bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystallization of a binary Lennard-Jones mixture
Authors: Jungblut Swetlana , Dellago Christoph
Published: March 2011

Transition interface path sampling combined with straightforward molecular dynamics simulation was applied to study the mechanism and kinetics of the crystallization of an undercooled 3:1 binary Lennard-Jones mixture with diameter ratio 0.85 and equal interaction strengths. We find that this mixture freezes via the formation of crystalline clusters consisting of a fcc-rich core and a bcc-rich surface layer, with an excess of large particles and particle species distributed randomly. A detailed comparison reveals that the transition mechanism is similar to that of the pure fluid but occurs with much smaller nucleation rates even at comparable degrees of undercooling. Also, the growth of the crystalline cluster in the mixture proceeds at a pace about 1 order of magnitude slower than in the pure system. Possibly, this slow dynamics of the mixture is related to the occurrence and subsequent relaxation of icosahedral structures in the growing crystal as well as in the liquid surrounding it.
Velocity field reconstruction in gravity-driven flow over unknown topography
Authors: Heining C.
Published: March 2011

A numerical method for reconstructing the velocity field of a viscous liquid flowing over unknown topography is presented. For a given fluid this procedure allows one to determine the velocity field as well as the topographic structure from the free-surface shape only. First, we confirm the results with previous computations in the thin-film limit and then generalize the numerical solution to arbitrary film thicknesses and focus on the velocity field. It is documented that even smoothly corrugated free-surface shapes require strongly undulated topographies to maintain the flow structure. Finally, we discuss details of the implementation in applications, solvability in general, and sensitivity of the solution.
Franck–Condon simulation of the A 1B2 → X 1A1 dispersed fluorescence spectrum of fluorobenzene and its rate of the internal conversion
Authors: He Rongxing , Yang Ling , Zhu Chaoyuan , Yamaki Masahiro , Lee Yuan-Pern , Lin Sheng Hsien
Published: March 2011

By using three different hybrid exchange-correlation functionals containing 20%, 35%, and 50% of exact Hartree–Fock (HF) exchange of the density functional theory and its time-dependent extension plus the Hartree–Fock and the configuration interaction of single excitation methods, equilibrium geometries, and their 30 vibrational–normal-mode frequencies of the ground S0(1A1) and the first excited S1(1B2) states of fluorobenzene (FB) were calculated. The dispersed fluorescence spectrum and internal conversion (IC) rate of the A 1B2 → X 1A1 transition were simulated by Franck–Condon (FC) calculations within the displaced harmonic oscillator approximation plus anharmonic and distorted corrections. The simulated spectral profile is primarily described by the Franck–Condon progression from the ring-breathing modes v9 and v10 which belong to totally symmetry modes. Anharmonic corrections simultaneously improve the intensity order of $9_1^0$910 and $10_1^0$1010 bands and diminish $1_1^0$110 transition that is fairly strong in harmonic simulations. It is concluded that the amount of Hartree–Fock exchange does impact the geometries and vibrational frequencies of FB molecule, but not the relative intensities of the transitions. It is anharmonic corrections that make the relative intensities of the transitions in good agreement with experimental results. Distorted corrections could assign most of the dominant overtones of out-of-plane nontotally symmetry modes, and the results agree well with the experimental assignments. Furthermore, it was found that the internal conversion rate is dominated by three promoting modes that are computed with lowing symmetry to C1. By choosing dephasing width as 10 cm−1 that is consistent with spectral simulation, we obtained the lifetimes of the A 1B2 → X 1A1 de-excitation as 11 and 19 ns, respectively, from TD(B3LYP) and HF/CIS calculations in comparison with the experimental value 14.75 ns.
Influence of the adatom diffusion on selective growth of GaN nanowire regular arrays
Authors: Gotschke T. , Schumann T. , Limbach F. , Stoica T. , Calarco R.
Published: March 2011

Molecular beam epitaxy (MBE) on patterned Si/AlN/Si(111) substrates was used to obtain regular arrays of uniform-size GaN nanowires (NWs). The silicon top layer has been patterned with e-beam lithography, resulting in uniform arrays of holes with different diameters (dh) and periods (P). While the NW length is almost insensitive to the array parameters, the diameter increases significantly with dh and P till it saturates at P values higher than 800 nm. A diffusion induced model was used to explain the experimental results with an effective diffusion length of the adatoms on the Si, estimated to be about 400 nm.
An efficient, fragment-based electronic structure method for molecular systems: Self-consistent polarization with perturbative two-body exchange and dispersion
Authors: Jacobson Leif D. , Herbert John M.
Published: March 2011

We report a fragment-based electronic structure method, intended for the study of clusters and molecular liquids, that incorporates electronic polarization (induction) in a self-consistent fashion but treats intermolecular exchange and dispersion interactions perturbatively, as post-self-consistent field corrections, using a form of pairwise symmetry-adapted perturbation theory. The computational cost of the method scales quadratically as a function of the number of fragments (monomers), but could be made to scale linearly by exploiting distance-dependent thresholds. Extensive benchmark calculations are reported using the S22 database of high-level ab initio binding energies for dimers, and we find that average errors can be reduced to <1 kcal/mol with a suitable choice of basis set. Comparison to ab initio benchmarks for water clusters as large as \documentclass[12pt]{minimal}\begin{document}$\mbox{\rm (H_2O)}_{20}$\end{document}(H2O)20 demonstrates that the method recovers ≳90% of the binding energy in these systems, at a tiny fraction of the computational cost. As such, this approach represents a promising path toward accurate, systematically improvable, and parameter-free simulation of molecular liquids.
First principles theoretical study of the hole-assisted conversion of CO to CO2 on the anatase TiO2(101) surface
Authors: Wanbayor Raina , Deák Peter , Frauenheim Thomas , Ruangpornvisuti Vithaya
Published: March 2011

First principles density functional theory calculations were carried out to investigate the adsorption and oxidation of CO on the positively charged (101) surface of anatase, as well as the desorption of CO2 from it. We find that the energy gain on adsorption covers the activation energy required for the oxidation, while the energy gain on the latter is sufficient for the desorption of CO2, leaving an oxygen vacancy behind. Molecular dynamics simulations indicate that the process can be spontaneous at room temperature. The oxidation process described here happens only in the presence of the hole. The possibility of a photocatalytic cycle is discussed assuming electron scavenging by oxygen.
A miniature cell for gas solubility measurements in oils and bitumen
Authors: Foroughi Hooman , Acosta Edgar J. , Kawaji Masahiro
Published: March 2011

A miniature cell has been designed and constructed to measure gas solubility in crude oils and bitumen. The cell was made of stainless steel with a total internal volume of 1.835 cc and only an oil sample of 0.4 cc was required for one set of measurements at different pressures. By using this small cell, the waiting time for reaching equilibrium was less than 10 min. The technique was validated by measuring CO2 gas solubility in two bitumen samples. The results were compared and found to be in very good agreement with available data. The apparatus was also used to study the effect of ashphaltene on CO2 solubility in bitumen. It was shown that ashphaltene had a negligible effect on CO2 solubility in bitumen.
Laser-induced breathing modes in metallic nanoparticles: A symmetric molecular dynamics study
Authors: Ng Ming-Yaw , Chang Yia-Chung
Published: March 2011

A highly efficient simulation method based on molecular dynamics and group theory is adopted to investigate the laser-induced breathing oscillation of gold and silver nanospheres. Nanoparticles with size ranging from 5.8 to 46.2 nm are discussed. The effect due to laser-induced heating is modeled by a symmetric sudden expansion of the nanospheres by increasing the interatomic distances. A long-range empirical potential model which is capable of describing the phonon dispersion curves of noble metals in the full frequency range is established. Group theory is fully exploited to increase the computation efficiency, and the oscillation behavior of nanospheres of over 3 × 106 atoms can be simulated efficiently. Oscillation frequencies of nanospheres are obtained by calculating the Fourier transform of the velocity autocorrelation function. The breathing modes of nanospheres are identified as the excitation of A1g modes with in-phase radial displacement of atoms in the nanospheres. The resulting oscillation spectra are in very good agreement with experimental data.
Inherited bareness of the belly reduces the time taken to shear ewes and hoggets
Authors: Scobie D. R. , O'Connell D. , Morris C. A. , Hickey S. M.
Published: March 2011

A series of three related experiments are described in which genetic parameters associated with belly bareness were estimated, and the fleeceweight and time taken to shear ewes and hoggets with a range of belly bareness were compared. The naturally bare area of skin on the belly was scored on lambs at weaning from a composite flock of New Zealand crossbred sheep. Belly bareness was scored on a scale from 1 where wool was found deep in the axilla and very small patches of bare skin were showing, to 5, where the entire belly was free of wool. The estimated heritability for bareness of the belly at weaning (n = 1749) was 0.31 ± 0.06. Lambs were shorn following weaning, and shorn again as hoggets (n = 876) 6 months later. Greasy fleeceweight at hogget shearing was genetically (–0.25 ± 0.13) and phenotypically correlated (–0.18 ± 0.04) with belly bareness recorded at weaning. Adult ewes of the composite flock (n = 195) were run with adult Romney ewes (n = 91) and all were scored for belly bareness before shearing. The time taken to shear each composite ewe declined (P < 0.001) from 88 s in ewes with woolly bellies to 68 s in sheep with no belly wool at all (score 5). Ewes from the composite flock had very bare bellies (mean score 4.2), and produced an average of 19 g of belly wool, 131 g of fleece skirtings and 2.2 kg of skirted fleece. Total weight of greasy wool declined with increasing belly bareness score (P < 0.001) within the composite flock from 3.3 kg for ewes with woolly bellies to 2.3 kg in sheep with no belly wool at all (score 5). In contrast, Romney ewes were shorn in 150 s and had very woolly bellies (mean score 1.1) with 364 g of belly wool, 525 g of fleece skirtings and 3.76 kg of skirted fleece. Romney ewes and composite flock ewes were mated at random to one of six sires from the composite flock. There was a decrease in fleeceweight as belly bareness score increased in the progeny of composite (P < 0.001) and Romney ewes (P = 0.037). Increasing belly bareness score reduced the time taken to shear each hogget (P = 0.015) from over 100 s for woolly bellies to 70 s for the barest (score 4). As hoggets, the progeny of Romney ewes (n = 46) carried more belly wool (251 versus 116 g), fleece skirtings (268 versus 119 g) and skirted fleece (2.1 versus 1.5 kg) than the progeny of ewes from the composite flock (n = 75). Collectively these experiments show that belly bareness is inherited, fleeceweight will decline with increased belly bareness and shearing speed will increase with increased belly bareness.
Onset of puberty and early-life reproduction in Angus females divergently selected for post-weaning residual feed intake
Authors: Donoghue K. A. , Arthur P. F. , Wilkins J. F. , Herd R. M.
Published: March 2011

Angus cattle that had been divergently selected for Low and High post-weaning residual feed intake (RFI) were used in two projects to evaluate early-life reproductive performance and onset of puberty in females. In the first project, data on the 1999-born females (n = 64) were evaluated for weight, subcutaneous fat (P8 fat depth) and reproductive performance over two breeding cycles. These females that were the result of 1.0–2.5 (mean of 1.8) generations of selection, had mean (±s.e.) post-weaning RFI of –0.82 ± 0.19 kg/day and 0.57 ± 0.18 kg/day for the Low and High RFI selection lines, respectively. In the second project, ultrasonography was used to scan the ovaries of the 2008-born heifers (n = 121) on four occasions following weaning. In these heifers the presence of corpus luteum provided evidence of ovulation, and hence the commencement of onset of puberty. The average of the estimated breeding value (EBV) for RFI of the parents of the Low RFI and the High RFI selection line heifers were –0.72 ± 0.05 and 0.37 ± 0.03 kg/day, respectively. In the first project, no significant selection line differences were evident for weight, age at first mating, pregnancy and calving rates (percentage of females that were pregnant, or the percentage that calved out of the total number used for mating), calf birthweight and weight of calf born per female exposed to bull. Females from the Low RFI line had significantly (P < 0.05) lower P8 fat depth relative to their High RFI contemporaries at most of the measurement dates (e.g. 9.2 ± 0.5 versus 12.0 ± 0.5 mm at the start of first mating). Low RFI females also calved significantly (P < 0.05) later in the calving season than High RFI females (35.7 ± 3.0 versus 27.6 ± 2.4 days). The results indicate that there is a delayed pregnancy date during the first mating season leading to a later calving date for the Low RFI heifers. The later first calving date was then maintained at subsequent calving. The later calving, however, did not impact on pregnancy and calving rates. In the second project, it was observed that irrespective of selection line, heifers that had attained onset of puberty had significantly (P < 0.05) greater P8 fat depth than those that had not. Hence the expectation was that, relative to High RFI heifers, the Low RFI heifers with their lower P8 fat, will attain onset of puberty at a slightly older age. This expected trend was observed but the difference was not significant, and further investigations are recommended.
Effect of total sulfur amino acids in corn - cassava - soybean diets on growth performance, carcass yield and blood chemical profile of male broiler chickens from 1 to 42 days of age
Authors: Rakangtong C. , Bunchasak C.
Published: March 2011

The experiment was conducted to determine the effects of total sulfur amino acid (TSAA) in diets on growth performance, carcass yield and blood chemical profile of commercial male broiler chickens from 1 to 42 days of age. Six graded levels of TSAA were fed during the starter (1–21 days of age) and the grower (22–42 days of age) periods at 61, 84, 100, 105, 110 and 115% of commercial recommendation. The experiment was a completely randomised design. In all, 1050 commercial male broiler chicks (Ross 308) were divided into six treatments, and each treatment consisted of seven replicates of 25 chicks each. Bodyweight gains of chicks that received TSAA at 100% of commercial concentrations were significantly greater than those that received the recommended National Research Council concentrations (84% of commercial levels, P < 0.05). The best feed-conversion ratio and feed cost per gain were found at the commercial recommendation level. Nonetheless, broilers that were fed TSAA at concentrations higher than the commercial recommendation levels did not exhibit positive effects on growth performance. With respect to carcass yield, the breast meat yield was increased by increasing TSAA in the diets (P < 0.05), particularly when supplied at commercial recommendation levels, whereas the eviscerated carcass and liver weights were not significantly affected. There was no significant effect of increasing TSAA in the diets on serum triglyceride, uric acid, total protein, albumin and globulin. In conclusion, broilers fed diets supplemented with TSAA at commercial concentrations gave the best growth performance, carcass yields and economic return.
Genetic visualization with an improved GCaMP calcium indicator reveals spatiotemporal activation of the spinal motor neurons in zebrafish
Authors: Muto Akira , Ohkura Masamichi , Kotani Tomoya , Higashijima Shin-ichi , Nakai Junichi , Kawakami Koichi
Published: March 2011

Animal behaviors are generated by well-coordinated activation of neural circuits. In zebrafish, embryos start to show spontaneous muscle contractions at 17 to 19 h postfertilization. To visualize how motor circuits in the spinal cord are activated during this behavior, we developed GCaMP-HS (GCaMP-
h
yper
s
ensitive), an improved version of the genetically encoded calcium indicator GCaMP, and created transgenic zebrafish carrying the GCaMP-HS gene downstream of the Gal4-recognition sequence, UAS (upstream activation sequence). Then we performed a gene-trap screen and identified the SAIGFF213A transgenic fish that expressed Gal4FF, a modified version of Gal4, in a subset of spinal neurons including the caudal primary (CaP) motor neurons. We conducted calcium imaging using the SAIGFF213A; UAS:GCaMP-HS double transgenic embryos during the spontaneous contractions. We demonstrated periodic and synchronized activation of a set of ipsilateral motor neurons located on the right and left trunk in accordance with actual muscle movements. The synchronized activation of contralateral motor neurons occurred alternately with a regular interval. Furthermore, a detailed analysis revealed rostral-to-caudal propagation of activation of the ipsilateral motor neuron, which is similar to but much slower than the rostrocaudal delay observed during swimming in later stages. Our study thus demonstrated coordinated activities of the motor neurons during the first behavior in a vertebrate. We propose the GCaMP technology combined with the Gal4FF-UAS system is a powerful tool to study functional neural circuits in zebrafish.
Uncovering the behaviors of individual cells within a multicellular microvascular community
Authors: Parsa Hesam , Upadhyay Ranjan , Sia Samuel K.
Published: March 2011

Although individual cells vary in behavior during the formation of tissues, the nature of such variations are largely uncharacterized. Here, we tracked the morphologies and motilities of ~300 human endothelial cells from an initial dispersed state to the formation of capillary-like structures, distilling the dynamics of tissue morphogenesis into an array of ~36,000 numerical phenotypes. Quantitative analysis of population averages revealed two previously unidentified phases in which the cells spread before forming connections with neighboring cells and where the microvascular plexus stabilized before spatially reorganizing. Analysis at the single-cell level showed that in contrast to the population-averaged behavior, most cells followed distinct temporal patterns that were not reflected in the bulk average. Interestingly, some of these behavioral patterns correlated to the cells’ final structural role within the plexus. Knowledge of how
individual
cells or groups of cells behave enhances our understanding of how native tissues self-organize and could ultimately enable more precise approaches for engineering tissues and synthesizing multicellular communities.
Creation and manipulation of common functional groups en route to a skeletally diverse chemical library
Authors: Cui Jiayue , Hao Jason , Ulanovskaya Olesya A. , Dundas Joseph , Liang Jie , Kozmin Sergey A.
Published: March 2011

We have developed an efficient strategy to a skeletally diverse chemical library, which entailed a sequence of enyne cycloisomerization, [4 + 2] cycloaddition, alkene dihydroxylation, and diol carbamylation. Using this approach, only 16 readily available building blocks were needed to produce a representative 191-member library, which displayed broad distribution of molecular shapes and excellent physicochemical properties. This library further enabled identification of a small molecule, which effectively suppressed glycolytic production of ATP and lactate in CHO-K1 cell line, representing a potential lead for the development of a new class of glycolytic inhibitors.
A synaptic organizing principle for cortical neuronal groups
Authors: Perin Rodrigo , Berger Thomas K. , Markram Henry
Published: March 2011

Neuronal circuitry is often considered a clean slate that can be dynamically and arbitrarily molded by experience. However, when we investigated synaptic connectivity in groups of pyramidal neurons in the neocortex, we found that both connectivity and synaptic weights were surprisingly predictable. Synaptic weights follow very closely the number of connections in a group of neurons, saturating after only 20% of possible connections are formed between neurons in a group. When we examined the network topology of connectivity between neurons, we found that the neurons cluster into small world networks that are not scale-free, with less than 2 degrees of separation. We found a simple clustering rule where connectivity is directly proportional to the number of common neighbors, which accounts for these small world networks and accurately predicts the connection probability between any two neurons. This pyramidal neuron network clusters into multiple groups of a few dozen neurons each. The neurons composing each group are surprisingly distributed, typically more than 100 μm apart, allowing for multiple groups to be interlaced in the same space. In summary, we discovered a synaptic organizing principle that groups neurons in a manner that is common across animals and hence, independent of individual experiences. We speculate that these elementary neuronal groups are prescribed Lego-like building blocks of perception and that acquired memory relies more on combining these elementary assemblies into higher-order constructs.
Distinct signatures of diversifying selection revealed by genome analysis of respiratory tract and invasive bacterial populations
Authors: Shea Patrick R. , Beres Stephen B. , Flores Anthony R. , Ewbank Amy L. , Gonzalez-Lugo Javier H. , Martagon-Rosado Alexandro J. , Martinez-Gutierrez Juan C. , Rehman Hina A. , Serrano-Gonzalez Monica , Fittipaldi Nahuel , Ayers Stephen D. , Webb Paul , Willey Barbara M. , Low Donald E. , Musser James M.
Published: March 2011

Many pathogens colonize different anatomical sites, but the selective pressures contributing to survival in the diverse niches are poorly understood. Group A
Streptococcus
(GAS) is a human-adapted bacterium that causes a range of infections. Much effort has been expended to dissect the molecular basis of invasive (sterile-site) infections, but little is known about the genomes of strains causing pharyngitis (streptococcal “sore throat”). Additionally, there is essentially nothing known about the genetic relationships between populations of invasive and pharyngitis strains. In particular, it is unclear if invasive strains represent a distinct genetic subpopulation of strains that cause pharyngitis. We compared the genomes of 86 serotype M3 GAS pharyngitis strains with those of 215 invasive M3 strains from the same geographical location. The pharyngitis and invasive groups were highly related to each other and had virtually identical phylogenetic structures, indicating they belong to the same genetic pool. Despite the overall high degree of genetic similarity, we discovered that strains from different host environments (i.e., throat, normally sterile sites) have distinct patterns of diversifying selection at the nucleotide level. In particular, the pattern of polymorphisms in the hyaluronic acid capsule synthesis operon was especially different between the two strain populations. This finding was mirrored by data obtained from full-genome analysis of strains sequentially cultured from nonhuman primates. Our results answer the long-standing question of the genetic relationship between GAS pharyngitis and invasive strains. The data provide previously undescribed information about the evolutionary history of pathogenic microbes that cause disease in different anatomical sites.
Crystallographic snapshots of the complete reaction cycle of nicotine degradation by an amine oxidase of the monoamine oxidase (MAO) family
Authors: Kachalova Galina , Decker Karl , Holt Andrew , Bartunik Hans D.
Published: March 2011

FAD-linked oxidases constitute a class of enzymes which catalyze dehydrogenation as a fundamental biochemical reaction, followed by reoxidation of reduced flavin. Here, we present high-resolution crystal structures showing the flavoenzyme 6-hydroxy-
l
-nicotine oxidase in action. This enzyme was trapped during catalytic degradation of the native substrate in a sequence of discrete reaction states corresponding to the substrate-reduced enzyme, a complex of the enzyme with the intermediate enamine product and formation of the final aminoketone product. The inactive
d
-stereoisomer binds in mirror symmetry with respect to the catalytic axis, revealing absolute stereospecificity of hydrogen transfer to the flavin. The structural data suggest deprotonation of the substrate when bound at the active site, an overall binary complex mechanism and oxidation by direct hydride transfer. The amine nitrogen has a critical role in the dehydrogenation step and may activate carbocation formation at the α-carbon via delocalization from the lone pair to σ* C

α

-H. Enzymatically assisted hydrolysis of the intermediate product occurs at a remote (P site) cavity. Substrate entry and product exit follow different paths. Structural and kinetic data suggest that substrate can also bind to the reduced enzyme, associated with slower reoxidation as compared to the rate of reoxidation of free enzyme. The results are of general relevance for the mechanisms of flavin amine oxidases.
Paternal imprint essential for the inheritance of telomere identity in
Drosophila
Authors: Gao Guanjun , Cheng Yan , Wesolowska Natalia , Rong Yikang S.
Published: March 2011

Chromatin remodeling during sperm maturation could erase epigenetic landmarks on the paternal genome, creating a challenge for its reestablishment on fertilization. Here, we show that selective retention of a chromosomal protein in mature sperm protects the identity of paternal telomeres in
Drosophila
. The
ms(3)k81
(
k81
) gene is a duplication of
hiphop
that encodes a telomeric protein. Although HipHop protects telomeres in somatic cells, K81 is produced exclusively in males and localizes to telomeres in postmitotic cells, including mature sperm. In embryos fathered by
k81
mutants, the maternal supplies fail to reestablish a protective cap on paternal telomeres, leading to their fusions. These fusions hinder the segregation of the paternal genome and result in haploid embryos with maternal chromosomes. The functional divergence between
hiphop
and
k81
manifests not only in their expression patterns but also in the protein functions that they encode. By swapping the two coding regions, we show that K81 can replace HipHop for somatic protection; however, HipHop cannot replace K81 in the germ line to specify telomere identity, because HipHop ectopically expressed in the testis is removed from chromatin during sperm maturation. HipHop lacks a short motif in K81 that is essential for K81 to survive the remodeling process. We show that the combined functions of HipHop and K81 are likely fulfilled by the single ancestral
hiphop
locus in other
Drosophila
species, supporting the hypothesis that the evolutionary process of subfunctionalization was responsible for the preservation of the
hiphop-k81
duplicate.
Hunter-gatherer genomic diversity suggests a southern African origin for modern humans
Authors: Henn Brenna M. , Gignoux Christopher R. , Jobin Matthew , Granka Julie M. , Macpherson J. M. , Kidd Jeffrey M. , Rodríguez-Botigué Laura , Ramachandran Sohini , Hon Lawrence , Brisbin Abra , Lin Alice A. , Underhill Peter A. , Comas David , Kidd Kenneth K. , Norman Paul J. , Parham Peter , Bustamante Carlos D. , Mountain Joanna L. , Feldman Marcus W.
Published: March 2011

Africa is inferred to be the continent of origin for all modern human populations, but the details of human prehistory and evolution in Africa remain largely obscure owing to the complex histories of hundreds of distinct populations. We present data for more than 580,000 SNPs for several hunter-gatherer populations: the Hadza and Sandawe of Tanzania, and the ≠Khomani Bushmen of South Africa, including speakers of the nearly extinct N|u language. We find that African hunter-gatherer populations today remain highly differentiated, encompassing major components of variation that are not found in other African populations. Hunter-gatherer populations also tend to have the lowest levels of genome-wide linkage disequilibrium among 27 African populations. We analyzed geographic patterns of linkage disequilibrium and population differentiation, as measured byFST, in Africa. The observed patterns are consistent with an origin of modern humans in southern Africa rather than eastern Africa, as is generally assumed. Additionally, genetic variation in African hunter-gatherer populations has been significantly affected by interaction with farmers and herders over the past 5,000 y, through both severe population bottlenecks and sex-biased migration. However, African hunter-gatherer populations continue to maintain the highest levels of genetic diversity in the world.
Analgesia mediated by soluble epoxide hydrolase inhibitors is dependent on cAMP
Authors: Inceoglu Bora , Wagner Karen , Schebb Nils H. , Morisseau Christophe , Jinks Steven L. , Ulu Arzu , Hegedus Christine , Rose Tristan , Brosnan Robert , Hammock Bruce D.
Published: March 2011

Pain is a major health concern even though numerous analgesic agents are available. Side effects and lack of wide-spectrum efficacy of current drugs justify efforts to better understand pain mechanisms. Stabilization of natural epoxy-fatty acids (EFAs) through inhibition of the soluble epoxide hydrolase (sEH) reduces pain. However, in the absence of an underlying painful state, inhibition of sEH is ineffective. Surprisingly, a pain-mediating second messenger, cAMP, interacts with natural EFAs and regulates the analgesic activity of sEH inhibitors. Concurrent inhibition of sEH and phosphodiesterase (PDE) dramatically reduced acute pain in rodents. Our findings demonstrate a mechanism of action of cAMP and EFAs in the pathophysiology of pain. Furthermore, we demonstrate that inhibition of various PDE isozymes, including PDE4, lead to significant increases in EFA levels through a mechanism independent of sEH, suggesting that the efficacy of commercial PDE inhibitors could result in part from increasing EFAs. The cross-talk between the two major pathways—one mediated by cAMP and the other by EFAs—paves the way to new approaches to understand and control pain.
Gain-of-function glutamate receptor interacting protein 1 variants alter GluA2 recycling and surface distribution in patients with autism
Authors: Mejias Rebeca , Adamczyk Abby , Anggono Victor , Niranjan Tejasvi , Thomas Gareth M. , Sharma Kamal , Skinner Cindy , Schwartz Charles E. , Stevenson Roger E. , Fallin M. Daniele , Kaufmann Walter , Pletnikov Mikhail , Valle David , Huganir Richard L. , Wang Tao
Published: March 2011

Glutamate receptor interacting protein 1 (GRIP1) is a neuronal scaffolding protein that interacts directly with the C termini of glutamate receptors 2/3 (GluA2/3) via its PDZ domains 4 to 6 (PDZ4–6). We found an association (
P
< 0.05) of a SNP within the PDZ4-6 genomic region with autism by genotyping autistic patients (
n
= 480) and matched controls (
n
= 480). Parallel sequencing identified five rare missense variants within or near PDZ4–6 only in the autism cohort, resulting in a higher cumulative mutation load (
P
= 0.032). Two variants correlated with a more severe deficit in reciprocal social interaction in affected sibling pairs from proband families. These variants were associated with altered interactions with GluA2/3 and faster recycling and increased surface distribution of GluA2 in neurons, suggesting gain-of-function because GRIP1/2 deficiency showed opposite phenotypes.
Grip1/2
knockout mice exhibited increased sociability and impaired prepulse inhibition. These results support a role for GRIP in social behavior and implicate
GRIP1
variants in modulating autistic phenotype.
Dynamics of endosomal sorting complex required for transport (ESCRT) machinery during cytokinesis and its role in abscission
Authors: Elia Natalie , Sougrat Rachid , Spurlin Tighe A. , Hurley James H. , Lippincott-Schwartz Jennifer
Published: March 2011

The final stage of cytokinesis is abscission, the cutting of the narrow membrane bridge connecting two daughter cells. The endosomal sorting complex required for transport (ESCRT) machinery is required for cytokinesis, and ESCRT-III has membrane scission activity in vitro, but the role of ESCRTs in abscission has been undefined. Here, we use structured illumination microscopy and time-lapse imaging to dissect the behavior of ESCRTs during abscission. Our data reveal that the ESCRT-I subunit tumor-susceptibility gene 101 (TSG101) and the ESCRT-III subunit charged multivesicular body protein 4b (CHMP4B) are sequentially recruited to the center of the intercellular bridge, forming a series of cortical rings. Late in cytokinesis, however, CHMP4B is acutely recruited to the narrow constriction site where abscission occurs. The ESCRT disassembly factor vacuolar protein sorting 4 (VPS4) follows CHMP4B to this site, and cell separation occurs immediately. That arrival of ESCRT-III and VPS4 correlates both spatially and temporally with the abscission event suggests a direct role for these proteins in cytokinetic membrane abscission.
A Nup133-dependent NPC-anchored network tethers centrosomes to the nuclear envelope in prophase
Authors: Bolhy Stéphanie , Bouhlel Imène , Dultz Elisa , Nayak Tania , Zuccolo Michela , Gatti Xavier , Vallee Richard , Ellenberg Jan , Doye Valérie
Published: March 2011

Centrosomes are closely associated with the nuclear envelope (NE) throughout the cell cycle and this association is maintained in prophase when they separate to establish the future mitotic spindle. At this stage, the kinetochore constituents CENP-F, NudE, NudEL, dynein, and dynactin accumulate at the NE. We demonstrate here that the N-terminal domain of the nuclear pore complex (NPC) protein Nup133, although largely dispensable for NPC assembly, is required for efficient anchoring of the dynein/dynactin complex to the NE in prophase. Nup133 exerts this function through an interaction network via CENP-F and NudE/EL. We show that this molecular chain is critical for maintaining centrosome association with the NE at mitotic entry and contributes to this process without interfering with the previously described RanBP2–BICD2-dependent pathway of centrosome anchoring. Finally, our study reveals that tethering of centrosomes to the nuclear surface at the G2/M transition contributes, along with other cellular mechanisms, to early stages of bipolar spindle assembly.
Herpesvirus telomeric repeats facilitate genomic integration into host telomeres and mobilization of viral DNA during reactivation
Authors: Kaufer Benedikt B. , Jarosinski Keith W. , Osterrieder Nikolaus
Published: March 2011

Some herpesviruses, particularly lymphotropic viruses such as Marek’s disease virus (MDV) and human herpesvirus 6 (HHV-6), integrate their DNA into host chromosomes. MDV and HHV-6, among other herpesviruses, harbor telomeric repeats (TMRs) identical to host telomeres at either end of their linear genomes. Using MDV as a natural virus-host model, we show that herpesvirus TMRs facilitate viral genome integration into host telomeres and that integration is important for establishment of latency and lymphoma formation. Integration into host telomeres also aids in reactivation from the quiescent state of infection. Our results and the presence of TMRs in many herpesviruses suggest that integration mediated by viral TMRs is a conserved mechanism, which ensures faithful virus genome maintenance in host cells during cell division and allows efficient mobilization of dormant viral genomes. This finding is of particular importance as reactivation is critical for virus spread between susceptible individuals and is necessary for continued herpesvirus evolution and survival.
Challenges of Applying the SHEA/HICPAC Metrics for Multidrug-Resistant Organisms to a Real-World Setting
Authors: Furuya E. Yoko , Larson Elaine , Landers Timothy , Jia Haomiao , Ross Barbara , Behta Maryam
Published: March 2011

Objective.

To test in a real-world setting the recommendations for measuring infection with multidrug-resistant organisms (MDRO) from the Society for Healthcare Epidemiology of America (SHEA) and the Centers for Disease Control and Prevention's Healthcare Infection Control Practices Advisory Committee (HICPAC).

Methods.

Using data from 3 hospital settings within a healthcare network, we applied the SHEA/HICPAC recommendations to measure methicillin-resistant Staphylococcus aureus (MRSA) infection and colonization. Data were obtained from the hospitals' electronic surveillance system and were supplemented by manual medical record review as necessary. Additionally, we tested (1) different definitions for nosocomial incidence, (2) the effect of excluding patients not at risk from the denominator for hospital-onset incidence, and (3) the appropriate time period to use when including or excluding patients with a prior history of MRSA infection or colonization from nosocomial rates. Negative binomial regression models were used to test for differences between rate definitions. A rating scale was created for each metric, assessing the extent to which manual or electronic data elements were required.

Results.

There was no statistically significant difference between using 72 hours or 3 calendar days as the cutoff to define hospital-onset incidence. Excluding patients not at risk from the denominator when calculating hospital-onset incidence led to statistically significant increases in rates. When excluding patients with a prior history of MRSA infection or colonization from nosocomial incidence rates, rates were similar regardless of whether we looked at 1, 2, or 3 years' worth of prior data.

Conclusions.

The SHEA/HICPAC MDRO metrics are useful but can be challenging to implement. We include in our description of the data sources and processes required to calculate these metrics information that may simplify the process for institutions.
Respiratory Protection by Respirators: The Predictive Value of User Seal Check for the Fit Determination in Healthcare Settings
Authors: Lam Simon Ching , Lee Joseph Kok Long , Lee Linda Yin King , Wong Ka Fai , Lee Cathy Nga Yan
Published: March 2011

The N95 respirator is one type that is recommended by the World Health Organization and the Centers for Disease Control and Prevention (CDC) to prevent inhalation of droplets that may act to transmit respiratory pathogens. However, the reliability of this respirator to prevent transmission is dependent on how well it is fitted to the wearer. For ill-fitting respirators, the average penetration by ambient aerosol was found to be 33%, compared with 4% for well-fitting respirators. Such penetration or leakage may be caused by the gap between the respirator and the wearer's face. Therefore, formal fit testing should be carried out prior to the use of N95 respirators. Quantitative fit testing measures “the adequacy of respirator fit by numerically measuring the amount of leakage into the respirator” using an electronic device.
Blood Concentrations of Chlorhexidine in Hospitalized Children Undergoing Daily Chlorhexidine Bathing
Authors: Lee Andrew , Harlan Robert , Breaud Autumn R. , Speck Kathleen , Perl Trish M. , Clarke William , Milstone Aaron M.
Published: March 2011

We collected serial blood samples from children in the intensive care unit who underwent daily bathing with 2% Chlorhexidine gluconate (CHG)-impregnated cloths. Low concentrations of CHG were detected in a few blood samples, indicating absorption through intact skin. There was no suggestion that CHG accumulated in the blood with repeated exposures.
Comparison of the Burdens of Hospital-Onset, Healthcare Facility-Associated Clostridium difficile Infection and of Healthcare-Associated Infection due to Methicillin-Resistant Staphylococcus aureus in Community Hospitals
Authors: Miller Becky A. , Chen Luke F. , Sexton Daniel J. , Anderson Deverick J.
Published: March 2011

We sought to determine the burden of nosocomial Clostridium difficile infection in comparison to other healthcare-associated infections (HAIs) in community hospitals participating in an infection control network. Our data suggest that C. difficilehas replaced MRSA as the most common etiology of HAI in community hospitals in the southeastern United States.
Performance of Two Bioherbicide Fungi for Waterhemp and Pigweed Control in Pumpkin and Soybean
Authors: Ortiz-Ribbing Loretta M. , Glassman Kenny R. , Roskamp Gordon K. , Hallett Steven G.
Published: March 2011

Common waterhemp (Amaranthus rudis) and pigweeds (Amaranthus spp.) are troublesome weeds in many cropping systems and have evolved resistance to several herbicides. Field trials to further develop Microsphaeropsis amaranthi and Phomopsis amaranthicola as bioherbicides for control of waterhemp and pigweeds were conducted to test the effectiveness of these organisms in irrigated and nonirrigated pumpkin and soybean plots over 2 years at three locations in western Illinois. The bioherbicide was applied with lecithin and vegetable oil at 187 liters ha–1 in 2008 and 374 liters ha–1 in 2009. Treatments included spore suspensions of M. amaranthi and P. amaranthicola alone, a mixture of both organisms, and sequential treatments of the organisms with halosulfuron-methyl (Sandea Herbicide) in pumpkin or glyphosate (Roundup Original Max Herbicide) in soybean. Bioherbicide effectiveness was estimated at approximately 7 and 14 days after treatment, as disease incidence, disease severity, percent weed control, and weed biomass reduction. Significant reductions in weed biomass occurred in treatments with one or both of the fungal organisms, and potential exists to tank mix M. amaranthi with halosulfuron-methyl. Leaf surface moisture and air temperatures following application may account for inconsistencies in field results between year and locations. These fungal organisms show potential as bioherbicides for weeds in the genus Amaranthus.
A New View of Sooty Blotch and Flyspeck
Authors: Gleason Mark L. , Batzer Jean C. , Sun Guangyu , Zhang Rong , Arias Maria M. Díaz , Sutton Turner B. , Crous Pedro W. , Ivanović Milan , McManus Patricia S. , Cooley Daniel R. , Mayr Ulrich , Weber Roland W. S. , Yoder Keith S. , Del Ponte Emerson M. , Biggs Alan R. , Oertel Bernhard
Published: March 2011

Sooty blotch and flyspeck (SBFS) fungi colonize the surface wax layer of the fruit of apple, pear, persimmon, banana, orange, papaya, and several other cultivated tree and vine crops. In addition to colonizing cultivated fruit crops, SBFS fungi also grow on the surfaces of stems, twigs, leaves, and fruit of a wide range of wild plants. The disease occurs worldwide in regions with moist growing seasons. SBFS is regarded as a serious disease by fruit growers and plant pathologists because it can cause substantial economic damage. The smudges and stipples of SBFS often result in downgrading of fruit from premium fresh-market grade to processing use. This review describes the major shifts that have occurred during the past decade in understanding the genetic diversity of the SBFS complex, clarifying its biogeography and environmental biology, and developing improved management strategies.
First Report of Powdery Mildew Caused by Erysiphe euonymi-japonici on Euonymus japonicus in Central China
Authors: Li C. W. , Zhang Y. , Liu Y. , Kang J. M. , Ma X. M. , Fu L. L.
Published: March 2011

Euonymus japonicus Thunb. is a popular, woody, ornamental plant in China. From June to September 2010, severe outbreaks of powdery mildew occurred on all investigated E. japonicus plants used for hedges in Zhoukou and Shangqiu cities of Henan province in central China, which is the second largest province in terms of ornamental plant cultivation. A large amount of fungicide was used to prevent the fungal disease, which caused serious environmental pollution and was estimated to result in a 40 to 60% increase in preservation cost of E. japonicus hedges. Gray-white colonies of powdery mildew fungi occurred mainly on the leaves of E. japonicus, on average approximately 50% of the leaves of an individual plant were infected by the fungi. On severely infected leaves, mycelia were amphigenous, thick, forming irregular white patches, and effused to cover the whole surface. Subsequently, these leaves became chlorotic, curled, and withered. The fungus was identified as Erysiphe euonymi-japonici (Vienn.-Bourg.) U. Braun & S. Takam on the basis of the following data of microscopic morphology with scanning electron microscopy and molecular phylogenetic analysis of the internal transcribed spacer (ITS) region. The fungus had unbranched conidiophores with an average length of 57.3 μm and width of 8.8 μm, which was composed of a cylindrical foot cell, 15 to 40 × 6 to 10 μm and one to three shorter cells or cells of about the same length. Conidia were borne singly, cylindrical, or ellipsoid-cylindrical, with an average length of 27.7 μm and width of 10.4 μm. Chasmothecia were not observed in the collected samples during the whole outbreak period. PCR amplification and sequencing of the ITS region was amplified using the universal primers ITS1 and ITS4 (4). The obtained ITS sequence was assigned Accession No. HQ012432 in GenBank, which had a 99 and 98% nt similarity with the ITS sequences (ITS region including the 5.8S rDNA) of two Erysiphe euonymi-japonici isolates from Japan and Argentina in GenBank (Accession Nos. AB250228 and AB250229 (3), respectively). To our knowledge, Erysiphe euonymi-japonici has not been reported previously from central China, although synonymous species, Oidium euonymi-japonici and Microsphaera euonymi-japonici, were reported in southwestern (Sichuan Province) (1) and eastern (Shandong Province) (2) regions. Herbarium specimens are available at the Key Laboratory of Plant Genetics and Molecular Breeding, Zhoukou Normal University, Zhoukou, China.

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