bluuebunny/crossref_metadata_2025 huggingface dataset:
Student evaluation of an OSCE in paediatrics at the University of the West Indies, Jamaica
Authors: Pierre Russell B , Wierenga Andrea , Barton Michelle , Branday J Michael , Christie Celia DC
Published: October 2004

Background

The Faculty of Medical Sciences, University of the West Indies first implemented the Objective Structured Clinical Examination (OSCE) in the final MB Examination in Medicine and Therapeutics during the 2000–2001 academic year. Simultaneously, the Child Health Department initiated faculty and student training, and instituted the OSCE as an assessment instrument during the Child Health (Paediatric) clerkship in year 5. The study set out to explore student acceptance of the OSCE as part of an evaluation of the Child Health clerkship.

Methods

A self-administered questionnaire was completed by successive groups of students immediately after the OSCE at the end of each clerkship rotation. Main outcome measures were student perception of examination attributes, which included the quality of instructions and organisation, the quality of performance, authenticity and transparency of the process, and usefulness of the OSCE as an assessment instrument compared to other formats.

Results

There was overwhelming acceptance of the OSCE in Child Health with respect to the comprehensiveness (90%), transparency (87%), fairness (70%) and authenticity of the required tasks (58–78%). However, students felt that it was a strong anxiety-producing experience. And concerns were expressed regarding the ambiguity of some questions and inadequacy of time for expected tasks.

Conclusion

Student feedback was invaluable in influencing faculty teaching, curriculum direction and appreciation of student opinion. Further psychometric evaluation will strengthen the development of the OSCE.
Macrophage activation by a DNA/cationic liposome complex requires endosomal acidification and TLR9-dependent and -independent pathways
Authors: Yasuda Kei , Ogawa Yoshiyuki , Yamane Ikuko , Nishikawa Makiya , Takakura Yoshinobu
Published: October 2004

Previously, we showed that bacterial DNA and vertebrate DNA/cationic liposome complexes stimulate potent inflammatory responses in cultured mouse macrophages. In the present study, we examined whether endocytosis and subsequent acidification are associated with these responses. The endocytosis inhibitor, cytochalasin B, reduced tmor necrosis factor α (TNF-α) production by a plasmid DNA (pDNA)/cationic liposome complex. The endosomal acidification inhibitor, monensin, inhibited cytokine production by pDNA or a calf thymus DNA/liposome complex. These results suggest, similarly to CpG motif-dependent responses, that endocytosis and subsequent endosomal acidification are also required for these inflammatory responses. It is intriguing that another inhibitor of endosomal acidification, bafilomycin A, stimulated the production of TNF-α mRNA and its protein after removal of the pDNA/liposome complex and inhibitors, although it inhibited the release of interleukin-6. Similar phenomena were observed in the activation of macrophages by CpG oligodeoxynucleotide, calf thymus DNA, and Escherichia coli DNA complexed with liposomes. Moreover, bafilomycin A also induced a high degree of TNF-α release after stimulation with naked pDNA. These results suggest that bafilomycin A increases TNF-α production induced by DNA at the transcriptional level via an as-yet unknown mechanism. Furthermore, we investigated the contribution of Toll-like receptor 9 (TLR9), the receptor of CpG motifs, to the cell activation by the DNA/cationic liposome complex using the macrophages from TLR9−/− mice. We observed a reduced inflammatory cytokine release from macrophages of TLR9−/− mice compared with wild-type mice. However, the cytokine production was not completely abolished, suggesting that the DNA/cationic liposome complex can induce macrophage activation via TLR9-dependent and -independent pathways.
Linking the “two-hit” response following injury to enhanced TLR4 reactivity
Authors: Murphy Thomas J , Paterson Hugh M , Kriynovich Sara , Zang Yan , Kurt-Jones Evelyn A , Mannick John A , Lederer James A
Published: October 2004

Severe injury can initiate an exaggerated systemic inflammatory response and multiple organ failure (MOF) if a subsequent immune stimulus, “second hit”, occurs. Using a mouse thermal injury model, we tested whether changes in innate immune cell reactivity following injury can contribute to the development of heightened inflammation and MOF. Using high-purity Escherichia coli lipopolysaccharide (LPS) to selectively stimulate Toll-like receptor 4 (TLR4), we demonstrate augmented interleukin (IL)-1β, tumor necrosis factor α (TNF-α), and IL-6 production by 1 day but particularly, at 7 days after injury. The in vivo significance of enhanced TLR4 responsiveness was explored by challenging sham or burn mice with LPS at 1 or 7 days after injury and determining mortality along with in vivo cytokine and chemokine levels. Mortality was high (75%) in LPS-challenged burn but not sham mice at 7 days, although not at 1 day, after injury. Death was associated with leukocyte sequestration in the lungs and livers along with increased proinflammatory cytokine and chemokine levels in these organs. Blocking TNF-α activity prevented this mortality, suggesting that excessive TNF-α production contributes to this lethal response. These findings demonstrate the potential lethality of excessive TLR4 reactivity after injury and provide an explanation for the exaggerated inflammatory response to a second hit, which can occur following severe injury.
JAK2 is necessary and sufficient for interferon-γ-induced transcription of the gene encoding gp91PHOX
Authors: Kakar Renu , Kautz Bryan , Eklund Elizabeth A
Published: October 2004

During the inflammatory response, interferon-γ (IFN-γ) increases transcription of the gene encoding gp91PHOX, a respiratory burst oxidase component. This gene (referred to as the CYBB gene) is transcribed in phagocytic cells differentiated beyond the promyelocyte stage, and transcription continues until cell death. Previous investigations identified a positive regulatory element in the proximal CYBB promoter rferred to as the hematopoiesis-associated factor 1 (HAF1)-cis element. This element is activated by a multiprotein complex, which includes the IFN consensus sequence-binding protein (ICSBP). Interaction of this complex with the HAF1-cis element requires ICSBP tyrosine phosphorylation, which is induced by IFN-γ stimulation of phagocytic cells. Previous studies also identified a negative cis element in the CYBB promoter. This element is repressed by the homeodomain protein HoxA10. HoxA10 tyrosine phosphorylation, which occurs in response to IFN-γ, decreases HoxA10 DNA binding and therefore repression of CYBB transcription. In these studies, we determine Janus tyrosine kinase 2 (JAK2) activation is necessary and sufficient for IFN-γ-induced CYBB transcription in phagocytic cells and also for ICSBP and HoxA10 tyrosine phosphorylation. Consistent with these results, we find JAK2 activation is sufficient to induce ICSBP interaction with the HAF1 element and abolish HoxA10 binding to the CYBBrepressor element. Therefore, these findings provide direct demonstration of JAK2 dependence of IFN-γ-induced CYBB transcription. In addition, these results identify a mechanism mediating this effect.
Effects of sentence writing in second language lexical acquisition
Authors: Barcroft Joe
Published: October 2004

This study compared the effects of writing new words in sentences with word picture repetition learning alone. Second language (L2) Spanish learners attempted to learn 24 new Spanish words in one of two conditions while viewing word picture pairs. In Experiment 1, in the no sentence writing condition, the participants viewed 4 repetitions of each word for 6 seconds each. In the sentence writing condition, they viewed 1 repetition of each word for 48 seconds and were asked to write the word in a Spanish sentence. In Experiment 2, the participants were shown one repetition of each word for 24 seconds in both the sentence writing and no sentence writing conditions. Immediate and delayed posttests on productive vocabulary knowledge were administered in both experiments. Scores were submitted to analyses of variance. Condition and time were independent variables. Target word production was scored based on syllables and whole words produced. Results of both experiments indicated strong negative effects for the sentence writing conditions, suggesting that sentence writing can inhibit word form learning during the initial stages of L2 lexical acquisition.
Discoid lupus erythematosus of the vulva
Authors: Bilenchi R , Pisani C , Poggiali S , Andreassi A , de Padova L A , di Perri T
Published: October 2004

Genital involvement is a rare manifestation in discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE), and there are few reports on vulvar clinical features. We describe a 41-year old Caucasian woman with bilateral vulvar DLE. Although vulvar lesions in lupus are probably more common than is realized, the present report is the first case of genital DLE documented in a female.
Hypocomplementemia in systemic lupus erythematosus and primary antiphospholipid syndrome: prevalence and clinical significance in 667 patients
Authors: Ramos-Casals M , Campoamor M T , Chamorro A , Salvador G , Segura S , Botero J C , Yagüe J , Cervera R , Ingelmo M , Font J
Published: October 2004

The objective of the study was to analyse the prevalence and clinical significance of hypocomplementemia in a large series of patients diagnosed either with systemic lupus erythematosus (SLE) or with primary antiphospholipid syndrome (APS) and its association with the main clinical, hematological and immunological features of these diseases. Between 1992 and 2003, complement determinations (C3 and C4 levels, CH50 activity) were performed in 597 consecutive patients diagnosed with SLE (530 women and 67 men, mean age 32.6 years) and 70 with primary APS (57 women and 13 men, mean age 38.7) visited in our department. Complement determinations are routinely made at the first visit of patients and yearly during the follow-up. SLE and primary APS were diagnosed according to current classification criteria. Hypocomplementemia was detected in 371 (62%) of SLE patients. Compared with patients with normal complement values, those with hypocomplementemia showed a higher prevalence of female gender ( P < 0.001), fever ( P = 0.021), nephropathy ( P < 0.001), cutaneous vasculitis ( P = 0.023), positive anti-dsDNA antibodies ( P = 0.012) and cryoglobulinemia ( P < 0.001). In addition, patients with hypocomplementemia showed a higher prevalence of APS-related features such as hemolytic anemia ( P = 0.001) and antiphospholipid antibodies ( P < 0.001). Hypocomplementemia was prospectively related to accumulated hospitalization in SLE patients but not with the accumulated number of lupus flares or with the survival after follow-up of five years. In contrast, 33 (47%) patients with primary APS presented low complement values, which were associated with a higher prevalence of livedo reticularis ( P = 0.022), thrombocytopenia ( P = 0.004), lupus anticoagulant ( P = 0.013), positive IgM-aCL ( P = 0.039), positive ANA ( P = 0.002) and anti-dsDNA ( P = 0.046). The diagnostic value of hypocomplementemia in patients with SLE is based on the association with disease activity, immune-complex mediated manifestations (glomerulonephritis, cryoglobulinemia) and APS-related features (livedo reticularis, hemolytic anemia and aPL). Hypocomplementemia was found in nearly half of patients with primary APS, and was associated with some APS features (livedo reticularis, thrombocytopenia, aPL) but also with SLE-related immunological markers (ANA and anti-dsDNA), identifying a subset of patients with primary APS with a higher risk of evolving to SLE. These results clearly support the routine determination of complement factors in the clinical follow-up of patients with SLE and primary APS.
Epidermal growth factor receptor (EGFR) gene Bsr I polymorphism is associated with systemic lupus erythematosus
Authors: Huang C-M , Tsai C-H , Chen C-L , Chang C-P , Lai C-C , Tsai F-J
Published: October 2004

The purpose of this study was to determine if epidermal growth factor receptor (EGFR) gene polymorphism was a marker of susceptibility to or severity of Chinese patients with systemic lupus erythematosus (SLE) in Taiwan. The study included 119 Chinese patients with SLE. One hundred unrelated healthy individuals living in central Taiwan served as control subjects. Polymorphisms of the EGFR Bsr I gene were typed from genomic DNA. The genotypes, allelic frequencies and carriage rates were compared between SLE patients and control subjects. The relationship between allelic frequencies and clinical manifestations of SLE was evaluated. For the genotype of EGFR gene Bsr I polymorphism, there was statistically significant differences between the SLE and control groups (chi-squared test, P = 0.009, ϰ2= 9.21). In addition, there was significant association between the two groups in allelic frequency of the T allele ( P = 0.02, ϰ2= 5.27). However, we did not detect any association between EGFR genotype and clinical or laboratory profiles in SLE patients. The results suggest that the EGFR gene Bsr I polymorphism is related to SLE.
Antiphospholipid antibodies and hypertension
Authors: Rollino C , Boero R , Elia F , Montaruli B , Massara C , Beltrame G , Ferro M , Quattrocchio G , Quarello F
Published: October 2004

Hypertension is a common manifestation of antiphospholipid syndrome (APS). Antiphospholipid antibodies (aPL) have been described in patients with hypertension secondary to renal artery stenosis (RAS). Twenty-six patients with RAS and 25 patients with severe essential hypertension (diastolic blood pressure >110 mmHg or ±3 hypertensive drugs) were studied and compared to 61 age- and sex-matched healthy subjects. Serum samples were tested for lupus anticoagulant (LA), anticardiolipin (aCL) IgG and IgM, antiprothrombin (aPT) IgG and IgM, anti-β2glycoprotein 1 (aβ2GP1) IgG and IgM. aPL were negative in all patients with RAS. Two patients with essential hypertension had positive aPL (8%) (LA in one patient confirmed in a second assay and aβ2GP1-IgG in the other patient confirmed one year later together with aCL IgG positivity). Among healthy subjects, one case (1.6%) was found to be positive for LA, aCL IgM, aβ2GP1 IgM, aPT IgG, aPT IgM. In conclusion, the association between RAS and aPL seems to be casual rather than an expression of an elective thrombotic localization of APS. The positive finding of aPL in 8% of patients with essential hypertension, a frequency higher than that of the control population, deserves further studies in larger series to better explore the relationship between aPL and hypertension.
CTLA-4 gene polymorphisms and systemic lupus erythematosus in a population-based study of whites and African-Americans in the southeastern United States
Authors: Parks C G , Hudson L L , Cooper G S , Dooley M A , Treadwell E L , St Clair E W , Gilkeson G S , Pandey J P
Published: October 2004

Cytotoxic lymphocyte antigen-4 (CTLA-4) plays an important role in regulating T cell activation, and may help to limit T cell response under conditions of inflammation. Genetic variability in CTLA-4 has been implicated in the development of several autoimmune diseases. Some studies have described associations between CTLA-4 polymorphisms and systemic lupus erythematosus (SLE), but findings have been inconsistent. We examined polymorphisms in the CTLA-4 gene promoter region (21722T/C, 21661A/G, 2318C/T) and exon 1 (+49G/A) with respect to SLE in a population-based case-control study in the southeastern US. Genotypes from 230 recently diagnosed cases and 276 controls were examined separately for African-Americans and whites. We observed no overall associations between SLE and the four CTLA-4 polymorphisms examined. Subgroup analyses revealed effect modification by age for the presence of the 21661G allele, yielding a significant positive association with SLE in younger (≤35 years) African-Americans (OR = 3.3). CTLA-4 genotypes also interacted with HLA-DR2 and GM allotype to contribute to risk of SLE. These findings suggest allelic variation in this region of CTLA-4 is not a major independent risk factor for SLE, but may contribute to risk of disease in younger African-Americans or in the presence of certain immunogenetic markers.
Neuropsychological development of children born to patients with systemic lupus erythematosus
Authors: Neri F , Chimini L , Bonomi F , Filippini E , Motta M , Faden D , Lojacono A , Rebaioli C Biasini , Frassi M , Danieli E , Tincani A
Published: October 2004

To verify the neuropsychological development in the offspring of patients with systemic lupus erythematosus (SLE), 47 children (23 male and 24 female) from affected women were studied. The tests applied were related to the children’s ages: Griffiths scale up to four years, WPPSI and metaphonological tests (MP, evaluating the phonological consciousness) from four to six years of age, WISC-R test and Rey test (evaluating the visual-space abilities) from six years onwards; finally, specific tests for the diagnosis of learning disabilities (LD) between the ages of seven and 13. Intelligence levels were always normal (mean IQ score 106.32; median 104; SD 9.05). Three out of eight examined children failed MP, therefore may develop LD and will need further evaluation later. Fourteen children were specifically studied for LD and three reported scores lower than normal, but only two (who were brothers) were defined dyslexic. Antiphospholipid antibodies (aPL) were positive in the mothers of the three children with impaired LD tests. Other maternal autoantibodies or drugs administered during pregnancy did not seem to be related to LD. In conclusion, maternal SLE does not impair intelligence levels, but may increase the occurrence of LD particularly in male children (2/8 males examined, 25%). Both maternal aPL and genetic background may have pathogenetic implications.
Induction and autoregulation of the anti-proneural geneBarduring retinal neurogenesis inDrosophila
Authors: Lim Janghoo , Choi Kwang-Wook
Published: October 2004

Neurogenesis in Drosophila eye imaginal disc is controlled by interactions of positive and negative regulatory genes. The basic helix-loop-helix (bHLH) transcription factor Atonal (Ato) plays an essential proneural function in the morphogenetic furrow to induce the formation of R8 founder neurons. Bar homeodomain proteins are required for transcriptional repression of ato in the basal undifferentiated retinal precursor cells to prevent ectopic neurogenesis posterior to the furrow of the eye disc. Thus, precise regulation of Bar expression in the basal undifferentiated cells is crucial for neural patterning in the eye. We show evidence that Bar expression in the basal undifferentiated cells is regulated by at least three different pathways, depending on the developmental time and the position in the eye disc. First, at the time of furrow initiation, Bar expression is induced independent of Ato by Hedgehog (Hh) signaling from the posterior margin of the disc. Second, during furrow progression, Bar expression is also induced by Ato-dependent EGFR (epidermal growth factor receptor) signaling from the migrating furrow. Finally, once initiated, Bar expression can be maintained by positive autoregulation. Therefore, we propose that the domain of Bar expression for Ato repression is established and maintained by a combination of non autonomous Hh/EGFR signaling pathways and autoregulation of Bar.
Caspase inhibition during apoptosis causes abnormal signalling and developmental aberrations inDrosophila
Authors: Pérez-Garijo Ainhoa , Martín Francisco A. , Morata Ginés
Published: October 2004

Programmed cell death or apoptosis plays an important role in the development of multicellular organisms and can also be induced by various stress events. In the Drosophila wing imaginal disc there is little apoptosis in normal development but X-rays can induce high apoptotic levels,which eliminate a large fraction of the disc cells. Nevertheless, irradiated discs form adult patterns of normal size, indicating the existence of compensatory mechanisms. We have characterised the apoptotic response of the wing disc to X-rays and heat shock and also the developmental consequences of compromising apoptosis. We have used the caspase inhibitor P35 to prevent the death of apoptotic cells and found that it causes increased non-autonomous cell proliferation, invasion of compartments and persistent misexpression of the wingless (wg) and decapentaplegic(dpp) signalling genes. We propose that a feature of cells undergoing apoptosis is to activate wg and dpp, probably as part of the mechanism to compensate for cell loss. If apoptotic cells are not eliminated,they continuously emit Wg and Dpp signals, which results in developmental aberrations. We suggest that a similar process of uncoupling apoptosis initiation and cell death may occur during tumour formation in mammalian cells.
Cardiorespiratory and tissue adenosine responses to hypoxia and reoxygenation in the short-horned sculpinMyoxocephalus scorpius
Authors: MacCormack T. J. , Driedzic W. R.
Published: October 2004

Adenosine is a product of adenylate phosphate breakdown that can exert protective effects on tissues during energy limitation. Accumulation of cardiac adenosine under hypoxia is well documented in mammals but has not been shown in fish. Adenosine content was measured in heart and brain tissue from short-horned sculpin Myoxocephalus scorpius L. exposed to acute hypoxia and to graded hypoxia and reoxygenation at 8°C. Cardiorespiratory parameters were recorded along with plasma lactate, K+,Ca2+ and Na+ levels and their relationship to adenosine levels investigated. Sculpin exhibited a large bradycardia during hypoxia,with a concomitant drop in cardiac output that recovers fully with reoxygenation. Ventilation rate also declined with hypoxia, suggesting a depression of activity. Plasma lactate concentration was significantly elevated after 4 h at 2.0 mg l-1 dissolved oxygen while K+ levels increased during acute hypoxia. Adenosine levels were maintained in heart under acute and graded hypoxia. Brain levels fluctuated under hypoxia and showed no change with reoxygenation. It is concluded that a depression of cardiac activity in conjunction with an adequate anaerobic metabolism allow sculpin to avoid excessive adenosine accumulation under conditions of moderate hypoxia. Cardiac adenosine levels decreased and plasma K+ levels and heart rate increased significantly at reoxygenation.
Presence and properties of cellulase and hemicellulase enzymes of the gecarcinid land crabs Gecarcoidea natalis and Discoplax hirtipes
Authors: Linton Stuart M. , Greenaway Peter
Published: October 2004

Digestive juice from the herbivorous gecarcinid land crabs Gecarcoidea natalis and Discoplax hirtipes exhibited total cellulase activity and activities of two cellulase enzymes; endo-β-1,4-glucanase and β-1,4-glucosidase. These enzymes hydrolysed native cellulose to glucose. The digestive juice of both species also contained laminarinase,licheninase and xylanase, which hydrolysed laminarin, lichenin and xylan,respectively, to component sugars. The pH optima of β-1,4-glucosidase,endo-β-1,4-glucanase and total cellulase from G. natalis were 4–5.5, 5.5 and 5.5–7, respectively. In the digestive juice from D. hirtipes, the corresponding values were 4–7, 5.5–7 and 4–9, respectively. The pH of the digestive juice was 6.69±0.03 for G. natalis and 6.03±0.04 for D. hirtipes and it is likely that the cellulases operate near maximally in vivo. In G. natalis, total cellulase activity and endo-β-1,4-glucanase activity were higher than in D. hirtipes, and the former species can thus hydrolyse cellulose more rapidly. β-1,4-glucosidase from G. natalis was inhibited less by glucono-d-lactone(Ki=11.12 mmol l-1) than was theβ-1,4-glucosidase from D. hirtipes (Ki=4.53 mmol l-1). The greater resistance to inhibition by theβ-1,4-glucosidase from G. natalis may contribute to the efficiency of the cellulase system in vivo by counteracting the effects of product inhibition and possibly dietary tannins. The activity ofβ-1,4-glucosidase in the digestive juice of D. hirtipes was higher than that of G. natalis.
Calcium handling in Sparus auratus: effects of water and dietary calcium levels on mineral composition, cortisol and PTHrP levels
Authors: Abbink Wout , Bevelander Gideon S. , Rotllant Josep , Canario Adelino V. M. , Flik Gert
Published: October 2004

Juvenile gilthead sea bream (Sparus auratus L.; 10–40 g body mass) were acclimatized in the laboratory to full strength (34‰) or dilute (2.5‰) seawater and fed normal, calcium-sufficient or calcium-deficient diet for nine weeks. Mean growth rate, whole-body calcium and phosphorus content and accumulation rates were determined, as well as plasma levels of ionic and total calcium, cortisol and parathyroid hormone related protein (PTHrP; a hypercalcemic hormone in fish). When confronted with limited calcium access (low salinity and calcium-deficient diet), sea bream show growth arrest. Both plasma cortisol and PTHrP increase when calcium is limited in water or diet, and a positive relationship was found between plasma PTHrP and plasma ionic calcium (R2=0.29, N=18, P<0.05). Furthermore, a strong correlation was found between net calcium and phosphorus accumulation (R2=0.92, N=16, P<0.01) and between body mass and whole-body calcium (R2=0.84, N=25, P<0.01) and phosphorus (R2=0.88, N=24, P<0.01)content. Phosphorus accumulation is strongly calcium dependent, as phosphorus accumulation decreases in parallel to calcium accumulation when the diet is calcium deficient but phosphorus sufficient. We conclude that PTHrP and cortisol are involved in the regulation of the hydromineral balance of these fish, with growth-related calcium accumulation as an important target.
Conservation of capa peptide-induced nitric oxide signalling in Diptera
Authors: Pollock Valerie P. , McGettigan James , Cabrero Pablo , Maudlin Ian M. , Dow Julian A. T. , Davies Shireen-A.
Published: October 2004

In D. melanogaster Malpighian (renal) tubules, the capa peptides stimulate production of nitric oxide (NO) and guanosine 3′,5′-cyclic monophosphate (cGMP), resulting in increased fluid transport. The roles of NO synthase (NOS), NO and cGMP in capa peptide signalling were tested in several other insect species of medical relevance within the Diptera(Aedes aegypti, Anopheles stephensi and Glossina morsitans) and in one orthopteran out-group, Schistocerca gregaria. NOS immunoreactivity was detectable by immunocytochemistry in tubules from all species studied. D. melanogaster, A. aegypti and A. stephensi express NOS in only principal cells,whereas G. morsitans and S. gregaria show more general NOS expression in the tubule. Measurement of associated NOS activity (NADPH diaphorase) shows that both D. melanogaster capa-1 and the two capa peptides encoded in the A. gambiae genome, QGLVPFPRVamide(AngCAPA-QGL) and GPTVGLFAFPRVamide (AngCAPA-GPT), all stimulate NOS activity in D. melanogaster, A. aegypti, A. stephensi and G. morsitans tubules but not in S. gregaria. Furthermore, capa-stimulated NOS activity in all the Diptera was inhibited by the NOS inhibitor l-NAME. All capa peptides stimulate an increase in cGMP content across the dipteran species, but not in the orthopteran S. gregaria. Similarly, all capa peptides tested stimulate fluid secretion in D. melanogaster, A. aegypti, A. stephensi and G. morsitans tubules but are either without effect or are inhibitory on S. gregaria. Consistent with these results, the Drosophila capa receptor was shown to be expressed in Drosophila tubules, and its closest Anopheles homologue was shown to be expressed in Anopheles tubules. Thus, we provide the first demonstration of physiological roles for two putative A. gambiae neuropeptides. We also demonstrate neuropeptide modulation of fluid secretion in tsetse tubule for the first time. Finally, we show the generality of capa peptide action, to stimulate NO/cGMP signalling and increase fluid transport, across the Diptera, but not in the more primitive Orthoptera.
Ontogeny of the gut motility control system in zebrafishDanio rerioembryos and larvae
Authors: Holmberg Anna , Schwerte Thorsten , Pelster Bernd , Holmgren Susanne
Published: October 2004

Using digital motion analysis, the ontogeny of the cholinergic, tachykinin and pituitary adenylate cyclase-activating polypeptide (PACAP) control systems was studied in zebrafish Danio rerio larvae, in vivo. For the first time we show that the regular propagating anterograde waves that occur in the zebrafish larval gut before and around the onset [at 5–6 days post fertilization (d.p.f.)] of feeding are modulated by acetylcholine or atropine, PACAP and NKA (neurokinin A). At 3 d.p.f., when no spontaneous motility has developed, application of acetylcholine did not affect the gut. However, at 4 d.p.f., acetylcholine increased and atropine reduced the frequency of propagating anterograde waves. At 5 d.p.f., NKA increased and PACAP reduced the wave frequency. This suggests that both excitatory and inhibitory pathways develop at an early stage in the gut, independent of exogenous feeding. Immunohistochemistry established the presence of gut neurons expressing PACAP and NKA in the proximal part of the developing gut from the first stage investigated (2 d.p.f.) and before regular motility was observed. 1 d.p.f. (PACAP) or 2 d.p.f. (NKA) stages later the whole gut was innervated. This supports physiological results that gut motility is under neuronal control during the period when regular motility patterns develop.
The effect of substrate on the efficacy of seismic courtship signal transmission in the jumping spider Habronattus dossenus (Araneae:Salticidae)
Authors: Elias Damian O. , Mason Andrew C. , Hoy Ronald R.
Published: October 2004

The jumping spider Habronattus dossenusGriswold 1987 (Salticidae)communicates using seismic signals during courtship and can be found on rocks,sand and leaf litter. We examined the filtering properties of, and tested the efficacy of male courtship signals on, these natural substrates. These substrates have drastically different filtering properties at the distances at which the males court. Rocks sharply attenuated all frequencies, with considerable variability among different rocks. Desert sand showed band-pass properties, attenuating frequencies contained in the animal's signal. Leaf litter passed all frequencies and was the most favourable signalling environment. In behavioural trials, the proportion of males mating successfully was significantly higher on leaf litter than on rocks or desert sand. Males did not modify their courtship behaviour on different substrates. Therefore, the effectiveness of male courtship seismic signals appears to be strongly constrained by the available substratum resources.
Elevated intra-abdominal pressure limits venous return during exercise inVaranus exanthematicus
Authors: Munns Suzanne L. , Hartzler Lynn K. , Bennett Albert F. , Hicks James W.
Published: October 2004

The effects of treadmill exercise on components of the cardiovascular(venous return, heart rate, arterial blood pressure) and respiratory systems(minute ventilation, tidal volume, breathing frequency, oxygen consumption,carbon dioxide production) and intra-abdominal pressure were investigated in the Savannah monitor lizard, Varanus exanthematicus B., at 35°C. Compared with resting conditions, treadmill exercise significantly increased lung ventilation, gular pumping, intra-abdominal pressure, mean arterial blood pressure and venous return (blood flow in the post caval vein). However,venous return declines at high levels of activity, and mean arterial pressure and venous return did not attain peak values until the recovery period,immediately following activity. Elevating intra-abdominal pressure in resting lizards (via saline infusion) resulted in significant reductions in venous return when the transmural pressure of the post caval vein became negative (i.e. when intra-abdominal pressure exceeded central venous pressure). Together these results suggest that increments in intra-abdominal pressure compress the large abdominal veins and inhibit venous return. During locomotion, the physical compression of the large abdominal veins may represent a significant limitation to cardiac output and maximal oxygen consumption in lizards.
Global Optimization of Morse Clusters by Potential Energy Transformations
Authors: Doye Jonathan P. K. , Leary Robert H. , Locatelli Marco , Schoen Fabio
Published: October 2004

The Morse potential is a simple model for the potential energy of atoms with a single parameter ρ that determines the width of the potential well and allows a wide variety of materials to be modeled. Morse clusters are particularly important for applications, but their global optimization is also an extremely hard problem, highly relevant to methods that are to be applied to find the optimal configuration of a biomolecule. In particular, large ρ values are very challenging and, until now, no unbiased global-optimization method has been able to detect all the (putative) global minima at ρ = 14 for clusters with up to N = 80 atoms. In this paper we introduce some techniques for transforming the original Morse potential that allow us to increase considerably the efficiency in locating the known global minima and also to discover some new optimal clusters. These methods are promising candidates for application to the optimization of biomolecules.
Haplotyping Populations by Pure Parsimony: Complexity of Exact and Approximation Algorithms
Authors: Lancia Giuseppe , Pinotti Maria Cristina , Rizzi Romeo
Published: October 2004

In this paper we address the pure parsimony haplotyping problem: Find a minimum number of haplotypes that explains a given set of genotypes. We prove that the problem is APX-hard and present a 2k− 1-approximation algorithm for the case in which each genotype has at most k ambiguous positions. We further give a new integer-programming formulation that has (for the first time) a polynomial number variables and constraints. Finally, we give approximation algorithms, not based on linear programming, whose running times are almost linear in the input size.
Protein Threading: From Mathematical Models to Parallel Implementations
Authors: Andonov Rumen , Balev Stefan , Yanev Nicola
Published: October 2004

This paper presents a new network-flow formulation for the problem of predicting 3D protein structures using threading. Several integer-programming models based on this formulation are proposed and compared. These models allow for an efficient decomposition and for the application of a parallel branch-and-cut algorithm, significantly reducing the running time. The efficiency of our approach has been confirmed by extensive computational experiments.
Multiple Sequence Alignment as a Facility-Location Problem
Authors: Just Winfried , Vedova Gianluca Della
Published: October 2004

A connection is made between certain multiple-sequence alignment problems and facility-location problems, and the existence of a PTAS (polynomial-time approximation scheme) for these problems is shown. Moreover, it is shown that multiple sequence alignment with SP-score and fixed gap penalties is MAX SNP-hard.
A Semidefinite Programming Approach to Side Chain Positioning with New Rounding Strategies
Authors: Chazelle Bernard , Kingsford Carl , Singh Mona
Published: October 2004

Side chain positioning is an important subproblem of the general protein-structure-prediction problem, with applications in homology modeling and protein design. The side chain positioning problem takes a fixed backbone and a protein sequence and predicts the lowest energy conformation of the protein's side chains on this backbone. We study a widely used version of the problem where the side chain positioning procedure uses a rotamer library and an energy function that can be expressed as a sum of pairwise terms. The problem is NP-complete; we show that it cannot even be approximated. In practice, it is tackled by a variety of general search techniques and specialized heuristics. Here, we propose formulating the side chain positioning problem as an instance of semidefinite programming (SDP). We introduce two novel rounding schemes and provide theoretical justification for their effectiveness under various conditions. We apply our method on simulated data, as well as on the computational redesign of two naturally occurring protein cores, and show that our SDP approach generally finds good solutions. Beyond the context of side chain positioning, our very general rounding schemes should be applicable elsewhere.
Steiner Trees and 3-D Macromolecular Conformation
Authors: Stanton Courtney , Smith J. MacGregor
Published: October 2004

One of the key issues in biochemistry and molecular modelling is the determination of 3-D minimum-energy configurations (MECs) for macromolecular structures such as proteins and DNA. Steiner minimal trees are seen as a useful algorithmic paradigm for modelling these structures. In this paper, we examine how Steiner minimal trees (SMTs) and the Steiner ratio value comparing minimum spanning trees (MSTs) are correlated with MEC energies in a physically meaningful manner. We conclude that the carbon and nitrogen atoms are Steiner points in the Steiner minimal tree of the proteins.
An Economic Model of Product Quality and IT Value
Authors: Thatcher Matt E. , Pingry David E.
Published: October 2004

We use an economic model to formalize the complex relationships among IT investments, intermediate performance measures (e.g., product quality and output levels), and economic performance (e.g., productivity, profits, and consumer surplus). We demonstrate that a profit-maximizing monopolist invests in IT (modeled as changes in parametric characteristics of the firm) to design a better-quality product and charge a higher price. While this profit-maximizing adjustment generates more consumer surplus, it also increases production costs in a way that adversely affects productivity. In contrast, a simple model extension shows that when a firm is unwilling or unable to improve product quality, then IT investments result in suboptimal improvements in profits, an increase in consumer surplus, and an increase in productivity. Together, these models highlight the way in which product quality moderates the relationship between IT investments and economic performance. We also demonstrate that these relationships are robust to the socially optimal case in which a social planner chooses price and quality to maximize social welfare. In addition, we demonstrate that the results of the monopoly model hold when considering the design and development of products offered free of charge (e.g., free online content), but that provide indirect benefits to the firm (e.g., more advertising revenues).
Desiring texts: the erotics of domestic space in the poetry of Lyn Hejinian and Rosmarie Waldrop
Authors: Selby Nick
Published: October 2004

This article examines the ways in which desire operates as a discursive site throughout Lyn Hejinian’s My Life (1987) and Rosmarie Waldrop’s ‘Inserting the Mirror’ (1987), and it argues that the articulation of desire in these prosepoems rests in the abjection
of the bodily to the textual. What these texts seek to locate, or the locus of their desire, is the means by which the erotic is inserted into the space of the domestic and the poetic. Central to the paper’s analysis of the desire which operates in these texts is Julia Kristeva’s
notion of abjection. The paper argues that in their attempts to reconstitute discourses of gender and sexuality, My Life, ‘Inserting the Mirror’ (and ‘language poetry’ more generally), confront the ways in which late-twentieth- century American ideology is articulated
through the assertion of an imaginary (in Kristeva’s sense) unified subjectivity. Such an assertion is precisely the desire that haunts contemporary America, such is the space that its sexual politics traverse.
Editorial: The When and the Where of Travis Bickle
Authors: Bennett G.H.
Published: October 2004

Later this year the United States will enter a period of self-reflection and remembrance – one of those periodic moments when the nation examines itself and its past in the light of some marker. Prompted by the 60th anniversary of D-Day and the Presidential election in November,
it will be a time for re-asserting and questioning American values. The questions will be wide-ranging and awkward.
Framing September 11
Authors: Ryan David
Published: October 2004

Immediately after September 11, Washington and US culture more generally created the framework within which it responded to those crimes. Various symbols, devices, rhetorical strategies and images were employed that soon obscured the broader meanings of September 11 and framed the US
response within the benign narratives, the constructs of nationhood, and the images that would link that date to the road to war. The semiotic struggle of mid-September 2001 saw Bush’s rhetoric and the use of the flag and photography privilege a certain interpretation over others. To
this end a series of conflations took place that facilitated the military response, ultimately encompassing Iraq. Within days the ‘power to persuade’ had been used effectively to define the events, and in so doing to limit the scope of critical discussion, alternative explanations
and understanding. At issue was the centrality of the US identity. It was imperative to place the events in the framework of the benign narratives rather than to consider US support for authoritarian regimes across the Middle East for five decades.
The Confidence Man: performing the magic of modernity
Authors: Mitchell Rick
Published: October 2004

Herman Melville appropriated the confidence man, a uniquely American figure, for his 1857 novel The Confidence Man: His Masquerade. Eschewing established conventions of realism, Melville wrote a seemingly impenetrable novel which both enacts and subverts the rapidly intensifying
commodification of experience in mid-nineteenth-century America. Published while Karl Marx was beginning to develop his theory of the fetishism of commodities in his private notebooks, The Confidence Man uncannily embodies and critiques the magical nature of the commodity, as well as
the often deceptive (though necessary) trait upon which commodity exchange is so dependent: confidence.
The Activity of Class I and II Alcohol Dehydrogenase Isoenzymes in the Sera of Patients with Liver Tumours
Authors: Chrostek Lech , Szmitkowski Maciej
Published: October 2004

We have measured the activity of class I and II alcohol dehydrogenase isoenzymes in the sera of patients with liver tumours, using class-specific fluorogenic naphthaldehydes as substrates. The activity of the tested isoenzymes was unchanged in primary tumours and significantly increased (class I) in metastatic liver tumours. The total enzyme activity was also increased (3-fold) in this group of patients. The elevated activity of class I isoenzymes in secondary tumours seems to be caused by the enzyme released from primary cells originating in the other organs, but increased total enzyme activity measured with chromogenic substrates may be proof of the presence of other classes of isoenzymes. These results show that the elevated class I isoenzymes and total enzyme activity in the sera of patients with liver tumours may indicate the metastatic origin of these tumours.
Association between PON1 L/M55 Polymorphism and Plasma Lipoproteins in Two Canadian Aboriginal Populations
Authors: Fanella Sergio , Harris Stewart B. , Young T. Kue , Hanley Anthony J.G. , Zinman Bernard , Connelly Philip W. , Hegele Robert A.
Published: October 2004

Serum paraoxonase circulates on a subfraction of high density lipoproteins and appears to use phospholipids on both low and high density lipoprotein particles as a physiological substrate. This functional relationship could explain the reported associations between common variation in the PON1 gene—at codons 55 and 192—and phenotypes related to atherosclerosis and lipoprotein metabolism. We evaluated associations between plasma lipoproteins and PON1 L/M55, PON1 Q/R192 and PON2 A/G148 polymorphisms in samples from two Canadian aboriginal populations, namely the Oji-Cree and the Inuit. In diabetic Oji-Cree, we found that carriers of PON1 M55 had a higher mean plasma triglyceride concentration than non-carriers. In non-diabetic Oji-Cree, we found that carriers of PON1 M55 had higher mean plasma concentrations of total and low density lipoporetein cholesterol and apo B than non-carriers. In Inuit, we found that carriers of PON1 M55 had higher mean plasma concentrations of total and low density lipoprotein cholesterol than non-carriers. The other polymorphic markers were not associated with variation in any plasma lipoprotein trait. Thus, the PON1 M55 allele appeared to be associated with deleterious changes in the plasma lipoprotein profile from two independent Canadian aboriginal samples. These results suggest that common variation in PON1 codon 55 is associated with variation of intermediate traits in plasma lipoprotein metabolism in aboriginal
Integrons: an Antibiotic Resistance Gene Capture and Expression System
Authors: Ploy Marie-Cécile , Lambert Thierry , Couty Jean-Pierre , Denis François
Published: October 2004

Bacteria can transfer genetic information to provide themselves with protection against most antibiotics. The acquisition of resistance gene arrays involves genetic mobile elements like plasmids and transposons. Another class of genetic structures, termed integrons, have been described and contain one or more gene cassettes located at a specific site. Integrons are defined by an intI gene encoding an integrase, a recombination site attI and a strong promoter. At least six classes of integrons have been determined according to their intI gene. Classes 1, 2 and 3 are the most studied and are largely implicated in the dissemination of antibiotic resistance. A gene cassette includes an open reading frame and, at the 3′-end, a recombination site attC. Integration or excision of cassettes occur by a site-specific recombination mechanism catalyzed by the integrase. However, insertion can occur, albeit rarely, at non-specific sites leading to a stable situation for the cassette. Cassettes are transcribed from the common promoter located in the 5′-conserved segment and expression of distal genes is reduced by the presence of upstream cassettes. Most gene cassettes encode antibiotic resistant determinants but antiseptic resistant genes have also been described. Integrons seem to have a major role in the spread of multidrug resistance in Gram-negative bacteria but integrons in Gram-positive bacteria were described recently. Moreover, the finding of super-integrons with gene-cassettes coding for other determinants (biochemical functions, virulence factors) in Vibrio isolates dating from 1888 suggests the likely implication of this multi-component cassette-integron system in bacterial genome evolution before the antibiotic era and to a greater extent than initially believed.