References of "Hiller, Karsten 50001985"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailMetabolome-wide analysis of stable isotope labeling - Is it worth the effort?
Weindl, Daniel UL; Wegner, André UL; Hiller, Karsten UL

in Frontiers in Physiology (2015), 6(344),

Detailed reference viewed: 98 (12 UL)
Full Text
Peer Reviewed
See detailA roadmap for interpreting (13)C metabolite labeling patterns from cells.
Buescher, Joerg M.; Antoniewicz, Maciek R.; Boros, Laszlo G. et al

in Current opinion in biotechnology (2015), 34

Measuring intracellular metabolism has increasingly led to important insights in biomedical research. (13)C tracer analysis, although less information-rich than quantitative (13)C flux analysis that ... [more ▼]

Measuring intracellular metabolism has increasingly led to important insights in biomedical research. (13)C tracer analysis, although less information-rich than quantitative (13)C flux analysis that requires computational data integration, has been established as a time-efficient method to unravel relative pathway activities, qualitative changes in pathway contributions, and nutrient contributions. Here, we review selected key issues in interpreting (13)C metabolite labeling patterns, with the goal of drawing accurate conclusions from steady state and dynamic stable isotopic tracer experiments. [less ▲]

Detailed reference viewed: 57 (2 UL)
Full Text
Peer Reviewed
See detailGlucose substitution prolongs maintenance of energy homeostasis and lifespan of telomere dysfunctional mice
Missios, Pavlos; Zhou, Youan; Guachalla, Luis Miguel et al

in Nature Communications (2014)

DNA damage and telomere dysfunction shorten organismal lifespan. Here we show that oral glucose administration at advanced age increases health and lifespan of telomere dysfunctional mice. The study ... [more ▼]

DNA damage and telomere dysfunction shorten organismal lifespan. Here we show that oral glucose administration at advanced age increases health and lifespan of telomere dysfunctional mice. The study reveals that energy consumption increases in telomere dysfunctional cells resulting in enhanced glucose metabolism both in glycolysis and in the tricarboxylic acid cycle at organismal level. In ageing telomere dysfunctional mice, normal diet provides insufficient amounts of glucose thus leading to impaired energy homeostasis, catabolism, suppression of IGF-1/mTOR signalling, suppression of mitochondrial biogenesis and tissue atrophy. A glucose-enriched diet reverts these defects by activating glycolysis, mitochondrial biogenesis and oxidative glucose metabolism. The beneficial effects of glucose substitution on mitochondrial function and glucose metabolism are blocked by mTOR inhibition but mimicked by IGF-1 application. Together, these results provide the first experimental evidence that telomere dysfunction enhances the requirement of glucose substitution for the maintenance of energy homeostasis and IGF-1/mTOR-dependent mitochondrial biogenesis in ageing tissues. [less ▲]

Detailed reference viewed: 85 (6 UL)
Full Text
Peer Reviewed
See detailFragment Formula Calculator (FFC): Determination of chemical formulas for fragment ions in mass spectrometric data
Wegner, André UL; Weindl, Daniel UL; Jäger, Christian UL et al

in Analytical Chemistry (2014), 86(4), 22212228

The accurate determination of mass isotopomer distributions (MID) is of great significance for stable isotope-labeling experiments. Most commonly, MIDs are derived from gas chromatography/electron ... [more ▼]

The accurate determination of mass isotopomer distributions (MID) is of great significance for stable isotope-labeling experiments. Most commonly, MIDs are derived from gas chromatography/electron ionization mass spectrometry (GC/EI-MS) measurements. The analysis of fragment ions formed during EI, which contain only specific parts of the original molecule can provide valuable information on the positional distribution of the label. The chemical formula of a fragment ion is usually applied to derive the correction matrix for accurate MID calculation. Hence, the correct assignment of chemical formulas to fragment ions is of crucial importance for correct MIDs. Moreover, the positional distribution of stable isotopes within a fragment ion is of high interest for stable isotope-assisted metabolomics techniques. For example, 13C-metabolic flux analyses (13C-MFA) are dependent on the exact knowledge of the number and position of retained carbon atoms of the unfragmented molecule. Fragment ions containing different carbon atoms are of special interest, since they can carry different flux information. However, the process of mass spectral fragmentation is complex, and identifying the substructures and chemical formulas for these fragment ions is nontrivial. For that reason, we developed an algorithm, based on a systematic bond cleavage, to determine chemical formulas and retained atoms for EI derived fragment ions. Here, we present the fragment formula calculator (FFC) algorithm that can calculate chemical formulas for fragment ions where the chemical bonding (e.g., Lewis structures) of the intact molecule is known. The proposed algorithm is able to cope with general molecular rearrangement reactions occurring during EI in GC/MS measurements. The FFC algorithm is able to integrate stable isotope labeling experiments into the analysis and can automatically exclude candidate formulas that do not fit the observed labeling patterns.1 We applied the FFC algorithm to create a fragment ion repository that contains the chemical formulas and retained carbon atoms of a wide range of trimethylsilyl and tert-butyldimethylsilyl derivatized compounds. In total, we report the chemical formulas and backbone carbon compositions for 160 fragment ions of 43 alkylsilyl-derivatives of primary metabolites. Finally, we implemented the FFC algorithm in an easy-to-use graphical user interface and made it publicly available at http://www.ffc.lu. [less ▲]

Detailed reference viewed: 207 (13 UL)
Full Text
Peer Reviewed
See detailNAR Molecular Biology Database Collection entry number 0953
Choi, C.; Münch, R.; Klein, J. et al

in Nucleic Acids Research (2014)

Detailed reference viewed: 76 (23 UL)
Full Text
Peer Reviewed
See detailSimultaneous extraction of proteins and metabolites from cells in culture
Sapcariu, Sean UL; Kanashova, Tamara; Weindl, Daniel UL et al

in MethodsX (2014)

Detailed reference viewed: 164 (17 UL)
Full Text
Peer Reviewed
See detailMethod validation for preparing urine samples for downstream proteomic and metabolomic applications.
Ammerlaan, Wim; Trezzi, Jean-Pierre UL; Mathay, Conny et al

in Biopreservation and biobanking (2014), 12(5), 351-7

BACKGROUND: Formal validation of methods for biospecimen processing in the context of accreditation in laboratories and biobanks is lacking. A protocol for processing of a biospecimen (urine) was ... [more ▼]

BACKGROUND: Formal validation of methods for biospecimen processing in the context of accreditation in laboratories and biobanks is lacking. A protocol for processing of a biospecimen (urine) was validated for fitness-for-purpose in terms of key downstream endpoints. METHODS: Urine processing was optimized for centrifugation conditions on the basis of microparticle counts at room temperature (RT) and at 4 degrees C. The optimal protocol was validated for performance (microparticle counts), and for reproducibility and robustness for centrifugation temperature (4 degrees C vs. RT) and brake speed (soft, medium, hard). Acceptance criteria were based on microparticle counts, cystatin C and creatinine concentrations, and the metabolomic profile. RESULTS: The optimal protocol was a 20-min, 12,000 g centrifugation at 4 degrees C, and was validated for urine collection in terms of microparticle counts. All reproducibility acceptance criteria were met. The protocol was robust for centrifugation at 4 degrees C versus RT for all parameters. The protocol was considered robust overall in terms of brake speeds, although a hard brake gave significantly fewer microparticles than a soft brake. CONCLUSIONS: We validated a urine processing method suitable for downstream proteomic and metabolomic applications. Temperature and brake speed can influence analytic results, with 4 degrees C and high brake speed considered optimal. Laboratories and biobanks should ensure these conditions are systematically recorded in the scope of accreditation. [less ▲]

Detailed reference viewed: 90 (2 UL)
Full Text
Peer Reviewed
See detailImmune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production
Michelucci, Alessandro UL; Cordes, Thekla UL; Ghelfi, Jenny UL et al

in Proceedings of the National Academy of Sciences of the United States of America (2013)

Immunoresponsive gene 1 (Irg1) is highly expressed in mammalian macrophages during inflammation, but its biological function has not yet been elucidated. Here, we identify Irg1 as the gene coding for an ... [more ▼]

Immunoresponsive gene 1 (Irg1) is highly expressed in mammalian macrophages during inflammation, but its biological function has not yet been elucidated. Here, we identify Irg1 as the gene coding for an enzyme producing itaconic acid (also known as methylenesuccinic acid) through the decarboxylation of cis-aconitate, a tricarboxylic acid cycle intermediate. Using a gain-and-loss-of-function approach in both mouse and human immune cells, we found Irg1 expression levels correlating with the amounts of itaconic acid, a metabolite previously proposed to have an antimicrobial effect. We purified IRG1 protein and identified its cis-aconitate decarboxylating activity in an enzymatic assay. Itaconic acid is an organic compound that inhibits isocitrate lyase, the key enzyme of the glyoxylate shunt, a pathway essential for bacterial growth under specific conditions. Here we show that itaconic acid inhibits the growth of bacteria expressing isocitrate lyase, such as Salmonella enterica and Mycobacterium tuberculosis. Furthermore, Irg1 gene silencing in macrophages resulted in significantly decreased intracellular itaconic acid levels as well as significantly reduced antimicrobial activity during bacterial infections. Taken together, our results demonstrate that IRG1 links cellular metabolism with immune defense by catalyzing itaconic acid production. [less ▲]

Detailed reference viewed: 462 (131 UL)
Full Text
Peer Reviewed
See detailIsotope Cluster-Based Compound Matching in Gas Chromatography/ Mass Spectrometry for Non-Targeted Metabolomics
Wegner, André UL; Sapcariu, Sean UL; Weindl, Daniel UL et al

in Analytical Chemistry (2013), 85(8), 4030-4037

Gas chromatography coupled to mass spectrometry (GC/MS) has emerged as a powerful tool in metabolomics studies. A major bottleneck in current data analysis of GC/MS-based metabolomics studies is compound ... [more ▼]

Gas chromatography coupled to mass spectrometry (GC/MS) has emerged as a powerful tool in metabolomics studies. A major bottleneck in current data analysis of GC/MS-based metabolomics studies is compound matching and identification, as current methods generate high rates of false positive and false -negative identifications. This is especially true for data sets containing a high amount of noise. In this work, a novel spectral similarity measure based on the specific fragmentation patterns of electron impact mass spectra is proposed. An important aspect of these algorithmic methods is the handling of noisy data. The performance of the proposed method compared to the dot product, the current gold standard, was evaluated on a complex biological data set. The analysis results showed significant improvements of the proposed method in compound matching and chromatogram alignment compared to the dot product. [less ▲]

Detailed reference viewed: 179 (18 UL)
Full Text
Peer Reviewed
See detailNTFD - A stand-alone application for the non-targeted detection of stable isotope labeled compounds in GC/MS data.
Hiller, Karsten UL; Wegner, André UL; Weindl, Daniel UL et al

in Bioinformatics (2013), 29(9), 1226-8

SUMMARY: Most current stable isotope-based methodologies are targeted and focus only on the well-described aspects of metabolic networks. Here, we present NTFD (non-targeted tracer fate detection), a ... [more ▼]

SUMMARY: Most current stable isotope-based methodologies are targeted and focus only on the well-described aspects of metabolic networks. Here, we present NTFD (non-targeted tracer fate detection), a software for the non-targeted analysis of all detectable compounds derived from a stable isotope-labeled tracer present in a GC/MS dataset. In contrast to traditional metabolic flux analysis approaches, NTFD does not depend on any a priori knowledge or library information. To obtain dynamic information on metabolic pathway activity, NTFD determines mass isotopomer distributions for all detected and labeled compounds. These data provide information on relative fluxes in a metabolic network. The graphical user interface allows users to import GC/MS data in netCDF format and export all information into a tab-separated format. AVAILABILITY: NTFD is C++- and Qt4-based, and it is freely available under an open-source license. Pre-compiled packages for the installation on Debian- and Redhat-based Linux distributions, as well as Windows operating systems, along with example data, are provided for download at http://ntfd.mit.edu/. CONTACT: gregstep@mit.edu. [less ▲]

Detailed reference viewed: 142 (5 UL)
Full Text
Peer Reviewed
See detailTranscriptional and metabolic adaptation of human neurons to the mitochondrial toxicant MPP(+).
Hiller, Karsten UL

in Cell Death & Differentiation (2013)

Detailed reference viewed: 53 (7 UL)
Full Text
Peer Reviewed
See detailFrom multi-omics to basic structures of biological systems.
Müller, Susann; Hiller, Karsten UL

in Current Opinion in Biotechnology (2013), 24

Detailed reference viewed: 173 (55 UL)
Full Text
Peer Reviewed
See detailPGC-1α supports glutamine metabolism in breast cancer
McGuirk, Shawn; Gravel, Simon-Pierre; Deblois, Geneviève et al

in Cancer & Metabolism (2013)

Detailed reference viewed: 70 (2 UL)
Full Text
Peer Reviewed
See detailTranscriptional and metabolic adaptation of human neurons to the mitochondrial toxicant MPP(+).
Krug, AK.; Gutbier, S.; Zhao, L. et al

in Cell Death & Disease (2013)

Assessment of the network of toxicity pathways by Omics technologies and bioinformatic data processing paves the road toward a new toxicology for the twenty-first century. Especially, the upstream network ... [more ▼]

Assessment of the network of toxicity pathways by Omics technologies and bioinformatic data processing paves the road toward a new toxicology for the twenty-first century. Especially, the upstream network of responses, taking place in toxicanttreated cells before a point of no return is reached, is still little explored. We studied the effects of the model neurotoxicant 1-methyl-4-phenylpyridinium (MPPþ) by a combined metabolomics (mass spectrometry) and transcriptomics (microarrays and deep sequencing) approach to provide unbiased data on earliest cellular adaptations to stress. Neural precursor cells (LUHMES) were differentiated to homogeneous cultures of fully postmitotic human dopaminergic neurons, and then exposed to the mitochondrial respiratory chain inhibitor MPPþ (5 lM). At 18–24 h after treatment, intracellular ATP and mitochondrial integrity were still close to control levels, but pronounced transcriptome and metabolome changes were seen. Data on altered glucose flux, depletion of phosphocreatine and oxidative stress (e.g., methionine sulfoxide formation) confirmed the validity of the approach. New findings were related to nuclear paraspeckle depletion, as well as an early activation of branches of the transsulfuration pathway to increase glutathione. Bioinformatic analysis of our data identified the transcription factor ATF-4 as an upstream regulator of early responses. Findings on this signaling pathway and on adaptive increases of glutathione production were confirmed biochemically. Metabolic and transcriptional profiling contributed complementary information on multiple primary and secondary changes that contribute to the cellular response to MPPþ. Thus, combined ‘Omics’ analysis is a new unbiased approach to unravel earliest metabolic changes, whose balance decides on the final cell fate. [less ▲]

Detailed reference viewed: 80 (8 UL)
Full Text
Peer Reviewed
See detailComplexity of dopamine metabolism
Meiser, Johannes UL; Weindl, Daniel UL; Hiller, Karsten UL

in Cell Communication and Signaling (2013), 11(34),

Parkinson's disease (PD) coincides with a dramatic loss of dopaminergic neurons within the substantia nigra. A key player in the loss of dopaminergic neurons is oxidative stress. Dopamine (DA) metabolism ... [more ▼]

Parkinson's disease (PD) coincides with a dramatic loss of dopaminergic neurons within the substantia nigra. A key player in the loss of dopaminergic neurons is oxidative stress. Dopamine (DA) metabolism itself is strongly linked to oxidative stress as its degradation generates reactive oxygen species (ROS) and DA oxidation can lead to endogenous neurotoxins whereas some DA derivatives show antioxidative effects. Therefore, DA metabolism is of special importance for neuronal redox-homeostasis and viability. In this review we highlight different aspects of dopamine metabolism in the context of PD and neurodegeneration. Since most reviews focus only on single aspects of the DA system, we will give a broader overview by looking at DA biosynthesis, sequestration, degradation and oxidation chemistry at the metabolic level, as well as at the transcriptional, translational and posttranslational regulation of all enzymes involved. This is followed by a short overview of cellular models currently used in PD research. Finally, we will address the topic from a medical point of view which directly aims to encounter PD. [less ▲]

Detailed reference viewed: 187 (17 UL)
Full Text
Peer Reviewed
See detailA biomolecular isolation framework for eco-systems biology
Roume, Hugo UL; Muller, Emilie UL; Cordes, Thekla UL et al

in ISME Journal (The) (2013), 7(1), 110-121

Mixed microbial communities are complex, dynamic and heterogeneous. It is therefore essential that biomolecular fractions obtained for high-throughput omic analyses are representative of single samples to ... [more ▼]

Mixed microbial communities are complex, dynamic and heterogeneous. It is therefore essential that biomolecular fractions obtained for high-throughput omic analyses are representative of single samples to facilitate meaningful data integration, analysis and modeling. We have developed a new methodological framework for the reproducible isolation of high-quality genomic DNA, large and small RNA, proteins, and polar and non-polar metabolites from single unique mixed microbial community samples. The methodology is based around reproducible cryogenic sample preservation and cell lysis. Metabolites are extracted first using organic solvents, followed by the sequential isolation of nucleic acids and proteins using chromatographic spin columns. The methodology was validated by comparison to traditional dedicated and simultaneous biomolecular isolation methods. To prove the broad applicability of the methodology, we applied it to microbial consortia of biotechnological, environmental and biomedical research interest. The developed methodological framework lays the foundation for standardized molecular eco-systematic studies on a range of different microbial communities in the future. [less ▲]

Detailed reference viewed: 201 (20 UL)
Full Text
Peer Reviewed
See detailProfiling metabolic networks to study cancer metabolism
Hiller, Karsten UL; Metallo, Christian M.

in Current Opinion in Biotechnology (2013)

Detailed reference viewed: 96 (7 UL)