Regulation of IL-1β-induced NFκB by hydroxylases links key hypoxic and inflammatory signaling pathways

Hypoxia is a prominent feature of chronically inflamed tissues. Oxygen-sensing hydroxylases control transcriptional adaptation to hypoxia through the regulation of hypoxia-inducible factor (HIF) and nuclear factor ?B (NF-?B), both of which can regulate the inflammatory response. Furthermore, pharmacologic hydroxylase inhibitors reduce inflammation in multiple animal models. However, the underlying mechanism(s) linking hydroxylase activity to inflammatory signaling remains unclear. IL-1ß, a major proinflammatory cytokine that regulates NF-?B, is associated with multiple inflammatory pathologies. We demonstrate that a combination of prolyl hydroxylase 1 and factor inhibiting HIF hydroxylase isoforms regulates IL-1ß-induced NF-?B at the level of (or downstream of) the tumor necrosis factor receptor-associated factor 6 complex. Multiple proteins of the distal IL-1ß-signaling pathway are subject to hydroxylation and form complexes with either prolyl hydroxylase 1 or factor inhibiting HIF. Thus, we hypothesize that hydroxylases regulate IL-1ß signaling and subsequent inflammatory gene expression. Furthermore, hydroxylase inhibition represents a unique approach to the inhibition of IL-1ß-dependent inflammatory signaling.

Geographical variation in carbon dioxide fluxes from soils in agro-ecosystems and its implications for life-cycle assessment

1. Exchange of carbon dioxide (CO2) from soils can contribute significantly to the global warming potential (GWP) of agro-ecosystems. Due to variations in soil type, climatic onditions and land management practices, exchange of CO2 can differ markedly in different geographical locations. The food industry is developing carbon footprints for their products necessitating integration of CO2 exchange from soils with other CO2 emissions along the food chain. It may be advantageous to grow certain crops in different geographical locations to minimize CO2 emissions from the soil, and this may provide potential to offset other emissions in the food chain, such as transport. 2. Values are derived for the C balance of soils growing horticultural crops in the UK, Spain and Uganda. Net ecosystem production (NEP) is firstly calculated from the difference in net primary production (NPP) and heterotrophic soil respiration (Rh). Both NPP and Rh were estimated from intensive direct field measurements. Secondly, net biome production (NBP) is calculated by subtracting the crop biomass from NEP to give an indication of C balance. The importance of soil exchange is discussed in the light of recent discussions on carbon footprints and within the context of food life-cycle assessment (LCA). 3. The amount of crop relative to the biomass and the Rh prevailing in the different countries were the dominant factors influencing the magnitude of NEP and NBP. The majority of the biomass for lettuce Lactuca sativa and vining peas Pisum sativum, was removed from the field as crop; therefore, NEP and NBP were mainly negative. This was amplified for lettuces grown in Uganda (-16·5 and -17 t C ha-1 year-1 compared to UK and Spain -4·8 to 7·4 and -5·1 to 6·3 t C ha-1 year-1 for NEP and NBP, respectively) where the climate elevated Rh. 4. Synthesis and applications. This study demonstrates the importance of soil emissions in the overall life cycle of vegetables. Variability in such emissions suggests that assigning a single value to food carbon footprints may not be adequate, even within a country. Locations with high heterotrophic soil respiration, such as Spain and Uganda (21·9 and 21·6 t C ha-1 year-1, respectively), could mitigate the negative effects of climate on the C costs of crop production by growth of crops with greater returns of residue to the soil. This would minimize net CO2 emissions from these agricultural ecosystems.

In-situ XPS study on the reducibility of Pd-promoted Cu/CeO2 catalysts for the oxygen-assisted water-gas-shift reaction

Cu/CeO2, Pd/CeO2, and CuPd/CeO2 catalysts were prepared and their reduction followed by in-situ XPS in order to explore promoter and support interactions in a bimetallic CuPd/CeO2 catalyst effective for the oxygen-assisted water-gas-shift (OWGS) reaction. Mutual interactions between Cu, Pd, and CeO2 components all affect the reduction process. Addition of only 1 wt% Pd to 30 wt% Cu/CeO2 greatly enhances the reducibility of both dispersed CuO and ceria support. In-vacuo reduction (inside XPS chamber) up to 400 °C results in a continuous growth of metallic copper and Ce3+ surface species, although higher temperatures results in support reoxidation. Supported copper in turn destabilizes metallic palladium metal with respect to PdO, this mutual perturbation indicating a strong intimate interaction between the Cu–Pd components. Despite its lower intrinsic reactivity towards OWGS, palladium addition at only 1 wt% loading significantly improved CO conversion in OWGS reaction over a monometallic 30 wt% Cu/CeO2 catalysts, possibly by helping to maintain Cu in a reduced state during reaction.

Phenols and aromatic amines as thermal stabilizers in polyolefin processing

Scavenging of C- and O-centered free radicals is mandatory in processing stabilization of polypropylene. Phenolic antioxidants act principally as O-radical scavengers only. Aromatic amines, N,N'-disubstituted 1,4-phenylenediamines (PD) and 4,4'disubstituted diphenylamines (DPA), scavenge both C- and O-centered radicals and have consequently a broader activity spectrum. PD cannot be used, however, in polypropylene because of formation of strongly discoloring and staining sacrificial transformation products. Such products formed from DPA have even more discoloring properties. A good processing stability and acceptable extent of discoloration can be achieved by blends of phenols with 4,4'-di-tert.octyl DPA. The effect is considered as a beneficial cooperation between the two chain-breaking antioxidants involving interactions with amine-based transformation products.

Detecting and monitoring the symptoms of Parkinson's disease using smartphones:a pilot study

Background: Remote, non-invasive and objective tests that can be used to support expert diagnosis for Parkinson's disease (PD) are lacking. Methods: Participants underwent baseline in-clinic assessments, including the Unified Parkinson's Disease Rating Scale (UPDRS), and were provided smartphones with an Android operating system that contained a smartphone application that assessed voice, posture, gait, finger tapping, and response time. Participants then took the smart phones home to perform the five tasks four times a day for a month. Once a week participants had a remote (telemedicine) visit with a Parkinson disease specialist in which a modified (excluding assessments of rigidity and balance) UPDRS performed. Using statistical analyses of the five tasks recorded using the smartphone from 10 individuals with PD and 10 controls, we sought to: (1) discriminate whether the participant had PD and (2) predict the modified motor portion of the UPDRS. Results: Twenty participants performed an average of 2.7 tests per day (68.9% adherence) for the study duration (average of 34.4 days) in a home and community setting. The analyses of the five tasks differed between those with Parkinson disease and those without. In discriminating participants with PD from controls, the mean sensitivity was 96.2% (SD 2%) and mean specificity was 96.9% (SD 1.9%). The mean error in predicting the modified motor component of the UPDRS (range 11-34) was 1.26 UPDRS points (SD 0.16). Conclusion: Measuring PD symptoms via a smartphone is feasible and has potential value as a diagnostic support tool.

Septin6 and Septin7 GTP binding proteins regulate AP-3- and ESCRT-dependent multivesicular body biogenesis

Septins (SEPTs) form a family of GTP-binding proteins implicated in cytoskeleton and membrane organization, cell division and host/pathogen interactions. The precise function of many family members remains elusive. We show that SEPT6 and SEPT7 complexes bound to F-actin regulate protein sorting during multivesicular body (MVB) biogenesis. These complexes bind AP-3, an adapter complex sorting cargos destined to remain in outer membranes of maturing endosomes, modulate AP-3 membrane interactions and the motility of AP-3-positive endosomes. These SEPT-AP interactions also influence the membrane interaction of ESCRT (endosomal-sorting complex required for transport)-I, which selects ubiquitinated cargos for degradation inside MVBs. Whereas our findings demonstrate that SEPT6 and SEPT7 function in the spatial, temporal organization of AP-3- and ESCRT-coated membrane domains, they uncover an unsuspected coordination of these sorting machineries during MVB biogenesis. This requires the E3 ubiquitin ligase LRSAM1, an AP-3 interactor regulating ESCRT-I sorting activity and whose mutations are linked with Charcot-Marie-Tooth neuropathies.

Ag alloyed Pd single-atom catalysts for efficient selective hydrogenation of acetylene to ethylene in excess ethylene

Semihydrogenation of acetylene in an ethylene-rich stream is an industrially important process. Conventional supported monometallic Pd catalysts offer high acetylene conversion, but they suffer from very low selectivity to ethylene due to overhydrogenation and the formation of carbonaceous deposits. Herein, a series of Ag alloyed Pd single-atom catalysts, possessing only ppm levels of Pd, supported on silica gel were prepared by a simple incipient wetness coimpregnation method and applied to the selective hydrogenation of acetylene in an ethylene-rich stream under conditions close to the front-end employed by industry. High acetylene conversion and simultaneous selectivity to ethylene was attained over a wide temperature window, surpassing an analogous Au alloyed Pd single-atom system we previously reported. Restructuring of AgPd nanoparticles and electron transfer from Ag to Pd were evidenced by in situ FTIR and in situ XPS as a function of increasing reduction temperature. Microcalorimetry and XANES measurements support both geometric and electronic synergetic effects between the alloyed Pd and Ag. Kinetic studies provide valuable insight into the nature of the active sites within these AgPd/SiO2 catalysts, and hence, they provide evidence for the key factors underpinning the excellent performance of these bimetallic catalysts toward the selective hydrogenation of acetylene under ethylene-rich conditions while minimizing precious metal usage.

Machine learning for large-scale wearable sensor data in Parkinson disease:concepts, promises, pitfalls, and futures

For the treatment and monitoring of Parkinson's disease (PD) to be scientific, a key requirement is that measurement of disease stages and severity is quantitative, reliable, and repeatable. The last 50 years in PD research have been dominated by qualitative, subjective ratings obtained by human interpretation of the presentation of disease signs and symptoms at clinical visits. More recently, “wearable,” sensor-based, quantitative, objective, and easy-to-use systems for quantifying PD signs for large numbers of participants over extended durations have been developed. This technology has the potential to significantly improve both clinical diagnosis and management in PD and the conduct of clinical studies. However, the large-scale, high-dimensional character of the data captured by these wearable sensors requires sophisticated signal processing and machine-learning algorithms to transform it into scientifically and clinically meaningful information. Such algorithms that “learn” from data have shown remarkable success in making accurate predictions for complex problems in which human skill has been required to date, but they are challenging to evaluate and apply without a basic understanding of the underlying logic on which they are based. This article contains a nontechnical tutorial review of relevant machine-learning algorithms, also describing their limitations and how these can be overcome. It discusses implications of this technology and a practical road map for realizing the full potential of this technology in PD research and practice. © 2016 International Parkinson and Movement Disorder Society.

Technology in Parkinson's disease:challenges and opportunities

The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinson's disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include noncompatible technology platforms, the need for wide-scale and long-term deployment of sensor technology (among vulnerable elderly patients in particular), and the gap between the "big data" acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open-source and/or open-hardware platforms that enable multichannel data capture sensitive to the broad range of motor and nonmotor problems that characterize PD and are adaptable into self-adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed-loop therapeutic systems with high patient adherence that also serve to (1) encourage the adoption of clinico-pathophysiologic phenotyping and early detection of critical disease milestones, (2) enhance the tailoring of symptomatic therapy, (3) improve subgroup targeting of patients for future testing of disease-modifying treatments, and (4) identify objective biomarkers to improve the longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the task force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and the quality of life of individuals with PD. © 2016 International Parkinson and Movement Disorder Society.