bluuebunny/crossref_metadata_2025 huggingface dataset:
Programmed Cell Death-Involved Aluminum Toxicity in Yeast Alleviated by Antiapoptotic Members with Decreased Calcium Signals
Authors: Zheng Ke , Pan Jian-Wei , Ye Lan , Fu Yu , Peng Hua-Zheng , Wan Bai-Yu , Gu Qing , Bian Hong-Wu , Han Ning , Wang Jun-Hui , Kang Bo , Pan Jun-Hang , Shao Hong-Hong , Wang Wen-Zhe , Zhu Mu-Yuan
Published: July 2006

The molecular mechanisms of aluminum (Al) toxicity and tolerance in plants have been the focus of ongoing research in the area of stress phytophysiology. Recent studies have described Al-induced apoptosis-like cell death in plant and animal cells. In this study, we show that yeast (Saccharomyces cerevisiae) exposed to low effective concentrations of Al for short times undergoes enhanced cell division in a manner that is dose and cell density dependent. At higher concentrations of Al or longer exposure times, Al induces cell death and growth inhibition. Several apoptotic features appear during Al treatment, including cell shrinkage, vacuolation, chromatin marginalization, nuclear fragmentation, DNA degradation, and DNA strand breaks, as well as concomitant cell aggregation. Yeast strains expressing Ced-9, Bcl-2, and PpBI-1 (a plant Bax inhibitor-1 isolated from Phyllostachys praecox), respectively, display more resistance to Al toxicity compared with control cells. Data from flow cytometric studies show these three antiapoptotic members do not affect reactive oxygen species levels, but decrease calcium ion (Ca2+) signals in response to Al stress, although both intracellular reactive oxygen species and Ca2+ levels were increased. The data presented suggest that manipulation of the negative regulation process of programmed cell death may provide a novel mechanism for conferring Al tolerance.
RNA Interference-Based Gene Silencing as an Efficient Tool for Functional Genomics in Hexaploid Bread Wheat
Authors: Travella Silvia , Klimm Theres E. , Keller Beat
Published: July 2006

Insertional mutagenesis and gene silencing are efficient tools for the determination of gene function. In contrast to gain- or loss-of-function approaches, RNA interference (RNAi)-induced gene silencing can possibly silence multigene families and homoeologous genes in polyploids. This is of great importance for functional studies in hexaploid wheat (Triticum aestivum), where most of the genes are present in at least three homoeologous copies and conventional insertional mutagenesis is not effective. We have introduced into bread wheat double-stranded RNA-expressing constructs containing fragments of genes encoding Phytoene Desaturase (PDS) or the signal transducer of ethylene, Ethylene Insensitive 2 (EIN2). Transformed plants showed phenotypic changes that were stably inherited over at least two generations. These changes were very similar to mutant phenotypes of the two genes in diploid model plants. Quantitative real-time polymerase chain reaction revealed a good correlation between decreasing mRNA levels and increasingly severe phenotypes. RNAi silencing had the same quantitative effect on all three homoeologous genes. The most severe phenotypes were observed in homozygous plants that showed the strongest mRNA reduction and, interestingly, produced around 2-fold the amount of small RNAs compared to heterozygous plants. This suggests that the effect of RNAi in hexaploid wheat is gene-dosage dependent. Wheat seedlings with low mRNA levels for EIN2 were ethylene insensitive. Thus, EIN2 is a positive regulator of the ethylene-signaling pathway in wheat, very similar to its homologs in Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa). Our data show that RNAi results in stably inherited phenotypes and therefore represents an efficient tool for functional genomic studies in polyploid wheat.
Ectopic Expression of KNOTTED1-Like Homeobox Protein Induces Expression of Cytokinin Biosynthesis Genes in Rice
Authors: Sakamoto Tomoaki , Sakakibara Hitoshi , Kojima Mikiko , Yamamoto Yuko , Nagasaki Hiroshi , Inukai Yoshiaki , Sato Yutaka , Matsuoka Makoto
Published: July 2006

Some phytohormones such as gibberellins (GAs) and cytokinins (CKs) are potential targets of the KNOTTED1-like homeobox (KNOX) protein. To enhance our understanding of KNOX protein function in plant development, we identified rice (Oryza sativa) genes for adenosine phosphate isopentenyltransferase (IPT), which catalyzes the rate-limiting step of CK biosynthesis. Molecular and biochemical studies revealed that there are eight IPT genes, OsIPT1 to OsIPT8, in the rice genome, including a pseudogene, OsIPT6. Overexpression of OsIPTs in transgenic rice inhibited root development and promoted axillary bud growth, indicating that OsIPTs are functional in vivo. Phenotypes of OsIPT overexpressers resembled those of KNOX-overproducing transgenic rice, although OsIPT overexpressers did not form roots or ectopic meristems, both of which are observed in KNOX overproducers. Expression of two OsIPT genes, OsIPT2 and OsIPT3, was up-regulated in response to the induction of KNOX protein function with similar kinetics to those of down-regulation of GA 20-oxidase genes, target genes of KNOX proteins in dicots. However, expression of these two OsIPT genes was not regulated in a feedback manner. These results suggest that OsIPT2 and OsIPT3 have unique roles in the developmental process, which is controlled by KNOX proteins, rather than in the maintenance of bioactive CK levels in rice. On the basis of these findings, we concluded that KNOX protein simultaneously decreases GA biosynthesis and increases de novo CK biosynthesis through the induction of OsIPT2 and OsIPT3 expression, and the resulting high-CK and low-GA condition is required for formation and maintenance of the meristem.
The role of physiological self‐antigen in the acquisition and maintenance of regulatory T‐cell function
Authors: Samy Eileen T. , Setiady Yulius Y. , Ohno Katsuhiro , Pramoonjago Patcharin , Sharp Colin , Tung Kenneth S. K.
Published: July 2006

Summary:  The CD4+CD25+ regulatory T cells (Tregs) are efficient regulators of autoimmunity, but the mechanism remains elusive. We summarize recent data for the conclusion that disease‐specific Tregs respond to tissue antigens to maintain physiological tolerance and prevent autoimmunity. First, polyclonal Tregs from antigen‐positive donors suppress autoimmune ovarian disease (AOD) or experimental autoimmune prostatitis in day 3 thymectomized (d3tx) mice more efficiently than Tregs from antigen‐negative donors. Second, Tregs of antigen‐negative adult mice respond to cognate antigen in vivo and rapidly gain disease‐specific Treg function. Third, in d3tx female recipients devoid of neonatal ovarian antigens, only female Tregs suppressed AOD; the male Tregs gain AOD‐suppressing function by responding to the ovarian antigen in the recipients and mask the supremacy of female Tregs in AOD suppression. Fourth, when Tregs completely suppress AOD, the ovary‐draining lymph node is the only location with evidence of profound and persistent (but reversible) host T‐cell suppression. Fifth, from these nodes, highly potent AOD‐suppressing Tregs are retrievable. We conclude that self‐tolerance involves the continuous priming of Tregs by autoantigens, and in autoimmune disease suppression, the effector T‐cell response is continuously negated by potent disease‐specific Tregs that accumulate at the site of autoantigen presentation.
FOXP3 ensembles in T‐cell regulation
Authors: Li Bin , Samanta Arabinda , Song Xiaomin , Furuuchi Keiji , Iacono Kathryn T. , Kennedy Sarah , Katsumata Makoto , Saouaf Sandra J. , Greene Mark I.
Published: July 2006

Summary:  Our recent studies have identified dynamic protein ensembles containing forkhead box protein 3 (FOXP3) that provide insight into the molecular complexity of suppressor T‐cell activities, and it is our goal to determine how these ensembles regulate FOXP3's transcriptional activity in vivo. In this review, we summarize our current understanding of how FOXP3 expression is induced and how FOXP3 functions in vivo as a transcriptional regulator by assembling a multisubunit complex involved in histone modification as well as chromatin remodeling.
Infectious tolerance and the long‐term acceptance of transplanted tissue
Authors: Waldmann Herman , Adams Elizabeth , Fairchild Paul , Cobbold Stephen
Published: July 2006

Summary:  Short courses of antibody treatment aimed at blocking the coreceptors CD4 and CD8 and/or costimulatory molecules such as CD40L are able to bring about long‐term acceptance and tolerance of allogeneic transplants. This tolerant state is operational, in that potential effector cells remain but are tightly regulated through the induction of antigen‐specific CD4+ regulatory T cells (Tregs). CD4+CD25+FoxP3+ Tregs appear to play a prominent role, although other categories of Tregs have been documented. Transforming growth factor β (TGFβ) has been found to play a major role in the induction of the tolerant state with therapeutic antibodies as well as promoting the induction of FoxP3+ T cells from naïve populations. The observation that Tregs can be found in tolerated grafts has led to the idea that they may interact with the grafted tissue to establish a state of acquired privilege symmetrical with a similar privileged microenvironment around antigen‐presenting cells in lymphoid tissues. Dampening of aggressive immune responses by Tregs allows antigen to persist and be presented in an innocuous way to promote tolerance in new cohorts of T cells throughout the life of the tolerated graft. Regulation may operate at many stages of an immune response, even as a censor at the terminal differentiation stages of effector function.
The roles for cytokines in the generation and maintenance of regulatory T cells
Authors: Wan Yisong Y. , Flavell Richard A.
Published: July 2006

Summary:  As an essential mechanism for self‐tolerance, immune suppression has attracted much attention since the discovery of suppressor T cells, now called regulatory T cells (Tregs), in the 1990s. Different types of Tregs have been described based on distinct expression patterns of surface markers and cytokines. Cytokines are not only essential for function but also important for the generation of Tregs. Interleukin‐2 (IL‐2), transforming growth factor‐β, IL‐10, and other immunoregulatory molecules have been shown to control the generation of Tregs. The presence of other types of cells, in particular antigen‐presenting cells (APCs), is critical for the generation of Tregs. Cytokines can serve as either initiators or intermediates for the interactions between APCs and Tregs. This review discusses our current knowledge of how cytokines regulate the generation and maintenance of Tregs.
Making regulatory T cells with defined antigen specificity: role in autoimmunity and cancer
Authors: Kretschmer Karsten , Apostolou Irina , Jaeckel Elmar , Khazaie Khashayarsha , Von Boehmer Harald
Published: July 2006

Summary:  There is increasing evidence that agonist ligand presentation either intrathymically or extrathymically plays a crucial if not essential role in the generation of regulatory T cells (Tregs). Thus, it is possible to induce Tregs of any desired specificity in vivo. The same goal can be achieved in vitro by expanding antigen‐specific CD4+ T cells and retrovirally transducing them. In contrast, in vitro expansion of Tregs is limited to antigens that have resulted in Treg generation in vivo. Antigen‐specific Tregs can be used in cellular therapy with the goal to prevent autoimmune disease or even to interfere with established autoimmunity. The latter requires that the Tregs can suppress effector cells that have already caused harm, which is possible because of the antigen‐dependent homing properties of Tregs, i.e. these cells can accumulate in antigen‐draining lymph nodes and exit into inflamed tissue. Generally, the in vivo interference is dependent on cytokines such as transforming growth factor‐β and interleukin‐10 that were dispensable in in vivo analysis of immunosuppression. The precise mechanisms of suppression remain enigmatic, however, but may be further elucidated by the molecular analysis of suppressed versus non‐suppressed T cells.
Regulatory T cells in the periphery
Authors: Lohr Jens , Knoechel Birgit , Abbas Abul K.
Published: July 2006

Summary:  Recognition of a systemic antigen by CD4+ T cells in a lymphopenic host leads to the sequential generation of pathogenic effector cells and protective CD25+ forkhead box protein (Foxp3+) regulatory T cells (Tregs) in the periphery. Such an experimental model is potentially valuable for defining the stimuli that determine the balance of effector and regulatory T cells. Our studies have shown that interleukin‐2 (IL‐2) enhances the development of effector cells and is essential for the peripheral generation of regulatory cells. Other models of peripheral Treg generation suggest that the concentration of antigen, the nature of the antigen‐presenting cells, and cytokines such as transforming growth factor‐β and IL‐10 may all influence the peripheral generation of Tregs.
Role of TCR specificity in CD4+CD25+ regulatory T‐cell selection
Authors: Picca Cristina Cozzo , Larkin Joseph , Boesteanu Alina , Lerman Melissa A. , Rankin Andrew L. , Caton Andrew J.
Published: July 2006

Summary:  CD4+CD25+ regulatory T cells play a crucial role in preventing autoimmune disease and can also modulate immune responses in settings such as transplantation and infection. We have developed a transgenic mouse system in which the role that T‐cell receptor (TCR) specificity for self‐peptides plays in the formation of CD4+CD25+ regulatory T cells can be examined. We have shown that interactions with a single self‐peptide can induce thymocytes bearing an autoreactive TCR to undergo selection to become CD4+CD25+ regulatory T cells and that thymocytes bearing TCRs with low affinity for the selecting peptide do not appear to undergo selection into this pathway. In addition, thymocytes with identical specificity for the selecting self‐peptide can undergo overt deletion versus abundant selection to become CD4+CD25+ regulatory T cells in response to variations in expression of the selecting peptide in different lineages of transgenic mice. Finally, we have shown that CD4+CD25+ T cells proliferate in response to their selecting self‐peptide in the periphery, but these cells do not proliferate in response to lymphopenia in the absence of the selecting self‐peptide. These studies are determining how the specificity of the TCR for self‐peptides directs the thymic selection and peripheral expansion of CD4+CD25+ regulatory T cells.
Human regulatory T cells and their role in autoimmune disease
Authors: Baecher‐Allan Clare , Hafler David A.
Published: July 2006

Summary:  As self‐recognition is fundamental to the efficient operation of the immune system, a number of mechanisms have evolved to keep this potential pathologic self‐reactivity in check. Thus, even though the majority of strongly self‐reactive T cells are deleted in the thymus during T‐cell maturation, a number of mature T cells that recognize self‐antigens can be found in the peripheral circulation in healthy individuals as well as in patients with autoimmune disease. These self‐reactive cells are kept in a non‐responsive state in healthy individuals while they appear to be involved in the etiology of a number of autoimmune diseases in patients. The primary role of a relatively recently identified T‐cell population, referred to as natural CD4+CD25+ regulatory T cells, is to modulate the activity of these self‐reactive cells. Although it is still unclear how these regulatory cells function, they can inhibit the activation of other potentially pathologic T cells in in vitro assays. Using such assays, regulatory T cells isolated from patients with a number of autoimmune diseases have been shown to exhibit reduced inhibitory function as compared with those isolated from healthy individuals. In this review, we discuss human natural regulatory T cells, what is known about their function, and their associations with specific autoimmune diseases.
The immunoregulatory effects of Qa‐1
Authors: Lu Linrong , Werneck Miriam B. F. , Cantor Harvey
Published: July 2006

Summary:  The immune system is not only well equipped to control infections but also tightly controlled to prevent autoimmune disease. Despite the negative selection of T‐cell clones in the thymus, mature T cells capable of recognizing self‐antigens are present in every individual. Several types of specialized regulatory cells maintain homeostasis and prevent expansion of autoreactive T cells. In this issue of Immunological Reviews, the role of CD4+ regulatory T cells is extensively discussed. Suppression of T‐cell responses by CD8+ T cells has received less attention. Here, we review research on Qa‐1‐restricted CD8+ regulatory T cells. We focus on the role of this class Ib major histocompatibility complex (MHC) molecule in both CD8+ regulatory T‐cell activity and protection of activated T cells.
The role of CD28 and cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) in regulatory T‐cell biology
Authors: Sansom David M. , Walker Lucy S. K.
Published: July 2006

Summary:  The profound influence of CD28 and cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) on T‐cell immunity has been known for over a decade, yet the precise roles played by these molecules still continue to emerge. Initially viewed as molecules that provide cell‐intrinsic costimulatory and inhibitory signals, recent evidence suggests that both CD28 and CTLA‐4 are also important in the homeostasis and function of a population of suppressive cells, termed regulatory T cells (Tregs). Here we review the main features of the CD28 and CTLA‐4 system and examine how these impact upon Treg biology.
Interleukin‐10‐secreting type 1 regulatory T cells in rodents and humans
Authors: Grazia Roncarolo Maria , Gregori Silvia , Battaglia Manuela , Bacchetta Rosa , Fleischhauer Katharina , Levings Megan K.
Published: July 2006

Summary:  Interleukin‐10 (IL‐10)‐secreting T regulatory type 1 (Tr1) cells are defined by their specific cytokine production profile, which includes the secretion of high levels of IL‐10 and transforming growth factor‐β(TGF‐β), and by their ability to suppress antigen‐specific effector T‐cell responses via a cytokine‐dependent mechanism. In contrast to the naturally occurring CD4+CD25+ T regulatory cells (Tregs) that emerge directly from the thymus, Tr1 cells are induced by antigen stimulation via an IL‐10‐dependent process in vitro and in vivo. Specialized IL‐10‐producing dendritic cells, such as those in an immature state or those modulated by tolerogenic stimuli, play a key role in this process. We propose to use the term Tr1 cells for all IL‐10‐producing T‐cell populations that are induced by IL‐10 and have regulatory activity. The full biological characterization of Tr1 cells has been hampered by the difficulty in generating these cells in vitro and by the lack of specific marker molecules. However, it is clear that Tr1 cells play a key role in regulating adaptive immune responses both in mice and in humans. Further work to delineate the specific molecular signature of Tr1 cells, to determine their relationship with CD4+CD25+ Tregs, and to elucidate their respective role in maintaining peripheral tolerance is crucial to advance our knowledge on this Treg subset. Furthermore, results from clinical protocols using Tr1 cells to modulate immune responses in vivo in autoimmunity, transplantation, and chronic inflammatory diseases will undoubtedly prove the biological relevance of these cells in immunotolerance.
Regulatory T‐cell physiology and application to treat autoimmunity
Authors: Tang Qizhi , Bluestone Jeffrey A.
Published: July 2006

Summary:  Endowed with the ability to actively suppress an immune response, regulatory T cells (Tregs) hold the promise of halting ongoing pathogenic autoimmunity and restoring self‐tolerance in patients suffering from autoimmune diseases. Through many in vitro and in vivo studies, we have learned that Tregs can function in the lymph nodes as well as in the peripheral tissues. In vivo, Tregs act through dendritic cells to limit autoreactive T‐cell activation, thus preventing their differentiation and acquisition of effector functions. By limiting the supply of activated pathogenic cells, Tregs prevent or slow down the progression of autoimmune diseases. However, this protective mechanism appears insufficient in autoimmune individuals, likely because of a shortage of Tregs cells and/or the development and accumulation of Treg‐resistant pathogenic T cells over the long disease course. Thus, restoration of self‐tolerance in these patients will likely require purging of pathogenic T cells along with infusion of Tregs with increased ability to control ongoing tissue injury. In this review, we highlight advances in dissecting Treg function in vivo in autoimmune settings and summarize multiple studies that have overcome the limitations of the low abundance of Tregs and their hypoproliferative phenotype to develop Treg‐based therapies.
Dendritic cells expand antigen‐specific Foxp3+CD25+CD4+ regulatory T cells including suppressors of alloreactivity
Authors: Yamazaki Sayuri , Inaba Kayo , Tarbell Kristin V. , Steinman Ralph M.
Published: July 2006

Summary:  Thymic derived naturally occurring CD25+CD4+ T regulatory cells (Tregs) suppress immune responses, including transplantation. Here we discuss the capacity of dendritic cells (DCs) to expand antigen‐specific Tregs, particularly polyclonal Tregs directed to alloantigens. Initial studies have shown that mature DCs are specialized antigen‐presenting cells (APCs) for expanding antigen‐specific CD25+ CD4+ Tregs from TCR transgenic mice. When triggered by specific antigen, these Tregs act back on immature DCs to block the upregulation of CD80 and CD86 costimulatory molecules. More recently, DCs have been used to expand alloantigen‐specific CD25+CD4+ Tregs from the polyclonal repertoire in the presence of interleukin‐2 (IL‐2). Allogeneic DCs are much more effective than allogeneic spleen cells for expanding CD25+CD4+ Tregs. The DC‐expanded Tregs continue to express high levels of Foxp3, even without supplemental IL‐2, whereas spleen cells poorly sustain Foxp3 expression. When suppressive activity is tested, relatively small numbers of DC‐expanded CD25+CD4+ Tregs exert antigen‐specific suppression in the mixed leukocyte reaction (MLR), blocking immune responses to the original stimulating strain 10 times more effectively than to third party stimulating cells. DC‐expanded Tregs also retard graft versus host disease (GVHD) across full major histocompatibility complex (MHC) barriers. In vitro and in vivo, the alloantigen‐specific CD25+CD4+ Tregs are much more effective suppressors of transplantation reactions than polyclonal populations. We suggest that the expansion of Tregs from a polyclonal repertoire via antigen‐presenting DCs will provide a means for antigen‐specific control of unwanted immune reactions.
The role of the transcription factor Foxp3 in the development of regulatory T cells
Authors: Kim Jeong M. , Rudensky Alexander
Published: July 2006

Summary:  Early studies of mice subjected to neonatal thymectomy and analyses of adoptive T‐cell transfer into lymphopenic hosts led to the identification of a specialized subset of regulatory CD4+ T cells capable of suppressing various manifestations of autoimmunity. Recently, a combination of genetic, molecular, and traditional cellular approaches provided novel powerful means to investigate the biology of these cells. Here, we review earlier and current work from our laboratory, establishing a dedicated function for the transcription factor Foxp3 in the process of regulatory T‐cell lineage commitment and a role for TCR‐ and cytokine‐mediated signals in regulation of Foxp3 expression.
Globally dispersed Y chromosomal haplotypes in wild and domestic sheep
Authors: Meadows J. R. S. , Hanotte O. , Drögemüller C. , Calvo J. , Godfrey R. , Coltman D. , Maddox J. F. , Marzanov N. , Kantanen J. , Kijas J. W.
Published: July 2006

To date, investigations of genetic diversity and the origins of domestication in sheep have utilised autosomal microsatellites and variation in the mitochondrial genome. We present the first analysis of both domestic and wild sheep using genetic markers residing on the ovine Y chromosome. Analysis of a single nucleotide polymorphism (oY1) in theSRYpromoter region revealed that alleleA‐oY1was present in all wild bighorn sheep (Ovis canadensis), two subspecies of thinhorn sheep (Ovis dalli), European Mouflon (Ovis musimon) and the Barbary (Ammontragis lervia).A‐oY1also had the highest frequency (71.4%) within 458 domestic sheep drawn from 65 breeds sampled from Africa, Asia, Australia, the Caribbean, Europe, the Middle East and Central Asia. Sequence analysis of a second locus, microsatelliteSRYM18, revealed a compound repeat array displaying fixed differences, which identified bighorn and thinhorn sheep as distinct from the European Mouflon and domestic animals. Combined genotypic data identified 11 male‐specific haplotypes that represented at least two separate lineages. Investigation of the geographical distribution of each haplotype revealed that one (H6) was both very common and widespread in the global sample of domestic breeds. The remaining haplotypes each displayed more restricted and informative distributions. For example, H5 was likely founded following the domestication of European breeds and was used to trace the recent transportation of animals to both the Caribbean and Australia. A high rate of Y chromosomal dispersal appears to have taken place during the development of domestic sheep as only 12.9% of the total observed variation was partitioned between major geographical regions.
Vinexin β regulates the phosphorylation of epidermal growth factor receptor on the cell surface
Authors: Mitsushima Masaru , Ueda Kazumitsu , Kioka Noriyuki
Published: July 2006

Epidermal growth factor (EGF) regulates various cellular events, including proliferation, differentiation, migration and oncogenesis. In this study, we found that exogenous expression of vinexin β enhanced the phosphorylation of 180‐kDa proteins in an EGF‐dependent manner in Cos‐7 cells. Western blot analysis using phospho‐specific antibodies against EGFR identified EGFR as a phosphorylated 180‐kDa protein. Vinexin β did not stimulate the phosphorylation of EGFR but suppressed the dephosphorylation, resulting in a sustained phosphorylation. Mutational analyses revealed that both the first and third SH3 domains were required for a sustained phosphorylation of EGFR. Small interfering RNA‐mediated knockdown of vinexin β reduced the phosphorylation of EGFR on the cell surface in HeLa cells. The sustained phosphorylation of EGFR induced by vinexin β was completely abolished by adding the EGFR‐specific inhibitor AG1478 even after EGF stimulation, suggesting that the kinase activity of EGFR is required for the sustained phosphorylation induced by vinexin β. We also found that E3 ubiquitin ligase c‐Cbl is a binding partner of vinexin β through the third SH3 domain. Expression of wild‐type vinexin β but not a mutant containing a mutation in the third SH3 domain decreased the cytosolic pool of c‐Cbl and increased the amount of membrane‐associated c‐Cbl. Furthermore, over‐expression of c‐Cbl suppressed the sustained phosphorylation of EGFR induced by vinexin β. These results suggest that vinexin β plays a role in maintaining the phosphorylation of EGFR on the plasma membrane through the regulation of c‐Cbl.
Gq/11‐induced intracellular calcium mobilization mediates Per2 acute induction in Rat‐1 fibroblasts
Authors: Takashima Naoyuki , Fujioka Atsuko , Hayasaka Naoto , Matsuo Ayako , Takasaki Jun , Shigeyoshi Yasufumi
Published: July 2006

Phase resetting is one of the essential properties of circadian clocks that is required for the adjustment to a particular environment and the induction of Per1 and Per2 clock genes is believed to be a primary molecular event during this process. Although the intracellular signal transduction pathway underlying Per1 gene activation has been well characterized, the mechanisms that control Per2 up‐regulation have not yet been elucidated. In our present study, we demonstrate that Gq/11 coupled receptors mediate serum‐induced immediate rat Per2 (rPer2) transactivation in Rat‐1 fibroblasts via intracellular Ca2+ mobilization. Stimulation of these cells with a high concentration of serum was found to rapidly increase the intracellular Ca2+ levels and strongly up‐regulated rPer2 gene. rPer2 induction by serum stimulation was abrogated by intracellular Ca2+ chelation and depletion of intracellular Ca2+ store, which suggests that the calcium mobilization is necessary for the up‐regulation of rPer2 gene. In addition, suppression of Gq/11 function was observed to inhibit both Ca2+ mobilization and rPer2 induction. Further, we demonstrated that endothelin‐induced acute rPer2 transactivation via Gq/11‐coupled endothelin receptors is also suppressed by a Gq/11 specific inhibitor. These findings together suggest that serum and endothelin utilize a common Gq/11‐PLC mediated pathway for the transactivation of rPer2, which involves the mobilization of calcium from the intracellular calcium store.
Health‐related quality of life among 3–4‐year‐old children born with very low birthweight
Authors: Chien Li‐Yin , Chou Yi‐Hung , Ko Yi‐Li , Lee Ching‐Fang
Published: July 2006

Aim.  This paper reports a study comparing health‐related quality of life at 3–4 years of age among children born with very low birthweight (≤1500 g) to a group of non‐very low birthweight controls, and to examine biological, environmental, demographic and health factors associated with quality of life of children born with very low birthweight.

Background.  Advances in modern medicine have increased the survival of infants with very low birthweight, but its impact on quality of life of children during preschool years has been less studied.

Methods.  The study sample included 118 children born with very low birthweight and 170 non‐very low birthweight controls in Taiwan. Primary caregivers of the study children completed structured questionnaires during the period November 2002 to April 2003. Health‐related quality of life was measured using the Mandarin version of the TZO‐AZL Preschool Children Quality of Life instrument. This tool has four dimensions: physical, emotional, cognitive and social functions. Higher scores indicate better quality of life.

Findings.  Children born with very low birthweight had statistically significantly lower mean quality of life scores in all the four dimensions compared with controls. Among the former, those who had current physical health problems scored lower in all dimensions of quality of life. Primary caregivers with higher educational levels and increased ages of the children were associated with improved scores in the emotional and social functions. Birth gestational age was negatively associated with cognitive function. Length of stay in the neonatal intensive care unit was negatively associated with scores for the social function aspect of quality of life.

Conclusion.  Regular monitoring of the quality of life among very low birthweight children is needed. Nurses need to assess the child's current health state, birth gestational age, and the primary caregiver's educational level in order to identify those who are at risk for low quality of life and intervene early.
The duality in using information and communication technology in elder care
Authors: Sävenstedt Stefan , Sandman P.O. , Zingmark Karin
Published: July 2006

Aim.  The aim of this paper is to report a study illuminating values and perceptions held by professional carers of older people about the use of information and communication technology applications.

Background.  Various information and communication technology applications have successfully been developed to help solve a variety of problems in elder care. Beside different technical barriers and the assumed negative attitudes among older people, staff values and attitudes have been found to be an important cause of resistance to change and slowness in introduction of information and communication technology in health care of older people.

Methods.  An interview study was conducted in 2004 with 10 healthcare personnel with 3–26 years experience of working in home care and nursing homes in Northern Sweden. Qualitative content analysis was used to identify recurring themes in the data.

Results.  The interpretation of values and perceptions among carers revealed a duality where the carers perceived information and communication technology as a promoter of both inhumane and humane care, a duality that seemed to make them defensive and resistant to change. Within the overall duality, other dualities were embedded that described both perceptions about the care of older people and about being a carer. There was evidence of resistance among professional carers towards an introduction of information and communication technology applications in elder care. Carers considered that the same attributes of information and communication technology that could promote humane care could also lead to dehumanized care.

Conclusion.  There should be an ethical discussion when introducing information and communication technology applications in elder care. The best caring alternative for all those concerned should be considered. It should promote aspects of wellbeing and dignity for frail older people and fears of inhumane care among carers must be recognized and discussed.
Effects of an osteoporosis educational programme for men
Authors: Tung W. C. , Lee Iris F. K.
Published: July 2006

Aim.  This paper reports an evaluation of the effects on knowledge, health beliefs and preventive behaviours of an osteoporosis educational programme for men.

Background.  Osteoporosis is an increasing global health concern, and educational programmes have been identified as a crucial strategy in its prevention. However, the effectiveness of osteoporosis educational programmes has mainly been evaluated in women.

Methods.  A randomized controlled trial was carried out to identify the effects of an osteoporosis educational programme for men. The study was conducted between September 2004 to February 2005, and 128 Hong Kong Chinese men were randomly assigned to an intervention or control group, with 64 in each group. The intervention group attended an osteoporosis educational programme. All participants completed pre‐ and post‐test self‐administered questionnaires: Osteoporosis Knowledge Test, Osteoporosis Health Belief Scale and Osteoporosis Self‐Efficacy Scale.

Results.  The intervention group showed a statistically significant increase in both knowledge (P < 0·0005) and health beliefs (P = 0·007) about osteoporosis and preventive behaviours in comparison with the control group. However, the difference in self‐efficacy between the two groups was not statistically significant (P = 0·154).

Conclusions.  An osteoporosis educational programme can increase men's knowledge levels and change their health beliefs about osteoporosis and preventive behaviours. This approach should be more widely used in nursing practice to promoting the adoption of osteoporosis prevention behaviours in men.
Caregiver bodywork: family members’ experiences of caring for a person with motor neurone disease
Authors: Ray Robin A. , Street Annette F.
Published: July 2006

Aim.  This paper reports a study of how family members caring for people living with motor neurone disease managed the deteriorating body, their own bodywork and the associated emotional labour.

Background.  People living with the neurodegenerative condition of motor neurone disease face the prospect of dying in 3–5 years from progressive loss of voluntary muscle mass and function, culminating in respiratory failure. Theories concerning the body in illness have been used to illustrate patient perspectives; however, family caregivers’ experiences of the body have been neglected.

Method.  An ethnographic case study was undertaken with 18 primary family caregivers and six peripheral caregivers. Primary caregivers participated over 10 months in three face‐to‐face, semi‐structured interviews which included mapping their support networks using ecomaps. Observational data were also recorded as field notes. Peripheral caregivers were interviewed once during the same time period. The data were generated between 2003 and 2004.

Findings.  Informal caregiving requires engagement in various aspects of bodywork. Three body concepts were identified: the visible body – how the disease affected the patient and caregivers; the dependent body – the resulting care requirements; and the social body – how living with motor neurone disease affected their social support networks. The visible body is a continual reminder of the ravages of the disease, while the dependent body demands physical and emotional care. Social interactions decline over time, depriving family caregivers of the much needed support for sustaining their commitment to the bodywork required in caregiving.

Conclusion.  The demands of bodywork for family caregivers are increased by the continual presence of emotional labour as they seek to implement the best way to support their relative with motor neurone disease. Nurses and allied healthcare workers need to assess each family situation, asking appropriate questions to establish the most appropriate interventions to facilitate supportive care.
Triangulation of qualitative approaches: hermeneutical phenomenology and grounded theory
Authors: Annells Merilyn
Published: July 2006

Aim.  In this paper, suggestions are offered about the appropriate use of hermeneutic phenomenology and grounded theory in one study.

Background.  As an alternative to selecting only one qualitative research approach to illuminate a topic of interest about which little is known, two qualitative approaches could be used in a study. Fear of ‘method slurring’ may prevent this alternative being used. Occasionally, however, credible qualitative researchers have advocated using various research approaches in one study, for example using hermeneutical phenomenology and grounded theory in triangulation. However, if pursuing this direction, several advances in thinking about using qualitative research approaches should be considered.

Discussion.  An experience is presented of deciding to use grounded theory and hermeneutic phenomenology in one study. Cautions, practical considerations and alternative options are offered for using these approaches in one study, and the implications of some other possible ways to ‘triangulate’ qualitative approaches are discussed.

Conclusion.  Different research approaches can be creatively and successfully used in one study if there has been adequate consideration of vital factors that determine if there is a good ‘fit’ of the approaches not only with the research problem and question, but also with each other, while also maintaining the integrity of each approach.
Teaching critical reflection skills for advanced mental health nursing practice: a deconstructive–reconstructive approach
Authors: Crowe Marie T. , O'Malley Jane
Published: July 2006

Aim.  This paper presents a literature review conducted to establish what was already known about critical reflection in the nursing literature and what work had been done on using a critical social theory framework as the basis for critical reflection.

Background.  Critical thinking emerged as a significant aspect of nursing education and practice in the late 1980s. It has been promoted as a means by which issues in clinical practice can be examined through a systematic process of exploration and reasoning. Traditionally, critical thinking has commonly involved an attempt to link practice with theory using a scenario or exemplar from practice to illustrate a practice dilemma. This process is often constructed as a retrospective narrative of events. This paper provides a deconstructive–reconstructive approach that differs from some traditional approaches by taking a critical social theory perspective with an emphasis on improving practice.

Methods.  The nursing literature reviewed was accessed through Cumulative Index of Nursing and Allied Health Literature (CINAHL). The search was restricted to English language and published between 1995 and 2005. Based on these findings, we developed a postgraduate advanced mental health nursing programme.

Findings.  There were 490 articles related to ‘nursing’ and ‘critical thinking’; 34 articles related to ‘nursing’ and ‘critical reflection’; 23 articles related to ‘nursing’ and ‘critical social theory’; 15 articles related to ‘mental health nursing’ and ‘critical thinking’; and two articles related to ‘mental health nursing’ and ‘critical reflection’. In the programme we developed based on these findings, students were facilitated to deconstruct concepts and knowledge integral to their own practice. In the reconstructive phase, students implement a change project in clinical practice, supported by a mentor.

Conclusion.  The deconstructive–reconstructive approach to the development of critical thinking skills provides advanced practitioner with the opportunity to integrate practice, theory and research.
Perceptions of Israeli student nurses regarding clinical specialties and factors that influence these perceptions
Authors: Ganz Freda DeKeyser , Kahana Shulamit
Published: July 2006

Aim.  This paper reports a study to determine the perceptions of baccalaureate nursing students towards clinical specialties and what factors influenced these perceptions.

Background.  Previous studies have shown that nursing students enter their professional education with preconceived perceptions about the different clinical specialties in nursing. Some investigators have found that factors such as clinical experience influence these perceptions, but others have not. Cultural and social influences, especially among non‐western cultures, have rarely been investigated.

Methods.  Israeli baccalaureate nursing students were surveyed in their first, third and fourth years of study during the years 1998–2004. They were asked to rank their preferences for clinical areas related to social need, social prestige, level of interest in the clinical area, job choice and what factors influenced their decisions related to job choice. Mean ranks and associations between class and calendar year cohorts were calculated.

Results.  Critical care was consistently ranked as the highest preference in all perception checklists, followed by emergency, maternity and paediatric nursing. Psychiatric, community and gerontological nursing were consistently found at the bottom of the list. High levels of association were found among students from different class cohorts and calendar years. Life experiences were ranked as the factor that most influenced career choice.

Conclusion.  Nursing students in Israel tend to perceive clinical areas in ways similar to other students around the world. These perceptions are strongly influenced by personal experiences and other personal contacts, most often not nursing instructors. Major changes in the local society seem for the most part to have little impact on these perceptions. Therefore there is a need for international nurse educators and recruiters to develop new, creative strategies to encourage nursing students to pursue careers in areas presently considered less popular.
Feasibility of combining e‐health for patients with e‐learning for students using synchronous technologies
Authors: Jones Ray , Skirton Heather , McMullan Miriam
Published: July 2006

Aim.  This paper is a report of a project to introduce and evaluate methods for using information and communication technologies to involve academic staff, students, and patients in a common synchronous e‐learning environment.

Background.  Although there is no strong evidence for this, there may be benefits in ‘efficiency’ and for patients and students from shared e‐learning. Asynchronous e‐learning methods in nursing education are well‐established, but synchronous methods have received less attention. However, if feasible, because they are more akin to face‐to‐face contact, they may be more suitable for patients and may provide a quicker development path for e‐learning.

Method.  We evaluated three synchronous technologies: (1) non‐commercial satellite interactive television (TV); (2) Internet videoconferencing; and (3) webcasting, through feasibility studies of ‘TV‐style’ panel discussions on health topics and seminars with interaction with viewers by e‐mail, inter‐site research meetings with face‐to‐face interaction, user surveys and literature reviews.

Results.  Interactive satellite TV required the booking of rooms with specialized receiving equipment. This limited accessibility contributed to the high cost per participant. Videoconferencing proved acceptable for cross‐site research meetings and is proposed for joint meetings for doctoral students with overseas centres but has the same access issues as interactive satellite TV. Webcasting is accessible to most users with Internet access and provides a feasible means of delivery of synchronous interactive material. Reported live webcasts have had audiences of thousands. Presentation formats: panel discussions with mixed patient–professional membership and mixed patient–professional audiences were acceptable to participants but engaging academic staff and students was problematic. This may be overcome with webcasting but there may still be barriers such as timetabling and students’ concerns about learning in the same ‘live’ environment as patients.

Conclusions.  Limitations in accessibility have been demonstrated for both satellite broadcasts and videoconferencing. Webcasting proved the most acceptable way of supporting a common synchronous environment. Having identified a feasible synchronous method we can now investigate hypothesized benefits for staff, students, and patients of combined e‐health e‐learning.
Areas of endemism of the Patagonian steppe: an approach based on insect distributional patterns using endemicity analysis
Authors: Cecilia Domínguez M. , Roig‐Juñent Sergio , Tassin Juan José , Ocampo Federico C. , Flores Gustavo E.
Published: July 2006

Aims  To delimit areas of endemism in the Patagonian steppe using endemicity analysis (EA), which evaluates areas of endemism by means of an endemicity index, and to compare the resulting endemic areas with those proposed for the Patagonian steppe by previous authors.

Location  The Patagonian steppe, a region of South America found approximately below parallel 36° S to the east of the Andes Mountains.

Methods  Distributional data for 159 species of insects collected in the Patagonian steppe, and consisting of 1317 georeferenced samples were used to identify areas of endemism. A data grid of presence and absence (with cells of 1° × 1°) was constructed. Initially, two different types of EA were performed, seeking areas defined by ‘four or more’ species. A first analysis was performed without taking into consideration those quadrats where no species had been recorded (empty quadrats), which in many cases meant a discontinuous distribution. The second analysis was performed assuming a continuous distribution for each species. A third analysis, assuming continuous distributions, was performed using ‘three or more’ as the number of species necessary for an area to be identified as an endemic area.

Results  In the first two analyses, EA recognized the same five areas of endemism: western Patagonia, south‐western Payunia, northern Suabandean, southern Subandean and Austral Patagonia. The results of the third analysis allowed the identification of three more areas of endemism: northern Payunia, Chubutian and Santacrucian.

Main conclusions  We identified five areas of endemism for the Patagonian steppe, some of which have been defined in previous contributions. These areas are: Western Patagonia, Payunia and Subandean Patagonia (which can be divided into septentrional and meridional), Central Patagonia (Chubutence and Santacrucense) and Austral Patagonia.