bluuebunny/crossref_metadata_2025 huggingface dataset:
Research Spotlight: Why was Arctic sea ice extent low in summer 2010?
Authors: Schultz Colin
Published: April 2011

Arctic sea ice extent has been declining in recent years, although ice extent varies with changes in atmospheric circulation, especially changes in the phase of the Arctic Oscillation. The negative phase of the Arctic Oscillation has generally favored survival of sea ice, but while an extreme negative phase of the Arctic Oscillation took place in winter 2009–2010, the September 2010 Arctic sea ice extent was the third lowest in the satellite record. Stroeve et al. investigated the causes of the low ice extent in 2010. They analyzed sea ice concentrations as well as sea level pressure and air temperature data from 1979 through 2010 and found that atmospheric circulation during winter 2009–2010 was different from previous negative Arctic Oscillation events. In typical negative events, winds drive thick multiyear ice in the Beaufort Sea northward to areas where the ice thickens and survives the summer melt season, but during the 2009–2010 winter, winds drove older ice across the Beaufort Sea into the warmer southern areas of the Beaufort and Chukchi seas. (Geophysical Research Letters, doi:10.1029/2010GL045662, 2011)
Research Spotlight: Groundwater is being depleted rapidly in California's Central Valley
Authors: Tretkoff Ernie
Published: April 2011

Groundwater is being depleted in California's Central Valley at a rapid rate, according to data from the Gravity Recovery and Climate Experiment (GRACE) satellite. Famiglietti et al. analyzed 78 months of GRACE data covering October 2003 to March 2010 to estimate water storage changes in California's Sacramento and San Joaquin river basins. They found that the basins are losing water at a rate of about 30 millimeters per year equivalent water height, or a total of about 30 cubic kilometers over the 78‐month period. Furthermore, they found that two thirds of this loss, or a total of 20 cubic kilometers for the study period, came from groundwater depletion in the Central Valley. Quantifying groundwater depletion can be challenging in many areas because of a lack of monitoring infrastructure and reporting requirements; the study shows that satellite‐based monitoring can be a useful way to track groundwater volumes. The authors warn that the current rate of groundwater depletion in the Central Valley may be unsustainable and could have “potentially dire consequences for the economic and food security of the United States.” (Geophysical Research Letters, doi:10.1029/2010GL046442, 2011)
Research Spotlight: Records suggest El Niño variability to continue in warmer world
Authors: Tretkoff Ernie
Published: April 2011

There has been some debate as to whether global warming could lead to a permanent El Niño state rather than a periodically varying El Niño–Southern Oscillation (ENSO), which occurs now. It has also been suggested that ice‐free Arctic summers could affect high‐latitude and midlatitude circulation patterns and climate variability. Now sediment records from the Arctic suggest that even as climate warms, the variability of ENSO will continue. Davies et al. analyzed the first annually resolved sediment core spanning 1000 years about 70 million years ago during the Late Cretaceous. (Geophysical Research Letters, doi:10.1029/2010GL046151, 2011)
Research Spotlight: What controls the shape of sediment channels in river deltas?
Authors: Tretkoff Ernie
Published: April 2011

When turbulent, sediment‐filled rivers empty into oceans and lakes, the channels often divide repeatedly to form triangular deltas. Some channels, however, travel long distances before bifurcating, creating elongated channels. Understanding how these patterns arise could be useful for designing wetland restoration schemes on river deltas. Seeking to explain the conditions under which elongated channels form, Falcini and Jerolmack considered an analogy with cold filaments in ocean currents, in which high potential vorticity (a measure that combines the rotation of a flow with its thermal gradient) helps a filament hold a coherent structure over long distances. The researchers introduced a model that incorporates sediment concentration and fluid vorticity, to derive a new “potential vorticity” equation that describes sedimentation patterns at the river mouth. Their model shows that a high potential vorticity is needed for the creation of elongated channels, and their comparison to modeling, laboratory, and field studies confirms that potential vorticity is a primary control on channel morphology. The new model could help to understand the shape of the iconic Mississippi River delta and may aid in the design of proposed channel diversions there and in other deltas. (Journal of Geophysical Research‐Earth Surface, doi:10.1029/2010JF001802, 2010)
Research Spotlight: Auroral emissions reach ground level
Authors: Tretkoff Ernie
Published: April 2011

Earth's auroral electrons radiate some of their energy in radio waves. Theories of the mechanism for emission of this radiation, known as auroral kilometric radiation (AKR), suggest that this radiation propagates away from Earth and cannot be detected at ground level. However, LaBelle and Anderson present the first evidence that AKR does penetrate to ground level. On three occasions in July 2004 the researchers detected radio emissions that appeared to be AKR at the South Pole Station in Antarctica. They compared these emissions with AKR emissions detected simultaneously by the U.S.‐Japanese Geotail satellite and found that they had the same frequency structure, suggesting that the emissions detected at ground level were indeed AKR. (Geophysical Research Letters, doi:10.1029/2010GL046411, 2011)
Research Spotlight: New method to assess coral reef health
Authors: Tretkoff Ernie
Published: April 2011

Coral reefs around the world are becoming stressed due to rising temperatures, ocean acidification, overfishing, and other factors. Measuring community level rates of photosynthesis, respiration, and biogenic calcification is essential to assessing the health of coral reef ecosystems because the balance between these processes determines the potential for reef growth and the export of carbon. Measurements of biological productivity have typically been made by tracing changes in dissolved oxygen in seawater as it passes over a reef. However, this is a labor‐intensive and difficult method, requiring repeated measurements. (Geophysical Research Letters, doi:10.1029/2010GL046179, 2011)
Research Spotlight: Corals expanding poleward due to warming climate
Authors: Tretkoff Ernie
Published: April 2011

Corals are important organisms for ecosystems and are sensitive indicators of the effects of climate warming. While corals are bleaching and dying in tropical areas due to climate warming, a new study shows that in temperate areas they are expanding their range poleward as water temperatures increase. Yamano et al. used 80 years of records to study the range of corals around Japan. Sea surface temperatures have risen in these temperate areas during that time. They found that four of the nine species of coral they studied expanded their range northward since the 1930s, while none had its range shrink southward. The corals expanded northward as quickly as 14 kilometers per year. The study suggests that rapid modifications of temperate coastal ecosystems could be taking place. (Geophysical Research Letters, doi:10.1029/2010GL046474, 2011)
Scientific Value of Real‐Time Global Positioning System Data
Authors: Hammond William C. , Brooks Benjamin A. , Bürgmann Roland , Heaton Thomas , Jackson Michael , Lowry Anthony R. , Anandakrishnan Sridhar
Published: April 2011

The Global Positioning System (GPS) is an example of a Global Navigation Satellite System (GNSS) that provides an essential complement to other geophysical networks because of its high precision, sensitivity to the longest‐period bands, ease of deployment, and ability to measure displacement and atmospheric properties over local to global scales. Recent and ongoing technical advances, combined with decreasing equipment and data acquisition costs, portend rapid increases in accessibility of data from expanding global geodetic networks. Scientists and the public are beginning to have access to these high‐rate, continuous data streams and event‐specific information within seconds to minutes rather than days to months. These data provide the opportunity to observe Earth system processes with greater accuracy and detail, as they occur.
European Earth Observation Program: “Positive Synergy” Between Science and Society
Authors: Showstack Randy
Published: April 2011

Within the European Space Agency's (ESA) Earth Observation programs, a “positive synergy between science and society” comes across “very strongly,” according to Stephen Briggs, head of the program planning and coordination service for ESA's Directorate of Earth Observation Programmes. Briggs offered insights into the Earth Observation programs, including missions, data policy, and cooperation with other space agencies, during a 4 April town hall meeting at the European Geosciences Union's (EGU) annual meeting in Vienna, Austria. “One of the aspects that strikes everyone in Earth observation is the fact that when studying Earth science, it's not like looking at cosmology. We're looking at aspects of the Earth which inevitably have some consequence for society,” Briggs said, pointing to recent ESA satellite imagery of natural disasters, forest cover, ice sheets, and oceans.
Climate Change “Hoax”: Comment on “Climate Science in a Postmodern World”
Authors: Hapke Bruce
Published: April 2011

In his Forum, Kenneth Verosub (Eos, 91(33), 291, doi:10.1029/2010EO330003, 2010) tries to explain the climate denial phenomenon as due to postmodernist misinterpretation of scientific results. Unfortunately, I fear that this is only a minor cause and that the true explanation is much more insidious, with serious ramifications for all scientists, not just climatologists. As documented in several recent publications [e.g., Mayer, 2010], climate scientists are currently bearing the brunt of a deliberate, antiscience, misinformation campaign that is financed by certain fossil fuel companies and propagated by certain conservative radio programs, television organizations, and think tanks. Verosub wonders why no one has offered an explanation for why scientists worldwide are engaged in this supposed hoax. But explanations are frequently offered on conservative talk shows. For example, I found myself listening to The War Room With Quinn and Rose last fall while driving in the Pittsburgh, Pa., area and was appalled by the scenario painted in the show by cohost Jim Quinn. Apparently, all academics are socialists. Further, the Earth is not warming—it has been getting cooler since 1999. Quinn continued with this gem: Climate warming is an international conspiracy, funded by billionaire George Soros, perpetrated by scientists everywhere, and intended to delude governments into spending vast sums of money to counter a non‐existent threat until the governments become bankrupt. Then in the ensuing chaos, socialists can take over and form a world socialist government.
Two Decades of Community Research on Gas in Shallow Marine Sediments
Authors: Leifer Ira , Hovland Martin , Zemskaya Tamara
Published: April 2011

Tenth International Conference on Gas in Marine Sediments; Listvyanka, Russia, 6–12 September 2010; The Tenth International Conference on Gas in Marine Sediments was held near Irkutsk, Russia, and was attended by 120 participants from 19 countries. The GIMS conference series has provided biannual discussions that have knit disparate researchers into a scientific community. The setting was important because the adjacent Lake Baikal contains the only documented freshwater hydrate methane seepage (methane hydrate is a metastable ice at high pressures and low temperatures) due to its great depth (1637 meters). The conference included 72 oral and 47 poster presentations and a day cruise during which gas hydrates were retrieved.
Stefan R. Falke Receives 2010 Charles S. Falkenberg Award
Authors: Hutchinson Charles F. , Meyer Carol B. , Husar Rudolf , Lindsay Francis , Falke Stefan R.
Published: April 2011

Stefan R. Falke received the Charles S. Falkenberg Award at the 2010 AGU Fall Meeting Honors Ceremony, held on 15 December 2010 in San Francisco, Calif. The award honors a “scientist under 45 years of age who has contributed to the quality of life, economic opportunities, and stewardship of the planet through the use of Earth science information and to the public awareness of the importance of understanding our planet.”
Research Spotlight: Rainfall variability increasing in northern Australia
Authors: Tretkoff Ernie
Published: April 2011

Rainfall variability, including the frequency of extreme floods and droughts, is increasing in northeastern Australia, a new study shows. Rainfall in Queensland is variable from year to year, partly due to El Niño–Southern Oscillation (ENSO) events. As massive corals grow, their skeletons create yearly growth patterns, similar to tree rings, and record a wealth of proxy information about the corals' environment over several centuries. Flood events show up in nearshore annually banded coral skeletons as luminescent lines. (Paleoceanography, doi:10.1029/2010PA002050, 2011)
Research Spotlight: Improved model reproduces the 2003 European heat wave
Authors: Schultz Colin
Published: April 2011

In August 2003, record‐breaking temperatures raged across much of Europe. In France, maximum temperatures of 37°C (99°F) persisted for 9 days straight, the longest such stretch since 1873. About 40,000 deaths (14,000 in France alone) were attributed to the extreme heat and low humidity. Various climate conditions must come into alignment to produce extreme weather like the 2003 heat wave, and despite a concerted effort, forecasting models have so far been unable to accurately reproduce the event—including the modern European Centre for Medium‐Range Weather Forecasts (ECMWF) ensemble modeling system for seasonal forecasts, which went into operation in 2007. (Geophysical Research Letters, doi:10.1029/2010GL046455, 2011)
Induction of CD4+CD25+Foxp3− regulatory T cells by Thy‐1 stimulation of CD4+ T cells
Authors: Conrad David M , Coombs Melanie R Power , Furlong Suzanne J , Forward Nicholas A , Hoskin David W
Published: April 2011

Thy‐1 (CD90) on mouse T cells has been reported to have both T‐cell activating and regulatory roles. In this study, we show that monoclonal antibody (mAb)‐mediated crosslinking of Thy‐1 on CD4+ mouse T‐cells‐induced regulatory T (Treg) cells that expressed CD25, CD39 and glucocorticoid‐induced tumor necrosis factor receptor family‐related gene, but not CD73, CD122 or Foxp3. The proliferation of CD4+ Tresponder cells in response to anti‐CD3/anti‐CD28mAb‐coated T‐cell expander beads or syngeneic dendritic cells and soluble anti‐CD3mAb was inhibited by Thy‐1‐induced Treg cells, in spite of elevated IL‐2 levels in the co‐cultures. Interestingly, stimulation with T‐cell expander beads caused Thy‐1‐induced Treg cells to synthesize large amounts of interleukin‐2 (IL‐2). IL‐10 was also elevated in co‐cultures of activated Tresponder cells and Thy‐1‐induced Treg cells. However, mAb‐mediated neutralization of IL‐10 did not restore Tresponder‐cell proliferation to control levels, which excluded IL‐10 as a potential mediator of Thy‐1‐induced Treg‐cell suppressor function. In addition, Thy‐1‐induced Treg cells did not inhibit IL‐2‐dependent proliferation of CTLL‐2 cells, suggesting that IL‐2 receptor signaling remained intact in the presence of Thy‐1‐induced Treg cells. We suggest that Treg cells induced by Thy‐1 ligation in vivo may contribute to the maintenance of T‐cell homeostasis.
Chemical Profiles of Essential Oils and Non-Polar Extractables from Sumac (Rhus spp.)
Authors: Rayne Sierra
Published: April 2011

Sumac is the common name for a genus (Rhus) with >250 individual species of flowering plants in the family Anacardiaceae. These plants are globally distributed in temperate and tropical regions and can grow on marginal lands, making them strong candidates for renewable bioproduct sources. Despite the extensive historical use of some members of Rhus spp. for tannins and other commercial phenolics, little is known about the non-phenolic components of extracts and essentials oils. The current review highlights opportunities available to extend these limited prior studies to other sumac species, and for obtaining value-added compounds to complement already established phenolic extractions in these commercial plant species. To date, a number of individual aldehydes, fatty acids, long chain alcohols, terpenes and terpenoids, and waxes of commercial or bioactive potential in essential oils and non-polar extractables from selected members of the Rhus genera have been identified. Additional studies are needed to broaden the phytochemical database from other sumac species, and to better quantify the potential yields of these valuable compounds from the plants under natural and agriculturally managed conditions.
Identification of target family directed bioisosteric replacements
Authors: Wassermann Anne Mai , Bajorath Jürgen
Published: April 2011

Shown are exemplary replacements of chemical groups that are bioisosteric for individual target families.
Dwelling with Media Stuff: Latencies and Logics of Materiality in Four Australian Homes
Authors: Nansen Bjorn , Arnold Michael , Gibbs Martin , Davis Hilary
Published: April 2011

Extending research into material, media, and cultural geographies of the home, our interest turns to the spatiotemporality of dwelling with information and communication technologies. We pose a number of questions: How do inhabitants and their media stuff adapt to the more rigid physical spaces of a building? How does the building respond to the more rapid changes to dwelling produced by this media stuff? And how are these differing times synchronised? In answer to these questions we present four case studies of homes in Melbourne, Australia, each representative of a particular strategy of synchronisation. They are: the found home, the imagined home, the designed home, and the renovated home. We identify logics informing these homes: the first naturalises the choices made, the second rationalises choices, and the third is one in which dwelling and (re)building are intertwined.
Growth in emission transfers via international trade from 1990 to 2008
Authors: Peters Glen P. , Minx Jan C. , Weber Christopher L. , Edenhofer Ottmar
Published: April 2011

Despite the emergence of regional climate policies, growth in global CO
2
emissions has remained strong. From 1990 to 2008 CO
2
emissions in developed countries (defined as countries with emission-reduction commitments in the Kyoto Protocol, Annex B) have stabilized, but emissions in developing countries (non-Annex B) have doubled. Some studies suggest that the stabilization of emissions in developed countries was partially because of growing imports from developing countries. To quantify the growth in emission transfers via international trade, we developed a trade-linked global database for CO
2
emissions covering 113 countries and 57 economic sectors from 1990 to 2008. We find that the emissions from the production of traded goods and services have increased from 4.3 Gt CO
2
in 1990 (20% of global emissions) to 7.8 Gt CO
2
in 2008 (26%). Most developed countries have increased their consumption-based emissions faster than their territorial emissions, and non–energy-intensive manufacturing had a key role in the emission transfers. The net emission transfers via international trade from developing to developed countries increased from 0.4 Gt CO
2
in 1990 to 1.6 Gt CO
2
in 2008, which exceeds the Kyoto Protocol emission reductions. Our results indicate that international trade is a significant factor in explaining the change in emissions in many countries, from both a production and consumption perspective. We suggest that countries monitor emission transfers via international trade, in addition to territorial emissions, to ensure progress toward stabilization of global greenhouse gas emissions.
Cytokine signaling through the JAK/STAT pathway is required for long-term memory in
Drosophila
Authors: Copf Tijana , Goguel Valérie , Lampin-Saint-Amaux Aurélie , Scaplehorn Niki , Preat Thomas
Published: April 2011

Cytokine signaling through the JAK/STAT pathway regulates multiple cellular responses, including cell survival, differentiation, and motility. Although significant attention has been focused on the role of cytokines during inflammation and immunity, it has become clear that they are also implicated in normal brain function. However, because of the large number of different genes encoding cytokines and their receptors in mammals, the precise role of cytokines in brain physiology has been difficult to decipher. Here, we took advantage of
Drosophila
’s being a genetically simpler model system to address the function of cytokines in memory formation. Expression analysis showed that the cytokine Upd is enriched in the
Drosophila
memory center, the mushroom bodies. Using tissue- and adult-specific expression of RNAi and dominant-negative proteins, we show that not only is Upd specifically required in the mushroom bodies for olfactory aversive long-term memory but the Upd receptor Dome, as well as the
Drosophila
JAK and STAT homologs Hop and Stat92E, are also required, while being dispensable for less stable memory forms.
Spinster is required for autophagic lysosome reformation and mTOR reactivation following starvation
Authors: Rong Yueguang , McPhee Christina K. , Deng Shuangshen , Huang Lei , Chen Lilian , Liu Mei , Tracy Kirsten , Baehrecke Eric H. , Yu Li , Lenardo Michael J.
Published: April 2011

Autophagy is a conserved cellular process to degrade and recycle cytoplasmic components. During autophagy, lysosomes fuse with an autophagosome to form an autolysosome. Sequestered components are degraded by lysosomal hydrolases and presumably released into the cytosol by lysosomal efflux permeases. Following starvation-induced autophagy, lysosome homeostasis is restored by autophagic lysosome reformation (ALR) requiring activation of the “target of rapamycin” (TOR) kinase. Spinster (Spin) encodes a putative lysosomal efflux permease with the hallmarks of a sugar transporter.
Drosophila spin
mutants accumulate lysosomal carbohydrates and enlarged lysosomes. Here we show that defects in
spin
lead to the accumulation of enlarged autolysosomes. We find that
spin
is essential for mTOR reactivation and lysosome reformation following prolonged starvation. Further, we demonstrate that the sugar transporter activity of Spin is essential for ALR.
Implicit race attitudes predict trustworthiness judgments and economic trust decisions
Authors: Stanley Damian A. , Sokol-Hessner Peter , Banaji Mahzarin R. , Phelps Elizabeth A.
Published: April 2011

Trust lies at the heart of every social interaction. Each day we face decisions in which we must accurately assess another individual's trustworthiness or risk suffering very real consequences. In a global marketplace of increasing heterogeneity with respect to nationality, race, and multiple other social categories, it is of great value to understand how implicitly held attitudes about group membership may support or undermine social trust and thereby implicitly shape the decisions we make. Recent behavioral and neuroimaging work suggests that a common mechanism may underlie the expression of implicit race bias and evaluations of trustworthiness, although no direct evidence of a connection exists. In two behavioral studies, we investigated the relationship between implicit race attitude (as measured by the Implicit Association Test) and social trust. We demonstrate that race disparity in both an individual's explicit evaluations of trustworthiness and, more crucially, his or her economic decisions to trust is predicted by that person's bias in implicit race attitude. Importantly, this relationship is robust and is independent of the individual's bias in explicit race attitude. These data demonstrate that the extent to which an individual invests in and trusts others with different racial backgrounds is related to the magnitude of that individual's implicit race bias. The core dimension of social trust can be shaped, to some degree, by attitudes that reside outside conscious awareness and intention.
Nucleosome positioning in a model of active chromatin remodeling enzymes
Authors: Padinhateeri Ranjith , Marko John F.
Published: April 2011

Accounting for enzyme-mediated active sliding, disassembly, and sequence-dependent positioning of nucleosomes, we simulate nucleosome occupancy over cell-cycle-scale times using a stochastic kinetic model. We show that ATP-dependent active nucleosome sliding and nucleosome removal processes are essential to obtain in vivo-like nucleosome positioning. While active sliding leads to dense nucleosome filling, sliding events alone cannot ensure sequence-dependent nucleosome positioning: Active nucleosome removal is the crucial remodeling event that drives positioning. We also show that remodeling activity changes nucleosome dynamics from glassy to liquid-like, and that remodeling dramatically influences exposure dynamics of promoter regions.
Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41)
Authors: Kimura Ikuo , Inoue Daisuke , Maeda Takeshi , Hara Takafumi , Ichimura Atsuhiko , Miyauchi Satoshi , Kobayashi Makio , Hirasawa Akira , Tsujimoto Gozoh
Published: April 2011

The maintenance of energy homeostasis is essential for life, and its dysregulation leads to a variety of metabolic disorders. Under a fed condition, mammals use glucose as the main metabolic fuel, and short-chain fatty acids (SCFAs) produced by the colonic bacterial fermentation of dietary fiber also contribute a significant proportion of daily energy requirement. Under ketogenic conditions such as starvation and diabetes, ketone bodies produced in the liver from fatty acids are used as the main energy sources. To balance energy intake, dietary excess and starvation trigger an increase or a decrease in energy expenditure, respectively, by regulating the activity of the sympathetic nervous system (SNS). The regulation of metabolic homeostasis by glucose is well recognized; however, the roles of SCFAs and ketone bodies in maintaining energy balance remain unclear. Here, we show that SCFAs and ketone bodies directly regulate SNS activity via GPR41, a Gi/o protein-coupled receptor for SCFAs, at the level of the sympathetic ganglion. GPR41 was most abundantly expressed in sympathetic ganglia in mouse and humans. SCFA propionate promoted sympathetic outflow via GPR41. On the other hand, a ketone body, β-hydroxybutyrate, produced during starvation or diabetes, suppressed SNS activity by antagonizing GPR41. Pharmacological and siRNA experiments indicated that GPR41-mediated activation of sympathetic neurons involves Gβγ-PLCβ-MAPK signaling. Sympathetic regulation by SCFAs and ketone bodies correlated well with their respective effects on energy consumption. These findings establish that SCFAs and ketone bodies directly regulate GPR41-mediated SNS activity and thereby control body energy expenditure in maintaining metabolic homeostasis.
Autophagosome targeting and membrane curvature sensing by Barkor/Atg14(L)
Authors: Fan Weiliang , Nassiri Ashley , Zhong Qing
Published: April 2011

The class III phosphatidylinositol 3-kinase (PI3KC3) is crucial for autophagosome biogenesis. It has been long speculated to nucleate the autophagosome membrane, but the biochemical mechanism of such nucleation activity remains unsolved. We recently identified Barkor/Atg14(L) as the targeting factor for PI3KC3 to autophagosome membrane. Here, we show that we have characterized the region of Barkor/Atg14(L) required for autophagosome targeting and identified the BATS [Barkor/Atg14(L) autophagosome targeting sequence] domain at the carboxyl terminus of Barkor. Bioinformatics and mutagenesis analyses revealed that the BATS domain binds to autophagosome membrane via the hydrophobic surface of an intrinsic amphipathic alpha helix. BATS puncta overlap with Atg16 and LC3, and partially with DFCP1, in a stress-inducible manner. Ectopically expressed BATS accumulates on highly curved tubules that likely represent intermediate autophagic structures. PI3KC3 recruitment and autophagy stimulation by Barkor/Atg14(L) require the BATS domain. Furthermore, our biochemical analyses indicate that the BATS domain directly binds to the membrane, and it favors membrane composed of phosphatidylinositol 3-phosphate [PtdIns(3)P] and phosphatidylinositol 4,5-biphosphate [PtdIns(4,5)P2]. By binding preferentially to curved membranes incorporated with PtdIns(3)P but not PtdIns(4,5)P2, the BATS domain is capable of sensing membrane curvature. Thus, we propose a novel model of PI3KC3 autophagosome membrane nucleation in which its autophagosome-specific adaptor, Barkor, accumulates on highly curved PtdIns(3)P enriched autophagic membrane via its BATS domain to sense and maintain membrane curvature.
Control of peptide nanotube diameter by chemical modifications of an aromatic residue involved in a single close contact
Authors: Tarabout Christophe , Roux Stéphane , Gobeaux Frédéric , Fay Nicolas , Pouget Emilie , Meriadec Cristelle , Ligeti Melinda , Thomas Daniel , IJsselstijn Maarten , Besselievre François , Buisson David-Alexandre , Verbavatz Jean-Marc , Petitjean Michel , Valéry Céline , Perrin Lionel , Rousseau Bernard , Artzner Franck , Paternostre Maité , Cintrat Jean-Christophe
Published: April 2011

Supramolecular self-assembly is an attractive pathway for bottom-up synthesis of novel nanomaterials. In particular, this approach allows the spontaneous formation of structures of well-defined shapes and monodisperse characteristic sizes. Because nanotechnology mainly relies on size-dependent physical phenomena, the control of monodispersity is required, but the possibility of tuning the size is also essential. For self-assembling systems, shape, size, and monodispersity are mainly settled by the chemical structure of the building block. Attempts to change the size notably by chemical modification usually end up with the loss of self-assembly. Here, we generated a library of 17 peptides forming nanotubes of monodisperse diameter ranging from 10 to 36 nm. A structural model taking into account close contacts explains how a modification of a few Å of a single aromatic residue induces a fourfold increase in nanotube diameter. The application of such a strategy is demonstrated by the formation of silica nanotubes of various diameters.
ECM components guide IL-10 producing regulatory T-cell (TR1) induction from effector memory T-cell precursors
Authors: Bollyky Paul L. , Wu Rebecca P. , Falk Ben A. , Lord James D. , Long S. Alice , Preisinger Anton , Teng Brandon , Holt Gregory E. , Standifer Nathan E. , Braun Kathleen R. , Xie Cindy Fang , Samuels Peter L. , Vernon Robert B. , Gebe John A. , Wight Thomas N. , Nepom Gerald T.
Published: April 2011

We describe a role for ECM as a biosensor for inflammatory microenvironments that plays a critical role in peripheral immune tolerance. We show that hyaluronan (HA) promotes induction of Foxp3- IL-10–producing regulatory T cells (TR1) from conventional T-cell precursors in both murine and human systems. This is, to our knowledge, the first description of an ECM component inducing regulatory T cells. Intact HA, characteristic of healing tissues, promotes induction of TR1 capable of abrogating disease in an IL-10–dependent mouse colitis model whereas fragmentary HA, typical of inflamed tissues, does not, indicating a decisive role for tissue integrity in this system. The TR1 precursor cells in this system are CD4+CD62L−FoxP3−, suggesting that effector memory cells assume a regulatory phenotype when they encounter their cognate antigen in the context of intact HA. Matrix integrity cues might thereby play a central role in maintaining peripheral tolerance. This TR1 induction is mediated by CD44 cross-linking and signaling through p38 and ERK1/2. This induction is suppressed, also in a CD44-dependent manner, by osteopontin, a component of chronically inflamed ECM, indicating that CD44 signaling serves as a nexus for fate decisions regarding TR1 induction. Finally, we demonstrate that TR1 induction signals can be recapitulated using synthetic matrices. These results reveal important roles for the matrix microenvironment in immune regulation and suggest unique strategies for immunomodulation.
Poly(A)-binding proteins are functionally distinct and have essential roles during vertebrate development
Authors: Gorgoni Barbara , Richardson William A. , Burgess Hannah M. , Anderson Ross C. , Wilkie Gavin S. , Gautier Philippe , Martins Joao P. Sousa , Brook Matthew , Sheets Michael D. , Gray Nicola K.
Published: April 2011

Translational control of many mRNAs in developing metazoan embryos is achieved by alterations in their poly(A) tail length. A family of cytoplasmic poly(A)-binding proteins (PABPs) bind the poly(A) tail and can regulate mRNA translation and stability. However, despite the extensive biochemical characterization of one family member (PABP1), surprisingly little is known about their in vivo roles or functional relatedness. Because no information is available in vertebrates, we address their biological roles, establishing that each of the cytoplasmic PABPs conserved in
Xenopus laevis
[PABP1, embryonic PABP (ePABP), and PABP4] is essential for normal development. Morpholino-mediated knockdown of PABP1 or ePABP causes both anterior and posterior phenotypes and embryonic lethality. In contrast, depletion of PABP4 results mainly in anterior defects and lethality at later stages. Unexpectedly, cross-rescue experiments reveal that neither ePABP nor PABP4 can fully rescue PABP1 depletion, establishing that PABPs have distinct functions. Comparative analysis of the uncharacterized PABP4 with PABP1 and ePABP shows that it shares a mechanistically conserved core role in promoting global translation. Consistent with this analysis, each morphant displays protein synthesis defects, suggesting that their roles in mRNA-specific translational regulation and/or mRNA decay, rather than global translation, underlie the functional differences between PABPs. Domain-swap experiments reveal that the basis of the functional specificity is complex, involving multiple domains of PABPs, and is conferred, at least in part, by protein–protein interactions.
Evolutionary dynamics of bacteria in a human host environment
Authors: Yang Lei , Jelsbak Lars , Marvig Rasmus Lykke , Damkiær Søren , Workman Christopher T. , Rau Martin Holm , Hansen Susse Kirkelund , Folkesson Anders , Johansen Helle Krogh , Ciofu Oana , Høiby Niels , Sommer Morten O. A. , Molin Søren
Published: April 2011

Laboratory evolution experiments have led to important findings relating organism adaptation and genomic evolution. However, continuous monitoring of long-term evolution has been lacking for natural systems, limiting our understanding of these processes in situ. Here we characterize the evolutionary dynamics of a lineage of a clinically important opportunistic bacterial pathogen,Pseudomonas aeruginosa, as it adapts to the airways of several individual cystic fibrosis patients over 200,000 bacterial generations, and provide estimates of mutation rates of bacteria in a natural environment. In contrast to predictions based on in vitro evolution experiments, we document limited diversification of the evolving lineage despite a highly structured and complex host environment. Notably, the lineage went through an initial period of rapid adaptation caused by a small number of mutations with pleiotropic effects, followed by a period of genetic drift with limited phenotypic change and a genomic signature of negative selection, suggesting that the evolving lineage has reached a major adaptive peak in the fitness landscape. This contrasts with previous findings of continued positive selection from long-term in vitro evolution experiments. The evolved phenotype of the infecting bacteria further suggests that the opportunistic pathogen has transitioned to become a primary pathogen for cystic fibrosis patients.
Chikungunya virus emergence is constrained in Asia by lineage-specific adaptive landscapes
Authors: Tsetsarkin Konstantin A. , Chen Rubing , Leal Grace , Forrester Naomi , Higgs Stephen , Huang Jing , Weaver Scott C.
Published: April 2011

Adaptation of RNA viruses to a new host or vector species often results in emergence of new viral lineages. However, lineage-specific restrictions on the adaptive processes remain largely unexplored. Recently, a Chikungunya virus (CHIKV) lineage of African origin emerged to cause major epidemics of severe, persistent, debilitating arthralgia in Africa and Asia. Surprisingly, this new lineage is actively replacing endemic strains in Southeast Asia that have been circulating there for 60 y. This replacement process is associated with adaptation of the invasive CHIKV strains to an atypical vector, the
Aedes albopictus
mosquito that is ubiquitously distributed in the region. Here we demonstrate that lineage-specific epistatic interactions between substitutions at amino acid positions 226 and 98 of the E1 envelope glycoprotein, the latter of which likely resulted from a founder effect, have for 60 y restricted the ability of endemic Asian CHIKV strains to adapt to this new vector. This adaptive constraint appears to be allowing invasion of the unoccupied vector niche by
Ae. albopictus
-adapted African strains. These results underscore how different adaptive landscapes occupied by closely related viral genotypes can profoundly affect the outcome of viral evolution and disease emergence.
Structural mechanism of the ATP-induced dissociation of rigor myosin from actin
Authors: Kühner Sebastian , Fischer Stefan
Published: April 2011

Myosin is a true nanomachine, which produces mechanical force from ATP hydrolysis by cyclically interacting with actin filaments in a four-step cycle. The principle underlying each step is that structural changes in separate regions of the protein must be mechanically coupled. The step in which myosin dissociates from tightly bound actin (the rigor state) is triggered by the 30 Å distant binding of ATP. Large conformational differences between the crystal structures make it difficult to perceive the coupling mechanism. Energetically accessible transition pathways computed at atomic detail reveal a simple coupling mechanism for the reciprocal binding of ATP and actin.
Facultative role for T cells in extrafollicular Toll-like receptor-dependent autoreactive B-cell responses in vivo
Authors: Sweet Rebecca A. , Ols Michelle L. , Cullen Jaime L. , Milam Ashley Viehmann , Yagita Hideo , Shlomchik Mark J.
Published: April 2011

Extrafollicular (EF) B-cell responses are increasingly being recognized as an alternative pathway of B-cell activation, particularly in autoimmunity. Critical cellular interactions required for the EF B-cell response are unclear. A key question in autoimmunity, in which Toll-like receptor (TLR) signals are costimulatory and could be sufficient for B-cell activation, is whether T cells are required for the response. This is pivotal, because autoreactive B cells are considered antigen-presenting cells for autoreactive T cells, but where such interactions occur has not been identified. Here, using AM14 site-directed transgenic rheumatoid factor (RF) mice, we report that B cells can be activated, differentiate, and isotype-switch independent of antigen-specific T-cell help, αβ T cells, CD40L signaling, and IL-21 signaling to B cells. However, T cells do dramatically enhance the response, and this occurs via CD40L and IL-21 signals. Surprisingly, the response is completely inducible T-cell costimulator ligand independent. These results establish that, although not required, T cells substantially amplify EF autoantibody production and thereby implicate T-independent autoreactive B cells as a potential vector for breaking T-cell tolerance. We suggest that these findings explain why autoreactivity first focuses on self-components for which B cells carry TLR ligands, because these will uniquely be able to activate B cells independently of T cells, with subsequent T–B interactions activating autoreactive T cells, resulting in chronic autoimmunity.
Recent progress on symplectic embedding problems in four dimensions
Authors: Hutchings Michael
Published: April 2011

We survey some recent progress on understanding when one four-dimensional symplectic manifold can be symplectically embedded into another. In 2010, McDuff established a number-theoretic criterion for the existence of a symplectic embedding of one four-dimensional ellipsoid into another. This result is related to previously known criteria for when a disjoint union of balls can be symplectically embedded into a ball. Numerical invariants defined using embedded contact homology give general obstructions to symplectic embeddings in four dimensions which turn out to be sharp in the above cases.
Accuracy and reliability of forensic latent fingerprint decisions
Authors: Ulery Bradford T. , Hicklin R. Austin , Buscaglia JoAnn , Roberts Maria Antonia
Published: April 2011

The interpretation of forensic fingerprint evidence relies on the expertise of latent print examiners. The National Research Council of the National Academies and the legal and forensic sciences communities have called for research to measure the accuracy and reliability of latent print examiners’ decisions, a challenging and complex problem in need of systematic analysis. Our research is focused on the development of empirical approaches to studying this problem. Here, we report on the first large-scale study of the accuracy and reliability of latent print examiners’ decisions, in which 169 latent print examiners each compared approximately 100 pairs of latent and exemplar fingerprints from a pool of 744 pairs. The fingerprints were selected to include a range of attributes and quality encountered in forensic casework, and to be comparable to searches of an automated fingerprint identification system containing more than 58 million subjects. This study evaluated examiners on key decision points in the fingerprint examination process; procedures used operationally include additional safeguards designed to minimize errors. Five examiners made false positive errors for an overall false positive rate of 0.1%. Eighty-five percent of examiners made at least one false negative error for an overall false negative rate of 7.5%. Independent examination of the same comparisons by different participants (analogous to blind verification) was found to detect all false positive errors and the majority of false negative errors in this study. Examiners frequently differed on whether fingerprints were suitable for reaching a conclusion.
Structural basis of differential ligand recognition by two classes of bis-(3′-5′)-cyclic dimeric guanosine monophosphate-binding riboswitches
Authors: Smith Kathryn D. , Shanahan Carly A. , Moore Emily L. , Simon Aline C. , Strobel Scott A.
Published: April 2011

The bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) signaling pathway regulates biofilm formation, virulence, and other processes in many bacterial species and is critical for their survival. Two classes of c-di-GMP-binding riboswitches have been discovered that bind this second messenger with high affinity and regulate diverse downstream genes, underscoring the importance of RNA receptors in this pathway. We have solved the structure of a c-di-GMP-II riboswitch, which reveals that the ligand is bound as part of a triplex formed with a pseudoknot. The structure also shows that the guanine bases of c-di-GMP are recognized through noncanonical pairings and that the phosphodiester backbone is not contacted by the RNA. Recognition is quite different from that observed in the c-di-GMP-I riboswitch, demonstrating that at least two independent solutions for RNA second messenger binding have evolved. We exploited these differences to design a c-di-GMP analog that selectively binds the c-di-GMP-II aptamer over the c-di-GMP-I RNA. There are several bacterial species that contain both types of riboswitches, and this approach holds promise as an important tool for targeting one riboswitch, and thus one gene, over another in a selective fashion.
Identification of key factors that reduce the variability of the single photon response
Authors: Caruso Giovanni , Bisegna Paolo , Andreucci Daniele , Lenoci Leonardo , Gurevich Vsevolod V. , Hamm Heidi E. , DiBenedetto Emmanuele
Published: April 2011

Rod photoreceptors mediate vision in dim light. Their biological function is to discriminate between distinct, very low levels of illumination, i.e., they serve as reliable photon counters. This role requires high reproducibility of the response to a particular number of photons. Indeed, single photon responses demonstrate unexpected low variability, despite the stochastic nature of the individual steps in the transduction cascade. We analyzed individual system mechanisms to identify their contribution to variability suppression. These include:(i)cooperativity of the regulation of the second messengers;(ii)diffusion of cGMP and Ca2+in the cytoplasm; and(iii)the effect of highly localized cGMP hydrolysis by activated phosphodiesterase resulting in local saturation. We find that(i)the nonlinear relationships between second messengers and current at the plasma membrane, and the cGMP hydrolysis saturation effects, play a major role in stabilizing the system;(ii)the presence of a physical space where the second messengers move by Brownian motion contributes to stabilization of the photoresponse; and(iii)keeping Ca2+at its dark level has only a minor effect on the variability of the system. The effects of diffusion, nonlinearity, and saturation synergize in reducing variability, supporting the notion that the observed high fidelity of the photoresponse is the result of global system function of phototransduction.
Uncovering space-independent communities in spatial networks
Authors: Expert Paul , Evans Tim S. , Blondel Vincent D. , Lambiotte Renaud
Published: April 2011

Many complex systems are organized in the form of a network embedded in space. Important examples include the physical Internet infrastucture, road networks, flight connections, brain functional networks, and social networks. The effect of space on network topology has recently come under the spotlight because of the emergence of pervasive technologies based on geolocalization, which constantly fill databases with people’s movements and thus reveal their trajectories and spatial behavior. Extracting patterns and regularities from the resulting massive amount of human mobility data requires the development of appropriate tools for uncovering information in spatially embedded networks. In contrast with most works that tend to apply standard network metrics to any type of network, we argue in this paper for a careful treatment of the constraints imposed by space on network topology. In particular, we focus on the problem of community detection and propose a modularity function adapted to spatial networks. We show that it is possible to factor out the effect of space in order to reveal more clearly hidden structural similarities between the nodes. Methods are tested on a large mobile phone network and computer-generated benchmarks where the effect of space has been incorporated.