bluuebunny/crossref_metadata_2025 huggingface dataset:
Afghanistan's Kuchi Pastoralists: Change and Adaptation
Authors: De Weijer Frauke
Published: July 2008

Afghanistan's nomadic peoples are now either migratory and livestockdependent pastoralists or recently settled but formerly migratory pastoralists, who still hold on to the cultural identity and refer to themselves as kuchi. Radical changes in both summer and winter pastures have taken place over the last centuries, and currently the pastoralists' access to the summer pastures in the central highlands is compromised. Customary mechanisms had come into existence over the last century, and still function in certain areas. However, in large areas, and in particular those where issues of grazing rights have become heavily politicized and strongly associated with ethnic identity, there is a high level of conflict over these user's rights, which have often proven to be inflammable. There are large differences in migration patterns and livelihood strategies between the pastoralists of the different regions. Income derived from livestock production is often supplemented by other income sources, like harvesting and casual labour, but also through the purchase of agricultural land. In recent years, an increased diversification of household income and a move towards a more semi-migratory lifestyle has taken place. Pastoralists still do make an important contribution to Afghanistan's national economy, as they did in the past (35 per cent of all exports were from livestock products). Recent estimates indicate that there around 2.5 million kuchi, of which 1.5 million are still migratory pastoralists and one million are currently not migratory and are former pastoralists. The drought of 1999 to 2004 severely affected pastoralist livelihoods and livestock numbers plummeted. Estimates on livestock numbers indicate that in the north they started reaching their pre-war levels, whereas the south and the east are still lagging behind. It has been estimated that kuchi own around 30 to 50 per cent of the national herd.
Acute heart failure in patients with acute myocardial infarction treated with primary percutaneous coronary intervention☆
Authors: Santoro Giovanni M. , Carrabba Nazario , Migliorini Angela , Parodi Guido , Valenti Renato
Published: July 2008

Background:

Scanty data exist about the relation between acute heart failure (HF) and acute myocardial infarction (AMI).

Aim:

To assess the impact of HF on outcome in AMI patients treated with primary percutaneous coronary intervention (PCI).

Methods and results:

Out of 2089 AMI patients, 82% did not present HF, 17% presented HF on admission and 1% developed HF after hospitalisation. Predictors of HF on admission were age, diabetes, prior MI, time delay to admission, anterior location, and TIMI grade 0–1 in the culprit vessel. Predictors of HF during hospitalisation were age and peak creatine kinase. The 1‐ and 6‐month mortalities were 1.1% and 2.2%, 8% and 12%, 26% and 33% in patients without HF, with HF on admission and after hospitalisation, respectively. The risk of death was higher in patients with HF than in patients without HF (HR 3.47), as well as in patients with HF after admission (HR 5.19) than in patients with HF on admission (HR 2.44).

Conclusions:

In a primary PCI setting, the incidence of HF on hospital admission remains high, but mortality is lower when compared with historical patient series. Primary PCI may prevent the development of HF during hospitalisation; however, when HF develops, the prognosis remains severe.
Color discrimination ellipses of trichromats measured with transient and steady state visual evoked potentials
Authors: GOMES BRUNO D. , SOUZA GIVAGO S. , LIMA MONICA G. , RODRIGUES ANDERSON R. , SAITO CÉZAR A. , FILHO MANOEL DA SILVA , SILVEIRA LUIZ CARLOS L.
Published: July 2008

The purpose of this work is to investigate the use of different forms of visual evoked potentials (VEPs) to measure color discrimination thresholds and to plot color discrimination ellipses (MacAdam, 1942). Five normal trichromats (24.5 ± 2.6 years-old) were monocularly tested. Stimuli consisted of sinusoidal isoluminant chromatic gratings made from chromaticity pairs located along four different color directions radiating from one reference point of the CIE 1976 chromaticity diagram (u′ = 0.225;v′ = 0.415). Heterochromatic flicker photometry (HFP) was used to obtain the isoluminance condition for every subject and for all chromaticity pairs. VEPs were elicited using two cycles per degree grating stimuli at three different temporal configurations: transient, onset (300 ms)/offset (700 ms), 1 Hz fundamental frequency; steady-state, onset (50 ms)/offset (50 ms), 10 Hz fundamental frequency; and steady-state pattern reversal at 5 Hz fundamental frequency (10 Hz phase reversal). VEP amplitude was measured using transient VEP N1-P1 components and steady state VEP first (10 Hz) and second (20 Hz) harmonics. VEP amplitude was plotted as a function of chromatic distance in the CIE 1976 color space and the data points were extrapolated to zero amplitude level to obtain chromatic discrimination thresholds. The results were compared with psychophysical measurements performed using the same stimulus configurations and with the pseudoisochromatic method of Mollon-Reffin (one-way ANOVA). For all subjects and all stimulation methods, the ellipses showed small sizes, low ellipticities, and were vertically oriented. Despite some consistent differences in the results obtained with different procedures, there was no statistical difference between ellipses obtained electrophysiologically and psychophysically. For steady state VEPs, ellipses obtained from second harmonic amplitudes were larger and more elongated in the tritan direction than those obtained with first harmonic amplitudes.
Very-long-term chromatic adaptation: Test of gain theory and a new method
Authors: BELMORE SUZANNE C. , SHEVELL STEVEN K.
Published: July 2008

This research had two goals. First, a new method of very-long-term chromatic adaptation was compared to an older method of long-wavelength ambient illumination. In the new method, the observer viewed for 1 h per day for 12 or 14 days a CRT screen composed of oriented lines that appeared red. One observer also replicated a previous procedure (Neitz et al., 2002) in which she was exposed to long-wavelength room illumination for 4 h per day for 14 days. For both methods, equilibrium yellow was measured each day about 20 h after the end of the adaptation period. Both methods of very-long-term chromatic adaptation gave similar results. Second, shifts in equilibrium yellow were measured over a 30:1 range of light levels to determine if changes in color percepts were explained solely by a gain change in cone sensitivities (von Kries coefficient law). The magnitude of shift of equilibrium yellow depended on the level of the test light, which was not consistent with a gain theory of very-long-term chromatic adaptation.
Irreversible color vision losses in patients with chronic mercury vapor intoxication
Authors: FEITOSA-SANTANA CLÁUDIA , BARBONI MIRELLA T.S. , OIWA NESTOR N. , PARAMEI GALINA V. , SIMÕES ANA LUISA A.C. , COSTA MARCELO F. DA , SILVEIRA LUIZ CARLOS L. , VENTURA DORA F.
Published: July 2008

This longitudinal study addresses the reversibility of color vision losses in subjects who had been occupationally exposed to mercury vapor. Color discrimination was assessed in 20 Hg-exposed patients (mean age = 42.4 ± 6.5 years; 6 females and 14 males) with exposure to Hg vapor during 10.5 ± 5.3 years and away from the work place (relative to 2002) for 6.8 ± 4.2 years. During the Hg exposure or up to one year after ceasing it, mean urinary Hg concentration was 47 ± 35.4 μg/g creatinine. There was no information on Hg urinary concentration at the time of the first tests, in 2002 (Ventura et al., 2005), but at the time of the follow-up tests, in 2005, this value was 1.4 ± 1.4 μg/g creatinine for patients compared with 0.5 ± 0.5 μg/g creatinine for controls (different group from the one in Ventura et al. (2005)). Color vision was monocularly assessed using the Cambridge Colour Test (CCT). Hg-exposed patients had significantly worse color discrimination (p < 0.02) than controls, as evaluated by the size of MacAdam's color discrimination ellipses and color discrimination thresholds along protan, deutan, and tritan confusion axes. There were no significant differences between the results of the study in Ventura et al. (2005) and in the present follow-up measurements, in 2005, except for worsening of the tritan thresholds in the best eye in 2005. Both chromatic systems, blue-yellow and red-green, were affected in the first evaluation (Ventura et al., 2005) and remained impaired in the follow-up testing, in 2005. These findings indicate that following a long-term occupational exposure to Hg vapor, even several years away from the source of intoxication, color vision impairment remains irreversible.
Structural and tectonic evolution of western Cuba fold and thrust belt
Authors: Saura Eduard , Vergés Jaume , Brown Dennis , Lukito Pujianto , Soriano Sofía , Torrescusa Susana , García Rolando , Sánchez Jorge R. , Sosa Carlos , Tenreyro Rafael
Published: July 2008

We present balanced and restored cross sections across the western Cuba fold and thrust belt to illustrate its structure and tectonic evolution, based on the interpretation of multichannel seismic profiles, field data and balancing techniques. The NNW–SSE trending Soroa cross section intersects, from south to north, (1) the Los Palacios Basin, (2) the Sierra del Rosario antiformal stack, (3) the Bahía Honda thrust unit, (4) the frontal ∼3‐km‐thick imbricated thrust sheets, and (5) the foredeep basin. At depth, a duplex that links the Sierra del Rosario unit and the frontal imbricates is defined using the thickness of the cover thrust sheets of the imbricated North American margin. The minimum calculated shortening is of 130 km in a SSE or south direction to fit large‐scale plate tectonic reconstructions. However, a more allochthonous alternative using thinner cover sequences is also discussed, which restores the Bahía Honda unit 220 km to the south of its present position. Syntectonic deposits in combination with a forward kinematic model provide a good constraint for the tectonic evolution of the orogen. The internally deformed Bahía Honda unit overthrusted the North America margin cover successions during Danian and Selandian times (∼65.5–60 Ma), before the stacking of these cover rocks during Selandian and Thanetian times (∼60–56 Ma). The growth of a large antiformal stack beneath the Sierra del Rosario occurred at early middle Eocene (∼56–45 Ma), generating about 4 km of structural relief between the paleoisland of Cuba and the synorogenic seafloor before the final infill of the foredeep.
Ice at Mars lander site
Authors: Showstack Randy
Published: July 2008

Eight dice‐sized bits of ice vanished within 4 days from a trench dug on Mars by the robotic arm on NASA's Phoenix lander, confirming what scientists suspected the material was. “It must be ice,” said mission principal investigator Peter Smith of the University of Arizona, Tucson. “These little clumps completely disappearing over the course of a few days: that is perfect evidence that it's ice. There had been some question whether the bright material was salt. Salt can't do that,” he said.
Physics and Chemistry, and the Archives of Snow and Firn: Workshop on the Microstructure and Properties of Firn; Hanover, New Hampshire, 10–11 March 2008
Authors: Baker Ian , Albert Mary R.
Published: July 2008

A workshop was held at Dartmouth College to share recent international developments and discuss future directions for research on relationships between the microstructure and the physical and chemical properties of snow and firn. Firn is snow that has remained on the ground for more than 1 year, during which time it may or may not have experienced some degree of wetting or melting. In the cold interiors of the Greenland and Antarctic ice sheets, firn starts on the surface as snow and remains frozen and cold through subsequent snowfalls over many decades, until it becomes compacted into ice, some 80–120 meters deep in the ice sheet.
Climate Change: A Multidisciplinary Approach, Second Edition
Authors: Kirk‐Davidoff Daniel
Published: July 2008

William Burroughs, who died in November 2007, was a wonderfully clear and evocative writer. Chapter 3 of his last work, Climate Change: A Multidisciplinary Approach, begins with the loveliest four‐paragraph description of the general circulation of the Earth's atmosphere I have ever encountered. His writing also shines in his descriptions of the climate record of the past few thousand years, and in his introduction to the measurement of climate change. Unfortunately, the book is marred by inconsistencies in its treatment of climate dynamics, as well as by a number of idiosyncratic choices of emphasis that detract from the book's quality as a general introduction to the science of climate change.
Remote Sensing of Sea Ice in the Northern Sea Route: Studies and Applications
Authors: Barry Roger G.
Published: July 2008

Given the rapid changes that are under way in Arctic sea ice extent, Remote Sensing of Sea Ice in the Northern Sea Route is a timely work. The Northern Sea Route (NSR), along the Arctic coast of Russia, has a long history, dating back to 1932, when the Soviet Union established the NSR administration to develop hydrometeorological services. Shipping along the sea route peaked in the 1980s, but there is renewed interest associated with a lengthening ice‐free season and mineral exploitation. Since July 1991, the NSR has been open to all merchant vessels.
On the correlation between ice water content and ice crystal size and its application to radiative transfer and general circulation models
Authors: Liou K. N. , Gu Y. , Yue Q. , McFarguhar G.
Published: July 2008

We performed correlation analysis involving ice water content (IWC) and mean effective ice crystal size (De) intended for application to climate models. For this purpose, ice crystal size distributions obtained from in situ measurements conducted from numerous field campaigns in the tropics, midlatitude, and Arctic regions were used and we show that IWC and De are well‐correlated in this regional division. Including temperature classification in midlatitude cases increases this correlation. We applied the correlation results to cloud radiative forcing calculations in terms of IWC, in which De is expressed as a baseline mean and deviation from uncertainty in small ice crystal measurements. The latter deviates from the mean by less than 2 W/m2 in net radiative forcing. Using the correlation results, simulations from the UCLA GCM showed substantial regional deviations in OLR and precipitation patterns from assuming a constant De.
Interannual memory effects for spring NDVI in semi‐arid South Africa
Authors: Richard Yves , Martiny Nadège , Fauchereau Nicolas , Reason Chris , Rouault Mathieu , Vigaud Nicolas , Tracol Yann
Published: July 2008

Almost 20 years of Normalized Difference Vegetative Index (NDVI) and precipitation (PPT) data are analysed to better understand the interannual memory effects on vegetation dynamics observed at regional scales in Southern Africa (SA). The study focuses on a semi‐arid region (25°S–31°S; 21°E–26°E) during the austral early summer (September–December). The memory effects are examined using simple statistical approaches (linear correlations and regressions) which require the definition of an early summer vegetation predictand (December NDVI minus September NDVI) and a consistent set of potential predictors (rainfall amount, number of rainy days, rainfall intensity, NDVI and Rain‐Use‐Efficiency) considered with 4 to 15‐month time‐lag. An analysis over six SA sub‐regions, corresponding to the six major land‐cover types of the area reveals two distinct memory effects. A “negative” memory effect (with both rainfall and vegetation) is detected at 7 to 10‐month time‐lag while a “positive” memory effect (with vegetation only) is observed at 12 to 14‐month time‐lag. These results suggest that interannual memory effects in early summer vegetation dynamics of semi‐arid South Africa may preferably be driven by biological rather than hydrological mechanisms.
Association of Antarctic polar stratospheric cloud formation on tropospheric cloud systems
Authors: Wang Zhien , Stephens Graeme , Deshler Terry , Trepte Charles , Parish Thomas , Vane Deborah , Winker Dave , Liu Dong , Adhikari Loknath
Published: July 2008

The formation of polar stratospheric clouds (PSCs) is critical to the development of polar ozone loss. However, the mechanisms of PSC formation remain poorly understood, which affects ozone loss models. Here, based on observations by the NASA A‐train satellites, we show that 66% ± 16% and 52% ± 17% of PSCs over west and east Antarctica during the period June–October 2006 were associated with deep tropospheric cloud systems, with maximum depths exceeding 7 km. The development of such deep tropospheric cloud systems should cool the lower stratosphere through adiabatic and radiative processes, favoring PSC development. These deep systems also transport lower tropospheric air into the upper troposphere and lower stratosphere. These new findings suggest that Antarctic PSC formation is closely connected to tropospheric meteorology and thus governed by synoptic scale dynamics, local topography, and large‐scale circulation. More dedicated studies are still needed to better understand Antarctic PSC formation.
Statistics of extreme geomagnetically induced current events
Authors: Pulkkinen A. , Pirjola R. , Viljanen A.
Published: July 2008

In this work, space weather events associated with extreme geoelectric field and geomagnetically induced current (GIC) magnitudes are investigated. The geoelectric field and consequent GIC are computed using geomagnetic field recordings over an extended time period and ground conductivity and technological system configurations favorable for large GIC. The statistics are derived for both overall occurrence of the geoelectric field and geoelectric field occurrence conditioned by the state of the magnetosphere and the solar wind. It is shown that in high‐latitude areas having resistive ground conductivity structures and in systems having characteristics favorable for large GIC, GIC amplitudes of about 200 A can be expected to occur 102–103 times (in 10‐s values) per year while GIC of about 2000 A occur only 10–100 times in 100 years. On the basis of the Dst index and the solar wind electric field values derived by Siscoe et al. (2006) and Tsurutani et al. (2003), it is estimated by means of derived conditional probability distributions that although magnitudes of about 10 V/km are possible, the most probable value for the maximum magnitude of the geoelectric field during the Carrington event of 1–2 September 1859 is about 4 V/km. The usage of derived conditional probabilities in space weather applications is also discussed.
BioBrick Promoter Measurement Kit Instruction Sheets
Authors: Kelly Jason
Published: July 2008

Instructions for inserting a test promoter into the measurement kit plasmid for characterization as well as instructions for measuring the activity of the test promoter in Standard Promoter Units (SPUs). These instructions were distributed to the teams participating in the International Genetically Engineered Machines competition (iGEM).
The Chemistry of Fungi
Authors: Hanson James R
Published: July 2008

Fungi occupy an important place in the natural world, as non-photosynthetic organisms, they obtain their nutrients from the degradation of organic material. They use many of their secondary metabolites to secure a place in a competitive natural environment and to protect themselves from predation. The diverse structures, biosyntheses and biological activities of fungal metabolites have attracted chemists for many years. Fungi are ubiquitous and their activities affect many aspects of our daily lives whether it be as sources of pharmaceuticals and food or as spoilage organisms and the causes of diseases in plants and man. The chemistry of the fungi involved in these activities has been the subject of considerable study particularly over the last fifty years. Although their ramifications can be large as in the spread of plant diseases, the quantities of the metabolites which could be isolated precluded much chemical work until the advent of spectroscopic methods. Whereas many natural products derived from plants were isolated prior to the 1960s on a scale which permitted extensive chemical degradation, this was rarely the case for fungal metabolites. This book is an introduction to the chemistry of fungal metabolites. The aim is to illustrate within the context of fungal metabolites, the historical progression from chemical to spectroscopic methods of structure elucidation, the development in biosynthetic studies from establishing sequences and mechanisms to chemical enzymology and genetics and the increasing understanding of the biological roles of natural products. The book begins with a historical introduction followed by a description of the general chemical features which contribute to the growth of fungi. There are many thousands of fungal metabolites whose structures are known and the book does not aim to list them all as there are databases to fulfill this role. The book's aim is to describe some of the more important metabolites classified according to their biosynthetic origin. Biosynthesis provides a unifying feature underlying the diverse structures of fungal metabolites and the chapters covering this area begin with a general outline of the relevant biosynthetic pathway before presenting a detailed description of particular metabolites. Investigations into these biosyntheses have utilized many subtle isotopic labelling experiments and compounds that are fungal pigments and those which are distinctive metabolites of the more conspicuous Basidiomycetes are treated separately. Many fungal metabolites are involved in the interactions of fungi with plants and others are toxic to man and some of these are described in further chapters. Fungi have the ability to transform chemicals in ways which can complement conventional reactions and the use of fungi as reagents forms the subject of the final chapter. This book will be particularly useful to anybody about to embark on a career in chemical microbiology by providing an overall perspective of fungal metabolites as well as an essential reference tool for more general chemists.
GPCR signalling in hypertension: role of GRKs
Authors: Harris David M. , Cohn Heather I. , Pesant Stéphanie , Eckhart Andrea D.
Published: July 2008

Hypertension is a prevalent condition in the developed world and disease severity is directly correlated with additional cardiovascular complications. It is estimated that 30% of the adult population in the United States has hypertension, which is classified as a systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg. A prolonged increase in afterload ultimately leads to congestive heart failure in the majority of cases. Currently, medication designed to treat hypertension is inadequate, thus new therapies need to be explored. Blood pressure is tightly regulated by blood vessel radius, which is established by hormones and/or peptides binding to GPCRs (G-protein-coupled receptors). Catecholamines and peptide hormones, such as AngII (angiotensin II), are elevated in hypertension and, therefore, signalling by these GPCRs is increased. Their signalling is tightly controlled by a class of proteins, the GRKs (GPCR kinases). Elevated levels of either GRK2 or GRK5 in both the lymphocytes and VSM (vascular smooth muscle) are associated with human hypertension and animal models of the disease. The focus of the present review is on the role GRKs, and their regulation of GPCRs, play in high blood pressure.
Growth and physiological responses of balansa clover and burr medic to low levels of salinity
Authors: Mapfumo Emmanuel , Behdani Mohammed A. , Rengel Zed , Barrett-Lennard Edward G.
Published: July 2008

This study investigated a wide range of morphological and physiological responses of burr medic (Medicago polymorpha L. cv. Scimitar) and balansa clover (Trifolium michelianum L. cv. Frontier) to different levels of salinity. Balansa clover and burr medic plants were grown in the greenhouse at 25°C day temperature and 16°C night temperature. Salt treatments were applied 6 weeks after germination, and plants were grown for a further 6 weeks before harvest. The salt treatments included a control, 20 mm, 40 mm, and 80 mm of NaCl. The shoot biomass yield was significantly affected by the species × salt interaction (P = 0.04). For balansa clover, the shoot biomass yield was greatest for the control treatment and lowest for the 20 mm NaCl treatment. For burr medic, the shoot biomass yield did not differ among salt treatments. Sodium (Na+) and potassium (K+) concentrations in leaves and stems increased with salinity. Compared with a non-saline control, sodium concentration in leaves in the 80 mm NaCl treatment was 3-fold higher for balansa clover and 2-fold higher for burr medic. Under various saline treatments, leaf Na+/K+ ratio stayed relatively constant in balansa clover (0.3–0.4) and burr medic (0.4–0.5), whereas stem Na+/K+ ratios for both species increased with salinity. The most sensitive parameters to salinity were Na+/K+ and Na+/Ca2+ ratios, whereas biomass, chlorophyll fluorescence, net photosynthesis, stomatal conductance, transpiration, and δ13C and δ15N discrimination were least sensitive. Therefore, accumulation of sodium in the plant tissues did not reach the threshold for causing reduction in growth.
Programmed death 1 ligand signaling regulates the generation of adaptive Foxp3
+
CD4
+
regulatory T cells
Authors: Wang Li , Pino-Lagos Karina , de Vries Victor C. , Guleria Indira , Sayegh Mohamed H. , Noelle Randolph J.
Published: July 2008

Although mature dendritic cells (DCs) are potent initiators of adaptive immune response, immature steady-state DCs contribute to immune tolerance. In this study, we show that
ex vivo
splenic DCs are capable of inducing conversion of naïve CD4
+
T cells to adaptive Foxp3
+
CD4
+
regulatory T cells (aTreg) in the presence of TGF-β. In particular, when compared with splenic CD8α
−
DCs, the CD8α
+
DC subset were superior in inducing higher frequencies of conversion. This was not attributable to the difference in basal level of costimulation, because deficiency of CD40 or CD80/86 signaling did not diminish the differential induction of Foxp3. Conversion was regulated by DC maturation status. Further insights into the molecular mechanisms of conversion were gained by analyzing the contribution of several costimulatory and coinhibitory receptors. Costimulatory signals through GITR suppressed conversion, whereas coinhibitory signaling via programmed death 1 ligand (PD-L1) but not PD-L2 was required for conversion.
Ex vivo
PD-L1
−/−
DCs failed to support Foxp3 induction in the presence of TGF-β.
In vivo
blocking PD-L1 signaling abolished conversion in a tumor-induced aTreg conversion model. Collectively, this study highlights the cellular and molecular parameters that might be exploited to control the
de novo
generation of aTregs and peripheral tolerance.
WRN Is Required for ATM Activation and the S-Phase Checkpoint in Response to Interstrand Cross-Link–Induced DNA Double-Strand Breaks
Authors: Cheng Wen-Hsing , Muftic Diana , Muftuoglu Meltem , Dawut Lale , Morris Christa , Helleday Thomas , Shiloh Yosef , Bohr Vilhelm A.
Published: July 2008

Werner syndrome (WS) is a human genetic disorder characterized by extensive clinical features of premature aging. Ataxia-telengiectasia (A-T) is a multisystem human genomic instability syndrome that includes premature aging in some of the patients. WRN and ATM, the proteins defective in WS and A-T, respectively, play significant roles in the maintenance of genomic stability and are involved in several DNA metabolic pathways. A role for WRN in DNA repair has been proposed; however, this study provides evidence that WRN is also involved in ATM pathway activation and in a S-phase checkpoint in cells exposed to DNA interstrand cross-link–induced double-strand breaks. Depletion of WRN in such cells by RNA interference results in an intra-S checkpoint defect, and interferes with activation of ATM as well as downstream phosphorylation of ATM target proteins. Treatment of cells under replication stress with the ATM kinase inhibitor KU 55933 results in a S-phase checkpoint defect similar to that observed in WRN shRNA cells. Moreover, γH2AX levels are higher in WRN shRNA cells than in control cells 6 and 16 h after exposure to psoralen DNA cross-links. These results suggest that WRN and ATM participate in a replication checkpoint response, in which WRN facilitates ATM activation in cells with psoralen DNA cross-link–induced collapsed replication forks.
UNC-18 Promotes Both the Anterograde Trafficking and Synaptic Function of Syntaxin
Authors: McEwen Jason M. , Kaplan Joshua M.
Published: July 2008

The SM protein UNC-18 has been proposed to regulate several aspects of secretion, including synaptic vesicle docking, priming, and fusion. Here, we show that UNC-18 has a chaperone function in neurons, promoting anterograde transport of the plasma membrane soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein Syntaxin-1. In unc-18 mutants, UNC-64 (Caenorhabditis elegans Syntaxin-1) accumulates in neuronal cell bodies. Colocalization studies and analysis of carbohydrate modifications both suggest that this accumulation occurs in the endoplasmic reticulum. This trafficking defect is specific for UNC-64 Syntaxin-1, because 14 other SNARE proteins and two active zone markers were unaffected. UNC-18 binds to Syntaxin through at least two mechanisms: binding to closed Syntaxin, or to the N terminus of Syntaxin. It is unclear which of these binding modes mediates UNC-18 function in neurons. The chaperone function of UNC-18 was eliminated in double mutants predicted to disrupt both modes of Syntaxin binding, but it was unaffected in single mutants. By contrast, mutations predicted to disrupt UNC-18 binding to the N terminus of Syntaxin caused significant defects in locomotion behavior and responsiveness to cholinesterase inhibitors. Collectively, these results demonstrate the UNC-18 acts as a molecular chaperone for Syntaxin transport in neurons and that the two modes of UNC-18 binding to Syntaxin are involved in different aspects of UNC-18 function.
The Structural and Functional Implications of Linked SNARE Motifs in SNAP25
Authors: Wang Li , Bittner Mary A. , Axelrod Daniel , Holz Ronald W.
Published: July 2008

We investigated the functional and structural implications of SNAP25 having two SNARE motifs (SN1 and SN2). A membrane-bound, intramolecular FRET probe was constructed to report on the folding of N-terminal SN1 and C-terminal SN2 in living cells. Membrane-bound constructs containing either or both SNARE motifs were also singly labeled with donor or acceptor fluorophores. Interaction of probes with other SNAREs was monitored by the formation of SDS-resistant complexes and by changes in FRET measured in vitro using spectroscopy and in the plasma membrane of living cells using TIRF microscopy. The probes formed the predicted SDS-resistant SNARE complexes. FRET measurements revealed that syntaxin induced a close association of the N-termini of SN1 and SN2. This association required that the SNARE motifs reside in the same molecule. Unexpectedly, the syntaxin-induced FRET was prevented by VAMP. Both full-length SNAP25 constructs and the combination of its separated, membrane-bound constituent chains supported secretion in permeabilized chromaffin cells that had been allowed to rundown. However, only full-length SNAP25 constructs enabled robust secretion from intact cells or permeabilized cells before rundown. The experiments suggest that the bidentate structure permits specific conformations in complexes with syntaxin and VAMP and facilitates the function of SN1 and SN2 in exocytosis.
All in One:Leishmania majorSTT3 Proteins Substitute for the Whole Oligosaccharyltransferase Complex inSaccharomyces cerevisiae
Authors: Parsaie Nasab Farnoush , Schulz Benjamin L. , Gamarro Francisco , Parodi Armando J. , Aebi Markus
Published: July 2008

The transfer of lipid-linked oligosaccharide to asparagine residues of polypeptide chains is catalyzed by oligosaccharyltransferase (OTase). In most eukaryotes, OTase is a hetero-oligomeric complex composed of eight different proteins, in which the STT3 component is believed to be the catalytic subunit. In the parasitic protozoa Leishmania major, four STT3 paralogues, but no homologues to the other OTase components seem to be encoded in the genome. We expressed each of the four L. major STT3 proteins individually in Saccharomyces cerevisiae and found that three of them, LmSTT3A, LmSTT3B, and LmSTT3D, were able to complement a deletion of the yeast STT3 locus. Furthermore, LmSTT3D expression suppressed the lethal phenotype of single and double deletions in genes encoding other essential OTase subunits. LmSTT3 proteins did not incorporate into the yeast OTase complex but formed a homodimeric enzyme, capable of replacing the endogenous, multimeric enzyme of the yeast cell. Therefore, these protozoan OTases resemble the prokaryotic enzymes with respect to their architecture, but they used substrates typical for eukaryotic cells: N-X-S/T sequons in proteins and dolicholpyrophosphate-linked high mannose oligosaccharides.
Odour character differences for enantiomers correlate with molecular flexibility
Authors: Brookes Jennifer C , Horsfield A.P , Stoneham A.M
Published: July 2008

The olfactory system sensitively discerns scents from many small molecules as the brain analyses signals from nasal receptors. These receptors are selective to some degree, though the mechanism for selectivity is still controversial. Enantiomers, chiral pairs of left- and right-handed structures, are an important class of molecules in assessing proposed mechanisms. We show that there is a correlation between molecular (structural) flexibility and whether or not the left- and right-handed enantiomers smell the same. In particular, for the fairly extensive class of enantiomers with six-membered ring flexibility, enantiomers do not smell the same. There are, of course, significant experimental uncertainties, which we discuss here. We discuss models of receptor selectivity, both those based on shape and those where discrimination is based on other factors, such as electron affinity, proton affinity or vibration frequencies. The differences in scent of these enantiomers appear to be consistent with simple generalizations of a ‘swipe card’ model in which, while the shape must be good enough, critical information for actuation is a separate factor.
Crystal structure of RimI from Salmonella typhimurium LT2, the GNAT responsible for Nα‐acetylation of ribosomal protein S18
Authors: Vetting Matthew W. , Bareich David C. , Yu Michael , Blanchard John S.
Published: July 2008

The three ribosomal proteins L7, S5, and S18 are included in the rare subset of prokaryotic proteins that are known to be Nα‐acetylated. The GCN5‐related N‐acetyltransferase (GNAT) protein RimI, responsible for the Nα‐acetylation of the ribosomal protein S18, was cloned from Salmonella typhimurium LT2 (RimIST), overexpressed, and purified to homogeneity. Steady‐state kinetic parameters for RimIST were determined for AcCoA and a peptide substrate consisting of the first six amino acids of the target protein S18. The crystal structure of RimIST was determined in complex with CoA, AcCoA, and a CoA‐S‐acetyl‐ARYFRR bisubstrate inhibitor. The structures are consistent with a direct nucleophilic addition–elimination mechanism with Glu103 and Tyr115 acting as the catalytic base and acid, respectively. The RimIST‐bisubstrate complex suggests that several residues change conformation upon interacting with the N terminus of S18, including Glu103, the proposed active site base, facilitating proton exchange and catalysis.
Differential ubiquitin binding of the UBA domains from human c‐Cbl and Cbl‐b: NMR structural and biochemical insights
Authors: Zhou Zi‐Ren , Gao Hong‐Chang , Zhou Chen‐Jie , Chang Yong‐Gang , Hong Jing , Song Ai‐Xin , Lin Dong‐Hai , Hu Hong‐Yu
Published: July 2008

The Cbl proteins, RING‐type E3 ubiquitin ligases, are responsible for ubiquitinating the activated tyrosine kinases and targeting them for degradation. Both c‐Cbl and Cbl‐b have a UBA (ubiquitin‐associated) domain at their C‐terminal ends, and these two UBA domains share a high sequence similarity (75%). However, only the UBA from Cbl‐b, but not from c‐Cbl, can bind ubiquitin (Ub). To understand the mechanism by which the UBA domains specifically interact with Ub with different affinities, we determined the solution NMR structures of these two UBA domains, cUBA from human c‐Cbl and UBAb from Cbl‐b. Their structures show that these two UBA domains share the same fold, a compact three‐helix bundle, highly resembling the typical UBA fold. Chemical shift perturbation experiments reveal that the helix‐1 and loop‐1 of UBAb form a predominately hydrophobic surface for Ub binding. By comparing the Ub‐interacting surface on UBAb and its counterpart on cUBA, we find that the hydrophobic patch on cUBA is interrupted by a negatively charged residue Glu12. Fluorescence titration data show that the Ala12Glu mutant of UBAb completely loses the ability to bind Ub, whereas the mutation disrupting the dimerization has no significant effect on Ub binding. This study provides structural and biochemical insights into the Ub binding specificities of the Cbl UBA domains, in which the hydrophobic surface distribution on the first helix plays crucial roles in their differential affinities for Ub binding. That is, the amino acid residue diversity in the helix‐1 region, but not the dimerization, determines the abilities of various UBA domains binding with Ub.
Phanerozoic Trends in the Global Diversity of Marine Invertebrates
Authors: Alroy John , Aberhan Martin , Bottjer David J. , Foote Michael , Fürsich Franz T. , Harries Peter J. , Hendy Austin J. W. , Holland Steven M. , Ivany Linda C. , Kiessling Wolfgang , Kosnik Matthew A. , Marshall Charles R. , McGowan Alistair J. , Miller Arnold I. , Olszewski Thomas D. , Patzkowsky Mark E. , Peters Shanan E. , Villier Loïc , Wagner Peter J. , Bonuso Nicole , Borkow Philip S. , Brenneis Benjamin , Clapham Matthew E. , Fall Leigh M. , Ferguson Chad A. , Hanson Victoria L. , Krug Andrew Z. , Layou Karen M. , Leckey Erin H. , Nürnberg Sabine , Powers Catherine M. , Sessa Jocelyn A. , Simpson Carl , Tomašových Adam , Visaggi Christy C.
Published: July 2008

It has previously been thought that there was a steep Cretaceous and Cenozoic radiation of marine invertebrates. This pattern can be replicated with a new data set of fossil occurrences representing 3.5 million specimens, but only when older analytical protocols are used. Moreover, analyses that employ sampling standardization and more robust counting methods show a modest rise in diversity with no clear trend after the mid-Cretaceous. Globally, locally, and at both high and low latitudes, diversity was less than twice as high in the Neogene as in the mid-Paleozoic. The ratio of global to local richness has changed little, and a latitudinal diversity gradient was present in the early Paleozoic.
Reduced Responses to Selection After Species Range Expansion
Authors: Pujol Benoit , Pannell John R.
Published: July 2008

Species range expansion reduces genetic variation at the margins of a species range and should thus compromise the adaptive potential of its marginal populations. Remarkably, this prediction has not previously been tested. Here, we show that populations of the plant Mercurialis annua, which expanded its range into Spain and Portugal from North Africa after the Pleistocene glaciation, respond to selection on a key life-history trait less well than populations from the species' historical refugium. Our results provide direct evidence of a decline in adaptive potential across the geographic range of a species after a shift in its distribution. Predicting evolutionary responses to environmental change will thus need to account for the genetic heterogeneity of species and the spatial dynamics of their geographic distributions.
Laser Altimeter Observations from MESSENGER's First Mercury Flyby
Authors: Zuber Maria T. , Smith David E. , Solomon Sean C. , Phillips Roger J. , Peale Stanton J. , Head James W. , Hauck Steven A. , McNutt Ralph L. , Oberst Jürgen , Neumann Gregory A. , Lemoine Frank G. , Sun Xiaoli , Barnouin-Jha Olivier , Harmon John K.
Published: July 2008

A 3200-kilometers-long profile of Mercury by the Mercury Laser Altimeter on the MESSENGER spacecraft spans ∼20% of the near-equatorial region of the planet. Topography along the profile is characterized by a 5.2-kilometer dynamic range and 930-meter root-mean-square roughness. At long wavelengths, topography slopes eastward by 0.02°, implying a variation of equatorial shape that is at least partially compensated. Sampled craters on Mercury are shallower than their counterparts on the Moon, at least in part the result of Mercury's higher gravity. Crater floors vary in roughness and slope, implying complex modification over a range of length scales.
Myosin I Can Act As a Molecular Force Sensor
Authors: Laakso Joseph M. , Lewis John H. , Shuman Henry , Ostap E. Michael
Published: July 2008

The ability to sense molecular tension is crucial for a wide array of cellular processes, including the detection of auditory stimuli, control of cell shape, and internalization and transport of membranes. We show that myosin I, a motor protein that has been implicated in powering key steps in these processes, dramatically alters its motile properties in response to tension. We measured the displacement generated by single myosin I molecules, and we determined the actin-attachment kinetics with varying tensions using an optical trap. The rate of myosin I detachment from actin decreases >75-fold under tension of 2 piconewtons or less, resulting in myosin I transitioning from a low (<0.2) to a high (>0.9) duty-ratio motor. This impressive tension sensitivity supports a role for myosin I as a molecular force sensor.
Inspiring Experiences in Science
Authors: Kovats Susan
Published: July 2008

Gorilla Mountain
. The Story of Wildlife Biologist Amy Vedder.
Rene Ebersole
. Franklin Watts (Scholastic), New York, and Joseph Henry (National Academies Press), Washington, DC, 2005. 128 pp. $9.95. ISBN 9780309095518.

Robo World
. The Story of Robot Designer Cynthia Breazeal.
Jordan D. Brown
. Franklin Watts (Scholastic), New York, and Joseph Henry (National Academies Press), Washington, DC, 2005. 128 pp. $9.95. ISBN 9780309095563.

Nature's Machines
. The Story of Biomechanist Mimi Koehl.
Deborah Parks
. Franklin Watts (Scholastic), New York, and Joseph Henry (National Academies Press), Washington, DC, 2005. 128 pp. $9.95. ISBN 9780309095594.

Three books from the Women's Adventures in Science series present the experiences and research of a wildlife biologist, a robot designer, and a biomechanist to encourage young readers' interests.
Cities Not Built to Last
Authors: Riddihough Guy
Published: July 2008

The City and the Stars
.
Arthur C. Clarke
. Frederick Muller, London, 1956, 256 pp.

Despite its shortcomings, Arthur C. Clarke's first novel conveys his "sweeping vistas, grand ideas, and ultimately optimistic view of humankind's future in the cosmos."
Cross-Reactivity between Immune Responses to
Helicobacter bilis
and
Helicobacter pylori
in a Population in Thailand at High Risk of Developing Cholangiocarcinoma
Authors: Pisani Paola , Whary Mark T. , Nilsson Ingrid , Sriamporn Supannee , Wadström Torkel , Fox James G. , Ljungh Åsa , Forman David
Published: July 2008

Helicobacter bilis
DNA has been detected in human tissue and is a candidate for etiologic investigations on the causes of hepatic and biliary tract diseases, but reliable serologic tests need to be developed in order to pursue such investigations. The scope of this study was to assess the specificity of two assays for
H. bilis
immune response allowing for
H. pylori
, and their cross-reactivity in a population in Thailand at high risk for cholangiocarcinoma. Plasma samples from 92 Thai volunteers were independently tested in two laboratories (Massachusetts Institute of Technology [MIT] and Lund). MIT performed three analyses of
H. pylori
and
H. bilis
based either on (i) outer membrane protein (OMP) with no preabsorption or on antigens derived from whole-cell sonicate before (ii) or after (iii) preabsorption with
H. pylori
sonicate protein. Lund used cell surface proteins from
H. pylori
and
H. bilis
as antigens. Testing for
H. bilis
was preabsorbed with a whole-cell lysate of
H. pylori
. More than 80% of the samples were positive for
H. pylori
in both laboratories. As tested by MIT, 58.7% (95% confidence interval, 47.9 to 68.9%) were positive for
H. bilis
by OMP and 44.5% (34.1 to 55.3%) were positive for
H. bilis
sonicate protein, but only 15.2% (8.6 to 24.2%) remained positive after preabsorption with
H. pylori
sonicate protein. Lund found 34.5% of the samples positive for
H. bilis
(22.0 to 41.0%), which was statistically compatible with all three MIT results. Serologic responses to OMPs of the two bacteria coincided in 66 and 45% of the samples in the MIT and Lund assays, respectively. We found high cross-reactivity between the immune responses to
H. pylori
and
H. bilis
antigens. More-specific
H. bilis
antigens need to be isolated to develop serologic tests suitable for epidemiological studies.
Identification of Enteroviruses in Naturally Infected Captive Primates
Authors: Nix W. Allan , Jiang Baoming , Maher Kaija , Strobert Elizabeth , Oberste M. Steven
Published: July 2008

In a recent study, we investigated cases of diarrheal disease among monkeys at a U.S. primate center. In that study, enteroviruses were detected in a high proportion of the fecal specimens tested. To determine whether the enterovirus detections represented the circulation of one or more simian enteroviruses within the colony or the transmission of human enteroviruses from animal handlers, we determined in the present study the serotype identity of each virus by reverse transcription-PCR and sequencing of a portion of the VP1 gene, a region whose sequence corresponds to antigenic type. Enteroviruses were identified in 37 of 56 specimens (66%), 30 of 40 rhesus macaques, 5 of 11 pigtail macaques, 2 of 4 sooty mangabeys, and 0 of 1 chimpanzee. No previously known human viruses were detected. Three previously known simian enterovirus serotypes—SV6, SV19, and SV46—were among the viruses identified, but more than half of the identified viruses were previously unknown; these have been assigned as new types: EV92 and EV103.