigma_{0}(^{186}{\rm W})$ that are consistent with our prompt $\gamma$-ray measurement. The cross-section measurements were found to be insensitive to choice of level density or photon strength model, and only weakly dependent on E$_{\rm crit}$. Total radiative-capture widths calculated with DICEBOX showed much greater model dependence, however, the recommended values could be reproduced with selected model choices. The decay schemes for all tungsten isotopes were improved in these analyses.Comment: 25 pages, 15 figures, 15 table

Exploring the behavioural drivers of veterinary surgeon antibiotic prescribing: a qualitative study of companion animal veterinary surgeons in the UK

Background: Multi-drug resistant bacteria are an increasing concern in both human and veterinary medicine. Inappropriate prescribing and use of antibiotics within veterinary medicine may be a contributory factor to antimicrobial resistance (AMR). The ‘One Health’ Initiative aims to work across species and environments to reduce AMR, however; little is currently known about the factors which influence antibiotic prescribing among veterinary surgeons in companion animal practice. This paper reports on qualitative data analysis of interviews with veterinary surgeons whose practice partially or wholly focuses on companion animals (N = 16). The objective of the research was to explore the drivers of companion animal veterinary surgeons’ antibiotic prescribing behaviours. The veterinary surgeons interviewed were all practising within the UK (England (n = 4), Scotland (n = 11), Northern Ireland (n = 1)). A behavioural thematic analysis of the data was undertaken, which identified barriers and facilitators to specific prescribing-related behaviours. Results: Five components of prescribing behaviours were identified: 1) confirming clinical need for antibiotics; 2) responding to clients; 3) confirming diagnosis; 4) determining dose, duration and type of antibiotic; and 5) preventing infection around surgery (with attendant appropriate and inappropriate antibiotic prescribing behaviours). Barriers to appropriate prescribing identified include: business, diagnostic, fear, habitual practice and pharmaceutical factors. Facilitators include: AMR awareness, infection prevention, professional learning and regulation and government factors. Conclusion: This paper uses a behavioural lens to examine drivers which are an influence on veterinary surgeons’ prescribing behaviours. The paper contributes new understandings about factors which influence antibiotic prescribing behaviours among companion animal veterinary surgeons. This analysis provides evidence to inform future interventions, which are focused on changing prescribing behaviours, in order to address the pressing public health concern of AMR