Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals.

The liver is a key organ of metabolic homeostasis with functions that oscillate in response to food intake. Although liver and gut microbiome crosstalk has been reported, microbiome-mediated effects on peripheral circadian clocks and their output genes are less well known. Here, we report that germ-free (GF) mice display altered daily oscillation of clock gene expression with a concomitant change in the expression of clock output regulators. Mice exposed to microbes typically exhibit characterized activities of nuclear receptors, some of which (PPARα, LXRβ) regulate specific liver gene expression networks, but these activities are profoundly changed in GF mice. These alterations in microbiome-sensitive gene expression patterns are associated with daily alterations in lipid, glucose, and xenobiotic metabolism, protein turnover, and redox balance, as revealed by hepatic metabolome analyses. Moreover, at the systemic level, daily changes in the abundance of biomarkers such as HDL cholesterol, free fatty acids, FGF21, bilirubin, and lactate depend on the microbiome. Altogether, our results indicate that the microbiome is required for integration of liver clock oscillations that tune output activators and their effectors, thereby regulating metabolic gene expression for optimal liver function.

Dominant-Negative Effects of Adult-Onset Huntingtin Mutations Alter the Division of Human Embryonic Stem Cells-Derived Neural Cells.

Mutations of the huntingtin protein (HTT) gene underlie both adult-onset and juvenile forms of Huntington's disease (HD). HTT modulates mitotic spindle orientation and cell fate in mouse cortical progenitors from the ventricular zone. Using human embryonic stem cells (hESC) characterized as carrying mutations associated with adult-onset disease during pre-implantation genetic diagnosis, we investigated the influence of human HTT and of an adult-onset HD mutation on mitotic spindle orientation in human neural stem cells (NSCs) derived from hESCs. The RNAi-mediated silencing of both HTT alleles in neural stem cells derived from hESCs disrupted spindle orientation and led to the mislocalization of dynein, the p150Glued subunit of dynactin and the large nuclear mitotic apparatus (NuMA) protein. We also investigated the effect of the adult-onset HD mutation on the role of HTT during spindle orientation in NSCs derived from HD-hESCs. By combining SNP-targeting allele-specific silencing and gain-of-function approaches, we showed that a 46-glutamine expansion in human HTT was sufficient for a dominant-negative effect on spindle orientation and changes in the distribution within the spindle pole and the cell cortex of dynein, p150Glued and NuMA in neural cells. Thus, neural derivatives of disease-specific human pluripotent stem cells constitute a relevant biological resource for exploring the impact of adult-onset HD mutations of the HTT gene on the division of neural progenitors, with potential applications in HD drug discovery targeting HTT-dynein-p150Glued complex interactions.

Diffantom: Whole-Brain Diffusion MRI Phantoms Derived from Real Datasets of the Human Connectome Project.

Food allergies are believed to be on the rise and currently management relies on the avoidance of the food. Hen's egg allergy is after cow's milk allergy the most common food allergy; eggs are used in many food products and thus difficult to avoid. A technological process using a combination of enzymatic hydrolysis and heat treatment was designed to produce modified hen's egg with reduced allergenic potential. Biochemical (SDS-PAGE, Size exclusion chromatography and LC-MS/MS) and immunological (ELISA, immunoblot, RBL-assays, animal model) analysis showed a clear decrease in intact proteins as well as a strong decrease of allergenicity. In a clinical study, 22 of the 24 patients with a confirmed egg allergy who underwent a double blind food challenge with the hydrolysed egg remained completely free of symptoms. Hydrolysed egg products may be beneficial as low allergenic foods for egg allergic patients to extent their diet. This article is protected by copyright. All rights reserved.

Enhancing actions of peptides derived from the γ-chain of fetal human hemoglobin on the immunostimulant activities of monophosphoryl lipid A.

Hemoglobin and its structures have been described since the 1990s to enhance a variety of biological activities of endotoxins (LPS) in a dose-dependent manner. To investigate the interaction processes in more detail, the system was extended by studying the interactions of newly designed peptides from the γ-chain of human hemoglobin with the adjuvant monophosphoryl lipid A (MPLA), a partial structure of lipid A lacking its 1-phosphate. It was found that some selected Hbg peptides, in particular two synthetic substructures designated Hbg32 and Hbg35, considerably increased the bioactivity of MPLA, which alone was only a weak activator of immune cells. These findings hold true for human mononuclar cells, monocytes and T lymphocytes. To understand the mechanisms of action in more detail, biophysical techniques were applied. These showed a peptide-induced change of the MPLA aggregate structure from multilamellar into a non-lamellar, probably inverted, cubic structure. Concomitantly, the peptides incorporated into the tightly packed MPLA aggregates into smaller units down to monomers. The fragmentation of the aggregates was an endothermic process, differing from a complex formation but rather typical for a catalytic reaction.

Enhancement of human adipose-derived stem cell expansion and stability for clinical use

Co-culture techniques associating both dermal fibroblasts and epidermal keratinocytes have shown to have better clinical outcome than keratinocyte culture alone for the treatment of severe burns. Since fat grafting has been shown to improve scar remodelling, new techniques such as cell-therapy-assisted surgical reconstruction with isolated and expanded autologous adipose-derived stem cells (ASCs) would be of benefit to increase graft acceptation. Therefore, integrating ASCs into standardized procedures for cultured skin grafting could be of benefit for the patient if cell quality and quantity could be maintained. The purpose of this study was to evaluate ASC processing from adult tissue with simple isolation (without enzymatic steps), expansion (low density of 325-3,000 cells/cm2) and storage conditions to assure methods to enhance the cellular resistance when transferred back to the patient. Co-culture with cell-banked skin progenitor cells (FE002-SK2) showed an increase of 40-50% ASCs yield at high passages alongside with a better preservation of morphology, proper adipogenic and osteogenic differentiation and efficient biocompatibility with 3D collagen scaffolds. ASCs can be considered as a valuable additional cell source to be delivered in biological bandages to the patient in a need of tissue reconstruction such as burn patients.

Optical characterization of sol-gel glasses derived from Eu3+ complex-forming precursors

Fabrication of new optical devices based upon the incorporation of rare earth ions via sol-gel methods depends on elimination of dopant ion clusters and residual hydroxyl groups from the final material. The optical absorption and/or luminescence properties of luminescent rare earth ions are influenced by the local bonding environment and the distribution of the rare-earth dopants in the matrix. Typically, dopants are incorporated into gel via dissolution of soluble species into the initial precursor sol. In this work, Eu3+ is used as optical probe, to assess changes in the local environment. Results of emission, excitation, fluorescence line narrowing and lifetimes studies of Eu3+-doped gels derived from Si(OCH3)4 and fluorinated/chelate Eu3+ precursors are presented. The precursors used in the sol-gel synthesis were: tris (6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionate) Eu(III), Eu (III) trifluoromethanesulfonate, Eu(III) acetylacetonate hydrate, Eu (III) trifluoroacetate trihidrate, tris (2,2,6,6-tetramethyl-3,5- heptanedionate) Eu(III) and Eu(NO3)3.6H2O. The results were interpreted in terms of the evolution of the Eu3+ fluorescence in systems varying from solution to the gels densified to 800ºC. The lifetimes studies indicate that the fluorinated precursors are effective at reducing the water content in densified gels.

Empirical analysis of solid management waste costs: Some evidence from Galicia, Spain

This paper analyses the factors that determine solid waste service costs. The empirical analysis is based on information derived from a survey conducted in a sample of Galician municipalities. The results reveal economies of scale in municipalities of fewer than 50,000 inhabitants, such that cooperation between these municipalities could lead to cost savings. It also appears that private delivery is not cheaper than public delivery. Finally, designating a larger proportion of the total waste volume to recycling does not imply greater costs.

Reduction and Analysis Methods of Indigo

Throughout history indigo was derived from various plants for example Dyer’s Woad (Isatis tinctoria L.) in Europe. In the 19th century were the synthetic dyes developed and nowadays indigo is mainly synthesized from by-products of fossil fuels. Indigo is a so-called vat dye, which means that it needs to be reduced to its water soluble leucoform before dyeing. Nowadays, most of the industrial reduction is performed chemically by sodium dithionite. However, this is considered environmentally unfavourable because of waste waters contaminating degradation products. Therefore there has been interest to find new possibilities to reduce indigo. Possible alternatives for the application of dithionite as the reducing agent are biologically induced reduction and electrochemical reduction. Glucose and other reducing sugars have recently been suggested as possible environmentally friendly alternatives as reducing agents for sulphur dyes and there have also been interest in using glucose to reduce indigo. In spite of the development of several types of processes, very little is known about the mechanism and kinetics associated with the reduction of indigo. This study aims at investigating the reduction and electrochemical analysis methods of indigo and give insight on the reduction mechanism of indigo. Anthraquinone as well as it’s derivative 1,8-dihydroxyanthraquinone were discovered to act as catalysts for the glucose induced reduction of indigo. Anthraquinone introduces a strong catalytic effect which is explained by invoking a molecular “wedge effect” during co-intercalation of Na+ and anthraquinone into the layered indigo crystal. The study includes also research on the extraction of plant-derived indigo from woad and the examination of the effect of this method to the yield and purity of indigo. The purity has been conventionally studied spectrophotometrically and a new hydrodynamic electrode system is introduced in this study. A vibrating probe is used in following electrochemically the leuco-indigo formation with glucose as a reducing agent.

Similar problems, different solutions: Comparing refuse collection in the Netherlands and Spain

Local public service provision can vary greatly because of differences in institutional arrangements, public service markets, and national traditions regarding government intervention. In this paper we compare the procedures adopted by the local governments of the Netherlands and Spain in arranging for the provision of solid waste collection. We find that Spain faces a consolidation problem, opting more frequently to implement policies of privatization and cooperation, at the expense of competition. By contrast, the Netherlands has, on average, larger municipalities, resorting somewhat less to privatization and cooperation, and more to competition. The two options - cooperation and competition - have their merits when striving to strike a balance between transaction costs and scale economies. The choices made in organizational reform seem to be related to several factors, among which the nature of the political system and the size of municipalities appear to be relevant.

Polygenic determinants of white matter volume derived from GWAS lack reproducibility in a replicate sample

A recent publication reported an exciting polygenic effect of schizophrenia (SCZ) risk variants, identified by a large genome-wide association study (GWAS), on total brain and white matter volumes in schizophrenic patients and, even more prominently, in healthy subjects. The aim of the present work was to replicate and then potentially extend these findings. According to the original publication, polygenic risk scores using single nucleotide polymorphism (SNP) information of SCZ GWAS (polygenic SCZ risk scores; PSS) were calculated in 122 healthy subjects, enrolled in a structural magnetic resonance imaging (MRI) study. These scores were computed based on P-values and odds ratios available through the Psychiatric GWAS Consortium. In addition, polygenic white matter scores (PWM) were calculated, using the respective SNP subset in the original publication. None of the polygenic scores, either PSS or PWM, were found to be associated with total brain, white matter or gray matter volume in our replicate sample. Minor differences between the original and the present study that might have contributed to lack of reproducibility (but unlikely explain it fully), are number of subjects, ethnicity, age distribution, array technology, SNP imputation quality and MRI scanner type. In contrast to the original publication, our results do not reveal the slightest signal of association of the described sets of GWAS-identified SCZ risk variants with brain volumes in adults. Caution is indicated in interpreting studies building on polygenic risk scores without replication sample.

Brain-Derived Neurotrophic Factor as a potential biomarker of cognitive recovery in schizophrenia

Brain-derived neurotrophic factor (BDNF) has been proposed as a biomarker of schizophrenia and, more specifically, as a biomarker of cognitive recovery. Evidence collected in this review indicates that BDNF is relevant in the pathophysiology of schizophrenia and could play a role as a marker of clinical response. BDNF has been shown to play a positive role as a marker in antipsychotic treatment, and it has been demonstrated that typical antipsychotics decrease BDNF levels while atypical antipsychotics maintain or increase serum BDNF levels. Furthermore, BDNF levels have been associated with severe cognitive impairments in patients with schizophrenia. Consequently, BDNF has been proposed as a candidate target of strategies to aid the cognitive recovery process. There is some evidence suggesting that BDNF could be mediating neurobiological processes underlying cognitive recovery. Thus, serum BDNF levels seem to be involved in some synaptic plasticity and neurotransmission processes. Additionally, serum BDNF levels significantly increased in schizophrenia subjects after neuroplasticity-based cognitive training. If positive replications of those findings are published in the future then serum BDNF levels could be definitely postulated as a peripheral biomarker for the effects of intensive cognitive training or any sort of cognitive recovery in schizophrenia. All in all, the current consideration of BDNF as a biomarker of cognitive recovery in schizophrenia is promising but still premature.

Market of biomass fuels in Finland : IEA Bioenergy Task 40 and EUBIONET III - Country report of Finland 2009

This study considered the current situation of solid and liquid biomass fuels in Finland. The fact that industry consumes more than half of the total primary energy, widely applied combined heat and power production and a high share of solid biomass fuels in the total energy consumption are specific to the Finnish energy system. Wood is the most important source of bioenergy in Finland, representing 20% of the total energy consumption in 2007. Almost 80% of the woodbased energy is recovered from industrial by-products and residues. As a member of the European Union, Finland has committed itself to the Union’s climate and energy targets, such as reducing its overall emissions of green house gases to at least 20% below 1990 levels by 2020, and increasing the share of renewable energy in the gross final consumption. The renewable energy target approved for Finland is 38%. The present National Climate and Energy Strategy was introduced in November 2008. The strategy covers climate and energy policy measures up to 2020, and in brief thereafter, up to 2050. In recent years, the actual emissions have exceeded the Kyoto commitment and the trend of emissions is on the increase. In 2007, the share of renewable energy in the gross final energy consumption was approximately 25% (360 PJ). Without new energy policy measures, the final consumption of renewable energy would increase to 380 PJ, which would be approximately only 31% of the final energy consumption. In addition, green house gas emissions would exceed the 1990 levels by 20%. Meeting the targets will need the adoption of more active energy policy measures in coming years. The international trade of biomass fuels has a substantial importance for the utilisation of bioenergy in Finland. In 2007, the total international trading of solid and liquid biomass fuels was approximately 77 PJ, of which import was 62 PJ. Most of the import is indirect and takes place within the forest industry’s raw wood imports. In 2007, as much as 21% of wood energy was based on foreign-origin wood. Wood pellets and tall oil form the majority of export streams of biomass fuels. The indirect import of wood fuels peaked in 2006 to 61 PJ. The foreseeable decline in raw wood import to Finland will decrease the indirect import of wood fuels. In 2004– 2007, the direct trade of solid and liquid biomass fuels has been on a moderate growth path. In 2007, the import of palm oil and export of bio-diesel emerged, as a large, 170 000 t/yr biodiesel plant came into operation in Porvoo.

Building complexity in O2-binding copper complexes : site-selective metalation and intermolecular O2-binding at dicopper and heterometallic complexes derived from an unsymmetric ligand

A novel unsymmetric dinucleating ligand (LN3N4) combining a tridentate and a tetradentate binding sites linked through a m-xylyl spacer was synthesized as ligand scaffold for preparing homo- and dimetallic complexes, where the two metal ions are bound in two different coordination environments. Site-selective binding of different metal ions is demonstrated. LN3N4 is able to discriminate between CuI and a complementary metal (M′ = CuI, ZnII, FeII, CuII, or GaIII) so that pure heterodimetallic complexes with a general formula [CuIM′(LN3N4)]n+ are synthesized. Reaction of the dicopper(I) complex [CuI 2(LN3N4)]2+ with O2 leads to the formation of two different copper-dioxygen (Cu2O2) intermolecular species (O and TP) between two copper atoms located in the same site from different complex molecules. Taking advantage of this feature, reaction of the heterodimetallic complexes [CuM′(LN3N4)]n+ with O2 at low temperature is used as a tool to determine the final position of the CuI center in the system because only one of the two Cu2O2 species is formed

Contaminação de aqüífero por hidrocarbonetos: estudo de caso na Vila Tupi, Porto Velho - Rondônia

Underground storage tanks (UST) are widely used in the Porto Velho area. A large number of these USTs are in bad condition due to corrosion processes causing groundwater contamination. A large number of these leaking underground fuel tanks (LUFT) are in urban areas but due to the lack of water quality monitoring, they are only detected when there is a high contamination level. This study identified petroleum hydrocarbons, derived from a LUFT, by a silica gel/petroleum ether partitioning gravimetric method and by gas chromatographic analysis of samples collected in wells dug in a gas station and in houses in the aforementioned neighborhood.