bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple strategies of Lake Victoria cichlids to cope with lifelong hypoxia include hemoglobin switching
Authors: Rutjes H. A. , Nieveen M. C. , Weber R. E. , Witte F. , Van den Thillart G. E. E. J. M.
Published: July 2007

Many fish species adapt to hypoxia by reducing their metabolic rate and increasing hemoglobin-oxygen (Hb-O2) affinity. Pilot studies with young broods of cichlids showed that the young could survive severe hypoxia in contrast with the adults. It was therefore hypothesized that early exposure results in improved oxygen transport. This hypothesis was tested using split brood experiments. Broods of Astatoreochromis alluaudi, Haplochromis ishmaeli, and a tilapia hybrid ( Oreochromis) were raised either under normoxia (NR; 80–90% air saturation) or hypoxia (HR; 10% air saturation). The activity of the mitochondrial citrate synthase was not different between NR and HR tilapia, but was significantly decreased in HR A. alluaudi and H. ishmaeli, indicating lowered maximum aerobic capacities. On the other hand, hemoglobin and hematocrit levels were significantly higher in all HR fish of the three species, reflecting a physiological adaptation to safeguard oxygen transport capacity. In HR tilapia, intraerythrocytic GTP levels were decreased, suggesting an adaptive increase of blood-O2affinity. Similar changes were not found in HR H. ishmaeli. In this species, however, all HR specimens exhibited a distinctly different iso-Hb pattern compared with their NR siblings, which correlated with a higher intrinsic Hb-O2affinity in the former. All HR cichlids thus reveal left-shifted Hb-O2equilibrium curves, mediated by either decreased allosteric interaction or, in H. ishmaeli, by the production of new hemoglobins. It is concluded that the adaptation to lifelong hypoxia is mainly due to improved oxygen transport.
Species differences in renal Src activity direct EGF receptor regulation in life or death response to EGF
Authors: Kiley Susan C. , Chevalier Robert L.
Published: July 2007

In rodent models of obstructive nephropathy, exogenous epidermal growth factor (EGF) attenuates tubule cell death in rats and exacerbates cell death in mice. To identify species differences in EGF receptor (EGFR) regulation and signaling, cell lysates were prepared from rat, mouse, and human proximal tubule cells (PTC) and compared by immunoblot analysis for expression and phosphorylation of Src and EGFR. Frozen kidney tissue was also analyzed. Results indicate mouse PTC have constitutive Src- and EGFR-kinase activities not detected in rat or human PTC. Immunoblots of rat, mouse, and human kidney homogenates confirmed this finding in vivo. Src-specific inhibitor PP2 and EGFR kinase inhibitor AG1478 decreased EGF-induced apoptosis in mouse PTC by 74% ( P < 0.001) and 70% ( P < 0.001), respectively. Expression of a constitutive Src mutant cDNA in rat PTC rendered cells susceptible to EGF-induced death. EGF decreased stretch-induced apoptosis by 66% ( P < 0.001) relative to vehicle control in human PTC, similar to rat PTC response. We conclude that elevated Src activity in mouse tubular cells alters downstream EGFR signaling and increases susceptibility to EGF-induced cell death. The unexpected finding that a therapeutic agent (EGF) in rats is detrimental in mice underscores the importance of determining which animal best represents the response of human kidneys to a given agent.
Directional Biases Reveal Utilization of Arm's Biomechanical Properties for Optimization of Motor Behavior
Authors: Goble Jacob A. , Zhang Yanxin , Shimansky Yury , Sharma Siddharth , Dounskaia Natalia V.
Published: July 2007

Strategies used by the CNS to optimize arm movements in terms of speed, accuracy, and resistance to fatigue remain largely unknown. A hypothesis is studied that the CNS exploits biomechanical properties of multijoint limbs to increase efficiency of movement control. To test this notion, a novel free-stroke drawing task was used that instructs subjects to make straight strokes in as many different directions as possible in the horizontal plane through rotations of the elbow and shoulder joints. Despite explicit instructions to distribute strokes uniformly, subjects showed biases to move in specific directions. These biases were associated with a tendency to perform movements that included active motion at one joint and largely passive motion at the other joint, revealing a tendency to minimize intervention of muscle torque for regulation of the effect of interaction torque. Other biomechanical factors, such as inertial resistance and kinematic manipulability, were unable to adequately account for these significant biases. Also, minimizations of jerk, muscle torque change, and sum of squared muscle torque were analyzed; however, these cost functions failed to explain the observed directional biases. Collectively, these results suggest that knowledge of biomechanical cost functions regarding interaction torque (IT) regulation is available to the control system. This knowledge may be used to evaluate potential movements and to select movement of “low cost.” The preference to reduce active regulation of interaction torque suggests that, in addition to muscle energy, the criterion for movement cost may include neural activity required for movement control.
Caricature Generator: The Dynamic Exaggeration of Faces by Computer
Authors: Brennan Susan E.
Published: July 2007

The author has researched and developed a theory of computation for caricature and has implemented this theory as an interactive computer graphics program. The Caricature Generator program is used to create caricatures by amplifying the differences between the face to be caricatured and a comparison face. This continuous, parallel amplification of facial features on the computer screen simulates the visualization process in the imagination of the caricaturist. The result is a recognizable, animated caricature, generated by computer and mediated by an individual who may or may not have facility for drawing, but who, like most human beings, is expert at visualizing and recognizing faces.
Judicial Reform and the Possibility of Democratic Rule in Jordan: A Policy Perspective on Judicial Independence
Authors: Burgis Michelle
Published: July 2007

Studying the independence of Jordan's judiciary provides an opportunity for appreciating current structural impediments to democratic governance and economic reform. In this article, judicial independence is critically explored through an examination of Jordan's legal system, its political culture as well as regional and international policy initiatives. A number of suggestions are advanced in a bid to encourage ongoing dialogue about the central role an independent judiciary must play in advancing the interests of all stakeholders in future reform efforts whether in Jordan or the wider Arab region.
Surveillance in Public Rituals
Authors: Bajc Vida
Published: July 2007

This article uses the second inauguration of President George W. Bush in January 2005 as a case study to show that surveillance procedures in state-sponsored public rituals themselves have a ritual form. This security meta-ritual is a practice of separation of insiders from outsiders through which the state security apparatus transforms a potentially dangerous everyday public life into a new social reality. In this newly created space of public interaction under maximum control, a safe space is created within which public ritual can take place without interruption.
Between the Lines: the Story of Machsom Watch
Authors: Halperin Irit
Published: July 2007

This article tells the story of Machsom Watch, a group that was founded in January 2001 in response to repeated reports in the press about human rights abuses of Palestinians crossing army checkpoints. The excessive Israeli response to the El Aksa Intifada, the prolonged closure and siege of villages and towns on the West Bank, provided the stimulus and the motivation for what at first seemed an impossible mission. The author, an Israeli peace activist and expressive therapist, explores the difficulties and strengths of the activists. She describes the political background of Israeli women peace activism from the first intifada (1987) until today and discusses, from a feminist perspective, the moral action of Israeli women's peace groups challenging militaristic Israeli society. The article describes the unique and radical actions of this group. The conflict between the identities of peace activist and Israeli citizen causes the activists to experience painful doubts about their self-identities.
Narrative Inquiry and Arts-Based Inquiry: Multinarrative Perspectives
Authors: Estrella Karen , Forinash Michele
Published: July 2007

This article introduces narrative inquiry and arts-based research methods and provides a discussion of the applicability of these methods for exploring the marginalized, controversial, and disruptive perspectives that have often been lost in more traditional research methodologies. Narrative and arts-based approaches to research offer the possibility of disruption to the dominant discourses within theory and research. In addition, they also provide an avenue toward reconciliation. The authors explore how these two research approaches can be used. Philosophical groundwork for their application to the work of conflict resolution and practices of reconciliation is offered.
Stories of Destruction and Renewal: A Drama Therapy Experience
Authors: Landy Robert J. , Hadari Avi
Published: July 2007

In a full-day workshop, the authors invited the participants to create personal and/or political stories around the theme of destruction. These stories were explored by the full group through methods derived from drama therapy, expressive therapies, and Gestalt therapy. Several stories were dramatized, as they captured the theme of the workshop. All group members reflected on the stories, and then all were asked to re-vision their stories from the point of view of renewal. Again, representative stories of renewal were dramatized. Finally, all group members reflected on the process of working toward the possibility of holding together balancing their tendencies toward destruction and creation. In doing so, the group attempted to come to some understanding of the concept of renewal from both political and personal perspectives. Participants from a variety of political and cultural perspectives were welcomed.
Expression in the Service of Humanity: Trauma and Temporality
Authors: Byers Julia Gentleman , Gere Susan H.
Published: July 2007

This article presents the spontaneously co-led workshop by a counseling psychologist and expressive therapist on their professional work with traumatized populations for the Imagine Conference in April 2006 in Tel Aviv, Israel. Integrating theories of healing from traumatic grief with clinical and personal experiences, participants were invited to connect to each other through the use of bubble wrap to contain and represent what brought them to the topic. This article describes the process of presenting theory and modeling the group safety, meaning-making, and reconnecting tasks of trauma work within a time-limited workshop for clinicians and trainers. Verbal and nonverbal techniques are used to demonstrate action-oriented approaches to traumatic grief.
The Development of a Feedback Environment and Role Clarity Model of Job Performance
Authors: Whitaker Brian G. , Dahling Jason J. , Levy Paul
Published: July 2007

Researchers have recently begun recognizing the impact of contextual factors on important organizational outcomes. This study, involving 170 subordinate-supervisor dyads, develops a model that demonstrates that subordinates who perceive a supportive feedback environment display increased feedback seeking, higher role clarity, and higher performance ratings. Furthermore, the results show that effort costs moderated the relationship between the coworker feedback environment and feedback seeking from coworkers. Implications are discussed.
Airway dendritic cell phenotypes in inflammatory diseases of the human lung
Authors: Lommatzsch M. , Bratke K. , Bier A. , Julius P. , Kuepper M. , Luttmann W. , Virchow J. C.
Published: July 2007

Airway dendritic cells (DCs) are key regulators of pulmonary immune responses. However, information is limited regarding the characteristics of airway DCs in human lung diseases.

Plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) were analysed using four-colour flow cytometry in bronchoalveolar lavage fluid (BALF) from nonsmoking controls and patients with sarcoidosis, idiopathic pulmonary fibrosis (IPF) and pneumonia (in the presence or absence of immunosuppression).

Compared with controls, immunocompetent patients with pneumonia displayed strongly enhanced pDC counts in BALF. In contrast, pDC counts in BALF from immunocompromised patients with pneumonia were even lower than in controls. This discrepancy was not explained by a different chemotactic milieu in the airways; all patients with pneumonia were characterised by strongly increased concentrations of the pDC-attracting chemokine, CXC chemokine ligand 10, in BALF. Patients with IPF were characterised by normal percentages of DC subtypes. However, the mDCs of patients with IPF were not as mature (CD83-positive) as those of controls. Patients with sarcoidosis displayed a unique increase in CD1a-negative mDCs in the airways. In addition, there was altered expression of costimulatory molecules (increased CD80 and decreased CD86 expression) on mDCs in patients with sarcoidosis.

These data suggest that inflammatory diseases of the human lung are associated with a differential phenotype and recruitment of airway dendritic cells.
HoxPred: automated classification of Hox proteins using combinations of generalised profiles
Authors: Thomas-Chollier Morgane , Leyns Luc , Ledent Valérie
Published: July 2007

Background

Correct identification of individual Hox proteins is an essential basis for their study in diverse research fields. Common methods to classify Hox proteins focus on the homeodomain that characterise homeobox transcription factors. Classification is hampered by the high conservation of this short domain. Phylogenetic tree reconstruction is a widely used but time-consuming classification method.

Results

We have developed an automated procedure, HoxPred, that classifies Hox proteins in their groups of homology. The method relies on a discriminant analysis that classifies Hox proteins according to their scores for a combination of protein generalised profiles. 54 generalised profiles dedicated to each Hox homology group were produced de novo from a curated dataset of vertebrate Hox proteins. Several classification methods were investigated to select the most accurate discriminant functions. These functions were then incorporated into the HoxPred program.

Conclusion

HoxPred shows a mean accuracy of 97%. Predictions on the recently-sequenced stickleback fish proteome identified 44 Hox proteins, including HoxC1a only found so far in zebrafish. Using the Uniprot databank, we demonstrate that HoxPred can efficiently contribute to large-scale automatic annotation of Hox proteins into their paralogous groups. As orthologous group predictions show a higher risk of misclassification, they should be corroborated by additional supporting evidence. HoxPred is accessible via SOAP and Web interface http://cege.vub.ac.be/hoxpred/. Complete datasets, results and source code are available at the same site.
Down-regulation of SFRP1 as a putative tumor suppressor gene can contribute to human hepatocellular carcinoma
Authors: Huang Jian , Zhang Yun-Li , Teng Xiao-Mei , Lin Yun , Zheng Da-Li , Yang Peng-Yuan , Han Ze-Guang
Published: July 2007

Background

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. SFRP1 (the secreted frizzled-related protein 1), a putative tumor suppressor gene mapped onto chromosome 8p12-p11.1, the frequent loss of heterozygosity (LOH) region in human HCC, encodes a Wingless-type (Wnt) signaling antagonist and is frequently inactivated by promoter methylation in many human cancers. However, whether the down-regulation of SFRP1 can contribute to hepatocarcinogenesis still remains unclear.

Methods

We investigated the expression of SFRP1 through real time RT-PCR and immunohistochemistry staining. The cell growth and colony formation were observed as the overexpression and knockdown of SFRP1. The DNA methylation status within SFRP1 promoter was analyzed through methylation-specific PCR or bisulphate-treated DNA sequencing assays. Loss of heterozygosity was here detected with microsatellite markers.

Results

SFRP1 was significantly down-regulated in 76.1% (35/46) HCC specimens at mRNA level and in 30% (30/100) HCCs indicated by immunohistochemistry staining, as compared to adjacent non-cancerous livers. The overexpression of SFRP1 can significantly inhibit the cell growth and colony formation of YY-8103, SMMC7721, and Hep3B cells. The RNA interference against the constitutional SFRP1 in the offspring SMMC7721 cells, which were stably transfected by ectopic SFRP1, can markedly promote cell growth of these cells. LOH of both microsatellite markers D8S532 and D8SAC016868 flanking the gene locus was found in 13% (6 of 46 HCCs) and 6.5% (3 of 46 HCCs) of the informative cases, respectively, where 5 of 8 HCC specimens with LOH showed the down-regulation of SFRP1. DNA hypermethylation within SFRP1 promoter was identified in two of three HCC specimens without SFRP1 expression. Moreover, the DNA methylation of SFRP1 promoter was significantly reduced, along with the re-expression of the gene, in those HCC cell lines, Bel7404, QGY7701, and MHCC-H, as treated by DAC.

Conclusion

Our data suggested that the down-regulation of SFRP1 as a candidate tumor suppressor gene, triggered by the epigenetic and/or genetic events, could contribute to the oncogenesis of HCC.
Crystal structure of hyperthermophilic esterase EstE1 and the relationship between its dimerization and thermostability properties
Authors: Byun Jung-Sue , Rhee Jin-Kyu , Kim Nam Doo , Yoon JeongHyeok , Kim Dong-Uk , Koh Eunhee , Oh Jong-Won , Cho Hyun-Soo
Published: July 2007

Background

EstE1 is a hyperthermophilic esterase belonging to the hormone-sensitive lipase family and was originally isolated by functional screening of a metagenomic library constructed from a thermal environmental sample. Dimers and oligomers may have been evolutionally selected in thermophiles because intersubunit interactions can confer thermostability on the proteins. The molecular mechanisms of thermostabilization of this extremely thermostable esterase are not well understood due to the lack of structural information.

Results

Here we report for the first time the 2.1-Å resolution crystal structure of EstE1. The three-dimensional structure of EstE1 exhibits a classic α/β hydrolase fold with a central parallel-stranded beta sheet surrounded by alpha helices on both sides. The residues Ser154, Asp251, and His281 form the catalytic triad motif commonly found in other α/β hydrolases. EstE1 exists as a dimer that is formed by hydrophobic interactions and salt bridges. Circular dichroism spectroscopy and heat inactivation kinetic analysis of EstE1 mutants, which were generated by structure-based site-directed mutagenesis of amino acid residues participating in EstE1 dimerization, revealed that hydrophobic interactions through Val274 and Phe276 on the β8 strand of each monomer play a major role in the dimerization of EstE1. In contrast, the intermolecular salt bridges contribute less significantly to the dimerization and thermostability of EstE1.

Conclusion

Our results suggest that intermolecular hydrophobic interactions are essential for the hyperthermostability of EstE1. The molecular mechanism that allows EstE1 to endure high temperature will provide guideline for rational design of a thermostable esterase/lipase using the lipolytic enzymes showing structural similarity to EstE1.
Type II restriction endonuclease R.Eco29kI is a member of the GIY-YIG nuclease superfamily
Authors: Ibryashkina Elena M , Zakharova Marina V , Baskunov Vladimir B , Bogdanova Ekaterina S , Nagornykh Maxim O , Den'mukhamedov Marat M , Melnik Bogdan S , Kolinski Andrzej , Gront Dominik , Feder Marcin , Solonin Alexander S , Bujnicki Janusz M
Published: July 2007

Background

The majority of experimentally determined crystal structures of Type II restriction endonucleases (REases) exhibit a common PD-(D/E)XK fold. Crystal structures have been also determined for single representatives of two other folds: PLD (R.BfiI) and half-pipe (R.PabI), and bioinformatics analyses supported by mutagenesis suggested that some REases belong to the HNH fold. Our previous bioinformatic analysis suggested that REase R.Eco29kI shares sequence similarities with one more unrelated nuclease superfamily, GIY-YIG, however so far no experimental data were available to support this prediction. The determination of a crystal structure of the GIY-YIG domain of homing endonuclease I-TevI provided a template for modeling of R.Eco29kI and prompted us to validate the model experimentally.

Results

Using protein fold-recognition methods we generated a new alignment between R.Eco29kI and I-TevI, which suggested a reassignment of one of the putative catalytic residues. A theoretical model of R.Eco29kI was constructed to illustrate its predicted three-dimensional fold and organization of the active site, comprising amino acid residues Y49, Y76, R104, H108, E142, and N154. A series of mutants was constructed to generate amino acid substitutions of selected residues (Y49A, R104A, H108F, E142A and N154L) and the mutant proteins were examined for their ability to bind the DNA containing the Eco29kI site 5'-CCGCGG-3' and to catalyze the cleavage reaction. Experimental data reveal that residues Y49, R104, E142, H108, and N154 are important for the nuclease activity of R.Eco29kI, while H108 and N154 are also important for specific DNA binding by this enzyme.

Conclusion

Substitutions of residues Y49, R104, H108, E142 and N154 predicted by the model to be a part of the active site lead to mutant proteins with strong defects in the REase activity. These results are in very good agreement with the structural model presented in this work and with our prediction that R.Eco29kI belongs to the GIY-YIG superfamily of nucleases. Our study provides the first experimental evidence for a Type IIP REase that does not belong to the PD-(D/E)XK or HNH superfamilies of nucleases, and is instead a member of the unrelated GIY-YIG superfamily.
Does a referral from home to hospital affect satisfaction with childbirth? A cross-national comparison
Authors: Christiaens Wendy , Gouwy Anneleen , Bracke Piet
Published: July 2007

Background

The Belgian and Dutch societies present many similarities but differ with regard to the organisation of maternity care. The Dutch way of giving birth is well known for its high percentage of home births and its low medical intervention rate. In contrast, home births in Belgium are uncommon and the medical model is taken for granted. Dutch and Belgian maternity care systems are compared with regard to the influence of being referred to specialist care during pregnancy or intrapartum while planning for a home birth. We expect that a referral will result in lower satisfaction with childbirth, especially in Belgium.

Methods

Two questionnaires were filled out by 605 women, one at 30 weeks of pregnancy and one within the first two weeks after childbirth, either at home or in a hospital. Of these, 563 questionnaires were usable for analysis. Women were invited to participate in the study by independent midwives and obstetricians during antenatal visits in 2004–2005. Satisfaction with childbirth was measured by the Mackey Satisfaction with Childbirth Rating Scale, which takes into account the multidimensional nature of the concept.

Results

Belgian women are more satisfied than Dutch women and home births are more satisfying than hospital births. Women who are referred to the hospital while planning for a home birth are less satisfied than women who planned to give birth in hospital and did. A referral has a greater negative impact on satisfaction for Dutch women.

Conclusion

There is no reason to believe Dutch women receive hospital care of lesser quality than Belgian women in case of a referral. Belgian and Dutch attach different meaning to being referred, resulting in a different evaluation of childbirth. In the Dutch maternity care system home births lead to higher satisfaction, but once a referral to the hospital is necessary satisfaction drops and ends up lower than satisfaction with hospital births that were planned in advance. We need to understand more about referral processes and how women experience them.
Nonspecific CD4+ T cells with uptake of antigen-specific dendritic cell-released exosomes stimulate antigen-specific CD8+ CTL responses and long-term T cell memory
Authors: Hao Siguo , Yuan Jinying , Xiang Jim
Published: July 2007

Dendritic cell (DC) and DC-derived exosomes (EXO) have been used extensively for tumor vaccination. However, its therapeutic efficiency is limited to only production of prophylactic immunity against tumors. T cells can uptake DC-released EXO. However, the functional effect of transferred exosomal molecules on T cells is unclear. In this study, we demonstrated that OVA protein-pulsed DC-derived EXO (EXOOVA) can be taken up by Con A-stimulated, nonspecific CD4+ T cells derived from wild-type C57BL/6 mice. The active EXO-uptaken CD4+ T cells (aTEXO), expressing acquired exosomal MHC I/OVA I peptide (pMHC I) complexes and costimulatory CD40 and CD80 molecules, can act as APCs capable of stimulating OVA-specific CD8+ T cell proliferation in vitro and in vivo and inducing efficient CD4+ Th cell-independent CD8+ CTL responses in vivo. The EXOOVA-uptaken CD4+ aTEXO cell vaccine induces much more efficient CD8+ T cell responses and immunity against challenge of OVA-transfected BL6-10 melanoma cells expressing OVA in wild-type C57BL/6 mice than EXOOVA. The in vivo stimulatory effect of the CD4+ aTEXO cell to CD8+ T cell responses is mediated and targeted by its CD40 ligand signaling/acquired exosomal CD80 and pMHC I complexes, respectively. In addition, CD4+ aTEXO vaccine stimulates a long-term, OVA-specific CD8+ T cell memory. Therefore, the EXOOVA-uptaken CD4+ T cells may represent a new, effective, EXO-based vaccine strategy in induction of immune responses against tumors and other infectious diseases.
Heteroaryl-susbstituted phenols as potential antioxidants
Authors: Ferrini Serena , Fusi Stefania , Ponticelli Fabio , Valoti Massimo
Published: July 2007

A series of O-heteroaryl phenols have been synthesised and structurally characterised. Photo-Fries rearrangement of these compounds represents a useful way to access the corresponding C-heteroaryl derivatives. The activity of the new phenolic compounds as radical scavengers towards the 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonate) (ABTS+•) has been evaluated. 2-tert-Butyl-4-(4-phenyl-isoxazol-3-ylmethoxy)-phenol (compound 3c) showed the highest scavenger activity (IC50 value (i.e. the concentration that scavenged 50% of the radicals) 3.17 × 10−6 M), which was one order of magnitude greater than that of the corresponding lead compound tert-butylhydroxy-anisole (BHA) (IC50 1.04 × 10−5 M). In further experiments, compound 3c showed dose-dependent inhibition of the oxidation of linoleic acid, as well as methaemoglobin formation, promoted by the presence of the radical generator 2,2′-azobis(amidino-propane) hydrochloride (AAPH) and it was markedly more potent than BHA in these assays.
Dihydroartemisinin exerts cytotoxic effects and inhibits hypoxia inducible factor-1α activation in C6 glioma cells
Authors: Huang Xiao-Jia , Ma Zhen-Qiu , Zhang Wei-Ping , Lu Yun-Bi , Wei Er-Qing
Published: July 2007

Artemisinin and its analogue dihydroartemisinin exert cytotoxic effects in some kinds of cancer cell lines. Here we determined whether dihydroartemisinin inhibits the growth and induces apoptosis of rat C6 glioma cells. We found dihydroartemisinin (5–25 μM) inhibited the growth and induced apoptosis of C6 cells in a concentration- and time-dependent manner; however, it was much less toxic to rat primary astrocytes. Dihydroartemisinin (5–25 μM) also increased the generation of reactive oxygen species in C6 cells. These effects of dihydroartemisinin were enhanced by ferrous ions (12.5–100 μM) and reduced by the iron chelator deferoxamine (25–200 μM). Immunoblotting analysis revealed that dihydroartemisinin (5–25 μM) significantly reduced hypoxia- and deferoxamine-induced expression of hypoxia inducible factor-1α and its target gene protein, vascular endothelial growth factor, in C6 cells. The results showed that dihydroartemisinin exerts a selective cytotoxic effect on C6 cells by increasing the reactive oxygen species and inhibiting hypoxia inducible factor-1α activation.
Novel methoxylated flavone inhibitors of cytochrome P450 1B1 in SCC-9 human oral cancer cells
Authors: Walle Thomas , Walle U Kristina
Published: July 2007

Dietary polyphenols, including flavonoids, have been implied to have cancer preventive properties. Suggested mechanisms include inhibition of carcinogen-activating cytochrome P450 (CYP) transcription and activities. These studies have focused mainly on CYP1A1. However, CYP1B1 has recently been shown to be of particular importance in smoking-induced oral and oesophageal cancer. Previous observations in our laboratory demonstrated that methoxylated flavonoids may be effective inhibitors of CYP1A1 transcription and activity as well as being orally bioavailable. In this study, an initial screening of 19 methoxylated flavones, using the ethoxyresorufin de-ethylation assay in human oral squamous cell carcinoma SCC-9 cells pretreated with 1μM benzo[a]pyrene, identified six strongly inhibitory compounds for further studies. The effect of these flavones on CYP1B1 mRNA expression was measured with quantitative branched DNA methodology. Four of the compounds −3′,4′-dimethoxyflavone and 5,7,4′-trimethoxyflavone and, in particular, 7,3′-dimethoxyflavone and 7,4′-dimethoxyflavone — were potent inhibitors of CYP1B1 mRNA expression. Two of the more common unmethylated polyphenols — curcumin and quercetin — were also potent inhibitors. Whereas most unmethylated polyphenols, such as curcumin and quercetin, have very poor bioavailability, the high metabolic stability of the methoxylated flavones studied here suggests that these CYP1B1 inhibitors may also be effective in-vivo.
Eugenosedin-A amelioration of lipopolysaccharide-induced up-regulation of p38 MAPK, inducible nitric oxide synthase and cyclooxygenase-2
Authors: Shen Kuo-Ping , Liou Shu-Fen , Hsieh Su-Ling , Chen Ing-Jun , Wu Bin-Nan
Published: July 2007

In this study, we investigate the protective effects of eugenosedin-A on p38 mitogen-activated protein kinase (MAPK), inflammatory nitric oxide (NO) and cyclooxygenase-2 (COX-2) pathways in a rat model of endotoxin shock. Rats were pretreated with eugenosedin-A, trazodone, yohimbine (1 mg kg−1, i.v.), aminoguanidine or ascorbic acid (15 mg kg−1, i.v.) 30 min before endotoxin challenge. Endotoxaemia was induced by a single i.v. injection of lipopolysaccharide (LPS, 10 mg kg−1). In rats not treated with eugenosedin-A, LPS increased plasma concentrations of NO and prostaglandin E2 (PGE2), and levels of p38 MAPK, inducible NO synthase (iNOS) and COX-2 proteins in the liver, lung, aorta and lymphocytes. In the pre-treated rats, eugenosedin-A not only inhibited the LPS-induced NO and PGE2 levels but also attenuated the LPS-induced increase in p38 MAPK and iNOS levels in the liver, aorta and lymphocytes. Eugenosedin-A also reduced LPS-induced COX-2 proteins in the aorta and lymphocytes. Likewise, aminoguanidine, ascorbic acid, yohimbine and trazodone were also found to decrease NO and PGE2 concentrations after endotoxin challenge. While aminoguanidine and ascorbic acid also attenuated the LPS-induced increase in p38 MAPK, iNOS and COX-2 proteins in the aorta and lymphocytes, trazodone and yohimbine inhibited only the increase in p38 MAPK, iNOS and COX-2 proteins in lymphocytes. Finally, eugenosedin-A (10−10-10−8 M) significantly inhibited the biphasic response induced by hydrogen peroxide (10−6-3 × 10−5 M) in rat denudated aorta. Taken together, the results of this study indicate that eugenosedin-A, as well as ascorbic acid, can attenuate free-radical-mediated aortic contraction and relaxation. It may therefore be able to reduce the damage caused by septic shock by inhibiting formation of p38 MAPK, iNOS, COX-2 and free radicals.
Recent developments in naturally derived antimalarials: cryptolepine analogues
Authors: Wright Colin W
Published: July 2007

Increasing resistance of Plasmodium falciparum to commonly used antimalarial drugs has made the need for new agents increasingly urgent. In this paper, the potential of cryptolepine, an alkaloid from the West African shrub Cryptolepis sanguinolenta, as a lead towards new antimalarial agents is discussed. Several cryptolepine analogues have been synthesized that have promising in-vitro and in-vivo antimalarial activity. Studies on the antimalarial modes of action of these analogues indicate that they may have different or additional modes of action to the parent compound. Elucidation of the mode of action may facilitate the development of more potent antimalarial cryptolepine analogues.
Spatiotemporal definition of neurite outgrowth, refinement and retraction in the developing mouse cochlea
Authors: Huang Lin-Chien , Thorne Peter R. , Housley Gary D. , Montgomery Johanna M.
Published: July 2007

The adult mammalian cochlea receives dual afferent innervation: the inner sensory hair cells are innervated exclusively by type I spiral ganglion neurons (SGN), whereas the sensory outer hair cells are innervated by type II SGN. We have characterized the spatiotemporal reorganization of the dual afferent innervation pattern as it is established in the developing mouse cochlea. This reorganization occurs during the first postnatal week just before the onset of hearing. Our data reveal three distinct phases in the development of the afferent innervation of the organ of Corti: (1) neurite growth and extension of both classes of afferents to all hair cells (E18-P0);(2) neurite refinement, with formation of the outer spiral bundles innervating outer hair cells (P0-P3); (3) neurite retraction and synaptic pruning to eliminate type I SGN innervation of outer hair cells, while retaining their innervation of inner hair cells (P3-P6). The characterization of this developmental innervation pattern was made possible by the finding that tetramethylrhodamine-conjugated dextran (TMRD) specifically labeled type I SGN. Peripherin and choline-acetyltransferase immunofluorescence confirmed the type II and efferent innervation patterns, respectively, and verified the specificity of the type I SGN neurites labeled by TMRD. These findings define the precise spatiotemporal neurite reorganization of the two afferent nerve fiber populations in the cochlea, which is crucial for auditory neurotransmission. This reorganization also establishes the cochlea as a model system for studying CNS synapse development, plasticity and elimination.
EGFL7 regulates the collective migration of endothelial cells by restricting their spatial distribution
Authors: Schmidt Maike , Paes Kim , De Mazière Ann , Smyczek Tanya , Yang Stacey , Gray Alane , French Dorothy , Kasman Ian , Klumperman Judith , Rice Dennis S. , Ye Weilan
Published: July 2007

During sprouting angiogenesis, groups of endothelial cells (ECs) migrate together in units called sprouts. In this study, we demonstrate that the vascular-specific secreted factor EGFL7 regulates the proper spatial organization of ECs within each sprout and influences their collective movement. In the homozygous Egfl7-knockout mice, vascular development is delayed in many organs despite normal EC proliferation, and 50% of the knockout embryos die in utero. ECs in the mutant vasculatures form abnormal aggregates and the vascular basement membrane marker collagen IV is mislocalized, suggesting that ECs fail to recognize the proper spatial position of their neighbors. Although the migratory ability of individual ECs in isolation is not affected by the loss of EGFL7, the aberrant spatial organization of ECs in the mutant tissues decreases their collective movement. Using in vitro and in vivo analyses, we showed that EGFL7 is a component of the interstitial extracellular matrix deposited on the basal sides of sprouts,a location suitable for conveying positional information to neighboring ECs. Taken together, we propose that EGFL7 defines the optimal path of EC movement by assuring the correct positioning of each EC in a nascent sprout.
The TFIID subunit TAF4 regulates keratinocyte proliferation and has cell-autonomous and non-cell-autonomous tumour suppressor activity in mouse epidermis
Authors: Fadloun Anas , Kobi Dominique , Pointud Jean-Christophe , Indra Arup Kumar , Teletin Marius , Bole-Feysot Christine , Testoni Barbara , Mantovani Roberto , Metzger Daniel , Mengus Gabrielle , Davidson Irwin
Published: July 2007

The TAF4 subunit of transcription factor TFIID was inactivated in the basal keratinocytes of foetal and adult mouse epidermis. Loss of TAF4 in the foetal epidermis results in reduced expression of the genes required for skin barrier function, leading to early neonatal death. By contrast, TAF4 inactivation in adult epidermis leads to extensive fur loss and an aberrant hair cycle characterised by a defective anagen phase. Although the mutant epidermis contains few normal anagen-phase hair follicles, many genes expressed at this stage are strongly upregulated indicating desynchronised and inappropriate gene expression. The TAF4 mutant adult epidermis also displays interfollicular hyperplasia associated with a potent upregulation of several members of the EGF family of mitogens. Moreover, loss of TAF4 leads to malignant transformation of chemically induced papillomas and the appearance of invasive melanocytic tumours. Together, our results show that TAF4 is an important regulator of keratinocyte proliferation and has cell-autonomous and non-cell-autonomous tumour suppressor activity.
Semaphorin signaling facilitates cleft formation in the developing salivary gland
Authors: Chung Ling , Yang Tsung-Lin , Huang Hsiu-Ru , Hsu Su-Ming , Cheng Hwai-Jong , Huang Pei-Hsin
Published: July 2007

Semaphorin signaling plays integral roles in multiple developmental processes. Branching morphogenesis is one such role that has not been thoroughly explored. Here, we show in mice that functional blockage of neuropilin 1 (Npn1) inhibits cleft formation in the developing submandibular gland (SMG) cultured ex vivo. This Npn1-dependent morphogenesis is mediated by Sema3A and Sema3C in an additive manner, and can be abolished by decreasing the expression of plexin A2 or plexin D1. VEGF, another known Npn1 ligand, has no apparent effects on SMG development. FGF signaling, which also mediates SMG branching morphogenesis, acts in parallel with semaphorin signaling. Finally,in contrast to the effect of FGF signaling, we find that semaphorins do not stimulate the proliferation of SMG epithelial cells. Instead, the semaphorin signals act locally on the epithelial cells to facilitate SMG cleft formation.
Plastic limit loads of cylinders with a circular opening under combined axial force and bending moment
Authors: Rahimi G. H , Alashti R. A
Published: July 2007

In this paper, limit analyses of cylindrical shells with a circular opening under the action of combined axial force and bending moment at the ends are carried out using both finite element methods and the approximate analytical lower-bound limit load of the weakest section of the cylinder. The finite element calculations consist of elastic-plastic and elastic compensation methods using an ANSYS suite of programs. The results obtained by the finite element methods are then compared with the approximate analytical lower-bound limit load of the cylinder, and the correlation between them is discussed.
An experimental and numerical hybrid technique for reconstructing boundary conditions in elastic analysis
Authors: Fujikawa M , Takashi M
Published: July 2007

A hybrid technique for stress and strain analyses combining experimental and numerical methods reducing experimental error and noise has recently attracted much attention. The previous hybrid techniques involve inevitable error and noise, particularly on the boundary of the target area of interest (TAI). In the present paper, the authors develop a new hybrid technique that can reconstruct boundary conditions from the full-field displacement distribution obtained by experiment. This technique starts from the idea of two matrices based on finite element analysis (FEM). One is the ‘relation matrix’ which gives the relation between displacement vectors on the boundary of and inside the target area. The other is the ‘smoothing matrix’ which ensures smoothness (continuity) of displacement along nodes on the boundary. This technique makes it possible to reconstruct proper or actual boundary conditions on the TAI automatically. Therefore, the distributions of displacement, stress, and strain calculated by the technique are more accurate and useful than those obtained by the previous one not only inside the TAI but also on its boundary.
Stress concentration around a spherical cavity in a cubic medium
Authors: Chiang Chun-Ron
Published: July 2007

An investigation of the stress concentration around a spherical cavity in a cubic medium is conducted by means of the equivalent inclusion method. Cases of uniformly applied tensile, shear, and hydrostatic (spherical) stresses are analysed and examined. Theoretical formulation and computational procedures are described in detail. Numerical results for some representative cubic crystals (niobium, molybdenum, nickel, and copper) are presented for illustration and important features of the ensuing stress concentration are discussed.
The effect of specimen geometry on plastic zone size: A study using the J integral
Authors: Kudari S K , Maiti B , Ray K. K
Published: July 2007

In this investigation the nature of the plastic zone ahead of a crack-tip in centrecracked tension, double-edge-notched tension, single-edge-notched tension, compact tension, extended compact tension, and single-edge-notched bend specimens have been assessed by elastic-plastic finite element analyses at different applied load levels ( J integral). The magnitudes of the plastic zone size (PZS) in the investigated specimens have been compared using a new reference standard J/aσy where a is crack length and σy is yield stress of the material. The results demonstrate that the PZS is almost invariant with respect to specimen geometry up to a critical value of J/aσy at a specific a/W ratio. However, beyond this critical value, the magnitudes of the PZS are found to depend on the specimen geometry, which has been attributed to the varying in-plane constraints at the crack tip in various specimens.
The statistical interpretation of strain gauge readings
Authors: Lightfoot E
Published: July 2007

This paper deals with two similar problems concerned with the interpretation of strain gauge readings when more than the required minimum of three gauges are applied, (a) on the cross-section of a structural member and (b) in a strain gauge rosette. In the latter case the best method of using the four readings from a standard 45° rosette is explained.
Creep deformation of statically indeterminate beams analysed by an electrical analogue
Authors: Rushton K. R.
Published: July 2007

The creep bending of statically indeterminate beams is studied by an electrical resistance network. The moment-curvature relationship due to creep, which is non-linear and time-dependent, is expressed in graphical form. An elastic solution is first obtained and is modified to allow for the creep curvature. An iterative method has to be adopted and the technique of obtaining convergence is discussed. Particular problems which are considered include the propped cantilever and a two-span continuous built-in beam.
Estimation of the useful life and strain history of a thick tube creeping under non-steady conditions
Authors: Smith E. M.
Published: July 2007

An estimate of the useful life of a thick tube creeping under non-steady environmental conditions is made using a life-hardening creep law in conjunction with a Larson-Miller rupture parameter. The method of selecting time intervals during computation is described and suggestions are made as to the appropriate points to start and end such computations. Data necessary to the calculations are summarized in an appendix.
Development of strain gauge techniques for the measurement of propeller shaft torque in distant water trawlers
Authors: Bennett R , Hatfield M
Published: July 2007

In the course of research and development work on deep sea fishing vessels, a continuing requirement is for a system to measure and record propeller shaft torque that will remain reliable and accurate on commercial fishing voyages of up to seven weeks duration, in the extreme environment of Arctic and North Atlantic waters, in all weathers, and at all seasons of the year. The system should be suitable for use in conjunction with dial indicators and recorders on voyages manned by development engineers and also suitable for use in automatic data logging systems.

A system has been developed and tried consisting of d.c. energized foil strain gauges and simple slip rings consisting of silver strip wrapped on to the shaft, with unamplified readout on to galvanometers of either direct reading light spot type or those in trace recorders. The system can be used for the measurement of both steady and oscillatory torques.

Almost 100 per cent reliability has been achieved on a number of installations.

Both calibrated and uncalibrated installations have been used. The calibrated systems have an accuracy of better than 1 per cent. From experience gained to date the conclusion is drawn that an uncalibrated system can be expected to have a mean accuracy of about ±31/2 per cent, using the maker's gauge factors and a mean value of 11.9 ×106 for the torsional modulus for mild steel. In several vessels special short lengths of intermediate shafting have been provided in duplicate, in order to facilitate frequent re-calibration.

Scatter in a given set of readings is low, the standard deviation being about 1 per cent at a surface stress of 3000——4000 lb/in2 (steaming power range) and up to about 21/2 per cent at stresses in the range 1200——2500 lb/in2 (trawling power). Determining scatter due to the variability of the instrument in the face of variations due to weather, ship displacement and other causes was one of the problems encountered during early trials on commercial voyages.

It was anticipated that zero drift could be a very severe problem but this has not been the case. The maximum drift over several weeks has been 21/2 per cent of maximum torque and it has frequently been negligible.

The system is now being applied to the measurement of thrust, using hollow shafts. Both torque and thrust signals are being fed into data loggers on certain trawlers. The problem of automatic logging of mean thrust and torque in the face of oscillations with periods of up to 14 seconds, induced by ship motion, without imposing heavy strains on analytical and computing facilities, has been solved.