The application of selective reaction monitoring confirms dysregulation of glycolysis in a preclinical model of schizophrenia.

BACKGROUND: Establishing preclinical models is essential for novel drug discovery in schizophrenia. Most existing models are characterized by abnormalities in behavioral readouts, which are informative, but do not necessarily translate to the symptoms of the human disease. Therefore, there is a necessity of characterizing the preclinical models from a molecular point of view. Selective reaction monitoring (SRM) has already shown promise in preclinical and clinical studies for multiplex measurement of diagnostic, prognostic and treatment-related biomarkers. METHODS: We have established an SRM assay for multiplex analysis of 7 enzymes of the glycolysis pathway which is already known to be affected in human schizophrenia and in the widely-used acute PCP rat model of schizophrenia. The selected enzymes were hexokinase 1 (Hk1), aldolase C (Aldoc), triosephosphate isomerase (Tpi1), glyceraldehyde-3-phosphate dehydrogenase (Gapdh), phosphoglycerate mutase 1 (Pgam1), phosphoglycerate kinase 1 (Pgk1) and enolase 2 (Eno2). The levels of these enzymes were analyzed using SRM in frontal cortex from brain tissue of PCP treated rats. RESULTS: Univariate analyses showed statistically significant altered levels of Tpi1 and alteration of Hk1, Aldoc, Pgam1 and Gapdh with borderline significance in PCP rats compared to controls. Most interestingly, multivariate analysis which considered the levels of all 7 enzymes simultaneously resulted in generation of a bi-dimensional chart that can distinguish the PCP rats from the controls. CONCLUSIONS: This study not only supports PCP treated rats as a useful preclinical model of schizophrenia, but it also establishes that SRM mass spectrometry could be used in the development of multiplex classification tools for complex psychiatric disorders such as schizophrenia.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Map-based multicriteria analysis to support interactive land use allocation

This article focuses on the use of map-based multicriteria analysis to develop a negotiation support tool for land use allocation. Spatial multicriteria analysis is used to make explicit trade-offs between objectives and to provide guidance and feedback on the land use changes negotiated by the participants. Digital maps are the means of communication among workshop participants, and an interactive mapping device (the 'Touch table') is used as the interface. Participants are informed about the relevant trade-offs on the map and use this information to change the land use maps. The approach is tested during a negotiation session as part of the land use planning process of the Bodegraven polder, a peat meadow area in the Netherlands. © 2011 Copyright Taylor and Francis Group, LLC

Ammonia exposure promotes algal biomass in an ombrotrophic peatland

Nitrogen pollution affects many peatlands with consequences for their biodiversity and ecosystem function. Microorganisms control nutrient cycling and constitute most of the biodiversity of peatlands but their response to nitrogen is poorly characterised and likely to depend on the form of deposition. Using a unique field experiment we show that ammonia exposure at realistic point source levels is associated with a general shift from heterotrophic (bacteria and fungi) to autotrophic (algal) dominance and an increase in total biomass. The biomass of larger testate amoebae increased, suggesting increased food supply for microbial predators. Results show the widespread impacts of N pollution and suggest the potential for microbial community-based bioindicators in these ecosystems

Weighing stars from birth to death: mass determination methods across the HRD

The mass of a star is the most fundamental parameter for its structure, evolution, and final fate. It is particularly important for any kind of stellar archaeology and characterization of exoplanets. There exists a variety of methods in astronomy to estimate or determine it. In this review we present a significant number of such methods, beginning with the most direct and model-independent approach using detached eclipsing binaries. We then move to more indirect and model-dependent methods, such as the quite commonly used isochrone or stellar track fitting. The arrival of quantitative asteroseismology has opened a completely new approach to determine stellar masses and to complement and improve the accuracy of other methods. We include methods for different evolutionary stages, from the pre-main sequence to evolved (super)giants and final remnants. For all methods uncertainties and restrictions will be discussed. We provide lists of altogether more than 200 benchmark stars with relative mass accuracies between $[0.3,2]\%$ for the covered mass range of M\in [0.1,16]\,\msun, $75\%$ of which are stars burning hydrogen in their core and the other $25\%$ covering all other evolved stages. We close with a recommendation how to combine various methods to arrive at a "mass-ladder" for stars.Comment: Invited review article for The Astronomy and Astrophysics Review. 146 pages, 16 figures, 11 tables. Accepted version by the Journal. It includes summary figure of accuracy/precision of methods for mass ranges and summary table for individual method

Weighing stars from birth to death : mass determination methods across the HRD

Funding: C.A., J.S.G.M., and M.G.P. received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 670519: MAMSIE). N.B. gratefully acknowledge financial support from the Royal Society (University Research Fellowships) and from the European Research Council (ERC-CoG-646928, Multi-Pop).The mass of a star is the most fundamental parameter for its structure, evolution, and final fate. It is particularly important for any kind of stellar archaeology and characterization of exoplanets. There exist a variety of methods in astronomy to estimate or determine it. In this review we present a significant number of such methods, beginning with the most direct and model-independent approach using detached eclipsing binaries. We then move to more indirect and model-dependent methods, such as the quite commonly used isochrone or stellar track fitting. The arrival of quantitative asteroseismology has opened a completely new approach to determine stellar masses and to complement and improve the accuracy of other methods. We include methods for different evolutionary stages, from the pre-main sequence to evolved (super)giants and final remnants. For all methods uncertainties and restrictions will be discussed. We provide lists of altogether more than 200 benchmark stars with relative mass accuracies between [0.3 ,2 ]% for the covered mass range of M ∈[0.1 ,16 ] M⊙ , 75 % of which are stars burning hydrogen in their core and the other 25 % covering all other evolved stages. We close with a recommendation how to combine various methods to arrive at a "mass-ladder" for stars.PostprintPeer reviewe

Weighing stars from birth to death: mass determination methods across the HRD

The mass of a star is the most fundamental parameter for its structure, evolution, and final fate. It is particularly important for any kind of stellar archaeology and characterization of exoplanets. There exist a variety of methods in astronomy to estimate or determine it. In this review we present a significant number of such methods, beginning with the most direct and model-independent approach using detached eclipsing binaries. We then move to more indirect and model-dependent methods, such as the quite commonly used isochrone or stellar track fitting. The arrival of quantitative asteroseismology has opened a completely new approach to determine stellar masses and to complement and improve the accuracy of other methods. We include methods for different evolutionary stages, from the pre-main sequence to evolved (super)giants and final remnants. For all methods uncertainties and restrictions will be discussed. We provide lists of altogether more than 200 benchmark stars with relative mass accuracies between [0.3,2]% for the covered mass range of M∈[0.1,16]M⊙, 75% of which are stars burning hydrogen in their core and the other 25% covering all other evolved stages. We close with a recommendation how to combine various methods to arrive at a “mass-ladder” for stars.Instituto de Astrofísica de La Plat

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The complete sequence of human chromosome 5

Chromosome 5 is one of the largest human chromosomes yet has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of noncoding and syntenic conservation with non-mammalian vertebrates, suggesting they are functionally constrained. In total, we compiled 177.7 million base pairs of highly accurate finished sequence containing 923 manually curated protein-encoding genes including the protocadherin and interleukin gene families and the first complete versions of each of the large chromosome 5 specific internal duplications. These duplications are very recent evolutionary events and play a likely mechanistic role, since deletions of these regions are the cause of debilitating disorders including spinal muscular atrophy (SMA)

Muscle directly meets the vast power demands in agile lizards

Level locomotion in small, agile lizards is characterized by intermittent bursts of fast running. These require very large accelerations, often reaching several times g. The power input required to increase kinetic energy is calculated to be as high as 214 W kg(−1) muscle (±20 W kg(−1) s.e.; averaged over the complete locomotor cycle) and 952 W kg(−1) muscle (±89 W kg(−1) s.e.; instantaneous peak power). In vitro muscle experiments prove that these exceptional power requirements can be met directly by the lizard's muscle fibres alone; there is no need for mechanical power amplifying mechanisms