bluuebunny/crossref_metadata_2025 huggingface dataset:
On some results of Moser and of Bangert
Authors: Rabinowitz P.H. , Stredulinsky E.
Published: September 2004

A new proof is given of results in (V. Bangert, AIHP Anal. Nonlin. 6 (1989) 95) on the existence of minimal (in the sense of Giaquinta and Guisti) heteroclinic solutions of a nonlinear elliptic PDE. Bangert’s work is based on an earlier paper of Moser (AIHP Anal. Nonlin. 3 (1986) 229). Unlike (V. Bangert, AIHP Anal. Nonlin. 6 (1989) 95), the proof here is variational in nature, and involves the minimization of a 'renormalized’ functional. It is meant to be the first step towards finding locally vs. globally minimal solutions of the PDE.

Nous donnons une démonstration nouvelle des résultats de Bangert sur l’existence d’une solution minimale (au sens de Giaquinta et Guisti) hétéroclinique d’un EDP elliptique nonlinéaire. Le travail de Bangert est basé sur un article de Moser (AIHP Anal. Nonlin. 3 (1986) 229). Contrairement à (V. Bangert, AIHP Anal. Nonlin. 6 (1989) 95), la démonstration est variationelle en nature, et utilise la minimisation d’une fonctionelle « renormalisée ». C’est une tentative de premier pas pour trouver des solutions minimales localement, plutôt que globalment de l’EDP.
An error estimate for the parabolic approximation of multidimensional scalar conservation laws with boundary conditions
Authors: Droniou J. , Imbert C. , Vovelle J.
Published: September 2004

We study the parabolic approximation of a multidimensional scalar conservation law with initial and boundary conditions. We prove that the rate of convergence of the viscous approximation to the weak entropy solution is of order

η^{1/3}

, where

η

is the size of the artificial viscosity. We use a kinetic formulation and kinetic techniques for initial-boundary value problems developed by the last two authors in a previous work.

Nous étudions l’approximation parabolique d’une loi de conservation scalaire multi-dimensionnelle avec conditions initiales et aux limites. Nous prouvons que la vitesse de convergence de l’approximation visqueuse vers la solution entropique est de l’ordre de

η^{1/3}

, où

η

est la taille de la viscosité artificielle. Nous utilisons une formulation et des techniques cinétiques développées pour des problèmes au bord par les deux derniers auteurs dans un travail précédent.
Investment prioritization based on broadscale spatial budgeting to meet downstream targets for suspended sediment loads
Authors: Lu Hua , Moran C. J. , Prosser Ian P. , DeRose Ronald
Published: September 2004

On the basis of a spatially distributed sediment budget across a large basin, costs of achieving certain sediment reduction targets in rivers were estimated. A range of investment prioritization scenarios were tested to identify the most cost‐effective strategy to control suspended sediment loads. The scenarios were based on successively introducing more information from the sediment budget. The relationship between spatial heterogeneity of contributing sediment sources on cost effectiveness of prioritization was investigated. Cost effectiveness was shown to increase with sequential introduction of sediment budget terms. The solution which most decreased cost was achieved by including spatial information linking sediment sources to the downstream target location. This solution produced cost curves similar to those derived using a genetic algorithm formulation. Appropriate investment prioritization can offer large cost savings because the magnitude of the costs can vary by several times depending on what type of erosion source or sediment delivery mechanism is targeted. Target settings which only consider the erosion source rates can potentially result in spending more money than random management intervention for achieving downstream targets. Coherent spatial patterns of contributing sediment emerge from the budget model and its many inputs. The heterogeneity in these patterns can be summarized in a succinct form. This summary was shown to be consistent with the cost difference between local and regional prioritization for three of four test catchments. To explain the effect for the fourth catchment, the detail of the individual sediment sources needed to be taken into account.
Mixing structures in the Mediterranean Sea from finite‐size Lyapunov exponents
Authors: d'Ovidio Francesco , Fernández Vicente , Hernández‐García Emilio , López Cristóbal
Published: September 2004

We characterize horizontal mixing and transport structures in the surface circulation of the Mediterranean Sea, as obtained from a primitive equation circulation model. We calculate the Finite Size Lyapunov Exponents (FSLEs) of the velocity data set, which give a direct measure of the local stirring. By proper election of the FSLE parameters, we focus on the mesoscale structures, locating a number of vortices embedded in an intricate network of high‐stretching lines. These lines control transport in the system. At the edge of the vortices, a dense tangle of line intersections appears, identifying strong mixing. The spatial distribution of FSLEs, averaged over one year, allows to classify areas in the Mediterranean basin according by their mixing activity. The space average of FSLEs on selected geographical regions gives a measure for quantifying and comparing the mixing seasonal variability.
A simple method for estimating variations in the predictability of ENSO
Authors: Tang Youmin , Kleeman Richard , Moore Andrew M.
Published: September 2004

Using a linear stochastic dynamical system, we further develop a recently proposed criteria of measuring variations in the predictability of ENSO. It is found that model predictability is intrinsically related to how the initial signal variance (ISV) projects on to its eigenmode space. When the ISV is large, the corresponding prediction is found to be reliable, whereas when the ISV is small, the prediction is likely to be less reliable. This finding was validated by results from a more realistic model prediction system for the period 1964–1998. A comparison of model skill and ISV for prediction made with and without data assimilation reveals that the role of data assimilation in improving model predictability may be mainly due to a further increase of ISV. Furthermore, model skill may result mainly from a few successful predictions associated with large ISV.
Daytime vertical and zonal velocities from 150‐km echoes: Their relevance to F‐region dynamics
Authors: Chau Jorge L. , Woodman Ronald F.
Published: September 2004

As it was suggested by Kudeki and Fawcett [1993], and later shown by Woodman and Villanueva [1995], vertical Doppler velocities of daytime 150‐km echoes represent the vertical E × B drift velocities at F region altitudes. Recently a special experiment was conducted to compare not only the vertical but also the zonal velocities from 150‐km echoes with those from an incoherent scatter radar (ISR) mode perpendicular to the magnetic field. The vertical velocity comparisons show that (1) there is a very good agreement between 150‐km velocity and the mean F‐region E × B drift, and (2) much better agreement is found with the extrapolated values from the ISR altitudinal profiles. On the other hand poor‐to‐good agreement is found between their zonal components. Our preliminary zonal velocity results, indicate that there is a poor agreement before noontime, while better agreement is found in the afternoon.
Isolation ofMycobacterium tuberculosismutants defective in the arrest of phagosome maturation
Authors: Pethe Kevin , Swenson Dana L. , Alonso Sylvie , Anderson Jennifer , Wang Carren , Russell David G.
Published: September 2004

Mycobacterium tuberculosisresides within the phagocytes of its host. It ensures its continued survival through arresting the normal maturation of its phagosome, which is retained within the early endosomal system of the macrophage. Although individual bacterial components have been shown to modulate phagosome biogenesis, the mechanism(s) active in live, intact bacteria remain elusive. We have developed a genetic screen that facilitates the isolation of mutants defective in arresting the maturation of their phagosomes. Macrophages were incubated with iron-dextran that was chased into lysosomes. The cells were subsequently infected withM. tuberculosisfrom a library of transposon-mutagenized bacteria. After four rounds of enrichment, the majority of mutants isolated were unable to prevent acidification of their phagosomes and were attenuated for intracellular survival. The genes affected range in function from those with no known homologues to putative transporters and lipid synthesis enzymes. Further characterization of these bacteria is needed. In addition to clarifying the processes active in modulation of phagosome biogenesis byM. tuberculosis, this screen may be applicable to other pathogens that restrict the maturation of their phagosome.
Topologically driven swelling of a polymer loop
Authors: Moore Nathan T. , Lua Rhonald C. , Grosberg Alexander Y.
Published: September 2004

Numerical studies of the average size of trivially knotted polymer loops with no excluded volume were undertaken. Topology was identified by Alexander and Vassiliev degree 2 invariants. Probability of a trivial knot, average gyration radius, and probability density distributions as functions of gyration radius were generated for loops of up to
N
= 3,000 segments. Gyration radii of trivially knotted loops were found to follow a power law similar to that of self-avoiding walks consistent with earlier theoretical predictions.
Analysis of
Rhizobium etli
and of its symbiosis with wild
Phaseolus vulgaris
supports coevolution in centers of host diversification
Authors: Aguilar O. Mario , Riva Omar , Peltzer Eitel
Published: September 2004

Common beans (
Phaseolus vulgaris
) comprise three major geographic genetic pools, one in Mexico, Central America, and Colombia, another in the southern Andes, and a third in Ecuador and northern Peru. Species
Rhizobium etli
is the predominant rhizobia found symbiotically associated with beans in the Americas. We have found polymorphism in the common nodulation gene
nod
C among
R. etli
strains from a wide range of geographical origins, which disclosed three
nod
C types. The different
nod
C alleles in American strains show varying predominance in their regional distributions in correlation with the centers of bean genetic diversification (BD centers). By cross-inoculating wild common beans from the three BD centers with soils from Mexico, Ecuador, Bolivia, and Northwestern Argentina, the
R. etli
populations from nodules originated from Mexican soil again showed allele predominance that was opposite to those originated from Bolivian and Argentinean soil, whereas populations from Ecuadorian soil were intermediate. These results also indicated that the preferential nodulation of beans by geographically related
R. etli
lineages was independent of the nodulating environment. Coinoculation of wild common beans from each of the three BD centers with an equicellular mixture of
R. etli
strains representative of the Mesoamerican and southern Andean lineages revealed a host-dependent distinct competitiveness: beans from the Mesoamerican genetic pool were almost exclusively nodulated by strains from their host region, whereas nodules of beans from the southern Andes were largely occupied by the geographically cognate
R. etli
lineages. These results suggest coevolution in the centers of host genetic diversification.
SUMO and ubiquitin in the nucleus: different functions, similar mechanisms?
Authors: Gill Grace
Published: September 2004

The small ubiquitin-related modifier SUMO posttranslationally modifies many proteins with roles in diverse processes including regulation of transcription, chromatin structure, and DNA repair. Similar to nonproteolytic roles of ubiquitin, SUMO modification regulates protein localization and activity. Some proteins can be modified by SUMO and ubiquitin, but with distinct functional consequences. It is possible that the effects of ubiquitination and SUMOylation are both largely due to binding of proteins bearing specific interaction domains. Both modifications are reversible, and in some cases dynamic cycles of modification may be required for activity. Studies of SUMO and ubiquitin in the nucleus are yielding new insights into regulation of gene expression, genome maintenance, and signal transduction.
Human Rif1, ortholog of a yeast telomeric protein, is regulated by ATM and 53BP1 and functions in the S-phase checkpoint
Authors: Silverman Joshua , Takai Hiroyuki , Buonomo Sara B.C. , Eisenhaber Frank , de Lange Titia
Published: September 2004

We report on the function of the human ortholog of Saccharomyces cerevisiae Rif1 (Rap1-interacting factor 1). Yeast Rif1 associates with telomeres and regulates their length. In contrast, human Rif1 did not accumulate at functional telomeres, but localized to dysfunctional telomeres and to telomeric DNA clusters in ALT cells, a pattern of telomere association typical of DNA-damage-response factors. After induction of double-strand breaks (DSBs), Rif1 formed foci that colocalized with other DNA-damage-response factors. This response was strictly dependent on ATM (ataxia telangiectasia mutated) and 53BP1, but not affected by diminished function of ATR (ATM- and Rad3-related kinase), BRCA1, Chk2, Nbs1, and Mre11. Rif1 inhibition resulted in radiosensitivity and a defect in the intra-S-phase checkpoint. The S-phase checkpoint phenotype was independent of Nbs1 status, arguing that Rif1 and Nbs1 act in different pathways to inhibit DNA replication after DNA damage. These data reveal that human Rif1 contributes to the ATM-mediated protection against DNA damage and point to a remarkable difference in the primary function of this protein in yeast and mammals.
Regulatory circuit design and evolution using phage λ
Authors: Atsumi Shota , Little John W.
Published: September 2004

Bistable gene regulatory circuits can adopt more than one stable epigenetic state. To understand how natural circuits have this and other systems properties, several groups have designed regulatory circuits de novo. Here we describe an alternative approach. We have modified an existing bistable circuit, that of phage λ. With this approach, we used powerful genetic selections to identify functional circuits and selected for variants with altered behavior. The λ circuit involves two antagonistic repressors, CI and Cro. We replaced λ Cro with a module that included Lac repressor and several lac operators. Using a combinatorial approach, we isolated variants with different types of regulatory behavior. Several resembled wild-type λ—they could grow lytically, could form highly stable lysogens, and carried out prophage induction. Another variant could form stable lysogens in the presence of a ligand for Lac repressor but switched to the lytic state when the ligand was removed. Several isolates evolved toward a desired behavior under selective pressure. These results strongly support the idea that complex circuits can arise during the course of evolution by a combination of simpler regulatory modules. They also underscore the advantages of modifying a natural circuit as an approach to understanding circuit design, systems behavior, and circuit evolution.
Association of the transcriptional corepressor TIF1β with heterochromatin protein 1 (HP1): an essential role for progression through differentiation
Authors: Cammas Florence , Herzog Marielle , Lerouge Thierry , Chambon Pierre , Losson Régine
Published: September 2004

The transcriptional intermediary factor 1β (TIF1β) is a corepressor for KRAB-domain-containing zinc finger proteins and is believed to play essential roles in cell physiology by regulating chromatin organization at specific loci through association with chromatin remodeling and histone-modifying activities and recruitment of heterochromatin protein 1 (HP1) proteins. In this study, we have engineered a modified embryonal carcinoma F9 cell line (TIF1βHP1box/-) expressing a mutated TIF1β protein (TIF1βHP1box) unable to interact with HP1 proteins. Phenotypic analysis of TIF1βHP1box/- and TIF1β+/- cells shows that TIF1β–HP1 interaction is not required for differentiation of F9 cells into primitive endoderm-like (PrE) cells on retinoic acid (RA) treatment but is essential for further differentiation into parietal endoderm-like (PE) cells on addition of cAMP and for differentiation into visceral endoderm-like cells on treatment of vesicles with RA. Complementation experiments reveal that TIF1β–HP1 interaction is essential only during a short window of time within early differentiating PrE cells to establish a selective transmittable competence to terminally differentiate on further cAMP inducing signal. Moreover, the expression of three endoderm-specific genes, GATA6, HNF4, and Dab2, is down-regulated in TIF1βHP1box/- cells compared with wild-type cells during PrE differentiation. Collectively, these data demonstrate that the interaction between TIF1β and HP1 proteins is essential for progression through differentiation by regulating the expression of endoderm differentiation master players.
Vilse, a conserved Rac/Cdc42 GAP mediating Robo repulsion in tracheal cells and axons
Authors: Lundström Annika , Gallio Marco , Englund Camilla , Steneberg Pär , Hemphälä Johanna , Aspenström Pontus , Keleman Krystyna , Falileeva Ludmilla , Dickson Barry J. , Samakovlis Christos
Published: September 2004

Slit proteins steer the migration of many cell types through their binding to Robo receptors, but how Robo controls cell motility is not clear. We describe the functional analysis of vilse, a Drosophila gene required for Robo repulsion in epithelial cells and axons. Vilse defines a conserved family of RhoGAPs (Rho GTPase-activating proteins), with representatives in flies and vertebrates. The phenotypes of vilse mutants resemble the tracheal and axonal phenotypes of Slit and Robo mutants at the CNS midline. Dosage-sensitive genetic interactions between vilse, slit, and robo mutants suggest that vilse is a component of robo signaling. Moreover, overexpression of Vilse in the trachea of robo mutants ameliorates the phenotypes of robo, indicating that Vilse acts downstream of Robo to mediate midline repulsion. Vilse and its human homolog bind directly to the intracellular domains of the corresponding Robo receptors and promote the hydrolysis of RacGTP and, less efficiently, of Cdc42GTP. These results together with genetic interaction experiments with robo, vilse, and rac mutants suggest a mechanism whereby Robo repulsion is mediated by the localized inactivation of Rac through Vilse.
A Benchmark for Methods in Reverse Engineering and Model Discrimination: Problem Formulation and Solutions
Authors: Kremling Andreas , Fischer Sophia , Gadkar Kapil , Doyle Francis J. , Sauter Thomas , Bullinger Eric , Allgöwer Frank , Gilles Ernst D.
Published: September 2004

A benchmark problem is described for the reconstruction and analysis of biochemical networks given sampled experimental data. The growth of the organisms is described in a bioreactor in which one substrate is fed into the reactor with a given feed rate and feed concentration. Measurements for some intracellular components are provided representing a small biochemical network. Problems of reverse engineering, parameter estimation, and identifiability are addressed. The contribution mainly focuses on the problem of model discrimination. If two or more model variants describe the available experimental data, a new experiment must be designed to discriminate between the hypothetical models. For the problem presented, the feed rate and feed concentration of a bioreactor system are available as control inputs. To verify calculated input profiles an interactive Web site (http://www.sysbio.de/projects/benchmark/) is provided. Several solutions based on linear and nonlinear models are discussed.
De Novo Repeat Classification and Fragment Assembly
Authors: Pevzner Paul A. , Tang Haixu , Tesler Glenn
Published: September 2004

Repetitive sequences make up a significant fraction of almost any genome, and an important and still open question in bioinformatics is how to represent all repeats in DNA sequences. We propose a new approach to repeat classification that represents all repeats in a genome as a mosaic of sub-repeats. Our key algorithmic idea also leads to new approaches to multiple alignment and fragment assembly. In particular, we show that our FragmentGluer assembler improves on Phrap and ARACHNE in assembly of BACs and bacterial genomes.
Sequence Comparison of Human and Mouse Genes Reveals a Homologous Block Structure in the Promoter Regions
Authors: Suzuki Yutaka , Yamashita Riu , Shirota Matsuyuki , Sakakibara Yuta , Chiba Joe , Mizushima-Sugano Junko , Nakai Kenta , Sugano Sumio
Published: September 2004

Comparative sequence analysis was carried out for the regions adjacent to experimentally validated transcriptional start sites (TSSs), using 3324 pairs of human and mouse genes. We aligned the upstream putative promoter sequences over the 1-kb proximal regions and found that the sequence conservation could not be further extended at, on average, 510 bp upstream positions of the TSSs. This discontinuous manner of the sequence conservation revealed a “block” structure in about one-third of the putative promoter regions. Consistently, we also observed that G+C content and CpG frequency were significantly different inside and outside the blocks. Within the blocks, the sequence identity was uniformly 65% regardless of their length. About 90% of the previously characterized transcription factor binding sites were located within those blocks. In 46% of the blocks, the 5′ ends were bounded by interspersed repetitive elements, some of which may have nucleated the genomic rearrangements. The length of the blocks was shortest in the promoters of genes encoding transcription factors and of genes whose expression patterns are brain specific, which suggests that the evolutional diversifications in the transcriptional modulations should be the most marked in these populations of genes.
An SNP Resource for Rice Genetics and Breeding Based on SubspeciesIndicaandJaponicaGenome Alignments
Authors: Feltus F. Alex , Wan Jun , Schulze Stefan R. , Estill James C. , Jiang Ning , Paterson Andrew H.
Published: September 2004

Dense coverage of the rice genome with polymorphic DNA markers is an invaluable tool for DNA marker-assisted breeding, positional cloning, and a wide range of evolutionary studies. We have aligned drafts of two rice subspecies,indicaandjaponica, and analyzed levels and patterns of genetic diversity. After filtering multiple copy and low quality sequence, 408,898 candidate DNA polymorphisms (SNPs/INDELs) were discerned between the two subspecies. These filters have the consequence that our data set includes only a subset of the available SNPs (in particular excluding large numbers of SNPs that may occur between repetitive DNA alleles) but increase the likelihood that this subset is useful: Direct sequencing suggests that 79.8% ± 7.5% of the in silico SNPs are real. The SNP sample in our database is not randomly distributed across the genome. In fact, 566 rice genomic regions had unusually high (328 contigs/48.6 Mb/13.6% of genome) or low (237 contigs/64.7 Mb/18.1% of genome) polymorphism rates. Many SNP-poor regions were substantially longer than most SNP-rich regions, covering up to 4 Mb, and possibly reflecting introgression between the respective gene pools that may have occurred hundreds of years ago. Although 46.2% ± 8.3% of the SNPs differentiate other pairs ofjaponicaandindicagenotypes, SNP rates in rice were not predictive of evolutionary rates for corresponding genes in another grass species, sorghum. The data set is freely available athttp://www.plantgenome.uga.edu/snp.
Evidence for Gradients of Human Genetic Diversity Within and Among Continents
Authors: Serre David , Pääbo Svante
Published: September 2004

Genetic variation in humans is sometimes described as being discontinuous among continents or among groups of individuals, and by some this has been interpreted as genetic support for “races.” A recent study in which >350 microsatellites were studied in a global sample of humans showed that they could be grouped according to their continental origin, and this was widely interpreted as evidence for a discrete distribution of human genetic diversity. Here, we investigate how study design can influence such conclusions. Our results show that when individuals are sampled homogeneously from around the globe, the pattern seen is one of gradients of allele frequencies that extend over the entire world, rather than discrete clusters. Therefore, there is no reason to assume that major genetic discontinuities exist between different continents or “races.”
Genome-Scale In Silico Models of E. coli Have Multiple Equivalent Phenotypic States: Assessment of Correlated Reaction Subsets That Comprise Network States
Authors: Reed Jennifer L. , Palsson Bernhard Ø.
Published: September 2004

The constraint-based analysis of genome-scale metabolic and regulatory networks has been successful in predicting phenotypes and useful for analyzing high-throughput data sets. Within this modeling framework, linear optimization has been used to study genome-scale metabolic models, resulting in the enumeration of single optimal solutions describing the best use of the network to support growth. Here mixed-integer linear programming was used to calculate and study a subset of the alternate optimal solutions for a genome-scale metabolic model of Escherichia coli (iJR904) under a wide variety of environmental conditions. Analysis of the calculated sets of optimal solutions found that: (1) only a small subset of reactions in the network have variable fluxes across optima; (2) sets of reactions that are always used together in optimal solutions, correlated reaction sets, showed moderate agreement with the currently known transcriptional regulatory structure in E. coli and available expression data, and (3) reactions that are used under certain environmental conditions can provide clues about network regulatory needs. In addition, calculation of suboptimal flux distributions, using flux variability analysis, identified reactions which are used under significantly more environmental conditions suboptimally than optimally. Together these results demonstrate the utilization of reactions in genome-scale models under a variety of different growth conditions.
Recurrent Sites for New Centromere Seeding
Authors: Ventura Mario , Weigl Stefania , Carbone Lucia , Cardone Maria Francesca , Misceo Doriana , Teti Mariagrazia , D'Addabbo Pietro , Wandall Annelise , Björck Erik , de Jong Pieter J. , She Xinwei , Eichler Evan E. , Archidiacono Nicoletta , Rocchi Mariano
Published: September 2004

Using comparative FISH and genomics, we have studied and compared the evolution of chromosome 3 in primates and two human neocentromere cases on the long arm of this chromosome. Our results show that one of the human neocentromere cases maps to the same 3q26 chromosomal region where a new centromere emerged in a common ancestor of the Old World monkeys ∼25-40 million years ago. Similarly, the locus in which a new centromere was seeded in the great apes' ancestor was orthologous to the site in which a new centromere emerged in the New World monkeys' ancestor. These data suggest the recurrent use of longstanding latent centromeres and that there is an inherent potential of these regions to form centromeres. The second human neocentromere case (3q24) revealed unprecedented features. The neocentromere emergence was not accompanied by any chromosomal rearrangement that usually triggers these events. Instead, it involved the functional inactivation of the normal centromere, and was present in an otherwise phenotypically normal individual who transmitted this unusual chromosome to the next generation. We propose that the formation of neocentromeres in humans and the emergence of new centromeres during the course of evolution share a common mechanism.
Comparative Analysis of Apicomplexa and Genomic Diversity in Eukaryotes
Authors: Templeton Thomas J. , Iyer Lakshminarayan M. , Anantharaman Vivek , Enomoto Shinichiro , Abrahante Juan E. , Subramanian G.M. , Hoffman Stephen L. , Abrahamsen Mitchell S. , Aravind L.
Published: September 2004

The apicomplexansPlasmodiumandCryptosporidiumhave developed distinctive adaptations via lineage-specific gene loss and gene innovation in the process of diverging from a common parasitic ancestor. The two lineages have acquired distinct but overlapping sets of surface protein adhesion domains typical of animal proteins, but in no case do they share multidomain architectures identical to animals.Cryptosporidium, but notPlasmodium, possesses an animal-typeO-linked glycosylation pathway, along with >30 predicted surface proteins having mucin-like segments. The two parasites have notable qualitative differences in conserved protein architectures associated with chromatin dynamics and transcription.Cryptosporidiumshows considerable reduction in the number of introns and a concomitant loss of spliceosomal machinery components. We also describe additional molecular characteristics distinguishing Apicomplexa from other eukaryotes for which complete genome sequences are available.
Widespread RNA Editing of EmbeddedAluElements in the Human Transcriptome
Authors: Kim Dennis D.Y. , Kim Thomas T.Y. , Walsh Thomas , Kobayashi Yoshifumi , Matise Tara C. , Buyske Steven , Gabriel Abram
Published: September 2004

More than one million copies of the ∼300-bpAluelement are interspersed throughout the human genome, with up to 75% of all known genes havingAluinsertions within their introns and/or UTRs. TranscribedAlusequences can alter splicing patterns by generating new exons, but other impacts of intragenicAluelements on their host RNA are largely unexplored. Recently, repeat elements present in the introns or 3′-UTRs of 15 human brain RNAs have been shown to be targets for multiple adenosine to inosine (A-to-I) editing. Using a statistical approach, we find that editing of transcripts with embeddedAlusequences is a global phenomenon in the human transcriptome, observed in 2674 (∼2%) of all publicly available full-length human cDNAs (n= 128,406), from >250 libraries and >30 tissue sources. In the vast majority of edited RNAs, A-to-I substitutions are clustered within transcribed sense or antisenseAlusequences. Edited bases are primarily associated with retained introns, extended UTRs, or with transcripts that have no corresponding known gene. Therefore,Alu-associated RNA editing may be a mechanism for marking nonstandard transcripts, not destined for translation.
The Society for Scholarly Publishing Annual Meeting
Authors: Gelfand Julia
Published: September 2004

The author gives an overview of the annual meeting of the Society of Scholarly Publishing and outlines the highlights of some of the sessions, including the keynote addresses on how the law and technology can affect scholarly publishing in the digital age, and research on how engineers communicate. Notes that the session on researcher perspectives on publishing was a personal highlight of the meeting, which was held in San Francisco.
“eLMS”: The e‐Learning Managed Solution: Enabling Learning into the Future
Authors: Harrison Marcia
Published: September 2004

Describes the development of a fully managed service at Cranfield University that supports various aspects of online, distributed or blended learning. The e‐Learning Managed Solution (eLMS) is capable of addressing different e‐learning strategies, allowing learning content to be repurposed across sectors and different programmes, allowing better management of workflows and providing durability of learning content.
Prediction of pKa and redox properties in the thioredoxin superfamily
Authors: Moutevelis Efrosini , Warwicker Jim
Published: September 2004

Electrostatic interactions play important roles in diverse biological phenomena controlling the function of many proteins. Polar molecules can be studied with the FDPB method solving the Poisson‐Boltzmann equation on a finite difference grid. A method for the prediction of pKas and redox potentials in the thioredoxin superfamily is introduced. The results are compared with experimental pKa data where available, and predictions are made for members lacking such data. Studying CxxC motif variation in the context of different background structures permits analysis of contributions to cysteine ΔpKas. The motif itself and the overall framework regulate pKa variation. The reported method includes generation of multiple side‐chain rotamers for the CxxC motif and is an effective predictive tool for functional pKa variation across the superfamily. Redox potential follows the trend in cysteine pKa variation, but some residual discrepancy indicates that a pH‐independent factor plays a role in determining redox potentials for at least some members of the superfamily. A possible molecular basis for this feature is discussed.
Probing the influence on folding behavior of structurally conserved core residues in P. aeruginosa apo‐azurin
Authors: Engman K. Cecilia , Sandberg Anders , Leckner Johan , Karlsson B. Göran
Published: September 2004

The effects on folding kinetics and equilibrium stability of core mutations in the apo‐mutant C112S of azurin from Pseudomonas aeruginosa were studied. A number of conserved residues within the cupredoxin family were recognized by sequential alignment as constituting a common hydrophobic core: I7, F15, L33, W48, F110, L50, V95, and V31. Of these, I7, V31, L33, and L50 were mutated for the purpose of obtaining information on the transition state and a potential folding nucleus. In addition, residue V5 in the immediate vicinity of the common core, as well as T52, separate from the core, were mutated as controls. All mutants exhibited a nonlinear dependence of activation free energy of folding on denaturant concentration, although the refolding kinetics of the V31A/C112S mutant indicated that the V31A mutation destabilizes the transition state enough to allow folding via a parallel transition state ensemble. Φ‐values could be calculated for three of the six mutants, V31A/C112S, L33A/C112S, and L50A/C112S, and the fractional values of 0.63, 0.33, and 0.50 (respectively) obtained at 0.5 M GdmCl suggest that these residues are important for stabilizing the transition state. Furthermore, a linear dependence of ln kobsH2O on ΔGU−NH2O of the core mutations and the putative involvement of ground‐state effects suggest the presence of native‐like residual interactions in the denatured state that bias this ensemble toward a folding‐competent state.
Structure and function of the Gondwanian hemoglobin of Pseudaphritis urvillii, a primitive notothenioid fish of temperate latitudes
Authors: Verde Cinzia , Howes Barry D. , De Rosa M. Cristina , Raiola Luca , Smulevich Giulietta , Williams Richard , Giardina Bruno , Parisi Elio , Di Prisco Guido
Published: September 2004

The suborder Notothenioidei dominates the Antarctic ichthyofauna. The non‐Antarctic monotypic family Pseudaphritidae is one of the most primitive families. The characterization of the oxygen‐transport system of euryhaline Pseudaphritis urvillii is herewith reported. Similar to most Antarctic notothenioids, this temperate species has a single major hemoglobin (Hb 1, over 95% of the total). Hb 1 has strong Bohr and Root effects. It shows two very uncommon features in oxygen binding: At high pH values, the oxygen affinity is exceptionally high compared to other notothenioids, and subunit cooperativity is modulated by pH in an unusual way, namely the curve of the Hill coefficient is bell‐shaped, with values approaching 1 at both extremes of pH. Molecular modeling, electronic absorption and resonance Raman spectra have been used to characterize the heme environment of Hb 1 in an attempt to explain these features, particularly in view of some potentially important nonconservative replacements found in the primary structure. Compared to human HbA, no major changes were found in the structure of the proximal cavity of the α‐chain of Hb 1, although an altered distal histidyl and heme position was identified in the models of the β‐chain, possibly facilitated by a more open heme pocket due to reduced steric constraints on the vinyl substituent groups. This conformation may lead to the hemichrome form identified by spectroscopy in the Met state, which likely fulfils a potentially important physiological role.
Cartilage is a metazoan tissue; integrating data from nonvertebrate sources
Authors: Cole Alison G. , Hall Brian K.
Published: September 2004

Connective tissues are responsible for much of the variation in morphology that we see today. Cartilage is a type of connective tissue that is often considered to be restricted to vertebrates, however, cartilaginous tissues are also found within invertebrates. Unfortunately, most definitions and classification schemes for cartilages suffer from a strong vertebrate bias, severely hampering the efforts of those who have attempted to include invertebrate tissues as cartilage. To encompass all types of cartilage, current classification systems need to be expanded. Here we present vesicular cell‐rich as a new cartilage classification. Invertebrate cartilages, comparable to vertebrate cartilages at both cell and tissue levels, are composed of similar molecules, yet the extent to which they may be homologous is unknown. One option for studying the evolution of tissues is to adopt molecular phylogenetic approaches. However, the paucity of published molecular data makes addressing the evolution of cartilage using molecular phylogenetic approaches unrealistic at this time. Cartilage likely evolved from a chondroid connective tissue precursor, and may have been independently derived many times. The appearance of cartilaginous tissues of unknown phylogenetic affinities in such a wide diversity of animal groups warrants further investigation.
A dendrobranchiate, Peisos petrunkevitchi (Decapoda, Sergestidae), with reptant‐like sperm: a spermiocladistic assessment
Authors: Scelzo Marcelo A. , Medina Antonio
Published: September 2004

The spermatozoon of Peisos petrunkevitchi differs significantly from those of any of the investigated dendrobranchiates in the anterior fusiform acrosome, lacking a spike, and embedded in (instead of capping) the nuclear region. In contrast, the position of the acrosome and the internal arrangement of its contents, as well as the apomorphic presence of a pair of centrioles (absent in all known dendrobranchiate spermatozoa) at the base of the acrosomal perforatorium, indicate a close affinity between this sperm plan and that found in reptants, especially anomurans and brachyurans. Based on the present and previous observations on decapod spermatozoal ultrastructure, we review the phylogeny of dendrobranchiate spermatozoa in the perspective of most recent phylogenetic analyses of malacostracan crustaceans.
crabp and maf highlight the novelty of the amphioxus club‐shaped gland
Authors: Jackman William R. , Mougey Jolee M. , Panopoulou Georgia D. , Kimmel Charles B.
Published: September 2004

The club‐shaped gland (csg) is a prominent organ during the development of amphioxus. However, the evolutionary significance of this pharyngeal structure has been a mystery because of the lack of an obvious corollary in vertebrates or other close relatives. To address the homology of the csg by molecular means, we report the cloning and expression patterns of two amphioxus genes expressed during its development, crabp and maf. Amphioxus maf is a bzip transcription factor expressed early in csg formation in the forming of the ventral duct of the gland. crabp encodes a cellular retinoic acid binding protein and is expressed widely in the csg later in its development. We compare these genes to the expression of AmphiKrox, a zinc‐finger transcription factor previously reported to be expressed during csg development. Together these genes mark different spatial and temporal aspects of csg formation. However, we find little evidence to suggest homology of the csg with other organs in amphioxus or other chordates. We therefore propose that the csg can be viewed as an evolutionary novelty that probably arose within the amphioxus lineage.
Variation in plasma glucose and pancreatic β cells in the turtle, Lissemys punctata (order: Chelonia; family: Trionychidae)
Authors: Chandavar Vidya R. , Naik Prakash R.
Published: September 2004

The present study relates to the determination of the plasma glucose level and volumetric analysis of β cells in pancreatic islets of the soft‐shelled turtle Lissemys punctata during different phases of its reproductive cycle. Reproductive events play a vital role in influencing the plasma glucose level and β‐cell behaviour in the pancreatic islets. The colour of the pancreas is either yellowish or pinkish, depending on endocrine activity. Islets are present throughout the gland and range from individual cells to small or large clumps, depending on the seasonal cycle. Splenic islets are dense with more blood capillaries and nerve innervations irrespective of sex and season. The endocrine cell mass forms irregular patches without connective tissue capsule. β cells occupy the inner region of the islets, being surrounded by other cell types. Lissemys punctata exhibits higher β‐cell activity during hibernation. Most insulin‐secreting cells acquire a larger size during the regressive period. An analysis indicates that β cells outnumber the non‐β endocrine cell mass in both number and per cent volume. There is negative correlation between islet mass and animal weight. Between the periods of reproductive cycles, a difference exists with respect to fasting plasma glucose and β‐cell volume.
Structure of the coxa and homeosis of legs in Nematocera (Insecta: Diptera)
Authors: Frantsevich Leonid
Published: September 2004

Construction of the middle and hind coxae was investigated in 95 species of 30 nematoceran families. As a rule, the middle coxa contains a separate coxite, the mediocoxite, articulated to the sternal process. In most families, this coxite is movably articulated to the eucoxite and to the distocoxite area; the coxa is radially split twice. Some groups are characterized by a single split.

The coxa in flies is restricted in its rotation owing to a partial junction either between the meron and the pleurite or between the eucoxite and the meropleurite. Hence the coxa is fastened to the thorax not only by two pivots (to the pleural ridge and the sternal process), but at the junction named above. Rotation is impossible without deformations; the role of hinges between coxites is to absorb deformations. This adaptive principle is confirmed by physical modelling.

Middle coxae of limoniid tribes Eriopterini and Molophilini are compact, constructed by the template of hind coxae. On the contrary, hind coxae in all families of Mycetophiloidea and in Psychodidae s.l. are constructed like middle ones, with the separate mediocoxite, centrally suspended at the sternal process. These cases are considered as homeotic mutations, substituting one structure with a no less efficient one.
Intraductal pancreatic calculi in patients with choledochal cyst
Authors: Taneja S , Nagi B , Kochhar R , Bhasin DK , Lal A , Singh K
Published: September 2004

Intraductal pancreatic calculi are a rare association in patients with choledochal cyst (CC). Reported herein is a retrospective analysis of the data on pancreatic calculi in 37 patients (10 children and 27 adults) who underwent endoscopic retrograde cholangiopancreatography (ERCP) for CC over a period of 15 years. Five patients (one child and four adults) were identified as having intraductal pancreatic calculi. Three had type I and two had type IV CC. Four underwent cyst excision. No intervention was carried out for the pancreatic calculi. There was no evidence of pancreatic insufficiency on follow up and none had recurrence of abdominal pain. One patient died of cholangitis, which was the initial presenting problem. Intraductal pancreatic calculi associated with CC, although uncommon, are not rare and are not always symptomatic.
Role of mammography in diagnosis of axillary abnormalities in women with normal breast examination
Authors: Muttarak M , Chaiwun B , Peh WCG
Published: September 2004

The mammograms of 43 patients presenting with palpable unilateral masses in the axilla and normal breasts on physical examination were retrospectively reviewed to determine the cause and imaging characteristics of axillary abnormalities, and the usefulness of mammography in detecting occult breast carcinoma. Cytological or histological confirmation was obtained in all patients. Forty of 43 patients had axillary lymphadenopathy while three had lipoma, fibroadenoma and haematoma, respectively. Causes of malignant lymphadenopathy (n = 22) were metastatic diseases from non‐mammary primary malignancy (n = 8), occult ipsilateral breast carcinoma (n = 5), and previous contralateral breast carcinoma (n = 9). Causes of benign lymphadenopathy (n = 18) were reactive nodal hyperplasia (n = 6), collagen vascular diseases (n = 2), and acute bacterial (n = 2) and tuberculous (n = 8) lymphadenitis. Nodal size was not significantly different between benign and malignant lymph nodes. Benign and malignant nodal margins were variable. Intranodal microcalcifications were found in two cases of breast carcinoma mestastasis. Intranodal macrocalcifications were found in three cases of tuberculous lymphadenitis. Occult primary breast carcinoma was detected on mammograms in four of five patients with axillary lymphadenopathy due to ipsilateral breast carcinoma. Mammographical features of benign and malignant lymphadenopathy may be indistinguishable, but presence of intranodal calcifications is helpful. Mammography is also valuable in depicting occult primary breast carcinoma.
New endoluminal technology: Efficacy and safety − whose responsibility?
Authors: Buckenham T
Published: September 2004

New endoluminal technology is being increasingly used in the management of arterial disease. With this increased usage of often experimental devices there is a growing responsibility for clinicians to collect data and report adverse events particularly in the longer term, when initial feasibility studies have been concluded. Many of these devices will have a perceived advantage so great that randomized controlled trials are not feasible. It is important that these perceptions are based on robust data not clinical impressions. The following article discusses methods of device assessment and looks at who is responsible for ongoing device evaluation.
Do written consent forms provide medicolegal protection from litigation in radiotherapy?
Authors: Christie DRH
Published: September 2004

Two methods were used in an attempt to determine whether written consent forms serve a useful medicolegal purpose in Australian radiotherapy departments. First a survey was posted to all practising radiation oncologists to ask about their use of written consent forms and whether they had ever been useful in any claims made against them. Second, the largest medical defence organization in Australia was contacted for de‐identified details about every claim ever made against a radiation oncologist. The survey yielded a response rate of 50.3%. Only one respondent indicated that any consent form had ever played a role in any claim and was not prepared to discuss it. Many radiation oncologists did not routinely use a consent form and its use could not be considered standard practice. The submitted consent forms generally did not contain warnings to the patient about specific risks of treatment. The details of the previous claims provided by the medical defence organization indicated that more often claims arose from circumstances in which a written consent form could not provide any useful protection such as radiation dose calculation errors. The medicolegal value of written consent forms in radiotherapy seems low, although further research may be necessary before dispensing with them completely.