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Showing papers by "Braunschweig University of Technology published in 2011"


Journal ArticleDOI
TL;DR: The quest for alternative drugs to the well-known cisplatin and its derivatives, which are still used in more than 50% of the treatment regimes for patients suffering from cancer, is highly needed, and organometallic compounds have recently been found to be promising anticancer drug candidates.
Abstract: The quest for alternative drugs to the well-known cisplatin and its derivatives, which are still used in more than 50% of the treatment regimes for patients suffering from cancer, is highly needed.1,2 Despite their tremendous success, these platinum compounds suffer from two main disadvantages: they are inefficient against platinum-resistant tumors, and they have severe side effects such as nephrotoxicity. The latter drawback is the consequence of the fact that the ultimate target of these drugs is ubiquitous: It is generally accepted that Pt anticancer drugs target DNA, which is present in all cells.3,4 Furthermore, as a consequence of its particular chemical structure, cisplatin in particular offers little possibility for rational improvements to increase its tumor specificity and thereby reduce undesired side effects. In this context, organometallic compounds, which are defined as metal complexes containing at least one direct, covalent metal−carbon bond, have recently been found to be promising anticancer drug candidates. Organometallics have a great structural variety (ranging from linear to octahedral and even beyond), have far more diverse stereochemistry than organic compounds (for an octahedral complex with six different ligands, 30 stereoisomers exist!), and by rational ligand design, provide control over key kinetic properties (such as hydrolysis rate of ligands). Furthermore, they are kinetically stable, usually uncharged, and relatively lipophilic and their metal atom is in a low oxidation state. Because of these fundamental differences compared to “classical coordination metal complexes”, organometallics offer ample opportunities in the design of novel classes of medicinal compounds, potentially with new metal-specific modes of action. Interestingly, all the typical classes of organometallics such as metallocenes, half-sandwich, carbene-, CO-, or π-ligands, which have been widely used for catalysis or biosensing purposes, have now also found application in medicinal chemistry (see Figure ​Figure11 for an overview of these typical classes of organometallics). Figure 1 Summary of the typical classes of organometallic compounds used in medicinal chemistry. In this Perspective, we report on the recent advances in the discovery of organometallics with proven antiproliferative activity. We are emphasizing those compounds where efforts have been made to identify their molecular target and mode of action by biochemical or cell biology studies. This Perspective covers more classes of compounds and in more detail than a recent tutorial review by Hartinger and Dyson.(5) Furthermore, whereas recent reviews and book contributions attest to the rapid development of bioorganometallic chemistry in general,6,7 this Perspective focuses on their potential application as anticancer chemotherapeutics. Another very recent review article categorizes inorganic anticancer drug candidates by their modes of action.(8) It should be mentioned that a full description of all currently investigated types of compounds is hardly possible anymore in a concise review. For example, a particularly promising class of organometallic anticancer compounds, namely, radiolabeled organometallics, has been omitted for space limitations. Recent developments of such compounds have been reviewed in detail by Alberto.(9)

1,364 citations


Journal ArticleDOI
TL;DR: This is the first report of a rationally derived lysine production strain that may be competitive with industrial applications and could serve as general concept for the rational development of microorganisms as efficient cellular factories for bio-production.

524 citations


Journal ArticleDOI
TL;DR: The amenability of in vitro display to high-throughput applications broadens the prospects for their wider use in basic and applied research.
Abstract: In vitro display technologies, best exemplified by phage and yeast display, were first described for the selection of antibodies some 20 years ago. Since then, many antibodies have been selected and improved upon using these methods. Although it is not widely recognized, many of the antibodies derived using in vitro display methods have properties that would be extremely difficult, if not impossible, to obtain by immunizing animals. The first antibodies derived using in vitro display methods are now in the clinic, with many more waiting in the wings. Unlike immunization, in vitro display permits the use of defined selection conditions and provides immediate availability of the sequence encoding the antibody. The amenability of in vitro display to high-throughput applications broadens the prospects for their wider use in basic and applied research.

499 citations


Journal ArticleDOI
TL;DR: The BRENDA enzyme information system is the main collection of enzyme functional and property data for the scientific community and now provides new viewing options such as the display of the statistics of functional parameters and the 3D view of protein sequence and structure features.
Abstract: The BRENDA (BRaunschweig ENzyme Database, http://www.brenda-enzymes.org) enzyme information system is the main collection of enzyme functional and property data for the scientific community. The majority of the data are manually extracted from the primary literature. The content covers information on function, structure, occurrence, preparation and application of enzymes as well as properties of mutants and engineered variants. The number of manually annotated references increased by 30% to more than 100 000, the number of ligand structures by 45% to almost 100 000. New query, analysis and data management tools were implemented to improve data processing, data presentation, data input and data access. BRENDA now provides new viewing options such as the display of the statistics of functional parameters and the 3D view of protein sequence and structure features. Furthermore a ligand summary shows comprehensive information on the BRENDA ligands. The enzymes are linked to their respective pathways and can be viewed in pathway maps. The disease text mining part is strongly enhanced. It is possible to submit new, not yet classified enzymes to BRENDA, which then are reviewed and classified by the International Union of Biochemistry and Molecular Biology. A new SBML output format of BRENDA kinetic data allows the construction of organism-specific metabolic models.

428 citations


Journal ArticleDOI
TL;DR: The vision and architecture of a Semantic Web of Things is described: a service infrastructure that makes the deployment and use of semantic applications involving Internet-connected sensors almost as easy as building, searching, and reading a web page today.
Abstract: The developed world is awash with sensors. However, they are typically locked into unimodal closed systems. To unleash their full potential, access to sensors should be opened such that their data and services can be integrated with data and services available in other information systems, facilitating novel applications and services that are based on the state of the real world. We describe our vision and architecture of a Semantic Web of Things: a service infrastructure that makes the deployment and use of semantic applications involving Internet-connected sensors almost as easy as building, searching, and reading a web page today.

337 citations


Journal ArticleDOI
TL;DR: In this paper, a superposed epoch analysis of dipolarization front crossings and their characteristic gradient scales was performed, revealing a rapid 50% decrease in plasma density and ion pressure, a factor of 2-3 increase in high-energy (30-200 keV) electron flux and electron temperature, and transient enhancements of ∼5 mV/m in duskward and earthward electric field components.
Abstract: [1] We discuss results of a superposed epoch analysis of dipolarization fronts, rapid (δt 10 nT) increases in the northward magnetic field component, observed during six Time History of Events and Macroscale Interactions during Substorms (THEMIS) conjunction events. All six fronts propagated earthward; time delays at multiple probes were used to determine their propagation velocity. We define typical magnetic and electric field and plasma parameter variations during dipolarization front crossings and estimate their characteristic gradient scales. The study reveals (1) a rapid 50% decrease in plasma density and ion pressure, (2) a factor of 2–3 increase in high-energy (30–200 keV) electron flux and electron temperature, and (3) transient enhancements of ∼5 mV/m in duskward and earthward electric field components. Gradient scales of magnetic field, plasma density, and particle flux were found to be comparable to the ion thermal gyroradius. Current densities associated with the Bz increase are, on average, 20 nA/m2, 5–7 times larger than the current density in the cross-tail current sheet. Because j · E > 0, the dipolarization fronts are kinetic-scale dissipative regions with Joule heating rates of 10% of the total bursty bulk flow energy.

325 citations


Journal ArticleDOI
TL;DR: This review summarizes the current state of knowledge of hydrothermal biomass conversion in subcritical water and major emphasis is put on the nature of the carbohydrate monomers, since the conversion of the respective polymers is analogous with the additional prior step of hydrolytic depolymerization.
Abstract: Subcritical water, that is, water above the boiling and below critical point, is a unique and sustainable reaction medium. Based on its solvent properties, in combination with the often considerable intrinsic water content of natural biomass, it is often considered as a potential solvent for biomass processing. Current knowledge on biomass transformation in subcritical water is, however, still rather scattered without providing a consistent picture. Concentrating on fundamental physical and chemical aspects, this review summarizes the current state of knowledge of hydrothermal biomass conversion in subcritical water. After briefly introducing subcritical water as a reaction medium, its advantages for biomass processing compared to other thermal processes are highlighted. Subsequently, the physical-chemical properties of subcritical water are discussed in the light of their impact on the occurring chemical reactions. The influence of major operational parameters, including temperature, pressure, and reactant concentration on hydrothermal biomass transformation processes are illustrated for selected carbohydrates. Major emphasis is put on the nature of the carbohydrate monomers, since the conversion of the respective polymers is analogous with the additional prior step of hydrolytic depolymerization.

299 citations


Journal ArticleDOI
TL;DR: In this paper, three-dimensional carbon fiber electrodes prepared by electrospinning and solution blowing are shown to be excellent electrode materials for bioelectrochemical systems such as microbial fuel cells or microbial electrolysis cells.
Abstract: Three-dimensional carbon fiber electrodes prepared by electrospinning and solution blowing are shown to be excellent electrode materials for bioelectrochemical systems such as microbial fuel cells or microbial electrolysis cells. The bioelectrocatalytic anode current density is shown to reach values of up to 30 A m−2, which represents the highest reported values for electroactive microbial biofilms.

297 citations


Journal ArticleDOI
TL;DR: In this article, the authors investigated the defixation and fixation and fixation of NH====== 4====== +====== in different soils and found that the amount of nitrogen available to plants in the defixed soil is varied with parent material, texture, clay content, clay mineral composition, potassium status of the soil and K saturation of the interlayers of 2:1 clay minerals, and moisture conditions.
Abstract: Fixed NH 4 + (NH 4 + f) and fixation and defixation of NH 4 + in soils have been the subject of a number of investigations with conflicting results. The results vary because of differences in methodology, soil type, mineralogical composition, and agro-climatic conditions. Most investigators have determined NH 4 + f using strong oxidizing agents (KOBr or KOH) to remove organic N and the remaining NH 4 + f does not necessarily reflect the fraction that is truly available to plants. The content of native NH 4 + f in different soils is related to parent material, texture, clay content, clay mineral composition, potassium status of the soil and K saturation of the interlayers of 2:1 clay minerals, and moisture conditions. Evaluation of the literature shows that the NH 4 + f-N content amounts to 10–90 mg kg−1 in coarse-textured soils (e.g., diluvial sand, red sandstone, granite), 60–270 mg kg−1 in medium-textured soils (loess, marsh, alluvial sediment, basalt) and 90–460 mg kg−1 in fine-textured soils (limestone, clay stone). Variable results on plant availability of NH 4 + f are mainly due to the fact that some investigators distinguished between native and recently fixed NH 4 + while others did not. Recently fixed NH 4 + is available to plants to a greater degree than the native NH 4 + f, and soil microflora play an important role in the defixation process. The temporal changes in the content of recently fixed NH 4 + suggest that it is actively involved in N dynamics during a crop growth season. The amounts of NH 4 + defixed during a growing season varied greatly within the groups of silty (20–200 kg NH 4 + -N ha−1 30 cm−1) as well as clayey (40–188 kg NH 4 + -N ha−1 30 cm−1) soils. The pool of recently fixed NH 4 + may therefore be considered in fertilizer management programs for increasing N use efficiency and reducing N losses from soils.

267 citations


Journal ArticleDOI
TL;DR: In this paper, an energy-oriented simulation model for planning of manufacturing systems is presented, where dynamic interactions of different processes as well as auxiliary equipments (e.g. compressed air generation) are taken into account when planning and controlling manufacturing systems.

265 citations


Journal ArticleDOI
TL;DR: This review gives a short overview over the instrumentation used in cryo-TEM experiments and over the sample preparation procedure.

Journal ArticleDOI
08 Sep 2011-Neuron
TL;DR: This work identified amyloid β (Aβ) as an NO target, which is nitrated at tyrosine 10 (3NTyr(10)-Aβ), and suggests a disease modifying role for NOS2 in AD and therefore represents a potential therapeutic target.

Journal ArticleDOI
TL;DR: It is demonstrated that energy-transfer paths can be controlled on the single-molecule level by the presence of a "jumper" dye that directs the excited-state energy either to a red or to an IR output dye.
Abstract: Fluorescence resonance energy transfer (FRET) represents a mechanism to transport light energy at the nanoscale, as exemplified by nature's light-harvesting complexes. Here we used DNA origami to arrange fluorophores that transport excited-state energy from an input dye to an output dye. We demonstrate that energy-transfer paths can be controlled on the single-molecule level by the presence of a "jumper" dye that directs the excited-state energy either to a red or to an IR output dye. We used single-molecule four-color FRET with alternating laser excitation to sort subpopulations and to visualize the control of energy transfer.

Journal ArticleDOI
TL;DR: In this paper, the authors show that transition metal-oxides (TMOs) such as molybdenum-, vanadium-, or tungstenoxide (MoO 3, V 2 O 5, and WO 3 ) with high work functions (WFs) of up to 6.9 eV have been shown to be promising alternatives to PEDOT:PSS.
Abstract: Organic solar cells (OSCs) based on polymers and small molecules have seen a tremendous increase in interest during the past few years. Signifi cant progress in this fi eld seeded the prospect for a cost-effective and easy-to-fabricate photovoltaic technology—typical advantages claimed for organic (opto-)electronic devices. Very recently, certifi ed cell effi ciencies in excess of 7% have been reported for polymer based cells. [ 1 ] For large-scale and high-throughput production of OSCs, liquid processing of the functional layers is desirable. Aside from the active organic layers, inter-layers are typically required to facilitate the extraction of the photo-generated charges. Specifi cally, on the anode side, polyethylene dioxythiophene:polystyrenesulfonate (PEDOT:PSS) is regularly used. [ 2 ] However, PEDOT:PSS is burdened with structural and electrical inhomogeneity [ 3,4 ] and has been demonstrated to be an origin of limited device lifetime. [ 5 ] Particularly, the aqueous PEDOT:PSS dispersion and the acidic nature can cause substantial degradation. [6,7 ] Very recently, transition metal-oxides (TMOs) such as molybdenum-, vanadium-, or tungsten-oxide (MoO 3 , V 2 O 5 , and WO 3 ) with high work functions (WFs) of up to 6.9 eV have been shown to be promising alternatives to PEDOT:PSS. [ 8‐11 ] TMOs have also been used as constituents of the connecting architecture in stacked organic light-emitting diodes and organic tandem solar cells. [ 12‐15 ] The unique energetics of these TMOs has so far been predominantly

Journal ArticleDOI
TL;DR: One of these counteradaptations, the nitrile-specifier protein identified in Pierid species, has been used to demonstrate mechanisms of coevolution of plants and their insect herbivores.

Journal ArticleDOI
28 Dec 2011-PLOS ONE
TL;DR: It is demonstrated that the composition of the skin microbiota affects the degree of attractiveness of human beings to this mosquito species, which may lead to the development of new mosquito attractants and personalized methods for protection against vectors of malaria and other infectious diseases.
Abstract: The African malaria mosquito Anopheles gambiae sensu stricto continues to play an important role in malaria transmission, which is aggravated by its high degree of anthropophily, making it among the foremost vectors of this disease. In the current study we set out to unravel the strong association between this mosquito species and human beings, as it is determined by odorant cues derived from the human skin. Microbial communities on the skin play key roles in the production of human body odour. We demonstrate that the composition of the skin microbiota affects the degree of attractiveness of human beings to this mosquito species. Bacterial plate counts and 16S rRNA sequencing revealed that individuals that are highly attractive to An. gambiae s.s. have a significantly higher abundance, but lower diversity of bacteria on their skin than individuals that are poorly attractive. Bacterial genera that are correlated with the relative degree of attractiveness to mosquitoes were identified. The discovery of the connection between skin microbial populations and attractiveness to mosquitoes may lead to the development of new mosquito attractants and personalized methods for protection against vectors of malaria and other infectious diseases.

Journal ArticleDOI
TL;DR: Remarkable antiproliferative effects, a strong induction of apoptosis, and enhancement of reactive oxygen species (ROS) formation as well as other effects on tumor cell metabolism confirmed the promising potential of the complexes as novel anticancer chemotherapeutics.
Abstract: Gold(I) complexes with a 1,3-diethylbenzimidazol-2-ylidene N-heterocyclic carbene (NHC) ligand of the type NHC-Au-L (L = -Cl, -NHC, or -PPh3) were comparatively evaluated as thioredoxin reductase (TrxR) inhibitors and antimitochondrial anticancer agents. Different effects were noted in various biochemical assays (e.g., inhibition of TrxR, cellular and mitochondrial uptake, or effects on mitochondrial membrane potential), and this was related to properties of the complexes such as bond dissociation energies and overall charge. Remarkable antiproliferative effects, a strong induction of apoptosis, and enhancement of reactive oxygen species (ROS) formation as well as other effects on tumor cell metabolism confirmed the promising potential of the complexes as novel anticancer chemotherapeutics.

Book ChapterDOI
01 Jan 2011
TL;DR: The investigation of fixed energy consumption from definition and description to improvement strategies is presented and six machine tools covering different manufacturing processes are selected in order to evaluate the future savings.
Abstract: Improving energy efficiency of manufacturing processes requires knowledge about the energy consumption as a function of the machine tool and cutting process itself. Both theoretical and empirical models of unit process energy consumption have emphasized the relevance of fixed energy consumption which ensures the machine readiness. However, the machine tool behavior during the stand-by mode is lack of thorough study. This paper presented the investigation of fixed energy consumption from definition and description to improvement strategies. Six machine tools covering different manufacturing processes are selected for this investigation in order to evaluate the future savings.

Journal ArticleDOI
TL;DR: Recent progress in the understanding of the structural and catalytic properties of molybdenum-containing enzymes in eukaryotes is reviewed, along with aspects of the biosynthesis of the cofactor and its insertion into apoprotein.

Journal ArticleDOI
28 Oct 2011-Science
TL;DR: A spacecraft flyby of an asteroid reveals a high-density body that is more like a planetesimal than a rubble pile, which contrasts with smaller asteroids visited by previous spacecraft, which are probably shattered bodies, fragments of larger parents, or reaccumulated rubble piles.
Abstract: Images obtained by the Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) cameras onboard the Rosetta spacecraft reveal that asteroid 21 Lutetia has a complex geology and one of the highest asteroid densities measured so far, 3.4 ± 0.3 grams per cubic centimeter. The north pole region is covered by a thick layer of regolith, which is seen to flow in major landslides associated with albedo variation. Its geologically complex surface, ancient surface age, and high density suggest that Lutetia is most likely a primordial planetesimal. This contrasts with smaller asteroids visited by previous spacecraft, which are probably shattered bodies, fragments of larger parents, or reaccumulated rubble piles.

Journal ArticleDOI
27 May 2011-PLOS ONE
TL;DR: It is found that suspensions of nanosized (∼100 nm initial mean diameter) titanium dioxide (nTiO2) led to toxicity in Daphnia magna at nominal concentrations and predicted levels as low as 0.24 mg/L (96-h EC50) based on measured concentrations and hypothesized a mechanistic chain of events for n TiO2 toxicity inD. magna that involves the coating of the organism surface with nTiO 2 combined with a molting disruption
Abstract: The production and use of nanoparticles (NP) has steadily increased within the last decade; however, knowledge about risks of NP to human health and ecosystems is still scarce. Common knowledge concerning NP effects on freshwater organisms is largely limited to standard short-term (≤48 h) toxicity tests, which lack both NP fate characterization and an understanding of the mechanisms underlying toxicity. Employing slightly longer exposure times (72 to 96 h), we found that suspensions of nanosized (∼100 nm initial mean diameter) titanium dioxide (nTiO2) led to toxicity in Daphnia magna at nominal concentrations of 3.8 (72-h EC50) and 0.73 mg/L (96-h EC50). However, nTiO2 disappeared quickly from the ISO-medium water phase, resulting in toxicity levels as low as 0.24 mg/L (96-h EC50) based on measured concentrations. Moreover, we showed that nTiO2 (∼100 nm) is significantly more toxic than non-nanosized TiO2 (∼200 nm) prepared from the same stock suspension. Most importantly, we hypothesized a mechanistic chain of events for nTiO2 toxicity in D. magna that involves the coating of the organism surface with nTiO2 combined with a molting disruption. Neonate D. magna (≤6 h) exposed to 2 mg/L nTiO2 exhibited a “biological surface coating” that disappeared within 36 h, during which the first molting was successfully managed by 100% of the exposed organisms. Continued exposure up to 96 h led to a renewed formation of the surface coating and significantly reduced the molting rate to 10%, resulting in 90% mortality. Because coating of aquatic organisms by manmade NP might be ubiquitous in nature, this form of physical NP toxicity might result in widespread negative impacts on environmental health.

Journal ArticleDOI
TL;DR: Cyanidin 3-xylosyl(sinapoylglucosyl)galactoside was found to exhibit a lower visual detection threshold and a higher pH stability than cyanidin 2-xyleosyl (feruloyl glucosol)galactsoside and cyanid in 3- xylosol(coumaroyl Glucosil)galACToside, which were found to be major anthocyanins.
Abstract: This study aimed to identify the pigment composition of black carrot (Daucus carota ssp. sativus var. atrorubens Alef.) cultivars Antonina, Beta Sweet, Deep Purple, and Purple Haze. Cyanidin 3-xylosyl(glucosyl)galactosides acylated with sinapic acid, ferulic acid, and coumaric acid were detected as major anthocyanins by high-performance liquid chromatography with diode array detection (HPLC-DAD) and with electrospray ionization multiple mass spectrometry (HPLC-ESI-MS(n)) analyses. The preparative isolation of these pigments was carried out by means of high-speed countercurrent chromatography (HSCCC). The color activity concept was applied to the isolated anthocyanins at three pH values. Cyanidin 3-xylosyl(sinapoylglucosyl)galactoside was found to exhibit a lower visual detection threshold and a higher pH stability than cyanidin 3-xylosyl(feruloylglucosyl)galactoside and cyanidin 3-xylosyl(coumaroylglucosyl)galactoside. The color parameters of the fresh roots of the four cultivars were described by the CIELab coordinates L* (lightness), C* (chroma), and h(ab) (hue angles). Total phenolics varied among the cultivars and ranged from 17.9 to 97.9 mg gallic acid equivalents (GAE)/100 g fresh weight (fw). For the content of monomeric anthocyanins, values between 1.5 and 17.7 mg/100 g fw were determined.

Journal ArticleDOI
TL;DR: A simple and straightforward comparative analysis of five popular schemes for bulk forcing terms into the lattice Boltzmann equation finds that the densities of the coexisting liquid and gas can be adjusted to match those at thermodynamic equilibrium if the particle interaction term includes next-nearest-neighbor contributions.
Abstract: Numerous schemes have been proposed to incorporate a bulk forcing term into the lattice Boltzmann equation. In this paper we present a simple and straightforward comparative analysis of five popular schemes [Shan and Chen, Phys. Rev. E 47, 1815 (1993); Phys Rev Lett. 81, 1618 (1998); He et al., Phys. Rev. E 57, R13 (1998); Guo et al., Phys. Rev. E 65, 046308 (2002); Kupershtokh et al., Comput. Math. Appl. 58, 965 (2009)] in which their differences and similarities are identified. From the analysis we classify the schemes into two groups; the behaviors of the schemes in each group are proven to be identical up to second order. Numerical test simulating the two-dimensional unsteady Taylor-Green vortex flow problem demonstrate that all five schemes are of comparable accuracy for single-phase flow. However, for two-phase flow the situation is different, which is demonstrated by incorporating these schemes into different Shan-Chen-type multiphase models. The forcing scheme in the original Shan-Chen (SC) multiphase model turns out to be inaccurate in terms of the resulting surface tension for different density ratios and relaxation times. In the numerical tests, a typical equation of state and interparticle interactions including next-nearest neighbors were incorporated into the SC model. Our results confirm that the surface-tension values obtained from the original SC lattice Boltzmann method (LBM) simulation depend on the value of the relaxation time τ. For τ 0.7Δt, the surface tension turns out to be systematically larger than the analytical one, exceeding it by more than a factor of 2 for τ=2Δt. In contrast, with the application of the scheme proposed by He et al., the SC LBM produces very accurate surface tensions independent of the value of τ. We also found that the densities of the coexisting liquid and gas can be adjusted to match those at thermodynamic equilibrium if the particle interaction term includes next-nearest-neighbor contributions. The obtained results will be useful for further studies of two-phase flow with high density ratios using the SC LBM approach.

Journal ArticleDOI
TL;DR: The project started in 2003 to create a connection between the enzyme data collection of the BRENDA enzyme database and a structured network of source tissues and cell types and is widely used by lab scientists, curators of genomic and biochemical databases and bioinformaticians.
Abstract: BTO, the BRENDA Tissue Ontology (http://www.BTO.brenda-enzymes.org) represents a comprehensive structured encyclopedia of tissue terms. The project started in 2003 to create a connection between the enzyme data collection of the BRENDA enzyme database and a structured network of source tissues and cell types. Currently, BTO contains more than 4600 different anatomical structures, tissues, cell types and cell lines, classified under generic categories corresponding to the rules and formats of the Gene Ontology Consortium and organized as a directed acyclic graph (DAG). Most of the terms are endowed with comments on their derivation or definitions. The content of the ontology is constantly curated with ∼1000 new terms each year. Four different types of relationships between the terms are implemented. A versatile web interface with several search and navigation functionalities allows convenient online access to the BTO and to the enzymes isolated from the tissues. Important areas of applications of the BTO terms are the detection of enzymes in tissues and the provision of a solid basis for text-mining approaches in this field. It is widely used by lab scientists, curators of genomic and biochemical databases and bioinformaticians. The BTO is freely available at http://www.obofoundry.org.

Journal ArticleDOI
TL;DR: The data show that APLP2 and APP are synergistically required to mediate neuromuscular transmission, spatial learning and synaptic plasticity.
Abstract: Despite its key role in Alzheimer pathogenesis, the physiological function(s) of the amyloid precursor protein (APP) and its proteolytic fragments are still poorly understood. Previously, we generated APPsα knock-in (KI) mice expressing solely the secreted ectodomain APPsα. Here, we generated double mutants (APPsα-DM) by crossing APPsα-KI mice onto an APLP2-deficient background and show that APPsα rescues the postnatal lethality of the majority of APP/APLP2 double knockout mice. Surviving APPsα-DM mice exhibited impaired neuromuscular transmission, with reductions in quantal content, readily releasable pool, and ability to sustain vesicle release that resulted in muscular weakness. We show that these defects may be due to loss of an APP/Mint2/Munc18 complex. Moreover, APPsα-DM muscle showed fragmented post-synaptic specializations, suggesting impaired postnatal synaptic maturation and/or maintenance. Despite normal CNS morphology and unaltered basal synaptic transmission, young APPsα-DM mice already showed pronounced hippocampal dysfunction, impaired spatial learning and a deficit in LTP that could be rescued by GABAA receptor inhibition. Collectively, our data show that APLP2 and APP are synergistically required to mediate neuromuscular transmission, spatial learning and synaptic plasticity.

Journal ArticleDOI
TL;DR: The microbial diversity of the anode chamber community during the biofilm selection process was studied using the low cost method flow-cytometry and it was demonstrated that the pH value as well as the microbial inocula had an impact on the resulting anode community structure.

Journal ArticleDOI
TL;DR: Based on the state-of-art knowledge on the pathways and reactions linked to microbial 1,5-diaminopentane metabolism, the review covers novel systems metabolic engineering approaches towards hyper-producing cell factories of Corynebacteria glutamicum or Escherichia coli.
Abstract: In the rising era of bio-economy, the five carbon compound 1,5-diaminopentane receives increasing interest as platform chemical, especially as innovative building block for bio-based polymers. The vital interest in bio-based supply of 1,5-diaminopentane has strongly stimulated research on the development of engineered producer strains. Based on the state-of-art knowledge on the pathways and reactions linked to microbial 1,5-diaminopentane metabolism, the review covers novel systems metabolic engineering approaches towards hyper-producing cell factories of Corynebacterium glutamicum or Escherichia coli. This is integrated into the whole value chain from renewable feedstocks via 1,5-diaminopentane to innovative biopolymers involving bioprocess engineering considerations for economic supply.

Journal ArticleDOI
TL;DR: For the first time, high-resolution spectroscopic imaging using an analytical transmission electron microscope with nonlinear multivariate statistical analysis for classification of multispectral image data results in a visual representation showing homogeneous phases of donor and acceptor.
Abstract: To increase efficiency of bulk heterojunctions for photovoltaic devices, the functional morphology of active layers has to be understood, requiring visualization and discrimination of materials with very similar characteristics. Here we combine high-resolution spectroscopic imaging using an analytical transmission electron microscope with nonlinear multivariate statistical analysis for classification of multispectral image data. We obtain a visual representation showing homogeneous phases of donor and acceptor, connected by a third composite phase, depending in its extent on the way the heterojunction is fabricated. For the first time we can correlate variations in nanoscale morphology determined by material contrast with measured solar cell efficiency. In particular we visualize a homogeneously blended phase, previously discussed to diminish charge separation in solar cell devices.

Journal ArticleDOI
TL;DR: The obtained results indicate that S. oneidensis mutants used in this study are able to bypass hindered direct electron transfer by alternative redox proteins as well as self-mediated pathways.

Journal ArticleDOI
TL;DR: The analysis of the first complete genome sequences of two important B. megaterium strains, the plasmidless strain DSM319 and QM B1551, which harbors seven indigenous plasmids, and documented extensive gene transfer between theplasmids and the chromosome.
Abstract: Bacillus megaterium is deep-rooted in the Bacillus phylogeny, making it an evolutionarily key species and of particular importance in understanding genome evolution, dynamics, and plasticity in the bacilli. B. megaterium is a commercially available, nonpathogenic host for the biotechnological production of several substances, including vitamin B(12), penicillin acylase, and amylases. Here, we report the analysis of the first complete genome sequences of two important B. megaterium strains, the plasmidless strain DSM319 and QM B1551, which harbors seven indigenous plasmids. The 5.1-Mbp chromosome carries approximately 5,300 genes, while QM B1551 plasmids represent a combined 417 kb and 523 genes, one of the largest plasmid arrays sequenced in a single bacterial strain. We have documented extensive gene transfer between the plasmids and the chromosome. Each strain carries roughly 300 strain-specific chromosomal genes that account for differences in their experimentally confirmed phenotypes. B. megaterium is able to synthesize vitamin B(12) through an oxygen-independent adenosylcobalamin pathway, which together with other key energetic and metabolic pathways has now been fully reconstructed. Other novel genes include a second ftsZ gene, which may be responsible for the large cell size of members of this species, as well as genes for gas vesicles, a second β-galactosidase gene, and most but not all of the genes needed for genetic competence. Comprehensive analyses of the global Bacillus gene pool showed that only an asymmetric region around the origin of replication was syntenic across the genus. This appears to be a characteristic feature of the Bacillus spp. genome architecture and may be key to their sporulating lifestyle.