bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex Differences in the Effects of Inherited Bitter Thiourea Sensitivity on Body Weight in 4–6‐Year‐Old Children
Authors: Keller Kathleen L. , Reid Adrienne , MacDougall Megan C. , Cassano Hope , Song Joo Lee , Deng Liyong , Lanzano Patricia , Chung Wendy K. , Kissileff Harry R.
Published: September 2009

Previous studies have shown that inherited taste blindness to bitter compounds like 6‐n‐propylthiouracil (PROP) may be a risk factor for obesity, but this literature has been highly controversial. The objectives of this study were (i) to confirm findings that show an interaction between PROP status and sex on BMI z‐score, and (ii) to determine if sex also interacts with variations in TAS2R38 (phenylthiocarbamide (PTC) genotype) to influence weight status in 4–6 year olds. Also, we tested whether nontaster children consumed more fat and total energy at laboratory‐based meals. Seventy‐two ethnically diverse children who ranged in weight status were classified as tasters (N = 52) or nontasters (N = 20) using a standard PROP screening solution. Anthropometric measures were taken, and at the end of each visit, children ate ad libitum from test meals intended for exploratory purposes. Genomic DNA was extracted from saliva and alleles at TAS2R38 were genotyped for A49P polymorphisms. In 75.8% of children, PTC genotype predicted PROP phenotype, whereas in 24.4%, genotype did not predict phenotype. PROP nontaster males had higher BMI z‐scores than taster‐males and females in both groups (P < 0.05), but due to a three‐way interaction between PROP phenotype, TAS2R38 genotype, and sex, this relationship was only true for children who were homozygous for the bitter‐insensitive allele (P < 0.0005). There were no differences in test‐meal intake as a function of PROP phenotype or TAS2R38 genotype. These results suggest that the TAS2R38 variation, PROP phenotype, and sex interact to impact obesity risk in children. Future studies should be done to determine how this trait influences energy balance.
Post-translational modifications of connexin26 revealed by mass spectrometry
Authors: Locke Darren , Bian Shengjie , Li Hong , Harris Andrew L.
Published: September 2009

Gap junctions play important roles in auditory function and skin biology; mutations in the Cx26 (connexin26) gene are the predominant cause of inherited non-syndromic deafness and cause disfiguring skin disorders. Mass spectrometry (MS) was used to identify PTMs (post-translational modifications) of Cx26 and to determine whether they occur at sites of disease-causing mutations. Cx26 was isolated from transfected HeLa cells by sequential immunoaffinity and metal chelate chromatography using a tandem C-terminal haemagglutinin epitope and a (His-Asn)6 sequence. In-gel and in-solution enzymatic digestions were carried out in parallel with trypsin, chymotrypsin and endoproteinase GluC. Peptides were fractionated using a reversed-phase matrix by stepwise elution with increasing concentrations of organic solvent. To improve detection of low-abundance peptides and to maximize sequence coverage, MALDI–TOF-MS (matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry; MS) and MALDI–TOF/TOF-MS/MS (matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry; MS/MS) spectra were acquired from each elution step using an Applied Biosystems 4800 tandem mass spectrometer. Acquisition, processing and interpretation parameters were optimized to improve ionization and fragmentation of hydrophobic peptides. MS and MS/MS coverage of Cx26 was significantly above that reported for other membrane proteins: 71.3% by MS, with 29.9% by MS/MS. MS coverage was 92.6% if peptides resulting from in-source collisions and/or partial enzymatic cleavages were considered. A variety of putative PTMs of Cx26 were identified, including acetylation, hydroxylation, γ-carboxyglutamation, methylation and phosphorylation, some of which are at sites of deafness-causing mutations. Knowledge of the PTMs of Cx26 will be instrumental in understanding how alterations in the cellular mechanisms of Cx26 channel biogenesis and function lead to losses in auditory function and disfiguring skin disorders.
The Influence of Speaking Rate on Nasality in the Speech of Hearing-Impaired Individuals
Authors: Dwyer Claire H. , Robb Michael P. , O’Beirne Greg A. , Gilbert Harvey R.
Published: September 2009

Purpose

The purpose of this study was to determine whether deliberate increases in speaking rate would serve to decrease the amount of nasality in the speech of severely hearing-impaired individuals.

Method

The participants were 11 severely to profoundly hearing-impaired students, ranging in age from 12 to 19 years (
M
= 16 years). Each participant provided a baseline speech sample (R1) followed by 3 training sessions during which participants were trained to increase their speaking rate. Following the training sessions, a second speech sample was obtained (R2). Acoustic and perceptual analyses of the speech samples obtained at R1 and R2 were undertaken. The acoustic analysis focused on changes in first (F
1
) and second (F
2
) formant frequency and formant bandwidths. The perceptual analysis involved listener ratings of the speech samples (at R1 and R2) for perceived nasality.

Results

Findings indicated a significant increase in speaking rate at R2. In addition, significantly narrower F
2
bandwidth and lower perceptual rating scores of nasality were obtained at R2 across all participants, suggesting a decrease in nasality as speaking rate increases.

Conclusion

The nasality demonstrated by hearing-impaired individuals is amenable to change when speaking rate is increased. The influences of speaking rate changes on the perception and production of nasality in hearing-impaired individuals are discussed.
Tongue Movements During Water Swallowing in Healthy Young and Older Adults
Authors: Steele Catriona M. , Van Lieshout Pascal
Published: September 2009

Purpose

The purpose of this study was to explore the nature and extent of variability in tongue movement during healthy swallowing as a function of aging and gender. In addition, changes were quantified in healthy tongue movements in response to specific differences in the nature of the swallowing task (discrete vs. sequential swallows).

Method

Electromagnetic midsagittal articulography (EMMA) was used to study the swallowing-related movements of markers located in midline on the anterior (blade), middle (body), and posterior (dorsum) tongue in a sample of 34 healthy adults in 2 age groups (under vs. over 50 years of age). Participants performed a series of reiterated water swallows, in either a discrete or a sequential manner.

Results

This study shows that age-related changes in tongue movements during swallowing are restricted to the domain of movement duration. The authors confirm that different tongue regions can be selectively modulated during swallowing tasks and that both functional and anatomical constraints influence the manner in which tongue movement modulation occurs. Sequential swallowing, in comparison to discrete swallowing, elicits simplification or down-scaling of several kinematic parameters.

Conclusion

The data illustrate task-specific stereotyped patterns of tongue movement in swallowing, which are robust to the effects of healthy aging in all aspects other than movement duration.
Visual Globes, Celestial Spheres, and the Perception of Straight and Parallel Lines
Authors: Rogers Brian , Rogers Cassandra
Published: September 2009

Helmholtz's famous distorted chessboard pattern has been used to make the point that perception of the straightness of peripherally viewed lines is not always veridical. Helmholtz showed that the curved lines of his chessboard pattern appear to be straight when viewed from a critical distance and he argued that, at this distance, the contours stimulated particular ‘direction circles’ in the field of fixation. We measured the magnitude of the distortion of peripherally viewed contours, and found that the straightness of elongated contours is indeed misperceived in the direction reported by Helmholtz, but that the magnitude of the effect varies with viewing conditions. On the basis of theoretical considerations, we conclude that there cannot, in principle, be particular retinal loci (‘loci’ is used here in the sense of an arc or an extended set of points that provide a basis for judging collinearity) to underpin our judgments of the straightness and parallelity of peripheral contours, because such judgments also require information about the 3-D surface upon which the contours are located. Moreover, we show experimentally that the contours in the real world that are judged to be straight and parallel can stimulate quite different retinal loci, depending on the shape of the 3-D surface upon which they are drawn.
Amodal Completion is Not Completed Only behind the Occluder
Authors: Takashima Midori , Fujii Teruo , Shiina Ken
Published: September 2009

We investigated amodal completion with changes in two parameters: figure orientation, and the shape of the occluding and occluded figures. First, Markovich's [2002, Visual Mathematics4(1); http://www.mi.sanu.ac.rs/vismath/fila ] figure was presented in vertical, horizontal, and diagonal orientations. The results supported Markovich's finding of amodal completion by smooth continuity and symmetry. Amodal completion was also affected by orientation: symmetrical shape tended to appear when the pattern had vertical axis whilst smooth continuity appeared in diagonal orientation. Next, the shape of the exposed side of the occluded figure was changed from straight to curved. Finally, the shape of the grey occluder was changed from a disk to a half-disk or a quarter-disk. The results then showed the influence of the visible contour on amodal completion. This shows that the contextual relation of the whole figure is significant in amodal completion.
A Few Binary Star Puzzles for Roberto on the Occasion of His Birthday
Authors: Preston George W.
Published: September 2009

Radial-velocity observations accumulated during the past 16 years are used to derive a preliminary orbit for the CEMP star CS 22881–036. The velocity amplitude is very small. No velocity variation is found for three additional CEMP stars observed over roughly the same time interval. Searches for companions of two CEMP double-lined spectroscopic binaries and of the RR Lyrae star TY Gru are reviewed. A disparity between the period distribution of disk carbon-star binaries and that of their parent population of normal binaries can be attributed qualitatively to a decline in accreted mass with increasing binary separation. Finally, possible reasons for failure to find expected companions of CEMP stars are discussed.
He and Ne Ages of Large Presolar Silicon Carbide Grains: Solving the Recoil Problem
Authors: Ott Ulrich , Heck Philipp R. , Gyngard Frank , Wieler Rainer , Wrobel Frédéric , Amari Sachiko , Zinner Ernst
Published: September 2009

Knowledge about the age of presolar grains provides important insights into Galactic chemical evolution and the dynamics of grain formation and destruction processes in the Galaxy. Determination from the abundance of cosmic ray interaction products is straightforward, but in the past has suffered from uncertainties in correcting for recoil losses of spallation products. The problem is less serious in a class of large (tens of μm) grains. We describe the correction procedure and summarise results for He and Ne ages of presolar SiC ‘Jumbo’ grains that range from close to zero to ∼850 Myr, with the majority being less than 200 Myr. We also discuss the possibility of extending our approach to the majority of smaller SiC grains and explore possible contributions from trapping of cosmic rays.
Nucleosynthesis of Light-Element Isotopes in Evolved Stars Experiencing Extended Mixing
Authors: Palmerini S. , Busso M. , Maiorca E. , Guandalini R.
Published: September 2009

We present computations of nucleosynthesis in red giants and Asymptotic Giant Branch (AGB) stars of Population I experiencing extended mixing. The assumed physical cause for mass transport is the buoyancy of magnetized structures, according to recent suggestions. The peculiar property of such a mechanism is to allow for both fast and slow mixing phenomena, as required for reproducing the spread in Li abundances displayed by red giants and as discussed in an accompanying paper. We explore here the effects of this kind of mass transport on CNO and intermediate-mass nuclei and compare the results with the available evidence from evolved red giants and from the isotopic composition of presolar grains of AGB origin. It is found that a good general accord exists between predictions and measurements; in this framework we also show which type of observational data best constrains the various parameters. We conclude that magnetic buoyancy, allowing for mixing at rather different speeds, can be an interesting scenario to explore for explaining together the abundances of CNO nuclei and of Li.
Monoenergetic Neutrons for Stellar Applications
Authors: Mosconi M. , Heil M. , Käppeler F. , Plag R. , Mengoni A. , Nolte R.
Published: September 2009

With modern techniques, neutron-capture cross sections can be determined with uncertainties of a few percent. However, Maxwellian averaged cross sections calculated from such data require a correction (because low-lying excited states are thermally populated in the hot stellar photon bath) which has to be determined by theoretical calculations. These calculations can be improved with information from indirect measurements, in particular by the inelastic scattering cross section. For low-lying levels, the inelastically scattered neutrons are difficult to separate from the dominant elastic channel. This problem is best solved by means of pulsed, monoenergetic neutron beams. For this reason, a pulsed beam of 30 keV neutrons with an energy spread of 7 to 9 keV FWHM and a width from 10 to 15 ns has been produced at Forschungszentrum Karlsruhe using the 7Li(p, n)7Be reaction directly at the reaction threshold. With this neutron beam the inelastic scattering cross section of the first excited level at 9.75 keV in 187Os was determined with a relative uncertainty of 6%. The use of monoenergetic neutron beams has been further pursued at the Physikalisch-Technische Bundesanstalt in Braunschweig, including the 3H(p, n)3He reaction for producing neutrons with an energy of 64 keV.
Presolar Diamond in Meteorites
Authors: Amari Sachiko
Published: September 2009

Presolar diamond, the carrier of the isotopically anomalous Xe component Xe–HL, was the first mineral type of presolar dust that was isolated from meteorites. The excesses in the light, p-process only isotopes 124Xe and 126Xe, and in the heavy, r-process only isotopes 134Xe and 136Xe relative to the solar ratios indicate that Xe–HL was produced in supernovae: they are the only stellar source where these two processes are believed to take place. Although these processes occur in supernovae, their physical conditions and timeframes are completely different. Yet the excesses are always correlated in diamond separates from meteorites. Furthermore, the p-process 124Xe/126Xe inferred from Xe–L and the r-process 134Xe/136Xe from Xe–H do not agree with the p-process and r-process ratios derived from the solar system abundance, and the inferred p-process ratio does not agree with those predicted from stellar models. The ‘rapid separation scenario’, where the separation of Xe and its radiogenic precursors Te and I takes place at the very early stage (7900 s after the end of the r-process), has been proposed to explain Xe–H. Alternatively, mixing of 20% of material that experienced neutron burst and 80% of solar material can reproduce the pattern of Xe–H, although Xe–L is not accounted for with this scenario.
Time-Scales of thesProcess: from Minutes to Ages
Authors: Käppeler F. , Bisterzo S. , Gallino R. , Heil M. , Pignatari M. , Reifarth R. , Straniero O. , Walter S. , Winckler N. , Wisshak K.
Published: September 2009

The time scales in thesprocess appears to be an approriate aspect to discuss at the occasion of Roberto's 70th anniversary, the more as this subject has been repeatedly addressed during the 20 years of collaboration between Torino and Karlsruhe. The two chronometers presented in this text were selected to illustrate the intense mutual stimulation of both groups. Based on a reliable set of accurate stellar (n,γ) cross sections determined mostly at FZK, the Torino group succeeded to develop a comprehensive picture of the variouss-process scenarios, which are most valuable for understanding the composition of the solar system as well as for the interpretation of an increasing number of astronomical observations.
Galactic Chemical Evolution of the s Process from AGB Stars
Authors: Serminato Alessandra , Gallino Roberto , Travaglio Claudia , Bisterzo Sara , Straniero Oscar
Published: September 2009

We follow the chemical evolution of the Galaxy for the s elements using a Galactic chemical evolution (GCE) model, as already discussed by Travaglio et al. (1999, 2001, 2004), with a full updated network and refined asymptotic giant branch (AGB) models. Calculations of the s contribution to each isotope at the epoch of the formation of the solar system is determined by following the GCE contribution by AGB stars only. Then, using the r-process residual method we determine for each isotope their solar system r-process fraction, and recalculate the GCE contribution of heavy elements accounting for both the s and r process. We compare our results with spectroscopic abundances at various metallicities of [Sr,Y,Zr/Fe], of [Ba,La/Fe], of [Pb/Fe], typical of the three s-process peaks, as well as of [Eu/Fe], which in turn is a typical r-process element. Analysis of the various uncertainties involved in these calculations are discussed.
Interpretation of CEMP(s) and CEMP(s + r) Stars with AGB Models
Authors: Bisterzo Sara , Gallino Roberto , Straniero Oscar , Aoki Wako
Published: September 2009

Asymptotic Giant Branch (AGB) stars play a fundamental role in s-process nucleosynthesis during their thermal pulsing phase. The theoretical predictions obtained by AGB models at different masses, s-process efficiencies, dilution factors and initial r-enrichment, are compared with spectroscopic observations of Carbon-Enhanced Metal-Poor stars enriched in s-process elements, CEMP(s), collected from the literature. We discuss here five stars as example, CS 22880-074, CS 22942-019, CS 29526-110, HE 0202-2204 and LP 625-44. All these objects lie on the main sequence or on the giant phase, clearly before the thermally pulsing AGB stage. The hypothesis of mass transfer from an AGB companion, would explain the observed s-process enhancement. CS 29526-110 and LP 625-44 are CEMP(s + r) objects, and are interpreted assuming that the molecular cloud, from which the binary system formed, was already enriched in r-process elements by SNII pollution. In several cases, the observed s-process distribution may be accounted for by AGB models of different initial masses with proper 13C-pocket efficiencies and dilution factors. Na (and Mg), produced via the neutron capture chain starting from 22Ne, may provide an indicator of the initial AGB mass.
The Solar Photospheric Nitrogen Abundance: Determination with 3D and 1D Model Atmospheres
Authors: Maiorca E. , Caffau E. , Bonifacio P. , Busso M. , Faraggiana R. , Steffen M. , Ludwig H.-G. , Kamp I.
Published: September 2009

We present a new determination of the solar nitrogen abundance making use of 3D hydrodynamical modelling of the solar photosphere, which is more physically motivated than traditional static 1D models. We selected suitable atomic spectral lines, relying on equivalent width measurements already existing in the literature. For atmospheric modelling we used the co5bold 3D radiation hydrodynamics code. We investigated the influence of both deviations from local thermodynamic equilibrium (non-LTE effects) and photospheric inhomogeneities (granulation effects) on the resulting abundance. We also compared several atlases of solar flux and centre-disc intensity presently available. As a result of our analysis, the photospheric solar nitrogen abundance is A(N) = 7.86 ± 0.12.
Chemical Evolution of the Juvenile Universe
Authors: Wasserburg G. J. , Qian Y.-Z.
Published: September 2009

Models of average Galactic chemical abundances are in good general agreement with observations for [Fe/H] > –1.5, but there are gross discrepancies at lower metallicities. Only massive stars contribute to the chemical evolution of the ‘juvenile universe’ corresponding to [Fe/H] ≲ –1.5. If Type II supernovae (SNe II) are the only relevant sources, then the abundances in the interstellar medium of the juvenile epoch are simply the sum of different SN II contributions. Both low-mass (∼8–11 M⊙) and normal (∼12–25 M⊙) SNe II produce neutron stars, which have intense neutrino-driven winds in their nascent stages. These winds produce elements such as Sr, Y and Zr through charged-particle reactions (CPR). Such elements are often called the ‘light r-process elements’, but are considered here as products of CPR and not the r process. The observed absence of production of the low-A elements (Na through Zn including Fe) when the true r-process elements (Ba and above) are produced requires that only low-mass SNe II be the site if the r process occurs in SNe II. Normal SNe II produce the CPR elements in addition to the low-A elements. This results in a two-component model that is quantitatively successful in explaining the abundances of all elements relative to hydrogen for –3 ≲ [Fe/H] ≲ –1.5. This model explicitly predicts that [Sr/Fe] ≥ –0.32. Recent observations show that there are stars with [Sr/Fe] ≲ –2 and [Fe/H] < –3. This proves that the two-component model is not correct and that a third component is necessary to explain the observations. The production of CPR elements associated with the formation of neutron stars requires that the third component must be massive stars ending as black holes. It is concluded that stars of ∼25–50 M⊙ (possibly up to ∼100 M⊙) are the appropriate candidates. These produce hypernovae (HNe) that have very high Fe yields and are observed today. Stars of ∼140–260 M⊙ are completely disrupted upon explosion. However, they produce an abundance pattern greatly deficient in elements of odd atomic numbers, which is not observed, and therefore they are not considered as a source here. Using a Salpeter initial mass function, it is shown that HNe are a source of Fe that far outweighs normal SNe II, with the former and the latter contributing ∼24% and ∼9% of the solar Fe abundance, respectively. It follows that the usual assignment of ∼⅓ of the solar Fe abundance to normal SNe II is not correct. This leads to a simple three-component model including low-mass and normal SNe II and HNe, which gives a good description of essentially all the data for stars with [Fe/H] ≲ –1.5. We conclude that HNe are more important than normal SNe II in the chemical evolution of the low-A elements from Na through Zn (including Fe), in sharp distinction to earlier models.
Binary Populations of Carbon-Enhanced Metal-Poor Stars
Authors: Izzard Robert G. , Glebbeek Evert , Stancliffe Richard J. , Pols Onno
Published: September 2009

We construct binary-star population nucleosynthesis models of carbon-enhanced metal-poor (CEMP) stars. We compare the CEMP to extremely metal-poor (EMP) ratio of our models to the observed ratio and find it is an order of magnitude too small. Through an increase in the efficiency of third dredge-up in low-mass, low-metallicity, thermally-pulsing Asymptotic Giant Branch (TP-AGB) stars our models better match the observations.
The Mystery of CEMPs+r Stars and the Dual Core-Flash Neutron Superburst
Authors: Lugaro M. , Campbell S. W. , de Mink S. E.
Published: September 2009

Carbon-enhanced metal-poor (CEMPs+r) stars show large enhancements of elements produced both by the slow and the rapid neutron capture processes (the s and r process, respectively) and represent a relatively large fraction, 30% to 50%, of the CEMP population. Many scenarios have been proposed to explain this peculiar chemical composition and most of them involve a binary companion producing the s-process elements during its Asymptotic Giant Branch (AGB) phase. The problem is that none of the proposed explanations appears to be able to account for all observational constraints, hence, alternatives are needed to be put forward and investigated. In this spirit, we propose a new scenario for the formation of CEMPs+r stars based on S. W. Campbell's finding that during the ‘dual core flash’ in low-mass stars of extremely low metallicity, when protons are ingested in the He-flash convective zone, a ‘neutron superburst’ is produced. Further calculations are needed to verify if this neutron superburst could make the r-process component observed in CEMPs+r, as well as their Fe abundances. The s-process component would then be produced during the following AGB phase.
The Effect of Aqueous Alteration and Metamorphism in the Survival of Presolar Silicate Grains in Chondrites
Authors: Trigo-Rodriguez Josep M. , Blum Jürgen
Published: September 2009

Relatively small amounts (typically between 2 and 200 ppm) of presolar grains have been preserved in the matrices of chondritic meteorites. The measured abundances of the different types of grains are highly variable from one chondrite to another, but are higher in unequilibrated chondrites that have experienced little or no aqueous alteration and/or metamorphic heating than in processed meteorites. A general overview of the abundances measured in presolar grains (particularly the recently identified presolar silicates) contained in primitive chondrites is presented. Here we will focus on the most primitive chondrite groups, as typically the highest measured abundances of presolar grains occur in primitive chondrites that have experienced little thermal metamorphism. Looking at the most aqueously altered chondrite groups, we find a clear pattern of decreasing abundance of presolar silicate grains with increasing levels of aqueous alteration. We conclude that measured abundances of presolar grains in altered chondrites are strongly biased by their peculiar histories. Scales quantifying the intensity of aqueous alteration and shock metamorphism in chondrites could correlate with the content of presolar silicates. To do this it would be required to infer the degree of destruction or homogenization of presolar grains in the matrices of primitive meteorites. To get an unbiased picture of the relative abundance of presolar grains in the different regions of the protoplanetary disk where first meteorites consolidated, future dedicated studies of primitive meteorites, IDPs, and collected materials from sample-return missions (like e.g. the planned Marco Polo) are urgently required.
The Puzzling Frequencies of CEMP and NEMP Stars
Authors: Pols O. R. , Izzard R. G. , Glebbeek E. , Stancliffe R. J.
Published: September 2009

We present the results of binary population simulations of carbon- and nitrogen-enhanced metal-poor (CEMP and NEMP) stars. We show that the observed paucity of very nitrogen-rich stars puts strong constraints on possible modifications of the initial mass function at low metallicity.
A Review of AGB Mass Loss Imaging Techniques
Authors: Marengo M.
Published: September 2009

Circumstellar imaging across the electromagnetic spectrum allows us to derive fundamental diagnostics for the physics of mass loss in the Asymptotic Giant Branch (AGB) phase. I review the current status of the field, with particular emphasis on the techniques that provide the strongest constraints for mass-loss modeling efforts.
Ecology and the ratchet of events: Climate variability, niche dimensions, and species distributions
Authors: Jackson Stephen T. , Betancourt Julio L. , Booth Robert K. , Gray Stephen T.
Published: September 2009

Climate change in the coming centuries will be characterized by interannual, decadal, and multidecadal fluctuations superimposed on anthropogenic trends. Predicting ecological and biogeographic responses to these changes constitutes an immense challenge for ecologists. Perspectives from climatic and ecological history indicate that responses will be laden with contingencies, resulting from episodic climatic events interacting with demographic and colonization events. This effect is compounded by the dependency of environmental sensitivity upon life-stage for many species. Climate variables often used in empirical niche models may become decoupled from the proximal variables that directly influence individuals and populations. Greater predictive capacity, and more-fundamental ecological and biogeographic understanding, will come from integration of correlational niche modeling with mechanistic niche modeling, dynamic ecological modeling, targeted experiments, and systematic observations of past and present patterns and dynamics.
Anomalous properties of the acoustic excitations in glasses on the mesoscopic length scale
Authors: Monaco Giulio , Mossa Stefano
Published: September 2009

The low-temperature thermal properties of dielectric crystals are governed by acoustic excitations with large wavelengths that are well described by plane waves. This is the Debye model, which rests on the assumption that the medium is an elastic continuum, holds true for acoustic wavelengths large on the microscopic scale fixed by the interatomic spacing, and gradually breaks down on approaching it. Glasses are characterized as well by universal low-temperature thermal properties that are, however, anomalous with respect to those of the corresponding crystalline phases. Related universal anomalies also appear in the low-frequency vibrational density of states and, despite a longstanding debate, remain poorly understood. By using molecular dynamics simulations of a model monatomic glass of extremely large size, we show that in glasses the structural disorder undermines the Debye model in a subtle way: The elastic continuum approximation for the acoustic excitations breaks down abruptly on the mesoscopic, medium-range-order length scale of ≈10 interatomic spacings, where it still works well for the corresponding crystalline systems. On this scale, the sound velocity shows a marked reduction with respect to the macroscopic value. This reduction turns out to be closely related to the universal excess over the Debye model prediction found in glasses at frequencies of ≈1 THz in the vibrational density of states or at temperatures of ≈10 K in the specific heat.
Polymer beacons for luminescence and magnetic resonance imaging of DNA delivery
Authors: Bryson Joshua M. , Fichter Katye M. , Chu Wen-Jang , Lee Jing-Huei , Li Jing , Madsen Louis A. , McLendon Patrick M. , Reineke Theresa M.
Published: September 2009

The delivery of nucleic acids with polycations offers tremendous potential for developing highly specific treatments for various therapeutic targets. Although materials have been developed and studied for polynucleotide transfer, the biological mechanisms and fate of the synthetic vehicle has remained elusive due to the limitations with current labeling technologies. Here, we have developed polymer beacons that allow the delivery of nucleic acids to be visualized at different biological scales. The polycations have been designed to contain repeated oligoethyleneamines, for binding and compacting nucleic acids into nanoparticles, and lanthanide (Ln) chelates [either luminescent europium (Eu
3+
) or paramagnetic gadolinium (Gd
3+
)]. The chelated Lns allow the visualization of the delivery vehicle both on the nm/μm scale via microscopy and on the sub-mm scale via MRI. We demonstrate that these delivery beacons effectively bind and compact plasmid (p)DNA into nanoparticles and protect nucleic acids from nuclease damage. These delivery beacons efficiently deliver pDNA into cultured cells and do not exhibit toxicity. Micrographs of cultured cells exposed to the nanoparticle complexes formed with fluorescein-labeled pDNA and the europium-chelated polymers reveal effective intracellular imaging of the delivery process. MRI of bulk cells exposed to the complexes formulated with pDNA and the gadolinium-chelated structures show bright image contrast, allowing visualization of effective intracellular delivery on the tissue-scale. Because of their versatility, these delivery beacons posses remarkable potential for tracking and understanding nucleic acid transfer in vitro, and have promise as in vivo theranostic agents.
Photolysis of iron–siderophore chelates promotes bacterial–algal mutualism
Authors: Amin Shady A. , Green David H. , Hart Mark C. , Küpper Frithjof C. , Sunda William G. , Carrano Carl J.
Published: September 2009

Marine microalgae support world fisheries production and influence climate through various mechanisms. They are also responsible for harmful blooms that adversely impact coastal ecosystems and economies. Optimal growth and survival of many bloom-forming microalgae, including climatically important dinoflagellates and coccolithophores, requires the close association of specific bacterial species, but the reasons for these associations are unknown. Here, we report that several clades of
Marinobacter
ubiquitously found in close association with dinoflagellates and coccolithophores produce an unusual lower-affinity dicitrate siderophore, vibrioferrin (VF). Fe-VF chelates undergo photolysis at rates that are 10–20 times higher than siderophores produced by free-living marine bacteria, and unlike the latter, the VF photoproduct has no measurable affinity for iron. While both an algal-associated bacterium and a representative dinoflagellate partner,
Scrippsiella trochoidea
, used iron from Fe-VF chelates in the dark, in situ photolysis of the chelates in the presence of attenuated sunlight increased bacterial iron uptake by 70% and algal uptake by >20-fold. These results suggest that the bacteria promote algal assimilation of iron by facilitating photochemical redox cycling of this critical nutrient. Also, binary culture experiments and genomic evidence suggest that the algal cells release organic molecules that are used by the bacteria for growth. Such mutualistic sharing of iron and fixed carbon has important implications toward our understanding of the close beneficial interactions between marine bacteria and phytoplankton, and the effect of these interactions on algal blooms and climate.
Microwell-mediated control of embryoid body size regulates embryonic stem cell fate via differential expression of WNT5a and WNT11
Authors: Hwang Yu-Shik , Chung Bong Geun , Ortmann Daniel , Hattori Nobuaki , Moeller Hannes-Christian , Khademhosseini Ali
Published: September 2009

Recently, various approaches for controlling the embryonic stem (ES) cell microenvironment have been developed for regulating cellular fate decisions. It has been reported that the lineage specific differentiation could be affected by the size of ES cell colonies and embryoid bodies (EBs). However, much of the underlying biology has not been well elucidated. In this study, we used microengineered hydrogel microwells to direct ES cell differentiation and determined the role of WNT signaling pathway in directing the differentiation. This was accomplished by forming ES cell aggregates within microwells to form different size EBs. We determined that cardiogenesis was enhanced in larger EBs (450 μm in diameter), and in contrast, endothelial cell differentiation was increased in smaller EBs (150 μm in diameter). Furthermore, we demonstrated that the EB-size mediated differentiation was driven by differential expression of WNTs, particularly noncanonical WNT pathway, according to EB size. The higher expression of WNT5a in smaller EBs enhanced endothelial cell differentiation. In contrast, the increased expression of WNT11 enhanced cardiogenesis. This was further validated by WNT5a-siRNA transfection assay and the addition of recombinant WNT5a. Our data suggest that EB size could be an important parameter in ES cell fate specification via differential gene expression of members of the noncanonical WNT pathway. Given the size-dependent response of EBs to differentiate to endothelial and cardiac lineages, hydrogel microwell arrays could be useful for directing stem cell fates and studying ES cell differentiation in a controlled manner.
Consanguinity, human evolution, and complex diseases
Authors: Bittles A. H. , Black M. L.
Published: September 2009

There is little information on inbreeding during the critical early years of human existence. However, given the small founding group sizes and restricted mate choices it seems inevitable that intrafamilial reproduction occurred and the resultant levels of inbreeding would have been substantial. Currently, couples related as second cousins or closer (
F
≥ 0.0156) and their progeny account for an estimated 10.4% of the global population. The highest rates of consanguineous marriage occur in north and sub-Saharan Africa, the Middle East, and west, central, and south Asia. In these regions even couples who regard themselves as unrelated may exhibit high levels of homozygosity, because marriage within clan, tribe, caste, or biraderi boundaries has been a long-established tradition. Mortality in first-cousin progeny is ≈3.5% higher than in nonconsanguineous offspring, although demographic, social, and economic factors can significantly influence the outcome. Improving socioeconomic conditions and better access to health care will impact the effects of consanguinity, with a shift from infant and childhood mortality to extended morbidity. At the same time, a range of primarily social factors, including urbanization, improved female education, and smaller family sizes indicate that the global prevalence of consanguineous unions will decline. This shift in marriage patterns will initially result in decreased homozygosity, accompanied by a reduction in the expression of recessive single-gene disorders. Although the roles of common and rare gene variants in the etiology of complex disease remain contentious, it would be expected that declining consanguinity would also be reflected in reduced prevalence of complex diseases, especially in population isolates.
Catalytic activities of NifEN: Implications for nitrogenase evolution and mechanism
Authors: Hu Yilin , Yoshizawa Janice M. , Fay Aaron W. , Lee Chi Chung , Wiig Jared A. , Ribbe Markus W.
Published: September 2009

NifEN is a key player in the biosynthesis of nitrogenase MoFe protein. It not only shares a considerable degree of sequence homology with the MoFe protein, but also contains clusters that are homologous to those found in the MoFe protein. Here we present an investigation of the catalytic activities of NifEN. Our data show that NifEN is catalytically competent in acetylene (C
2
H
2
) and azide (N
3
−
) reduction, yet unable to reduce dinitrogen (N
2
) or evolve hydrogen (H
2
). Upon turnover, C
2
H
2
gives rise to an additional
S
= 1/2 signal, whereas N
3
−
perturbs the signal originating from the NifEN-associated FeMoco homolog. Combined biochemical and spectroscopic studies reveal that N
3
−
can act as either an inhibitor or an activator for the binding and/or reduction of C
2
H
2
, while carbon monoxide (CO) is a potent inhibitor for the binding and/or reduction of both N
3
−
and C
2
H
2
. Taken together, our results suggest that NifEN is a catalytic homolog of MoFe protein; however, it is only a “skeleton” version of the MoFe protein, as its associated clusters are simpler in structure and less versatile in function, which, in turn, may account for its narrower range of substrates and lower activities of substrate reduction. The resemblance of NifEN to MoFe protein in catalysis points to a plausible, sequential appearance of the two proteins in nitrogenase evolution. More importantly, the discrepancy between the two systems may provide useful insights into nitrogenase mechanism and allow reconstruction of a fully functional nitrogenase from the “skeleton” enzyme, NifEN.
A frequent kinase domain mutation that changes the interaction between PI3Kα and the membrane
Authors: Mandelker Diana , Gabelli Sandra B. , Schmidt-Kittler Oleg , Zhu Jiuxiang , Cheong Ian , Huang Chuan-Hsiang , Kinzler Kenneth W. , Vogelstein Bert , Amzel L. Mario
Published: September 2009

Mutations in oncogenes often promote tumorigenesis by changing the conformation of the encoded proteins, thereby altering enzymatic activity. ThePIK3CAoncogene, which encodes p110α, the catalytic subunit of phosphatidylinositol 3-kinase alpha (PI3Kα), is one of the two most frequently mutated oncogenes in human cancers. We report the structure of the most common mutant of p110α in complex with two interacting domains of its regulatory partner (p85α), both free and bound to an inhibitor (wortmannin). The N-terminal SH2 (nSH2) domain of p85α is shown to form a scaffold for the entire enzyme complex, strategically positioned to communicate extrinsic signals from phosphopeptides to three distinct regions of p110α. Moreover, we found that Arg-1047 points toward the cell membrane, perpendicular to the orientation of His-1047 in the WT enzyme. Surprisingly, two loops of the kinase domain that contact the cell membrane shift conformation in the oncogenic mutant. Biochemical assays revealed that the enzymatic activity of the p110α His1047Arg mutant is differentially regulated by lipid membrane composition. These structural and biochemical data suggest a previously undescribed mechanism for mutational activation of a kinase that involves perturbation of its interaction with the cellular membrane.
A genomic screen identifies TYRO3 as a MITF regulator in melanoma
Authors: Zhu Shoutian , Wurdak Heiko , Wang Yan , Galkin Anna , Tao Haiyan , Li Jie , Lyssiotis Costas A. , Yan Feng , Tu Buu P. , Miraglia Loren , Walker John , Sun Fanxiang , Orth Anthony , Schultz Peter G. , Wu Xu
Published: September 2009

Malignant melanoma is the most aggressive form of cutaneous carcinoma, accounting for 75% of all deaths caused by skin cancers. Microphthalmia-associated transcription factor (MITF) is a master gene regulating melanocyte development and functions as a “lineage addiction” oncogene in malignant melanoma. We have identified the receptor protein tyrosine kinase TYRO3 as an upstream regulator of
MITF
expression by a genome-wide gain-of-function cDNA screen and show that TYRO3 induces
MITF-M
expression in a SOX10-dependent manner in melanoma cells. Expression of
TYRO3
is significantly elevated in human primary melanoma tissue samples and melanoma cell lines and correlates with
MITF-M
mRNA levels.
TYRO3
overexpression bypasses BRAF(V600E)-induced senescence in primary melanocytes, inducing transformation of non-tumorigenic cell lines. Furthermore, TYRO3 knockdown represses cellular proliferation and colony formation in melanoma cells, and sensitizes them to chemotherapeutic agent-induced apoptosis;
TYRO3
knockdown in melanoma cells also inhibits tumorigenesis in vivo. Taken together, these data indicate that TYRO3 may serve as a target for the development of therapeutic agents for melanoma.
Structural basis of activation-dependent binding of ligand-mimetic antibody AL-57 to integrin LFA-1
Authors: Zhang Hongmin , Liu Jin-huan , Yang Wei , Springer Timothy , Shimaoka Motomu , Wang Jia-huai
Published: September 2009

The activity of integrin LFA-1 (α
L
β
2
) to its ligand ICAM-1 is regulated through the conformational changes of its ligand-binding domain, the I domain of α
L
chain, from an inactive, low-affinity closed form (LA), to an intermediate-affinity form (IA), and then finally, to a high-affinity open form (HA). A ligand-mimetic human monoclonal antibody AL-57 (activated LFA-1 clone 57) was identified by phage display to specifically recognize the affinity-upregulated I domain. Here, we describe the crystal structures of the Fab fragment of AL-57 in complex with IA, as well as in its unligated form. We discuss the structural features conferring AL-57's strong selectivity for the high affinity, open conformation of the I domain. The AL-57-binding site overlaps the ICAM-1 binding site on the I domain. Furthermore, an antibody Asp mimics an ICAM Glu by forming a coordination to the metal-ion dependent adhesion site (MIDAS). The structure also reveals better shape complementarity and a more hydrophobic interacting interface in AL-57 binding than in ICAM-1 binding. The results explain AL-57's antagonistic mimicry of LFA-1's natural ligands, the ICAM molecules.
Trafficking of Crumbs3 during Cytokinesis Is Crucial for Lumen Formation
Authors: Schlüter Marc A. , Pfarr Catherine S. , Pieczynski Jay , Whiteman Eileen L. , Hurd Toby W. , Fan Shuling , Liu Chia-Jen , Margolis Ben
Published: September 2009

Although lumen generation has been extensively studied through so-called cyst-formation assays in Madin-Darby canine kidney (MDCK) cells, an underlying mechanism that leads to the initial appearance of a solitary lumen remains elusive. Lumen formation is thought to take place at early stages in aggregates containing only a few cells. Evolutionarily conserved polarity protein complexes, namely the Crumbs, Par, and Scribble complexes, establish apicobasal polarity in epithelial cells, and interference with their function impairs the regulated formation of solitary epithelial lumina. Here, we demonstrate that MDCK cells form solitary lumina during their first cell division. Before mitosis, Crumbs3a becomes internalized and concentrated in Rab11-positive recycling endosomes. These compartments become partitioned in both daughter cells and are delivered to the site of cytokinesis, thus forming the first apical membrane, which will eventually form a lumen. Endosome trafficking in this context appears to depend on the mitotic spindle apparatus and midzone microtubules. Furthermore, we show that this early lumen formation is regulated by the apical polarity complexes because Crumbs3 assists in the recruitment of aPKC to the forming apical membrane and interference with their function can lead to the formation of a no-lumen or multiple-lumen phenotype at the two-cell stage.
Yeast Sec1p Functions before and after Vesicle Docking
Authors: Hashizume Kristina , Cheng Yi-Shan , Hutton Jenna L. , Chiu Chi-hua , Carr Chavela M.
Published: September 2009

Sec1/Munc18 (SM) proteins bind cognate soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes and stimulate vesicle membrane fusion. Before fusion, vesicles are docked to specific target membranes. Regulation of vesicle docking is attributed to some but not all SM proteins, suggesting specialization of this earlier function. Yeast Sec1p seems to function only after vesicles are docked and SNARE complexes are assembled. Here, we show that yeast Sec1p is required before and after SNARE complex assembly, in support of general requirements for SM proteins in both vesicle docking and fusion. Two classes of sec1 mutants were isolated. Class A mutants are tightly blocked in cell growth and secretion at a step before SNARE complex assembly. Class B mutants have a SNARE complex binding defect, with a range in severity of cell growth and secretion defects. Mapping the mutations onto an SM protein structure implicates a peripheral bundle of helices for the early, docking function and a deep groove, opposite the syntaxin-binding cleft on nSec1/Munc-18, for the interaction between Sec1p and the exocytic SNARE complex.