bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction between relaxase MbeA and accessory protein MbeC of the conjugally mobilizable plasmid ColE1
Authors: Varsaki Athanasia , Lamb Heather K. , Eleftheriadou Olga , Vandera Elpiniki , Thompson Paul , Moncalián Gabriel , de la Cruz Fernando , Hawkins Alastair R. , Drainas Constantin
Published: February 2012

mbeA
and
mbeC
bind by isothermal titration calorimetry (View interaction)
The pros and cons of Confucian values in transport infrastructure development in China
Authors: de Jong Martin
Published: February 2012

China’s economic growth and the high pace with which it plans and constructs its infrastructure networks have led to a renewed interest in its decision-making models and the Confucian values which are believed to underlie it. This article makes an attempt to show what these Confucian values entail, through what mechanisms they influence organisational and decision-making processes, what their positive and negative sides are, to what extent they permeate transport infrastructure planning in China and why it is not easy or straightforward to emulate these policy practices elsewhere. Adopting certain features imbued with Confucian values, such as aspects of collectivism, conceptions of the common good, moral reflection and empathy are not pointless in a non-Asian context, but the specific context of such ‘other’ institutional environments must always be taken into account. Asian countries have grown stronger by selectively learning Western lessons; Western countries could reinforce the performance of their planning and policy-making processes in the future by looking eastwards and drawing inspiration from them while acknowledging vital differences.
New Working Group on “Cultural Protocols” Convenes at New York University, 19 August 2011
Authors: Sunder Madhavi
Published: February 2012

Protocols in international law seem to be proliferating. Examples of official protocols at international law abound, from the 1967 Stockholm Protocol Regarding Developing Countries (amending the Berne Convention on copyright), to the 1997 Kyoto Protocol on climate change, to the recent Nagoya Protocol on Access and Benefit Sharing in 2010. But what exactly is a “protocol” compared to other international legal instruments, such as declarations and treaties? And why does there seem to be a flurry of new protocols today, in domains as vast as intellectual property and indigenous people's rights? On 19 August a new “working group” convened at the New York University School of Law to begin to study protocols, especially with an eye toward their use as a tool to protect indigenous cultural property—hence, the term “cultural protocols.” The working group is the brainchild of Dr. Jane Anderson of the University of Massachusetts and Professor Barton Beebe of the New York University School of Law.
Rethinking Collaboration in Networked Music
Authors: Makelberge Nicolas
Published: February 2012

This paper argues that today's sampling culture, emerging out of pioneering efforts in electroacoustic music in the 1950s carries a similar ethos of autonomy found in many significant advances in music instrumentation throughout history. By looking at the evolution of musical instruments, the author hopes to address these continuous effort towards autonomy, which, if proves legitimate should be of great concern for networked music research that deals with all forms of music praxis of varying reciprocity and group dynamics. By further looking into what sets collaboration apart from cooperation and collective creation, and elaborating on the ‘social’ of music, this paper hopes to extend the discourse on current trends of accessing, shaping and sharing music in solitude, from something often seen as unfortunate and anti-social, to something less so.
Building on the Foundations of Network Music: Exploring interaction contexts and shared robotic instruments
Authors: Vallis Owen , Diakopoulos Dimitri , Hochenbaum Jordan , Kapur Ajay
Published: February 2012

Historically, network music has explored the practice and theory of interconnectivity, utilising the network itself as a creative instrument. The Machine Orchestra (TMO) has extended this historical idea by developing the custom software suiteSignal, and creating a shared, social instrument consisting of musical robotics.Signalis a framework for musical synchronisation and data sharing, designed to support the use of musical robotics in an attempt to more fully address ideas of interconnectivity and embodied performance.Signal, in combination with musical robotics, also facilitates the exploration of interaction contexts, such as at the note level, score level and sound-processing level. In this way, TMO is simultaneously building upon the historical contributions and developing aesthetics of network music.
Syneme: Live
Authors: Fields Kenneth
Published: February 2012

Network music foregrounds thematerials and processes of communicationand in so doing repositions the acousmatic and other strata of electroacoustic music practice. The type of network music considered in this paper, at base defines a member of its category as music which undergoes an electrical-optical conversion, referring to its transport over fibre-optic research network backbones. A more compelling motivation for us is the realisation that network music entails the exploration of disjunctchronotopicframes (stated less poetically as ‘latency in the network’) using probes of sonic material travelling near the speed of light. This article is an overview of a three-year project investigating music performance over high-speed research networks, a project funded by the Canada Research Chair programme (Syneme). The aim of the project was fourfold: to investigate aspects of physical and social networks in the production of network music (The Network); to investigate a branch of study continuing but critically distinct from Internet music as marked by ingenious strategies mounted to overcome the conditions of slow networks (Liveness); to embed ourselves in new practices (Telemusic Studio) and technologies (Artsmesh); and to compose network music pieces (Net Works). Our narrative picks up from where high-speed P2P networking crosses a threshold producing a successor to the Internet akin to the methodological shift that occurred in electroacoustics when CPUs achieved rendering speeds that allowed for real-time audio.
Pi2 pulsations driven by ballooning instability
Authors: Keiling Andreas
Published: February 2012

With the evidence set forth in this study, we argue that ballooning modes are viable candidates for the generation of high‐latitude Pi2 pulsations. In the scenario proposed here, it is the spatial separation ballooning wave perturbations along an energized boundary in the near‐Earth plasma sheet combined with a westward ion diamagnetic drift, which imprint a temporal signature, namely, Pi2 pulsation, on conjugate, stationary ground stations. The ballooning wave perturbations are connected via field‐aligned currents to the ionosphere causing Pi2 perturbations in the ground magnetic field. The observational evidence for this mechanism was conjugate spacecraft and ground data, showing correlated diamagnetic plasma perturbations and ground magnetic field oscillations, for two spatially separated, simultaneously occurring Pi2 events on 23 March 2007. The plasma perturbations were westward‐drifting waves with azimuthal mode number, m, of approximately 40 consistent with drift ballooning modes. During the Pi2 events, particle energy and energy flux gradually increased until the onset of major particle injections, causing auroral intensifications and additional larger‐amplitude Pi2s. The ground Pi2s, also shown to be westward‐traveling, were superposed on a slowly decreasing H component which abruptly turned into a substorm bay. A ballooning‐driven, high‐latitude Pi2 differs from a high‐latitude Pi2 that starts synchronized with substorm onset and that has been attributed to the transient response mechanism in that it is the frequency of drift ballooning mode in the near‐Earth plasma sheet that determines the Pi2 frequency and not the bounce frequency of Alfvén waves along a field line. The geophysical context for this type of Pi2 is a class of substorms that develop from a plasma instability in the near‐Earth plasma sheet. If this instability does not lead to a substorm breakup, it could lead to a pseudo‐breakup. Hence, it is also likely that some Pi2s associated with pseudo‐breakup are caused by the mechanism described here.
Scatterometer and reanalysis wind products over the western tropical Indian Ocean
Authors: Collins C. , Reason C. J. C. , Hermes J. C.
Published: February 2012

Accurate knowledge of the wind stress field is fundamental for understanding the ocean dynamics of a particular region. Ocean circulation models typically require this as forcing field and to be specified as one of the boundary conditions. Despite its importance, there are still substantial uncertainties in obtaining sufficiently accurate wind stress fields for many regions as well as sizeable differences between wind stress products for the same region. In this study, an assessment is made of three different wind products (one satellite scatterometer and two reanalyses) for the western tropical Indian Ocean, an area of complex ocean dynamics which has important influences on regional climate. In addition to this assessment, an investigation of the local scale spatial variability in the winds is made. It is found that the wind fields over the western Indian Ocean have prominent semiannual and annual cycles, but there are significant differences in these cycles when comparing different products. For example, for ERA‐interim, the annual cycle of wind speed associated with the Somali Jet display a longer Southwest monsoon season compared to QuikSCAT and NCEP. Both the scatterometer and two reanalysis products display analogous large‐scale wind features; however, differences were noted in the strengths of wind speed and wind stress curl. It is also evident that the local scale wind features associated with orographic effects are better resolved by QuikSCAT and ERA‐interim than NCEP. These differences in wind products have important implications for regional ocean dynamics and modeling.
On the systematic reduction of data complexity in multimodel atmospheric dispersion ensemble modeling
Authors: Riccio A. , Ciaramella A. , Giunta G. , Galmarini S. , Solazzo E. , Potempski S.
Published: February 2012

The aim of this work is to explore the effectiveness of theoretical information approaches for the reduction of data complexity in multimodel ensemble systems. We first exploit a weak form of independence, i.e. uncorrelation, as a mechanism for detecting linear relationships. Then, stronger and more general forms of independence measure, such as mutual information, are used to investigate dependence structures for model selection. A distance matrix, measuring the interdependence between data, is derived for the investigated measures, with the scope of clustering correlated/dependent models together. Redundant information is discarded by selecting a few representative models from each cluster. We apply the clustering analysis in the context of atmospheric dispersion modeling, by using the ETEX‐1 data set. We show how the selection of a small subset of models, according to uncorrelation or mutual information distance criteria, usually suffices to achieve a statistical performance comparable to, or even better than, that achieved from the whole ensemble data set, thus providing a simpler description of ensemble results without sacrificing accuracy.
Modeling of pesticide emissions from agricultural ecosystems
Authors: Li Rong
Published: February 2012

Pesticides are applied to crops and soils to improve agricultural yields, but the use of pesticides has become highly regulated because of concerns about their adverse effects on human health and environment. Estimating pesticide emission rates from soils and crops is a key component for risk assessment for pesticide registration, identification of pesticide sources to the contamination of sensitive ecosystems, and appreciation of transport and fate of pesticides in the environment. Pesticide emission rates involve processes occurring in the soil, in the atmosphere, and on vegetation surfaces and are highly dependent on soil texture, agricultural practices, and meteorology, which vary significantly with location and/or time. To take all these factors into account for simulating pesticide emissions from large agricultural ecosystems, this study coupled a comprehensive meteorological model with a dynamic pesticide emission model. The combined model calculates hourly emission rates from both emission sources: current applications and soil residues resulting from historical use. The coupled modeling system is used to compute a gridded (36 × 36 km) hourly toxaphene emission inventory for North America for the year 2000 using a published U.S. toxaphene residue inventory and a Mexican toxaphene residue inventory developed using its historical application rates and a cropland inventory. To my knowledge, this is the first such hourly toxaphene emission inventory for North America. Results show that modeled emission rates have strong diurnal and seasonal variations at a given location and over the entire domain. The simulated total toxaphene emission from contaminated agricultural soils in North America in 2000 was about 255 t, which compares reasonably well to a published annual estimate. Most emissions occur in spring and summer, with domain‐wide emission rates in April, May and, June of 36, 51, and 35 t/month, respectively. The spatial distribution of emissions depends on the distribution of toxaphene soil residues, and high emission rates coincide with heavily contaminated areas.
Observations of planetary waves and nonmigrating tides by the Mars Climate Sounder
Authors: Guzewich Scott D. , Talaat Elsayed R. , Waugh Darryn W.
Published: February 2012

Temperature profiles from the Mars Reconnaissance Orbiter's (MRO) Mars Climate Sounder (MCS) indicate the presence of several types of stationary planetary waves and nonmigrating thermal tides in the Martian atmosphere. We analyze 35 months of MCS data to identify the dominant waves. With the contribution of the zonal mean and migrating tides removed, the temperature perturbations remaining are due to planetary waves, nonmigrating tides, and topographic and surface albedo/thermal inertia effects. We characterize waves with satellite‐relative wave numbers 1 through 4 in the Martian middle atmosphere (40–80 km). In tropical latitudes, eastward propagating diurnal Kelvin waves are the dominant component observed in the satellite‐relative wave number 2 through 4 fields; we identify these as diurnal Kelvin waves 1 through 3, respectively. The Kelvin waves have very long vertical wavelengths and amplitudes of 1–3 K. This is the first unambiguous detection of diurnal Kelvin wave 3. We also identify the zonally symmetric diurnal tide and an eastward propagating semidiurnal wave 1 tide, possibly the semidiurnal Kelvin wave 1. Stationary planetary waves with wave numbers 1 and 2 produce 5–10 K amplitudes in the middle and high latitudes of both hemispheres.
Summer melt rates on Penny Ice Cap, Baffin Island: Past and recent trends and implications for regional climate
Authors: Zdanowicz Christian , Smetny‐Sowa Anna , Fisher David , Schaffer Nicole , Copland Luke , Eley Joe , Dupont Florent
Published: February 2012

At latitude 67°N, Penny Ice Cap on Baffin Island is the southernmost large ice cap in the Canadian Arctic, yet its past and recent evolution is poorly documented. Here we present a synthesis of climatological observations, mass balance measurements and proxy climate data from cores drilled on the ice cap over the past six decades (1953 to 2011). We find that starting in the 1980s, Penny Ice Cap entered a phase of enhanced melt rates related to rising summer and winter air temperatures across the eastern Arctic. Presently, 70 to 100% (volume) of the annual accumulation at the ice cap summit is in the form of refrozen meltwater. Recent surface melt rates are found to be comparable to those last experienced more than 3000 years ago. Enhanced surface melt, water percolation and refreezing have led to a downward transfer of latent heat that raised the subsurface firn temperature by 10°C (at 10 m depth) since the mid‐1990s. This process may accelerate further mass loss of the ice cap by pre‐conditioning the firn for the ensuing melt season. Recent warming in the Baffin region has been larger in winter but more regular in summer, and observations on Penny Ice Cap suggest that it was relatively uniform over the 2000‐m altitude range of the ice cap. Our findings are consistent with trends in glacier mass loss in the Canadian High Arctic and regional sea‐ice cover reduction, reinforcing the view that the Arctic appears to be reverting back to a thermal state not seen in millennia.
Dynamic modeling of predictive uncertainty by regression on absolute errors
Authors: Pianosi F. , Raso L.
Published: February 2012

Uncertainty of hydrological forecasts represents valuable information for water managers and hydrologists. This explains the popularity of probabilistic models, which provide the entire distribution of the hydrological forecast. Nevertheless, many existing hydrological models are deterministic and provide point estimates of the variable of interest. Often, the model residual error is assumed to be homoscedastic; however, practical evidence shows that the hypothesis usually does not hold. In this paper we propose a simple and effective method to quantify predictive uncertainty of deterministic hydrological models affected by heteroscedastic residual errors. It considers the error variance as a hydrological process separate from that of the hydrological forecast and therefore predictable by an independent model. The variance model is built up using time series of model residuals, and under some conditions on the same residuals, it is applicable to any deterministic model. Tools for regression analysis applied to the time series of residual errors, or better their absolute values, combined with physical considerations of the hydrological features of the system can help to identify the most suitable input to the variance model and the most parsimonious model structure, including dynamic structure if needed. The approach has been called dynamic uncertainty modeling by regression on absolute errors and is demonstrated by application to two test cases, both affected by heteroscedasticity but with very different dynamics of uncertainty. Modeling results and comparison with other approaches, i.e., a constant, a cyclostationary, and a static model of the variance, confirm the validity of the proposed method.
On generating conductivity fields with known fractal dimension and nonstationary increments
Authors: O'Malley Daniel , Cushman John H. , O'Rear Patrick
Published: February 2012

Fractional Brownian motion (fBm) is a stochastic process that has stationary increments with long‐range correlations and known fractal dimension. We study a multiple‐dimensional extension of fBm with nonstationary increments that allows for trends in the statistical structure while maintaining the Gaussian nature and fractal dimension of fBm. Two methods for simulating this extension are employed and described in detail. One approach combines Cholesky decomposition with a generalization of random midpoint displacement. The other makes repeated use of the Cholesky decomposition. The resulting fields can be employed in various geophysical settings, e.g., as log conductivity fields in hydrology and topographic elevation in geomorphology.
Apak competes with p53 for direct binding to intron 1 of p53AIP1 to regulate apoptosis
Authors: Yuan Lin , Tian Chunyan , Wang Hongye , Song Shanshan , Li Deyang , Xing Guichun , Yin Yuxin , He Fuchu , Zhang Lingqiang
Published: February 2012

The KRAB‐type zinc‐finger protein Apak was recently identified as a negative regulator of p53‐mediated apoptosis. However, the mechanism of this selective regulation is not fully understood. Here, we show that Apak recognizes the TCTTN2−30TTGT consensus sequence through its zinc‐fingers. This sequence is specifically found in intron 1 of the proapoptotic p53 target gene p53AIP1 and largely overlaps with the p53‐binding sequence. Apak competes with p53 for binding to this site to inhibit p53AIP1 expression. Upon DNA damage, Apak dissociates from the DNA, which abolishes its inhibitory effect on p53‐mediated apoptosis.
Erratum: Black reefs: iron-induced phase shifts on coral reefs
Authors: Kelly Linda Wegley , Barott Katie L , Dinsdale Elizabeth , Friedlander Alan M , Nosrat Bahador , Obura David , Sala Enric , Sandin Stuart A , Smith Jennifer E , Vermeij Mark J A , Williams Gareth J , Willner Dana , Rohwer Forest
Published: February 2012

Correction to: The ISME Journal (2012) 6, 638–649; doi:10.1038/ismej.2011.114; published online 1 September 2011 Since the publication of this article, the authors have noticed an omission in the acknowledgements section: This work was carried under a permit from the Palmyra Atoll National Wildlife Refuge, US Fish and Wildlife Service at the Department of the Interior.
Crystal structure and functional characterization of a glucosamine-6-phosphate N-acetyltransferase from Arabidopsis thaliana
Authors: Riegler Heike , Herter Thomas , Grishkovskaya Irina , Lude Anja , Ryngajllo Malgorzata , Bolger Marie E. , Essigmann Bernd , Usadel Björn
Published: February 2012

GlcNAc (N-acetylglucosamine) is an essential part of the glycan chain in N-linked glycoproteins. It is a building block for polysaccharides such as chitin, and several glucosaminoglycans and proteins can be O-GlcNAcylated. The deacetylated form, glucosamine, is an integral part of GPI (glycosylphosphatidylinositol) anchors. Both are incorporated into polymers by glycosyltransferases that utilize UDP-GlcNAc. This UDP-sugar is synthesized in a short pathway comprising four steps starting from fructose 6-phosphate. GNA (glucosamine-6-phosphate N-acetyltransferase) catalyses the second of these four reactions in the de novo synthesis in eukaryotes. A phylogenetic analysis revealed that only one GNA isoform can be found in most of the species investigated and that the most likely Arabidopsis candidate is encoded by the gene At5g15770 (AtGNA). qPCR (quantitative PCR) revealed the ubiquitous expression of AtGNA in all organs of Arabidopsis plants. Heterologous expression of AtGNA showed that it is highly active between pH 7 and 8 and at temperatures of 30–40°C. It showed Km values of 231 μM for glucosamine 6-phosphate and 33 μM for acetyl-CoA respectively and a catalytic efficiency comparable with that of other GNAs characterized. The solved crystal structure of AtGNA at a resolution of 1.5 Å (1 Å=0.1 nm) revealed a very high structural similarity to crystallized GNA proteins from Homo sapiens and Saccharomyces cerevisiae despite less well conserved protein sequence identity.
New carnivorous sponges (Cladorhizidae:Poecilosclerida:Demospongiae) from off Diego Ramírez Archipelago (south Chile), with comments on taxonomy and biogeography of the family
Authors: Lopes Daniela A. , Bravo Alejandro , Hajdu Eduardo
Published: February 2012

Eight new species of carnivorous sponges are described from southern South America, off Diego Ramírez Archipelago (south Chile): Abyssocladia diegoramirezensis, sp. nov., A. umbellata, sp. nov., Asbestopluma (Asbestopluma) bitrichela, sp. nov., A. (A.) magnifica, sp. nov., A. (A.) microstrongyla, sp. nov., A. (Helophloeina) delicata, sp. nov., Chondrocladia (Chondrocladia) schlatteri, sp. nov. and C. (Meliiderma) latrunculioides, sp. nov. Most of these sponges were sampled from an antipatharian coral collected accidentaly by demersal fisheries, which indicates an unexpected high diversity and abundance of carnivorous sponges in this area. The taxonomy and biogeography of the family Cladorhizidae is discussed, with an emphasis on cladorhizid versus phellodermid affinities of Abyssocladia, and on the possibility that species bearing either cleistochelae or arcuate chelae as the sole chelae morphotype may belong in this genus. A synthesis of the geographic as well as bathymetric distribution of cladorhizids is presented.
Transgene-mediated cosuppression and RNA interference enhance germ-line apoptosis in
Caenorhabditis elegans
Authors: Adamo Adele , Woglar Alexander , Silva Nicola , Penkner Alexandra , Jantsch Verena , La Volpe Adriana
Published: February 2012

Introduction of multiple copies of a germ-line–expressed gene elicits silencing of the corresponding endogenous gene during
Caenorhabditis elegans
oogenesis; this process is referred to as germ-line cosuppression. Transformed plasmids assemble into extrachromosomal arrays resembling extra minichromosomes with repetitive structures. Loss of the transgene extrachromosomal array leads to reversion of the silencing phenomenon. Cosuppression and RNAi depend upon some of the same genes. In the
C. elegans
germ line, about half the cells undergo a physiological programmed cell death that shares most genetic requirements with somatic apoptosis. In addition, apoptosis is stimulated by DNA damage and synaptic failure mediated through different apoptotic checkpoints. We found that both germ-line cosuppression and RNAi of germ-line–expressed genes enhance apoptosis during
C. elegans
oogenesis. In contrast, apoptosis is not enhanced by extrachromosomal arrays carrying genes not driven by germ-line–specific promoters that thus do not elicit transgene-mediated cosuppression/silencing. Similarly, introduction of doubled-stranded RNA that shares no homology with endogenous genes has no effect on apoptosis. “Silencing-induced apoptosis” is dependent upon
sir-2.1
and
cep-1
(the worm p53 ortholog), and is accompanied by a rise in RAD-51 foci, a marker for ongoing DNA repair, indicating induction of DNA double-strand breaks. This finding suggests that the DNA damage-response pathway is involved. RNAi and cosuppression have been postulated as defense mechanisms against genomic intruders. We speculate that the mechanism here described may trigger the elimination of germ cells that have undergone viral infection or transposon activation.
Unified quantitative model of AMPA receptor trafficking at synapses
Authors: Czöndör Katalin , Mondin Magali , Garcia Mikael , Heine Martin , Frischknecht Renato , Choquet Daniel , Sibarita Jean-Baptiste , Thoumine Olivier R.
Published: February 2012

Trafficking of AMPA receptors (AMPARs) plays a key role in synaptic transmission. However, a general framework integrating the two major mechanisms regulating AMPAR delivery at postsynapses (i.e., surface diffusion and internal recycling) is lacking. To this aim, we built a model based on numerical trajectories of individual AMPARs, including free diffusion in the extrasynaptic space, confinement in the synapse, and trapping at the postsynaptic density (PSD) through reversible interactions with scaffold proteins. The AMPAR/scaffold kinetic rates were adjusted by comparing computer simulations to single-particle tracking and fluorescence recovery after photobleaching experiments in primary neurons, in different conditions of synapse density and maturation. The model predicts that the steady-state AMPAR number at synapses is bidirectionally controlled by AMPAR/scaffold binding affinity and PSD size. To reveal the impact of recycling processes in basal conditions and upon synaptic potentiation or depression, spatially and temporally defined exocytic and endocytic events were introduced. The model predicts that local recycling of AMPARs close to the PSD, coupled to short-range surface diffusion, provides rapid control of AMPAR number at synapses. In contrast, because of long-range diffusion limitations, extrasynaptic recycling is intrinsically slower and less synapse-specific. Thus, by discriminating the relative contributions of AMPAR diffusion, trapping, and recycling events on spatial and temporal bases, this model provides unique insights on the dynamic regulation of synaptic strength.
The water footprint of humanity
Authors: Hoekstra Arjen Y. , Mekonnen Mesfin M.
Published: February 2012

This study quantifies and maps the water footprint (WF) of humanity at a high spatial resolution. It reports on consumptive use of rainwater (green WF) and ground and surface water (blue WF) and volumes of water polluted (gray WF). Water footprints are estimated per nation from both a production and consumption perspective. International virtual water flows are estimated based on trade in agricultural and industrial commodities. The global annual average WF in the period 1996–2005 was 9,087 Gm
3
/y (74% green, 11% blue, 15% gray). Agricultural production contributes 92%. About one-fifth of the global WF relates to production for export. The total volume of international virtual water flows related to trade in agricultural and industrial products was 2,320 Gm
3
/y (68% green, 13% blue, 19% gray). The WF of the global average consumer was 1,385 m
3
/y. The average consumer in the United States has a WF of 2,842 m
3
/y, whereas the average citizens in China and India have WFs of 1,071 and 1,089 m
3
/y, respectively. Consumption of cereal products gives the largest contribution to the WF of the average consumer (27%), followed by meat (22%) and milk products (7%). The volume and pattern of consumption and the WF per ton of product of the products consumed are the main factors determining the WF of a consumer. The study illustrates the global dimension of water consumption and pollution by showing that several countries heavily rely on foreign water resources and that many countries have significant impacts on water consumption and pollution elsewhere.
Transcriptional pausing coordinates folding of the aptamer domain and the expression platform of a riboswitch
Authors: Perdrizet George A. , Artsimovitch Irina , Furman Ran , Sosnick Tobin R. , Pan Tao
Published: February 2012

Riboswitches are
cis
-acting elements that regulate gene expression by affecting transcriptional termination or translational initiation in response to binding of a metabolite. A typical riboswitch is made of an upstream aptamer domain and a downstream expression platform. Both domains participate in the folding and structural rearrangement in the absence or presence of its cognate metabolite. RNA polymerase pausing is a fundamental property of transcription that can influence RNA folding. Here we show that pausing plays an important role in the folding and conformational rearrangement of the
Escherichia coli
btuB riboswitch during transcription by the
E. coli
RNA polymerase. This riboswitch consists of an approximately 200 nucleotide, coenzyme B12 binding aptamer domain and an approximately 40 nucleotide expression platform that controls the ribosome access for translational initiation. We found that transcriptional pauses at strategic locations facilitate folding and structural rearrangement of the full-length riboswitch, but have minimal effect on the folding of the isolated aptamer domain. Pausing at these regulatory sites blocks the formation of alternate structures and plays a chaperoning role that couples folding of the aptamer domain and the expression platform. Pausing at strategic locations may be a general mechanism for coordinated folding and conformational rearrangements of riboswitch structures that underlie their response to environmental cues.
Unwinding the differences of the mammalian PERIOD clock proteins from crystal structure to cellular function
Authors: Kucera Nicole , Schmalen Ira , Hennig Sven , Öllinger Rupert , Strauss Holger M. , Grudziecki Astrid , Wieczorek Caroline , Kramer Achim , Wolf Eva
Published: February 2012

The three PERIOD homologues mPER1, mPER2, and mPER3 constitute central components of the mammalian circadian clock. They contain two PAS (PER-ARNT-SIM) domains (PAS-A and PAS-B), which mediate homo- and heterodimeric mPER-mPER interactions as well as interactions with transcription factors and kinases. Here we present crystal structures of PAS domain fragments of mPER1 and mPER3 and compare them with the previously reported mPER2 structure. The structures reveal homodimers, which are mediated by interactions of the PAS-B β-sheet surface including a highly conserved tryptophan (Trp448
mPER1
, Trp419
mPER2
, Trp359
mPER3
). mPER1 homodimers are additionally stabilized by interactions between the PAS-A domains and mPER3 homodimers by an N-terminal region including a predicted helix-loop-helix motive. We have verified the existence of these homodimer interfaces in solution and inside cells using analytical gel filtration and luciferase complementation assays and quantified their contributions to homodimer stability by analytical ultracentrifugation. We also show by fluorescence recovery after photobleaching analyses that destabilization of the PAS-B/tryptophan dimer interface leads to a faster mobility of mPER2 containing complexes in human U2OS cells. Our study reveals structural and quantitative differences between the homodimeric interactions of the three mouse PERIOD homologues, which are likely to contribute to their distinct clock functions.
Viral reassortment as an information exchange between viral segments
Authors: Greenbaum Benjamin D. , Li Olive T. W. , Poon Leo L. M. , Levine Arnold J. , Rabadan Raul
Published: February 2012

Viruses have an extraordinary ability to diversify and evolve. For segmented viruses, reassortment can introduce drastic genomic and phenotypic changes by allowing a direct exchange of genetic material between coinfecting strains. For instance, multiple influenza pandemics were caused by reassortments of viruses typically found in separate hosts. What is unclear, however, are the underlying mechanisms driving these events and the level of intrinsic bias in the diversity of strains that emerge from coinfection. To address this problem, previous experiments looked for correlations between segments of strains that coinfect cells in vitro. Here, we present an information theory approach as the natural mathematical framework for this question. We study, for influenza and other segmented viruses, the extent to which a virus’s segments can communicate strain information across an infection and among one another. Our approach goes beyond previous association studies and quantifies how much the diversity of emerging strains is altered by patterns in reassortment, whether biases are consistent across multiple strains and cell types, and if significant information is shared among more than two segments. We apply our approach to a new experiment that examines reassortment patterns between the 2009 H1N1 pandemic and seasonal H1N1 strains, contextualizing its segmental information sharing by comparison with previously reported strain reassortments. We find evolutionary patterns across classes of experiments and previously unobserved higher-level structures. Finally, we show how this approach can be combined with virulence potentials to assess pandemic threats.
Molecular mechanism of pharmacological activation of BK channels
Authors: Gessner Guido , Cui Yong-Mei , Otani Yuko , Ohwada Tomohiko , Soom Malle , Hoshi Toshinori , Heinemann Stefan H.
Published: February 2012

Large-conductance voltage- and Ca
2+
-activated K
+
(Slo1 BK) channels serve numerous cellular functions, and their dysregulation is implicated in various diseases. Drugs activating BK channels therefore bear substantial therapeutic potential, but their deployment has been hindered in part because the mode of action remains obscure. Here we provide mechanistic insight into how the dehydroabietic acid derivative Cym04 activates BK channels. As a representative of NS1619-like BK openers, Cym04 reversibly left-shifts the half-activation voltage of Slo1 BK channels. Using an established allosteric BK gating model, the Cym04 effect can be simulated by a shift of the voltage sensor and the ion conduction gate equilibria toward the activated and open state, respectively. BK activation by Cym04 occurs in a splice variant-specific manner; it does not occur in such Slo1 BK channels using an alternative neuronal exon 9, which codes for the linker connecting the transmembrane segment S6 and the cytosolic RCK1 domain—the S6/RCK linker. In addition, Cym04 does not affect Slo1 BK channels with a two-residue deletion within this linker. Mutagenesis and model-based gating analysis revealed that BK openers, such as Cym04 and NS1619 but not mallotoxin, activate BK channels by functionally interacting with the S6/RCK linker, mimicking site-specific shortening of this purported passive spring, which transmits force from the cytosolic gating ring structure to open the channel's gate.
Ganglioside GM1 induces phosphorylation of mutant huntingtin and restores normal motor behavior in Huntington disease mice
Authors: Di Pardo Alba , Maglione Vittorio , Alpaugh Melanie , Horkey Melanie , Atwal Randy S. , Sassone Jenny , Ciammola Andrea , Steffan Joan S. , Fouad Karim , Truant Ray , Sipione Simonetta
Published: February 2012

Huntington disease (HD) is a progressive neurodegenerative monogenic disorder caused by expansion of a polyglutamine stretch in the huntingtin (Htt) protein. Mutant huntingtin triggers neural dysfunction and death, mainly in the corpus striatum and cerebral cortex, resulting in pathognomonic motor symptoms, as well as cognitive and psychiatric decline. Currently, there is no effective treatment for HD. We report that intraventricular infusion of ganglioside GM1 induces phosphorylation of mutant huntingtin at specific serine amino acid residues that attenuate huntingtin toxicity, and restores normal motor function in already symptomatic HD mice. Thus, our studies have identified a potential therapy for HD that targets a posttranslational modification of mutant huntingtin with critical effects on disease pathogenesis.
Crystallographic basis for calcium regulation of sodium channels
Authors: Sarhan Maen F. , Tung Ching-Chieh , Van Petegem Filip , Ahern Christopher A.
Published: February 2012

Voltage-gated sodium channels underlie the rapid regenerative upstroke of action potentials and are modulated by cytoplasmic calcium ions through a poorly understood mechanism. We describe the 1.35 Å crystal structure of Ca
2+
-bound calmodulin (Ca
2+
/CaM) in complex with the inactivation gate (DIII-IV linker) of the cardiac sodium channel (Na
V
1.5). The complex harbors the positions of five disease mutations involved with long Q-T type 3 and Brugada syndromes. In conjunction with isothermal titration calorimetry, we identify unique inactivation-gate mutations that enhance or diminish Ca
2+
/CaM binding, which, in turn, sensitize or abolish Ca
2+
regulation of full-length channels in electrophysiological experiments. Additional biochemical experiments support a model whereby a single Ca
2+
/CaM bridges the C-terminal IQ motif to the DIII-IV linker via individual N and C lobes, respectively. The data suggest that Ca
2+
/CaM destabilizes binding of the inactivation gate to its receptor, thus biasing inactivation toward more depolarized potentials.
Global climate evolution during the last deglaciation
Authors: Clark Peter U. , Shakun Jeremy D. , Baker Paul A. , Bartlein Patrick J. , Brewer Simon , Brook Ed , Carlson Anders E. , Cheng Hai , Kaufman Darrell S. , Liu Zhengyu , Marchitto Thomas M. , Mix Alan C. , Morrill Carrie , Otto-Bliesner Bette L. , Pahnke Katharina , Russell James M. , Whitlock Cathy , Adkins Jess F. , Blois Jessica L. , Clark Jorie , Colman Steven M. , Curry William B. , Flower Ben P. , He Feng , Johnson Thomas C. , Lynch-Stieglitz Jean , Markgraf Vera , McManus Jerry , Mitrovica Jerry X. , Moreno Patricio I. , Williams John W.
Published: February 2012

Deciphering the evolution of global climate from the end of the Last Glacial Maximum approximately 19 ka to the early Holocene 11 ka presents an outstanding opportunity for understanding the transient response of Earth’s climate system to external and internal forcings. During this interval of global warming, the decay of ice sheets caused global mean sea level to rise by approximately 80 m; terrestrial and marine ecosystems experienced large disturbances and range shifts; perturbations to the carbon cycle resulted in a net release of the greenhouse gases CO
2
and CH
4
to the atmosphere; and changes in atmosphere and ocean circulation affected the global distribution and fluxes of water and heat. Here we summarize a major effort by the paleoclimate research community to characterize these changes through the development of well-dated, high-resolution records of the deep and intermediate ocean as well as surface climate. Our synthesis indicates that the superposition of two modes explains much of the variability in regional and global climate during the last deglaciation, with a strong association between the first mode and variations in greenhouse gases, and between the second mode and variations in the Atlantic meridional overturning circulation.
Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species
Authors: Jackson Andrew P. , Berry Andrew , Aslett Martin , Allison Harriet C. , Burton Peter , Vavrova-Anderson Jana , Brown Robert , Browne Hilary , Corton Nicola , Hauser Heidi , Gamble John , Gilderthorp Ruth , Marcello Lucio , McQuillan Jacqueline , Otto Thomas D. , Quail Michael A. , Sanders Mandy J. , van Tonder Andries , Ginger Michael L. , Field Mark C. , Barry J. David , Hertz-Fowler Christiane , Berriman Matthew
Published: February 2012

Antigenic variation enables pathogens to avoid the host immune response by continual switching of surface proteins. The protozoan blood parasite
Trypanosoma brucei
causes human African trypanosomiasis (“sleeping sickness”) across sub-Saharan Africa and is a model system for antigenic variation, surviving by periodically replacing a monolayer of variant surface glycoproteins (VSG) that covers its cell surface. We compared the genome of
Trypanosoma brucei
with two closely related parasites
Trypanosoma congolense
and
Trypanosoma vivax
, to reveal how the variant antigen repertoire has evolved and how it might affect contemporary antigenic diversity. We reconstruct
VSG
diversification showing that
Trypanosoma congolense
uses variant antigens derived from multiple ancestral
VSG
lineages, whereas in
Trypanosoma brucei VSG
have recent origins, and ancestral gene lineages have been repeatedly co-opted to novel functions. These historical differences are reflected in fundamental differences between species in the scale and mechanism of recombination. Using phylogenetic incompatibility as a metric for genetic exchange, we show that the frequency of recombination is comparable between
Trypanosoma congolense
and
Trypanosoma brucei
but is much lower in
Trypanosoma vivax
. Furthermore, in showing that the C-terminal domain of
Trypanosoma brucei VSG
plays a crucial role in facilitating exchange, we reveal substantial species differences in the mechanism of
VSG
diversification. Our results demonstrate how past
VSG
evolution indirectly determines the ability of contemporary parasites to generate novel variant antigens through recombination and suggest that the current model for antigenic variation in
Trypanosoma brucei
is only one means by which these parasites maintain chronic infections.
Timing of climate variability and grassland productivity
Authors: Craine Joseph M. , Nippert Jesse B. , Elmore Andrew J. , Skibbe Adam M. , Hutchinson Stacy L. , Brunsell Nathaniel A.
Published: February 2012

Future climates are forecast to include greater precipitation variability and more frequent heat waves, but the degree to which the timing of climate variability impacts ecosystems is uncertain. In a temperate, humid grassland, we examined the seasonal impacts of climate variability on 27 y of grass productivity. Drought and high-intensity precipitation reduced grass productivity only during a 110-d period, whereas high temperatures reduced productivity only during 25 d in July. The effects of drought and heat waves declined over the season and had no detectable impact on grass productivity in August. If these patterns are general across ecosystems, predictions of ecosystem response to climate change will have to account not only for the magnitude of climate variability but also for its timing.
Regenerative capacity of adult cortical thymic epithelial cells
Authors: Rode Immanuel , Boehm Thomas
Published: February 2012

Involution of the thymus is accompanied by a decline in the number of thymic epithelial cells (TECs) and a severely restricted peripheral repertoire of T-cell specificities. TECs are essential for T-cell differentiation; they originate from a bipotent progenitor that gives rise to cells of cortical (cTEC) and medullary (mTEC) phenotypes, via compartment-specific progenitors. Upon acute selective near-total ablation during embryogenesis, regeneration of TECs fails, suggesting that losses from the pool of TEC progenitors are not compensated. However, it is unclear whether this is also true for the compartment-specific progenitors. The decline of cTECs is a prominent feature of thymic involution. Because cTECs support early stages of T-cell development and hence determine the overall lymphopoietic capacity of the thymus, it is possible that the lack of sustained regenerative capacity of cTEC progenitor cells underlies the process of thymic involution. Here, we examine this hypothesis by cell-type–specific conditional ablation of cTECs. Expression of the human diphtheria toxin receptor (hDTR) gene under the regulatory influence of the chemokine receptor
Ccx-ckr1
gene renders cTECs sensitive to the cytotoxic effects of diphtheria toxin (DT). As expected, DT treatment of preadolescent and adult mice led to a dramatic loss of cTECs, accompanied by a rapid demise of immature thymocytes. Unexpectedly, however, the cTEC compartment regenerated after cessation of treatment, accompanied by the restoration of T-cell development. These findings provide the basis for the development of targeted interventions unlocking the latent regenerative potential of cTECs to counter thymic involution.
Dissociable prior influences of signal probability and relevance on visual contrast sensitivity
Authors: Wyart Valentin , Nobre Anna Christina , Summerfield Christopher
Published: February 2012

According to signal detection theoretical analyses, visual signals occurring at a cued location are detected more accurately, whereas frequently occurring ones are reported more often but are not better distinguished from noise. However, conventional analyses that estimate sensitivity and bias by comparing true- and false-positive rates offer limited insights into the mechanisms responsible for these effects. Here, we reassessed the prior influences of signal probability and relevance on visual contrast detection using a reverse-correlation technique that quantifies how signal-like fluctuations in noise predict trial-to-trial variability in choice discarded by conventional analyses. This approach allowed us to estimate separately the sensitivity of true and false positives to parametric changes in signal energy. We found that signal probability and relevance both increased energy sensitivity, but in dissociable ways. Cues predicting the relevant location increased primarily the sensitivity of true positives by suppressing internal noise during signal processing, whereas cues predicting greater signal probability increased both the frequency and the sensitivity of false positives by biasing the baseline activity of signal-selective units. We interpret these findings in light of “predictive-coding” models of perception, which propose separable top-down influences of expectation (probability driven) and attention (relevance driven) on bottom-up sensory processing.