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See detailThe exposome and health: Where chemistry meets biology
Vermeulen, Roel; Schymanski, Emma UL; Barabási, Albert-László et al

in Science (2020), 367(6476), 392--396

Despite extensive evidence showing that exposure to specific chemicals can lead to disease, current research approaches and regulatory policies fail to address the chemical complexity of our world. To ... [more ▼]

Despite extensive evidence showing that exposure to specific chemicals can lead to disease, current research approaches and regulatory policies fail to address the chemical complexity of our world. To safeguard current and future generations from the increasing number of chemicals polluting our environment, a systematic and agnostic approach is needed. The \textquotedblleftexposome\textquotedblright concept strives to capture the diversity and range of exposures to synthetic chemicals, dietary constituents, psychosocial stressors, and physical factors, as well as their corresponding biological responses. Technological advances such as high-resolution mass spectrometry and network science have allowed us to take the first steps toward a comprehensive assessment of the exposome. Given the increased recognition of the dominant role that nongenetic factors play in disease, an effort to characterize the exposome at a scale comparable to that of the human genome is warranted. [less ▲]

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See detailTracking complex mixtures of chemicals in our changing environment
Escher, Beate I.; Stapleton, Heather M.; Schymanski, Emma UL

in Science (2020), 367(6476), 388--392

Chemicals have improved our quality of life, but the resulting environmental pollution has the potential to cause detrimental effects on humans and the environment. People and biota are chronically ... [more ▼]

Chemicals have improved our quality of life, but the resulting environmental pollution has the potential to cause detrimental effects on humans and the environment. People and biota are chronically exposed to thousands of chemicals from various environmental sources through multiple pathways. Environmental chemists and toxicologists have moved beyond detecting and quantifying single chemicals to characterizing complex mixtures of chemicals in indoor and outdoor environments and biological matrices. We highlight analytical and bioanalytical approaches to isolating, characterizing, and tracking groups of chemicals of concern in complex matrices. Techniques that combine chemical analysis and bioassays have the potential to facilitate the identification of mixtures of chemicals that pose a combined risk. [less ▲]

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See detailDopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson's disease.
Burbulla, Lena F.; Song, Pingping; Mazzulli, Joseph R. et al

in Science (2017), 357(6357), 1255-1261

Mitochondrial and lysosomal dysfunction have been implicated in substantia nigra dopaminergic neurodegeneration in Parkinson's disease (PD), but how these pathways are linked in human neurons remains ... [more ▼]

Mitochondrial and lysosomal dysfunction have been implicated in substantia nigra dopaminergic neurodegeneration in Parkinson's disease (PD), but how these pathways are linked in human neurons remains unclear. Here we studied dopaminergic neurons derived from patients with idiopathic and familial PD. We identified a time-dependent pathological cascade beginning with mitochondrial oxidant stress leading to oxidized dopamine accumulation and ultimately resulting in reduced glucocerebrosidase enzymatic activity, lysosomal dysfunction, and alpha-synuclein accumulation. This toxic cascade was observed in human, but not in mouse, PD neurons at least in part because of species-specific differences in dopamine metabolism. Increasing dopamine synthesis or alpha-synuclein amounts in mouse midbrain neurons recapitulated pathological phenotypes observed in human neurons. Thus, dopamine oxidation represents an important link between mitochondrial and lysosomal dysfunction in PD pathogenesis. [less ▲]

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See detailWavelike charge density fluctuations and van der Waals interactions at the nanoscale
Ambrosetti, Alberto; Ferri, Nicola; DiStasio Jr., Robert A. et al

in Science (2016), 351(6278), 1171-1176

Recent experiments on noncovalent interactions at the nanoscale have challenged the basic assumptions of commonly used particle- or fragment-based models for describing van der Waals (vdW) or dispersion ... [more ▼]

Recent experiments on noncovalent interactions at the nanoscale have challenged the basic assumptions of commonly used particle- or fragment-based models for describing van der Waals (vdW) or dispersion forces. We demonstrate that a qualitatively correct description of the vdW interactions between polarizable nanostructures over a wide range of finite distances can only be attained by accounting for the wavelike nature of charge density fluctuations. By considering a diverse set of materials and biological systems with markedly different dimensionalities, topologies, and polarizabilities, we find a visible enhancement in the nonlocality of the charge density response in the range of 10 to 20 nanometers. These collective wavelike fluctuations are responsible for the emergence of nontrivial modifications of the power laws that govern noncovalent interactions at the nanoscale. [less ▲]

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See detailReproducibility in density functional theory calculations of solids
Lejaeghere, K.; Bihlmayer, G.; Tkatchenko, Alexandre UL et al

in Science (2016), 351

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See detailSystems proteomics of liver mitochondria function.
Williams, Evan UL; Wu, Yibo; Jha, Pooja et al

in Science (2016), 352(6291), 0189

Recent improvements in quantitative proteomics approaches, including Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS), permit reproducible large-scale protein measurements across ... [more ▼]

Recent improvements in quantitative proteomics approaches, including Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS), permit reproducible large-scale protein measurements across diverse cohorts. Together with genomics, transcriptomics, and other technologies, transomic data sets can be generated that permit detailed analyses across broad molecular interaction networks. Here, we examine mitochondrial links to liver metabolism through the genome, transcriptome, proteome, and metabolome of 386 individuals in the BXD mouse reference population. Several links were validated between genetic variants toward transcripts, proteins, metabolites, and phenotypes. Among these, sequence variants in Cox7a2l alter its protein's activity, which in turn leads to downstream differences in mitochondrial supercomplex formation. This data set demonstrates that the proteome can now be quantified comprehensively, serving as a key complement to transcriptomics, genomics, and metabolomics--a combination moving us forward in complex trait analysis. [less ▲]

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See detailIs low fertility really a problem? Population aging, dependency, and consumption
Lee, Ronald; Mason, Andrew; Olivera Angulo, Javier UL et al

in Science (2014), 346(6206), 229-234

Longer lives and fertility far below the replacement level of 2.1 births per woman are leading to rapid population aging in many countries. Many observers are concerned that aging will adversely affect ... [more ▼]

Longer lives and fertility far below the replacement level of 2.1 births per woman are leading to rapid population aging in many countries. Many observers are concerned that aging will adversely affect public finances and standards of living. Analysis of newly available National Transfer Accounts data for 40 countries shows that fertility well above replacement would typically be most beneficial for government budgets. However, fertility near replacement would be most beneficial for standards of living when the analysis includes the effects of age structure on families as well as governments. And fertility below replacement would maximize per capita consumption when the cost of providing capital for a growing labor force is taken into account. Although low fertility will indeed challenge government programs and very low fertility undermines living standards, we find that moderately low fertility and population decline favor the broader material standard of living. [less ▲]

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See detailPINK1 loss-of-function mutations affect mitochondrial complex I activity via NdufA10 ubiquinone uncoupling.
Morais, Vanessa A.; Haddad, Dominik; Craessaerts, Katleen et al

in Science (2014), 344(6180), 203-7

Under resting conditions, Pink1 knockout cells and cells derived from patients with PINK1 mutations display a loss of mitochondrial complex I reductive activity, causing a decrease in the mitochondrial ... [more ▼]

Under resting conditions, Pink1 knockout cells and cells derived from patients with PINK1 mutations display a loss of mitochondrial complex I reductive activity, causing a decrease in the mitochondrial membrane potential. Analyzing the phosphoproteome of complex I in liver and brain from Pink1(-/-) mice, we found specific loss of phosphorylation of serine-250 in complex I subunit NdufA10. Phosphorylation of serine-250 was needed for ubiquinone reduction by complex I. Phosphomimetic NdufA10 reversed Pink1 deficits in mouse knockout cells and rescued mitochondrial depolarization and synaptic transmission defects in pink(B9)-null mutant Drosophila. Complex I deficits and adenosine triphosphate synthesis were also rescued in cells derived from PINK1 patients. Thus, this evolutionary conserved pathway may contribute to the pathogenic cascade that eventually leads to Parkinson's disease in patients with PINK1 mutations. [less ▲]

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See detailImportance de la langue maternelle pour le development des enfants au Luxembourg
Aleksic, Gabrijela UL

Article for general public (2013)

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See detailThree-dimensional structural view of the central metabolic network of Thermotoga maritima.
Zhang, Ying; Thiele, Ines UL; Weekes, Dana et al

in Science (2009), 325(5947), 1544-1549

Metabolic pathways have traditionally been described in terms of biochemical reactions and metabolites. With the use of structural genomics and systems biology, we generated a three-dimensional ... [more ▼]

Metabolic pathways have traditionally been described in terms of biochemical reactions and metabolites. With the use of structural genomics and systems biology, we generated a three-dimensional reconstruction of the central metabolic network of the bacterium Thermotoga maritima. The network encompassed 478 proteins, of which 120 were determined by experiment and 358 were modeled. Structural analysis revealed that proteins forming the network are dominated by a small number (only 182) of basic shapes (folds) performing diverse but mostly related functions. Most of these folds are already present in the essential core (approximately 30%) of the network, and its expansion by nonessential proteins is achieved with relatively few additional folds. Thus, integration of structural data with networks analysis generates insight into the function, mechanism, and evolution of biological networks. [less ▲]

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See detailThe Arabidopsis circadian clock incorporates a cADPR-based feedback loop
Dodd, A. N.; Gardner, M. J.; Hotta, C. T. et al

in SCIENCE (2007), 318(5857), 1789-1792

Transcriptional feedback loops are a feature of circadian clocks in both animals and plants. We show that the plant circadian clock also incorporates the cytosolic signaling molecule cyclic adenosine ... [more ▼]

Transcriptional feedback loops are a feature of circadian clocks in both animals and plants. We show that the plant circadian clock also incorporates the cytosolic signaling molecule cyclic adenosine diphosphate ribose (cADPR). cADPR modulates the circadian oscillator’s transcriptional feedback loops and drives circadian oscillations of Ca2+ release. The effects of antagonists of cADPR signaling, manipulation of cADPR synthesis, and mathematical simulation of the interaction of cADPR with the circadian clock indicate that cADPR forms a feedback loop within the plant circadian clock. [less ▲]

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See detailChanges in surface water supply across Africa with predicted climate change
De Wit, M.; Stankiewicz, Jacek UL

in Science (2006), 311(5769), 1917-1921

Across Africa, perennial drainage density as a function of mean annual rainfall defines three regimes separated by threshold values of precipitation. This nonlinear response of drainage to rainfall will ... [more ▼]

Across Africa, perennial drainage density as a function of mean annual rainfall defines three regimes separated by threshold values of precipitation. This nonlinear response of drainage to rainfall will most seriously affect regions in the intermediate, unstable regime. A 10% decrease in precipitation in regions on the upper regime boundary (1000 millimeters per year) would reduce drainage by 17%, whereas in regions receiving 500 millimeters per year, such a drop would cut 50% of surface drainage. By using predicted precipitation changes, we calculate that a decrease in perennial drainage will significantly affect present surface water access across 25% of Africa by the end of this century. [less ▲]

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See detailTime and Aging--Mechanisms and Meanings
Wollscheid-Lengeling, Evi UL

in Science (2005), 2005(15),

A recent European Molecular Biology Laboratory Conference on Science and Society entitled "Time & Aging--Mechanisms & Meanings" fascinated scientists from different research areas as well as nonscientists ... [more ▼]

A recent European Molecular Biology Laboratory Conference on Science and Society entitled "Time & Aging--Mechanisms & Meanings" fascinated scientists from different research areas as well as nonscientists. Topics discussed included not only the biological aging process but also the psychological effects of aging and social influences that affect this process. [less ▲]

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See detailSequence interpretation. Functional annotation of mouse genome sequences.
Nadeau, J. H.; Balling, Rudi UL; Barsh, G. et al

in Science (2001), 291(5507), 1251-5

Detailed reference viewed: 139 (7 UL)