bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of IGF signaling and the androgen receptor in prostate cancer progression
Authors: Wu Jennifer D. , Haugk Kathy , Woodke Libby , Nelson Peter , Coleman Ilsa , Plymate Stephen R.
Published: April 2006

The insulin‐like growth factor type I receptor (IGF‐IR) has been suggested to play an important role in prostate cancer progression and possibly in the progression to androgen‐independent (AI) disease. The term AI may not be entirely correct, in that recent data suggest that expression of androgen receptor (AR) and androgen‐regulated genes is the primary association with prostate cancer progression after hormone ablation. Therefore, signaling through other growth factors has been thought to play a role in AR‐mediated prostate cancer progression to AI disease in the absence of androgen ligand. However, existing data on how IGF‐IR signaling interacts with AR activation in prostate cancer are conflicting. In this Prospect article, we review some of the published data on the mechanisms of IGF‐IR/AR interaction and present new evidence that IGF‐IR signaling may modulate AR compartmentation and thus alter AR activity in prostate cancer cells. Inhibition of IGF‐IR signaling can result in cytoplasmic AR retention and a significant change in androgen‐regulated gene expression. Translocation of AR from the cytoplasm to the nucleus may be associated with IGF‐induced dephosphorylation. Since fully humanized antibodies targeting the IGF‐IR are now in clinical trials, the current review is intended to reveal the mechanisms of potential therapeutic effects of these antibodies on AI prostate cancers. J. Cell. Biochem. 99: 392–401, 2006. © 2006 Wiley‐Liss, Inc.
Differential expression of HNF4α isoforms in liver stem cells and hepatocytes
Authors: Li Keguo , Zhang Haiquan , Wang Yanjun , Wang Yun , Feng Meifu
Published: April 2006

The hepatocyte nuclear factor (HNF4α) has been implicated in liver development and hepatocellular differentiation. The HNF4α expression in liver stem cells has not yet been fully investigated. Here, we describe the expression characterization of HNF4α in liver stem cells isolated from 2‐acetylaminofluorene/partial hepatectomy (AAF/PH) rat model by a combination of density‐gradient centrifugation and selective enzymatic digestion. The obtained cells were identified by flow cytometry (FCM) immediately and then by immunocytochemisty and reverse transcription‐polymerase chain reaction (RT‐PCR) after 5 d culture. The cultured stem cells were subjected to analysis of the expression of various HNF4α isoforms using RT‐PCR, Western blotting, and electrophoretic mobility shift assay (EMSA). Results showed that HNF4α isoforms, α1, α2, α7, and α8 were present in liver stem cells, which contrasted with only α1 and α2 expression in hepatocytes. The distinct expression patterns of HNF4α isoforms in liver stem cells may contribute to maintain the “stemness” of these cells. J. Cell. Biochem. 99: 558–564, 2006. © 2006 Wiley‐Liss, Inc.
T‐cell epitopes of the La/SSB autoantigen: Prediction based on the homology modeling of HLA‐DQ2/DQ7 with the insulin‐B peptide/HLA‐DQ8 complex
Authors: Kosmopoulou Aggeliki , Vlassi Metaxia , Stavrakoudis Athanassios , Sakarellos Constantinos , Sakarellos‐Daitsiotis Maria
Published: April 2006

T‐cell epitopes are important components of the inappropriate response of the immune system to self‐proteins in autoimmune diseases. In this study, the candidate T‐cell epitopes of the La/SSB autoantigen, the main target of the autoimmune response in patients with Sjogren's Syndrome (SS), and Systemic Lupus Erythematosus (SLE) were predicted using as a template the HLA‐DQ2 and DQ7 molecules, which are genetically linked to patients with SS and SLE. Modeling of DQ2 and DQ7 was based on the crystal structure of HLA‐DQ8, an HLA molecule of high risk factor of type I diabetes, which is also an autoimmune disease. The quality and reliability of the modeled DQ2 and DQ7 was confirmed by the Ramachandran plot and the TINKER molecular modeling software. Common and/or similar candidate T‐cell epitopes, obtained by comparing three different approaches the Taylor's sequence pattern, the TEPITOPE quantitative matrices, and the MULTIPRED artificial neural network, were subjected to homology modeling with the crystal structure of the insulin‐B peptide complexed with HLA‐DQ8, and the best superposed candidate epitopes were placed into the modeled HLA‐DQ2 and DQ7 binding grooves to perform energy minimization calculations. Six T‐cell epitopes were predicted for HLA‐DQ7 and nine for HLA‐DQ2 covering parts of the amino‐terminal and the central regions of the La/SSB autoantigen. Residues corresponding to the P1, P4, and P9 pockets of the HLA‐DQ2 and DQ7 binding grooves experience very low SASA because they are less exposed to the microenvironment of the groove. The proposed T‐cell epitopes complexed with HLA‐DQ2/DQ7 were further evaluated for their binding efficiency according to their potential interaction energy, binding affinity, and IC50 values. Our approach constitutes the ground work for a rapid and reliable experimentation concerning the T‐cell epitope mapping of autoantigens, and could lead to the development of T‐cell inhibitors as immunotherapeutics in autoimmune diseases. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1033–1044, 2006
A Cationic Water‐Soluble Poly(p‐phenylenevinylene) Derivative: Highly Sensitive Biosensor for Iron‐Sulfur Protein Detection
Authors: Cheng Fan , Zhang Guang‐Wei , Lu Xiao‐Mei , Huang Yan‐Qin , Chen Yi , Zhou Ying , Fan Qu‐Li , Huang Wei
Published: April 2006

Summary: A new water‐soluble cationic ammonium‐functionalized poly(p‐phenylenevinylene) (PPV‐NEtMe) was successfully synthesized and exhibited high sensitivity (Ksv = 6.9 × 107 M−1) on rubredoxin, a type of anionic iron‐sulfur (Fe‐S) proteins. Further investigation showed that the biosensitivity of the cationic conjugated polymer is strongly dependent on the nature of the buffer solution and the concentration of the conjugated polymer used in the analyses.

The schematic diagram of anionic rubredoxin detected by PPV‐NEtMe.

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The schematic diagram of anionic rubredoxin detected by PPV‐NEtMe.
Direct Melt Intercalation of Polylactide Chains into Nano‐Galleries: Interlayer Expansion and Nano‐Composite Structure
Authors: Yoshida Osamu , Okamoto Masami
Published: April 2006

Summary: The polylactide‐based nano‐composites were prepared via melt extrusion method using different types of intercalants and nano‐fillers having different surface charge density. In order to understand the direct polymer melt intercalation into the nano‐galleries, the interdigitated layer structure of the organically modified layered filler (OMLF), where the intercalants are oriented with some inclination to the host layer in the interlayer space, was proposed. After polymer melt intercalation, the smaller initial interlayer opening led to the larger interlayer expansion, suggesting the large amount of the intercalation of the polymer chains. Consequently, the nano‐composite exhibited finer dispersion of the nano‐fillers when compared with the nano‐composites prepared from OMLFs with larger initial interlayer opening.

Illustration of a model of interlayer structure of the qC14(OH) in gallery space of HTO.

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Illustration of a model of interlayer structure of the qC14(OH) in gallery space of HTO.
Prognostic significance of PU.1 in follicular lymphoma
Authors: Torlakovic EE , Bilalovic N , Golouh R , Zidar A , Angel S
Published: April 2006

Very few prognostic factors are known in follicular lymphoma (FL), a common malignancy of germinal centre (GC) B‐cells. The Follicular Lymphoma International Prognostic Index (FLIPI) thus far appears to be the most important predictor of clinical outcome. This study explores the predictive power of the degree of GC differentiation for outcome in FL. Samples from 73 patients with FL were evaluated by immunohistochemistry for expression of GC markers. Strong PU.1, CD20, and CD75 expression were significantly associated with longer progression‐free survival (PFS) and overall survival (OS). Results for PFS were independent of the International Prognostic Index or the Italian Lymphoma Intergroup prognostic index for CD75 and PU.1, but only PU.1 expression was independent of FLIPI for PFS and OS. Oct‐2 was weakly expressed overall, but more strongly in higher grades of FL; it had a trend for negative linear association with PU.1 and strong positive linear association with CD27, which possibly reflects its role in terminal B‐cell differentiation. We show that the level of GC differentiation, as determined by the levels of PU.1, CD75, CD20, Bcl‐6, and CD10 expression, has an association with outcome in patients with FL. While this is determined qualitatively in most studies of diffuse large B‐cell lymphoma, in FL there is a quantitative positive association between a high level of expression of GC antigens and longer OS and PFS even when data are stratified by the FLIPI score. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Organization of Functionalized Gold Nanoparticles by Controlled Protein Interactions
Authors: Kohut Ananiys , Voronov Andriy , Peukert Wolfgang
Published: April 2006

Gold colloidal particles were synthesized and modified by molecular self‐assembly. In addition, the reaction of biotinylated colloids with a tetrameric protein, avidin, was studied by optical absorption spectroscopy and dynamic light scattering. The modification involves the chemisorption of octadecanethiol on the gold, with the further attachment of alkyl biotin and cross‐linking with avidin molecules. The specific interaction of avidin with biotin leads to the controlled cross‐linking of particles. The degree of flocculation was quantified using a semi‐empirical flocculation parameter and its dependence on the biotinylation system was studied. The measured data were in good agreement, showing the possibility of regulating the aggregation rate and size of the aggregates using the experimental time, degree of biotinylation, and avidin concentration. The morphology of the self‐assembled gold monolayers, from the aggregated particles, was imaged by high‐resolution scanning electron microscopy. The structure of the thin particulate film depends on the bulk aggregate size and aggregation rate.
Cover Picture: Core/Shell Fluorescent Silica Nanoparticles for Chemical Sensing: Towards Single‐Particle Laboratories (Small 6/2006)
Authors: Burns Andrew , Sengupta Prabuddha , Zedayko Tara , Baird Barbara , Wiesner Ulrich
Published: April 2006

The cover picture illustrates quantitative chemical imaging of pH in mast cells facilitated by core/shell silica nanoparticle sensors incorporating two fluorescent dye species. These 70‐nm particles maximize the exposure of the sensor dye in the outer silica shell, while sequestering the reference dye within the particle core to minimize perturbations. Ratiometric comparison of the sensor and reference fluorescence allows the pH to be measured down to the single‐particle scale. Confocal fluorescence images of the red and green channels are shown superimposed on a bright‐field image of the cell under investigation (inset) and were analyzed to yield the false‐spectrum image of pH in various intracellular vesicles. For more information, please read the Communication “Core/Shell Fluorescent Silica Nanoparticles for Chemical Sensing: Towards Single‐Particle Laboratories” by U. Wiesner and co‐workers on page 723 ff.
Is Surgery Beneficial for MEN1 Patients with Small (≤2 cm), Nonfunctioning Pancreaticoduodenal Endocrine Tumor? An Analysis of 65 Patients from the GTE
Authors: Triponez Frederic , Goudet Pierre , Dosseh David , Cougard Patrick , Bauters Catherine , Murat Arnaud , Cadiot Guillaume , Niccoli‐Sire Patricia , Calender Alain , Proye Charles A. G.
Published: April 2006

Background

The management of small, nonfunctioning pancreaticoduodenal endocrine tumors (NFPET) in multiple endocrine neoplasia type 1 (MEN1) patients is still controversial. We therefore investigated the effect of surgery on survival and tumor progression in MEN1 patients with NFPET ≤2 cm by analyzing data from the Groupe des Tumeurs Endocrines (GTE) registry.

Materials and Methods

Among 579 MEN1 patients in the registry, 65 had NFPET ≤ 2 cm. Fifteen (23%) underwent pancreatectomy, 9 at least segmental pancreatectomies and 6 biopsies or enucleations (the surgery group), and 50 (77%) were followed conservatively (the no surgery group). Age at MEN1 and NFPET diagnosis was similar in both groups, as was size of the primary tumor. Seven (10.8%) patients had metastases. Five metastases were synchronous, and 2 (one in each group) were metachronous. Tumor size was similar in patients with or without metastasis.

Results

There was no perioperative mortality. The average follow‐up time after NFPET diagnosis was 6.7 years in the surgery group and 3.3 years in the no surgery group. Three (4.6%) patients died during follow‐up, 2 due to NFPET and 1 due to thymus tumor. The 2 patients who died of NFPET had undergone pancreatic surgery at the time of NFPET diagnosis. The 2 groups did not differ significantly with respect to tumor progression [5/15 (33%) vs 6/38 (16%), P = 0.16]. Overall life expectancy of patients with NFPET ≤2 cm was not different than that of the 229 MEN1 patients in the registry without any pancreaticoduodenal tumor (P = 0.33).

Conclusions

This study suggests that surgery may not be beneficial for MEN1 patients with NFPET ≤2 cm.
Selective Use of Adrenal Venous Sampling in the Lateralization of Aldosterone‐producing Adenomas
Authors: Tan Yah Yuen , Ogilvie Jennifer B. , Triponez Frederick , Caron Nadine R. , Kebebew Electron K. , Clark Orlo H. , Duh Quan‐Yang
Published: April 2006

Introduction

It has been suggested that routine adrenal venous sampling (AVS) is necessary to lateralize an aldosterone‐producing adenoma in patients with primary hyperaldosteronism. However, the success rate of AVS is variable, with potential risks. We review our experience at University of California San Francisco (UCSF), where AVS is used only selectively, to determine outcomes with this approach.

Methods

All patients undergoing adrenalectomy for aldosteronoma at UCSF from January 1995 to October 2004 were included. Outcome after adrenalectomy was determined based on plasma levels of aldosterone and potassium, rates of persistent hypertension, and reduced use of antihypertensive medications.

Results

Altogether, 65 patients were included in the study, 52 (80%) of whom had their adrenal tumors lateralized based on computed tomography scans, magnetic resonance imaging, or both. The remaining 13 (20%) patients had doubtful localization of their lesions on imaging. We did not routinely perform AVS in patients with definitive imaging findings. Thus, only 4 (8%) patients with definitive imaging findings underwent AVS, and one was unsuccessful. Of the 13 patients with doubtful lateralization on imaging, 8 underwent AVS. With this practice, biochemical cure rates after adrenalectomy were up to 100%, and hypertension resolved or was improved in 85% of patients.

Conclusions

AVS may be performed selectively only when preoperative imaging cannot definitively lateralize the aldosteronoma. This practice in our center has resulted in high cure rates. During the era of improved imaging resolution and experience, mandatory routine AVS is not necessary to achieve high cure rates for aldosteronomas.
Expanding to fill the gap: A possible role for inert biopolymers in regulating the extent of the ‘macromolecular crowding’ effect
Authors: Hall Damien , Dobson Christopher M.
Published: April 2006

We discuss the potential for inert biopolymers existing in cells to play a role in regulating the macromolecular crowding effect via their ability to undergo shape changing structural transitions. We have explored this possibility by the use of theory and experiment. The theoretical component utilized Monte‐Carlo based simulations to examine the folding of a hypothetical protein in a concentrated environment of hard spheres which are themselves capable of reversible expansion and contraction. The experimental component of the study involved examination of the effect of different sized crowding agents on the thermally induced denaturation of cytochrome c [in phosphate buffered saline solution containing 1.0 M guanidinium hydrochloride at pH 7.0]. On the basis of our findings we suggest that in a crowded solution environment the presence of a non‐reactive polymer capable of reversible expansion/contraction via folding and unfolding may alter the excluded volume component of the solution. This ability would confer on the non‐reactive polymer a novel role in influencing other processes in solution affected by macromolecular crowding.
Activated leukocyte cell adhesion molecule is a component of the endothelial junction involved in transendothelial monocyte migration
Authors: Masedunskas Andrius , King Judy A. , Tan Fang , Cochran Ruth , Stevens Troy , Sviridov Dmitri , Ofori-Acquah Solomon F.
Published: April 2006

Transendothelial leukocyte migration is a major aspect of the innate immune response. It is essential in repair and regeneration of damaged tissues and is regulated by multiple cell adhesion molecules (CAMs) including members of the immunoglobulin (Ig) superfamily. Activated leukocyte cell adhesion molecule (ALCAM/CD166) is an Ig CAM expressed by activated monocytes and endothelial cells. Hitherto, the functional relevance of ALCAM expression by endothelial cells and activated monocytes remained unknown. In this report, we demonstrate soluble recombinant human ALCAM significantly inhibited the rate of transendothelial migration of monocyte cell lines. Direct involvement of ALCAM in transendothelial migration was evident from the robust inhibition of this process by ALCAM blocking antibodies. However, soluble recombinant ALCAM had no impact on monocyte migration or adhesion to endothelium. Localization of ALCAM specifically at cell–cell junctions in endothelial cells supported its role in transendothelial migration. This study is the first to localize ALCAM to endothelial cell junctions and demonstrate a functional relevance for co‐expression of ALCAM by activated monocytes and endothelial cells.
Einsatz verschiedenartiger Arbeitsmittel in den frühen Phasen der Produktentwicklung - eine ergebnis- und prozessorientierte Analyse
Authors: Schütze Martina , Ulbricht Sabine
Published: April 2006

Zusammenfassung. Vor dem Hintergrund empirischer Befunde zur Nutzung von CAD-Systemen beim konstruktiven Entwerfen in der Ausbildung sowie der Berufspraxis wird im vorliegenden Beitrag über eine laborexperimentelle Studie zur Bewertung des Unterstützungspotenzials verschiedener Arbeitsmittel in den frühen Phasen des Konstruktionsprozesses berichtet. Eine Stichprobe von 66 Studierenden einer ingenieurtechnischen Fakultät bearbeitete ein Entwurfsproblem unter den experimentellen Bedingungen der Entwurfsentwicklung durch Freihandskizzieren mit Papier und Bleistift, mit einem digitalen Graphiktablett oder mittels des Rechnerprogramms AutoCAD 14. Im Ergebnis der Analysen kann gezeigt werden, dass Freihandskizzieren - unabhängig vom Arbeitsmittel - dem Entwerfen mittels CAD in allen betrachteten effektivitäts- und effizienzbestimmenden Kriterien überlegen war. Prozessorientierte Analysen des äußeren Handlungsablaufes sowie handlungsbegleitender mentaler Prozesse geben erste Hinweise auf mögliche Ursachen dieser Befunde aus handlungspsychologischer Sicht. Aus den Analysen und Resultaten werden Schlussfolgerungen für die Konstruktionsausbildung abgeleitet.
Tragedy of the commons in plant water use
Authors: Zea‐Cabrera Eduardo , Iwasa Yoh , Levin Simon , Rodríguez‐Iturbe Ignacio
Published: April 2006

In this paper we address the following question: how can efficient water use strategies evolve and persist when natural selection favors aggressive but inefficient individual water use? A tragedy of the commons, in which the competitive evolutionary outcome is lower than the ecosystem optimum (in this case defined as maximum productivity), arises because of (1) a trade‐off between resource uptake rate and resource use efficiency and (2) the open access character of soil water as a resource. Competitive superiority is determined by the lowest value of the steady state soil moisture, which can be minimized by increasing water uptake or by increasing drought tolerance. When the competing types all have the same drought tolerance, the most aggressive water users exclude efficient ones, even though they produce a lower biomass when in monoculture. However, plants with low water uptake can exclude aggressive ones if they have enough drought tolerance to produce a lower steady state soil moisture. In that case the competitive superior is also the best monoculture, and there is no tragedy of the commons. Spatial segregation in soil moisture dynamics favors the persistence of conservative water use strategies and the evolution of lower maximum transpiration rates. Increasing genetic relatedness between competing plants favors the evolution of conservative water use strategies. Some combinations of soil moisture spatial segregation and intensity of kin selection may favor the evolution and maintenance of multiple types of plant water use. This occurs because a cyclical pattern of species replacement can arise where no single type can exclude all other types.
Transport properties of Mo6S3I6 nanowire networks
Authors: Berčič Boštjan , Pirnat Urša , Kusar Primož , Dvorsek Damjan , Mihailovic Dragan , Vengust Damjan , Podobnik Boštjan
Published: April 2006

We present measurements of resistivity on Mo6S3I6 nanowire networks under different conditions. The room-temperature values of conductivity of as-grown nanowire networks are on the order of σ300K=0.04S∕m and show linear current-voltage characteristics, indicating that—in agreement with band structure calculations—there is a finite density of states at the Fermi level. The conductivity of pristine samples is thermally activated, closely following three-dimensional variable range hopping (VRH) behavior of the form σ=σ0exp−(T0∕T)β, where β=1∕4. Removal of interstitial iodine from the network by annealing in a vacuum gives rise to a cross over to one-dimensional VRH with β=1∕2 and a concurrent increase in room-temperature conductivity. The introduction of water vapor leads to a decrease in conductivity and reveals that the resistivity of the network is sensitive to interstitial water molecules.
New multiplicativity results for qubit maps
Authors: King Christopher , Koldan Nilufer
Published: April 2006

Let Φ be a trace-preserving, positivity-preserving (but not necessarily completely positive) linear map on the algebra of complex 2×2 matrices, and let Ω be any finite-dimensional completely positive map. For p=2 and p⩾4, we prove that the maximal p-norm of the product map Φ⊗Ω is the product of the maximal p-norms of Φ and Ω. Restricting Φ to the class of completely positive maps, this settles the multiplicativity question for all qubit channels in the range of values p⩾4.
A semiflexible chain model of local denaturation in double-stranded DNA
Authors: Jeon Jae-Hyung , Sung Wokyung , Ree Francis H.
Published: April 2006

Double-stranded DNA (dsDNA) is known to form a locally denatured structure (“bubble”) below its denaturation temperature (Tc). We have investigated the physical behavior of the bubbles using a model of dsDNA as two wormlike chains containing interacting complementary base pairs. The model incorporates two biologically relevant features, i.e., semiflexibility of the strand and overdamping nature of aqueous background. Computer simulations using the Langevin equation are performed to examine the size distribution and dynamics of bubbles. The results show that the entropy associated with semiflexibility of DNA sensitively affects the size distribution and lifetime of bubble. In particular, the lifetime grows with bubble size m as m2.7 at temperature close to Tc, which is consistent with our analysis based on a stochastic model of bubble size dynamics.
Role of titanium and silicon dioxide in amorphous silicon nanowire growth by solid state reaction
Authors: Song Youngsik , Choi Jaewu
Published: April 2006

The role of titanium and silicon dioxide in vertical growth of amorphous silicon nanowires by solid state reaction was studied by Raman spectroscopy, scanning electron microscopy, and transmission electron microscopy. Denser, longer, and straighter silicon nanowires over large areas were grown from seedbeds with thick silicon dioxide than from seedbeds with native oxide. The study revealed that the reactive nature of silicon dioxide with titanium plays an important role in synthesis of nanowires and physical properties of seedbeds.
Fungi and animals may share a common ancestor to nuclear receptors
Authors: Phelps Chris , Gburcik Valentina , Suslova Elena , Dudek Peter , Forafonov Fedor , Bot Nathalie , MacLean Morag , Fagan Richard J. , Picard Didier
Published: April 2006

Nuclear receptors (NRs) are a large family of transcription factors. One hallmark of this family is the ligand-binding domain (LBD), for its primary sequence, structure, and regulatory function. To date, NRs have been found exclusively in animals and sponges, which has led to the generally accepted notion that they arose with them. We have overcome the limitations of primary sequence searches by combining sequence profile searches with structural predictions at a genomic scale, and have discovered that the heterodimeric transcription factors Oaf1/Pip2 of the budding yeast
Saccharomyces cerevisiae
contain putative LBDs resembling those of animal NRs. Although the Oaf1/Pip2 LBDs are embedded in an entirely different architecture, the regulation and function of these transcription factors are strikingly similar to those of the mammalian NR heterodimer peroxisome proliferator-activated receptor α/retinoid X receptor (PPARα/RXR). We demonstrate that the induction of Oaf1/Pip2 activity by the fatty acid oleate depends on oleate’s direct binding to the Oaf1 LBD. The alteration of two amino acids in the predicted ligand-binding pocket of Oaf1 abolishes both ligand binding and the transcriptional response. Hence, LBDs may have arisen as allosteric switches, for example, to respond to nutritional and metabolic ligands, before the animal and fungal lineages diverged.
Short blocks from the noncoding parts of the human genome have instances within nearly all known genes and relate to biological processes
Authors: Rigoutsos Isidore , Huynh Tien , Miranda Kevin , Tsirigos Aristotelis , McHardy Alice , Platt Daniel
Published: April 2006

Using an unsupervised pattern-discovery method, we processed the human intergenic and intronic regions and catalogued all variable-length patterns with identically conserved copies and multiplicities above what is expected by chance. Among the millions of discovered patterns, we found a subset of 127,998 patterns, termed pyknons, which have additional nonoverlapping instances in the untranslated and protein-coding regions of 30,675 transcripts from 20,059 human genes. The pyknons arrange combinatorially in the untranslated and coding regions of numerous human genes where they form mosaics. Consecutive instances of pyknons in these regions show a strong bias in their relative placement, favoring distances of ≈22 nucleotides. We also found pyknons to be enriched in a statistically significant manner in genes involved in specific processes, e.g., cell communication, transcription, regulation of transcription, signaling, transport, etc. For ≈1/3 of the pyknons, the intergenic/intronic instances of their reverse complement lie within 380,084 nonoverlapping regions, typically 60–80 nucleotides long, which are predicted to form double-stranded, energetically stable, hairpin-shaped RNA secondary structures; additionally, the pyknons subsume ≈40% of the known microRNA sequences, thus suggesting a possible link with posttranscriptional gene silencing and RNA interference. Cross-genome comparisons reveal that many of the pyknons have instances in the 3′ UTRs of genes from other vertebrates and invertebrates where they are overrepresented in similar biological processes, as in the human genome. These unexpected findings suggest potential unique functional connections between the coding and noncoding parts of the human genome.
Apolipoprotein B is conformationally flexible but anchored at a triolein/water interface: A possible model for lipoprotein surfaces
Authors: Wang Libo , Walsh Mary T. , Small Donald M.
Published: April 2006

Apolipoprotein B (apoB) is one of a unique group of proteins that form and bind to fat droplets, stabilize the emulsified fat, and direct their metabolism. ApoB, secreted on lipoproteins (emulsions), remains bound during lipid metabolism yet exhibits conformational flexibility. It has amphipathic β-strand (AβS)-rich domains and amphipathic α-helix (AαH)-rich domains. We showed that two consensus AβS peptides of apoB bound strongly to hydrophobic interfaces [triolein/water (TO/W) and dodecane/water], were elastic, and were not pushed off the interface when the surface was compressed. In contrast, an AαH peptide modeling helical parts of apoB was forced off the TO/W interface by compression and readsorbed when the interface was expanded. In this report, the surface behavior of apoB-100 was studied at the TO/W interface. Solubilized apoB lowered the interfacial tension of TO/W in a concentration-dependent fashion. At equilibrium tension, if the surface was compressed, part of apoB was pushed off but quickly readsorbed when the surface was expanded. Even when the surface area was compressed by ≈55%, part of the apoB molecule remained bound. The maximum surface pressure that apoB could withstand without being partially ejected was 13 mN/m. ApoB showed high elasticity at the TO/W interface. Based on studies of the consensus AβS and AαH peptides, we suggest that AβSs anchor apoB and are its nonexchangeable motif, whereas its conformational flexibility arises from both the elastic nature of the AβS and the ability of AαH domains of the molecule to desorb and readsorb rapidly in response to surface pressure changes.
The relevance of nonlinear stacking interactions in simple models of double-stranded DNA
Authors: Saccomandi Giuseppe , Sgura Ivonne
Published: April 2006

Single molecule DNA experiments provide interesting data that allow a better understanding of the mechanical interactions between the strands and the nucleotides of this molecule. In some sense, these experiments complement the classical ones about DNA thermal denaturation. It is well known that the original Peyrard–Bishop (PB) model by means of a harmonic stacking potential and a nonlinear substrate potential has been able to predict the existence of a critical temperature of full denaturation of the molecule. In the present paper, driven by the findings of single molecule experiments, we substitute the original harmonic intra-strand stacking potential with a Duffing type potential. By elementary and analytical arguments, we show that with this choice it is possible to obtain a sharp transition in the classical domain wall solution of the PB model and the compactification of the classical solitary wave solutions of other models for the dynamics of DNA. We discuss why these solutions may improve our knowledge of the DNA dynamics in several directions.
Avian influenza H5N1 in viverrids: implications for wildlife health and conservation
Authors: Roberton S.I , Bell D.J , Smith G.J.D , Nicholls J.M , Chan K.H , Nguyen D.T , Tran P.Q , Streicher U , Poon L.L.M , Chen H , Horby P , Guardo M , Guan Y , Peiris J.S.M
Published: April 2006

The Asian countries chronically infected with avian influenza A H5N1 are ‘global hotspots’ for biodiversity conservation in terms of species diversity, endemism and levels of threat. Since 2003, avian influenza A H5N1 viruses have naturally infected and killed a range of wild bird species, four felid species and a mustelid. Here, we report fatal disseminated H5N1 infection in a globally threatened viverrid, the Owston's civet, in Vietnam, highlighting the risk that avian influenza H5N1 poses to mammalian and avian biodiversity across its expanding geographic range.
Digit ratio (2D : 4D) moderates the impact of sexual cues on men's decisions in ultimatum games
Authors: Van den Bergh Bram , Dewitte Siegfried
Published: April 2006

Three experimental studies demonstrate that ‘sex-related cues’ impact human decision-making in ultimatum games. In the ultimatum game, two individuals divide a sum of money. The proposer offers a portion of the money to the other player, the responder. If the responder accepts the offer, the money is distributed in agreement with the proposer's offer. If the responder rejects the offer, neither player receives anything. Our studies show that exposure to pictures of sexy women or lingerie increases the likelihood of accepting unfair offers. Digit ratios of responders are reliably associated with their behaviour: males with lower digit ratios are more likely to reject an unfair split in neutral contexts, but more likely to accept unfair offers in sex-related contexts.
Two fluid compartments in the renal inner medulla: a view through the keyhole of the concentrating process
Authors: Pinter G.G , Shohet J.L
Published: April 2006

Approximately four decades ago, the countercurrent theory became influential in studies on the concentrating process in the mammalian kidney. The theory successfully represented the concentrating process in the outer medulla, but the problem of the concentrating mechanism in the inner medulla, as defined by Homer Smith has remained essentially intractable.

In a recent comprehensive review by Knepper and coworkers of various theories and models, attention was refocused on the possible role of hyaluronate (HA) in the inner medullary concentrating process. The authors proposed a hypothesis that HA can convert hydrostatic pressure to concentrating work.

Here, we briefly survey the earlier ideas on the role imputed to HA and present a new hypothesis which is different from that of Knepper and coworkers. We estimate that the hydrostatic pressures available in the inner medulla can account only for a very small fraction of the concentrating work. We hypothesize that the role of HA is tied up with extravasated plasma albumin and suggest that owing to the property of HA solutions to exclude other macromolecules, extravasated plasma albumin and HA constitute two fluid compartments in the interstitium in the inner medulla. In this proposed two-compartment model, the Gibbs-Donnan distribution influences the movement of ions and water between the HA and the extravasated albumin compartment.

To relate the hypothetical role of HA to the concentrating process, we briefly describe new results obtained by other investigators on the accumulation of urea in the inner medulla. This subject has been critically reviewed recently by Yang & Bankir.

Many processes have been identified as contributing to the concentrating process in the mammalian inner medulla. We speculate that among these many processes, the primary responsibility for the final concentration of the excreted urine may be portioned out differently in different mammalian species.
Action potential morphology heterogeneity in the atrium and its effect on atrial reentry: a two-dimensional and quasi-three-dimensional study
Authors: Kuo Samuel R , Trayanova Natalia A
Published: April 2006

Atrial fibrillation (AF) is believed to be perpetuated by recirculating spiral waves. Atrial structures are often characterized with action potentials of varying morphologies; however, the role of the structure-dependent atrial electrophysiological heterogeneity in spiral wave behaviour is not well understood. The purpose of this study is to determine the effect of action potential morphology heterogeneity associated with the major atrial structures in spiral wave maintenance. The present study also focuses on how this effect is further modulated by the presence of the inherent periodicity in atrial structure. The goals of the study are achieved through the simulation of electrical behaviour in a two-dimensional atrial tissue model that incorporates the representation of action potentials in various structurally distinct regions in the right atrium. Periodic boundary conditions are then imposed to form a cylinder (quasi three-dimensional), thus allowing exploration of the additional effect of structure periodicity on spiral wave behaviour. Transmembrane potential maps and phase singularity traces are analysed to determine effects on spiral wave behaviour. Results demonstrate that the prolonged refractoriness of the crista terminalis (CT) affects the pattern of spiral wave reentry, while the variation in action potential morphology of the other structures does not. The CT anchors the spiral waves, preventing them from drifting away. Spiral wave dynamics is altered when the ends of the sheet are spliced together to form a cylinder. The main effect of the continuous surface is the generation of secondary spiral waves which influences the primary rotors. The interaction of the primary and secondary spiral waves decreased as cylinder diameter increased.
Activation sequence as a key factor in spatio-temporal optimization of myocardial function
Authors: Solovyova O , Katsnelson L.B , Konovalov P , Lookin O , Moskvin A.S , Protsenko Yu.L , Vikulova N , Kohl P , Markhasin V.S
Published: April 2006

Using one-dimensional models of myocardial tissue, implemented as chains of virtual ventricular muscle segments that are kinematically connected in series, we studied the role of the excitation sequence in spatio-temporal organization of cardiac function. Each model element was represented by a well-verified mathematical model of cardiac electro-mechanical activity. We found that homogeneous chains, consisting of identical elements, respond to non-simultaneous stimulation by generation of complex spatio-temporal heterogeneities in element deformation. These are accompanied by the establishment of marked gradients in local electro-mechanical properties of the elements (heterogeneity in action potential duration, Ca
2+
transient characteristics and sarcoplasmic reticulum Ca
2+
loading). In heterogeneous chains, composed of elements simulating fast and slow contracting cardiomyocytes from different transmural layers, we found that only activation sequences where stimulation of the slower elements preceded that of faster ones gave rise to optimization of the system's electro-mechanical function, which was confirmed experimentally. Based on the results obtained, we hypothesize that the sequence of activation of cardiomyocytes in different ventricular layers is one of the key factors of spatio-temporal organization of myocardium. Moreover, activation sequence and regional differences in intrinsic electro-mechanical properties of cardiac muscle must be matched in order to optimize myocardial function.
Enabling computer models of the heart for high-performance computers and the grid
Authors: Pitt-Francis Joe , Garny Alan , Gavaghan David
Published: April 2006

Although it is now feasible to compute multi-cellular models of the heart on a personal desktop or laptop computer, it is not feasible to undertake the detailed sweeps of high-dimensional parameter spaces required if we are to undertake
in silico
experimentation of the complex processes that constitute heart disease. For this research, modelling requirements move rapidly beyond the limit of commodity computers' resource both in terms of their memory footprint and the speed of calculation, so that multi-processor architectures must be considered. In addition, as such models have become more mature and have been validated against experimental data, there is increasing pressure for experimentalists to be able to make use of these models themselves as a key tool for hypothesis formulation and in planning future experimental studies to test those hypotheses.

This paper discusses our initial experiences in a large-scale project (the Integrative Biology (IB) e-Science project) aimed at meeting these dual aims. We begin by putting the research in context by describing in outline the overall aims of the IB project, in particular focusing on the challenge of enabling novice users to make full use of high-performance resources without the need to gain detailed technical expertise in computing. We then discuss our experience of adapting one particular heart modelling package, Cellular Open Resource, and show how the solving engine of this code was dissected from the rest of the package, ported to C++ and parallelized using the Message-Passing Interface. We show that good parallel efficiency and realistic memory reduction can be achieved on simple geometries. We conclude by discussing lessons learnt in this process.
Multinucleate cell angiohistiocytoma. Report of five cases
Authors: Pérez Lidia Pérez , Zulaica Ander , Rodríguez Luis , Campo M. Carmen , Peñaranda José Manuel Suárez , Fernández‐Redondo Virginia , Toribio Jaime
Published: April 2006

Background:  Multinucleate cell angiohistiocytoma is an infrequent and most likely non‐neoplastic disorder usually seen in acral regions in elderly women. It presents clinically as asymptomatic red‐to‐brown tumors, with a tendency to confluence. It must be distinguished from other diverse cutaneous lesions, notably dermatofibroma, Kaposi sarcoma, and angiofibroma.

Methods:  We report the clinical, histopathological, and immunohistochemical findings of five patients, all women aged between 51 and 78 years. All except the first presented lesions on both of the lower limbs. None of the patients developed spontaneous resolution of the lesions and one was successfully treated by cryosurgery.

Comments:  Multinucleate cells are characteristic, but neither exclusive nor pathognomonic, of multinucleate cell angiohistiocytoma, since they can also appear in other inflammatory, neoplastic, or reactive processes. The presence of these cells and vascular proliferation in dermis media are the principal histopathological findings in this infrequent entity. In immunohistochemical studies, the multinucleate cells are often positive for vimentin and factor XIIIa.
Autophagic vacuolar myopathy in twin girls
Authors: Holton J. L. , Beesley C. , Jackson M. , Venner K. , Bhardwaj N. , Winchester B. , Al‐Memar A.
Published: April 2006

Hereditary autophagic vacuolar myopathy (AVM) may occur in several diseases including the rimmed vacuolar myopathies, acid maltase deficiency, Danon disease, infantile autophagic vacuolar myopathy and X‐linked myopathy with excessive autophagy (XMEA). In the latter three conditions the vacuoles are lined by membranes with sarcolemmal features. We present two unusual cases of autophagic vacuolar myopathy in twin girls born at term with no family history of neurological disease. After initial normal developmental milestones they developed progressive leg weakness and wasting with contractures from the age of 12 years. Investigations showed raised CK, normal female karyotype, normal acid maltase activity, normal nerve conduction and myopathic EMG features. Frozen sections of skeletal muscle were stained using routine tinctorial and histochemical methods. Immunohistochemical staining for spectrin, merosin, dystrophin, complement membrane attack complex and sarcoglycans was performed and ultrastructural examination undertaken. Direct sequence analysis of the lamp‐2 gene using genomic DNA extracted from lymphocytes was performed. Histological analysis of the muscle biopsies demonstrated myofibres with vacuoles lacking glycogen and lipid many of which were delineated using immunohistochemistry for merosin, dystrophin and sarcoglycans. Ultrastructural examination showed duplication of the myofibre basal lamina with associated autophagic material. Vacuoles within myofibres were either membrane bound containing autophagic material or lined by plasma membrane and basal lamina. Intermyofibrillar glycogen was increased. Sequence analysis of the coding region and intron/exon boundaries of the lamp‐2 gene was normal. This is the first report of female cases of AVM with sarcolemmal features. We suggest that these patients may represent manifesting carriers of XMEA, or alternatively, a new form of disease with a similar phenotype having autosomal recessive inheritance.
Spatial distribution of Aspergillus flavus and its toxigenic strains on commercial cottonseed from south Texas and its relationship to aflatoxin contamination
Authors: Jaime‐Garcia R. , Cotty P. J.
Published: April 2006

The structure of Aspergillus flavus communities associated with south Texas cottonseed was determined by analysing samples from 178 truckloads of commercial cottonseed from 35 gins, extending from Fort Bend County in the north to the Rio Grande Valley in the south, from September 1999 to October 2001. The number of colony‐forming units (CFU) of A. flavus on the cottonseed, and the percentage of S strain (%S) were both correlated with aflatoxin contamination of cottonseed. The number of CFU differed between both regions and seasons, while %S differed only between regions. Comparison of maps of CFU and %S revealed that CFU shows a higher variation across years, while %S shows higher spatial variation. The Rio Grande Valley had significantly lower CFU and %S strain than the Coastal Bend and Upper Coast regions. Cottonseed produced in 1999 had significantly more A. flavus than that produced in either 2000 or 2001. Identification of factors dictating geographical variation in S‐strain incidence may provide insights that will lead to improved aflatoxin management.
Peroxisome Proliferator‐Activated Receptor α, δ, γ1 and γ2 Expressions are Present in Human Monocyte‐Derived Dendritic Cells and Modulate Dendritic Cell Maturation by Addition of Subtype‐Specific Ligands
Authors: Jakobsen M. A. , Petersen R. K. , Kristiansen K. , Lange M. , Lillevang S. T.
Published: April 2006

It has recently been shown by Chang et al. (J Immunol 2000;165:3584–91) that the maturation of dendritic cells (DC) in the presence of long‐chain fatty acids redirects DC into Th0/Th2‐inducing cells suggesting the involvement of a receptor for long‐chain fatty acids like members of the peroxisome proliferator‐activated receptors (PPAR) superfamily. Here, we show that immature and mature monocyte‐derived DC (Mo‐DC) express PPARα, PPARδ, PPARγ1 and PPARγ2 mRNA with the highest level of PPARγ1 mRNA. We were only able to observe the expression of PPARγ1 protein by Western blotting probably because the protein level of the other subtypes is below the detection limit. Synthetic ligands specific for PPARα, PPARδ or PPARγ added at day 0–6 have similar effect on the maturation of Mo‐DC driving the maturation of Mo‐DC with atypical phenotype, reduced expression of IL‐10, IL‐12 p35 and IL‐12 p40 mRNA and with reduced stimulatory effects in mixed leucocyte reaction (MLR). Our data suggest that naturally occurring PPAR ligands like fatty acids and fatty acid derivates have anti‐inflammatory effects by redirecting DC into a less stimulatory mode.