bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of mice harboring a Sox6 conditional null allele
Authors: Dumitriu Bogdan , Dy Peter , Smits Patrick , Lefebvre Véronique
Published: May 2006

Sox6 belongs to the family of Sry‐related HMG box transcription factors, which determine cell fate and differentiation in various lineages. Sox6 is expressed in several tissues, including cartilage, testis, neuronal, and erythropoietic tissues. Mice lacking Sox6 have revealed critical roles for Sox6 in several of these tissues, but their multiple defects and early lethality has limited studies in specific cell types and in postnatal mice. We show here that we have generated mice harboring a Sox6 conditional null allele (Sox6fl+) by flanking the second coding exon with loxP sites. This allele encodes wildtype Sox6 protein, is expressed normally, and is efficiently converted into a null allele (Sox6fl−) by Cre‐mediated recombination in somatic and germ cells. Sox6fl+/fl+ mice are indistinguishable from wildtype mice, and Sox6fl−/fl− mice from Sox6−/− mice. These Sox6 conditional null mice will thus be valuable for further uncovering the roles of Sox6 in various processes in vivo. genesis 44:219–224, 2006. Published 2006 Wiley‐Liss, Inc.
Mouse ZIP1 and ZIP3 genes together are essential for adaptation to dietary zinc deficiency during pregnancy
Authors: Dufner‐Beattie Jodi , Huang Zhixin L. , Geiser Jim , Xu Wenhao , Andrews Glen K.
Published: May 2006

Subfamily II of the solute‐linked carrier 39A superfamily contains three well‐conserved zinc transporters (ZIPs1, 2, 3) whose physiological functions are unknown. We generated mice homozygous for knockout alleles of ZIP1 and both ZIP1 and ZIP 3 (double‐knockout). These mice were apparently normal when dietary zinc was replete, but when dietary zinc was limited during pregnancy embryos from ZIP1 or ZIP3 knockout mice were two to three times more likely to develop abnormally than those in wildtype mice, and 91% (71/78) of embryos developed abnormally in ZIP1, ZIP3 double‐knockout mice. Analysis of the patterns of expression of these genes in mice revealed predominate expression in intestinal stromal cells, nephric‐tubular epithelial cells, pancreatic ductal epithelial cells, and hepatocytes surrounding the central vein. This suggests that these zinc transporters function, at least in part, in the redistribution and/or retention of zinc rather than its acquisition from the diet. In conclusion, mutations in the ZIP1 and ZIP3 zinc transporter genes are silent when dietary intake of zinc is normal, but can dramatically compromise the success of pregnancy when dietary intake of zinc is limiting. genesis 44:239–251, 2006. Published 2006 Wiley‐Liss, Inc.
Adenosine A2A receptor‐mediated cell death of mouse thymocytes involves adenylate cyclase and Bim and is negatively regulated by Nur77
Authors: Kiss Ildikó , Oskolás Henriett , Tóth Réka , Bouillet Philippe , Tóth Katalin , Fülöp András , Scholtz Beáta , Ledent Catherine , Fésüs László , Szondy Zsuzsa
Published: May 2006

Adenosine is generated in the microenvironment of emerging thymocytes through normal mechanisms of lymphocyte selection. In a normal thymus, most of the adenosine is catabolized by adenosine deaminase; however, in an environment where up to 95% of the cells undergo programmed cell death, a sufficient amount of adenosine is accumulated to trigger cell surface adenosine receptors. Here we show that accumulated adenosine can induce apoptosis in immature mouse thymocytes, mostly via adenosine A2A receptors. The signaling pathway is coupled to adenylate cyclase activation, induction of the Nur77 transcription factor, Nur77‐dependent genes, such as Fas ligand and TRAIL, and the pro‐apoptotic BH3‐only protein Bim. We analyzed several knockout and transgenic mouse lines and found that adenosine‐induced killing of mouse thymocytes requires Bim, occurs independently of “death receptor” signaling and is inhibited by Bcl‐2 and Nur77. Collectively our data demonstrate that adenosine‐induced cell death involves signaling pathways originally found in negative selection of thymocytes and suggest a determining role of Bim and a regulatory role for Nur77.
Olig gene function in CNS development and disease
Authors: Ligon Keith L. , Fancy Stephen P.J. , Franklin Robin J.M. , Rowitch David H.
Published: May 2006

Olig1 and Olig2 encode basic helix‐loop‐helix (bHLH) transcription factors that are expressed in both the developing and mature vertebrate central nervous system. While numerous studies have established critical functions for Olig genes during the formation of motor neurons and oligodendrocytes of the ventral neural tube, their roles at later stages of development and in adulthood have remained relatively obscure. Recent studies, however, reveal that in the fetal dorsal spinal cord and neural progenitor cells of the adult brain, Olig expression continues to mark, and may regulate, the formation of oligodendroglia. Studies of Olig expression in human brain tumors and repair of demyelinating lesions suggest the possibility of additional functions in a variety of neurological diseases. © 2005 Wiley‐Liss, Inc.
Gene‐specific mechanisms of p53 transcriptional control and prospects for cancer therapy
Authors: Resnick‐Silverman Lois , Manfredi James J.
Published: May 2006

The regulation of gene‐specific activation is critical to the tumor suppressor function by p53. p53 is a well‐characterized transcription factor that responds to DNA damage and other genotoxic stresses by the activation of downstream targets that are involved with repair, differentiation, senescence, growth arrest, and apoptosis. Sequence‐specific binding to DNA, conformation, post‐translational modifications, cofactor binding, stability, and subcellular localization all influence the performance of p53. The purpose of this review is to define features that play a key role in gene‐specific activation and to show that these are often incapacitated in cancer cells. Using such knowledge to design selective strategies for the restoration of p53 wild‐type function in cancer cells represents a promising cancer therapy. J. Cell. Biochem. 99: 679–689, 2006. © 2006 Wiley‐Liss, Inc.
A role of the mitotic spindle checkpoint in the cellular response to DNA replication stress
Authors: Duensing Anette , Teng Xiaoyi , Liu Ying , Tseng Michelle , Spardy Nicole , Duensing Stefan
Published: May 2006

Replication stress is a frequent and early event during tumorigenesis. Whereas the cellular responses to a persistent block of replication fork progression have been extensively studied, relatively little is known about how cells respond to low‐intensity replication stress. However, transient replication fork perturbations are likely to occur even more frequently in tumor cells than a permanent replication arrest. We report here that transient, low intensity replication stress leads to a rapid activation of the DNA replication checkpoint but to a significantly delayed apoptotic response in a small but significant number of cells. This late apoptotic response was independent of p53 and we found evidence for cell death during mitosis in a proportion of cells. To further explore the role of p53 in the response to replication stress, we analyzed mouse embryonic fibroblasts (MEFs) deficient of p53 in comparison to wild‐type or p63‐ or p73‐deficient MEFs. We detected a significant increase of apoptosis and morphological signs of failed mitosis such as multinucleation in p53‐deficient MEFs following replication stress, but not in wild‐type or p63‐ or p73‐deficient cells. Multinucleated p53‐deficient MEFs frequently retained cyclin B1 expression indicating a persistently activated mitotic spindle checkpoint. Collectively, our results suggest that the cellular response to replication stress involves the mitotic spindle checkpoint in a proportion of cells. These findings imply that the mitotic spindle checkpoint may act in concert with DNA damage and cell‐cycle checkpoints as an early anti‐tumor barrier and provide a possible explanation for its frequent relaxation in human cancer. J. Cell. Biochem. 99: 759–769, 2006. © 2006 Wiley‐Liss, Inc.
Microglial α7 nicotinic acetylcholine receptors drive a phospholipase C/IP3pathway and modulate the cell activation toward a neuroprotective role
Authors: Suzuki Tomohisa , Hide Izumi , Matsubara Akiyo , Hama Chihiro , Harada Kana , Miyano Kanako , Andrä Matthias , Matsubayashi Hiroaki , Sakai Norio , Kohsaka Shinichi , Inoue Kazuhide , Nakata Yoshihiro
Published: May 2006

Microglia perform both neuroprotective and neurotoxic functions in the brain, with this depending on their state of activation and their release of mediators. Upon P2X7receptor stimulation, for example, microglia release small amounts of TNF, which protect neurons, whereas LPS causes massive TNF release leading to neuroinflammation. Here we report that, in rat primary cultured microglia, nicotine enhances P2X7receptor‐mediated TNF release, whilst suppressing LPS‐induced TNF release but without affecting TNF mRNA expression via activation of α7 nicotinic acetylcholine receptors (α7 nAChRs). In microglia, nicotine elicited a transient increase in intracellular Ca2+levels, which was abolished by specific blockers of α7 nAChRs. However, this response was independent of extracellular Ca2+and blocked by U73122, an inhibitor of phospholipase C (PLC), and xestospongin C, a blocker of the IP3receptor. Repeated experiments showed that currents were not detected in nicotine‐stimulated microglia. Moreover, nicotine modulation of LPS‐induced TNF release was also blocked by xestospongin C. Upon LPS stimulation, inhibition of TNF release by nicotine was associated with the suppression of JNK and p38 MAP kinase activation, which regulate the post‐transcriptional steps of TNF synthesis. In contrast, nicotine did not alter any MAP kinase activation, but enhanced Ca2+response in P2X7receptor‐activated microglia. In conclusion, microglial α7 nAChRs might drive a signaling process involving the activation of PLC and Ca2+release from intracellular Ca2+stores, rather than function as conventional ion channels. This novel α7 nAChR signal may be involved in the nicotine modification of microglia activation towards a neuroprotective role by suppressing the inflammatory state and strengthening the protective function. © 2006 Wiley‐Liss, Inc.
Checkpoint kinase 1‐mediated phosphorylation of Cdc25C and bad proteins are involved in antitumor effects of loratadine‐induced G2/M phase cell‐cycle arrest and apoptosis
Authors: Chen Jinn‐Shiun , Lin Shyr‐Yi , Tso Wei‐Ling , Yeh Geng‐Chang , Lee Wen‐Sen , Tseng How , Chen Li‐Ching , Ho Yuan‐Soon
Published: May 2006

In this study, we first demonstrated that loratadine (LOR), a promising world widely used oral anti‐histamine, effectively inhibits growth of tumors derived from human colon cancer cells (COLO 205) in an in vivo setting. In vitro study demonstrated that the anti‐tumor effects of LOR in COLO 205 cells were mediated by causing G2/M phase cell growth cycle arrest and caspase 9‐mediated apoptosis. Cell‐cycle arrest induced by LOR (75 µM, 24 h) was associated with a significant decrease in protein levels of cyclin B1, cell division cycle (Cdc) 25B, and Cdc25C, leading to accumulation of Tyr‐15‐phosphorylated Cdc2 (inactive form). Interestingly, LOR (75 µM, for 4 h) treatment also resulted in a rapid and sustained phosphorylation of Cdc25C at Ser‐216, leading to its translocation from the nucleus to the cytoplasm because of increased binding with 14‐3‐3. We further demonstrated that the LOR‐induced Cdc25C (Ser‐216) phosphorylation was blocked in the presence of checkpoint kinase 1 (Chk1) specific inhibitor (SB‐218078). The cells treated with LOR in the presence of Chk1 specific inhibitor (SB‐218078) were then released from G2/M arrest into apoptosis. These results implied that Chk1‐mediated phosphorylation of Cdc25C plays a major role in response to LOR‐mediated G2/M arrest. Although the Chk1‐mediated cell growth arrest in response to DNA damage is well documented, our results presented in this study was the first report to describe the Chk1‐mediated G2/M cell‐cycle arrest by the histamine H1 antagonist, LOR. © 2006 Wiley‐Liss, Inc.
Anti‐angiogenic drugs: from bench to clinical trials
Authors: Quesada Ana R. , Muñoz‐Chápuli Ramón , Medina Miguel A.
Published: May 2006

Angiogenesis, the generation of new capillaries through a process of pre‐existing microvessel sprouting, is under stringent control and normally occurs only during embryonic and post‐embryonic development, reproductive cycle, and wound repair. However, in many pathological conditions (solid tumor progression, metastasis, diabetic retinopathy, hemangioma, arthritis, psoriasis and atherosclerosis among others), the disease appears to be associated with persistent upregulated angiogenesis. The development of specific anti‐angiogenic agents arises as an attractive therapeutic approach for the treatment of cancer and other angiogenesis‐dependent diseases. The formation of new blood vessels is a complex multi‐step process. Endothelial cells resting in the parent vessels are activated by an angiogenic signal and stimulated to synthesize and release degradative enzymes allowing endothelial cells to migrate, proliferate and finally differentiate to give rise to capillary tubules. Any of these steps may be a potential target for pharmacological intervention. In spite of the disappointing results obtained initially in clinical trials with anti‐angiogenic drugs, recent reports with positive results in phases II and III trials encourage expectations in their therapeutic potential. This review discusses the current approaches for the discovery of new compounds that inhibit angiogenesis, with emphasis on the clinical developmental status of anti‐angiogenic drugs. © 2006 Wiley Periodicals, Inc. Med Res Rev, 26, No. 4, 483–530, 2006
Incidence and survival of childhood Langerhans cell histiocytosis in Northwest England from 1954 to 1998
Authors: Alston R.D. , Tatevossian R.G. , McNally R.J.Q. , Kelsey A. , Birch J.M. , Eden T.O.B.
Published: May 2006

Background

Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of pathological Langerhans cells, for which the aetiology and pathogenesis remain largely unknown.

Procedure

Information on the 101 children with LCH registered with the population‐based Manchester Children's Tumour Registry (MCTR) between 1954 and 1998 was extracted from the records of the MCTR. This included age, sex, date of diagnosis, systems affected at diagnosis and follow‐up.

Results

The overall incidence rate for LCH was 2.6 cases per million child years. In those under 1 year of age the incidence rate was 9.0 cases per million child years, compared to 0.7 cases per million in those aged 10–14 years (P < 0.0001 for age trend). There was no evidence of seasonal variation in presentation by month of birth or first symptom. Bone was the most common site of disease involvement (67% of cases), followed by skin (37%) and soft tissue (22%). The overall survival rate has improved over time, from 57% in 1954–1968 to 74% in 1985–1998. Ninety percent of deaths were due to disease progression, the remainder were due to complications of intensive therapy. The site of LCH lesions and extent of disease present at diagnosis strongly predicted survival outcome. Patients with initial liver involvement had a 5‐year survival rate of 25% compared with 93% for those with bone lesions alone at diagnosis.

Conclusions

Incidence rates varied significantly by age at diagnosis, and have been stable over time. Survival has improved considerably over time, but varies strongly by age and systems affected at diagnosis. Pediatr Blood Cancer 2007;48:555–560. © 2006 Wiley‐Liss, Inc.
Prediction of infinite dilution solvent activity coefficient in rubbery polymer solutions using Engaged Species Induced Clustering (ENSIC) model
Authors: Haidong Feng
Published: May 2006

It is extremely important to predict infinite dilution solvent activity coefficients in rubbery polymers in design and operation of polymer‐related processes. Many models have been developed to predict the activity coefficients. However, the accuracies of these models are not satisfactory. This article advances a method for predicting the infinite solvent dilution activity coefficients in the rubbery polymers, using the Engaged Species Induced Clustering (ENSIC) model. It elucidates the physiochemical significance and mathematical meaning of the parameters in the ENSIC model. In this article, the ENSIC approach has been proven to agree extremely well with the experimental data in both correlating the finite dilution solvent activity coefficient and predicting the infinite dilution solvent activity coefficient for rubbery polymer/solvent systems. In other words, both the ENSIC equation and its derivative at extremely low solvent concentration are in good agreement with the experimental data. In addition, the article indicates that the ENSIC model is much more accurate than another kind of empirical models‐ the F–H and related models in predicting the infinite dilution solvent activity coefficients in polymer solutions. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 1668–1675, 2006
Evaluation of antiinflammatory activity of the total flavonoids of Laggera pterodonta on acute and chronic inflammation models
Authors: Wu Yihang , Zhou Changxin , Li Xiangping , Song Liyan , Wu Xiumei , Lin Wenyan , Chen Haiyong , Bai Hua , Zhao Jun , Zhang Rongping , Sun Handong , Zhao Yu
Published: May 2006

The antiinflammatory effect of the total flavonoids of Laggera pterodonta (TFLP) was evaluated with various in vivo models of both acute and chronic inflammation. In the acute inflammation tests, TFLP significantly inhibited xylene‐induced mouse ear oedema, carrageenan‐induced rat paw oedema and acetic acid‐induced mouse vascular permeability. In the carrageenan‐induced rat pleurisy model, TFLP efficiently suppressed inflammatory exudate and leukocyte migration, reduced the serum levels of lysozyme (LZM) and malondialdehyde (MDA), increased the activity of serum superoxide dismutase (SOD), and also decreased the contents of total protein, nitric oxide (NO) and prostaglandin E2 (PGE2) in the pleural exudates. No marked effect of TFLP on the activity of serum glutathione peroxidase (GSH‐PX) was observed. In the chronic inflammation experiment, TFLP inhibited cotton pellet‐induced rat granuloma. The antiinflammatory mechanisms of TFLP are probably associated with the inhibition of prostaglandin formation, influence on the antioxidant systems and the suppression of LZM release. The acute toxicity study revealed that TFLP was nontoxic in mice up to an oral dose of 7.5 g/kg body weight. Copyright © 2006 John Wiley & Sons, Ltd.
Self-excited oscillations in the wake of two-dimensional bluff bodies and their control
Authors: Schumm Michael , Berger Eberhard , Monkewitz Peter A.
Published: May 2006

The onset of Kármán-vortex shedding is studied experimentally in the wake of different two-dimensional bluff bodies, namely an oblong cylinder, circular cylinders and plates of rectangular cross-section. Different control measures, such as wake heating, transverse body oscillations and base bleed are investigated. As the steady-periodic Kármán shedding has previously been identified as a limit-cycle, i.e. as self-excited oscillations, the experiments are interpreted in the framework of the Stuart–Landau model. The coefficients of the Stuart–Landau equation for the characteristic vortex shedding amplitude, i.e. the linear temporal growth rate, linear frequency and the Landau constant, are fully determined for the two cylinders and in part for the plate. For this purpose transients are generated by suddenly switching transverse body oscillations or base bleed on or off. The analysis of these transients by a refined method based on complex demodulation provides reliable estimates of the model coefficients and yields an experimental validation of the concept that a global instability mode grows or decays as a whole. Also, it is demonstrated that the coefficients of the Stuart–Landau equation are independent of the experimental technique used to produce the transients.
Horizontal wave propagation in the equatorial waveguide
Authors: Ripa P.
Published: May 2006

The dispersive (i.e. non-Kelvin) linear wave field on the equatorial β-plane, in a single vertical mode, is fully described by a single potential φ. Long Rossby waves, which are weakly dispersive, are represented in this field. This description is free from the problem of the ‘spurious solution’ encountered when working with an evolution equation for the meridional velocity; addition of this unwanted solution represents a gauge transformation that leaves the physical fields unaltered.

The general solution of the ray equations is found, including trajectories, and the amplitudes and phase fields. This solution is asymptotically valid for either high or low frequencies. The ray paths are identical in both limits, but the phase field is not, reflecting the isotropy of Poincaré waves, in one case, and the zonal anisotropy of Rossby waves, in the other.

Two examples are studied by ray theory: meridional normal modes and wave radiation from a point source in the equator. In the first case, the exact dispersion relation is obtained. In the second one, northern and southern caustics bend towards the equator, meeting there at focal points. The full solution is the superposition of many leaves and has a structure that would be hard to find in a normal modes expansion.
Risk factors for encephalitis and death from West Nile virus infection
Authors: MURRAY K. , BARANIUK S. , RESNICK M. , ARAFAT R. , KILBORN C. , CAIN K. , SHALLENBERGER R. , YORK T. L. , MARTINEZ D. , HELLUMS J. S. , HELLUMS D. , MALKOFF M. , ELGAWLEY N. , McNEELY W. , KHUWAJA S. A. , TESH R. B.
Published: May 2006

We conducted a nested case-control study to determine potential risk factors for developing encephalitis from West Nile virus (WNV) infection. Retrospective medical chart reviews were completed for 172 confirmed WNV cases hospitalized in Houston between 2002 and 2004. Of these cases, 113 had encephalitis, including 17 deaths, 47 had meningitis, and 12 were fever cases; 67% were male. Homeless patients were more likely to be hospitalized from WNV compared to the general population. A multiple logistic regression model identified age [odds ratio (OR) 1·1, P<0·001], history of hypertension, including those cases taking hypertension-inducing drugs (OR 2·9, P=0·012), and history of cardiovascular disease (OR 3·5, P=0·061) as independent risk factors for developing encephalitis from WNV infection. After adjusting for age, race/ethnicity (being black) (OR 12·0, P<0·001), chronic renal disease (OR 10·6, P<0·001), hepatitis C virus (OR 23·1, P=0·0013), and immunosuppression (OR 3·9, P=0·033) were identified as risk factors for death from WNV infection.
Inhibition of fatty acid amide hydrolase produces analgesia by multiple mechanisms
Authors: Chang Leon , Luo Lin , Palmer James A , Sutton Steven , Wilson Sandy J , Barbier Ann J , Breitenbucher James Guy , Chaplan Sandra R , Webb Michael
Published: May 2006

British Journal of Pharmacology (2006) 148, 114. doi:10.1038/sj.bjp.0706773
Nonlocal to local transition of electron kinetic property in magnetized plasma
Authors: You S. J. , Chang H. Y.
Published: May 2006

The spatially resolved measurements of electron energy distribution functions (EEDFs) in a magnetized capacitive discharge reveal that the nonlocal electron kinetic property, the coincident property of the EEDFs of the total energy [kinetic energy (u) + potential energy(ϕ)] in different spatial positions, disappears as the magnetic field increases. This result can be understood as a transition of electron kinetic property from a nonlocal to a local regime induced by the magnetic field. This transition results from the fact that the magnetic field decreases the electron diffusion in the coordinates space but increases the electron diffusion in the energy space.
Research note: Leaf cooling curves: measuring leaf temperature in sunlight
Authors: Leigh Andrea , Close John D. , Ball Marilyn C. , Siebke Katharina , Nicotra Adrienne B.
Published: May 2006

Despite the obvious benefits of using thermography under field conditions, most infrared studies at the leaf level are generally conducted in the laboratory. One reason for this bias is that accuracy can potentially be compromised in sunlight because reflected radiation from the leaf might affect the calculation of the temperature measurement. We have developed a method for measuring leaf temperature in sunlight by using thermal imagery to generate cooling curves from which the time constant for cooling, τ, can be calculated. The original temperature of the sunlit leaf may be determined by extrapolating backwards in time. In the absence of specular reflection, there is close agreement between the extrapolated sunlit temperature and the sunlit temperature recorded by the camera. However, when reflected radiation is high, the difference between the initial (incorrect) temperature determined from the sunlit image and the temperature extrapolated from the cooling curve can be > 2°C. Notably, our results demonstrate a close agreement between the extrapolated sunlit temperature and the temperature of the leaf approximately 1 s after being shaded, suggesting that this shaded image provides a good estimate of the original sunlit temperature. Thus, our technique provides two means for measuring leaf surface temperature in sunlight.
Langerhans cells cross-present antigen derived from skin
Authors: Stoitzner Patrizia , Tripp Christoph H. , Eberhart Andreas , Price Kylie M. , Jung Jae Y. , Bursch Laura , Ronchese Franca , Romani Nikolaus
Published: May 2006

Dendritic cells (DC) efficiently cross-present exogenous antigen on MHC class I molecules to CD8+T cells. However, little is known about cross-presentation by Langerhans cells (LC), the DCs of the epidermis. Therefore, we investigated this issue in detail. Isolated murine LCs were able to cross-present soluble ovalbumin protein on MHC-class I molecules to antigen-specific CD8+T cells, albeit less potently than the CD8+DC subsets from spleen. Furthermore, LCs cross-presented cell-associated ovalbumin peptide and protein expressed by neighboring keratinocytes. Use of transporter associated with antigen processing (TAP-1)-deficient mice suggested a TAP-dependent pathway. Similar observations were made with migratory LC. Antigen expressed in the epidermis was ingested by LCs during migration from the epidermis and presented to antigen-specific T cellsin vitro. Cross-presentation of ovalbumin protein by LCs induced IFN-γ production and cytotoxicity in antigen-specific CD8+T cells. Additionally, epicutaneous application of ovalbumin protein inducedin vivoproliferation of OT-I T cells in the draining lymph nodes; this was markedly enhanced when antigen was applied to inflamed, barrier-disrupted skin. Thus, LCs cross-present exogenous antigen to CD8+T cells and induce effector functions, like cytokine production and cytotoxicity, and may thereby critically contribute in epicutaneous vaccination approaches.
Semantic numerical representation in blind subjects: The role of vision in the spatial format of the mental number line
Authors: Castronovo Julie , Seron Xavier
Published: May 2006

Does vision play a role in the elaboration of the semantic representation of small and large numerosities, notably in its spatial format? To investigate this issue, we decided to compare in the auditory modality the performance of congenitally and early blind people with that of a sighted control group, in two number comparison tasks (to 5 and to 55) and in one parity judgement task. Blind and sighted participants presented exactly the same distance and SNARC (Spatial Numerical Association of Response Codes) effects, indicating that they share the same semantic numerical representation. In consequence, our results suggest that the spatial dimension of the numerical representation is not necessarily attributable to the visual modality and that the absence of vision does not preclude the elaboration of this representation for 1-digit (Experiment 1) and 2-digit numerosities (Experiment 2). Moreover, as classical semantic numerical effects were observed in the auditory modality, the postulate of the amodal nature of the mental number line for both small and large magnitudes was reinforced.
The role of visual attention in action priming
Authors: Vainio Lari , Ellis Rob , Tucker Mike
Published: May 2006

It has been demonstrated that the task-irrelevant left–right orientation of an object is capable of facilitating left–right-hand responses when the object is orientated towards the responding hand. We investigated the role of attention in this orientation effect. Experiment 1 showed that object orientation facilitates responses of the hand that is compatible with the object's orientation, despite the entire object being irrelevant. However, when a task-relevant fixation point was displayed over the prime object in Experiment 2, the effect was not observed. Together Experiments 1 and 2 suggest that the orientation information of viewed objects primes the action selection processes even when the object is irrelevant, but only when attention is not allocated to a competing stimulus during the prime presentation. Experiment 3 suggested that the elimination of the effect in Experiment 2 could not be attributed to the elimination of an attentional shift to the graspable part of the prime. Finally, Experiment 4 showed that object orientation can evoke an abstract response code, influencing the selection of finger responses.
Integrative Array Analyzer: a software package for analysis of cross-platform and cross-species microarray data
Authors: Pan Fei , Kamath Kiran , Zhang Kangyu , Pulapura Sudip , Achar Avinash , Nunez-Iglesias Juan , Huang Yu , Yan Xifeng , Han Jiawei , Hu Haiyan , Xu Min , Hu Jianjun , Zhou Xianghong Jasmine
Published: May 2006

Summary: The rapid accumulation of microarray data translates into an urgent need for tools to perform integrative microarray analysis. Integrative Array Analyzer is a comprehensive analysis and visualization software toolkit, which aims to facilitate the reuse of the large amount of cross-platform and cross-species microarray data. It is composed of the data preprocess module, the co-expression analysis module, the differential expression analysis module, the functional and transcriptional annotation module and the graph visualization module.

Availability:  

Contact:  xjzhou@usc.edu
Ensemble classifier for protein fold pattern recognition
Authors: Shen Hong-Bin , Chou Kuo-Chen
Published: May 2006

Motivation: Prediction of protein folding patterns is one level deeper than that of protein structural classes, and hence is much more complicated and difficult. To deal with such a challenging problem, the ensemble classifier was introduced. It was formed by a set of basic classifiers, with each trained in different parameter systems, such as predicted secondary structure, hydrophobicity, van der Waals volume, polarity, polarizability, as well as different dimensions of pseudo-amino acid composition, which were extracted from a training dataset. The operation engine for the constituent individual classifiers was OET-KNN (optimized evidence-theoretic k-nearest neighbors) rule. Their outcomes were combined through a weighted voting to give a final determination for classifying a query protein. The recognition was to find the true fold among the 27 possible patterns.

Results: The overall success rate thus obtained was 62% for a testing dataset where most of the proteins have <25% sequence identity with the proteins used in training the classifier. Such a rate is 6–21% higher than the corresponding rates obtained by various existing NN (neural networks) and SVM (support vector machines) approaches, implying that the ensemble classifier is very promising and might become a useful vehicle in protein science, as well as proteomics and bioinformatics.

Availability: The ensemble classifier, called PFP-Pred, is available as a web-server at for public usage.

Contact:  lifesci-sjtu@san.rr.com

Supplementary information: Supplementary data are available on Bioinformatics online.
A Mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways inC. elegans
Authors: Taubert Stefan , Van Gilst Marc R. , Hansen Malene , Yamamoto Keith R.
Published: May 2006

TheCaenorhabditis elegansNuclear Hormone Receptor NHR-49 coordinates expression of fatty acid (FA) metabolic genes during periods of feeding and in response to fasting. Here we report the identification of MDT-15, a subunit of theC. elegansMediator complex, as an NHR-49-interacting protein and transcriptional coactivator. Knockdown ofmdt-15by RNA interference (RNAi) prevented fasting-induced mRNA accumulation of NHR-49 targets in vivo, and fasting-independent expression of other NHR-49 target genes, including two FA-Δ9-desaturases (fat-5,fat-7). Interestingly,mdt-15RNAi affected additional FA-metabolism genes (including the third FA-Δ9-desaturase,fat-6) that are regulated independently of NHR-49, suggesting that distinct unidentified regulatory factors also recruit MDT-15 to selectively modulate metabolic gene expression. The deregulation of FA-Δ9-desaturases by knockdown ofmdt-15correlated with dramatically decreased levels of unsaturated FAs and multiple deleterious phenotypes (short life span, sterility, uncoordinated locomotion, and morphological defects). Importantly, dietary addition of specific polyunsaturated FAs partially suppressed these pleiotropic phenotypes. Thus, failure to properly govern FA-Δ9-desaturation contributed to decreased nematode viability. Our findings imply that a single subunit of the Mediator complex, MDT-15, integrates the activities of several distinct regulatory factors to coordinate metabolic and hormonal regulation of FA metabolism.
Transcriptional and post-transcriptional regulation of the circadian clock of cyanobacteria and Neurospora
Authors: Brunner Michael , Schafmeier Tobias
Published: May 2006

Circadian clocks are self-sustained oscillators modulating rhythmic transcription of large numbers of genes. Clock-controlled gene expression manifests in circadian rhythmicity of many physiological and behavioral functions. In eukaryotes, expression of core clock components is organized in a network of interconnected positive and negative feedback loops. This network is thought to constitute the pacemaker that generates circadian rhythmicity. The network of interconnected loops is embedded in a supra-net via a large number of interacting factors that affect expression and function of core clock components on transcriptional and post-transcriptional levels. In particular, phosphorylation and dephosphorylation of clock components are critical processes ensuring robust self-sustained circadian rhythmicity and entrainment of clocks to external cues. In cyanobacteria, three clock proteins have the capacity to generate a self-sustained circadian rhythm of autophosphorylation and dephosphorylation independent of transcription and translation. This phosphorylation rhythm regulates the function of these clock components, which then facilitate rhythmic gene transcription, including negative feedback on their own genes. In this article, we briefly present the mechanism of clock function in cyanobacteria. We then discuss in detail the contribution of transcriptional feedback and protein phosphorylation to various functional aspects of the circadian clock of Neurospora crassa.
Iterative gene prediction and pseudogene removal improves genome annotation
Authors: van Baren Marijke J. , Brent Michael R.
Published: May 2006

Correct gene prediction is impaired by the presence of processed pseudogenes: nonfunctional, intronless copies of real genes found elsewhere in the genome. Gene prediction programs frequently mistake processed pseudogenes for real genes or exons, leading to biologically irrelevant gene predictions. While methods exist to identify processed pseudogenes in genomes, no attempt has been made to integrate pseudogene removal with gene prediction, or even to provide a freestanding tool that identifies such erroneous gene predictions. We have created PPFINDER (for Processed Pseudogene finder), a program that integrates several methods of processed pseudogene finding in mammalian gene annotations. We used PPFINDER to remove pseudogenes from N-SCAN gene predictions, and show that gene prediction improves substantially when gene prediction and pseudogene masking are interleaved. In addition, we used PPFINDER with gene predictions as a parent database, eliminating the need for libraries of known genes. This allows us to run the gene prediction/PPFINDER procedure on newly sequenced genomes for which few genes are known.
Per capita alcohol consumption and sickness absence
Authors: Norström Thor
Published: May 2006

Aim  The purpose of the study was to assess the relationship between aggregate alcohol consumption and sickness absence in Sweden.

Data and methods  Two indicators of sickness absence were used, one based on sickness insurance data, the other on data from the labour force surveys. Alcohol consumption was gauged by sales of pure alcohol (100%) per inhabitant 15 years of age and older. Because changes in the economy may affect alcohol consumption as well as sickness absence, two macroeconomic indicators were included as control variables: unemployment and real wages. The study period was 1935–2002. The data were analysed through the Box–Jenkins method for time‐series analyses.

Findings  A 1‐litre increase in total consumption was associated with a 13% increase in sickness absence among men (P < 0.05). The relationship was not statistically significant for women.

Conclusions  Previous research has documented that aggregate alcohol consumption is related to a large number of harm indicators, such as cirrhosis and accident mortality. The present findings add yet another indicator to this list.
Portfolios: a developmental influence?
Authors: Cayne Julia V
Published: May 2006

A situational analysis had demonstrated a need to help staff within an orthopaedic/trauma unit review past and plan future learning One way of doing this is through the preparation of a portfolio An action research project was undertaken to explore two research questions Is the process of portfolio preparation in itself developmental? If so, what factors influence this developmental process7 Development was seen as a process of change indicated through application of the characteristics of adult learners The action involved meeting as a learning group to explore the process and discuss the problems Questionnaires were completed by group members to raise issues for further discussion at interview The interviews formed a summative evaluation of the process up to the last group meeting Data were analysed through a process of thematic content analysis, resulting in the identification of various categories These categories were then used to explore the two research questions Findings suggest that the process itself does influence development by acting as an initiator to reflection on experience Owing to the short time span and small numbers involved, the project was intended as an exploratory study and as such it has provided direction for future research
Caregiver/resident relationships: surrogate family bonds and surrogate grieving in a skilled nursing facility*
Authors: Sumaya‐Smith Isabel
Published: May 2006

The study investigated the occurrence of surrogate family bonds and surrogate grieving by staff members (n= 25) at a rural skilled nursing facility Staff members were educated on both concepts then given a structured interview to test for occurrence and identification with these concepts Public opinion, as well as the literature, describes the caregiver/resident relationship as ahistorical, lacking close emotional bonds However, staff members are often observed to report close emotional bonds and grieving over the death of residents This study tested the hypotheses that self‐reported caregiver surrogate family bonds and self‐reported caregiver surrogate grieving would exist at a significantly higher rate than the literature would predict Chi‐square analysis supported the hypothesis for surrogate family bonds, χ2 (1, n= 25) = 17 64, P < 0 001 Surrogate family bonds were found to occur in 92% of the present sample However, surrogate grieving was not supported and was found to occur in only 52% of the sample
Bladder instillations and bladder washouts in the management of catheterized patients
Authors: Gethffe Kathryn A
Published: May 2006

Considerable controversy exists over the instillation of solutions into the bladder of catheterized patients The main purpose of this paper is to present existing research‐based evidence on the potential advantages and disadvantages of their use to assist practitioners to clarify the issues and to make informed decisions during client care
An investigation into how the health care assistants perceive their role as ‘support workers’ to the qualified staff
Authors: Workman Barbara A
Published: May 2006

This qualitative study investigates the support worker's role as perceived by health care assistants (HCAs) who have undergone some training and National Vocational Qualification assessments The findings suggest that the HCAs consider that they support the trained nurses by acting as a link in the communication chain between the patient and carers, and by providing ‘time’ for the trained nurse to use in therapeutic activities The indications are that the HCAs perceive little difference between then roles and those of qualified nurses, and that they experience ambiguity as to their proper role The researcher sought to apply role theory in an inductive approach to data interpretation, from which it is posited that the HCAs' role ambiguity arises because the qualified nurses' own role lacks clarity and this affects their expectations of the HCA's role Having had some training, the roles are more ambiguous now than before as the HCAs are no longer untrained carers but nor are they qualified professionals It is also suggested that the qualified nurses perceive the HCAs as a threat to their own roles in that the HCAs are seen as depriving them of their ‘real’ nursing role, thus they are experiencing ‘role deprivation’ Recommendations to clarify role expectations and reduce role ambiguities are suggested to alleviate an avoidable source of stress for both the qualified nurse and the HCA
Problem‐based learning in an undergraduate nursing programme: a case study
Authors: Andrews Margaret , Jones Peter Reece
Published: May 2006

Over the past 15 years, the ‘theory‐practice gap’ has been a recurrent theme in the nurse education literature Numerous explanations are put forward for its existence, along with many suggestions as to how the apparent divide can be bridged A key component of nursing practice is problem‐solving but not all nurses are competent at finding suitable solutions to the problems they face in practice settings Therefore ways of developing learner proficiency in problem‐solving is crucial and should occupy a substantial part of teacher activity One recent educational method for promoting problem‐solving skills is problem‐based learning [PBL] using the hypothetico‐deductive technique This approach encourages students to work through problem situations, generating hypotheses and testing these against the relevant literature and personal experience The process itself is seen as the essential element in developing problem‐solving skills, so that when the students are qualified they can apply the same methods to patient care This paper explores the use of the PBL approach with a group of 11 fourth‐year undergraduate students The method employed was a case study design using observation as the main data collection technique Subsequent analysis focused on (a) practice, (b) teaching method, (c) knowledge attainment, and (d) the role of the teacher
Changes in Rb+ and Ca2+ influx in winter wheat roots before, during and after exposure to low temperature and short days
Authors: Jensén Paul , Erlandson Gunvor
Published: May 2006

Influx of Rb+(86Rb+) and Ca2+ (45Ca2+) in roots of intact winter wheat (Triticum aestivum L. cv. Weibulls Starke II) was determined at intervals before, during and after exposure to cold acclimation conditions (2°C and 8 h light period). The plants were grown in nutrient medium of two ionic strengths. During the initial two weeks of growth at 16°C and 16 h light period, Rb+ influx into roots decreased with increasing age, probably as a consequence of a decreasing proportion of metabolically active roots. The presence of 10−4M 2,4‐dinitrophenol (DNP) reduced Rb+ influx to a low and constant level, indicating that metabolic influx was the dominant process. In contrast, Ca2+ influx in plants grown in full strength nutrient solution was higher in the presence than in the absence of DNP. This effect may have been due to an active extrusion mechanism mediating re‐export of absorbed Ca2+(45Ca2+) during the uptake experiment. With the metabolic uncoupler inhibiting such extrusion the Ca2+(45Ca2+) influx mesured would increase. During cold treatment, Rb+ influx remained at a low level, and was further decreased when DNP was present in the uptake solution. This effect may have been due to inhibition of residual active influx of Rb+ at 2°C by the uncoupler and/or to a decrease in membrane permeability. In contrast to Rb+, Ca2+ influx increased during cold treatment, which could again be explained as inhibition of re‐export. The presence of DNP reduced Ca2+ influx at 2°C, indicating decreased membrane permeability by DNP at low temperature. After transfer of plants from cold acclimation conditions to 16°C, Rb+ and Ca2+ influx increased in plants grown at both ionic strengths. Influx levels were independent of the length of the cold acclimation period (1, 6 and 8 weeks), but the patterns were different for the two ions. After each of the cold acclimation periods, Rb+ influx increased during the first week and decreased or remained at the same level during the second week, while Ca2+ influx always decreased during the second week of post‐cold treatment.
Response ofPlantago majorseeds to the red/far‐red ratio as influenced by other environmental factors
Authors: Pons T. L.
Published: May 2006

Seeds ofPlantago majorL. ssp.majorwere exposed to continuous light of various red/far‐red ratios (R/FR). Germination was strongly inhibited at low R/FR. The quantitative response of the seeds to the R/FR appeared to depend on various environmental factors. A low R/FR was less inhibitory after a stratification pretreatment, at higher temperatures, in the presence of nitrate and at high osmotic potentials. This is discussed in relation to the concept of a variable requirement of Pfrfor germination, which depends on state of dormancy as influenced by pretreatment and on conditions during the germination test. The data are also discussed in relation to field emergence. The species is known to form a persistent seed bank, among other things due to its almost absolute light requirement. It is predicted that germination is effectively inhibited under a leaf canopy in summer after dispersal, and perhaps even in spring to some extent when R/FR is not so low but temperatures are low.