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Showing papers by "Stockholm University published in 2005"


Journal ArticleDOI
TL;DR: The software suite GROMACS (Groningen MAchine for Chemical Simulation) that was developed at the University of Groningen, The Netherlands, in the early 1990s is described, which is a very fast program for molecular dynamics simulation.
Abstract: This article describes the software suite GROMACS (Groningen MAchine for Chemical Simulation) that was developed at the University of Groningen, The Netherlands, in the early 1990s. The software, written in ANSI C, originates from a parallel hardware project, and is well suited for parallelization on processor clusters. By careful optimization of neighbor searching and of inner loop performance, GROMACS is a very fast program for molecular dynamics simulation. It does not have a force field of its own, but is compatible with GROMOS, OPLS, AMBER, and ENCAD force fields. In addition, it can handle polarizable shell models and flexible constraints. The program is versatile, as force routines can be added by the user, tabulated functions can be specified, and analyses can be easily customized. Nonequilibrium dynamics and free energy determinations are incorporated. Interfaces with popular quantum-chemical packages (MOPAC, GAMES-UK, GAUSSIAN) are provided to perform mixed MM/QM simulations. The package includes about 100 utility and analysis programs. GROMACS is in the public domain and distributed (with source code and documentation) under the GNU General Public License. It is maintained by a group of developers from the Universities of Groningen, Uppsala, and Stockholm, and the Max Planck Institute for Polymer Research in Mainz. Its Web site is http://www.gromacs.org.

13,116 citations


Journal ArticleDOI
TL;DR: In this paper, the authors explore the social dimension that enables adaptive ecosystem-based management, focusing on experiences of adaptive governance of social-ecological systems during periods of abrupt change and investigates social sources of renewal and reorganization.
Abstract: ▪ Abstract We explore the social dimension that enables adaptive ecosystem-based management. The review concentrates on experiences of adaptive governance of social-ecological systems during periods of abrupt change (crisis) and investigates social sources of renewal and reorganization. Such governance connects individuals, organizations, agencies, and institutions at multiple organizational levels. Key persons provide leadership, trust, vision, meaning, and they help transform management organizations toward a learning environment. Adaptive governance systems often self-organize as social networks with teams and actor groups that draw on various knowledge systems and experiences for the development of a common understanding and policies. The emergence of “bridging organizations” seem to lower the costs of collaboration and conflict resolution, and enabling legislation and governmental policies can support self-organization while framing creativity for adaptive comanagement efforts. A resilient social-eco...

4,495 citations


Journal ArticleDOI
14 Apr 2005-Nature
TL;DR: It is proposed that, in the absence of PARP1, spontaneous single-strand breaks collapse replication forks and trigger homologous recombination for repair and exploited in order to kill BRCA2-deficient tumours by PARP inhibition alone.
Abstract: Poly(ADP-ribose) polymerase (PARP1) facilitates DNA repair by binding to DNA breaks and attracting DNA repair proteins to the site of damage. Nevertheless, PARP1-/- mice are viable, fertile and do not develop early onset tumours. Here, we show that PARP inhibitors trigger gamma-H2AX and RAD51 foci formation. We propose that, in the absence of PARP1, spontaneous single-strand breaks collapse replication forks and trigger homologous recombination for repair. Furthermore, we show that BRCA2-deficient cells, as a result of their deficiency in homologous recombination, are acutely sensitive to PARP inhibitors, presumably because resultant collapsed replication forks are no longer repaired. Thus, PARP1 activity is essential in homologous recombination-deficient BRCA2 mutant cells. We exploit this requirement in order to kill BRCA2-deficient tumours by PARP inhibition alone. Treatment with PARP inhibitors is likely to be highly tumour specific, because only the tumours (which are BRCA2-/-) in BRCA2+/- patients are defective in homologous recombination. The use of an inhibitor of a DNA repair enzyme alone to selectively kill a tumour, in the absence of an exogenous DNA-damaging agent, represents a new concept in cancer treatment.

4,262 citations


Book
01 Jan 2005
TL;DR: Insects, mass extinctions, and the K/T boundary The tertiary Mammalian radiations Pleistocene dispersal and species lifespans Island faunas and the future Glossary References Index.
Abstract: Section 1. Diversity and Evolution: Introduction Species: their nature and number How many species of insects? Reconstructing evolutionary history Section 2. Fossil Insects: Insect fossilization Dating and ages Major fossil Insect deposits Section 3. Arthropods and the Origin of Insects: Onychophora: the velvet-worms Tardigrada: the water-bears Arthropoda: the jointed animals Hexapoda: the six-legged arthropods Section 4. The insects: Morphology of insects Relationships among the insect orders Section 5. Earliest insects: Archaeognatha: the bristletails Zygentoma: the silverfish +Rhyniognatha Section 6. Insects Take to the Skies: Pterygota, Wings, and flight Ephemeroptera: the mayflies +Palaeodictyopterida: extinct beaked insects Odonatoptera: dragonflies and early relatives Neoptera Section 7. The Polyneopterous Orders: Plecopterida Orthopterida Plecoptera: the stoneflies Embiodea: the webspinners Zoraptera: the Zorapterans Orthoptera: the grasshoppers, crickets, and kin Phasmatodea: the stick- and leaf insects +Titanoptera: the titanic crawlers +Caloneurodea: the Caloneurodeans Dermaptera: the earwigs Grylloblattodea: the ice crawlers Mantophasmatodea: the African rock crawlers Dictyoptera Blattodea: the roaches Citizen roach: the termites Mantodea: the mantises Section 8. The Paraneopteran Orders: Psocoptera: the 'bark'lice Phthiraptera: the true lice Fringe wings: Thysanoptera (thrips) The sucking bugs: Hemiptera Section 9. The Holometabola: problematic fossil orders The origins of complete metamorphosis On wings of lace: Neuropterida Section 10. Coleoptera: early fossils and overview of past diversity Archostemata Adephaga Myxophaga Polyphaga Strepsiptera: the enigmatic order Section 11. Hymenoptera: Ants, Bees, and Other Wasps: The Euhymenoptera and parasitism Aculeata Evolution of insect sociality Section 12. Antliophora: Scorpionflies, Flies, and Fleas: Mecopterida: mecopterans and relatives Siphonaptera: the fleas Evolution of ectoparasites and blood-feeders Diptera: the true flies Section 13. Amphiesmenoptera: The Caddisflies and Lepidoptera: Trichoptera: the caddisflies Lepidoptera: the moths and butterflies Section 14. Insects Become Modern: Cretaceous and Tertiary Periods: The Cretaceous flowering of the world: the Angiosperm Radiations Plant sex and insects: insect pollination Radiations of Phytophagous insects Austral arthropods: remnants of Gondwana? Insects, mass extinctions, and the K/T boundary The tertiary Mammalian radiations Pleistocene dispersal and species lifespans Island faunas Section 15. Epilogue: Why so many insect species? The future Glossary References Index.

2,505 citations


Journal ArticleDOI
12 Aug 2005-Science
TL;DR: Social and ecological vulnerability to disasters and outcomes of any particular extreme event are influenced by buildup or erosion of resilience both before and after disasters occur.
Abstract: Social and ecological vulnerability to disasters and outcomes of any particular extreme event are influenced by buildup or erosion of resilience both before and after disasters occur. Resilient social-ecological systems incorporate diverse mechanisms for living with, and learning from, change and unexpected shocks. Disaster management requires multilevel governance systems that can enhance the capacity to cope with uncertainty and surprise by mobilizing diverse sources of resilience.

2,277 citations


Journal ArticleDOI
TL;DR: Evidence suggests that treatment of alcohol-related problems should be incorporated into a public health response to alcohol problems, and that early intervention in primary care is feasible and effective, and a variety of behavioural and pharmacological interventions are available to treat alcohol dependence.

1,683 citations


01 May 2005
TL;DR: Insect diversity and evolution: Introduction Species: their nature and number How many species of insects? Reconstructing evolutionary history Section 2. Fossil insects: Insect fossilization dating and ages Major fossil Insect deposits Section 3. Arthropods and the Origin of Insects: Onychophora: the velvet-worms Tardigrada: the water-bears Arthropoda: the jointed animals Hexapoda: six-legged arthropods Section 4. The insects: Morphology of insects Relationships among the insect orders Section 5. Earliest insects:
Abstract: Section 1. Diversity and Evolution: Introduction Species: their nature and number How many species of insects? Reconstructing evolutionary history Section 2. Fossil Insects: Insect fossilization Dating and ages Major fossil Insect deposits Section 3. Arthropods and the Origin of Insects: Onychophora: the velvet-worms Tardigrada: the water-bears Arthropoda: the jointed animals Hexapoda: the six-legged arthropods Section 4. The insects: Morphology of insects Relationships among the insect orders Section 5. Earliest insects: Archaeognatha: the bristletails Zygentoma: the silverfish +Rhyniognatha Section 6. Insects Take to the Skies: Pterygota, Wings, and flight Ephemeroptera: the mayflies +Palaeodictyopterida: extinct beaked insects Odonatoptera: dragonflies and early relatives Neoptera Section 7. The Polyneopterous Orders: Plecopterida Orthopterida Plecoptera: the stoneflies Embiodea: the webspinners Zoraptera: the Zorapterans Orthoptera: the grasshoppers, crickets, and kin Phasmatodea: the stick- and leaf insects +Titanoptera: the titanic crawlers +Caloneurodea: the Caloneurodeans Dermaptera: the earwigs Grylloblattodea: the ice crawlers Mantophasmatodea: the African rock crawlers Dictyoptera Blattodea: the roaches Citizen roach: the termites Mantodea: the mantises Section 8. The Paraneopteran Orders: Psocoptera: the 'bark'lice Phthiraptera: the true lice Fringe wings: Thysanoptera (thrips) The sucking bugs: Hemiptera Section 9. The Holometabola: problematic fossil orders The origins of complete metamorphosis On wings of lace: Neuropterida Section 10. Coleoptera: early fossils and overview of past diversity Archostemata Adephaga Myxophaga Polyphaga Strepsiptera: the enigmatic order Section 11. Hymenoptera: Ants, Bees, and Other Wasps: The Euhymenoptera and parasitism Aculeata Evolution of insect sociality Section 12. Antliophora: Scorpionflies, Flies, and Fleas: Mecopterida: mecopterans and relatives Siphonaptera: the fleas Evolution of ectoparasites and blood-feeders Diptera: the true flies Section 13. Amphiesmenoptera: The Caddisflies and Lepidoptera: Trichoptera: the caddisflies Lepidoptera: the moths and butterflies Section 14. Insects Become Modern: Cretaceous and Tertiary Periods: The Cretaceous flowering of the world: the Angiosperm Radiations Plant sex and insects: insect pollination Radiations of Phytophagous insects Austral arthropods: remnants of Gondwana? Insects, mass extinctions, and the K/T boundary The tertiary Mammalian radiations Pleistocene dispersal and species lifespans Island faunas Section 15. Epilogue: Why so many insect species? The future Glossary References Index.

1,663 citations


Journal ArticleDOI
10 Feb 2005-Nature
TL;DR: This reconstruction of Northern Hemisphere temperatures for the past 2,000 years is reconstructed by combining low-resolution proxies with tree-ring data, using a wavelet transform technique to achieve timescale-dependent processing of the data.
Abstract: A number of reconstructions of millennial-scale climate variability have been carried out in order to understand patterns of natural climate variability, on decade to century timescales, and the role of anthropogenic forcing These reconstructions have mainly used tree-ring data and other data sets of annual to decadal resolution Lake and ocean sediments have a lower time resolution, but provide climate information at multicentennial timescales that may not be captured by tree-ring data Here we reconstruct Northern Hemisphere temperatures for the past 2,000 years by combining low-resolution proxies with tree-ring data, using a wavelet transform technique to achieve timescale-dependent processing of the data Our reconstruction shows larger multicentennial variability than most previous multi-proxy reconstructions, but agrees well with temperatures reconstructed from borehole measurements and with temperatures obtained with a general circulation model According to our reconstruction, high temperatures--similar to those observed in the twentieth century before 1990--occurred around ad 1000 to 1100, and minimum temperatures that are about 07 K below the average of 1961-90 occurred around ad 1600 This large natural variability in the past suggests an important role of natural multicentennial variability that is likely to continue

1,573 citations


Journal ArticleDOI
TL;DR: It is advocated that the use of generic organic carbon-water distribution coefficients in the risk assessment of organic compounds is not warranted and that bioremediation endpoints could be evaluated on the basis of freely dissolved concentrations instead of total concentrations in sediment/soil.
Abstract: Evidence is accumulating that sorption of organic chemicals to soils and sediments can be described by “dual-mode sorption”: absorption in amorphous organic matter (AOM) and adsorption to carbonaceous materials such as black carbon (BC), coal, and kerogen, collectively termed “carbonaceous geosorbents” (CG). Median BC contents as a fraction of total organic carbon are 9% for sediments (number of sediments, n ≈ 300) and 4% for soils (n = 90). Adsorption of organic compounds to CG is nonlinear and generally exceeds absorption in AOM by a factor of 10−100. Sorption to CG is particularly extensive for organic compounds that can attain a more planar molecular configuration. The CG adsorption domain probably consists of surface sites and nanopores. In this review it is shown that nonlinear sorption to CG can completely dominate total sorption at low aqueous concentrations (<10-6 of maximum solid solubility). Therefore, the presence of CG can explain (i) sorption to soils and sediments being up to 2 orders of m...

1,339 citations


Journal ArticleDOI
TL;DR: This article reviewed research published since 1990 into educational stratification and social (occupational or class) mobility, focusing on the importance of parental socioeconomic circumstances, and with particular emphasis on comparative studies, concluding that the 1990s witnessed a resurgence of micro-level models, mostly of a rational choice type, that signals an increased interest in moving beyond description in strat...
Abstract: Studies of how characteristics of the family of origin are associated with educational and labor market outcomes indicate the degree of openness of societies and have a long tradition in sociology. We review research published since 1990 into educational stratification and social (occupational or class) mobility, focusing on the importance of parental socioeconomic circumstances, and with particular emphasis on comparative studies. Large-scale data now available from many countries and several time points have led to more and better descriptions of inequality of opportunity across countries and over time. However, partly owing to problems of comparability of measurement, unambiguous conclusions about trends and ranking of countries have proven elusive. In addition, no strong evidence exists that explains intercountry differences. We conclude that the 1990s witnessed a resurgence of microlevel models, mostly of a rational choice type, that signals an increased interest in moving beyond description in strat...

1,071 citations


Journal ArticleDOI
27 Jan 2005-Nature
TL;DR: The results indicate that direct protein–lipid interactions are critical during translocon-mediated membrane insertion, and the basic features of this code are determined, including a ‘biological’ hydrophobicity scale.
Abstract: Membrane proteins depend on complex translocation machineries for insertion into target membranes. Although it has long been known that an abundance of nonpolar residues in transmembrane helices is the principal criterion for membrane insertion, the specific sequence-coding for transmembrane helices has not been identified. By challenging the endoplasmic reticulum Sec61 translocon with an extensive set of designed polypeptide segments, we have determined the basic features of this code, including a 'biological' hydrophobicity scale. We find that membrane insertion depends strongly on the position of polar residues within transmembrane segments, adding a new dimension to the problem of predicting transmembrane helices from amino acid sequences. Our results indicate that direct protein-lipid interactions are critical during translocon-mediated membrane insertion.

Journal ArticleDOI
TL;DR: Three inducible bacteriolytic proteins, designated P7, P9A and P9B, from the hemolymph of immunized pupae of the giant silk moth Hyalophora cecropia have been purified using a two-step procedure with cation-exchange chromatography, showing a great similarity to that of the lysozyme from the wax moth Galleria mellonella.
Abstract: Three inducible bacteriolytic proteins, designated P7, P9A and P9B, from the hemolymph of immunized pupae of the giant silk moth Hyalophora cecropia have been purified using a two-step procedure with cation-exchange chromatography. Purified protein P7 has a molecular weight of 15000 and its amino acid composition shows a great similarity to that of the lysozyme from the wax moth Galleria mellonella. Moreover, heat stability, pH-rate profile and bacteriolytic specificity also indicate that protein P7 is a lysozyme. The other purified proteins, P9A and P9B, are highly potent against Escherichia coli and some other gram-negative bacteria. The amino acid compositions of proteins P9A and P9B are very similar, although the contents of glutamic acid and methionine were different. The molecular weights of these very basic proteins are around 7000. The P9 proteins are heat stable; their activities were retained after 30 min incubation at 100 degrees C. Both forms of protein P9 clearly differ from the lysozyme class of enzymes and they may represent a new type of bacteriolytic protein.

Journal ArticleDOI
TL;DR: Cell-penetrating peptides are short peptides of less than 30 amino acids that are able to penetrate cell membranes and translocate different cargoes into cells, whose properties make them potential drug delivery agents, of interest for future use.

Journal ArticleDOI
TL;DR: The results show that age trajectories for episodic and semantic memory differ and underscore the need to control for cohort and retest effects in cross-sectional and longitudinal studies, respectively.
Abstract: Five-year changes in episodic and semantic memory were examined in a sample of 829 participants (35-80 years). A cohort-matched sample (N=967) was assessed to control for practice effects. For episodic memory, cross-sectional analyses indicated gradual age-related decrements, whereas the longitudinal data revealed no decrements before age 60, even when practice effects were adjusted for. Longitudinally, semantic memory showed minor increments until age 55, with smaller decrements in old age as compared with episodic memory. Cohort differences in educational attainment appear to account for the discrepancies between cross-sectional and longitudinal data. Collectively, the results show that age trajectories for episodic and semantic memory differ and underscore the need to control for cohort and retest effects in cross-sectional and longitudinal studies, respectively.

Journal ArticleDOI
TL;DR: In this article, the authors compared a number of calculation methods for TWI and evaluated them in terms of their correlation with the following measured variables: vascular plant species richness, soil pH, groundwater level, soil moisture, and a constructed wetness degree.
Abstract: . The topographic wetness index (TWI, ln(a/tanβ)), which combines local upslope contributing area and slope, is commonly used to quantify topographic control on hydrological processes. Methods of computing this index differ primarily in the way the upslope contributing area is calculated. In this study we compared a number of calculation methods for TWI and evaluated them in terms of their correlation with the following measured variables: vascular plant species richness, soil pH, groundwater level, soil moisture, and a constructed wetness degree. The TWI was calculated by varying six parameters affecting the distribution of accumulated area among downslope cells and by varying the way the slope was calculated. All possible combinations of these parameters were calculated for two separate boreal forest sites in northern Sweden. We did not find a calculation method that performed best for all measured variables; rather the best methods seemed to be variable and site specific. However, we were able to identify some general characteristics of the best methods for different groups of measured variables. The results provide guiding principles for choosing the best method for estimating species richness, soil pH, groundwater level, and soil moisture by the TWI derived from digital elevation models.

Journal ArticleDOI
Robin Room1
TL;DR: A heavy load of symbolism surrounds psychoactive substance use, for reasons which are discussed, and processes of stigmatization and marginalization and their effect on adverse outcomes are discussed.
Abstract: A heavy load of symbolism surrounds psychoactive substance use, for reasons which are discussed. Psychoactive substances can be prestige commodities, but one or another aspect of their use seems to attract near--universal stigma and marginalization. Processes of stigmatization include intimate process of social control among family and friends; decisions by social and health agencies; and governmental policy decisions. What is negatively moralized commonly includes incurring health, casualty or social problems, derogated even by other heavy users; intoxication itself; addiction or dependence, and the loss of control such terms describe; and in some circumstances use per se. Two independent literatures on stigma operate on different premises: studies oriented to mental illness and disability consider the negative effects of stigma on the stigmatized, and how stigma may be neutralized, while studies of crime generally view stigma more benignly, as a form of social control. The alcohol and drug literature overlap both topical areas, and includes examples of both orientations. Whole poverty and heavy substance use are not necessary related, poverty often increases the harm for a given level of use. Marginalization and stigma commonly add to this effect. Those in treatment for alcohol or drug problems are frequently and disproportionately marginalized. Studies of social inequality and substance use problems need to pay attention also to processes of stigmatization and marginalization and their effect on adverse outcomes.

Journal ArticleDOI
01 Jan 2005-Nature
TL;DR: The changes in oxygen-isotope composition across the Eocene/Oligocene boundary are too large to be explained by Antarctic ice-sheet growth alone and must therefore also indicate contemporaneous global cooling and/or Northern Hemisphere glaciation.
Abstract: The ocean depth at which the rate of calcium carbonate input from surface waters equals the rate of dissolution is termed the calcite compensation depth. At present, this depth is 4,500 m, with some variation between and within ocean basins. The calcite compensation depth is linked to ocean acidity, which is in turn linked to atmospheric carbon dioxide concentrations and hence global climate1. Geological records of changes in the calcite compensation depth show a prominent deepening of more than 1 km near the Eocene/Oligocene boundary ( 34 million years ago)2 when significant permanent ice sheets first appeared on Antarctica3, 4, 5, 6, but the relationship between these two events is poorly understood. Here we present ocean sediment records of calcium carbonate content as well as carbon and oxygen isotopic compositions from the tropical Pacific Ocean that cover the Eocene/Oligocene boundary. We find that the deepening of the calcite compensation depth was more rapid than previously documented and occurred in two jumps of about 40,000 years each, synchronous with the stepwise onset of Antarctic ice-sheet growth. The glaciation was initiated, after climatic preconditioning7, by an interval when the Earth's orbit of the Sun favoured cool summers. The changes in oxygen-isotope composition across the Eocene/Oligocene boundary are too large to be explained by Antarctic ice-sheet growth alone and must therefore also indicate contemporaneous global cooling and/or Northern Hemisphere glaciation.

Journal ArticleDOI
TL;DR: In this article, the authors determine the dominant physical controls on catchment-scale water residence time and specifically test the hypothesis that residence time is related to the size of the basin Residence times were estimated by simple convolution models that described the transfer of precipitation isotopic composition to the stream network.
Abstract: 624 km 2 ) that represent diverse geologic and geomorphic conditions in the western Cascade Mountains of Oregon Our primary objective was to determine the dominant physical controls on catchment-scale water residence time and specifically test the hypothesis that residence time is related to the size of the basin Residence times were estimated by simple convolution models that described the transfer of precipitation isotopic composition to the stream network We found that base flow mean residence times for exponential distributions ranged from 08 to 33 years Mean residence time showed no correlation to basin area (r 2 < 001) but instead was correlated (r 2 = 091) to catchment terrain indices representing the flow path distance and flow path gradient to the stream network These results illustrate that landscape organization (ie, topography) rather than basin area controls catchment-scale transport Results from this study may provide a framework for describing scale-invariant transport across climatic and geologic conditions, whereby the internal form and structure of the basin defines the first-order control on base flow residence time

Journal ArticleDOI
TL;DR: It is reported here that a single neurotoxin, beta-N-methylamino-L-alanine, may be produced by all known groups of cyanobacteria, including cyanobacterial symbionts and free-living cyanob bacteria.
Abstract: Cyanobacteria can generate molecules hazardous to human health, but production of the known cyanotoxins is taxonomically sporadic. For example, members of a few genera produce hepatotoxic microcystins, whereas production of hepatotoxic nodularins appears to be limited to a single genus. Production of known neurotoxins has also been considered phylogenetically unpredictable. We report here that a single neurotoxin, β-N-methylamino-l-alanine, may be produced by all known groups of cyanobacteria, including cyanobacterial symbionts and free-living cyanobacteria. The ubiquity of cyanobacteria in terrestrial, as well as freshwater, brackish, and marine environments, suggests a potential for wide-spread human exposure.

Journal ArticleDOI
TL;DR: It is established that Chk1 is a key regulator of genome maintenance by the homologous recombination repair (HRR) system, and that RAD51 is phosphorylated on Thr 309 in a ChK1-dependent manner, highlighting a crucial role for the Chk2 signalling pathway in protecting cells against lethal DNA lesions through regulation of HRR.
Abstract: The essential checkpoint kinase Chk1 is required for cell-cycle delays after DNA damage or blocked DNA replication. However, it is unclear whether Chk1 is involved in the repair of damaged DNA. Here we establish that Chk1 is a key regulator of genome maintenance by the homologous recombination repair (HRR) system. Abrogation of Chk1 function with small interfering RNA or chemical antagonists inhibits HRR, leading to persistent unrepaired DNA double-strand breaks (DSBs) and cell death after replication inhibition with hydroxyurea or DNA-damage caused by camptothecin. After hydroxyurea treatment, the essential recombination repair protein RAD51 is recruited to DNA repair foci performing a vital role in correct HRR. We demonstrate that Chk1 interacts with RAD51, and that RAD51 is phosphorylated on Thr 309 in a Chk1-dependent manner. Consistent with a functional interplay between Chk1 and RAD51, Chk1-depleted cells failed to form RAD51 nuclear foci after exposure to hydroxyurea, and cells expressing a phosphorylation-deficient mutant RAD51(T309A) were hypersensitive to hydroxyurea. These results highlight a crucial role for the Chk1 signalling pathway in protecting cells against lethal DNA lesions through regulation of HRR.

Journal ArticleDOI
Neil Gehrels1, Craig L. Sarazin2, P. T. O'Brien3, Bing Zhang4, L. M. Barbier1, Scott Barthelmy1, A. J. Blustin5, David N. Burrows6, J. K. Cannizzo7, J. K. Cannizzo1, Jay Cummings8, Jay Cummings1, Michael R. Goad3, Stephen T. Holland1, Stephen T. Holland9, Cheryl Hurkett3, J. A. Kennea6, Andrew J. Levan3, C. B. Markwardt1, C. B. Markwardt10, Keith O. Mason5, Peter Mészáros6, M. J. Page5, David Palmer11, Evert Rol3, T. Sakamoto1, T. Sakamoto8, Richard Willingale3, Lorella Angelini1, Lorella Angelini7, Andrew P. Beardmore3, Patricia T. Boyd7, Patricia T. Boyd1, A. A. Breeveld5, Sergio Campana12, M. M. Chester6, Guido Chincarini13, Guido Chincarini14, L. R. Cominsky15, Giancarlo Cusumano14, M. de Pasquale5, Edward E. Fenimore11, Paolo Giommi, Caryl Gronwall6, Dirk Grupe6, Joanne E. Hill6, D. Hinshaw1, Jens Hjorth16, D. Hullinger10, D. Hullinger1, Kevin Hurley17, Sylvio Klose, Shiho Kobayashi6, Chryssa Kouveliotou18, Hans A. Krimm1, Hans A. Krimm9, Vanessa Mangano12, F. E. Marshall1, Katherine E. McGowan5, A. Moretti12, Richard Mushotzky1, Kazuhiro Nakazawa, Jay P. Norris1, John A. Nousek6, J. P. Osborne3, K. L. Page3, A. M. Parsons1, Sandeep K. Patel9, M. Perri, T. S. Poole5, P. Romano12, P. W. A. Roming6, Stuart Rosen5, G. Sato, Patricia Schady5, Alan P. Smale, Jesper Sollerman19, R. L. C. Starling20, Martin Still1, Martin Still9, Masaya Suzuki21, Gianpiero Tagliaferri12, Tadayuki Takahashi, Makoto Tashiro21, Jack Tueller1, Alan A. Wells3, Nicholas E. White1, Ralph A. M. J. Wijers20 
06 Oct 2005-Nature
TL;DR: In this article, the authors reported the detection of the X-ray afterglow from the short burst GRB 050509B and its location on the sky is near a luminous, non-star-forming elliptical galaxy at a redshift of 0.225.
Abstract: Gamma-ray bursts (GRBs) are either ‘long and soft’, or ‘short and hard’. The long-duration type leave a strong afterglow and have been extensively studied. So we have a good idea of what causes them: explosions of massive stars in distant star-forming galaxies. Short GRBs, with no strong afterglow, were harder to pin down. The Swift satellite, launched last November, is designed to study bursts as soon as they happen. Having shown its worth with long GRBs (reported in the 18 August issue of Nature), Swift has now bagged a short burst, GRB 050509B, precisely measured its location and detected the X-ray afterglow. Four papers this week report on this and another recent short burst. Now, over 20 years after they were first recognized, the likely origin of the short GRBs is revealed as a merger between neutron stars of a binary system and the instantaneous production of a black hole. Gamma-ray bursts (GRBs) come in two classes1: long (> 2 s), soft-spectrum bursts and short, hard events. Most progress has been made on understanding the long GRBs, which are typically observed at high redshift (z ≈ 1) and found in subluminous star-forming host galaxies. They are likely to be produced in core-collapse explosions of massive stars2. In contrast, no short GRB had been accurately (< 10″) and rapidly (minutes) located. Here we report the detection of the X-ray afterglow from—and the localization of—the short burst GRB 050509B. Its position on the sky is near a luminous, non-star-forming elliptical galaxy at a redshift of 0.225, which is the location one would expect3,4 if the origin of this GRB is through the merger of neutron-star or black-hole binaries. The X-ray afterglow was weak and faded below the detection limit within a few hours; no optical afterglow was detected to stringent limits, explaining the past difficulty in localizing short GRBs.

Journal ArticleDOI
TL;DR: In this article, the authors present a roadmap for a wilderness of complexity and unpredictability for marketing research in marketing, which they call the "wilderness of complexity, unpredictability, and complexity".
Abstract: Qualitative research in marketing : roadmap for a wilderness of complexity and unpredictability

Journal ArticleDOI
TL;DR: In this article, a general approach for obtaining systematic sequences of atomic single-particle basis sets for use in correlated electronic structure calculations of molecules was developed, and all the constituent functions are defined as the solutions of variational problems.

Journal ArticleDOI
TL;DR: It is proposed that Chk1 is required during normal S phase to avoid aberrantly increased initiation of DNA replication, thereby protecting against DNA breakage.
Abstract: Human checkpoint kinase 1 (Chk1) is an essential kinase required to preserve genome stability. Here, we show that Chk1 inhibition by two distinct drugs, UCN-01 and CEP-3891, or by Chk1 small interfering RNA (siRNA) leads to phosphorylation of ATR targets. Chk1-inhibition triggered rapid, pan-nuclear phosphorylation of histone H2AX, p53, Smc1, replication protein A, and Chk1 itself in human S-phase cells. These phosphorylations were inhibited by ATR siRNA and caffeine, but they occurred independently of ATM. Chk1 inhibition also caused an increased initiation of DNA replication, which was accompanied by increased amounts of nonextractable RPA protein, formation of single-stranded DNA, and induction of DNA strand breaks. Moreover, these responses were prevented by siRNA-mediated downregulation of Cdk2 or the replication initiation protein Cdc45, or by addition of the CDK inhibitor roscovitine. We propose that Chk1 is required during normal S phase to avoid aberrantly increased initiation of DNA replication, thereby protecting against DNA breakage. These results may help explain why Chk1 is an essential kinase and should be taken into account when drugs to inhibit this kinase are considered for use in cancer treatment.

Journal ArticleDOI
27 May 2005-Science
TL;DR: A global topology analysis of the Escherichia coli inner membrane proteome is reported, suggesting that a large fraction of all inner membrane proteins can be produced in sufficient quantities for biochemical and structural work.
Abstract: The protein complement of cellular membranes is notoriously resistant to standard proteomic analysis and structural studies. As a result, membrane proteomes remain ill-defined. Here, we report a global topology analysis of the Escherichia coli inner membrane proteome. Using C-terminal tagging with the alkaline phosphatase and green fluorescent protein, we established the periplasmic or cytoplasmic locations of the C termini for 601 inner membrane proteins. By constraining a topology prediction algorithm with this data, we derived high-quality topology models for the 601 proteins, providing a firm foundation for future functional studies of this and other membrane proteomes. We also estimated the overexpression potential for 397 green fluorescent protein fusions; the results suggest that a large fraction of all inner membrane proteins can be produced in sufficient quantities for biochemical and structural work.

Journal ArticleDOI
TL;DR: In this paper, a new model for explaining the emergence of the party family of extreme right-wing populist parties in Western Europe is presented, which combines ethnonationalist xenophobia, based on the doctrine of ethnopluralism, with anti-political-establishment populism.
Abstract: . This article presents a new model for explaining the emergence of the party family of extreme right-wing populist parties in Western Europe. As the old master frame of the extreme right was rendered impotent by the outcome of the Second World War, it took the innovation of a new, potent master frame before the extreme right was able to break electoral marginalization. Such a master frame – combining ethnonationalist xenophobia, based on the doctrine of ethnopluralism, with anti-political-establishment populism – evolved in the 1970s, and was made known as a successful frame in connection with the electoral breakthrough of the French Front National in 1984. This event started a process of cross-national diffusion, where embryonic extreme right-wing groups and networks elsewhere adopted the new frame. Hence, the emergence of similar parties, clustered in time (i.e., the birth of a new party family) had less to do with structural factors influencing different political systems in similar ways as with cross-national diffusion of frames. The innovation and diffusion of the new master frame was a necessary, but not a sufficient, condition for the emergence of extreme right-wing populist parties. In order to complete the model, a short list of different political opportunity structures is added.

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TL;DR: Three different approaches that have been used to resolve temporal diet variation through analysis of stable isotopes are reviewed and urged for more laboratory experiments aimed at improving the understanding of differential assimilation of dietary components, isotopic fractionation and metabolic routing.
Abstract: Assessments of temporal variation in diets are important for our understanding of the ecology of many vertebrates. Ratios of naturally occurring stable isotopes in animal tissues are a combination of the source elements and tissue specific fractionation processes, and can thus reveal dietary information. We review three different approaches that have been used to resolve temporal diet variation through analysis of stable isotopes. The most straightforward approach is to compare samples from the same type of tissue that has been sampled over time. This approach is suited to address either long or short-term dietary variation, depending on sample regime and which tissue that is sampled. Second, one can compare tissues with different metabolic rates. Since the elements in a given tissue have been assimilating during time spans specific to its metabolic rate, tissues with different metabolic rates will reflect dietary records over different periods. Third, comparisons of sections from tissues with progressive growth, such as hair, feathers, claws and teeth, will reveal temporal variation since these tissues will retain isotopic values in a chronological order. These latter two approaches are mainly suited to address questions regarding intermediate and short-term dietary variation. Knowledge of tissue specific metabolic rates, which determine the molecular turnover for a specific tissue, is of central importance for all these comparisons. Estimates of isotopic fractionation between source and measured target are important if specific hypotheses regarding the source elements are addressed. Estimates of isotopic fractionation, or at least of differences in fractionation between tissues, are necessary if different tissues are compared. We urge for more laboratory experiments aimed at improving our understanding of differential assimilation of dietary components, isotopic fractionation and metabolic routing. We further encourage more studies on reptiles and amphibians, and generally more studies utilizing multiple tissues with different turnover rates.

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TL;DR: It was concluded that gender roles and psychological factors are more important than biological factors for the sex differences in stress responses, and an adequate balance between catabolic and anabolic processes is considered necessary for long term health and survival.

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03 Mar 2005-Nature
TL;DR: It is reported that TDP1 is sequestered into multi-protein single-strand break repair (SSBR) complexes by direct interaction with DNA ligase IIIα and that these complexes are catalytically inactive in SCAN1 cells, and implicate this process in the maintenance of genetic integrity in post-mitotic neurons.
Abstract: Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) is a neurodegenerative disease that results from mutation of tyrosyl phosphodiesterase 1 (TDP1). In lower eukaryotes, Tdp1 removes topoisomerase 1 (top1) peptide from DNA termini during the repair of double-strand breaks created by collision of replication forks with top1 cleavage complexes in proliferating cells. Although TDP1 most probably fulfils a similar function in human cells, this role is unlikely to account for the clinical phenotype of SCAN1, which is associated with progressive degeneration of post-mitotic neurons. In addition, this role is redundant in lower eukaryotes, and Tdp1 mutations alone confer little phenotype. Moreover, defects in processing or preventing double-strand breaks during DNA replication are most probably associated with increased genetic instability and cancer, phenotypes not observed in SCAN1 (ref. 8). Here we show that in human cells TDP1 is required for repair of chromosomal single-strand breaks arising independently of DNA replication from abortive top1 activity or oxidative stress. We report that TDP1 is sequestered into multi-protein single-strand break repair (SSBR) complexes by direct interaction with DNA ligase IIIalpha and that these complexes are catalytically inactive in SCAN1 cells. These data identify a defect in SSBR in a neurodegenerative disease, and implicate this process in the maintenance of genetic integrity in post-mitotic neurons.

Posted Content
TL;DR: This article found that both pre- and post-birth factors contribute to intergenerational transmissions, and that pre-birthing factors are more important for mother's education and less important for father's income.
Abstract: We use unique Swedish data to estimate intergenerational associations between adoptees and their biological and adoptive parents. We argue that the impact from biological parents captures broad pre-birth factors, including genes and prenatal environment, and the impact from adoptive parents represents broad post-birth factors, such as childhood environment, for the intergenerational association in education and income. We find that both pre- and post-birth factors contribute to intergenerational transmissions, and that pre-birth factors are more important for mother's education and less important for father's income. We also find some evidence for a positive interaction effect between post-birth environment and pre-birth factors.