bluuebunny/crossref_metadata_2025 huggingface dataset:
Formation of nanoparticles of blue haze enhanced by anthropogenic pollution
Authors: Zhang Renyi , Wang Lin , Khalizov Alexei F. , Zhao Jun , Zheng Jun , McGraw Robert L. , Molina Luisa T.
Published: October 2009

The molecular processes leading to formation of nanoparticles of blue haze over forested areas are highly complex and not fully understood. We show that the interaction between biogenic organic acids and sulfuric acid enhances nucleation and initial growth of those nanoparticles. With onecis-pinonic acid and three to five sulfuric acid molecules in the critical nucleus, the hydrophobic organic acid part enhances the stability and growth on the hydrophilic sulfuric acid counterpart. Dimers or heterodimers of biogenic organic acids alone are unfavorable for new particle formation and growth because of their hydrophobicity. Condensation of low-volatility organic acids is hindered on nano-sized particles, whereas ammonia contributes negligibly to particle growth in the size range of 3–30 nm. The results suggest that initial growth from the critical nucleus to the detectable size of 2–3 nm most likely occurs by condensation of sulfuric acid and water, implying that anthropogenic sulfur emissions (mainly from power plants) strongly influence formation of terrestrial biogenic particles and exert larger direct and indirect climate forcing than previously recognized.
Statistical mechanics of logarithmic REM: duality, freezing and extreme value statistics of
1/f
noises generated by Gaussian free fields
Authors: Fyodorov Yan V , Le Doussal Pierre , Rosso Alberto
Published: October 2009

We compute the distribution of the partition functions for a class of one-dimensional random
energy models with logarithmically correlated random potential, above and at the glass
transition temperature. The random potential sequences represent various versions of the
1/f
noise generated by sampling the two-dimensional Gaussian free field (2D GFF) along
various planar curves. Our method extends the recent analysis of Fyodorov and Bouchaud
(2008 J. Phys. A: Math. Theor.
41 372001) from the circular case to an interval and is
based on an analytical continuation of the Selberg integral. In particular, we unveil a
duality relation satisfied by the suitable generating function of free energy cumulants in the
high temperature phase. It reinforces the freezing scenario hypothesis for that generating
function, from which we derive the distribution of extrema for the 2D GFF on the
[0,1]
interval. We provide numerical checks of the circular case and the interval case and discuss
universality and various extensions. The relevance to the distribution of the length of a
segment in Liouville quantum gravity is noted.
Dcp1-Bodies in Mouse Oocytes
Authors: Swetloff Adam , Conne Beatrice , Huarte Joachim , Pitetti Jean-Luc , Nef Serge , Vassalli Jean-Dominique
Published: October 2009

Processing bodies (P-bodies) are cytoplasmic granules involved in the storage and degradation of mRNAs. In somatic cells, their formation involves miRNA-mediated mRNA silencing. Many P-body protein components are also found in germ cell granules, such as in mammalian spermatocytes. In fully grown mammalian oocytes, where changes in gene expression depend entirely on translational control, RNA granules have not as yet been characterized. Here we show the presence of P-body-like foci in mouse oocytes, as revealed by the presence of Dcp1a and the colocalization of RNA-associated protein 55 (RAP55) and the DEAD box RNA helicase Rck/p54, two proteins associated with P-bodies and translational control. These P-body-like structures have been called Dcp1-bodies and in meiotically arrested primary oocytes, two types can be distinguished based on their size. They also have different protein partners and sensitivities to the depletion of endogenous siRNA/miRNA and translational inhibitors. However, both type progressively disappear during in vitro meiotic maturation and are virtually absent in metaphase II–arrested secondary oocytes. Moreover, this disassembly of hDcp1a-bodies is concomitant with the posttranslational modification of EGFP-hDcp1a.
RhoG Promotes Neural Progenitor Cell Proliferation in Mouse Cerebral Cortex
Authors: Fujimoto Satoshi , Negishi Manabu , Katoh Hironori
Published: October 2009

In early cortical development, neural progenitor cells (NPCs) expand their population in the ventricular zone (VZ), and produce neurons. Although a series of studies have revealed the process of neurogenesis, the molecular mechanisms regulating NPC proliferation are still largely unknown. Here we found that RhoG, a member of Rho family GTPases, was expressed in the VZ at early stages of cortical development. Expression of constitutively active RhoG promoted NPC proliferation and incorporation of bromodeoxyuridine (BrdU) in vitro, and the proportion of Ki67-positive cells in vivo. In contrast, knockdown of RhoG by RNA interference suppressed the proliferation, BrdU incorporation, and the proportion of Ki67-positive cells in NPCs. However, knockdown of RhoG did not affect differentiation and survival of NPC. The RhoG-induced promotion of BrdU incorporation required phosphatidylinositol 3-kinase (PI3K) activity but not the interaction with ELMO. Taken together, these results indicate that RhoG promotes NPC proliferation through PI3K in cortical development.
Tight Functional Coupling of Kinesin-1A and Dynein Motors in the Bidirectional Transport of Neurofilaments
Authors: Uchida Atsuko , Alami Nael H. , Brown Anthony
Published: October 2009

We have tested the hypothesis that kinesin-1A (formerly KIF5A) is an anterograde motor for axonal neurofilaments. In cultured sympathetic neurons from kinesin-1A knockout mice, we observed a 75% reduction in the frequency of both anterograde and retrograde neurofilament movement. This transport defect could be rescued by kinesin-1A, and with successively decreasing efficacy by kinesin-1B and kinesin-1C. In wild-type neurons, headless mutants of kinesin-1A and kinesin-1C inhibited both anterograde and retrograde movement in a dominant-negative manner. Because dynein is thought to be the retrograde motor for axonal neurofilaments, we investigated the effect of dynein inhibition on anterograde and retrograde neurofilament transport. Disruption of dynein function by using RNA interference, dominant-negative approaches, or a function-blocking antibody also inhibited both anterograde and retrograde neurofilament movement. These data suggest that kinesin-1A is the principal but not exclusive anterograde motor for neurofilaments in these neurons, that there may be some functional redundancy among the kinesin-1 isoforms with respect to neurofilament transport, and that the activities of the anterograde and retrograde neurofilament motors are tightly coordinated.
Utp9p Facilitates Msn5p-mediated Nuclear Reexport of Retrograded tRNAs in Saccharomyces cerevisiae
Authors: Eswara Manoja B.K. , McGuire Andrew T. , Pierce Jacqueline B. , Mangroo Dev
Published: October 2009

Utp9p is a nucleolar protein that is part of a subcomplex containing several U3 snoRNA-associated proteins including Utp8p, which is a protein that shuttles aminoacyl-tRNAs from the nucleolus to the nuclear tRNA export receptors Los1p and Msn5p in Saccharomyces cerevisiae . Here we show that Utp9p is also an intranuclear component of the Msn5p-mediated nuclear tRNA export pathway. Depletion of Utp9p caused nuclear accumulation of mature tRNAs derived from intron-containing precursors, but not tRNAs made from intronless pre-tRNAs. Utp9p binds tRNA directly and saturably, and copurifies with Utp8p, Gsp1p, and Msn5p, but not with Los1p or aminoacyl-tRNA synthetases. Utp9p interacts directly with Utp8p, Gsp1p, and Msn5p in vitro. Furthermore, Gsp1p forms a complex with Msn5p and Utp9p in a tRNA-dependent manner. However, Utp9p does not shuttle between the nucleus and the cytoplasm. Because tRNA splicing occurs in the cytoplasm and the spliced tRNAs are retrograded back to the nucleus, we propose that Utp9p facilitates nuclear reexport of retrograded tRNAs. Moreover, the data suggest that Utp9p together with Utp8p translocate aminoacyl-tRNAs from the nucleolus to Msn5p and assist with formation of the Msn5p-tRNA-Gsp1p-GTP export complex.
Knowledge-based instantiation of full atomic detail into coarse-grain RNA 3D structural models
Authors: Jonikas Magdalena A. , Radmer Randall J. , Altman Russ B.
Published: October 2009

Motivation: The recent development of methods for modeling RNA 3D structures using coarse-grain approaches creates a need to bridge low- and high-resolution modeling methods. Although they contain topological information, coarse-grain models lack atomic detail, which limits their utility for some applications.

Results: We have developed a method for adding full atomic detail to coarse-grain models of RNA 3D structures. Our method [Coarse to Atomic (C2A)] uses geometries observed in known RNA crystal structures. Our method rebuilds full atomic detail from ideal coarse-grain backbones taken from crystal structures to within 1.87–3.31 Å RMSD of the full atomic crystal structure. When starting from coarse-grain models generated by the modeling tool NAST, our method builds full atomic structures that are within 1.00 Å RMSD of the starting structure. The resulting full atomic structures can be used as starting points for higher resolution modeling, thus bridging high- and low-resolution approaches to modeling RNA 3D structure.

Availability: Code for the C2A method, as well as the examples discussed in this article, are freely available at www.simtk.org/home/c2a.

Contact:  russ.altman@stanford.edu
Interaction of the HIV-1 frameshift signal with the ribosome
Authors: Mazauric Marie-Hélène , Seol Yeonee , Yoshizawa Satoko , Visscher Koen , Fourmy Dominique
Published: October 2009

Ribosomal frameshifting on viral RNAs relies on the mechanical properties of structural elements, often pseudoknots and more rarely stem-loops, that are unfolded by the ribosome during translation. In human immunodeficiency virus (HIV)-1 type B a long hairpin containing a three-nucleotide bulge is responsible for efficient frameshifting. This three-nucleotide bulge separates the hairpin in two domains: an unstable lower stem followed by a GC-rich upper stem. Toeprinting and chemical probing assays suggest that a hairpin-like structure is retained when ribosomes, initially bound at the slippery sequence, were allowed multiple EF-G catalyzed translocation cycles. However, while the upper stem remains intact the lower stem readily melts. After the first, and single step of translocation of deacylated tRNA to the 30 S P site, movement of the mRNA stem-loop in the 5′ direction is halted, which is consistent with the notion that the downstream secondary structure resists unfolding. Mechanical stretching of the hairpin using optical tweezers only allows clear identification of unfolding of the upper stem at a force of 12.8 ± 1.0 pN. This suggests that the lower stem is unstable and may indeed readily unfold in the presence of a translocating ribosome.
Complex vocal imitation during ontogeny in a bat
Authors: Knörnschild Mirjam , Nagy Martina , Metz Markus , Mayer Frieder , von Helversen Otto
Published: October 2009

Vocal imitation—the ability to learn a previously unknown acoustic signal from a tutor—is considered to be a key innovation in the evolution of speech. This faculty is very rare and patchily distributed within the animal kingdom, suggesting multiple instances of convergent evolution. It has long been predicted that bats should be capable of vocal imitation and our results provide evidence for this phenomenon. We report that pups of the bat
Saccopteryx bilineata
learn a complex vocalization through vocal imitation. During ontogeny, pups of both sexes imitate territorial song from adult males, starting with simple precursor songs that develop into genuine renditions. The resemblance of pup renditions to their acoustic model is not caused by physical maturation effects, is independent of pups' gender and relatedness towards adult males and becomes more pronounced during ontogeny, showing that auditory experience is essential for vocal development. Our findings indicate that the faculty of vocal imitation is more widespread than previously thought and emphasize the importance of research on audiovocal communication in bats for a better understanding of the evolutionary origin of vocal imitation.
Ovulation mode modifies paternity monopolization in mammals
Authors: Soulsbury Carl D.
Published: October 2009

There are two forms of ovulation: spontaneous and induced. As copulation triggers ovulation for induced ovulators, males can predict the timing of ovulation and may have greater paternity monopolization than spontaneous ovulators. However, this prediction has never, to my knowledge, been tested. Using a cross-species comparison I examined the percentage of offspring sired within a litter (single paternity) and in social species the percentage of offspring sired by the dominant male (alpha paternity). My results indicate that ovulation mode alters the ability of males to monopolize paternity, with males of induced ovulators having higher single paternity and greater alpha paternity where male–female association is intermittent.
Personalized ventilation as a control measure for airborne transmissible disease spread
Authors: Pantelic Jovan , Sze-To Gin Nam , Tham Kwok Wai , Chao Christopher Y. H. , Khoo Yong Chuan Mike
Published: October 2009

The protective role of personalized ventilation (PV) against plausible airborne transmissible disease was investigated using cough droplets released from a ‘coughing machine’ simulating the human cough at different distances (1, 1.75 and 3 m) from the PV user. Particle image velocimetry was used to characterize and visualize the interaction between the cough-generated multiphase flow and PV-induced flow in the inhalation zone of the thermal breathing manikin. A dose–response model for unsteady imperfectly mixed environment was used to estimate the reduction in infection risk of two common diseases that can be transmitted by airborne mode. PV was able to both reduce the peak aerosol concentration levels and shorten the exposure time at all the examined injection distances. PV could reduce the infection risks of two diseases, influenza A and tuberculosis, by between 27 and 65 per cent. The protection offered by PV is less effective at a distance of 1.75 m than the other distances, as shown in the risk assessment results, as the PV-generated flow was blown off by the cough-generated flow for the longest time. Results of this study demonstrate the ability of desktop PV to mitigate the infection risk of airborne transmissible disease.
Travelling waves of a diffusive Kermack–McKendrick epidemic model with non-local delayed transmission
Authors: Wang Zhi-Cheng , Wu Jianhong
Published: October 2009

We obtain full information about the existence and non-existence of travelling wave solutions for a general class of diffusive Kermack–McKendrick SIR models with non-local and delayed disease transmission. We show that this information is determined by the basic reproduction number of the corresponding ordinary differential model, and the minimal wave speed is explicitly determined by the delay (such as the latent period) and non-locality in disease transmission, and the spatial movement pattern of the infected individuals. The difficulty is the lack of order-preserving property of the general system, and we obtain the threshold dynamics for spatial spread of the disease by constructing an invariant cone and applying Schauder’s fixed point theorem.
Low-quality females prefer low-quality males when choosing a mate
Authors: Holveck Marie-Jeanne , Riebel Katharina
Published: October 2009

Mate choice studies routinely assume female preferences for indicators of high quality in males but rarely consider developmental causes of within-population variation in mating preferences. By contrast, recent mate choice models assume that costs and benefits of searching or competing for high-quality males depend on females' phenotypic quality. A prediction following from these models is that manipulation of female quality should alter her choosiness or even the direction of her mating preferences. We here provide (to our knowledge) the first example where an experimental manipulation of female quality induced a mating preference for low-quality males. Zebra finches (Taeniopygia guttata) reared in small or large experimental broods became high- or low-quality adults, respectively. Only high-quality females preferred high-quality males' mate-advertising songs, while all low-quality females preferred low-quality males' song. Subsequent breeding trials confirmed this pattern: latency until egg laying was shortest in quality-matched pairs, indicating that quality-matched birds were accepted faster as partners. Females produced larger eggs when mated with high-quality males, regardless of their own quality, indicating consensus regarding male quality despite the expression of different choices. Our results demonstrate the importance of considering the development of mating preferences to understand their within-population variation and environmentally induced change.
Antimicrobial chemicals in hoopoe preen secretions are produced by symbiotic bacteria
Authors: Martín-Vivaldi Manuel , Peña Aránzazu , Peralta-Sánchez Juan Manuel , Sánchez Lourdes , Ananou Samir , Ruiz-Rodríguez Magdalena , Soler Juan José
Published: October 2009

Animals frequently use metabolites produced by symbiotic bacteria as agents against pathogens and parasites. Secretions from the preen gland of birds are used for this purpose, although its chemicals apparently are produced by the birds themselves. European hoopoes
Upupa epops
and green woodhoopoes
Phoeniculus purpureus
harbour symbiotic bacteria in the uropygial gland that might be partly responsible for the chemical composition of secretions. Here we investigate the antimicrobial activity of the volatile fraction of chemicals in hoopoe preen secretions, and, by means of experimental antibiotic injections, test whether symbiotic bacteria living within the uropygial gland are responsible for their production. Hoopoes produce two different kinds of secretions that differ drastically in their chemical composition. While the malodorous dark secretions produced by nestlings included a complex mix of volatiles, these chemicals did not appear in white secretions produced by non-nesting birds. All volatiles detected showed strong antibacterial activity, and a mixture of the chemicals at the concentrations measured in nestling glands inhibited the growth of all bacterial strains assayed. We found support for the hypothesized role of bacteria in the production of such antimicrobial chemicals because experimental clearance of bacteria from glands of nestlings with antibiotics resulted in secretions without most of the volatiles detected in control individuals. Thus, the presence of symbiotic bacteria in the uropygial gland provides hoopoes with potent antimicrobials for topical use.
The unexpected but understandable dynamics of mating, paternity and paternal care in the ocellated wrasse
Authors: Alonzo Suzanne H. , Heckman Kellie L.
Published: October 2009

Although theory generally predicts that males should reduce paternal care in response to cues that predict increased sperm competition and decreased paternity, empirical patterns are equivocal. Some studies have found the predicted decrease in male care with increased sperm competition, while even more studies report no effect of paternity or sperm competition on male care. Here, we report the first example, to our knowledge, of paternal care increasing with the risk and intensity of sperm competition, in the ocellated wrasse (
Symphodus ocellatus
). Theory also predicts that if paternal care varies and is important to female fitness, female choice among males and male indicators traits of expected paternal care should evolve. Despite a non-random distribution of mating success among nests, we found no evidence for female choice among parental males. Finally, we document the highest published levels of extra-pair paternity for a species with exclusive and obligate male care: genetic paternity analyses revealed cuckoldry at 100 per cent of nests and 28 per cent of all offspring were not sired by the male caring for them. While not predicted by any existing theory, these unexpected reproductive patterns become understandable if we consider how male and female mating and parental care interact simultaneously in this and probably many other species.
Rooks perceive support relations similar to six-month-old babies
Authors: Bird Christopher D. , Emery Nathan J.
Published: October 2009

Some corvids have demonstrated cognitive abilities that rival or exceed those of the great apes; for example, tool use in New Caledonian crows, and social cognition, episodic-like memory and future planning in Western scrub-jays. Rooks appear to be able to solve novel tasks through causal reasoning rather than simple trial-and-error learning. Animals with certain expectations about how objects interact would be able to narrow the field of candidate causes substantially, because some causes are simply ‘impossible’. Here we present evidence that rooks hold such expectations and appear to possess perceptual understanding of support relations similar to that demonstrated by human babies, which is more comprehensive than that of chimpanzees.
Conservative ecological and evolutionary patterns in liverwort–fungal symbioses
Authors: Bidartondo Martin I. , Duckett Jeffrey G.
Published: October 2009

Liverworts, the most ancient group of land plants, form a range of intimate associations with fungi that may be analogous to the mycorrhizas of vascular plants. Most thalloid liverworts contain arbuscular mycorrhizal glomeromycete fungi similar to most vascular plants. In contrast, a range of leafy liverwort genera and one simple thalloid liverwort family (the Aneuraceae) have switched to basidiomycete fungi. These liverwort switches away from glomeromycete fungi may be expected to parallel switches undergone by vascular plants that target diverse lineages of basidiomycete fungi to form ectomycorrhizas. To test this hypothesis, we used a cultivation-independent approach to examine the basidiomycete fungi associated with liverworts in varied worldwide locations by generating fungal DNA sequence data from over 200 field collections of over 30 species. Here we show that eight leafy liverwort genera predominantly and consistently associate with members of theSebacina vermiferaspecies complex and that Aneuraceae thalloid liverworts associate nearly exclusively withTulasnellaspecies. Furthermore, within sites where multiple liverwort species co-occur, they almost never share the same fungi. Our analyses reveal a strikingly conservative ecological and evolutionary pattern of liverwort symbioses with basidiomycete fungi that is unlike that of vascular plant mycorrhizas.
Sigma viruses from three species of
Drosophila
form a major new clade in the rhabdovirus phylogeny
Authors: Longdon Ben , Obbard Darren J. , Jiggins Francis M.
Published: October 2009

The sigma virus (DMelSV), which is a natural pathogen of
Drosophila melanogaster
, is the only
Drosophila
-specific rhabdovirus that has been described. We have discovered two new rhabdoviruses,
D. obscura
and
D. affinis
, which we have named DObsSV and DAffSV, respectively. We sequenced the complete genomes of DObsSV and DMelSV, and the L gene from DAffSV. Combining these data with sequences from a wide range of other rhabdoviruses, we found that the three sigma viruses form a distinct clade which is a sister group to the Dimarhabdovirus supergroup, and the high levels of divergence between these viruses suggest that they deserve to be recognized as a new genus. Furthermore, our analysis produced the most robustly supported phylogeny of the
Rhabdoviridae
to date, allowing us to reconstruct the major transitions that have occurred during the evolution of the family. Our data suggest that the bias towards research into plants and vertebrates means that much of the diversity of rhabdoviruses has been missed, and rhabdoviruses may be common pathogens of insects.
A kinetic model that explains the effect of inorganic phosphate on the mechanics and energetics of isometric contraction of fast skeletal muscle
Authors: Linari Marco , Caremani Marco , Lombardi Vincenzo
Published: October 2009

A conventional five-step chemo-mechanical cycle of the myosin–actin ATPase reaction, which implies myosin detachment from actin upon release of hydrolysis products (ADP and phosphate, Pi) and binding of a new ATP molecule, is able to fit the [Pi] dependence of the force and number of myosin motors during isometric contraction of skeletal muscle. However, this scheme is not able to explain why the isometric ATPase rate of fast skeletal muscle is decreased by an increase in [Pi] much less than the number of motors. The question can be solved assuming the presence of a branch in the cycle: in isometric contraction, when the force generation process by the myosin motor is biased at the start of the working stroke, the motor can detach at an early stage of the ATPase cycle, with Pi still bound to its catalytic site, and then rapidly release the hydrolysis products and bind another ATP. In this way, the model predicts that in fast skeletal muscle the energetic cost of isometric contraction increases with [Pi]. The large dissociation constant of the product release in the branched pathway allows the isometric myosin–actin reaction to fit the equilibrium constant of the ATPase.
Words as alleles: connecting language evolution with Bayesian learners to models of genetic drift
Authors: Reali Florencia , Griffiths Thomas L.
Published: October 2009

Scientists studying how languages change over time often make an analogy between biological and cultural evolution, with words or grammars behaving like traits subject to natural selection. Recent work has exploited this analogy by using models of biological evolution to explain the properties of languages and other cultural artefacts. However, the mechanisms of biological and cultural evolution are very different: biological traits are passed between generations by genes, while languages and concepts are transmitted through learning. Here we show that these different mechanisms can have the same results, demonstrating that the transmission of frequency distributions over variants of linguistic forms by Bayesian learners is equivalent to the Wright–Fisher model of genetic drift. This simple learning mechanism thus provides a justification for the use of models of genetic drift in studying language evolution. In addition to providing an explicit connection between biological and cultural evolution, this allows us to define a ‘neutral’ model that indicates how languages can change in the absence of selection at the level of linguistic variants. We demonstrate that this neutral model can account for three phenomena: the s-shaped curve of language change, the distribution of word frequencies, and the relationship between word frequencies and extinction rates.
Female reproductive strategies in orangutans, evidence for female choice and counterstrategies to infanticide in a species with frequent sexual coercion
Authors: Knott Cheryl Denise , Emery Thompson Melissa , Stumpf Rebecca M. , McIntyre Matthew H.
Published: October 2009

Intersexual conflicts over mating can engender antagonistic coevolution of strategies, such as coercion by males and selective resistance by females. Orangutans are exceptional among mammals for their high levels of forced copulation. This has typically been viewed as an alternative mating tactic used by the competitively disadvantaged unflanged male morph, with little understanding of how female strategies may have shaped and responded to this behaviour. Here, we show that male morph is not by itself a good predictor of mating dynamics in wild Bornean orangutans but that female conception risk mediated the occurrence and quality of male–female interactions. Near ovulation, females mated cooperatively only with prime flanged males who they encountered at higher rates. When conception risk was low, willingness to associate and mate with non-prime males increased. Our results support the hypothesis that, together with concealed ovulation, facultative association is a mechanism of female choice in a species in which females can rarely avoid coercive mating attempts. Female resistance, which reduced copulation time, may provide an additional mechanism for mate selection. However, coercive factors were also important as prime males were frequently aggressive to females and females used mating strategies consistent with infanticide avoidance.
Attention focusing in a sit-and-wait forager: a spider controls its prey-detection ability in different web sectors by adjusting thread tension
Authors: Nakata Kensuke
Published: October 2009

Focusing attention is a way for animals to search for and to obtain food efficiently. This study examines whether a sit-and-wait forager, the orb-web spider
Cyclosa octotuberculata
, focuses its attention on limited foraging areas. Video records of foraging activity revealed that the spiders detected prey trapped in the west and east sectors of their web less frequently than prey trapped in the north and south sectors. Comparison of photos of the web hub area with and without spiders present revealed that the spiders pulled radii towards the centre when waiting for prey. Radius pulling is stronger in the north and south web sectors than in the west and east sectors, possibly causing more tension in radii running vertically. Experimental manipulation indicated that the spiders responded to prey quicker when thread tension was increased. The results suggest that
C. octotuberculata
focus their attention on the web areas above and below the spider by adjusting the tension in web threads; and this causes higher prey detection rates in these areas.
Genome structure of a Saccharomyces cerevisiae strain widely used in bioethanol production
Authors: Argueso Juan Lucas , Carazzolle Marcelo F. , Mieczkowski Piotr A. , Duarte Fabiana M. , Netto Osmar V.C. , Missawa Silvia K. , Galzerani Felipe , Costa Gustavo G.L. , Vidal Ramon O. , Noronha Melline F. , Dominska Margaret , Andrietta Maria G.S. , Andrietta Sílvio R. , Cunha Anderson F. , Gomes Luiz H. , Tavares Flavio C.A. , Alcarde André R. , Dietrich Fred S. , McCusker John H. , Petes Thomas D. , Pereira Gonçalo A.G.
Published: October 2009

Bioethanol is a biofuel produced mainly from the fermentation of carbohydrates derived from agricultural feedstocks by the yeast Saccharomyces cerevisiae. One of the most widely adopted strains is PE-2, a heterothallic diploid naturally adapted to the sugar cane fermentation process used in Brazil. Here we report the molecular genetic analysis of a PE-2 derived diploid (JAY270), and the complete genome sequence of a haploid derivative (JAY291). The JAY270 genome is highly heterozygous (∼2 SNPs/kb) and has several structural polymorphisms between homologous chromosomes. These chromosomal rearrangements are confined to the peripheral regions of the chromosomes, with breakpoints within repetitive DNA sequences. Despite its complex karyotype, this diploid, when sporulated, had a high frequency of viable spores. Hybrid diploids formed by outcrossing with the laboratory strain S288c also displayed good spore viability. Thus, the rearrangements that exist near the ends of chromosomes do not impair meiosis, as they do not span regions that contain essential genes. This observation is consistent with a model in which the peripheral regions of chromosomes represent plastic domains of the genome that are free to recombine ectopically and experiment with alternative structures. We also explored features of the JAY270 and JAY291 genomes that help explain their high adaptation to industrial environments, exhibiting desirable phenotypes such as high ethanol and cell mass production and high temperature and oxidative stress tolerance. The genomic manipulation of such strains could enable the creation of a new generation of industrial organisms, ideally suited for use as delivery vehicles for future bioenergy technologies.
A T9G Mutation in the Prototype TATA-Box TCACTATATATAG Determines Nucleosome Formation and Synergy with Upstream Activator Sequences in Plant Promoters
Authors: Ranjan Amol , Ansari Suraiya A. , Srivastava Rakesh , Mantri Shrikant , Asif Mehar H. , Sawant Samir V. , Tuli Rakesh
Published: October 2009

We had earlier reported that mutations to G and C at the seventh and eighth positions in the prototype TATA-box TCACTATATATAG inhibited light-dependent activation of transcription from the promoter. In this study, we characterized mutations at the ninth position of the prototype TATA-box. Substitution of T at the ninth position with G or C enhanced transcription from the promoter in transgenic tobacco (Nicotiana tabacum) plants. The effect of T9G/C mutations was not light dependent, although the 9G/C TATA-box showed synergy with the light-responsive element (lre). However, the 9G/C mutants in the presence of lre failed to respond to phytochromes, sugar, and calcium signaling, in contrast to the prototype TATA-box with lre. The 9G/C mutation shifted the point of initiation of transcription, and transcription activation was dependent upon the type of activating element present upstream. The synergy in activation was noticed with lre and legumin activators but not with rbcS, Pcec, and PR-1a activators. The 9G mutation resulted in a micrococcal nuclease-sensitive region over the TATA-box, suggesting a nucleosome-free region, in contrast to the prototype promoter, which had a distinct nucleosome on the TATA-box. Thus, the transcriptional augmentation with mutation at the ninth position might be because of the loss of a repressive nucleosomal structure on the TATA-box. In agreement with our findings, the promoters containing TATAGATA as identified by genome-wide analysis of Arabidopsis (Arabidopsis thaliana) are not tightly repressed.
Imaging mass spectrometry of gastric carcinoma in formalin‐fixed paraffin‐embedded tissue microarray
Authors: Morita Yoshifumi , Ikegami Koji , Goto‐Inoue Naoko , Hayasaka Takahiro , Zaima Nobuhiro , Tanaka Hiroki , Uehara Takashi , Setoguchi Tomohiko , Sakaguchi Takanori , Igarashi Hisashi , Sugimura Haruhiko , Setou Mitsutoshi , Konno Hiroyuki
Published: October 2009

The popularity of imaging mass spectrometry (IMS) of tissue samples, which enables the direct scanning of tissue sections within a short time‐period, has been considerably increasing in cancer proteomics. Most pathological specimens stored in medical institutes are formalin‐fixed; thus, they had been regarded to be unsuitable for proteomic analyses, including IMS, until recently. Here, we report an easy‐to‐use screening method that enables the analysis of multiple samples in one experiment without extractions and purifications of proteins. We scanned, with an IMS technique, a tissue microarray (TMA) of formalin‐fixed paraffin‐embedded (FFPE) specimens. We detected a large amount of signals from trypsin‐treated FFPE‐TMA samples of gastric carcinoma tissues of different histological types. Of the signals detected, 54 were classified as signals specific to cancer with statistically significant differences between adenocarcinomas and normal tissues. We detected a total of 14 of the 54 signals as histological type‐specific with the support of statistical analyses. Tandem MS revealed that a signal specific to poorly differentiated cancer tissue corresponded to histone H4. Finally, we verified the IMS‐based finding by immunohistochemical analysis of more than 300 specimens spotted on TMAs; the immunoreactivity of histone H4 was remarkably strong in poorly differentiated cancer tissues. Thus, the application of IMS to FFPE‐TMA can enable high‐throughput analysis in cancer proteomics to aid in the understanding of molecular mechanisms underlying carcinogenesis, invasiveness, metastasis, and prognosis. Further, results obtained from the IMS of FFPE‐TMA can be readily confirmed by commonly used immunohistochemical analyses. (Cancer Sci 2009)
l‐Type amino acid transporter 1 inhibitors inhibit tumor cell growth
Authors: Oda Koji , Hosoda Noriko , Endo Hiroshi , Saito Kunio , Tsujihara Kenji , Yamamura Michio , Sakata Takeshi , Anzai Naohiko , Wempe Michael F. , Kanai Yoshikatsu , Endou Hitoshi
Published: October 2009

Most tumor cell membranes overexpress l‐type amino acid transporter 1, while normal cell membranes contain l‐type amino acid transporter 2; both are Na+‐independent amino acid transporters. Therefore, compounds that selectively inhibit l‐type amino acid transporter 1 offer researchers with a novel cancer molecular target. Synthetic chemistry efforts and in vitro screening have produced a variety of novel compounds possessing high in vitrol‐type amino acid transporter 1 selectivity; KYT‐0353 was one such compound. The present studies illustrate that KYT‐0353 inhibited 14C‐leucine uptake and cell growth in human colon cancer‐derived HT‐29 cells; IC50s were 0.06 μm and 4.1 μm, respectively. KYT‐0353 also inhibited 14C‐leucine uptake in mouse renal proximal tubule cells expressing l‐type amino acid transporter 1, and inhibited cell growth; IC50s were 0.14 μm and 16.4 μm, respectively. Compared to control animals, intravenously administered KYT‐0353 (12.5 mg/kg and 25.0 mg/kg) showed statistically significant growth inhibition against HT‐29 tumors transplanted to nude mice with maximal inhibition ratios of 65.9% and 77.2%, respectively. Body weight increase with time – a safety indicator – was slightly depressed at 12.5 mg/kg and 25.0 mg/kg with maximal ratios of 3.7% (day 2) and 6.3% (day 11), respectively. Thus, KYT‐0353 showed significant growth inhibitory effects on HT‐29 cells both in vitro and in vivo, whereas it only caused a slight body weight depression. Therefore, KYT‐0353 appears to have potential as a novel anti‐tumor agent, presumably via selective in vivol‐type amino acid transporter 1 inhibition. (Cancer Sci 2009)
Screening for hepatitis B in chemotherapy patients: survey of current oncology practices
Authors: TRAN T. T. , RAKOSKI M. O. , MARTIN P. , POORDAD F.
Published: October 2009

Background  Hepatitis B virus (HBV) reactivation occurs in up to 78% of patients receiving cytotoxic chemotherapy for nonhepatic malignancies. Reactivation can lead to hepatic dysfunction, jaundice and fulminant hepatic failure. Current recommendations include screening patients at risk for HBV prior to immunosuppressive therapy and initiating antiviral prophylaxis in patients with chronic HBV.

Aim  To investigate current practice among oncologists regarding HBV screening and antiviral prophylaxis in candidates for chemotherapy.

Methods  A survey was sent to American Medical Association registered oncologists assessing demographics and HBV screening practices. Statistical analysis was performed using Fisher’s exact test.

Results  In all, 265 responses were received. Office‐based physicians were less likely to screen for HBV prior to chemotherapy (P < 0.001). Years in practice varied: 51% with <5 years, 29% with 5–15 years and 18% with >15 years, with no difference in screening practices between groups (P = N.S.). Responders screen for HBV as follows: never – 20%, only in the presence of abnormal liver biochemistries – 30%, risk factors or history of hepatitis – 38%. In patients with known HBV, 75% of oncologists refer to specialists, 7% initiate therapy, while 15% do not refer or initiate therapy, most of whom are in an office setting (P = 0.02).

Conclusions  Twenty per cent of oncologists never screen for HBV prior to initiating chemotherapy. Office‐based physicians were less likely to screen, treat or refer to a specialist prior to chemotherapy. Greater education regarding risk of HBV reactivation is needed for clinicians treating patients with immunosuppressive therapies.

Aliment Pharmacol Ther 31, 240–246
Review article: influenza A (H1N1) virus in patients with inflammatory bowel disease
Authors: RAHIER J.‐F. , YAZDANPANAH Y. , VIGET N. , TRAVIS S. , COLOMBEL J.‐F.
Published: October 2009

Background  Infection with influenza A (H1N1)v (swine flu) has caused widespread anxiety, among patients who are potentially immunocompromised, such as those being treated for inflammatory bowel disease.

Aim  To provide guidance for physicians and their patients on the risk, prevention and management of influenza A (H1N1)v infection.

Methods  Medline was searched using the following key words: ‘swine flu’, ‘immunosuppression’, inflammatory bowel disease’, ‘recommendations’, ‘immunization’, ‘vaccination’. Organizations such as European Centre for Disease Prevention and Control, the Centers for Disease Control and Prevention and the World Health Organization were consulted for recent papers and recommendations regarding immunocompromised patients and influenza A (H1N1)v infection.

Results  Pandemic influenza A (H1N1) virus predominantly affects young patients. Those who are immunocompromised because of underlying disease or treatment are considered at higher risk of complications from influenza A (H1N1). They should be offered prevention (vaccination, postexposure prophylaxis) or treatment with antiviral drugs, if affected. Pneumococcal infection is a complication of influenza infection; therefore, pneumococcal vaccination appears advisable. Seasonal influenza vaccination is also recommended. Withdrawal of immunosuppressive treatment appears advisable during severe active infection if possible.

Conclusions  Pragmatic advice is the best that can be offered in the current circumstances because of paucity of evidence. Investigation into the impact of influenza A (H1N1)v infection in young people with chronic conditions is needed.
A computerized system for detecting signals due to drug–drug interactions in spontaneous reporting systems
Authors: Qian Yifeng , Ye Xiaofei , Du Wenmin , Ren Jingtian , Sun Yalin , Wang Hainan , Luo Baozhang , Gao Qingbin , Wu Meijing , He Jia
Published: October 2009

WHAT IS ALREADY KNOWN ABOUT THE SUBJECT

• Concomitant use of different drugs may yield excessive risk for adverse drug reactions and it is a challenging task to do surveillance on the safety profile of the interaction between different drugs.

• Currently, several methods are used by pharmacoepidemiologists and statisticians to detect possible drug–drug interactions in spontaneous reporting systems.

• However, with the increasing number of reports in the system, there is a growing need for a computerized system that could facilitate the process of data arrangement and detection of drug interaction.

WHAT THIS STUDY ADDS

• We had already developed a computerized system to detect adverse drug reaction signals due to single drugs.

• After the development of this system, interaction between different drugs could also be detected automatically and intelligently.

AIMS In spontaneous reporting systems (SRS), there is a growing need for the automated detection of adverse drug reactions (ADRs) resulting from drug–drug interactions. In addition, special attention is also needed for systems facilitating automated data preprocessing. In our study, we set up a computerized system to signal possible drug–drug interactions by which data acquisition and signal detection could be carried out automatically and the process of data preprocessing could also be facilitated.

METHODS This system was developed with Microsoft Visual Basic 6.0 and Microsoft Access was used as the database. Crude ADR reports submitted to Shanghai SRS from January 2007 to December 2008 were included in this study. The logistic regression method, the Ω shrinkage measure method, an additive model and a multiplicative model were used for automatic detection of drug–drug interactions where two drugs were used concomitantly.

RESULTS A total of 33 897 crude ADR reports were acquired from the SRS automatically. The 10 drug combinations most frequently reported were found and the 10 most suspicious drug–drug ADR combinations for each method were detected automatically after the performance of the system.

CONCLUSIONS Since the detection of drug–drug interaction depends upon the skills and memory of the professionals involved, is time consuming and the number of reports is increasing, this system might be a promising tool for the automated detection of possible drug–drug interactions in SRS.
Population pharmacokinetic analysis of cilostazol in healthy subjects with genetic polymorphisms of CYP3A5, CYP2C19 andABCB1
Authors: Yoo Hee‐Doo , Cho Hea‐Young , Lee Yong‐Bok
Published: October 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The interindividual variability of the pharmacokinetic parameters of cilostazol is relatively large.

• Cilostazol undergoes extensive hepatic metabolism via the P450 enzymes, primarily CYP3A and, to a lesser extent, CYP2C19.

• Indeed, <1% of the administered dose of cilostazol is excreted unchanged in the urine.

WHAT THIS STUDY ADDS

• A population pharmacokinetic analysis of cilostazol was conducted to evaluate the impact of CYP3A, CYP2C19 andABCB1polymorphisms on cilostazol dispositionin vivo.

• Genetic polymorphisms of CYP3A5 and CYP2C19 explain the substantial interindividual variability in the pharmacokinetics of cilostazol.

• ABCB1genotypes do not to appear to be associated with the disposition of cilostazol.

AIMSTo investigate the influence of genetic polymorphisms in the CYP3A5, CYP2C19 andABCB1genes on the population pharmacokinetics of cilostazol in healthy subjects.

METHODSSubjects who participated in four separate cilostazol bioequivalence studies with the same protocols were included in this retrospective analysis. One hundred and four healthy Korean volunteers were orally administered a single 50‐ or 100‐mg dose of cilostazol. We estimated the population pharmacokinetics of cilostazol using a nonlinear mixed effects modelling (nonmem) method and explored the possible influence of genetic polymorphisms in CYP3A (CYP3A5*3), CYP2C19 (CYP2C19*2andCYP2C19*3) andABCB1(C1236T, G2677T/A and C3435T) on the population pharmacokinetics of cilostazol.

RESULTSA two‐compartment model with a first‐order absorption and lag time described the cilostazol serum concentrations well. The apparent oral clearance (CL/F) was estimated to be 12.8 l h−1. The volumes of the central and the peripheral compartment were characterized as 20.5 l and 73.1 l, respectively. Intercompartmental clearance was estimated at 5.6 l h−1. Absorption rate constant was estimated at 0.24 h−1and lag time was predicted at 0.57 h. The genetic polymorphisms of CYP3A5 had a significant (P< 0.001) influence on the CL/Fof cilostazol. When CYP2C19 was evaluated, a significant difference (P< 0.01) was observed among the three genotypes (extensive metabolizers, intermediate metabolizers and poor metabolizers) for the CL/F. In addition, a combination of CYP3A5 and CYP2C19 genotypes was found to be associated with a significant difference (P< 0.005) in the CL/F. When including these genotypes, the interindividual variability of the CL/Fwas reduced from 34.1% in the base model to 27.3% in the final model. However, no significant differences between theABCB1genotypes and cilostazol pharmacokinetic parameters were observed.

CONCLUSIONSThe results of the present study indicate that CYP3A5 and CYP2C19 polymorphisms explain the substantial interindividual variability that occurs in the metabolism of cilostazol.