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961.
Watching the movie scene in which a tarantula crawls on James Bond's chest can make us literally shiver--as if the spider crawled on our own chest. What neural mechanisms are responsible for this "tactile empathy"? The observation of the actions of others activates the premotor cortex normally involved in the execution of the same actions. If a similar mechanism applies to the sight of touch, movies depicting touch should automatically activate the somatosensory cortex of the observer. Here we found using fMRI that the secondary but not the primary somatosensory cortex is activated both when the participants were touched and when they observed someone or something else getting touched by objects. The neural mechanisms enabling our own sensation of touch may therefore be a window also to our understanding of touch. 相似文献
962.
963.
Auguin D Barthe P Augé-Sénégas MT Stern MH Noguchi M Roumestand C 《Journal of biomolecular NMR》2004,28(2):137-155
The programmed cell death occurs as part of normal mammalian development. The induction of developmental cell death is a highly regulated process and can be suppressed by a variety of extracellular stimuli. Recently, the ability of trophic factors to promote survival have been attributed, at least in part, to the phosphatidylinositide 3'-OH kinase (PI3K)/Protein Kinase B (PKB, also named Akt) cascade. Several targets of the PI3K/PKB signaling pathway have been identified that may underlie the ability of this regulatory cascade to promote cell survival. PKB possesses a N-terminal Pleckstrin Homology (PH) domain that binds specifically and with high affinity to PtIns(3,4,5)P(3) and PtIns(3,4)P(2), the PI3K second messengers. PKB is then recruited to the plasma membrane by virtue of its interaction with 3'-OH phosphatidylinositides and activated. Recent evidence indicates that PKB is active in various types of human cancer; constitutive PKB signaling activation is believed to promote proliferation and increased cell survival, thereby contributing to cancer progression. Thus, it has been shown that induction of PKB activity is augmented by the TCL1/MTCP1 oncoproteins through a physical association requiring the PKB PH domain. Here we present the three-dimensional solution structure of the PH domain of the human protein PKB (isoform beta). PKBbeta-PH is an electrostatically polarized molecule that adopts the same fold and topology as other PH-domains, consisting of a beta-sandwich of seven strands capped on one top by an alpha-helix. The opposite face presents three variable loops that appear poorly defined in the NMR structure. Measurements of (15)N spin relaxation times and heteronuclear (15)N[(1)H]NOEs showed that this poor definition is due to intrinsic flexibility, involving complex motions on different time scales. Chemical shift mapping studies correctly defined the binding site of Ins(1,3,4,5)P(4) (the head group of PtIns(3,4,5)P(3)), as was previously proposed from a crystallographic study. More interestingly, these studies allowed us to define a putative alternative low-affinity binding site for Ins(1,4,5)P(3). The binding of this sugar to PKBbeta-PH might also involve non-specific association that could explain the stabilization of the protein in solution in the presence of Ins(1,4,5)P(3). 相似文献
964.
Ikegami T Verdier L Sakhaii P Grimme S Pescatore B Saxena K Fiebig KM Griesinger C 《Journal of biomolecular NMR》2004,29(3):339-349
A molecule with an anisotropic magnetic susceptibility is spontaneously aligned in a static magnetic field. Alignment of such a molecule yields residual dipolar couplings and pseudocontact shifts. Lanthanide ions have recently been successfully used to provide an anisotropic magnetic susceptibility in target molecules either by replacing a calcium ion with a lanthanide ion in calcium-binding proteins or by attaching an EDTA derivative to a cysteine residue via a disulfide bond. Here we describe a novel enantiomerically pure EDTA derived tag that aligns stronger due to its shorter linker and does not suffer from stereochemical diversity upon lanthanide complexation. We observed residual (15)N,(1)H-dipolar couplings of up to 8 Hz at 800 MHz induced by a single alignment tensor from this tag. 相似文献
965.
Christian?BauerEmail author Jens?Buchgeister Liselotte?Schebek 《The International Journal of Life Cycle Assessment》2004,9(6):360-364
Reliability of Life Cycle Assessment (LCA) results depends on the availability and quality of Life Cycle Inventory (LCI) data.
In order to provide high-quality LCI data for background systems in LCA and to make it applicable to a wider range of fields,
harmonization strategies for already existing datasets and databases are required. In view of the high significance of LCI
data as a basis of major fields of action within a sustainability strategy, the German Helmholtz Association (HGF), under
the leadership of the Forschungszentrum Karlsruhe (FZK) has taken up this issue in its research programme. In 2002, the FZK
conducted a preliminary study on ‘Quality Assurance and User-oriented Supply of a Life Cycle Inventory Data’ funded by the
Federal Ministry of Education and Research (BMBF). Within the framework of this study, a long-term concept for improving the
scientific fundamentals and practical use of LCI data was developed in association with external experts. The focus is on
establishing a permanent German ‘Network on Life Cycle Inventory Data’ which will serve as the German information and cooperation
platform for all scientific and non-scientific actors in the field of life cycle analysis. This network will integrate expertise
on LCA in Germany, harmonise methodology and data, and use the comprehensive expert panel as an efficient basis for further
scientific development and practical use of LCA. At the same time, this network will serve as a platform for cooperation on
an international level. Current developments address methodological definitions for the initial information infrastructure.
As a novel element, user needs are differentiated in parallel according to the broad application fields of LCI-data from product
declaration to process design. Case studies will be used to define tailored interfaces for the database, since different data
quality levels will be encountered. 相似文献
966.
Wulf-Peter?SchmidtEmail author Elisabeth?Dahlqvist Matthias?Finkbeiner Stephan?Krinke Silvia?Lazzari Dirk?Oschmann Sophie?Pichon Christian?Thiel 《The International Journal of Life Cycle Assessment》2004,9(6):405-416
Goal, Scope and Background The automotive industry has a long history in improving the environmental performance of vehicles - fuel economy and emission
improvements, introduction of recycled and renewable materials, etc. The European Union also aims at improving the environmental
performance of products by reducing, in particular, waste resulting from End-of-Life Vehicles (ELVs) for example. The European
Commission estimates that ELVs contribute to approximately 1 % of the total waste in Europe [9]. Other European Union strategies
are considering more life cycle aspects, as well as other impacts including resource or climate change. This article is summarizing
the results of a European Commission funded project (LIRECAR) that aims at identifying the environmental impacts and relevance
for combinations of recycling / recovery and lightweight vehicle design options over the whole life cycle of a vehicle - i.e.
manufacturing, use and recycling/recovery. Three, independent and scientific LCA experts reviewed the study according to ISO
14040. From the beginning, representatives of all Life Cycle Stakeholders have been involved (European materials & supplier
associations, an environmental Non-Governmental Organization, recycler’s association).
Model and System Definition The study compared 3 sets of theoretical vehicle weight scenarios: 1000 kg reference (material range of today’s end-of-life,
mid-sized vehicles produced in the early 1990’s) and 2 lightweight scenarios for 100 kg and 250 kg less weight based on reference
functions (in terms of comfort, safety, etc.) and a vehicle concept. The scenarios are represented by their material range
of a broad range of lightweight strategies of most European car manufacturers. In parallel, three End-of-Life (EOL) scenarios
are considered: EOL today and two theoretical extreme scenarios (100% recycling, respectively, 100% recovery of shredder residue
fractions that are disposed of today). The technical and economical feasibility of the studied scenarios is not taken into
consideration (e.g. 100% recycling is not possible).
Results and Discussion Significant differences between the various, studied weight scenarios were determined in several scenarios for the environmental
categories of global warming, ozone depletion, photochemical oxidant creation (summer smog), abiotic resource depletion, and
hazardous waste. However, these improvement potentials can be only realized under well defined conditions (e.g. material compositions,
specific fuel reduction values and EOL credits) based on case-by-case assessments for improvements over the course of the
life cycle. Looking at the studied scenarios, the relative contribution of the EOL phase represents 5% or less of the total
life cycle impact for most selected impact categories and scenarios. The EOL technology variations studied do not impact significantly
the considered environmental impacts. Exceptions include total waste, as long as stockpile goods (overburden, tailings and
ore/coal processing residues) and EOL credits are considered.
Conclusions and Recommendations LIRECAR focuses only on lightweight/recycling, questions whereas other measures (changes in safety or comfort standards, propulsion
improvements for CO2, user behavior) are beyond the scope of the study. The conclusions are also not necessarily transferable to other vehicle
concepts. However, for the question of end-of-life options, it can be concluded that LIRECAR cannot support any general recommendation
and/or mandatory actions to improve recycling if lightweight is affected. Also, looking at each vehicle, no justification
could be found for the general assumption that lightweight and recycling greatly influence the affected environmental dimension
(Global Warming Potential or resource depletion and waste, respectively). LIRECAR showed that this general assumption is not
true under all analyzed circumstances and not as significant as suggested. Further discussions and product development targets
shall not focus on generic targets that define the approach/technology concerned with how to achieve environmental improvement
(weight reduction [kg], recycling quota [%]), but on overall life cycle improvement). To enable this case-by-case assessment,
exchanges of necessary information with suppliers are especially relevant. 相似文献
967.
Géraldine?Verquin Ga?lle?Fontaine Marc?Bria Elena?Zhilinskaya Edmond?Abi-Aad Antoine?Abouka?s Brigitte?Baldeyrou Christian?Bailly Jean-Luc?BernierEmail author 《Journal of biological inorganic chemistry》2004,9(3):345-353
Oxovanadium(IV) complexes of hydroxysalen derivatives have been prepared and tested as DNA reactive agents. The nuclease activity has been investigated under oxidative or reducing conditions, on the basis of the various oxidation states of vanadium: VIII, VIV and VV. In the absence of an activating agent, none of the compounds tested was able to induce cleavage of DNA, whereas in the presence of mercaptopropionic acid (MPA) or Oxone the four complexes induced DNA modifications. Under both conditions, the para-hydroxy complex was found to be the most active compound. Reaction of these salen complexes with DNA occurs essentially at guanine residues and is more efficient in the presence of Oxone than under reducing conditions. The extent of Oxone-mediated DNA oxidation by the four vanadyl complexes was clearly superior to VOSO4
and was observed without piperidine treatment. EPR studies provided information on the reactive metal-oxo species involved under each conditions and a mechanism of reaction with DNA is discussed.Electronic Supplementary Material Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00775-004-0529-0Abbreviations BPE buffer
bis-phosphate EDTA buffer
- DMPO
5,5-dimethylpyrroline
N-oxide
- DMS
dimethyl sulfate
- HFS
hyperfine structure
- Lin
linear
- MPA
3-mercaptopropionic acid
- Nck
nicked
- salen
(salicylidene)ethylenediamine
- Sc
supercoiled
- TBE buffer
tris-borate EDTA buffer
- Tris
tris(hydroxymethyl)aminomethane 相似文献
968.
Bogdan S Grewe O Strunk M Mertens A Klämbt C 《Development (Cambridge, England)》2004,131(16):3981-3989
Regulation of growth cone and cell motility involves the coordinated control of F-actin dynamics. An important regulator of F-actin formation is the Arp2/3 complex, which in turn is activated by Wasp and Wave. A complex comprising Kette/Nap1, Sra-1/Pir121/CYFIP, Abi and HSPC300 modulates the activity of Wave and Wasp. We present the characterization of Drosophila Sra-1 (specifically Rac1-associated protein 1). sra-1 and kette are spatially and temporally co-expressed, and both encoded proteins interact in vivo. During late embryonic and larval development, the Sra-1 protein is found in the neuropile. Outgrowing photoreceptor neurons express high levels of Sra-1 also in growth cones. Expression of double stranded sra-1 RNA in photoreceptor neurons leads to a stalling of axonal growth. Following knockdown of sra-1 function in motoneurons, we noted abnormal neuromuscular junctions similar to what we determined for hypomorphic kette mutations. Similar mutant phenotypes were induced after expression of membrane-bound Sra-1 that lacks the Kette-binding domain, suggesting that sra-1 function is mediated through kette. Furthermore, we could show that both proteins stabilize each other and directly control the regulation of the F-actin cytoskeleton in a Wasp-dependent manner. 相似文献
969.
The CNS of bilateral symmetric organisms is characterized by intensive contralateral axonal connections. Genetic screens in Drosophila have identified only a few genes required for guiding commissural growth cones toward and across the midline. Two evolutionarily conserved signaling molecules, Netrin and Slit, are expressed in the CNS midline cells. Netrin acts primarily as an attractive signaling cue, whereas Slit mediates repulsive functions. Here, we describe a detailed analysis of the Drosophila gene schizo, which is required for commissure formation. schizo leads to a commissural phenotype reminiscent of netrin mutant embryos. Double-mutant analyses indicate that Netrin and Schizo act independently. The schizo mutant phenotype can be suppressed by either expressing netrin in the CNS midline cells or by a reduction of the slit gene dose, indicating that the balance of attractive and repulsive signaling is impaired in schizo mutants. Overexpression of the schizo RNA in the CNS midline using the GAL4/UAS system leads to a slit phenocopy, suggesting that schizo primarily antagonizes Slit signaling. This is further supported by cell type-specific rescue experiments. The schizo gene generates at least two proteins containing a conserved Sec7 and a pleckstrin homology domain (PH) characteristic for guanine nucleotide exchange factors (GEF) acting on ARF GTPases, which are known to regulate endocytosis. In support of the notion that schizo regulates Slit expression via endocytosis, we found that block of endocytosis leads to a schizo-like phenotype. We thus propose that the balance of the two signaling cues Netrin and Slit can be regulated, controlling membrane dynamics. 相似文献
970.
Brett A. Melbourne Kendi F. Davies Chris R. Margules David B. Lindenmayer Denis A. Saunders Christian Wissel Klaus Henle 《Biodiversity and Conservation》2004,13(1):275-284
We summarise the contributions of empiricists, modellers, and practitioners in this issue of Biodiversity and Conservation, and highlight the most important areas for future research on species survival in fragmented landscapes. Under the theme uncertainty in research and management, we highlight five areas for future research. First, we know little about the effects of density dependence on the viability of metapopulations, a requirement for fragmented landscapes. Second, successful early attempts suggest that it is worth developing more rigorous calibration methods for population viability analysis with spatially explicit, individual-based models. In particular, the balance between model complexity, ease of calibration, and precision, needs to be addressed. Third, we need to improve methods to discriminate between models, including alternatives to time-series approaches. Fourth, when our ability to reduce model uncertainty is weak, we need to incorporate this uncertainty in population viability analysis. Fifth, population viability analysis and decision analysis can be integrated to make uncertainty an explicit part of the decision process. An important future direction is extending the decision framework to adaptive management. Under the theme tools for quantifying risk and predicting species sensitivity to fragmentation, we highlight three areas for future research. First, we need to develop tools to support comparative approaches to population viability analysis. Second, population modelling can be used to find rules of thumb to support conservation decisions when very little is known about a species. Rules of thumb need to be extended to the problem of managing for multiple species. Third, species traits might be useful for predicting sensitivity but predictions could be further refined by considering the relative importance of population processes at different scales. Under the theme tools for reassembling fragmented landscapes, we consider the focal species approach, and highlight aspects of the approach that require more rigorous testing. Finally, we highlight two important areas for future research not presented in the previous themes or papers in this volume. First, we need to incorporate the deterministic effects of habitat modification into the modelling framework of population viability analysis. Second, an avenue of research that remains largely unexplored is the combination of landscape-scale experiments and population modelling, especially using data from existing fragmentation experiments and from experiments designed to test the effects of defragmenting landscapes. 相似文献