Gait analysis in a <i>Mecp2</i> knockout mouse model of Rett syndrome reveals early-onset and progressive motor deficits

Rett syndrome (RTT) is a genetic disorder characterized by a range of features including cognitive impairment, gait abnormalities and a reduction in purposeful hand skills. Mice harbouring knockout mutations in the &lt;i&gt;Mecp2&lt;/i&gt; gene display many RTT-like characteristics and are central to efforts to find novel therapies for the disorder. As hand stereotypies and gait abnormalities constitute major diagnostic criteria in RTT, it is clear that motor and gait-related phenotypes will be of importance in assessing preclinical therapeutic outcomes. We therefore aimed to assess gait properties over the prodromal phase in a functional knockout mouse model of RTT. In male &lt;i&gt;Mecp2&lt;/i&gt; knockout mice, we observed alterations in stride, coordination and balance parameters at 4 weeks of age, before the onset of other overt phenotypic changes as revealed by observational scoring. These data suggest that gait measures may be used as a robust and early marker of &lt;i&gt;Mecp2&lt;/i&gt;-dysfunction in future preclinical therapeutic studies

Effect of trace dissolved oxygen on the cathodic kinetics of carbon dioxide corrosion of carbon steel.

Summary: The corrosion of carbon steel in carbon dioxide saturated brine solutions is controlled by a mixed activation-mass transfer process in the cathodic reaction mechanism. Cathodic polarisation curves of carbon steel in carbonic acid solutions exhibit a limiting current behaviour that is dependent on the rate of mass transfer. In studies using the jet impingement technique, the magnitude of this limiting current behaviour has been found to be strongly affected by the presence of trace levels of dissolved oxygen. This paper presents a theoretical assessment of the mass transfer limited cathodic current to illustrate the pronounced effect of dissolved oxygen contamination <15ppb. Discussion is presented regarding the implications of dissolved oxygen contamination on the interpretation of the mechanism of carbon dioxide corrosion

Flow Dependence of Carbon Dioxide Corrosion Using Short Electrodes by Jet Impingement

The jet impingement technique is a valuable methodology for the evaluation of carbon dioxide corrosion and inhibition under high flow velocities. This technique commonly employs short electrodes that remain within a region of the developing diffusion boundary layer induced by the reactively corroding surface. The employment of such electrodes has been associated with the poor correlation of corrosion rates determined from field and laboratory measurements by various apparatus. This paper presents an investigation into the flow relationship of the carbon dioxide corrosion mechanism in non-scaling synthetic brine solutions at 30 C with a carbon dioxide partial pressure of 1.88 bar. The effect of the developing diffusion boundary layer on the corrosion rate and its dependence on the flow velocity is investigated by jet impingement using dissimilar electrode lengths in the flow direction.It is shown that the measured corrosion rate is dependent on the state of development of the diffusion boundary layer with a relationship that is contrary to the average rate of mass transfer. A more developed diffusion boundary layer exhibits a greater rate of carbon dioxide corrosion at a lower average mass transfer than in a developing diffusion boundary layer with a higher average mass transfer. This phenomenon illustrates an antagonistic effect of the diffusion boundary layer on the mechanism of carbon dioxide corrosion that is likely to strongly influence the correlation of corrosion rates obtained using various laboratory apparatus and field applications

Age-associated changes in long-chain fatty acid profile during healthy aging promote pro-inflammatory monocyte polarization via PPARγ

Differences in lipid metabolism associate with age-related disease development and lifespan. Inflammation is a common link between metabolic dysregulation and aging. Saturated fatty acids (FAs) initiate pro-inflammatory signalling from many cells including monocytes; however, no existing studies have quantified age-associated changes in individual FAs in relation to inflammatory phenotype. Therefore, we have determined the plasma concentrations of distinct FAs by gas chromatography in 26 healthy younger individuals (age 50 years). Linear mixed models were used to explore the association between circulating FAs, age and cytokines. We showed that plasma saturated, poly- and mono-unsaturated FAs increase with age. Circulating TNF-α and IL-6 concentrations increased with age, whereas IL-10 and TGF-β1 concentrations decreased. Oxidation of MitoSOX Red was higher in leucocytes from FA adults, and plasma oxidized glutathione concentrations were higher. There was significant colinearity between plasma saturated FAs, indicative of their metabolic relationships. Higher levels of the saturated FAs C18:0 and C24:0 were associated with lower TGF-β1 concentrations, and higher C16:0 were associated with higher TNF-α concentrations. We further examined effects of the aging FA profile on monocyte polarization and metabolism in THP1 monocytes. Monocytes preincubated with C16:0 increased secretion of pro-inflammatory cytokines in response to phorbol myristate acetate-induced differentiation through ceramide-dependent inhibition of PPARγ activity. Conversely, C18:1 primed a pro-resolving macrophage which was PPARγ dependent and ceramide dependent and which required oxidative phosphorylation. These data suggest that a midlife adult FA profile impairs the switch from proinflammatory to lower energy, requiring anti-inflammatory macrophages through metabolic reprogramming

Planet Hunters. VI: An Independent Characterization of KOI-351 and Several Long Period Planet Candidates from the Kepler Archival Data

We report the discovery of 14 new transiting planet candidates in the Kepler field from the Planet Hunters citizen science program. None of these candidates overlapped with Kepler Objects of Interest (KOIs) at the time of submission. We report the discovery of one more addition to the six planet candidate system around KOI-351, making it the only seven planet candidate system from Kepler. Additionally, KOI-351 bears some resemblance to our own solar system, with the inner five planets ranging from Earth to mini-Neptune radii and the outer planets being gas giants; however, this system is very compact, with all seven planet candidates orbiting $\lesssim 1$ AU from their host star. A Hill stability test and an orbital integration of the system shows that the system is stable. Furthermore, we significantly add to the population of long period transiting planets; periods range from 124-904 days, eight of them more than one Earth year long. Seven of these 14 candidates reside in their host star's habitable zone.Comment: 27 pages, 6 figures, 5 tables, Accepted to AJ (in press) (updated title from original astro-ph submission

Safety profile of autologous macrophage therapy for liver cirrhosis

This work was supported by a Medical Research Council UK grant (Biomedical Catalyst Major Awards Committee; reference MR/M007588/1) to S.J. Forbes. We thank Z.M. Younossi (Center for Outcomes Research in Liver Diseases, Washington, DC, USA) for academic use of the CLDQ instrument and L.J. Fallowfield (Sussex Health Outcomes Research & Education in Cancer (SHORE-C), University of Sussex, UK) for advice about health-related quality of life assessment.Peer reviewedPostprintPostprintPostprintPostprin

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin