bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of severe osteoporosis with alendronate in a patient with lysinuric protein intolerance
Authors: Gömez L. , García‐Cazorla A. , Gutiérrez A. , Artuch R. , Varea V. , Martín J. , Pinillos S. , Vilaseca M. A.
Published: July 2006

Lysinuric protein intolerance is an inborn error of cationic amino acid transport of which osteoporosis is a major feature. Treatment with oral bisphosphonates improves bone mineral density even in severe osteoporosis.
Density‐dependent egg mortality in early stages of gall induction by the fruit gall midge Asphondylia aucubae Yukawa and Ohsaki
Authors: Imai Kensuke , Ohsaki Naota
Published: July 2006

Density‐dependent mortality has been considered a symptom of intraspecific competition. We examined the occurrence of such mortality in the early stages of gall induction by the gall midge Asphondylia aucubae Yukawa et Ohsaki (Diptera: Cecidomyiidae). Female midges deposit eggs into young fruit of the dioecious shrub Aucuba japonica Thunberg to induce gall formation. Each host fruit received 0–67 eggs (mean 18.5 eggs) from multiple females, whereas established galls each contained one to ten larvae. Midges suffered intense mortality (65–90%) at the egg stage. Egg mortality occurred even in fruit in which no larvae had hatched, suggesting that this mortality cannot be wholly attributed to larval interference. Egg mortality was affected by fruit size, i.e., resource capacity. Midges distributed more eggs in larger fruit. Egg mortality increased as the per‐fruit density increased relative to fruit size. In contrast, the mortality of hatchlings was density‐independent. Our results suggest that A. aucubae intensely compete for gall‐induction substrates, which are spatiotemporally rare resources.
Different biomass‐allocation patterns among four tree species in heavily disturbed sites on a volcanic mountain in Hokkaido, northern Japan
Authors: Shibuya Masato , Yajima Takashi , Yoshida Mihoko , Sasaoka Eiji
Published: July 2006

We have compared biomass‐allocation patterns and frequency of sprouting among saplings of four tree species (Larix kaempferi, Betula platyphylla var. japonica, Populus maximowiczii, and Populus sieboldii) growing on a volcanic mountain in Hokkaido, northern Japan. Growing conditions were very harsh on the mountainside. Leaf mass and fine root mass relative to root mass were larger in L. kaempferi, and L. kaempferi root mass was less than for the other species. Sprouting ratios were high for the broadleaved species. Different allometries and sprouting ratios among species suggest that survival strategies for L. kaempferi were different from those for the broadleaved species. L. kaempferi has greater ability to increase leaf mass under harsh growing conditions; this probably results in large photosynthetic production by L. kaempferi on the volcano. In contrast, the two Populus species and Betula platyphylla seem to maintain populations through their ability to produce sprouts from large root systems.
Self-assembled GaInNAs/GaAsN quantum dot lasers: solid source molecular beam epitaxy growth and high-temperature operation
Authors: Yoon S. F. , Liu C. Y. , Sun Z. Z. , Yew K. C.
Published: July 2006

Self-assembled GaInNAs quantum dots (QDs) were grown on GaAs (001) substrate using solid-source molecular-beam epitaxy (SSMBE) equipped with a radio-frequency nitrogen plasma source. The GaInNAs QD growth characteristics were extensively investigated using atomic-force microscopy (AFM), photoluminescence (PL), and transmission electron microscopy (TEM) measurements. Self-assembled GaInNAs/GaAsN single layer QD lasers grown using SSMBE have been fabricated and characterized. The laser worked under continuous wave (CW) operation at room temperature (RT) with emission wavelength of 1175.86 nm. Temperature-dependent measurements have been carried out on the GaInNAs QD lasers. The lowest obtained threshold current density in this work is ∼1.05 kA/cm2from a GaInNAs QD laser (50 × 1,700 µm2) at 10 °C. High-temperature operation up to 65 °C was demonstrated from an unbonded GaInNAs QD laser (50 × 1,060 µm2), with high characteristic temperature of 79.4 K in the temperature range of 10–60 °C.
Evolution of wetting layer in InAs/GaAs quantum dot system
Authors: Chen Y.H. , Ye X.L. , Wang Z.G.
Published: July 2006

For InAs/GaAs quantum dot system, the evolution of the wetting layer (WL) with the InAs deposition thickness has been studied by reflectance difference spectroscopy (RDS). Two transitions related to the heavy- and light-hole in the WL have been distinguished in RD spectra. Taking into account the strain and segregation effects, a model has been presented to deduce the InAs amount in the WL and the segregation coefficient of the indium atoms from the transition energies of heavy- and light-holes. The variation of the InAs amount in the WL and the segregation coefficient are found to rely closely on the growth modes. In addition, the huge dots also exhibits a strong effect on the evolution of the WL. The observed linear dependence of In segregation coefficient upon the InAs amount in the WL demonstrates that the segregation is enhanced by the strain in the WL.
Gold nanoparticle ensembles as heaters and actuators: melting and collective plasmon resonances
Authors: Govorov Alexander O. , Zhang Wei , Skeini Timur , Richardson Hugh , Lee Jaebeom , Kotov Nicholas A.
Published: July 2006

We describe the peculiar conditions under which optically driven gold nanoparticles (NPs) can significantly increase temperature or even melt a surrounding matrix. The heating and melting processes occur under light illumination and involve the plasmon resonance. For the matrix, we consider water, ice, and polymer. Melting and heating the matrix becomes possible if a nanoparticle size is large enough. Significant enhancement of the heating effect can appear in ensembles of NPs due to an increase of a volume of metal and electric-field amplification.
Saccharomyces cerevisiae telomerase subunit Est3p binds DNA and RNA and stimulates unwinding of RNA/DNA heteroduplexes
Authors: Sharanov Yu.S. , Zvereva M.I. , Dontsova O.A.
Published: July 2006

Telomerase is a key participant of telomere length maintenance system in majority of eukaryotes. It synthesizes telomere repeats at 3′‐end of telomere DNA according to its own RNA template. In addition to the reverse transcriptase subunit Est2p and telomerase RNA TLC1, yeast telomerase contain Est1p, necessary for telomerase attachment to telomere and telomerase activation, and Est3p, a subunit with unknown function. We have isolated Est3p and examined its biochemical properties. Est3p binds both DNA and RNA oligonucleotides containing telomere repeat sequences and stimulates dissociation of RNA/DNA heteroduplexes. The importance of these properties of Est3p for telomerase function is discussed.
The umbilical coiling index and adverse perinatal outcome
Authors: Kashanian M. , Akbarian A. , Kouhpayehzadeh J.
Published: July 2006

Objective: Evaluation of the relationship between umbilical coiling index (UCI) and adverse perinatal outcome.

Method: A prospective study was performed on 699 pregnant women who were 37–40 weeks. UCI was determined by dividing the total number of the complete vascular coiling by the total umbilical cord length in centimeters. Then the relationship between UCI and neonatal weight, amniotic fluid index, meconium, Apgar score, and fetal distress were evaluated.

Results: There was a significant difference between normo‐ and hypocoiled groups according to the Apgar score less than 7 in minute 5, AFI ≤ 5; and between normo‐ and hypercoiled groups according to Apgar score less than 7 in minute 5, AFI ≤ 5, meconium, and fetal distress. Neonatal weight in normocoiled was higher than hypercoiled group. AFI ≤ 5, meconium and fetal distress were higher in hypercoiled than hypocoiled group. Neonatal weight in hypercoiled was less than that in the hypocoiled group, respectively.

Conclusion: Abnormal UCI may relate to adverse perinatal outcome.
Recurrence risks for schizophrenia in a Swedish National Cohort
Authors: LICHTENSTEIN PAUL , BJÖRK CAMILLA , HULTMAN CHRISTINA M. , SCOLNICK EDWARD , SKLAR PAMELA , SULLIVAN PATRICK F.
Published: July 2006

Objective. Recurrence risk estimates for schizophrenia are fundamental to our understanding of this complex disease. Widely cited estimates are from small/older samples. If these estimates are biased upwards, then the rationale for molecular genetic studies of schizophrenia may not be as solid.

Method. We created a population-based, Swedish national cohort by linking two Swedish national registers into a relational database (the Swedish Hospital Discharge Register and the Multi-Generation Register). Affection was defined as the lifetime presence of at least two in-patient hospitalizations with a core schizophrenia diagnosis.

Results. Merging the Swedish national registers created a population-based cohort of 7739202 individuals of known parentage. The lifetime prevalence of the narrow definition of schizophrenia was 0·407% and we estimated that one in every 79 extended Swedish families had been impacted by schizophrenia. The proportion of affected families with multiple affected members was 3·81%. Recurrence risk estimates for all relative types were strikingly similar to those reported in smaller and older studies. For example, we estimated λsibs at 8·55 [95% confidence interval (CI) 7·86–9·57] compared with a literature estimate of 8·6.

Conclusions. In the largest and most comprehensive sample yet studied, we confirm the accepted estimates of recurrence risks for schizophrenia, and provide more accurate estimates of recurrence risks of schizophrenia in relatives, an estimate of the familial impact of schizophrenia, and the multiplex proportion (essential for gauging the generalizability of findings from multiplex pedigrees). These data may be valuable for planning and interpreting genetic studies of schizophrenia.
The death of the Master: the Gospel of John and R. L. Stevenson's The Master of Ballantrae
Authors: Jack Alison
Published: July 2006

In this paper, I argue that the influence of John's Gospel on R. L. Stevenson's novel The Master of Ballantrae is significant on several levels. On the level of narrative, I show that both texts are narrated from a perspective which shifts uneasily from omniscience to uncertainty. John's Gospel, particularly its closing chapters, offers a powerful model for the telling of the story of The Master of Ballantrae. The reliability both of Mr MacKellar, the novel's narrator, and of the mysterious editor of the material which makes up John's Gospel, is open to question. On the level of plot, the death, burial and ‘resurrection’ of James Durie, the ‘Master’, at least on one reading of the novel's title, mirrors the death, burial and resurrection of the Johannine Christ. This is no straightforward importation of one set of ideas onto another, rather an imaginative and sophisticated retelling of the climax of the Gospel story. Finally, on the level of characterisation, several of the characters in The Master of Ballantrae share features with players in the Gospel narrative, particularly those who appear in the Passion and resurrection scenes. Pilate's vacillations and Thomas's doubts flesh out our understanding of the characters who witness the death throes of the warring Durie brothers.

Robert Louis Stevenson had grown up hearing the Bible read at home and in church. Despite rejecting the faith of his parents in his twenties, he nevertheless continued to be drawn to the images and cadences of the Bible, and particularly of the Gospels. The relationship between The Master of Ballantrae and John's Gospel is not one of simple dependence: but the influence of the Gospel on the novel, I argue, is clear and distinctive.
Traditional gathering of native hula plants in alien-invaded Hawaiian forests: adaptive practices, impacts on alien invasive species and conservation implications
Authors: TICKTIN TAMARA , WHITEHEAD A. NĀMAKA , FRAIOLA HŌ‘ALA
Published: July 2006

Traditional resource management (TRM) systems in tropical forests can provide insights on sustainable resource use, but despite the growing prevalence of degraded tropical forest habitats, few studies have assessed the relationships between TRM and conservation in these environments. In Hawaii, the traditional gathering of native wild plants used for hula (chants and dance) and lei (garlands) is carried out in forests increasingly dominated by alien invasive species. Ethnographic methods and exploratory experimental harvests were employed to examine: gathering of hula plants in the past and present, ecological impacts of contemporary gathering practices of three important native hula species in alien-dominated forests, and relationships between traditional practices and past and modern conservation. Past gathering traditions included practices to increase and conserve hula plant populations. Harvest of Microlepia strigosa fern fronds significantly decreased M. strigosa cover over the short term. Cover of alien species significantly increased after frond-harvest of Sphenomeris chinensis. Regeneration of the fruit-harvested shrub, Melicope anisata, was significantly negatively correlated with the level of understorey invasive species. These results suggest that in Hawai‘i’s alien-dominated forests, gathering of some species may increase spread of alien invasive species or exacerbate regeneration problems caused by invasive species. However, some expert cultural practitioners have adapted traditional practices to ensure hula plant conservation by incorporating weeding of alien invasive species into their protocols. The re-strengthening and adaptation of traditional Hawaiian knowledge and social institutions to the modern context can provide opportunities to improve conservation of Hawai‘i’s culturally-important native plants and their habitats.
Magnetospheric influence on the Moon's exosphere
Authors: Wilson Jody K. , Mendillo Michael , Spence Harlan E.
Published: July 2006

Atoms in the thin lunar exosphere are liberated from the Moon's regolith by some combination of sunlight, plasma, and meteorite impact. We have observed exospheric sodium, a useful tracer species, on five nights of full Moon in order to test the effect of shielding the lunar surface from the solar wind plasma by the Earth's magnetosphere. These observations, conducted under the dark sky conditions of lunar eclipses, have turned out to be tests of the differential effects of energetic particle populations that strike the Moon's surface when it is in the magnetotail. We find that the brightness of the lunar sodium exosphere at full Moon is correlated with the Moon's passage through the Earth's magnetotail plasma sheet. This suggests that omnipresent exospheric sources (sunlight or micrometeors) are augmented by variable plasma impact sources in the solar wind and Earth's magnetotail.
Three‐dimensional GCM modeling of nitric oxide in the lower thermosphere
Authors: Dobbin A. L. , Aylward A. D. , Harris M. J.
Published: July 2006

The coupled middle atmosphere and thermosphere (CMAT) general circulation model has been used to predict the global distribution of nitric oxide (NO) in the lower thermosphere. This three‐dimensional (3‐D) model incorporates a complex ion and neutral chemical scheme, high‐resolution solar flux data and variable auroral energy inputs. Comparison of simulated NO densities with those observed by the Student Nitric Oxide Explorer (SNOE) show that the CMAT model is able to recreate large‐scale features in the observed NO distribution under differing geophysical conditions. While previous studies have used 1‐D photochemical models to speculate on the latitudinal extent of aurorally produced NO, we have simulated NO production and transport in three dimensions under both geomagnetically stable and disturbed conditions. We have shown that the spatial and temporal distribution of aurorally produced NO is highly variable with location and local time. CMAT simulations suggest that under moderate geomagnetic conditions, the most equatorward geographic latitudes to be influenced by aurorally produced NO are 30°S and 45°N. Under conditions of high geomagnetic activity, aurorally produced NO is present at latitudes poleward of 15°S and 28°N. The asymmetry in latitudinal extent is attributed to the greater offset between geographic and geomagnetic poles in the southern hemisphere. NO density maxima are predicted to occur between 14 and 48 hours after a period of high geomagnetic activity, their spatial and temporal distribution depending on location with respect to the auroral oval and local time at which auroral forcing occurs.
Use of Euler potentials for describing magnetosphere‐ionosphere coupling
Authors: Wolf R. A. , Spiro R. W. , Sazykin S. , Toffoletto F. R. , Le Sager P. , Huang T.‐S.
Published: July 2006

We present a general formulation of the basic equations of large‐scale magnetosphere‐ionosphere coupling in terms of Euler potentials and describe a specific numerical implementation of this formulation in the context of the Rice Convection Model (RCM). When written in terms of Euler potentials, both the Vasyliunas magnetosphere‐ionosphere coupling equation and the expression for bounce‐averaged adiabatic drift assume particularly elegant forms, while the equation for the conservation of ionospheric current is only slightly more complicated to solve than the corresponding formula for a dipole case. For simplicity, large‐scale models of convection in the inner magnetosphere have typically assumed strict symmetry between the northern and southern hemispheres, explicitly assuming the internal planetary magnetic field to be a dipole aligned with Earth's rotation axis and oriented perpendicular to the solar wind flow velocity. These approximations have precluded the realistic treatment of ionospheric longitude and seasonal effects as well as dipole‐tilt and IMF‐By‐penetration effects in the magnetosphere. We present a scheme for constructing an Euler‐potential‐based computational mesh, in which the Euler potential α is set to zero at the dip equator for a reference altitude of 90 km, and β lines in the northern ionosphere follow lines of constant centered dipole magnetic longitude but are spaced equally in terms of total latitude‐integrated magnetic flux. Properties of the Euler‐potential‐based grid are illustrated using an IGRF model for the Earth's internal field. Our procedure yields an Euler‐potential‐based grid that covers the entire ionosphere, except for the southern polar cap and cusp.
Two‐day wave coupling of the low‐latitude atmosphere‐ionosphere system
Authors: Pancheva D. V. , Mukhtarov P. J. , Shepherd M. G. , Mitchell N. J. , Fritts D. C. , Riggin D. M. , Franke S. J. , Batista P. P. , Abdu M. A. , Batista I. S. , Clemesha B. R. , Kikuchi T.
Published: July 2006

Vertical coupling in the low‐latitude atmosphere‐ionosphere system driven by the 2‐day wave in the tropical MLT region has been investigated. The problem is studied from an observational point of view. Three different types of data were analyzed in order to detect and extract the 2‐day wave signals. The 2‐day wave event during the period from 1 December 2002 to 28 February 2003 was identified in the neutral winds by radar measurements located at four tropical stations. The 2‐day variations in the ionospheric electric currents (registered by perturbations in the geomagnetic field) and in the F‐region electron densities were detected in the data from 23 magnetometer and seven ionosonde stations situated at low latitudes. Two features for each kind of wave were investigated in detail: the variation with time of the wave amplitude and the zonal wave number. The results show that the westward propagating global 2‐day wave with zonal wave number 2 seen in the ionospheric currents and in F‐region plasma is forced by the simultaneous 2‐day wave activity in the MLT region. The main forcing agent in this atmosphere‐ionosphere coupling seems to be the modulated tides, particularly the semidiurnal tide. This tide has a larger vertical wavelength than the diurnal tide and propagates well into the thermosphere. The parameter that appears to be affected, and thus drives the observed 2‐day wave response of the ionosphere, is the dynamo electric field.
Mesoscale modeling of Central American smoke transport to the United States: 2. Smoke radiative impact on regional surface energy budget and boundary layer evolution
Authors: Wang Jun , Christopher Sundar A.
Published: July 2006

During 20 April to 21 May 2003, large amounts of smoke aerosols from Central American Biomass Burning (CABB) fires were transported to southeastern United States. Using a coupled aerosol, radiation, and meteorology model built upon the heritage of the Regional Atmospheric Modeling System (RAMS) with new capabilities called the Assimilation and Radiation Online Modeling of Aerosols (AROMA), this paper, the second of a two‐part series, investigates smoke radiative impact on the regional surface energy budget, temperature and relevant boundary layer processes. Comparisons with limited ground‐based observations and MODIS aerosol optical thickness (AOT) showed that model consistently simulated the smoke AOT and smoke radiative impacts on the 2 m air temperature (2mT) and downward shortwave irradiance (DSWI). Over 30 days the 24‐hour mean smoke AOT was 0.18 (at 0.55 μm) near the smoke source region (Yucatan Peninsula and southern Mexico), and 0.09 in downwind region (e.g., southern Texas), both showing a diurnal variation of 24%. Maximum AOT occurred during late afternoon and minimum during early morning in smoke source region. The smoke radiative effects were dominant mostly during the daytime and resulted in the decrease of DSWI, sensible heat and latent heat by 22.5 Wm−2, 6.2 Wm−2, and 6.2 Wm−2, respectively, near the source region, in contrast to 15.8 Wm−2, 4.7 Wm−2, and 7.9 Wm−2, respectively, in downwind regions. Both maximum and minimum 2mT were decreased, and the overall diurnal temperature range (DTR) was reduced by 0.31°C and 0.26°C in the smoke source and downwind regions, respectively. The smoke absorption of solar radiation increased the lapse rate by 0.1–0.5 K/day in the planetary boundary layer (PBL), thus warming the air over the ocean surface. However, over the land surface where the coupling between the lower PBL and the cooler land surface is strong, such warming only occurred in the upper PBL and is amendable to the diurnal variation of smoke emission. The simulation numerically verifies the smoke self‐trapping feedback mechanism proposed by Robock (1988), where the increase of the atmospheric stability in the PBL caused by the smoke radiative effects further traps more smoke aerosols in the lower PBL. Such feedbacks, when coupled with favorable synoptic systems, may have important implications for air quality modeling and hydrological processes.
Interfacial varactor characteristics of ferroelectric thin films on high-resistivity Si substrate
Authors: Lan Wen-An , Wang Tsan-Chun , Huang Ling-Hui , Wu Tai-Bor
Published: July 2006

Ferroelectric Ba(Zr0.25Ti0.75)O3 (BZT) thin films were deposited on high-resistivity Si substrate without or with inserting a high-k buffer layer of Ta2O5. The varactor characteristics of the BZT capacitors in metal-oxide-semiconductor structure were studied. At low frequency (1MHz), the capacitors exhibit a negatively tunable characteristic, i.e., [C(V)−C(0)]∕C(0)<0, against dc bias V, but opposite tunable characteristics were found at microwave frequencies (>1GHz). The change of voltage-dependent characteristic is attributed to the effect of low-resistivity interface induced by charged defects formed from interfacial oxidation of Si in screening the microwave from penetrating into the bulk of Si.
Experimental implementation of a quantum algorithm in a multiqubit NMR system formed by an oriented 7∕2 spin
Authors: Das Ranabir , Kumar Anil
Published: July 2006

A growing appreciation among researchers is the use of quadrupolar nuclei with spin >1∕2 as a suitable candidate for quantum information processing. Such systems have multiple qubits per nuclei and large quadrupolar couplings, resulting in well separated lines in the spectrum. Preparation of pseudopure states and implementation of logic gates have been demonstrated in these systems. Two-qubit quantum algorithms have also been implemented in spin-3∕2 systems. In this letter we report implementation of three-qubit Deutsch-Jozsa algorithm [Proc. R. Soc. London, Ser. A 693, 553 (1992)] in a spin-7∕2 system of Cs133 nucleus oriented in a liquid crystalline matrix.
Photoaddressable bistable reflective liquid crystal display
Authors: Lin Tsung-Hsien , Jau Hung-Chang , Hung San-Yi , Fuh Huei-Ru , Fuh Andy Y.-G.
Published: July 2006

This work presents a bistable reflective liquid crystal display. The mechanism is based on the laser-induced adsorption of azo dyes on the polymer-coated glass substrate. This reflective liquid crystal display is very simple to fabricate and can be optically written, erased, and rewritten with a high contrast. A simulation is performed to fit the measured electro-optical characteristics of this device.
Charge deep-level transient spectroscopy study of high-energy-electron-beam-irradiated hydrogenated amorphous silicon
Authors: Klaver A. , Nádaždy V. , Zeman M. , van Swaaij R. A. C. M. M.
Published: July 2006

We present a study of changes in the defect density of states in hydrogenated amorphous silicon (a-Si:H) due to high-energy electron irradiation using charged deep-level transient spectroscopy. It was found that defect states near the conduction band were removed, while in other band gap regions the defect-state density increased. A similar trend is observed for a-Si:H which has been subjected to light soaking, but in that case the majority of defect states are created around midgap, whereas with electron-beam degradation more defect states are created near the valence-band tail.
How many O2(Δ1) molecules are consumed per dissociated I2 in chemical oxygen-iodine lasers?
Authors: Rybalkin V. , Katz A. , Waichman K. , Vingurt D. , Dahan Z. , Barmashenko B. D. , Rosenwaks S.
Published: July 2006

Direct measurements of the dissociation of I2 molecules at the optical axis of a supersonic chemical oxygen-iodine laser (COIL) as a function of I2 flow rate were carried out. This enabled us to determine the number of consumed O2(Δ1) molecules per dissociated I2 molecule. The number depends on the experimental conditions: it is 4.2±0.4 for typical conditions and I2 densities applied for the operation of the COIL, but increases at lower I2 densities. Possible dissociation mechanisms consistent with our results are discussed and the importance of dissociating I2 prior to its mixing with O2(Δ1) is stressed.
Structural basis for unique mechanisms of folding and hemoglobin binding by a malarial protease
Authors: Wang Stephanie X. , Pandey Kailash C. , Somoza John R. , Sijwali Puran S. , Kortemme Tanja , Brinen Linda S. , Fletterick Robert J. , Rosenthal Philip J. , McKerrow James H.
Published: July 2006

Falcipain-2 (FP2), the major cysteine protease of the human malaria parasite
Plasmodium falciparum
, is a hemoglobinase and promising drug target. Here we report the crystal structure of FP2 in complex with a protease inhibitor, cystatin. The FP2 structure reveals two previously undescribed cysteine protease structural motifs, designated FP2
nose
and FP2
arm
, in addition to details of the active site that will help focus inhibitor design. Unlike most cysteine proteases, FP2 does not require a prodomain but only the short FP2
nose
motif to correctly fold and gain catalytic activity. Our structure and mutagenesis data suggest a molecular basis for this unique mechanism by highlighting the functional role of two Tyr within FP2
nose
and a conserved Glu outside this motif. The FP2
arm
motif is required for hemoglobinase activity. The structure reveals topographic features and a negative charge cluster surrounding FP2
arm
that suggest it may serve as an exo-site for hemoglobin binding. Motifs similar to FP2
nose
and FP2
arm
are found only in related plasmodial proteases, suggesting that they confer malaria-specific functions.
Repression and loss of gene expression outpaces activation and gain in recently duplicated fly genes
Authors: Oakley Todd H. , Østman Bjørn , Wilson Asa C. V.
Published: July 2006

Evolutionists widely acknowledge that regulatory genetic changes are of paramount importance for morphological and genomic evolution. Nevertheless, mechanistic complexity and a paucity of data from nonmodel organisms have prevented testing and quantifying universal hypotheses about the macroevolution of gene regulatory mechanisms. Here, we use a phylogenetic approach to provide a quantitative demonstration of a previously hypothesized trend, whereby the evolutionary rate of repression or loss of gene expression regions is significantly higher than the rate of activation or gain. Such a trend is expected based on case studies in regulatory evolution and under models of molecular evolution where duplicated genes lose duplicated expression patterns in a complementary fashion. The trend is important because repression of gene expression is a hypothesized mechanism for the origin of evolutionarily novel morphologies through specialization.
MPS1-dependent mitotic BLM phosphorylation is important for chromosome stability
Authors: Leng Mei , Chan Doug W. , Luo Hao , Zhu Cihui , Qin Jun , Wang Yi
Published: July 2006

Spindle assembly checkpoint (SAC) ensures bipolar attachment of chromosomes to the mitotic spindle and is essential for faithful chromosome segregation, thereby preventing chromosome instability (CIN). Genetic evidence suggests a causal link between compromised SAC, CIN, and cancer. Bloom syndrome (BS) is a genetic disorder that predisposes affected individuals to cancer. BS cells exhibit elevated rates of sister chromatid exchange, chromosome breaks, and CIN. The BS gene product, BLM, is a member of the RecQ helicases that are required for maintenance of genome stability. The BLM helicase interacts with proteins involved in DNA replication, recombination, and repair and is required for the repair of stalled-replication forks and in the DNA damage response. Here we present biochemical evidence to suggest a role of BLM phosphorylation during mitosis in maintaining chromosome stability. BLM is associated with the SAC kinase MPS1 and is phosphorylated at S144 in a MPS1-dependent manner. Phosphorylated BLM interacts with polo-like kinase 1, a mitotic kinase that binds to phospho-serine/threonine through its polo-box domain (PBD). Furthermore, BS cells expressing BLM-S144A show normal levels of sister chromatid exchange but fail to maintain the mitotic arrest when SAC is activated and exhibit a broad distribution of chromosome numbers. We propose that MPS1-dependent BLM phosphorylation is important for ensuring accurate chromosome segregation, and its deregulation may contribute to cancer.
Cellular asymmetry and individuality in directional sensing
Authors: Samadani Azadeh , Mettetal Jerome , van Oudenaarden Alexander
Published: July 2006

It is generally assumed that single cells in an isogenic population, when exposed to identical environments, exhibit the same behavior. However, it is becoming increasingly clear that, even in a genetically identical population, cellular behavior can vary significantly among cells. Here we explore this variability in the gradient-sensing response of
Dictyostelium
cells when exposed to repeated spatiotemporal pulses of chemoattractant. Our experiments show the response of a single cell to be highly reproducible from pulse to pulse. In contrast, a large variability in the response direction and magnitude is observed from cell to cell, even when different cells are exposed to the same pulse. First, these results indicate that the gradient-sensing network has inherent asymmetries that can significantly impact the ability of cells to faithfully sense the direction of extracellular signals (cellular asymmetry). Second, we find that the magnitude of this asymmetry varies greatly among cells. Some cells are able to accurately follow the direction of an extracellular stimulus, whereas, in other cells, the intracellular asymmetry dominates, resulting in a polarization axis that is independent of the direction of the extracellular cue (cellular individuality). We integrate these experimental findings into a model that treats the effective signal a cell detects as the product of the extracellular signal and the asymmetric intracellular signal. With this model we successfully predict the population response. This cellular individuality and asymmetry might fundamentally limit the fidelity of signal detection; in contrast, however, it might be beneficial by diversifying phenotypes in isogenic populations.
Vascularized organoid engineered by modular assembly enables blood perfusion
Authors: McGuigan Alison P. , Sefton Michael V.
Published: July 2006

Tissue engineering is one approach to address the donor-organ shortage, but to attain clinically significant viable cell densities in thick tissues, laboratory-constructed tissues must have an internal vascular supply. We have adopted a biomimetic approach and assembled microscale modular components, consisting of submillimeter-sized collagen gel rods seeded with endothelial cells (ECs) into a (micro)vascularized tissue; in some prototypes the gel contained HepG2 cells to illustrate the possibilities. The EC-covered modules then were assembled into a larger tube and perfused with medium or whole blood. The interstitial spaces among the modules formed interconnected channels that enabled this perfusion. Viable cell densities were high, within an order of magnitude of cell densities within tissues, and the percolating nature of the flow through the construct was evident in microcomputed tomography and Doppler ultrasound measurements. Most importantly, the ECs retained their nonthrombogenic phenotype and delayed clotting times and inhibited the loss of platelets associated with perfusion of whole blood through the construct. Unlike the conventional scaffold and cell-seeding paradigm of other tissue-engineering approaches, this modular construct has the potential to be scalable, uniform, and perfusable with whole blood, circumventing the limitations of other approaches.
Microsomal prostaglandin E synthase-1 is a critical factor of stroke-reperfusion injury
Authors: Ikeda-Matsuo Yuri , Ota Azusa , Fukada Tetsuya , Uematsu Satoshi , Akira Shizuo , Sasaki Yasuharu
Published: July 2006

Although augmented prostaglandin E
2
(PGE
2
) synthesis and accumulation have been demonstrated in the lesion sites of rodent transient focal ischemia models, the role of PGE
2
in neuronal survival has been controversial, showing both protective and toxic effects. Here we demonstrate the induction of microsomal PGE synthase 1 (mPGES-1), an inducible terminal enzyme for PGE
2
synthesis, in neurons, microglia, and endothelial cells in the cerebral cortex after transient focal ischemia. In mPGES-1 knockout (KO) mice, in which the postischemic PGE
2
production in the cortex was completely absent, the infarction, edema, apoptotic cell death, and caspase-3 activation in the cortex after ischemia were all reduced compared with those in wild-type (WT) mice. Furthermore, the behavioral neurological dysfunctions observed after ischemia in WT mice were significantly ameliorated in KO mice. The ameliorated symptoms observed in KO mice after ischemia were reversed to almost the same severity as WT mice by intracerebroventricular injection of PGE
2
into KO mice. Our observations suggest that mPGES-1 may be a critical determinant of postischemic neurological dysfunctions and a valuable therapeutic target for treatment of human stroke.
Glatiramer acetate fights against Alzheimer’s disease by inducing dendritic-like microglia expressing insulin-like growth factor 1
Authors: Butovsky Oleg , Koronyo-Hamaoui Maya , Kunis Gilad , Ophir Eran , Landa Gennady , Cohen Hagit , Schwartz Michal
Published: July 2006

Alzheimer’s disease (AD) is characterized by plaque formation, neuronal loss, and cognitive decline. The functions of the local and systemic immune response in this disease are still controversial. Using AD double-transgenic (APP/PS1) mice, we show that a T cell-based vaccination with glatiramer acetate, given according to a specific regimen, resulted in decreased plaque formation and induction of neurogenesis. It also reduced cognitive decline, assessed by performance in a Morris water maze. The vaccination apparently exerted its effect by causing a phenotype switch in brain microglia to dendritic-like (CD11c) cells producing insulin-like growth factor 1.
In vitro
findings showed that microglia activated by aggregated β-amyloid, and characterized as CD11b
+
/CD11c
−
/MHC class II
−
/TNF-α
+
cells, impeded neurogenesis from adult neural stem/progenitor cells, whereas CD11b
+
/CD11c
+
/MHC class II
+
/TNF-α
−
microglia, a phenotype induced by IL-4, counteracted the adverse β-amyloid-induced effect. These results suggest that dendritic-like microglia, by facilitating the necessary adjustment, might contribute significantly to the brain’s resistance to AD and argue against the use of antiinflammatory drugs.
N-Mycand the cyclin-dependent kinase inhibitors p18Ink4cand p27Kip1coordinately regulate cerebellar development
Authors: Zindy Frederique , Knoepfler Paul S. , Xie Suqing , Sherr Charles J. , Eisenman Robert N. , Roussel Martine F.
Published: July 2006

Conditional N-Mycdeletion limits the proliferation of granule neuron progenitors (GNPs), perturbs foliation, and leads to reduced cerebellar mass. We show that c-MycmRNA levels increase in N-Myc-null GNPs and that simultaneous deletion of both c- and N-Mycexacerbates defective cerebellar development. Moreover, N-Mycloss has been shown to trigger the precocious expression of two cyclin-dependent kinase inhibitors, Kip1 and Ink4c, in the cerebellar primordium. We now further demonstrate that the engineered disruption of theKip1andInk4cgenes in N-Myc-null cerebella partially rescues GNP cell proliferation and cerebellar foliation. These results provide definitive genetic evidence that expression of N-Mycand concomitant down-regulation ofInk4candKip1contribute to the proper development of the cerebellum.
Solution structure of Urm1 and its implications for the origin of protein modifiers
Authors: Xu Junjie , Zhang Jiahai , Wang Li , Zhou Jie , Huang Hongda , Wu Jihui , Zhong Yang , Shi Yunyu
Published: July 2006

Protein modifiers are involved in diverse biological processes and regulate the activity or function of target proteins by covalently conjugating to them. Although ubiquitin and a number of ubiquitin-like protein modifiers (Ubls) in eukaryotes have been identified, no protein modifier has been found in prokaryotes; thus, their evolutionary origin remains a puzzle. To infer the evolutionary relationships between the protein modifiers and sulfur carrier proteins, we solved the solution NMR structure of the Urm1 (ubiquitin-related modifier-1) protein from
Saccharomyces cerevisiae
. Both structural comparison and phylogenetic analysis of the ubiquitin superfamily, with emphasis on the Urm1 family, indicate that Urm1 is the unique “molecular fossil” that has the most conserved structural and sequence features of the common ancestor of the entire superfamily. The similarities of 3D structure and hydrophobic and electrostatic surface features between Urm1 and MoaD (molybdopterin synthase small subunit) suggest that they may interact with partners in a similar manner, and similarities between Urm1–Uba4 and MoaD–MoeB establish an evolutionary link between ATP-dependent protein conjugation in eukaryotes and ATP-dependent cofactor sulfuration.
Identification and characterization of a lysophosphatidylcholine acyltransferase in alveolar type II cells
Authors: Chen Xueni , Hyatt Brian A. , Mucenski Michael L. , Mason Robert J. , Shannon John M.
Published: July 2006

Pulmonary surfactant is a complex of lipids and proteins produced and secreted by alveolar type II cells that provides the low surface tension at the air–liquid interface. The phospholipid most responsible for providing the low surface tension in the lung is dipalmitoylphosphatidylcholine. Dipalmitoylphosphatidylcholine is synthesized in large part by phosphatidylcholine (PC) remodeling, and a lysophosphatidylcholine (lysoPC) acyltransferase is thought to play a critical role in its synthesis. However, this acyltransferase has not yet been identified. We have cloned full-length rat and mouse cDNAs coding for a lysoPC acyltransferase (LPCAT). LPCAT encodes a 535-aa protein of ≈59 kDa that contains a transmembrane domain and a putative acyltransferase domain. When transfected into COS-7 cells and HEK293 cells, LPCAT significantly increased lysoPC acyltransferase activity. LPCAT preferred lysoPC as a substrate over lysoPA, lysoPI, lysoPS, lysoPE, or lysoPG and prefers palmitoyl-CoA to oleoyl-CoA as the acyl donor. This LPCAT was preferentially expressed in the lung, specifically within alveolar type II cells. Expression in the fetal lung and in rat type II cells correlated with the expression of the surfactant proteins. LPCAT expression in fetal lung explants was sensitive to dexamethasone and FGFs. KGF was a potent stimulator of LPCAT expression in cultured adult type II cells. We hypothesize that LPCAT plays a critical role in regulating surfactant phospholipid biosynthesis and suggest that understanding the regulation of LPCAT will offer important insight into surfactant phospholipid biosynthesis.
Reversal of RNA missplicing and myotonia after muscleblind overexpression in a mouse poly(CUG) model for myotonic dystrophy
Authors: Kanadia Rahul N. , Shin Jihae , Yuan Yuan , Beattie Stuart G. , Wheeler Thurman M. , Thornton Charles A. , Swanson Maurice S.
Published: July 2006

RNA-mediated pathogenesis is a recently developed disease model that proposes that certain types of mutant genes produce toxic transcripts that inhibit the activities of specific proteins. This pathogenesis model was proposed first for the neuromuscular disease myotonic dystrophy (DM), which is associated with the expansion of structurally related (CTG)
n
and (CCTG)
n
microsatellites in two unrelated genes. At the RNA level, these expansions form stable hairpins that alter the pre-mRNA splicing activities of two antagonistic factor families, the MBNL and CELF proteins. It is unclear which altered activity is primarily responsible for disease pathogenesis and whether other factors and biochemical pathways are involved. Here, we show that overexpression of Mbnl1
in vivo
mediated by transduction of skeletal muscle with a recombinant adeno-associated viral vector rescues disease-associated muscle hyperexcitability, or myotonia, in the
HSA
LR
poly(CUG) mouse model for DM. Myotonia reversal occurs concurrently with restoration of the normal adult-splicing patterns of four pre-mRNAs that are misspliced during postnatal development in DM muscle. Our results support the hypothesis that the loss of MBNL1 activity is a primary pathogenic event in the development of RNA missplicing and myotonia in DM and provide a rationale for therapeutic strategies designed either to overexpress MBNL1 or inhibit MBNL1 interactions with CUG and CCUG repeat expansions.
Quitting Among Non‐Treatment‐Seeking Marijuana Users: Reasons and Changes in Other Substance Use
Authors: Copersino Marc L. , Boyd Susan J. , Tashkin Donald P. , Huestis Marilyn A. , Heishman Stephen J. , Dermand John C. , Simmons Michael S. , Gorelick David A.
Published: July 2006

This study examines the self‐reported reasons for quitting marijuana use, changes in other substance use during the quit attempt, and reasons for the resumption of use in 104 non‐treatment‐seeking adult marijuana smokers. Reasons for quitting were shown to be primarily motivated by concerns about the negative impact of marijuana on health and on self‐and social image. The spontaneous quitting of marijuana use is often associated with an increase in the use of legal substances such as alcohol, tobacco, and sleeping aids, but not with the initiation of new substance use. These findings suggest areas for further research on spontaneous recovery from marijuana use.
Enhancing challenged students’ recognition of mathematical relations through differential outcomes training
Authors: Estévez Angeles F. , Vivas Ana B. , Alonso Diego , Marí-Beffa Paloma , Fuentes Luis J. , Overmier J. Bruce
Published: July 2006

Previous studies have reported that the differential outcomes procedure enhances learning and memory in special populations with cognitive deficits (see Goeters, Blakely, & Poling, 1992, for a review). In the present study we extend these findings to healthy adults who were asked to discriminate between the symbols “ > ” and “ < ” in mathematical statements. In Experiment 1, the performance of participants who showed difficulties in discriminating between these symbols was better (shorter response times) for the differential outcomes condition than for the nondifferential outcomes condition. In Experiment 2, the difficulty of the task was increased by using signed decimal numbers. Similar to Experiment 1, participants who initially had difficulties in discriminating between the symbols showed better performance (higher accuracy) for the differential outcomes condition than for the nondifferential outcomes condition, but only when both numbers were negative. These findings suggest that the differential outcomes procedure can be used to improve performance of challenged healthy adults on discrimination tasks with mathematical symbols and relations.
Mechanisms of the associated nontargets effect: Processes influenced by statistical learning in a simple visual environment
Authors: Reynolds Ann , Miller Jeff
Published: July 2006

In three visual search experiments participants were asked to make a target response if either of two targets was present and to make a nontarget response if neither target was present. Some target-absent displays included only nontarget features that never occurred in the same displays as target features, whereas other target-absent displays included nontarget features that did sometimes occur with target features. Nontarget responses were reliably faster in the former case than in the latter. This “associated nontargets effect” appears to arise from participants’ ability to learn and to use contingencies between the presence of certain nontargets and the absence of any target.
Identification of Golgi-localized acyl transferases that palmitoylate and regulate endothelial nitric oxide synthase
Authors: Fernández-Hernando Carlos , Fukata Masaki , Bernatchez Pascal N. , Fukata Yuko , Lin Michelle I. , Bredt David S. , Sessa William C.
Published: July 2006

Lipid modifications mediate the subcellular localization and biological activity of many proteins, including endothelial nitric oxide synthase (eNOS). This enzyme resides on the cytoplasmic aspect of the Golgi apparatus and in caveolae and is dually acylated by both N-myristoylation and S-palmitoylation. Palmitoylation-deficient mutants of eNOS release less nitric oxide (NO). We identify enzymes that palmitoylate eNOS in vivo. Transfection of human embryonic kidney 293 cells with the complementary DNA (cDNA) for eNOS and 23 cDNA clones encoding the Asp-His-His-Cys motif (DHHC) palmitoyl transferase family members showed that five clones (2, 3, 7, 8, and 21) enhanced incorporation of [3H]-palmitate into eNOS. Human endothelial cells express all five of these enzymes, which colocalize with eNOS in the Golgi and plasma membrane and interact with eNOS. Importantly, inhibition of DHHC-21 palmitoyl transferase, but not DHHC-3, in human endothelial cells reduces eNOS palmitoylation, eNOS targeting, and stimulated NO production. Collectively, our data describe five new Golgi-targeted DHHC enzymes in human endothelial cells and suggest a regulatory role of DHHC-21 in governing eNOS localization and function.