Ketogenic diets attenuate cyclooxygenase and lipoxygenase gene expression in multiple sclerosis

Background: Adapted ketogenic diet (AKD) and caloric restriction (CR) have been suggested as alternative therapeutic strategies for inflammatory, hyperproliferative and neurodegenerative diseases. Pro-inflammatory eicosanoids have been implicated in the pathogenesis of multiple sclerosis since they augment vascular permeability and induce leukocyte migration into the brain. We explored the impact of ketogenic diets on gene expression of biosynthetic enzymes for pro- (ALOX5, COX1, COX2) and anti-inflammatory (ALOX15) eicosanoids in patients with relapsing-remitting multiple sclerosis. Methods: 60 adults were prospectively recruited for this six months randomized controlled trial and the impact of dietary treatment on the Multiple Sclerosis Quality of Life-54 index (ClinicalTrials.gov (NCT01538355) has previously been published. Here we explored 24 patients (8 controls, 5 on CR and 11 on AKD). For statistical analysis we combined the two diet groups to a single pooled treatment group. Findings: Inter-group comparison indicated that expression of the pro-inflammatory ALOX5 in the pooled treatment group was significantly (p <0.05) reduced when compared with the control group. Moreover, intra-group comparison (same individuals before and after dietary treatment) suggested significantly impaired expression of other pro-inflammatory enzymes, such as COX1 (p < 0.001) and COX2 ( p < 0.05). Finally, pretreatment cross-group analysis revealed a significant positive correlation between expression of pro-inflammatory ALOX5 and COX2 and an inverse correlation of ALOX5 and COX1 expression with the MSQoL-54 index. Interpretation: Ketogenic diets can reduce the expression of enzymes involved in the biosynthesis of pro-inflammatory eicosanoids. Pharmacological interference with eicosanoid biosynthesis might constitute a strategy supplementing current therapeutic approaches for MS. (C) 2018 The Authors. Published by Elsevier B.V

Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): protocol of a randomized controlled study

BACKGROUND: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults that may lead to progressive disability. Since pharmacological treatments may have substantial side effects, there is a need for complementary treatment options such as specific dietary approaches. Ketone bodies that are produced during fasting diets (FDs) and ketogenic diets (KDs) are an alternative and presumably more efficient energy source for the brain. Studies on mice with experimental autoimmune encephalomyelitis showed beneficial effects of KDs and FDs on disease progression, disability, cognition and inflammatory markers. However, clinical evidence on these diets is scarce. In the clinical study protocol presented here, we investigate whether a KD and a FD are superior to a standard diet (SD) in terms of therapeutic effects and disease progression. METHODS: This study is a single-center, randomized, controlled, parallel-group study. One hundred and eleven patients with relapsing-remitting MS with current disease activity and stable immunomodulatory therapy or no disease-modifying therapy will be randomized to one of three 18-month dietary interventions: a KD with a restricted carbohydrate intake of 20-40 g/day; a FD with a 7-day fast every 6 months and 14-h daily intermittent fasting in between; and a fat-modified SD as recommended by the German Nutrition Society. The primary outcome measure is the number of new T2-weighted MRI lesions after 18 months. Secondary endpoints are safety, changes in relapse rate, disability progression, fatigue, depression, cognition, quality of life, changes of gut microbiome as well as markers of inflammation, oxidative stress and autophagy. Safety and feasibility will also be assessed. DISCUSSION: Preclinical data suggest that a KD and a FD may modulate immunity, reduce disease severity and promote remyelination in the mouse model of MS. However, clinical evidence is lacking. This study is the first clinical study investigating the effects of a KD and a FD on disease progression of MS

Infrared and Raman spectra of lignin substructures : Dibenzodioxocin

Vibrational spectroscopy is a very suitable tool for investigating the plant cell wall in situ with almost no sample preparation. The structural information of all different constituents is contained in a single spectrum. Interpretation therefore heavily relies on reference spectra and understanding of the vibrational behavior of the components under study. For the first time, we show infrared (IR) and Raman spectra of dibenzodioxocin (DBDO), an important lignin substructure. A detailed vibrational assignment of the molecule, based on quantum chemical computations, is given in the Supporting Information; the main results are found in the paper. Furthermore, we show IR and Raman spectra of synthetic guaiacyl lignin (dehydrogenation polymer-G-DHP). Raman spectra of DBDO and G-DHP both differ with respect to the excitation wavelength and therefore reveal different features of the substructure/polymer. This study confirms the idea previously put forward that Raman at 532 nm selectively probes end groups of lignin, whereas Raman at 785 nm and IR seem to represent the majority of lignin substructures.Peer reviewe

Environmental parameters of shallow water habitats in the SW Baltic Sea

The coastal waters of the Baltic Sea are subject to high variations in environmental conditions, triggered by natural and anthropogenic causes. Thus, in situ measurements of water parameters can be strategic for our understanding of the dynamics in shallow water habitats. In this study we present the results of a monitoring program at low water depths (1–2.5 m), covering 13 stations along the Baltic coast of Schleswig-Holstein, Germany. The provided dataset consists of records for dissolved inorganic nutrient concentrations taken twice a month and continuous readings at 10 min intervals for temperature, salinity and oxygen content. Data underwent quality control procedures and were flagged. On average, a data availability of >90 % was reached for the monitoring period within 2016–2018. The obtained monitoring data reveal great temporal and spatial variabilities of key environmental factors for shallow water habitats in the southwestern Baltic Sea. Therefore the presented information could serve as realistic key data for experimental manipulations of environmental parameters as well as for the development of oceanographic, biogeochemical or ecological models

Coulomb plasmas in outer envelopes of neutron stars

Outer envelopes of neutron stars consist mostly of fully ionized, strongly coupled Coulomb plasmas characterized by typical densities about 10^4-10^{11} g/cc and temperatures about 10^4-10^9 K. Many neutron stars possess magnetic fields about 10^{11}-10^{14} G. Here we briefly review recent theoretical advances which allow one to calculate thermodynamic functions and electron transport coefficients for such plasmas with an accuracy required for theoretical interpretation of observations.Comment: 4 pages, 2 figures, latex2e using cpp2e.cls (included). Proc. PNP-10 Workshop, Greifswald, Germany, 4-9 Sept. 2000. Accepted for publication in Contrib. Plasma Phys. 41 (2001) no. 2-

GPS-derived orbits for the GOCE satellite

The first ESA (European Space Agency) Earth explorer core mission GOCE (Gravity field and steady-state Ocean Circulation Explorer) was launched on 17 March 2009 into a sun-synchronous dusk-dawn orbit with an exceptionally low initial altitude of about 280km. The onboard 12-channel dual-frequency GPS (Global Positioning System) receiver delivers 1Hz data, which provides the basis for precise orbit determination (POD) for such a very low orbiting satellite. As part of the European GOCE Gravity Consortium the Astronomical Institute of the University of Bern and the Department of Earth Observation and Space Systems are responsible for the orbit determination of the GOCE satellite within the GOCE High-level Processing Facility. Both quick-look (rapid) and very precise orbit solutions are produced with typical latencies of 1day and 2 weeks, respectively. This article summarizes the special characteristics of the GOCE GPS data, presents POD results for about 2months of data, and shows that both latency and accuracy requirements are met. Satellite Laser Ranging validation shows that an accuracy of 4 and 7cm is achieved for the reduced-dynamic and kinematic Rapid Science Orbit solutions, respectively. The validation of the reduced-dynamic and kinematic Precise Science Orbit solutions is at a level of about 2c

Reduced Mass and Diversity of the Colonic Microbiome in Patients with Multiple Sclerosis and Their Improvement with Ketogenic Diet

Background: Colonic microbiome is thought to be involved in auto-immune multiple sclerosis (MS). Interactions between diet and the colonic microbiome in MS are unknown. Methods: We compared the composition of the colonic microbiota quantitatively in 25 MS patients and 14 healthy controls.Fluorescence in situ hybridization (FISH) with 162 ribosomal RNA derived bacterial FISH probes was used. Ten of the MS patients received a ketogenic diet for 6 months. Changes in concentrations of 35 numerically substantial bacterial groups were monitored at baseline and at 2, 12, and 23/24 weeks. Results: No MS typical microbiome pattern was apparent.The total concentrations and diversity of substantial bacterial groups were reduced in MS patients (P < 0.001). Bacterial groups detected with EREC (mainly Roseburia), Bac303 (Bacteroides), and Fprau (Faecalibacterium prausnitzii) probes were diminished the most. The individual changes were multidirectional and inconsistent. The effects of a ketogenic diet were biphasic. In the short term, bacterial concentrations and diversity were further reduced. They started to recover at week 12 and exceeded significantly the baseline values after 23–24 weeks on the ketogenic diet. Conclusions: Colonic biofermentative function is markedly impaired in MS patients.The ketogenic diet normalized concentrations of the colonic microbiome after 6 months

Efficient laser-driven proton acceleration from cylindrical and planar cryogenic hydrogen jets.

We report on recent experimental results deploying a continuous cryogenic hydrogen jet as a debris-free, renewable laser-driven source of pure proton beams generated at the 150 TW ultrashort pulse laser Draco. Efficient proton acceleration reaching cut-off energies of up to 20 MeV with particle numbers exceeding 109 particles per MeV per steradian is demonstrated, showing for the first time that the acceleration performance is comparable to solid foil targets with thicknesses in the micrometer range. Two different target geometries are presented and their proton beam deliverance characterized: cylindrical (∅ 5 μm) and planar (20 μm × 2 μm). In both cases typical Target Normal Sheath Acceleration emission patterns with exponential proton energy spectra are detected. Significantly higher proton numbers in laser-forward direction are observed when deploying the planar jet as compared to the cylindrical jet case. This is confirmed by two-dimensional Particle-in-Cell (2D3V PIC) simulations, which demonstrate that the planar jet proves favorable as its geometry leads to more optimized acceleration conditions

Identification of small non-coding RNAs from mitochondria and chloroplasts

Small non-protein-coding RNAs (ncRNAs) have been identified in a wide spectrum of organisms ranging from bacteria to humans. In eukarya, systematic searches for ncRNAs have so far been restricted to the nuclear or cytosolic compartments of cells. Whether or not small stable non-coding RNA species also exist in cell organelles, in addition to tRNAs or ribosomal RNAs, is unknown. We have thus generated cDNA libraries from size-selected mammalian mitochondrial RNA and plant chloroplast RNA and searched for small ncRNA species in these two types of DNA-containing cell organelles. In total, we have identified 18 novel candidates for organellar ncRNAs in these two cellular compartments and confirmed expression of six of them by northern blot analysis or RNase A protection assays. Most candidate ncRNA genes map to intergenic regions of the organellar genomes. As found previously in bacteria, the presumptive ancestors of present-day chloroplasts and mitochondria, we also observed examples of antisense ncRNAs that potentially could target organelle-encoded mRNAs. The structural features of the identified ncRNAs as well as their possible cellular functions are discussed. The absence from our libraries of abundant small RNA species that are not encoded by the organellar genomes suggests that the import of RNAs into cell organelles is of very limited significance or does not occur at all