bluuebunny/crossref_metadata_2025 huggingface dataset:
A role for ion channels in glioma cell invasion
Authors: MCFERRIN MICHAEL B. , SONTHEIMER HARALD
Published: December 2005

Many cells, including neuronal and glial progenitor cells, stem cells and microglial cells, have the capacity to move through the extracellular spaces of the developing and mature brain. This is particularly pronounced in astrocyte-derived tumors, gliomas, which diffusely infiltrate the normal brain. Although a significant body of literature exists regarding signals that are involved in the guidance of cells and their processes, little attention has been paid to cell-shape and cell-volume changes of migratory cells. However, extracellular spaces in the brain are very narrow and represent a major obstacle that requires cells to dynamically regulate their volume. Recent studies in glioma cells show that this involves the secretion of Cl− and K+ with water. Pharmacological inhibition of Cl− channels impairs their ability to migrate and limits tumor progression in experimental tumor models. One Cl−-channel inhibitor, chlorotoxin, is currently in Phase II clinical trials to treat malignant glioma. This article reviews our current knowledge of cell-volume changes and the role of ion channels during the migration of glioma cells. It also discusses evidence that supports the importance of channel-mediated cell-volume changes in the migration of immature neurons and progenitor cells during development. New unpublished data is presented, which demonstrates that Cl− and K+ channels involved in cell shrinkage localize to lipid-raft domains on the invadipodia of glioma cells and that their presence might be regulated by trafficking of these proteins in and out of lipid rafts.
New observations on the compact myelin proteome
Authors: ROTH ALEJANDRO D. , IVANOVA ANNA , COLMAN DAVID R.
Published: December 2005

Myelin formation and maintenance depends on the establishment of two structurally and biochemically discernible domains: (a) compact myelin, that is multilamellar stacks of plasma membrane sheets; and (b) cytoplasmic channels that border the compact myelin domains, attach them to the cell body and anchor the myelin sheath to the axonal membrane. To identify proteins involved in the organization of these domains we took advantage of the high lipid content of compact myelin to separate it cleanly from other neural membranes and then used reverse-phase HPLC coupled to Electro-Spray Double Mass Spectrometry (‘MudPIT’) to characterize the proteome of this sample. MudPIT allowed us to sidestep the bias of 2D-PAGE against either highly charged or transmembrane proteins. Thus, of 97 proteins that presented at least two, fully tryptic peptides (a stringent threshold), seven were well known myelin markers, including the mayor CNS myelin proteins: proteolipid protein and myelin basic protein, which are not resolvable by 2D-PAGE. Furthermore, we have confirmed and extended the known compact myelin proteome by 22 proteins and confirmed that CNS and PNS myelinated tracts present Sirtuin 2, a tubulin deacetylase, and Septin 7, a small GTPase that is likely to be involved in membrane and cytoplasm partitioning.
Identification of novel cell-adhesion molecules in peripheral nerves using a signal-sequence trap
Authors: SPIEGEL IVO , ADAMSKY KONSTANTIN , EISENBACH MENAHEM , ESHED YAEL , SPIEGEL ADRIAN , MIRSKY RHONA , SCHERER STEVEN S. , PELES ELIOR
Published: December 2005

The development and maintenance of myelinated nerves in the PNS requires constant and reciprocal communication between Schwann cells and their associated axons. However, little is known about the nature of the cell-surface molecules that mediate axon–glial interactions at the onset of myelination and during maintenance of the myelin sheath in the adult. Based on the rationale that such molecules contain a signal sequence in order to be presented on the cell surface, we have employed a eukaryotic-based, signal-sequence-trap approach to identify novel secreted and membrane-bound molecules that are expressed in myelinating and non-myelinating Schwann cells. Using cDNA libraries derived from dbcAMP-stimulated primary Schwann cells and 3-day-old rat sciatic nerve mRNAs, we generated an extensive list of novel molecules expressed in myelinating nerves in the PNS. Many of the identified proteins are cell-adhesion molecules (CAMs) and extracellular matrix (ECM) components, most of which have not been described previously in Schwann cells. In addition, we have identified several signaling receptors, growth and differentiation factors, ecto-enzymes and proteins that are associated with the endoplasmic reticulum and the Golgi network. We further examined the expression of several of the novel molecules in Schwann cells in culture and in rat sciatic nerve by primer-specific, real-time PCR and in situ hybridization. Our results indicate that myelinating Schwann cells express a battery of novel CAMs that might mediate their interactions with the underlying axons.
Der Verhaltensfragebogen bei Entwicklungsstörungen (VFE)
Authors: Steinhausen Hans-Christoph , Winkler Metzke Christa
Published: December 2005

Zusammenfassung. Hintergrund: Im deutschsprachigen Bereich besteht ein signifikantes Defizit an Verhaltensfragebögen zur Diagnostik bei Kindern mit schweren Entwicklungsstörungen, speziell geistiger Behinderung. Fragestellung: Die aus Australien stammende Developmental Behaviour Checklist (DBC) ist ein in der Verhaltensdiagnostik bei Kindern und Jugendlichen mit schweren Entwicklungsstörungen international breit eingesetzter Fragebogen zur Erfassung von Problemen des Verhaltens und der Emotionen. Die DBC wurde als Verhaltensfragebogen bei Entwicklungsstörungen (VFE) übersetzt und anhand der Daten einer umfangreiche Stichprobe von N = 721 Kindern und Jugendlichen mit geistiger Behinderung in Deutschland hinsichtlich ihrer psychometrischen Eigenschaften überprüft. Methode: Die psychometrischen Analysen umfassten verschiedene Analysen zur Validität und Reliabilität. Für die Normierung wurden Effekte von Alter, Geschlecht und Behinderungsgrad überprüft. Ergebnisse: Die fünf Faktoren der DBC konnten für den VFE repliziert werden. Neben der faktoriellen konnte auch die diskriminante und die kriteriumsbezogene Validität nachgewiesen werden. Die internen Konsistenzen waren für vier der fünf Subskalen gut bis sehr gut. Die Retest-Reliablität war nach einem beträchtlichen Intervall von 1.8 Jahren sehr hoch. Die Normierung berücksichtigt den Grad der Behinderung. Schlussfolgerungen: Mit der VFE in Übersetzung der DBC liegt ein sorgfältig konstruiertes Verhaltensinventar für Kinder und Jugendliche mit schweren Entwicklungsstörungen vor, das angemessene psychometrische Kennwerte aufweist und über deutsche Normwerte verfügt.
Kosten-Nutzen-Aspekte psychosozialer Interventionen bei somatisierenden Patienten in der Hausarztpraxis
Authors: Larisch Astrid , Fisch Verena , Fritzsche Kurt
Published: December 2005

Zusammenfassung. Theoretischer Hintergrund: Somatisierende Patienten führen durch das hohe Inanspruchnahmeverhalten medizinischer Leistungen zu inadäquaten Kosten im Gesundheitssystem. Fragestellung: Führen psychosoziale Interventionen des Hausarztes bei somatisierenden Patienten zu einer Reduktion der Gesundheitskosten? Methode: 42 Hausärzte und 127 Patienten nahmen an einer randomisierten kontrollierten Studie zur Verbesserung der Behandlung von somatisierenden Patienten teil. In dieser Kosten-Nutzen-Analyse wurden Arztbesuche, Arbeitsunfähigkeitstage, stationäre Aufenthalte, Medikamente sowie das Training berücksichtigt. Ergebnisse: In der Interventionsgruppe (IG) wurde gegenüber der Kontrollgruppe (KG) eine zusätzliche Ersparnis der direkten Kosten von 38,2% (262 eeee) pro Patient und Quartal erzielt. Die stärkste Kostenreduktion fand sich im stationären Bereich: IG 63,2% vs. KG 15,2%. Unter Berücksichtigung der indirekten Kosten reduzierte sich die zusätzliche Ersparnis der IG auf 11,9% (49,5 eeee). Schlussfolgerungen: Gezieltes Training zur Verbesserung der psychosozialen Kompetenz von Hausärzten bei der Behandlung von somatisierenden Patienten führte zu einer größeren Reduktion von Gesundheitskosten als die alleinige Routinebehandlung durch die Psychosomatische Grundversorgung.
Mechanisms for climate variability during glacial and interglacial periods
Authors: Loving Jolene L. , Vallis Geoffrey K.
Published: December 2005

This paper suggests and explores mechanisms relevant to millennial‐scale climate variability during glacial periods. In particular, we present the results of model studies that are able to reproduce many aspects of observed glacial climate variability (e.g., Dansgaard‐Oeschger oscillations) without external forcing and that provide a natural explanation for the prevalence of high‐amplitude variability in glacial climates and the relative stability of the Holocene. We show that the role of sea ice is critical to cold climate variability because of the effective reduction in the high‐latitude meridional sea surface temperature gradient resulting from sea ice expansion and the associated role of sea ice in inhibiting heat flux from the ocean to atmosphere. Thus as sea ice expands in a cooler climate, the high‐latitude oceanic heat loss to the atmosphere is inhibited, the thermohaline circulation weakens, and the sinking regions move equatorward, leading to a shallower and weaker deep circulation. This weak circulation is unstable, and intermittent high‐amplitude oscillations occur on a timescale and with a spatial structure very similar to Dansgaard‐Oeschger cycles. Consistent results are found using both a three‐dimensional ocean circulation model coupled to an energy balance atmospheric model and with a much simpler ocean box model. In general, freshening plays a secondary role in the weakening of the North Atlantic thermohaline circulation. Significant freshening is required to alter the stable northern deepwater formation that occurs in a warm climate such as today's Holocene, but once this freshening threshold is achieved, the thermohaline circulation shifts to reverse overturning with sinking in the tropics.
Spinning the “Ferrous Wheel”: The importance of the microbial community in an iron budget during the FeCycle experiment
Authors: Strzepek R. F. , Maldonado M. T. , Higgins J. L. , Hall J. , Safi K. , Wilhelm S. W. , Boyd P. W.
Published: December 2005

Several studies have shown the importance of the microbial community in specific aspects of the biogeochemical iron (Fe) cycle such as uptake or regeneration. During FeCycle, a 10‐day study of Fe biogeochemistry within an unperturbed mesoscale in situ SF6 labeled patch of HNLC waters, we investigated the role of both microzooplankton (herbivores and bacterivores) and viruses in regenerating Fe in the upper ocean. In summer 2003 we measured grazer‐mediated Fe regeneration rates. The proportion of bacterial Fe released via grazing was severalfold greater than that mobilized from phytoplankton during herbivory. However, as the algal Fe pool (mainly Synechococcus) was severalfold larger than the bacterial pool, the absolute Fe regeneration rates were similar for both herbivores (17 pmol Fe L−1 d−1) and bacterivores (20 pmol Fe L−1 d−1). In all grazing experiments we observed that 90% (bacterivory) and 25% (herbivory) of the labeled Fe resided in the dissolved fraction after 24 hours. This trend has previously been reported in similar laboratory culture studies, which invoked the formation of dissolved, and/or colloidal metal ligands, associated with digestion, to make the released Fe less bioavailable. This explanation may not be valid for our study as another FeCycle experiment (Maldonado et al., 2005) demonstrated that resident phytoplankton could obtain Fe bound to a wide range of strong‐binding ligands. In situ estimates of virally mediated Fe regeneration during FeCycle ranged from 0.4 to 28 pmol L−1 d−1. It is not known why such a wide range of virally mediated regeneration rates was observed. Such variability prevented a direct comparison on the relative roles of grazers and viruses in Fe recycling. The rates of grazer‐mediated regeneration accounted for 30% to >100% of the bacterial and phytoplankton Fe demand measured during FeCycle, indicating the key role of the microbial food web in Fe recycling.
Upper tropospheric divergence in tropical convective systems from Meteosat‐8
Authors: Schmetz Johannes , Borde Régis , Holmlund Kenneth , König Marianne
Published: December 2005

The upper level wind field divergence in tropical convective cloud systems is directly inferred from satellite tracked Atmospheric Motion Vectors (AMVs) using successive images at 15 minute intervals in the water vapor channel (6.2 μm) of Meteosat‐8. The use of radiances in the strongly absorbing 6.2 μm channel confines the feature tracking to the upper troposphere, enabling the derivation of consistent wind fields. A Lagrangian approach following the convective cloud systems throughout a day shows a pronounced diurnal cycle of the divergence with maximum values of 450 * 10−6 s−1. A comparison with the ECMWF forecast system shows that the forecast does not depict the observed spatial structure and does not reach the maximum values of observed divergence at the scale of tropical cloud systems. Divergence averages over the study area of about 1300 * 1400 km2 agree within a factor of two.
Thermalization cross sections of suprathermal N(4S) atoms in collisions with atmospheric molecules
Authors: Nakayama Tomoki , Takahashi Kenshi , Matsumi Yutaka
Published: December 2005

Translational relaxation of suprathermal N(4S) in collisions with N2, O2, He and Ar, which is relevant to nitric oxide formation in the thermosphere, has been studied experimentally. The suprathermal N(4S) atoms which have an average translational energy of 0.93 ± 0.10 eV (21.4 ± 2.2 kcal mol−1) in the laboratory frame were produced by 193 nm photolysis of NO2. Doppler profiles of the N(4S) atoms were recorded by laser‐induced fluorescence detection of N(4S) around 120.07 nm, from which the average kinetic energy of the N(4S) atoms were obtained as a function of thermalization time. Monte‐Carlo calculations employing an elastic hard‐sphere collision model have been performed to estimate the hard‐sphere collision radii and thermalization cross sections. The thermalization cross sections, which reproduced the experimental results, were (3.2 ± 0.4), (2.8 ± 0.4), (1.8 ± 0.2) and (2.3 ± 0.2) in unit of 10−15 cm2 for N(4S) + N2, O2, He and Ar, respectively.
On the low‐frequency electrical polarization of bacterial cells in sands
Authors: Ntarlagiannis Dimitrios , Yee Nathan , Slater Lee
Published: December 2005

We performed electrical measurements on sands flushed with bacterial suspensions of varying concentration. The first experiment was conducted with Shewanella putrefaciens (biomass 0–0.5 mg/L) and the second with Escherichia coli (biomass 0–42 mg/L). We measured a biomass‐dependent low‐frequency (10 Hz) polarization. At cell density <12 mg/L polarization decreased (up to 60 %) relative to before introduction of cells; the decrease was greater when the sand was artificially Fe‐coated to enhance the affinity of cells to the mineral surface. At cell density >12 mg/L polarization increased (up to 15%). We attribute the decrease in polarization at low cell density to alteration of the mineral‐fluid interface due to mineral‐cell interactions. The polarization enhancement at higher cell density is possibly a pore throat mechanism resulting from decreased ionic mobility and/or electron transfer due to cell accumulation in pores.
Mean winds, tides, and quasi‐2 day wave in the polar lower thermosphere observed in European Incoherent Scatter (EISCAT) 8 day run data in November 2003
Authors: Nozawa S. , Brekke A. , Maeda S. , Aso T. , Hall C. M. , Ogawa Y. , Buchert S. C. , Röttger J. , Richmond A. D. , Roble R. , Fujii R.
Published: December 2005

Simultaneous European Incoherent Scatter (EISCAT) radar observations using two EISCAT radars, the Tromsø (69.6°N, 19.2°E) UHF radar and the EISCAT Svalbard radar (Longyearbyen, 78.2°N, 16.0°E), were conducted for 8 consecutive days, from 11 to 19 November 2003, to study the lower thermospheric wind dynamics in the polar region. Altitude profiles of the amplitudes of the diurnal and semidiurnal components at Tromsø and Longyearbyen are similar. The semidiurnal amplitudes in the meridional and zonal components exhibit maxima at 105–107 km, with values of ∼70–90 m s−1. The semidiurnal phases vary with roughly a 30 km vertical wavelength between 98 and 110 km. The quasi‐2 day wave (Q2DW) was not detected in the lower thermosphere at either Tromsø or Longyearbyen during the period, while it was found between 70 and 82 km in the mesosphere with the colocated Tromsø MF radar. This observational result suggests that in general, the Q2DW attenuates in the mesosphere and cannot penetrate into the lower thermosphere in winter. Ion drag acceleration of the wind is generally negligible below 107 km at Tromsø and below 118 km at Longyearbyen, but significant ion drag acceleration is found above these heights. A comparison of mean wind and tidal amplitudes and phases with National Center for Atmospheric Research Thermosphere‐Ionosphere‐Mesosphere‐Electrodynamics General Circulation Model predictions for the period shows some agreement.
Radio frequency radiation beam pattern of lightning return strokes: Inferred from FORTE satellite observations
Authors: Shao Xuan‐Min , Jacobson Abram R. , Fitzgerald T. Joseph
Published: December 2005

The fast propagating return stroke is expected to produce a radiation pattern differing from a dipole pattern, with a “correction” of (1 −vcos θ/c)−1or the so‐calledFfactor. The FORTE satellite measures lightning Very High Frequency (VHF) radiation at different angles from the up space and offers the first opportunity of examining theFfactor. In this report, we studied a group of FORTE‐detected lightning events that were also observed by the National Lightning Detection Network (NLDN). NLDN provided the discharges' geolocations and helped to identify the discharge types. During the summers of 1998 and 1999, 25,721 coincident events were found. Among these, 2092 were found to be narrow (<100 ns), VHF‐intense and highly polarized bursts and were found to be associated with the beginning of return strokes. Through careful statistical analysis regarding the distributions of the event occurrence, we found that the overall ensemble of events can be considered to have an isotropic pattern in the upper half‐space. The subset of the narrow bursts displays a beam pattern that agrees with theFfactor at a propagating speed ofv= 0.75c. The latter is inferred by comparing FORTE observations to a free‐space transmission line (TL) model. The analysis shows that the ground does not affect the narrow‐burst beam pattern observed from the upper half‐space; the source for the narrow burst needs to be a few tens of meters above the surface of the Earth and is apparently associated with the junction point of the attachment process. The physical size of the corresponding discharge is estimated to be less than 20 m. The analysis also suggests that a single upward current is responsible for the observations, rather than a bidirectional current as suggested by others for the attachment process. Similarly, the traveling current source (TCS) model that consists of a simultaneous downward current is found less suitable for the initiation of return strokes.
New Illusions of Sliding Motion in Depth
Authors: Pinna Baingio , Spillmann Lothar
Published: December 2005

Apparent sliding motion in the so-called Ouchi illusion has been attributed to the global integration of local motion vectors arising from the aperture effect (Fermüller et al, 2000 Vision Research 40 77–96; Mather, 2000 Perception 29 721–727). In a number of variants of the Ouchi illusion, we here demonstrate that sliding motion will also arise without a directional motion bias from local elements. Specifically, we show that in a disk-annulus pattern made from wiggly lines, sliding motion occurs although the local orientations within the disk and annulus are the same. We then argue that in an array of square-shaped checks, sliding motion originates from the interaction between the explicit orientation of the checks and the implicit orientation of the invisible diagonals. Finally, we demonstrate that a central array of filled black circles surrounded by a grey edge appears to slide relative to a surround of empty circles. We tentatively account for sliding motion in this figure by differences in speed signals, figure-ground segregation and apparent depth due to contrast polarity, edge blur, demarcation by a frame, and difference in shape.
The Role of Facial Attractiveness and Facial Masculinity/Femininity in Sex Classification of Faces
Authors: Hoss Rebecca A , Ramsey Jennifer L , Griffin Angela M , Langlois Judith H
Published: December 2005

We tested whether adults (experiment 1) and 4–5-year-old children (experiment 2) identify the sex of highly attractive faces faster and more accurately than not very attractive faces in a reaction-time task. We also assessed whether facial masculinity/femininity facilitated identification of sex. Results showed that attractiveness facilitated adults' sex classification of both female and male faces and children's sex classification of female, but not male, faces. Moreover, attractiveness affected the speed and accuracy of sex classification independently of masculinity/femininity. High masculinity in male faces, but not high femininity in female faces, also facilitated sex classification for both adults and children. These findings provide important new data on how the facial cues of attractiveness and masculinity/femininity contribute to the task of sex classification and provide evidence for developmental differences in how adults and children use these cues. Additionally, these findings provide support for Langlois and Roggman's (1990 Psychological Science 1 115–121) averageness theory of attractiveness.
Using soil and climatic data to estimate the performance of trees, carbon sequestration and recharge potential at the catchment scale
Authors: Harper R. J. , Smettem K. R. J. , Tomlinson R. J.
Published: December 2005

There is considerable interest in integrating deep-rooted perennial plants into the dryland farming systems of southern Australia as soil, water supplies and biodiversity are continually threatened by salinity. In addition to wood products, trees could provide new products, such as bioenergy, environmental services, such as the sequestration of carbon, reductions in recharge to groundwater and biodiversity protection. Before marketing these services, it is necessary to determine the optimal distribution of trees across the landscape, in terms of land suitability, their productivity, and proximity to existing processing and transport infrastructure. Similarly, understanding how recharge varies across landscapes will allow the targeting of trees to areas where they are most needed for salinity control.
Catchment scale (1:100 000) soil and landform datasets are now available across much of the agricultural area of Australia. While these data are at a scale inappropriate for management at the enterprise (farm) scale, they will allow broad planning for new plant-based industries, such as whether there is sufficient suitable land available before embarking on a new enterprise and the likely productivity of that land. In this paper, we outline an approach that combines existing soil and landform data with estimates of climate to produce estimates of likely wood yield, carbon sequestration and potential for recharge to groundwater. Using the 283 686 ha Collie catchment of south-western Australia as an example, this analysis indicated broad areas where land is suitable for forestry, where forestry is unlikely to succeed, or where it was not required because leakage to groundwater is negligible. It also provides broad estimates of wood production and carbon sequestration. The approach is applicable to the integration of deep-rooted perennial plants into farming systems in other regions confronted with multiple natural resource management issues.
Na+channel-mediated Ca2+entry leads to glutamate secretion in mouse neocortical preplate
Authors: Platel J.-C. , Boisseau S. , Dupuis A. , Brocard J. , Poupard A. , Savasta M. , Villaz M. , Albrieux M.
Published: December 2005

Before synaptogenesis, early excitability implicating voltage-dependent and transmitter-activated channels is known to be crucial for neuronal development. We previously showed that preplate (PP) neurons of the mouse neocortex express functional Na+channels as early as embryonic day 12. In this study, we investigated the role of these Na+channels in signaling during early development. In the neocortex of embryonic-day-13 mice, activation of Na+channels with veratridine induced a large Ca2+response throughout the neocortex, even in cell populations that lack the Na+channel. This Na+-dependent Ca2+activity requires external Ca2+and is completely blocked by inhibitors of Na+/Ca2+exchangers. Moreover, veratridine-induced Ca2+increase coincides with a burst of exocytosis in the PP. In parallel, we show that Na+channel stimulation enhances glutamate secretion in the neocortical wall. Released glutamate triggers further Ca2+response in PP and ventricular zone, as indicated by the decreased response to veratridine in the presence of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor and NMDA-receptor inhibitors. Therefore, the combined activation of the Na+channel and the Na+/Ca2+exchanger triggers Ca2+signaling in the PP neurons, leading to glutamate secretion, which amplifies the signal and serves as an autocrine/paracrine transmitter before functional synapses are formed in the neocortex. Membrane depolarization induced by glycine receptors activation could be one physiological activator of this Na+channel-dependent pathway.
Ribosome exit tunnel can entropically stabilize α-helices
Authors: Ziv Guy , Haran Gilad , Thirumalai D.
Published: December 2005

Several experiments have suggested that newly synthesized polypeptide chains can adopt helical structures deep within the ribosome exit tunnel. We hypothesize that confinement in the roughly cylindrical tunnel can entropically stabilize α-helices. The hypothesis is validated by using theory and simulations of coarse-grained off-lattice models. The model helix, which is unstable in the bulk, is stabilized in a cylindrical cavity provided the diameter (
D
) of the cylinder exceeds a critical value
D
*. When
D
<
D
* both the helical content and the helix–coil transition temperature (

T
f

) decrease abruptly. Surprisingly, we find that the stability of the α-helix depends on the number (
N
) of amino acid residues. Entropic stabilization, as measured by changes in

T
f

, increases nonlinearly as
N
increases. The simulation results are in quantitative agreement with a standard helix–coil theory that takes into account entropy cost of confining a polypeptide chain in a cylinder. The results of this work are in qualitative accord with most of the findings of a recent experiment in which
N
-dependent ribosome-induced helix stabilization of transmembrane sequences was measured by fluorescence resonance energy transfer.
SoDA: implementation of a 3D alignment algorithm for inference of antigen receptor recombinations
Authors: Volpe Joseph M. , Cowell Lindsay G. , Kepler Thomas B.
Published: December 2005

Motivation: The antigen receptors of adaptive immunity—T-cell receptors and immunoglobulins—are encoded by genes assembled stochastically from combinatorial libraries of gene segments. Immunoglobulin genes then experience further diversification through hypermutation. Analysis of the somatic genetics of the immune response depends explicitly on inference of the details of the recombinatorial process giving rise to each of the participating antigen receptor genes. We have developed a dynamic programming algorithm to perform this reconstruction and have implemented it as web-accessible software called SoDA (Somatic Diversification Analysis).

Results: We tested SoDA against a set of 120 artificial immunoglobulin sequences generated by simulation of recombination and compared the results with two other widely used programs. SoDA inferred the correct gene segments more frequently than the other two programs. We further tested these programs using 30 human immunoglobulin genes from Genbank and here highlight instances where the recombinations inferred by the three programs differ. SoDA appears generally to find more likely recombinations.

Availability: SoDA is freely available for use via the web at the

Contact:  kepler@duke.edu
EDGE: extraction and analysis of differential gene expression
Authors: Leek Jeffrey T. , Monsen Eva , Dabney Alan R. , Storey John D.
Published: December 2005

Summary: EDGE (Extraction of Differential Gene Expression) is an open source, point-and-click software program for the significance analysis of DNA microarray experiments. EDGE can perform both standard and time course differential expression analysis. The functions are based on newly developed statistical theory and methods. This document introduces the EDGE software package.

Availability: EDGE is freely available for non-commercial users. EDGE can be downloaded for Windows, Macintosh and Linux/UNIX from

Contact:  jtleek@u.washington.edu
RNAshapes: an integrated RNA analysis package based on abstract shapes
Authors: Steffen Peter , Voß Björn , Rehmsmeier Marc , Reeder Jens , Giegerich Robert
Published: December 2005

Summary: We introduce RNAshapes, a new software package that integrates three RNA analysis tools based on the abstract shapes approach: the analysis of shape representatives, the calculation of shape probabilities and the consensus shapes approach. This new package is completely reimplemented in C and outruns the original implementations significantly in runtime and memory requirements. Additionally, we added a number of useful features like suboptimal folding with correct dangling energies, structure graph output, shape matching and a sliding window approach.

Availability: RNAshapes is freely available at as C source code, and as compiled binaries for the most common computer architectures. For Microsoft Windows, we also offer a graphical user interface with convenient access to the complete functionality of the package.

Contact:  psteffen@techfak.uni-bielefeld.de
A general HELP inequality connected with symmetric operators
Authors: Langer Matthias
Published: December 2005

In this paper, a general HELP (Hardy–Everitt–Littlewood–Pólya) inequality is considered which is connected with a symmetric operator in a Hilbert space and abstract boundary mappings. A criterion for the validity of such an inequality in terms of the abstract Titchmarsh–Weyl function is proved and applied to Sturm–Liouville operators, difference operators, a Hamiltonian system and a block operator matrix.
Calculating the Greeks by cubature formulae
Authors: Teichmann Josef
Published: December 2005

We provide cubature formulae for the calculation of derivatives of expected values in the spirit of Terry Lyons and Nicolas Victoir. In financial mathematics derivatives of option prices with respect to initial values, so called Greeks, are of particular importance as hedging parameters. The proof of existence of cubature formulae for Greeks is based on universal formulae, which lead to the calculation of Greeks in an asymptotic sense—even without Hörmander's condition. Cubature formulae then allow to calculate these quantities very quickly. Simple examples are added to the theoretical exposition.
On a class of non-coaxial plasticity models for granular soils
Authors: Yu H.S , Yuan X
Published: December 2005

The non-coaxiality of the directions of principal stresses and principal plastic strain rates in granular soils under stress rotations has long been observed and recognized in soil tests using both simple shear and hollow cylinder apparatuses. A few constitutive theories have also been proposed in the literature to account for the effect of stress rotations and the subsequent non-coaxial soil behaviour, particularly in the context of shear band analysis. However, the lack of corresponding general numerical methods makes it difficult to investigate the influence of non-coaxial stress–strain behaviour on the results of geotechnical boundary value problems. This paper presents a numerical evaluation of a class of non-coaxial, elastic–plastic models that are developed by combining the conventional plastic potential theory and the double shearing theory. The general non-coaxial constitutive theories are first formulated and then a finite element implementation of the theories is carried out. To evaluate the non-coaxial theories, the problem of simple shear of soils is chosen to investigate the predicted behaviour of soils under simple shear loading conditions where the axes of principal stresses rotate. In particular, the influence of initial stress states and the degree of non-coaxiality are examined. It is found that the numerical results predicted using the non-coaxial model are in general agreement with the experimental observations reported in the literature.
Concentration of blood-borne agonists at the endothelium
Authors: Plank M.J , Comerford A , David T , Wall D.J.N
Published: December 2005

The delivery of endothelial ligands and macromolecules, such as lipoproteins, from the circulation to the arterial wall is of central importance in modulating endothelial cell function and physiology and, consequently, in the onset of vascular disease. Given the strong spatial correlation between areas of disturbed blood flow and occurrence of atherosclerotic plaque, a detailed understanding of the effects of different fluid flow characteristics on the delivery of factors in the bloodstream to the endothelium is an essential step towards understanding the observed localization of vascular disease to certain focal sites within the vasculature. In this paper, a model of biochemical mass transport in a two-dimensional flow chamber with spatially varying wall shear stress is presented. The advantage of the relatively simple arterial geometry is that all the essential features of blood flow
in vivo
are captured, but the underlying effects on mass transport, and, hence, on endothelial cell function, are not masked by complex three-dimensional flow. Indeed, it is demonstrated that a previously derived similarity solution, in terms of the shear stress on the endothelial wall, is an asymptotically close approximation to the exact solution to the advection–diffusion equation. The mathematical analysis is then used to identify fundamental links between the wall shear stress and the distribution of chemical species along the endothelium. The physiological implications of these links are discussed, in particular the location of maximum chemical concentration on the endothelium, which is of great significance to the regulation of intracellular signalling and, consequently, endothelial cell function.
Evaluating bacterial pathogen DNA preservation in museum osteological collections
Authors: Barnes Ian , Thomas Mark G
Published: December 2005

Reports of bacterial pathogen DNA sequences obtained from archaeological bone specimens raise the possibility of greatly improving our understanding of the history of infectious diseases. However, the survival of pathogen DNA over long time periods is poorly characterized, and scepticism remains about the reliability of these data.

In order to explore the survival of bacterial pathogen DNA in bone specimens, we analysed samples from 59 eighteenth and twentieth century individuals known to have been infected with either
Mycobacterium tuberculosis
or
Treponema pallidum
. No reproducible evidence of surviving pathogen DNA was obtained, despite the use of extraction and PCR-amplification methods determined to be highly sensitive. These data suggest that previous studies need to be interpreted with caution, and we propose that a much greater emphasis is placed on understanding how pathogen DNA survives in archaeological material, and how its presence can be properly verified and used.
Insect eggs exert rapid control over an oxygen–water tradeoff
Authors: Zrubek Brandy , Woods H. Arthur
Published: December 2005

In terrestrial environments, the exchange of respiratory gases exacts a water cost: obtaining oxygen or carbon dioxide requires losing water. Insect eggs should be especially sensitive to this tradeoff—because they are unable to forage for water, have high surface area-to-volume ratios, and experience large temperature-driven changes in oxygen demand. Previous work from our laboratory, on eggs of a common hawkmoth,Manduca sexta, has shown that, during development, metabolic rate and water loss rates rise in parallel. These correlative data suggest that eggshell conductance increases to accommodate increasing metabolic demand. Here, we test this idea experimentally by subjecting eggs ofM. sextato 15, 21 (normoxia) and 35% oxygen for 24 h, while measuring rates of metabolism (as carbon dioxide emission) and water loss. Hypoxia depressed egg metabolic rates, but led to pronounced, rapid increases in water loss. By contrast, hyperoxia had no significant effect on metabolism or water loss. These data demonstrate that insect eggs actively participate in balancing oxygen gain and water loss, and that they use tissue oxygen status, or some correlate of it, as a cue for increasing eggshell conductance. Rapid control over conductance may allow eggs to conserve water during an initial period of low metabolic demand, thereby deferring water costs of respiratory gas exchange until late in development.
Flexible diet choice offsets protein costs of pathogen resistance in a caterpillar
Authors: Lee K.P , Cory J.S , Wilson K , Raubenheimer D , Simpson S.J
Published: December 2005

Mounting effective resistance against pathogens is costly in terms of energy and nutrients. However, it remains unexplored whether hosts can offset such costs by adjusting their dietary intake so as to recoup the specific resources involved. We test this possibility by experimentally challenging caterpillars (Spodoptera littoralis) with a highly virulent entomopathogen (nucleopolyhedrovirus), under dietary regimes varying in the content of protein and digestible carbohydrate. We found that dietary protein influenced both resistance to pathogen attack and constitutive immune function to a greater extent than did dietary carbohydrate, indicating higher protein costs of resistance than energy costs. Moreover, when allowed to self-compose their diet, insects surviving viral challenge increased their relative intake of protein compared with controls and those larvae dying of infection, thus demonstrating compensation for protein costs associated with resistance. These results suggest that the change in the host's nutritional demands to fight infection induces a compensatory shift in feeding behaviour.
Dynamics of deletion genotypes in an experimental insect virus population
Authors: Simón Oihane , Williams Trevor , Caballero Primitivo , López-Ferber Miguel
Published: December 2005

Defective viruses, that are deficient in certain essential genes, are maintained in the population by transcomplementation, exploiting the gene products of complete genotypes in co-infected cells. This process becomes prevalent only when cells are frequently infected by several virus particles, and only then will the fitness of defective viruses be subjected to frequency-dependent selection. Deletion variants that are not infectious
per os
are present in a multicapsid nucleopolyhedrovirus (SfMNPV, Baculoviridae) that infects the fall armyworm,
Spodoptera frugiperda
. These variants enhance the pathogenicity and, therefore, the likelihood of transmission of the virus when co-infecting cells with complete genotypes, resulting in occlusion bodies (OBs) that may contain both genotypes co-occluded. Mixtures of complete (B) and defective (C) variants in ratios of 90% B+10% C, 50% B+50% C and 10% B+90% C were used to inoculate by injection
S. frugiperda
larvae. Viral OBs extracted from diseased insects were subjected to four or five successive rounds of
per os
infection. Following successive passages, genotype frequencies in all three experimental populations converged to a single equilibrium frequency comprising ∼20% of deletion genotype C and ∼80% of complete genotype B. This mirrors the relative proportions of deletion (22%) and complete (78%) genotypes observed in the wild-type SfMNPV population. The pathogenicity of experimental populations at the final passage was not significantly different from that of the wild-type isolate. In contrast, OBs of all genotype mixtures were significantly more pathogenic than OBs of genotype B alone. A population genetics model, in which virus populations were assigned linear frequency-dependent transmissibility values, was in remarkably close agreement to empirical data. Clearly, non-infectious deletion variants can profoundly affect the likelihood of transmission and the genetic structure and stability of virus populations.
UV matters in shoaling decisions
Authors: Modarressie Ricarda , Rick Ingolf P , Bakker Theo C.M
Published: December 2005

Shoaling behaviour in fish is influenced by numerous factors, such as familiarity, kinship, group size and shoal composition. Grouping decisions are based on both olfactory and visual cues. The visual system of many vertebrates is extended into the ultraviolet (UV) wave range as in three-spined sticklebacks (
Gasterosteus aculeatus
, L.). We investigated whether the presence or absence of UV wavelengths has an influence on shoaling behaviour in this species. Reproductively non-active three-spined sticklebacks were given the choice between two shoals, equal in numbers of individuals, which could be seen either through a UV-transmitting [UV(+)] or a UV-blocking [UV(−)] filter. Test fish preferred to join the shoal seen under UV(+) conditions. Due to differences in quantal flux between the UV(+) and UV(−) filters used, control experiments with neutral-density optical filters were performed in order to clarify the role of luminance. Here, test fish spent significantly more time near shoals that were seen in a darker environment, suggesting a potential trade-off between UV radiation and lower brightness during shoal choice.

To our knowledge, these results demonstrate for the first time that shoaling decisions are influenced by UV wavelengths.
Alignment of capsid protein VP1 sequences of all human rhinovirus prototype strains: conserved motifs and functional domains
Authors: Laine Pia , Blomqvist Soile , Savolainen Carita , Andries Koen , Hovi Tapani
Published: December 2005

An alignment was made of the deduced amino acid sequences of the entire capsid protein VP1 of all human rhinovirus (HRV) prototype strains to examine conserved motifs in the primary structure. A set of previously proposed crucially important amino acids in the footprints of the two known receptor molecules was not conserved in a receptor group-specific way. In contrast, VP1 and VP3 amino acids in the minor receptor-group strains corresponding to most of the predicted ICAM-1 footprint definitely differed from those of the ICAM-1-using major receptor-group strains. Previous antiviral-sensitivity classification showed an almost-complete agreement with the species classification and a fair correlation with amino acids aligning in the antiviral pocket. It was concluded that systematic alignment of sequences of related virus strains can be used to test hypotheses derived from molecular studies of individual model viruses and to generate ideas for future studies on virus structure and replication.
A link between translation of the hepatitis C virus polyprotein and polymerase function; possible consequences for hyperphosphorylation of NS5A
Authors: McCormick Christopher J. , Brown David , Griffin Stephen , Challinor Lisa , Rowlands David J. , Harris Mark
Published: December 2005

Hyperphosphorylation of NS5A is thought to play a key role in controlling hepatitis C virus (HCV) RNA replication. Using a tetracycline-regulable baculovirus delivery system to introduce non-culture-adapted HCV replicons into HepG2 cells, we found that a point mutation in the active site of the viral polymerase, NS5B, led to an increase in NS5A hyperphosphorylation. Although replicon transcripts lacking elements downstream of NS5A also had altered NS5A hyperphosphorylation, this did not explain the changes resulting from polymerase inactivation. Instead, two additional findings may be related to the link between polymerase activity and NS5A hyperphosphorylation. Firstly, we found that disabling polymerase activity, either by targeted mutation of the polymerase active site or by use of a synthetic inhibitor, stimulated translation from the replicon transcript. Secondly, when the rate of translation of non-structural proteins from replicon transcripts was reduced by use of a defective encephalomyocarditis virus internal ribosome entry site, there was a substantial decrease in NS5A hyperphosphorylation, but this was not observed when non-structural protein expression was reduced by simply lowering replicon transcript levels using tetracycline. Therefore, one possibility is that the point mutation within the active site of NS5B causes an increase in NS5A hyperphosphorylation because of an increase in translation from each viral transcript. These findings represent the first demonstration that NS5A hyperphosphorylation can be modulated without use of kinase inhibitors or mutations within non-structural proteins and, as such, provide an insight into a possible means by which HCV replication is controlled during a natural infection.
Dendritic cells pulsed with hepatitis C virus NS3 protein induce immune responses and protection from infection with recombinant vaccinia virus expressing NS3
Authors: Yu Hong , Huang Hui , Xiang Jim , Babiuk Lorne A. , van Drunen Littel-van den Hurk Sylvia
Published: December 2005

Infections withHepatitis C virus(HCV) pose a serious health problem worldwide. In this study, the hypothesis that adoptive transfer of dendritic cells (DCs) pulsed with HCV NS3 protein and matured with an oligodeoxynucleotide (ODN) containing CpG motifs (CpG)ex vivowould initiate potent HCV-specific protective immune responsesin vivowas tested. NS3 protein was efficiently transduced into DCs and treatment of DCs with CpG ODN induced phenotypic maturation and specifically increased the expression of CD40. DCs matured with CpG ODN produced higher interleukin 12 levels and a stronger allogeneic T-cell response compared with untreated DCs. Notably, there were no differences between NS3-pulsed DCs and DCs pulsed with a control protein with respect to phenotype, cytokine production or mixed lymphocyte reaction, indicating that transduction with NS3 protein did not impair DC functions. Compared with the untreated NS3-pulsed DCs, the NS3-pulsed DCs matured with CpG ODN induced stronger cellular immune responses including enhanced cytotoxicity, higher interferon-γproduction and stronger lymphocyte proliferation. Upon challenge with a recombinant vaccinia virus expressing NS3, all mice immunized with NS3-pulsed DCs showed a significant reduction in vaccinia virus titres when compared with mock-immunized mice. However, the NS3-pulsed DCs matured with CpG ODN induced higher levels of protection compared with the untreated NS3-pulsed DCs. These data are the first to show that NS3-pulsed DCs induce specific immune responses and provide protection from viral challenge, and also demonstrate that CpG ODNs, which have a proven safety profile, would be useful in the development of DC vaccines.
536. Saruma Henryi
Authors: Hsu Eric
Published: December 2005

Summary.  Saruma henryi Oliver is described and illustrated. The distribution, ecology, taxonomy and cultural requirements of this unusual member of the Aristolochiaceae are discussed.
539. Rosa Chinensis f. Spontanea
Authors: Rix Martyn
Published: December 2005

Summary.  The wild form of the commonly cultivated Rosa chinensis Jacq., f. spontanea Rehder & Wilson, is illustrated and described. The history of its discovery and introduction to cultivation in western gardens is given. The typification and synonymy of R. chinensis are discussed.