bluuebunny/crossref_metadata_2025 huggingface dataset:
AtREC8 and AtSCC3 are essential to the monopolar orientation of the kinetochores during meiosis
Authors: Chelysheva Liudmila , Diallo Stéphanie , Vezon Daniel , Gendrot Ghislaine , Vrielynck Nathalie , Belcram Katia , Rocques Nathalie , Márquez-Lema Angustias , Bhatt Anuj M. , Horlow Christine , Mercier Raphaël , Mézard Christine , Grelon Mathilde
Published: September 2005

The success of the first meiotic division relies (among other factors) on the formation of bivalents between homologous chromosomes, the monopolar orientation of the sister kinetochores at metaphase I and the maintenance of centromeric cohesion until the onset of anaphase II. The meiotic cohesin subunit, Rec8 has been reported to be one of the key players in these processes, but its precise role in kinetochore orientation is still under debate. By contrast, much less is known about the other non-SMC cohesin subunit, Scc3. We report the identification and the characterisation of AtSCC3, the sole Arabidopsis homologue of Scc3. The detection of AtSCC3 in mitotic cells, the embryo lethality of a null allele Atscc3-2, and the mitotic defects of the weak allele Atscc3-1 suggest that AtSCC3 is required for mitosis. AtSCC3 was also detected in meiotic nuclei as early as interphase, and bound to the chromosome axis from early leptotene through to anaphase I. We show here that both AtREC8 and AtSCC3 are necessary not only to maintain centromere cohesion at anaphase I, but also for the monopolar orientation of the kinetochores during the first meiotic division. We also found that AtREC8 is involved in chromosome axis formation in an AtSPO11-1-independent manner. Finally, we provide evidence for a role of AtSPO11-1 in the stability of the cohesin complex.
mazEF: a chromosomal toxin-antitoxin module that triggers programmed cell death in bacteria
Authors: Engelberg-Kulka Hanna , Hazan Ronen , Amitai Shahar
Published: September 2005

mazEF is a toxin-antitoxin module located on the Escherichia coli chromosome and that of some other bacteria, including pathogens. mazF specifies for a stable toxin, MazF, and mazE specifies for a labile antitoxin, MazE, that antagonizes MazF. MazF is a sequence-specific mRNA endoribonuclease that initiates a programmed cell death pathway in response to various stresses. The mazEF-mediated death pathway can act as a defense mechanism that prevents the spread of bacterial phage infection, allowing bacterial populations to behave like multicellular organisms.
ATP modulates siRNA interactions with an endogenous human Dicer complex
Authors: PELLINO JANICE L. , JASKIEWICZ LUKASZ , FILIPOWICZ WITOLD , SONTHEIMER ERIK J.
Published: September 2005

Short interfering RNA (siRNA) binding by Dicer is important for RNA interference in Drosophila, but human Dicer (hDcr) has been reported to lack siRNA binding activity. We used native gel electrophoresis to characterize the siRNA-binding activity of endogenous hDcr-containing complexes in extracts from human cells. We identified a complex (D) that contains hDcr, as demonstrated by antibody supershift. Complex D appears to contain double-stranded siRNAs, and requires structural features of authentic siRNAs. Glycerol gradient sedimentation indicates that Complex D is ~250 kDa, slightly larger than hDcr alone. In addition, we found that purified recombinant hDcr (rhDcr) alone has siRNA binding activity. Complex D migrates more slowly than the rhDcr/siRNA complex in a native gel, suggesting that it contains at least one additional factor. hDcr directly contacts siRNAs within Complex D, as indicated by crosslinking. The endogenous complex is significantly enhanced by ATP, unlike the siRNA-binding activity of purified rhDcr, suggesting the existence of additional factors that can enforce the ATP dependence of endogenous hDcr/siRNA interactions. Complex D could impinge upon the RISC assembly pathway in humans, similar to an analogous complex in Drosophila.
Rsp5 ubiquitin ligase modulates translation accuracy in yeast Saccharomyces cerevisiae
Authors: KWAPISZ MARTA , CHOŁBIŃSKI PIOTR , HOPPER ANITA K. , ROUSSET JEAN-PIERRE , ŻOŁĄDEK TERESA
Published: September 2005

Rsp5p is an essential yeast ubiquitin protein ligase that ubiquitinates multiple proteins involved in various processes. Recent studies indicate that ubiquitination also affects translation. Here, we show that the strain with the rsp5–13 mutation exhibits altered sensitivity to antibiotics and a slower rate of translation. Using a sensitive dual-gene reporter system, we demonstrate that stop codon readthrough efficiency is decreased in the rsp5–13 mutant, while both +1 and −1 frameshifting were unaffected. The effect of the rsp5–13 mutation on readthrough could be reversed by increased expression of ubiquitin and partially suppressed by overproduction of the elongation factor eEF1A. As assessed by fluorescence in situ hybridization, the rsp5–13 mutant cells accumulate tRNA nuclear pools, perhaps depleting tRNA from the cytoplasm. Nuclear accumulation of tRNA is observed only when rsp5–13 cells are grown in media with high amino acid content. This defect, also reversed by overproduction of the elongation factor eEF1A, may be the primary reason for altered translational decoding accuracy.
Spurious splicing within the XIAP 5′ UTR occurs in the Rluc/Fluc but not the βgal/CAT bicistronic reporter system
Authors: HOLCIK MARTIN , GRABER TYSON , LEWIS STEPHEN M. , LEFEBVRE CHARLES A. , LACASSE ERIC , BAIRD STEPHEN
Published: September 2005

X-chromosome-linked inhibitor of apoptosis, XIAP, has been shown to contain a strong internal ribosome entry site (IRES) within its 5′ untranslated region (UTR) that promotes translation of XIAP mRNA under conditions of cellular stress. This claim came under scrutiny in a recent report demonstrating that the XIAP 5′ UTR undergoes splicing when inserted between the two reporter cistrons of the dual luciferase plasmid Rluc/Fluc. In this paper, we demonstrate that the splicing within the XIAP 5′ UTR specifically occurs only in the context of mRNA produced from the Rluc/Fluc but not the pβgal/CAT bicistronic reporter plasmid.
Size, constant sequences, and optimal selection
Authors: LEGIEWICZ MICHAL , LOZUPONE CATHERINE , KNIGHT ROB , YARUS MICHAEL
Published: September 2005

Because the abundance of functional molecules in RNA sequence space has many unexplored aspects, we compared the outcome of 11 independent selections, performed using the same affinity selection protocol and contiguous randomized regions of 16, 22, 26, 50, 70, and 90 nucleotides. All affinity selections targeted the simplest isoleucine aptamer, an asymmetric internal loop. This loop should be abundant in all selections, so that it can be compared across all experiments. In some cases, two primer sets intended to favor selection of different structures have also been compared. The simplest isoleucine aptamer dominates all selections except with the shortest tract, 16 contiguous randomized nucleotides. Here the isoleucine aptamer cannot be accommodated and no other motif can be selected. Our results suggest an optimum length for selection; surprisingly, both the shortest and the longest randomized tracts make it more difficult to recover the motif. Estimated apparent initial abundances suggest that the simplest isoleucine motif was 20- to 40-fold more frequent in selection with 50- or 70-nucleotide randomized regions than with any other length. Considering primer sets, a pre-formed stable stem within fixed flanking sequences had a five-to 10-fold negative effect on apparent motif abundance at all lengths. Differing random tract lengths also determined the probable motif permutation and the most abundant helix lengths. These data support a significant but lesser role for primer sequences in the outcome of selections.
Efficacy of Cognitive—Behavioural Therapy for Children and Adolescents With Anxiety Disorders
Authors: Hudson Jennifer L.
Published: September 2005

Support for the efficacy of cognitive—behavioural therapy (CBT) for anxious youth has accumulated. Significant treatment effects are observed and maintained over the long term for the majority of children receiving individual, family or group-based treatments. Nevertheless, all children do not improve. In fact, there is evidence to suggest that a significant percentage of children continue to experience anxiety following treatment and will seek additional treatment for their anxiety. This article will review the substantial evidence for CBT, the current information available on predictors of outcome and mechanisms of change. The article will also discuss the need for adequately powered randomised clinical trials that continue to refine and evaluate treatments for anxious children in an effort to improve outcomes for those children whose needs are not being met by our current treatments.
Co-morbidity and Associated Clinical Problems in Schizophrenia: Their Nature and Implications for Comprehensive Cognitive—Behavioural Treatment
Authors: Tarrier Nicholas
Published: September 2005

Schizophrenia is a multifaceted disorder that can affect many aspects of the sufferer's life. Recent advances in the use of cognitive—behaviour therapy as an adjunct treatment for schizophrenia have been shown to result in significant improvements in psychotic symptoms. However, to date, much less attention has been paid to other co-morbid and emotional disorders that often co-exist with psychosis and that can be a severe burden to the sufferer. This article briefly reviews clinical trials of cognitive—behavioural treatments for schizophrenia and their outcome and then goes on to describe clinically important co-morbid or associated clinical problems: social anxiety, posttraumatic stress disorder (PTSD), depression and suicide risk. Because the psychotic symptoms usually receive priority, there has been little in the cognitive—behavioural literature on the nature and treatment of these co-morbid disorders. The nature of these problems and issues relating to their treatment are discussed.
Mean fluorescence intensity rate is a useful marker in the detection of paroxysmal nocturnal hemoglobinuria clones
Authors: Hevessy Zsuzsa , Nagy Béla , Kiss Flóra , Kiss Attila , Kappelmayer János
Published: September 2005

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder of the pluripotent stem cell resulting from the somatic mutation of the X-linked PIG-A gene, involved in the synthesis of the glycosylphosphatidyl-inositol anchor of membrane proteins such as CD55, CD59 and CD14. In the past decade, flow cytometry has become a valuable diagnostic tool in the detection of deficient expression of the GPI-anchored proteins. We report the diagnosis of PNH in four patients confirmed by flow cytometry. Red blood cells, granulocytes and monocytes were classified as PNH types I, II and III according to the mean fluorescence intensities (MFI) of membrane proteins. MFI rate is a numerical data reflecting the severity of decreased antigen expression, and it is obtained by dividing the MFI of the type II or type III cells by the MFI of the respective cells obtained for a normal sample. We found that the investigation of granulocytes and monocytes was more informative than red blood cells when percent negativity was evaluated. In addition, the lowest MFI rate (mean 0.011) was obtained for CD14 on monocytes while CD59 and CD55 gave higher values on all three investigated cell types (0.021–0.34). Thus, CD14 on monocytes seems to be the most reliable marker for establishing the PNH clone size and the severity of antigen deficiency.
Multicentre physiological reference values for some urinary component-to-creatinine (creatininium) concentration ratios
Authors: Fuentes-Arderiu Xavier , Mas-Serra Roser , de-Nó-Lengaran Carmen , Espejo-López Francisco , Filgueiras-Martínez Paula , Gassiot-Cordomí Paula , Idoate-Cervantes Isabel , Poncela-García María Victoria , Porras-Gracia Juan , Sanz-Lobo Irene , del Mar Viloria-Peñas María , Juvé-Cuxart Santiago
Published: September 2005

Nine clinical laboratories in different regions of Spain have shared the search for reference individuals and the production of reference values for urinary component-to-creatininium concentration ratios measured in first morning urine samples using RD/Hitachi analysers. These urinary quantities include albumin, calcium(II), chloride, magnesium(II), phosphate, potassium ion, protein, sodium ion, urate and urea. All the logistic work was done in co-operation with the reagents' and analysers' supplier (Roche Diagnostics España, S.L., Sant Cugat del Vallès, Catalonia, Spain). From the blend of reference values obtained by each laboratory, the multicentre reference limits were estimated parametrically after mathematical transformation of original data.
Fabrication and Electrical and Mechanical Properties of Carbon Nanotube Interconnections
Authors: Wang M. S. , Wang J. Y. , Chen Q. , Peng L.‐M.
Published: September 2005

Individual carbon nanotubes (CNTs) have been cut, manipulated, and soldered via electron‐beam‐induced deposition of amorphous carbon (a‐C) and using a scanning tunneling microscope inside a transmission electron microscope. All CNT structures, including simple tube–tube connections, crossed junctions, T‐junctions, zigzag structures, and even nanotube networks, have been successfully constructed with a high degree of control, and their electrical and mechanical properties have been measured in situ inside the transmission electron microscope. It is found that multiple CNTs may be readily soldered together with moderate junction resistance and excellent mechanical resilience and strength, and the junction resistance may be further reduced by current‐induced graphitization of the deposited a‐C on the junction.
Scents and Sensibility: A Molecular Logic of Olfactory Perception (Nobel Lecture)
Authors: Axel Richard
Published: September 2005

A sense of occasion: Around 20 years after the start of their pioneering studies on the function of the nose and brain in odor perception, R. Axel and L. Buck have received the 2004 Nobel Prize for Medicine or Physiology. The picture shows schematically the coding of different odors in the olfactory epithelium (OE) and olfactory bulb (OB).
Cover Picture: Real‐Time Observation of Ionization‐Induced Hydrophobic→Hydrophilic Switching (Angew. Chem. Int. Ed. 38/2005)
Authors: Ishiuchi Shun‐ichi , Sakai Makoto , Tsuchida Yuji , Takeda Akihiro , Kawashima Yasutake , Fujii Masaaki , Dopfer Otto , Müller‐Dethlefs Klaus
Published: September 2005

The intermolecular binding motif of the argon atom in a phenol⋅⋅⋅Ar dimer has been monitored on the picosecond timescale by time‐resolved UV–UV(pump)–IR(probe) ionization depletion spectroscopy. The cover picture shows the dynamic process, which involves a shift of the initially π‐bound Ar atom to a hydrophilic, hydrogen‐bound site. For more details, see the Communication by M. Fujii, K. Müller‐Dethlefs, and co‐workers on page 6149 ff.
Systematic review of endovenous laser treatment for varicose veins
Authors: Mundy L , Merlin T L , Fitridge R A , Hiller J E
Published: September 2005

Background

The safety and effectiveness of endovenous laser treatment (EVLT) for varicose veins are not yet fully evaluated.

Methods

Medical bibliographic databases, the internet and reference lists were searched from January 1966 to September 2004. Only case series were available for inclusion in the review.

Results

Thirteen studies met the inclusion criteria. Self-limiting features, such as pain, ecchymosis, induration and phlebitis, were commonly encountered after treatment. Deep vein thrombosis and incorrect placement of the laser in vessels were uncommon adverse events. No study has yet assessed the effectiveness of laser therapy in comparison to saphenofemoral junction ligation with saphenous vein stripping. Occlusion of the saphenous vein and abolition of venous reflux occurred in 87·9–100 per cent of limbs, with low rates of re-treatment and recanalization.

Conclusion

From the low-level evidence available it seems that EVLT benefits most patients in the short term, but rates of recanalization, re-treatment, occlusion and reflux may alter with longer follow-up. The lack of such data, in addition to the small numbers of patients in the available studies, demonstrates the need for a randomized clinical trial of EVLT versus conventional surgery.
Systematic review comparing laparoscopic and open repair for perforated peptic ulcer
Authors: Lunevicius R , Morkevicius M
Published: September 2005

Background

The advantages of laparoscopic over open repair for perforated peptic ulcer are not as obvious as they may seem. This paper summarizes the published trials comparing the two approaches.

Methods

Two randomized prospective, five non-randomized prospective and eight retrospective studies were included in the analysis. Relevant trials were identified from the Medline/Pubmed database and the reference lists of the retrieved papers were then analysed. The outcome measures used were operating time, postoperative analgesic requirements, length of hospital stay, return to normal diet and usual activities, and complication and mortality rates. Published data were tested for heterogeneity by means of a χ2 test. Meta-analysis methods were used to measure the pooled estimate of the effect size. In total, 1113 patients are represented from 15 selected studies, of whom 535 were treated by laparoscopic repair and 578 by open repair; 102 patients (19·1 per cent) underwent conversion to open repair.

Results

Statistically significant findings in favour of laparoscopic repair were less analgesic use, shorter hospital stay, less wound infection and lower mortality rate. Shorter operating time and less suture-site leakage were advantages of open repair. Three variables (hospital stay, operating time and analgesic use) were significantly heterogeneous in the papers analysed.

Conclusion

Laparoscopic repair seems better than open repair for low-risk patients. However, limited knowledge about its benefits and risks compared with open repair suggests that the latter, more familiar, approach may be more appropriate in high-risk patients. Further studies are needed.
Helicobacter pylori infection and gastric cancer
Authors: O'Morain C
Published: September 2005

Screening cannot yet be recommended
Pretarget sorting of retinocollicular axons in the mouse
Authors: Plas Daniel T. , Lopez Joshua E. , Crair Michael C.
Published: September 2005

The map of the retina onto the optic tectum is a highly conserved feature of the vertebrate visual system; the mechanism by which this mapping is accomplished during development is a long‐standing problem of neurobiology. The early suggestion by Roger Sperry that the map is formed through interactions between retinal ganglion cell axons and target cells within the tectum has gained significant experimental support and widespread acceptance. Nonetheless, reports in a variety of species indicate that some aspects of retinotopic order exist within the optic tract, leading to the suggestion that this “preordering” of retinal axons may play a role in the formation of the mature tectal map. A satisfactory account of pretarget order must provide the mechanism by which such axon order develops. Insofar as this mechanism must ultimately be determined genetically, the mouse suggests itself as the natural species in which to pursue these studies. Quantitative and repeatable methods are required to assess the contribution of candidate genes in mouse models. For these reasons, we have undertaken a quantitative study of the degree of retinotopic order within the optic tract and nerve of wild‐type mice both before and after the development of the retinotectal map. Our methods are based on tract tracing using lipophilic dyes, and our results indicate that there is a reestablishment of dorsoventral but not nasotemporal retinal order when the axons pass through the chiasm and that this order is maintained throughout the subsequent tract. Furthermore, this dorsoventral retinotopic order is well established by the day after birth, long before the final target zone is discernible within the tectum. We conclude that pretarget sorting of axons according to origin along the dorsoventral axis of the retina is both spatially and chronologically appropriate to contribute to the formation of the retinotectal map, and we suggest that these methods be used to search for the molecular basis of such order by using available mouse genetic models. J. Comp. Neurol. 491:305–319, 2005. © 2005 Wiley‐Liss, Inc.
Spatiotemporal expression of GM1 in murine medial pallial neural progenitor cells
Authors: Liour Sean S. , Dinkins Michael B. , Su Chen‐Ying , Yu Robert K.
Published: September 2005

The expression of gangliosides is developmentally regulated in the central nervous system. The expression of GM1 in the neural progenitor cells of the telencephalonic ventricular zone (VZ) has been reported in several studies. However, information on the spatial and temporal regulation of GM1 expression in the VZ is still lacking. In this study, we characterized the expression of GM1 in the developing mouse telencephalon. At E13, GM1 is expressed in neuronal cells as well as in the VZ. The initial expression of GM1 in the VZ is restricted to regions close to the medial pallium. Fluorescence‐activated cell sorting (FACS) analysis and characterization of E14 GM1‐positive cells showed that they contain progenitor cells that proliferate in response to epidermal growth factor (EGF) and/or basic fibroblast growth factor (bFGF) stimulation. The results obtained from quantitative gene expression analysis of region‐specific genes (Emx1, Lhx2, Ngn1, Ngn2, Pax6, Dlx2, Gsh2, Mash1, and Nkx2.1), using real‐time polymerase chain reaction indicate that FACS of GM1‐expressing cells in the fetal forebrain enriches for the medial pallial neural progenitor cells. J. Comp. Neurol. 491:330–338, 2005. © 2005 Wiley‐Liss, Inc.
Identification of roughskin newt medullary vasotocin target neurons with a fluorescent vasotocin conjugate
Authors: Lewis Christine M. , Dolence E. Kurt , Hubbard Catherine S. , Rose James D.
Published: September 2005

Arginine8 vasotocin (AVT), a neurohypophyseal peptide in nonmammalian vertebrates, plays a key role in the regulation of social behaviors related to reproduction. In male roughskin newts (Taricha granulosa), AVT is an important facilitator of several reproductive behaviors, including courtship clasping of females. Although AVT is known to act in certain brain regions and AVT receptors have been localized to some extent, specific target neurons for this peptide have not been identified in any species. Internalization of a receptor‐specific conjugate of AVT and the fluorescent dye Oregon green was used to identify AVT target cells in the medulla of male roughskin newts. Medullary neurons are of interest because they appear to mediate facilitation of clasping by AVT. Direct application of AVT‐Oregon green to the fourth ventricular surface of the medulla in vivo resulted in conjugate internalization by a widespread population of medullary neurons, particularly in the medial reticular formation and nuclei of cranial nerves V, VII, VIII, IX, and X. Some fourth‐ventricle ependymal cells were also labeled. Reticulospinal neurons, which play an important role in clasping, were identified by retrograde labeling with tetramethylrhodamine dextran amine. AVT‐Oregon green was internalized by 72% of these neurons. These results show that AVT can directly affect a very large and diverse medullary neuronal population, which may underlie the peptide's role in multiple neuroendocrinological processes, including autonomic and behavioral regulation. Selectivity of the AVT action may arise through interactions between AVT and steroids such as corticosterone. J. Comp. Neurol. 491:381–389, 2005. © 2005 Wiley‐Liss, Inc.
Performance analysis of multiroute packet combining scheme for real‐time communications in wireless multihop networks
Authors: Hirayama Yasuhiro , Nakagawa Nobuyuki , Okada Hiraku , Yamazato Takaya , Katayama Masaaki
Published: September 2005

In this research, real‐time packet communications on wireless multihop networks is considered. Since the communications quality is substantially degraded by packet delay in real‐time packet communications, packet retransmission is not usually used. In order to suppress the effect of packet errors in the communications channel on communications quality in such cases, this paper proposes an application of a multiroute packet combining scheme on a wireless multihop network. The performance of the proposed scheme depends on the time required for transmission of a packet on each route and the start time of packet combining at the destination node, in addition to the number of transmitted duplicate packets at the source node. In order to evaluate the constantly changing system performance from the viewpoint of the quality of service (QoS) required in real‐time communications, the distribution function of the time needed for attaining a certain required packet error rate and the average packet error rate attainable at a certain time are analytically derived. From numerical examples, it is proven that there exists a number of transmitted duplicate packets minimizing the required time for attaining the required packet error rate, and also a number of transmitted duplicate packets minimizing the average packet rate attainable within an allowed delay time. © 2005 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 89(1): 34–44, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.20238
A study on multibeam pulse chasing for bistatic radar
Authors: Matsuda Shoji , Hashiguchi Hiroyuki , Fukao Shoichiro
Published: September 2005

To improve the volume search efficiency of a bistatic radar with the transmitting antenna and the receiving antenna positioned apart, a known beam scanning method is pulse chasing that scans the receive beam at high speed in response to the propagation of the transmitted pulses. However, in normal pulse chasing, the receive beam width cannot be narrower than some value in order to receive all of the transmitted pulses without losses. In other words, a limit is the antenna gain cannot be increased. The problem is the receive signal‐to‐noise ratio (SNR) decreases compared to when pulse chasing is not performed. In this paper, we propose multibeam pulse chasing, a beam scanning technique using multiple receive beams based on digital beam forming, as the solution. We show that even if the transmitted pulse width is relatively long, if the number of multibeams is increased, the received SNR does not exhibit a decrease. Furthermore, we study a method to decrease the number of multibeams by dropping a portion of the receive pulses when pulse compression is applied as the transmission and reception methods, and present the computational result of the relationship between the number of multibeams and the received SNR when the Taylor window is applied. © 2005 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 89(1): 11–21, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.20240
Evaluation method of small anechoic chamber by site attenuation distribution using spherical dipole antenna
Authors: Kitani Atsuto , Kuwabara Nobuo , Kawabata Masato , Amemiya Fujio
Published: September 2005

Site attenuation has been evaluated by means of a half‐wave dipole antenna. Since this antenna type requires a size on the order of a half wavelength, it is not suitable for evaluation of small anechoic chambers. In this paper, a method of evaluation of small anechoic chambers using a spherical dipole antenna with a diameter of 15 cm is discussed. First, the spherical dipole antenna is modeled by wire grids and the site attenuation and antenna factor are derived. It is found that in the range of 30 MHz through 1000 MHz the discrepancy between the analytical values and the measured values of the site attenuation is less than ±4 dB, while that of the antenna factor is less than ±2 dB. Next, the site attenuation taking account of the reflection characteristics of the anechoic chamber is analyzed by the ray tracing method. As parameters, the antenna factor and the radiation pattern derived from the wire grid model are used for the antenna characteristics, and the reflection coefficient derived from the multilayer plane approximation method is used for the reflection characteristics of the absorber. It is found that the discrepancy between the analytical values and the measured values for the site attenuation distribution at a frequency of 600 MHz is less than ±3 dB, and the ray tracing method is found useful for the analysis of the site attenuation distribution using a spherical dipole antenna. Further, when the new approach is applied to a small anechoic chamber in which absorbers with different characteristics are included, the present method is found effective for evaluation of the areas with good properties and of the effect of the absorbers. © 2005 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 89(1): 1–10, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.20255
The introduction of social adaptation within evacuation modelling
Authors: Gwynne S. , Galea E. R. , Lawrence P. J.
Published: September 2005

In recent history, a number of tragic events have borne a consistent message; the social structures that existed prior to and during the evacuation significantly affected the decisions made and the actions adopted by the evacuating population in response to the emergency. This type of influence over behaviour has long been neglected in the modelling community. This paper is an attempt to introduce some of these considerations into evacuation models and to demonstrate their impact. To represent this type of behaviour within evacuation models a mechanism to represent the membership and position within social hierarchies is established. In addition, individuals within the social groupings are given the capacity to communicate relevant pieces of data such as the need to evacuate—impacting the response time—and the location of viable exits—impacting route selection. Furthermore, the perception and response to this information is also affected by the social circumstances in which individuals find themselves. Copyright © 2005 John Wiley & Sons, Ltd.
A role for endogenous reverse transcriptase in tumorigenesis and as a target in differentiating cancer therapy
Authors: Sinibaldi‐Vallebona Paola , Lavia Patrizia , Garaci Enrico , Spadafora Corrado
Published: September 2005

An unexpected result emerging from completion of the genome sequencing project is that a large portion of mammalian genomes is constituted by retrotransposons. A large body of published data supports the conclusion that retrotransposons are biologically active elements and indicates that retrotransposition is an ongoing process in mammalian genomes. Retroelements can act as insertional mutagens altering the coding integrity of genes and, recently, have been found to also affect the expression of cellular genes at the epigenetic level: in this light, they are a potential threat in that these events can trigger the onset of several pathologies including cancer. Retroelement genes, and particularly the gene coding for reverse transcriptase (RT), are typically expressed at high levels in transformed cells and tumors. In recent work, we have found that drug‐mediated inhibition of the endogenous RT activity, or silencing of expression of active retrotransposons of the LINE‐1 family by RNA interference, down‐regulate cell growth and induce the activation of differentiating functions in several cancer cell lines. Moreover, the inhibition of endogenous RT activity in vivo antagonizes the growth of human tumors in animal models. In this review, we discuss newly emerging concepts on the role of retrotransposons and suggest that an abnormally high level of the RT activity that they encode may contribute to the loss of control in the proliferation and differentiation programs typical of transformed cells. In this light, RT‐coding elements may be regarded as promising targets in the development of novel, differentiation‐inducing approaches to cancer therapy. © 2005 Wiley‐Liss, Inc.
Genome-Wide Response of the Human Hep3B Hepatoma Cell to Proinflammatory Cytokines, From Transcription to Translation *
Authors: Coulouarn Cédric , Lefebvre Grégory , Daveau Romain , Letellier Franck , Hiron Martine , Drouot Laurent , Daveau Maryvonne , Salier Jean-Philippe
Published: September 2005

Given the unknown timing of the onset of an acute systemic inflammation in humans, the fine tuning of cascades and pathways involved in the associated hepatocyte response cannot be appraised

in vivo

. Therefore, the authors used a genome-wide and kinetic analysis in the human Hep3B hepatoma cell line challenged with a conditioned medium from bacterial lipopolysaccharide-stimulated macrophages. A complete coverage of the liver transcriptome disclosed 648 mRNAs whose change in abundance allowed for their clustering in mRNA subsets with an early, intermediate, or late regulation. The contribution of transcription, stability, or translation was appraised with genome-wide studies of the changes in nuclear primary transcripts, mRNA decay, or polysome-associated mRNAs. A predominance of mRNAs with decreased stability and the fact that translation alone controls a significant number of acute phase–associated proteins are prominent findings. Transcription and stability act independently or, more rarely, cooperate or even counteract in a gene-by-gene manner, which results in a unidirectional change in mRNA abundance. Waves of mRNAs for groups of functionally related proteins are up- or downregulated in an ordered fashion. This includes an early regulation of transcription-associated proteins, an intermediate repression of detoxication and metabolism proteins, and finally an enhanced translation and transport of a number of membranous or secreted proteins along with an enhanced protein degradation.
In conclusion
, this study provides a comprehensive and simultaneous overview of events in the human hepatocyte during the inflammatory acute phase.

Supplementary material for this article can be found on the H

epatology

website

(
http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html
). (Hepatology 2005;42:946–955.)
Hepatitis C Virus Inhibits Intracellular Interferon Alpha Expression in Human Hepatic Cell Lines *
Authors: Zhang Ting , Lin Rong-Tuan , Li Yuan , Douglas Steven D. , Maxcey Catherine , Ho Chun , Lai Jian-Ping , Wang Yan-Jian , Wan Qi , Ho Wen-Zhe
Published: September 2005

The chronicity of hepatitis C virus (HCV) infection raises the question of how HCV is able to persist in hepatic cells. We show that human primary hepatocytes and human hepatic cell lines (Huh7 and HepG2) spontaneously produce interferon (IFN)-α that is inhibited in the HCV replicon cells (Huh.8 and FCA-1). Silencing IFN-α gene expression by IFN-α small interfering RNA (siRNA) in the HCV replicon cells resulted in increased HCV replicon expression. The activation of IFN-α expression by interferon regulatory factor (IRF-7) led to the inhibition of HCV replicon expression, whereas the anti–IFN-α receptor antibody could partially block IRF-7–mediated HCV replicon inhibition. In addition, the blockade of IFN-α receptor by anti–IFN-α receptor antibody on the replicon cells increased HCV replicon expression. Among the HCV nonstructural (NS) proteins tested, NS5A is the most potent inhibitor of IFN-α expression by the hepatic cells. Investigation of the mechanism of HCV action on IFN-α showed that IRF-7–induced IFN-α promoter activation was inhibited in the HCV replicon cells. Furthermore, IRF-7 expression was restricted in the HCV replicon cells.
In conclusion
, we provide direct evidence that HCV undermines the intracellular innate immunity of the target cells, which may account for HCV persistence in hepatic cells. (Hepatology 2005;42:00–00.) (Hepatology 2005;42:819–827.)
Intrahepatic CD8+ T-Cell Failure During Chronic Hepatitis C Virus Infection *
Authors: Spangenberg Hans Christian , Viazov Sergei , Kersting Nadine , Neumann-Haefelin Christoph , McKinney Denise , Roggendorf Michael , von Weizsäcker Fritz , Blum Hubert E. , Thimme Robert
Published: September 2005

The precise mechanisms responsible for the failure of intrahepatic hepatitis C virus (HCV)-specific CD8+ T cells to control the virus during persistent infection have not been fully defined. We therefore studied the CD8+ T-cell response in 27 HLA-A2–positive patients using four previously well-defined HLA-A2–restricted HCV epitopes. The corresponding HCV sequences were determined in several patients and compared with the intrahepatic HCV-specific CD8+ T-cell response. The results of the study indicate: (1) intrahepatic HCV-specific CD8+ T cells are present in the majority of patients with chronic HCV infection and overlap significantly with the response present in the peripheral blood. (2) A large fraction of intrahepatic HCV-specific CD8+ T cells are impaired in their ability to secrete interferon γ (IFN-γ). This dysfunction is specific for HCV-specific CD8+ T cells, since intrahepatic Flu-specific CD8+ T cells readily secrete this cytokine. (3) T-cell selection of epitope variants may have occurred in some patients. However, it is not an inevitable consequence of a functional virus-specific CD8+ T-cell response, since several patients with IFN-γ–producing CD8+ T-cell responses harbored HCV sequences identical or cross-reactive with the prototype sequence. (4) The failure of intrahepatic virus–specific CD8+ T cells to sufficiently control the virus occurs despite the presence of virus-specific CD4+ T cells at the site of disease.
In conclusion
, different mechanisms contribute to the failure of intrahepatic CD8+ T cells to eliminate HCV infection, despite their persistence and accumulation in the liver. (Hepatology 2005;42:828–837.)
Antioxidative Function of L-FABP in L-FABP Stably Transfected Chang Liver Cells *
Authors: Wang Guqi , Gong Yuewen , Anderson Judy , Sun Dongfeng , Minuk Gerald , Roberts Michael S. , Burczynski Frank J.
Published: September 2005

Liver fatty acid binding protein (L-FABP) contains amino acids that are known to possess antioxidant function. In this study, we tested the hypothesis that L-FABP may serve as an effective endogenous cytoprotectant against oxidative stress. Chang liver cells were selected as the experimental model because of their undetectable L-FABP mRNA level. Full-length L-FABP cDNA was subcloned into the mammalian expression vector pcDNA3.1 (pcDNA-FABP). Chang cells were stably transfected with pc-DNA-FABP or vector (pcDNA3.1) alone. Oxidative stress was induced by incubating cells with 400 μmol/L H2O2 or by subjecting cells to hypoxia/reoxygenation. Total cellular reactive oxygen species (ROS) was determined using the fluorescent probe DCF. Cellular damage induced by hypoxia/reoxygenation was assayed by lactate dehydrogenase (LDH) release. Expression of L-FABP was documented by regular reverse transcription polymerase chain reaction (RT-PCR), real-time RT-PCR, and Western blot. The pcDNA-FABP–transfected cells expressed full-length L-FABP mRNA, which was absent from vector-transfected control cells. Western blot showed expression of 14-kd L-FABP protein in pcDNA-FABP–transfected cells, but not in vector-transfected cells. Transfected cells showed decreased DCF fluorescence intensity under oxidative stress (H2O2 and hypoxia/reoxygenation) conditions versus control in inverse proportion to the level of L-FABP expression. Lower LDH release was observed in the higher L-FABP–expressed cells in hypoxia/reoxygenation experiments.
In conclusion
, we successfully transfected and cloned a Chang liver cell line that expressed the L-FABP gene. The L-FABP–expressing cell line had a reduced intracellular ROS level versus control. This finding implies that L-FABP has a significant role in oxidative stress. (Hepatology 2005;42:871–879.)
Altered Monocyte Responses to Defined TLR Ligands in Patients With Primary Biliary Cirrhosis *
Authors: Mao Tin Ky , Lian Zhe-Xiong , Selmi Carlo , Ichiki Yasunori , Ashwood Paul , Ansari Aftab A. , Coppel Ross L. , Shimoda Shinji , Ishibashi Hiromi , Gershwin Eric M.
Published: September 2005

The role of the adaptive immune response, with regard to the development of autoantibodies, has been extensively studied in primary biliary cirrhosis (PBC). However, the importance of innate immunity has been noted only recently. Based on the proposed role of microorganisms in the pathogenesis of the disease, we hypothesize that patients with PBC possess a hyper-responsive innate immune system to pathogen-associated stimuli that may facilitate the loss of tolerance. To address this issue, we isolated peripheral blood monocytes from 33 patients with PBC and 26 age-matched healthy controls and stimulated such cells

in vitro

with defined ligands for toll-like receptor (TLR) 2 (lipoteichoic acid; LTA), TLR3 (polyIC), TLR4 (lipopolysaccharide; LPS), TLR5 (flagellin), and TLR9 (CpG-B). Supernatant fluids from the cultures were analyzed for levels of 5 different pro-inflammatory cytokines, interleukin (IL)-1β, IL-6, IL-8, IL-12p70, and TNF-α. After

in vitro

challenge with TLR ligands, PBC monocytes produced higher relative levels of pro-inflammatory cytokines, particularly IL-1β, IL-6, IL-8, and TNF-α, compared with controls.
In conclusion
, monocytes from patients with PBC appear more sensitive to signaling via select TLRs, resulting in secretion of selective pro-inflammatory cytokines integral to the inflammatory response that may be critical in the breakdown of self-tolerance. (Hepatology 2005;42:802–808.)
Large-Scale Search of Single Nucleotide Polymorphisms for Hepatocellular Carcinoma Susceptibility Genes in Patients With Hepatitis C *
Authors: Kato Naoya , Ji Guijin , Wang Yue , Baba Masanori , Hoshida Yujin , Otsuka Motoyuki , Taniguchi Hiroyoshi , Moriyama Masaru , Dharel Narayan , Goto Tadashi , Shao Run-Xuan , Matsuura Tadashi , Ishii Keisuke , Shiina Shuichiro , Kawabe Takao , Muramatsu Masaaki , Omata Masao
Published: September 2005

Hepatitis C virus (HCV) infection is a major risk factor for developing hepatocellular carcinoma (HCC). The host genetic factors that are involved in the development of HCC in patients with HCV infection remain to be investigated. To search for single nucleotide polymorphisms (SNPs) in HCC susceptibility genes, 393 SNPs in 171 candidate genes were examined in 188 Japanese patients with chronic HCV infection, including 77 patients with HCC. HCC-related SNPs were then examined in another 188 patients (including 93 patients with HCC) with chronic HCV infection. Haplotype analyses of HCC-related genes were performed in a total of 376 patients. Of the 393 SNPs, 31 SNPs in 29 genes were significantly associated with HCC based on an initial screening (

P

< .05). Of these 31 SNPs, 3 SNPs of 3 genes (SCYB14, GFRA1, and CRHR2) were significantly associated with HCC in a secondary screening. Haplotype analyses of these 3 genes identified 2 haplotype blocks associated with HCC.
In conclusion
, these SNPs and haplotypes located in the SCBY14, CRHR2, and GFRA1 genes will be used as markers to identify a subgroup of Japanese patients with chronic HCV infection who are at high risk of developing HCC.

Supplementary material for this article can be found on the Hepatology website

(
http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html
). (Hepatology 2005;42:846–853.)
Alendronate Improves Bone Mineral Density in Primary Biliary Cirrhosis: A Randomized Placebo-Controlled Trial * #
Authors: Zein Claudia O. , Jorgensen Roberta A. , Clarke Bart , Wenger Doris E. , Keach Jill C. , Angulo Paul , Lindor Keith D.
Published: September 2005

Bone loss is a well-recognized complication of primary biliary cirrhosis (PBC). Although it has been suggested that alendronate might improve bone mineral density (BMD) in PBC, no randomized placebo-controlled trial has been conducted. The primary aim of this study was to compare the effects of alendronate versus placebo on BMD and biochemical measurements of bone turnover in patients with PBC-associated bone loss. We conducted a double-blinded, randomized, placebo-controlled trial. Patients with a PBC and BMD

t

score of less than −1.5 were randomized to receive 70 mg per week of alendronate or placebo over 1 year. BMD of the lumbar spine and proximal femur were measured at entry and at 1 year. Changes from baseline in BMD and biochemical measurements of bone turnover were assessed. Thirty-four patients were enrolled. Seventeen patients were randomized to each arm. After 1 year, a significantly larger improvement (

P

= .005) in spine BMD was observed in the alendronate group (0.09 ± 0.03 g/cm2 SD from baseline) compared with the placebo group (−0.003 ± 0.02 g/cm2 SD from baseline). A larger improvement (

P

= .046) was also observed in the femoral BMD of alendronate patients versus placebo. BMD changes were independent of concomitant estrogen therapy. The rate of adverse effects was similar in both groups.
In conclusion
, in patients with PBC-related bone loss, alendronate significantly improves BMD compared with placebo. Although in this study oral alendronate appears to be well tolerated in patients with PBC, larger studies are needed to formally evaluate safety. (Hepatology 2005;42:762–771.)
Nuclear Translocation of UDCA by the Glucocorticoid Receptor Is Required to Reduce TGF-β1–Induced Apoptosis in Rat Hepatocytes *
Authors: Solá Susana , Amaral Joana D. , Castro Rui E. , Ramalho Rita M. , Borralho Pedro M. , Kren Betsy T. , Tanaka Hirotoshi , Steer Cifford J. , Rodrigues Cecília M. P.
Published: September 2005

Ursodeoxycholic acid (UDCA) inhibits classical mitochondrial pathways of apoptosis by either directly stabilizing mitochondrial membranes or modulating specific upstream targets. Furthermore, UDCA regulates apoptosis-related genes from transforming growth factor β1 (TGF-β1)–induced hepatocyte apoptosis by a nuclear steroid receptor (NSR)–dependent mechanism. In this study, we further investigated the potential role of the glucocorticoid receptor (GR) in the antiapoptotic function of UDCA. Our results with short interference RNA (siRNA) technology confirmed that UDCA significantly reduces TGF-β1–induced apoptosis of primary rat hepatocytes through a GR-dependent effect. Immunoprecipitation assays and confocal microscopy showed that UDCA enhanced free GR levels with subsequent GR nuclear translocation. Interestingly, when a carboxy-terminus deleted form of GR was used, UDCA no longer increased free GR and/or GR translocation, nor did it protect against TGF-β1–induced apoptosis. In co-transfection experiments with GR response element reporter and overexpression constructs, UDCA did not enhance the transactivation of GR with TGF-β1. Finally, using a flourescently labeled UDCA molecule, the bile acid appeared diffuse in the cytosol but was aggregated in the nucleus of hepatocytes. Both siRNA assays and transfection experiments with either wild-type or mutant forms of GR showed that nuclear trafficking occurs through a GR-dependent mechanism.
In conclusion
, these results further clarify the antiapoptotic mechanism(s) of UDCA and suggest that GR is crucial for the nuclear translocation of this bile acid for reducing apoptosis. (Hepatology 2005;42:925–934.)