bluuebunny/crossref_metadata_2025 huggingface dataset:
Does activity level in online support groups for distressed adolescents determine emotional relief
Authors: Barak Azy , Dolev-Cohen Michal
Published: August 2006

Online support groups are widely used for numerous types of distress areas, but relatively little has been empirically examined to date in regard to their effectiveness in providing emotional relief to participants as claimed. The current study aimed at testing a possible moderator affecting participants' emotional relief when using an online support group: the degree of active involvement. This subject was explored by investigating the number of main and response messages that 20 randomly selected participants posted, as well as the number of replies they received, over the course of three months of participation in an open, online support group intended for suicidal and severely distressed adolescents. Level of distress was measured by a thematic analysis of main messages posted by the participants that was conducted by three pre‐trained, expert judges. Results revealed that although the level of participants’ distress did not change over time, on the average, it was significantly correlated with activity level: the higher the number of posts and replies, the lower the level of distress in following months. Implications of these findings for the application and facilitation of online support groups are discussed.
Technically incompetent or generally misguided: Learning from a failed counselling research project
Authors: West William , Hanley Terry
Published: August 2006

In a world that is becoming consistently more dependent upon technology, this paper intends to urge researchers to be appropriately cautious when designing projects that utilise new media. It does this by frankly discussing a research project that turned out to be a resounding failure due to a lack of forward thinking. The study intended to recreate face‐to‐face interviews with UK‐based Quaker counsellors using email to contact counterparts in the US. A discussion regarding this failure is entered into and suggestions for avoiding similar mishaps in the future are made. Finally the culture of researchers only reporting success stories is challenged.
Developing youth‐friendly online counselling services in the United Kingdom: A small scale investigation into the views of practitioners
Authors: Hanley Terry
Published: August 2006

This study focused upon the development of online counselling services for young people in the UK. It used online forums to host an asynchronous focus group with the intention of bringing together the views of a small sample of counsellors and counsellors in training regarding the subject matter. The focus group lasted a one‐month period and initiated 10 threads of discussion and received 41 message postings. These dialogues were analysed using a Grounded Theory approach. Findings suggested that although there is a great potential for offering therapy in this medium, services need to be appropriately regulated and good practice promoted. Issues around where the parameters of regulation should lie are discussed and recommendations for the minimum requirements of training or experience that counsellors working in this field should possess are made.
Using technology to serve patients and practitioners: A comprehensive tobacco‐cessation program for cancer patients
Authors: Mallen Michael J. , Blalock Janice A. , Cinciripini Paul M.
Published: August 2006

The infusion of technology into clinical practice has increased in recent years. Tobacco use has been reported to be the most preventable cause of illness and death in our society. The following article details the use of technology in the development of a comprehensive, institution‐wide, tobacco‐cessation program at a large cancer centre. Technologies, including Internet‐based data collection, electronic database systems, asynchronous‐email communication, and telephone counselling, were utilized to support the program's infrastructure, to coordinate the patient's care within the institution, and to deliver therapeutic services. Preliminary data from the clinical program are presented. A discussion about incorporating technology into clinical practice is presented, including suggestions for practitioners who may be interested in expanding or extending their services with new technologies.
Virtue out of necessity? Reflections on a telephone supervision relationship
Authors: Robson Maggie , Whelan Linda
Published: August 2006

This paper reflects upon the usefulness of supervision conducted over the telephone based on the experience of a supervisor and one of her supervisees. The development of the supervision relationship is charted with reference to the Hawkins and Shohet () Developmental Model of Supervision and both authors give their account of the developing relationship. The role of the supervisor is discussed in relation to the literature. The challenges and benefits to the supervisory relationship are considered when a previously face‐to‐face relationship had to change to one conducted over the phone. The paper concludes that the quality of the relationship was maintained but wonders if this was only possible because of the strength of the relationship that had been established face‐to‐face.
Feasibility of telemedicine intervention for childhood depression
Authors: Nelson Eve-Lynn , Barnard Martha , Cain Sharon
Published: August 2006

Context: Childhood depression is associated with high short‐term and long‐term morbidity. Cognitive‐behavioural therapy (CBT) for depression has been supported as an effective treatment in the traditional clinic setting. But many families face barriers to depression treatment, including distance to providers, provider shortages, stigma, and other challenges. Telemedicine or interactive televideo offers an innovative way to provide therapy at a distance. The family and therapist see and hear each other in real‐time using videoconference.

Objective: This pilot project evaluated the same cognitive‐behavioural therapy treatment for childhood depression in two different settings — face‐to‐face (F2F) or over interactive televideo (ITV).

Participants: Twenty‐eight children with depression and their caregivers completed an eight‐session, empirically supported CBT course for parent and child.

Results: All parent and child CBT skills were implemented successfully over telemedicine. An 82% remission from depression was observed immediately post‐treatment and this rate did not significantly differ across groups (χ2(n=28) = 2.19, NS).

Conclusion: In this feasibility study, all therapy elements were successfully implemented in the telemedicine context. Compared with the same protocol implemented face‐to‐face, cognitive behavioural therapy delivered over interactive televideo led to a similar rate of remission from depression. This supports continued research on telemedicine to help bridge the gap between high need in mental health care and low access, particularly for disorders such as childhood depression.
A convenient cell fusion assay for the study of SARS‐CoV entry and inhibition
Authors: Sha YongGang , Wu YingLiang , Cao ZhiJian , Xu XiuLing , Wu WenLan , Jiang DaHe , Mao Xin , Liu Hui , Zhu Ying , Gong Rui , Li WenXin
Published: August 2006

SARS‐CoV spike (S) protein‐mediated cell fusion is important for the viral entry mechanism and identification of SARS‐CoV entry inhibitors. In order to avoid the high risks involved in handling SARS‐CoV and to facilitate the study of viral fusion mechanism, we established the cell lines: SR‐COS7 cells that stably express both SARS‐CoV S protein and red fluorescence protein, R‐COS7 cells that stably express red fluorescence protein, and AG‐COS7 cells that stably express both ACE2 and green fluorescence protein, respectively. When SR‐COS7 cells or R‐COS7 cells were cocultured with AG‐COS7 cells, syncytia with yellow fluorescence were conveniently observed after 12 h in SR‐COS7 cells plus AG‐COS7 cells, but not in R‐COS7 cells plus AG‐COS7 cells. The cell‐to‐cell fusion efficiency was simply determined for quantitative analysis based on the number of syncytium detected by flow cytometry. Such new cell‐to‐cell fusion model was further assessed by the potent HR2 peptide inhibitor, which led to the obvious decrease of the cell‐to‐cell fusion efficiency. The successful fusion and inhibition of cell‐based binding assay shows that it can be well used for the study of SARS‐CoV entry and inhibition.
iubmb Life, 58: 480 ‐ 486, 2006
The β12‐β13 loop of protein phosphatase‐1 is involved in activity regulation
Authors: Xie Xiujie , Xue Chengzhe , Huang Wei , Wei Qun
Published: August 2006

Protein phosphatase‐1 (PP1) is a member of the eukaryotic serine/threonine phosphatase gene family. The β12‐β13 loop is a prominent non‐conserved region among the family, and extends from the surface and overhangs the active site. To investigate the function of the β12‐β13 loop of PP1, we systematically examined all residues by site‐directed deletion mutation. Deleting residues Y272, E275 or F276, caused enzyme activity to increase, while deleting residue C273, caused enzyme activity to decrease, when G274 was deleted no remarkable activity increase was observed, and almost all activity was lost when D277, N278 or A279 were deleted. These observations implied that each amino acid has a different effect on the activity of phosphatase, which may result from their different side chains and locations. The activity change of these PP1 mutants, from Y272 to A279, was comparable to that of calcineurin mutants, from Y311 to K318. By comparison, except for D277 (N316) and A279 (K318) of PP1 (calcineurin), each pair of equivalent mutants in the β12‐β13 loop of PP1 and calcineurin have coincident activity change although they are non‐conserved, which suggests that the β12‐β13 loop of PP1 is not only involved in activity regulation but also involved in regulation similar to that of calcineurin.
iubmb Life, 58: 487 ‐ 492, 2006
Sphingosine and ceramide signalling in apoptosis
Authors: Woodcock Joanna
Published: August 2006

The sphingomyelin pathway is activated in response to many apoptotic stimuli leading to the accumulation of breakdown products ceramide and sphingosine. Ceramide has received much attention as an apoptotic second messenger whereas sphingosine has largely been overlooked as a mediator of apoptosis. Recent studies however provide strong clues to a second messenger role for sphingosine and identification of effectors reveal a possible mechanism involved in sphingosine‐mediated cell death. This mini‐review overviews the current knowledge of the role of ceramide and sphingosine in apoptosis and discusses their biological effects. The review attempts to reconcile the apoptotic effects of these lipids with the downstream effectors that have been identified.
iubmb Life, 58: 462 ‐ 466, 2006
Phospholipid signalling through phospholipase D and phosphatidic acid
Authors: Cazzolli Rosanna , Shemon Anne N. , Fang Michelle Q. , Hughes William E.
Published: August 2006

Phospholipase D (PLD) hydrolyzes the phosphodiester bond of the predominant membrane phospholipid, phosphatidylcholine producing phosphatidic acid and free choline. This activity can participate in signal transduction pathways and impact on vesicle trafficking for secretion and endocytosis, as well as receptor signalling. Phospholipids can regulate PLD activity directly, through specific intermolecular interactions, or indirectly, through their effect on the localization or activity of PLD's protein effectors. This short review highlights these various phospholipid inputs into the regulation of PLD activity and also reviews potential roles for PLD‐generated phosphatidic acid, particularly a mechanism by which the phospholipid may participate in the process of vesicular trafficking.
iubmb Life, 58: 457 ‐ 461, 2006
Regulation of phosphoinositide signaling by the inositol polyphosphate 5‐phosphatases
Authors: Astle Megan V. , Seaton Gillian , Davies Elizabeth M. , Fedele Clare G. , Rahman Parvin , Arsala Laima , Mitchell Christina A.
Published: August 2006

Phosphoinositide signaling molecules control cellular growth, proliferation and differentiation, intracellular vesicle trafficking, and cytoskeletal rearrangement. The inositol polyphosphate 5‐phosphatase family remove the D‐5 position phosphate from PtdIns(3,4,5)P3, PtdIns(4,5)P2 and PtdIns(3,5)P2 forming PtdIns(3,4)P2, PtdIns(4)P and PtdIns(3)P respectively. This enzyme family, comprising ten mammalian members, exhibit seemingly non‐redundant functions including the regulation of synaptic vesicle recycling, hematopoietic cell function and insulin signaling. Here we highlight recently established insights into the functions of two well characterized 5‐phosphatases OCRL and SHIP2, which have been the subject of extensive functional studies, and the characterization of recently identified members, SKIP and PIPP, in order to highlight the diverse and complex functions of this enzyme family.
iubmb Life, 58: 451 ‐ 456, 2006
Character sheaves on disconnected groups, VIII
Authors: Lusztig G.
Published: August 2006

In this paper we continue the study of character sheaves on a reductive group. To each subset of the set of simple reflections in the Weyl group we associate an algebra of the same kind as an Iwahori Hecke algebra with unequal parameters in terms of parabolic character sheaves. We also prove a Mackey type formula for character sheaves. We define a duality operation for character sheaves. We also prove a quasi-rationality property for character sheaves.
Character sheaves on disconnected groups, IX
Authors: Lusztig G.
Published: August 2006

We associate a two-sided cell to any (parabolic) character sheaf. We study the interaction between the duality operator for character sheaves and the operation of “twisted induction".
A Cleavable Propeptide InfluencesToxoplasmaInfection by Facilitating the Trafficking and Secretion of the TgMIC2–M2AP Invasion Complex
Authors: Harper Jill M. , Huynh My-Hang , Coppens Isabelle , Parussini Fabiola , Moreno Silvia , Carruthers Vern B.
Published: August 2006

Propeptides regulate protein function and trafficking in many eukaryotic systems and have emerged as important features of regulated secretory proteins in parasites of the phylum Apicomplexa. Regulated protein secretion from micronemes and host cell invasion are inextricably linked and essential processes for the apicomplexan parasite Toxoplasma gondii. TgM2AP is a propeptide-containing microneme protein found in a heterohexameric complex with the microneme protein TgMIC2, a protein that has a demonstrated fundamental role in gliding motility and invasion. TgM2AP function is also central to these processes, because disruption of TgM2AP (m2apKO) results in secretory retention of TgMIC2, leading to reduced TgMIC2 secretion from the micronemes and impaired invasion. Because the TgM2AP propeptide is predicted to be processed in an intracellular site near where TgMIC2 is retained in m2apKO parasites, we hypothesized that the propeptide and its proteolytic removal influence trafficking and secretion of the complex. We found that proTgM2AP traffics through endosomal compartments and that deletion of the propeptide leads to defective trafficking of the complex within or near this site, resulting in aberrant processing and decreased secretion of TgMIC2, impaired invasion, and reduced virulence in vivo, mirroring the phenotypes observed in m2apKO parasites. In contrast, mutation of several cleavage site residues resulted in normal localization, but it affected the stability and secretion of the complex from the micronemes. Therefore, the propeptide and its cleavage site influence distinct aspects of TgMIC2–M2AP function, with both impacting the outcome of infection.
TheNeurospora crassaWhite Collar-1 dependent Blue Light Response Requires Acetylation of Histone H3 Lysine 14 by NGF-1
Authors: Grimaldi Benedetto , Coiro Pierluca , Filetici Patrizia , Berge Emanuela , Dobosy Joseph R. , Freitag Michael , Selker Eric U. , Ballario Paola
Published: August 2006

Blue light-induced transcription in Neurospora crassa is regulated by the White Collar-1 (WC-1) photoreceptor. We report that residue K14 of histone H3 associated with the light-inducible albino-3 (al-3) promoter becomes transiently acetylated after photoinduction. This acetylation depends on WC-1. The relevance of this chromatin modification was directly evaluated in vivo by construction of a Neurospora strain with a mutated histone H3 gene (hH3K14Q). This strain phenocopies a wc-1 blind mutant and shows a strong reduction of light-induced transcriptional activation of both al-3 and vivid (vvd), another light-inducible gene. We mutated Neurospora GCN Five (ngf-1), which encodes a homologue of the yeast HAT Gcn5p, to generate a strain impaired in H3 K14 acetylation and found that it was defective in photoinduction. Together, our findings reveal a direct link between histone modification and light signaling in Neurospora and contribute to the developing understanding of the molecular mechanisms operating in light-inducible gene activation.
Synaptic Vesicle Mobility and Presynaptic F-Actin Are Disrupted in aN-ethylmaleimide–sensitive Factor Allele ofDrosophila
Authors: Nunes Paula , Haines Nicola , Kuppuswamy Venkat , Fleet David J. , Stewart Bryan A.
Published: August 2006

N-ethylmaleimide sensitive factor (NSF) can dissociate the soluble NSF attachment receptor (SNARE) complex, but NSF also participates in other intracellular trafficking functions by virtue of SNARE-independent activity. Drosophila that express a neural transgene encoding a dominant-negative form of NSF2 show an 80% reduction in the size of releasable synaptic vesicle pool, but no change in the number of vesicles in nerve terminal boutons. Here we tested the hypothesis that vesicles in the NSF2 mutant terminal are less mobile. Using a combination of genetics, pharmacology, and imaging we find a substantial reduction in vesicle mobility within the nerve terminal boutons of Drosophila NSF2 mutant larvae. Subsequent analysis revealed a decrease of filamentous actin in both NSF2 dominant-negative and loss-of-function mutants. Lastly, actin-filament disrupting drugs also decrease vesicle movement. We conclude that a factor contributing to the NSF mutant phenotype is a reduction in vesicle mobility, which is associated with decreased presynaptic F-actin. Our data are consistent with a model in which actin filaments promote vesicle mobility and suggest that NSF participates in establishing or maintaining this population of actin.
Clathrin-dependent Association of CVAK104 with Endosomes and theTrans-Golgi Network
Authors: Düwel Michael , Ungewickell Ernst J.
Published: August 2006

CVAK104 is a novel coated vesicle-associated protein with a serine/threonine kinase homology domain that was recently shown to phosphorylate the β2-subunit of the adaptor protein (AP) complex AP2 in vitro. Here, we demonstrate that a C-terminal segment of CVAK104 interacts with the N-terminal domain of clathrin and with the α-appendage of AP2. CVAK104 localizes predominantly to the perinuclear region of HeLa and COS-7 cells, but it is also present on peripheral vesicular structures that are accessible to endocytosed transferrin. The distribution of CVAK104 overlaps extensively with that of AP1, AP3, the mannose 6-phosphate receptor, and clathrin but not at all with its putative phosphorylation target AP2. RNA interference-mediated clathrin knockdown reduced the membrane association of CVAK104. Recruitment of CVAK104 to perinuclear membranes of permeabilized cells is enhanced by guanosine 5′-O-(3-thio)triphosphate, and brefeldin A redistributes CVAK104 in cells. Both observations suggest a direct or indirect requirement for GTP-binding proteins in the membrane association of CVAK104. Live-cell imaging showed colocalization of green fluorescent protein-CVAK104 with endocytosed transferrin and with red fluorescent protein-clathrin on rapidly moving endosomes. Like AP1-depleted COS-7 cells, CVAK104-depleted cells missort the lysosomal hydrolase cathepsin D. Together, our data suggest a function for CVAK104 in clathrin-dependent pathways between the trans-Golgi network and the endosomal system.
Association of 14-3-3 Proteins to β1-Adrenergic Receptors Modulates Kv11.1 K+Channel Activity in Recombinant Systems
Authors: Tutor Antonio S. , Delpón Eva , Caballero Ricardo , Gómez Ricardo , Núñez Lucía , Vaquero Miguel , Tamargo Juan , Mayor Federico , Penela Petronila
Published: August 2006

We identify a new mechanism for the β1-adrenergic receptor (β1AR)-mediated regulation of human ether-a-go-go–related gene (HERG) potassium channel (Kv11.1). We find that the previously reported modulatory interaction between Kv11.1 channels and 14-3-3ε proteins is competed by wild type β1AR by means of a novel interaction between this receptor and 14-3-3ε. The association between β1AR and 14-3-3ε is increased by agonist stimulation in both transfected cells and heart tissue and requires cAMP-dependent protein kinase (PKA) activity. The β1AR/14-3-3ε association is direct, since it can be recapitulated using purified 14-3-3ε and β1AR fusion proteins and is abolished in cells expressing β1AR phosphorylation–deficient mutants. Biochemical and electrophysiological studies of the effects of isoproterenol on Kv11.1 currents recorded using the whole-cell patch clamp demonstrated that β1AR phosphorylation–deficient mutants do not recruit 14-3-3ε away from Kv11.1 and display a markedly altered agonist-mediated modulation of Kv11.1 currents compared with wild-type β1AR, increasing instead of inhibiting current amplitudes. Interestingly, such differential modulation is not observed in the presence of 14-3-3 inhibitors. Our results suggest that the dynamic association of 14-3-3 proteins to both β1AR and Kv11.1 channels is involved in the adrenergic modulation of this critical regulator of cardiac repolarization and refractoriness.
Valosin-containing Protein (p97) Is a Regulator of Endoplasmic Reticulum Stress and of the Degradation of N-End Rule and Ubiquitin-Fusion Degradation Pathway Substrates in Mammalian Cells
Authors: Wójcik Cezary , Rowicka Maga , Kudlicki Andrzej , Nowis Dominika , McConnell Elizabeth , Kujawa Marek , DeMartino George N.
Published: August 2006

Valosin-containing protein (VCP; p97; cdc48 in yeast) is a hexameric ATPase of the AAA family (ATPases with multiple cellular activities) involved in multiple cellular functions, including degradation of proteins by the ubiquitin (Ub)–proteasome system (UPS). We examined the consequences of the reduction of VCP levels after RNA interference (RNAi) of VCP. A new stringent method of microarray analysis demonstrated that only four transcripts were nonspecifically affected by RNAi, whereas ∼30 transcripts were affected in response to reduced VCP levels in a sequence-independent manner. These transcripts encoded proteins involved in endoplasmic reticulum (ER) stress, apoptosis, and amino acid starvation. RNAi of VCP promoted the unfolded protein response, without eliciting a cytosolic stress response. RNAi of VCP inhibited the degradation of R-GFP (green fluorescent protein) and Ub-G76V-GFP, two cytoplasmic reporter proteins degraded by the UPS, and of α chain of the T-cell receptor, an established substrate of the ER-associated degradation (ERAD) pathway. Surprisingly, RNAi of VCP had no detectable effect on the degradation of two other ERAD substrates, α1-antitrypsin and δCD3. These results indicate that VCP is required for maintenance of normal ER structure and function and mediates the degradation of some proteins via the UPS, but is dispensable for the UPS-dependent degradation of some ERAD substrates.
Invasion of Host Cells bySalmonella typhimuriumRequires Focal Adhesion Kinase and p130Cas
Authors: Shi Jing , Casanova James E.
Published: August 2006

Salmonella typhimurium colonizes the intestinal epithelium by injecting an array of effector proteins into host cells that induces phagocytic uptake of attached bacteria. However, the host molecules targeted by these effectors remain poorly defined. Here, we demonstrate that S. typhimurium induces formation of focal adhesion-like complexes at sites of bacterial attachment and that both focal adhesion kinase (FAK) and the scaffolding protein p130Cas are required for Salmonella uptake. Entry of Salmonella into FAK−/−cells is dramatically impaired and can be restored to control levels by expression of wild-type FAK. Surprisingly, reconstitution of bacterial internalization requires neither the kinase domain of FAK nor activation of c-Src, but does require a C-terminal PXXP motif through which FAK interacts with Cas. Infection of Cas−/−cells is also impaired, and reconstitution of invasiveness requires the central Cas YXXP repeat domain. The invasion defect in Cas−/−cells can be suppressed by overexpression of FAK, suggesting a functional link between FAK and Cas in the regulation of Salmonella invasion. Together, these findings reveal a novel role for focal adhesion proteins in the invasion of host cells by Salmonella.
Mammalian CLASP1 and CLASP2 Cooperate to Ensure Mitotic Fidelity by Regulating Spindle and Kinetochore Function
Authors: Pereira Ana L. , Pereira António J. , Maia Ana R.R. , Drabek Ksenija , Sayas C. Laura , Hergert Polla J. , Lince-Faria Mariana , Matos Irina , Duque Cristina , Stepanova Tatiana , Rieder Conly L. , Earnshaw William C. , Galjart Niels , Maiato Helder
Published: August 2006

CLASPs are widely conserved microtubule plus-end–tracking proteins with essential roles in the local regulation of microtubule dynamics. In yeast, Drosophila, and Xenopus, a single CLASP orthologue is present, which is required for mitotic spindle assembly by regulating microtubule dynamics at the kinetochore. In mammals, however, only CLASP1 has been directly implicated in cell division, despite the existence of a second paralogue, CLASP2, whose mitotic roles remain unknown. Here, we show that CLASP2 localization at kinetochores, centrosomes, and spindle throughout mitosis is remarkably similar to CLASP1, both showing fast microtubule-independent turnover rates. Strikingly, primary fibroblasts from Clasp2 knockout mice show numerous spindle and chromosome segregation defects that can be partially rescued by ectopic expression of Clasp1 or Clasp2. Moreover, chromosome segregation rates during anaphase A and B are slower in Clasp2 knockout cells, which is consistent with a role of CLASP2 in the regulation of kinetochore and spindle function. Noteworthy, cell viability/proliferation and spindle checkpoint function were not impaired in Clasp2 knockout cells, but the fidelity of mitosis was strongly compromised, leading to severe chromosomal instability in adult cells. Together, our data support that the partial redundancy of CLASPs during mitosis acts as a possible mechanism to prevent aneuploidy in mammals.
Insulin Signaling Diverges into Akt-dependent and -independent Signals to Regulate the Recruitment/Docking and the Fusion of GLUT4 Vesicles to the Plasma Membrane
Authors: Gonzalez Eva , McGraw Timothy E.
Published: August 2006

Insulin modulates glucose disposal in muscle and adipose tissue by regulating the cellular redistribution of the GLUT4 glucose transporter. Protein kinase Akt/PKB is a central mediator of insulin-regulated translocation of GLUT4; however, the GLUT4 trafficking step(s) regulated by Akt is not known. Here, we use acute pharmacological Akt inhibition to show that Akt is required for insulin-stimulated exocytosis of GLUT4 to the plasma membrane. Our data also suggest that the AS160 Rab GAP is not the only Akt target required for insulin-stimulated GLUT4 translocation. Using a total internal reflection microscopy assay, we show that Akt activity is specifically required for an insulin-mediated prefusion step involving the recruitment and/or docking of GLUT4 vesicles to within 250 nm of the plasma membrane. Moreover, the insulin-stimulated fusion of GLUT4 vesicles with the plasma membrane can occur independently of Akt activity, although based on inhibition by wortmannin, it is dependent on phosphatidylinositol 3′ kinase activity. Hence, to achieve full redistribution of GLUT4 into the plasma membrane, insulin signaling bifurcates to independently regulate both fusion and a prefusion step(s).
Induction of squamous cell carcinoma of forestomach in diabetic rats by single alloxan treatment
Authors: Kodama Yasushi , Ozaki Kiyokazu , Sano Tomoya , Matsuura Tetsuro , Akagi Hiroyuki , Narama Isao
Published: August 2006

Male rats of WBN/Kob strain are one of the diabetic model animals and develop long‐lasting diabetic symptoms and some complications from about 40 weeks of age without any treatment. A single intravenous dose of alloxan, a non‐genotoxic diabetogenic chemical, frequently induced proliferative lesions of squamous epithelium in tongue, esophagus and forestomach of male and female WBN/Kob rats, and hastened the onset and acceleration of diabetic conditions. Histopathologically, proliferative changes of squamous cell of forestomach varied with the severity of hyperplasia in alloxan‐treated rats (100% of 31 males and 94.1% of 17 females) and progressed to SCC in approximately 20% of all rats. Metastasis to regional lymph nodes was also observed in two cases. Proliferative changes were most severe in the forestomach and were constantly accompanied with chronic suppurative inflammation of the mucosal epithelium with infection of filamentous fungi and/or bacterial colonies. In contrast, forestomach of the spontaneously diabetic male rats showed only slight hyperplasia of the mucosal epithelium confined to the limiting ridge in approximately 30% of the cases. All non‐diabetic female rats showed neither proliferative changes nor the inflammatory process in the mucosa. Immunohistochemically, COX‐2 and iNOS were positive in these chronic suppurative inflammatory lesions accompanied by proliferative squamous epithelium. From these results, it is suggested that chronic inflammatory processes play an important role in the pathogenesis of alloxan‐induced SCC. An experimental system of alloxan‐induced SCC might serve as a suitable model for the study of the inflammation‐related promotion of carcinogenesis. (Cancer Sci2006; 97: 1023–1030)
Prediction of carcinogenic potential by a toxicogenomic approach using rat hepatoma cells
Authors: Tsujimura Kazunari , Asamoto Makoto , Suzuki Shugo , Hokaiwado Naomi , Ogawa Kumiko , Shirai Tomoyuki
Published: August 2006

The long‐term rodent bioassay is the standard method to predict the carcinogenic hazard of chemicals for humans. However, this assay is costly, and the results take at least two years to produce. In the present study, we conducted gene expression profiling of cultured cells exposed to carcinogenic chemicals with the aim of providing a basis for rapid and reliable prediction of carcinogenicity using microarray technology. We selected 39 chemicals, including 17 rat hepatocarcinogens and eight compounds demonstrating carcinogenicity in organs other than the liver. The remaining 14 were non‐carcinogens. When rat hepatoma cells (MH1C1) were treated with the chemicals for 3 days at a non‐toxic dose, analysis of gene expression changes with our in‐house microarray allowed a set of genes to be identified differentiating hepatocarcinogens from non‐carcinogens, and all carcinogens from non‐carcinogens, by statistical methods. Moreover, optimization of the two gene sets for classification with an SVM and LOO‐CV resulted in selection of 39 genes. The highest predictivity was achieved with 207 genes for differentiation between non‐hepatocarcinogens and non‐carcinogens. The overlap between the two selected gene sets encompassed 26 genes. This gene set contained significant genes for prediction of carcinogenicity, with a concordance of 84.6% by LOO‐CV SVM. Using nine external samples, correct prediction of carcinogenicity by SVM was 88.9%. These results indicate that short‐term bioassay systems for carcinogenicity using gene expression profiling in hepatoma cells have great promise. (Cancer Sci2006; 97: 1002–1010)
Physical activity and colorectal cancer: The Fukuoka Colorectal Cancer Study
Authors: Isomura Kayoko , Kono Suminori , Moore Malcolm A. , Toyomura Kengo , Nagano June , Mizoue Tetsuya , Mibu Ryuichi , Tanaka Masao , Kakeji Yoshihiro , Maehara Yoshihiko , Okamura Takeshi , Ikejiri Koji , Futami Kitaroh , Yasunami Yohichi , Maekawa Takafumi , Takenaka Kenji , Ichimiya Hitoshi , Imaizumi Nobutoshi
Published: August 2006

The number of cases of colorectal cancer in Japan has increased over the past few decades, and incidence rates are now among the highest in the world. The present investigation within the Fukuoka Colorectal Cancer Study, including 778 cases and 767 controls aged 20–74 years, examined the association between physical activity and colorectal cancer risk by subsite. Employment‐associated and leisure time physical activity was assessed by a questionnaire and interview. Division of sites into the proximal and distal colon, as well as the rectum, revealed clear site‐dependent protective effects, with adjustment for smoking, alcohol consumption, BMI and age. In males, greater job‐related physical activity was associated with significant reduction of risk in the distal colon and rectum (P = 0.047 and 0.02, respectively), whereas total and moderate or hard non‐job physical activity exerted effects limited to the rectum (P = 0.01 and 0.004, respectively). In females, job‐related physical activity and moderate or hard non‐job physical activity was also protective, but only in the distal colon. Separate assessment of the influence of BMI 10 years previous to the study showed increase in risk with obesity in males but not in females, limited to distal colon and rectum. The results of the present study indicate that physical activity associated with work and leisure‐time exerts beneficial effects in Japanese, but not on the proximal colon. (Cancer Sci 2006; 97: 1099–1104)
A long‐term record of carbon exchange in a boreal black spruce forest: means, responses to interannual variability, and decadal trends
Authors: DUNN ALLISON L. , BARFORD CAROL C. , WOFSY STEVEN C. , GOULDEN MICHAEL L. , DAUBE BRUCE C.
Published: August 2006

We present a decadal (1994–2004) record of carbon dioxide flux in a 160‐year‐old black spruce forest/veneer bog complex in central Manitoba, Canada. The ecosystem shifted from a source (+41 g C m−2, 1995) to a sink (−21 g C m−2, 2004) of CO2 over the decade, with an average net carbon balance near zero. Annual mean temperatures increased 1–2° during the period, consistent with the decadal trend across the North American boreal biome. We found that ecosystem carbon exchange responded strongly to air temperature, moisture status, potential evapotranspiration, and summertime solar radiation. The seasonal cycle of ecosystem respiration significantly lagged that of photosynthesis, limited by the rate of soil thaw and the slow drainage of the soil column. Factors acting over long time scales, especially water table depth, strongly influenced the carbon budget on annual time scales. Net uptake was enhanced and respiration inhibited by multiple years of rainfall in excess of evaporative demand. Contrary to expectations, we observed no correlation between longer growing seasons and net uptake, possibly because of offsetting increases in ecosystem respiration. The results indicate that the interactions between soil thaw and water table depth provide critical controls on carbon exchange in boreal forests underlain by peat, on seasonal to decadal time scales, and these factors must be simulated in terrestrial biosphere models to predict response of these regions to future climate.
Characterization of the expanded T‐cell populations in patients with Wegener's granulomatosis
Authors: GISCOMBE R. , WANG X. B. , KAKOULIDOU M. , LEFVERT A. K.
Published: August 2006

Objectives.  Wegener's granulomatosis (WG) is a chronic inflammatory disease characterized by granulomatosis inflammation, systemic vasculitis and glomerulonephritis. In patients, the peripheral T cells are characterized by mono/oligoclonal CD4+/CD8+ T‐cell AV/BV receptor expansions, with aberrant expression of activation markers. This study was designed to characterize the phenotypic differences between the expanded and nonexpanded T‐cell populations. Expression of markers for activation, costimulation and adhesion molecules was examined. As earlier studies have shown aberrant expression of CD28/CD152, we also analysed the expression of another costimulatory system, the tumour necrotic factor receptor (TNFR) superfamily proteins.

Design.  Fluorocrome‐conjugated monoclonal antibodies and flow cytometry was used to analyse the expression of the different markers on the surface of the expanded and nonexpanded subsets of T cells.

Setting.  The Karolinska Hospital and Karolinska Institutet in Stockholm, Sweden.

Subjects.  Nine patients with WG (six men and three women) had 16 TCRAV/BV CD4+/CD8+ expanded populations that were characterized.

Results.  The expanded TCRA/BV CD4+ and CD8+ cells had lower percentages of cells expressing CD28 and higher of those expressing CD152 (CTLA‐4). The expanded CD4+ population had more cells expressing HLA‐DR, CD57 and CCR5 (CD195), whilst the expression of CD25 was present on fewer of the expanded cells. The expanded CD8+ population contained more cells expressing CD137 (4‐1BB), CD137 (4‐1BBL), CD30 (Ki‐1), CD40 and CD134 (OX40),

Conclusions.  There were marked differences in the phenotypes of expanded and nonexpanded T‐cell populations.
Vascular smooth muscle cell phenotypic plasticity and the regulation of vascular calcification
Authors: IYEMERE V. P. , PROUDFOOT D. , WEISSBERG P. L. , SHANAHAN C. M.
Published: August 2006

Vascular smooth muscle cells (VSMCs) exhibit an extraordinary capacity to undergo phenotypic change during development, in vitro and in association with disease. Unlike other muscle cells they do not terminally differentiate. Development and maintenance of the mature contractile phenotype is regulated by a number of interacting transcription factors. In response to injury contractile VSMCs can be induced to change phenotype, proliferate and migrate to effect repair. On completion of the repair process VSMCs return to a nonproliferating contractile phenotype. In this way, in the context of atherosclerosis, a protective fibrous cap is formed and maintained at sites of injury. However in disease, when modulatory signals are perturbed, this phenotypic transition is dysregulated and VSMCs are induced to undergo inappropriate differentiation into cells with features of other mesenchymal lineages such as osteoblasts, chondrocytes and adipocytes. Moreover, evidence is accumulating that these aberrant phenotypic transitions contribute to the pathogenesis of vascular diseases such as atherosclerosis and Monckeberg's Sclerosis. Indeed, the osteo/chondrocytic conversion of VSMCs and the association of this phenotype with vascular calcification is a paradigm for how inappropriate differentiation can influence disease processes. Understanding of the mechanisms and signalling pathways involved in this particular phenotype change is well advanced offering the possibility for the design of successful therapeutic interventions in the future.
Rising trend of asthma prevalence among Turkish schoolchildren (ISAAC phases I and III)
Authors: Ones U. , Akcay A. , Tamay Z. , Guler N. , Zencir M.
Published: August 2006

Background:  Asthma is a common chronic illness in childhood. The aim of the study was to examine time trends in the prevalence of asthma using the ISAAC questionnaire in 6‐ to 12‐year‐old schoolchildren in Istanbul and factors affecting asthma prevalence.

Methods:  Two cross‐sectional surveys were performed, 9 years apart (1995 and 2004) using the ISAAC protocol. The survey conducted in 1995 was repeated in 2004 using the same questionnaire in the same age group, in the same schools in the same season. The 2500 questionnaires were distributed to the children to be completed by their parents at home.

Results:  A total of 2387 children (response rate 95.5%) in the 2004 study and 2216 children (response rate 94.3%) in 1995 were included in the final analysis. The overall lifetime prevalence of wheeze increased from 15.1% to 25.3%; prevalence odds ratio (POR) = 1.91, 95% confidence interval (95% CI) = 1.64–2.21, and P < 0.001. The overall 12‐month prevalence of wheeze increased from 8.2% to 11.3%; POR = 1.43, 95% CI = 1.18–1.75, and P < 0.001. The prevalence of asthma increased significantly from 9.8% to 17.8%; POR = 1.99, 95% CI = 1.67–2.36, and P < 0.001. In both 1995 and 2004, family history of asthma, eczema diagnosed by a physician, food allergy diagnosed by a physician, frequent otitis, frequent sinusitis were associated significantly with high risk for asthma.

Conclusions:  In the 9‐year period from 1995 to 2004, the prevalence of asthma symptoms has increased in 6‐ to 12‐year‐old schoolchildren in Istanbul. Risk factors affecting asthma prevalence remained unchanged during the 9‐year period.
Stem cell research: cloning, therapy and scientific fraud
Authors: Rusnak AJ , Chudley AE
Published: August 2006

Stem cell research has generated intense excitement, awareness, and debate. Events in the 2005–2006 saw the rise and fall of a South Korean scientist who had claimed to be the first to clone a human embryonic stem cell line. From celebration of the potential use of stem cells in the treatment of human disease to disciplinary action taken against the disgraced scientists, the drama has unfolded throughout the world media. Prompted by an image of therapeutic cloning presented on a South Korean stamp, a brief review of stem cell research and the events of the Woo‐suk Hwang scandal are discussed.
Dystrophic epidermolysis bullosa pruriginosa in Italy: clinical and molecular characterization
Authors: Drera B , Castiglia D , Zoppi N , Gardella R , Tadini G , Floriddia G , De Luca N , Pedicelli C , Barlati S , Zambruno G , Colombi M
Published: August 2006

Dystrophic epidermolysis bullosa (DEB) pruriginosa (DEB‐Pr) is a rare variant of DEB due to COL7A1 dominant and recessive mutations, which is characterized by severe itching and lichenoid or nodular prurigo‐like lesions, mainly involving the extremities. Less than 30 patients have been described showing variable disease expression, and frequently, delayed age of onset. We report the clinical and molecular characterization of seven Italian DEB patients, three affected with recessive DEB‐Pr and four with dominant DEB‐Pr. In all the patients, the signs were typical of a mild DEB phenotype, until the onset of pruritus, which was followed by worsening of the clinical picture, with appearance of the distinctive lichenified lesions of DEB‐Pr. Nine mutations were found in the COL7A1 gene, three of which were novel and one was de novo. DEB‐Pr patients with either dominant or recessive mutations were shown to synthesize a normal or variably reduced amount of type VII collagen, which was correctly deposited at the dermal–epidermal junction. Since six of these mutations have been reported in DEB patients in the absence of intense pruritus, these data implicate a role of yet unidentified phenotype‐modifying factors in the pathogenesis of DEB‐Pr.
Commentary – Genetic diversity and science communication – some issues of ‘translation’ and language
Authors: Richards MPM
Published: August 2006

This commentary concerns some key themes from the symposium. While molecular genetics may provide new opportunities to articulate biological concepts of race, the ideological baggage associated with the term suggests that it is best dropped from discussions. In screening programmes and genetic practice, ethnic identity is likely to be an uncertain surrogate to identify individuals with particular genetic variants. Precise language and explanation will aid communication about genetic matters. Talking of genes for particular traits or diseases is unhelpful. School teaching of classic Mendelian genetics is ineffective and should be replaced with some teaching of elementary developmental biology based on matters of everyday salience and interest. Social science literature is replete with unfounded claims of geneticization.
Pathogenic Variation of Fusarium Isolates Associated with Head Blight of Wheat in Australia
Authors: Akinsanmi O. A. , Backhouse D. , Simpfendorfer S. , Chakraborty S.
Published: August 2006

This paper examines the level of pathogenic diversity in Australian Fusarium pseudograminearum and Fusarium graminearum isolates for head blight from the assessment of 51 wheat germplasm lines, barley, triticale, rye, maize and sorghum plants. A set of nine putative wheat differentials were selected and assessed with 10 F. graminearum and 12 F. pseudograminearum isolates. Isolates of both species were pathogenic on all the wheat germplasm lines, barley triticale and rye. The isolates differed largely in a quantitative way with only small differential effects and were statistically demarcated into three pathogenicity groups: low, intermediate and high. Such distribution patterns suggest that wheat germplasm lines employ different resistance mechanisms to each group of isolates and the three pathogenicity groups may have different mechanisms controlling pathogenicity. The aggressiveness of F. graminearum and F. pseudograminearum isolates on the wheat germplasm lines were marginally correlated (r = 0.40). Durum wheats were ranked as the most susceptible while Sumai 3, Ituo Komugi, Sotome A, Sotome and Nobeokabouzu komugi were consistently grouped as resistant by both species. These findings reiterate the need to consider pathogen variability in the screening, selection and improvement of resistance to head blight in wheat.
A Suspension Culture Method for the Rapid Mass Culture of Cistella japonica Mycelium
Authors: Yamanobe T. , Oribe Y.
Published: August 2006

Different methods were investigated for the rapid mass culture of Cistella japonica by using water extracts of some nutritional sources. In an agar culture test, there was little difference in mycelial growth in water extracts of wheat bran, rice bran and potato. In suspension culture with wheat bran extract, which is easily and cheaply available, the mycelium of C. japonica increased seven times more than that in agar culture after a month's incubation. C. japonica from suspension culture was pathogenic to Chamaecyparis obtusa. These results suggest that suspension culture in water extract of wheat bran can be adopted for the rapid mass culturing of C. japonica for use in inoculation tests.
Genetic Variability in Phytophthora palmivora (Butl.) Using RAPD Markers
Authors: Sudheesh K. G. , Sreekumar V. B.
Published: August 2006

Phytophthora palmivora causes bud rot, fruit and immature nut fall in India, and causes significant coconut yield losses. Genetic variability was estimated in 70 isolates representing seven populations from the Kerala and Karnataka regions using random amplified polymorphic DNA (RAPD) markers. RAPDs generated a total of 163 markers with 15 decamer primers, of which 92% were found to be polymorphic. The number of polymorphic loci within a single population varied from 45 to 92 with estimated hetrozygosities ranging from 0.08 to 0.23. The majority of the genetic diversity was distributed within populations (68.25%) and only 31.75% were among populations. Genetic relationships estimated by the unweighted pair‐group method with arithmatic averaging (UPGMA) revealed clear separation of Kerala and Karnataka populations.