bluuebunny/crossref_metadata_2025 huggingface dataset:
Odour quality discrimination for behavioural antagonist compounds in three tortricid species
Authors: Stephens Andrea E.A. , Suckling David Maxwell , El‐Sayed Ashraf M.
Published: April 2008

The antennal and behavioural response of three tortricid species (Lepidoptera: Tortricidae) to their corresponding sex pheromones and known or putative behavioural antagonists was tested by electroantennography and in field trials. The species and their pheromones and known or proposed behavioural antagonist were lightbrown apple moth, Epiphyas postvittana (Walker) [pheromone: 95% (E)‐11‐tetradecenyl acetate (E11‐14Ac) and 5% (E,E)‐9,11‐tetradecadienyl acetate (E9E11‐14Ac); antagonist: (Z)‐11‐tetradecenyl acetate (Z11‐14Ac)], codling moth, Cydia pomonella (L.) [pheromone: (E,E)‐8,10‐dodecadien‐1‐ol (codlemone); antagonist: (E,E)‐8,10‐dodecadienyl acetate (codlemone acetate)], and gorse pod moth, Cydia ulicetana (Haworth) [pheromone: (E,E)‐8,10‐dodecadienyl acetate (codlemone acetate); putative antagonist: (E,E)‐8,10‐dodecadien‐1‐ol (codlemone)]. In all three species, the antennal response to the antagonists was not significantly different from the antennal response to con‐specific sex pheromone compounds. In the field trapping experiments, significantly fewer males of all three species were attracted to the respective pheromone when blended with the behavioural antagonist compound. However, this response varied between the species, with lightbrown apple moth and codling moth showing stronger responses to the antagonist compounds than gorse pod moth. Both lightbrown apple moth and codling moth males were able to discriminate between pure pheromone and pheromone blended with the antagonist when placed in traps side‐by‐side separated by ca. 10 cm. The presence of the behavioural antagonist not only affected the catch of males of both species within their own traps but also affected the catch in the neighbouring trap that contained con‐specific sex pheromone; the catch of gorse pod moth was not reduced by the presence of codlemone in the neighbouring trap. These results suggest that strong behavioural antagonists such as codlemone acetate for codling moth and Z11‐14Ac for lightbrown apple moth induce their inhibition effect at a substantial distance downwind from the odour source; however, most of those males that were able to overcome this inhibition effect at the early stage of orientation to odour source, were able to discriminate between the pheromone source and the pheromone source admixed with behavioural antagonist. Moderate behavioural antagonists such as codlemone for gorse pod moth did not elicit a discrimination effect.
Performance of specialist and generalist herbivores feeding on cabbage cultivars is not explained by glucosinolate profiles
Authors: Poelman Erik H. , Galiart Ron J. F. H. , Raaijmakers Ciska E. , Van Loon Joop J. A. , Van Dam Nicole M.
Published: April 2008

Plants display a wide range of chemical defences that may differ in effectiveness against generalist and specialist insect herbivores. Host plant‐specific secondary chemicals such as glucosinolates (GS) in Brassicaceae typically reduce the performance of generalist herbivores, whereas specialists have adaptations to detoxify these compounds. The concentration of glucosinolates may also alter upon herbivory, allowing the plant to tailor its response to specifically affect the performance of the attacking herbivore. We studied the performance of three Lepidoptera species, two specialists [Pieris rapae L. (Pieridae), Plutella xylostella L. (Yponomeutidae)] and one generalist [Mamestra brassicae L. (Noctuidae)], when feeding on eight cultivars of Brassica oleracea L. and a native congener (Brassica nigra L.) and related this to the GS content. We tested the hypotheses (i) that a generalist herbivore is more affected by high GS concentrations, and (ii) that generalist feeding has a stronger effect on GS levels. Although performance of the three herbivores was different on the B. oleracea cultivars, M. brassicae and P. xylostella had a similar ranking order of performance on the eight cultivars. In most of the cultivars, the concentration of indole GS was significantly higher after feeding by P. rapae or M. brassicae than after P. xylostella feeding. As a consequence, the total concentration of GS in the cultivars showed a different ranking order for each herbivore species. The generalist M. brassicae performed equally well as the specialist P. xylostella on cultivars with high concentrations of GS. Our findings suggest that secondary metabolites other than GSs or differences in nutrient levels affect performance of the species studied.
Aggregation pheromone of the agave weevil,Scyphophorus acupunctatus
Authors: Ruiz‐Montiel Cesar , García‐Coapio Guadalupe , Rojas Julio C. , Malo Edi A. , Cruz‐López Leopoldo , Del Real Ignacio , González‐Hernández Héctor
Published: April 2008

The agave weevil,Scyphophorus acupunctatusGyllenhal (Coleoptera: Curculionidae), is the most important insect pest of wild and cultivated agaves in the world. Combined gas chromatography‐electroantennography (GC‐EAD) analysis of male volatile extracts showed that four peaks elicited antennal responses from males and females. The peaks were identified by GC‐mass spectrometry (GC‐MS) as 2‐methyl‐4‐heptanol (1), 2‐methyl‐4‐octanol (2), 2‐methyl‐4‐heptanone (3), and 2‐methyl‐4‐octanone (4). Electroantennogram (EAG) recordings of both sexes to 0.01‐, 0.1‐, 1‐, and 10‐µg stimulus load of synthetic compounds showed that the dose of the tested compounds and weevil sex significantly influenced the antennal response ofS. acupunctatus. However, there was no sexual dimorphism in the antennal responses to the four synthetic compounds evaluated because the EAG profiles revealed no interaction between doses by sex. Antennae ofS. acupunctatuswere most sensitive to compounds 2 and 4, reaching the threshold at a 0.01‐µg stimulus load. Weevil antennae were less sensitive to compounds 1 and 3, and the threshold response to these compounds was 0.1 µg. Behavioural evaluation of the synthetic compounds showed them to be attractive to both males and females in a Y‐tube olfactometer. Field experiments confirmed the laboratory results, showing that all components, singly or in blends, were attractive to the weevils. In general, traps baited with the quaternary blend of compounds 1–4 captured significantly more weevils than traps baited with males. However, compounds 3 and 4 were sufficient to obtain captures equivalent to those by the quaternary blend. The potential use of the aggregation pheromone in the development of a mass‐trapping programme as a viable pest management alternative forS. acupunctatusis discussed.
Selective CB2 up‐regulation in women affected by endometrial inflammation
Authors: Iuvone Teresa , De Filippis Daniele , Di Spiezio Sardo Attilio , D'Amico Alessandra , Simonetti Sara , Sparice Stefania , Esposito Giuseppe , Bifulco Giuseppe , Insabato Luigi , Nappi Carmine , Guida Maurizio
Published: April 2008

Endometritis is defined as an inflammation of the endometrial mucosa of the uterus. In endometritis large amounts of toxic mediators, including nitric oxide (NO) are released by inflammatory cells. As a consequence of nitric oxide‐dependent injury, the cells respond by triggering protective mechanisms, by changing the endo‐cannabinoid system (ECS) which comprises both CB1 and CB2 cannabinoid receptors and their endogenous ligands. The aim of our study was to seek out evidence for the presence of cannabinoid receptors in inflammatory endometrial tissue as well as for their potential role in endometrial inflammation. Our results showed a selective up‐regulation of both transcription and expression of CB2 receptors in biopsies from women affected by endometrial inflammation compared to healthy women. The experiments with the nitric oxide‐donor S‐Nitroso‐L‐Glutathione (GSNO) suggest that such a selective up‐regulation may be related to the nitric oxide release occurring during endometrial inflammation. In addition, we demonstrated an increase in chymase expression, a marker of mast cells, in biopsies of women affected by endometritis. Therefore our results support the hypothesis that the up‐regulation of CB2 occurs mainly on mast cells and that it might tend to sensitize these cells to the anti‐inflammatory effect exerted by endogenous cannabinoids by binding their receptor and thus preventing the mast cell degranulation and the release of pro‐inflammatory mediators. In conclusion, we believe that the selective CB2 up‐regulation might play a role as a novel prognostic factor in endometrial inflammation.
Overexpression of vascular endothelial growth factor (VEGF) receptors on keratinocytes in psoriasis: regulated by calcium independent of VEGF
Authors: Man Xiao‐Yong , Yang Xiao‐Hong , Cai Sui‐Qing , Bu Zhang‐Yu , Zheng Min
Published: April 2008

Psoriasis is a common chronic inflammatory disease of the skin characterized by epidermal hyperplasia and angiogenesis. Recently, vascular endothelial growth factor receptors (VEGFRs, including VEGFR‐1, VEGFR‐2 and VEGFR‐3) were found to be expressed in normal human epidermis and associated with proliferation and migration of keratinocytes. The purpose of this study is to investigate the expression of VEGFRs on psoriatic keratinocytes and the roles of calcium and VEGF in regulating VEGFR expression. Skin samples from 17 patients with chronic plaque psoriasis and 11 normal controls were included. The expression of VEGFRs in psoriatic keratinocytes at mRNA and protein levels was determined by reverse transcriptase‐polymerase chain reaction (RT‐PCR) and Western blot analysis. Localization of the VEGFRs in skin lesions was determined by immuno‐fluorescent method. Since keratinocyte proliferation and differentiation rely on calcium concentrations, and VEGF is overexpressed in psoriatic epidermis, we further investigated the roles of calcium and VEGF in regulating the expression of VEGFRs. Overexpression of VEGFR‐1, VEGFR‐2 and VEGFR‐3 in psoriatic epidermis was demonstrated both at mRNA and protein levels in vitro. VEGFRs were strongly labeled in non‐lesional, perilesional and lesional psoriatic keratinocytes in all viable epidermal stratums in vivo. Furthermore, both exogenous VEGF165 and calcium enhanced the expression of VEGFRs. Calcium also enhanced the expression of VEGF in non‐lesional psoriatic keratinocytes, while targeted blockade of VEGF activity by bevacizum‐ab could not inhibit calcium‐induced up‐regulation of protein levels of VEGFRs. We conclude from these results that VEGFRs are overexpressed in lesional psoriatic epidermal keratinocytes. Both calcium and VEGF regulate VEGFRs expression in psoriatic epidermis. More importantly, calcium is a potential regulator for VEGFR independent of VEGF.
Trichostatin A causes p53 to switch oxidative‐damaged colorectal cancer cells from cell cycle arrest into apoptosis
Authors: Habold C. , Poehlmann A. , Bajbouj K. , Hartig R. , Korkmaz K.S. , Roessner A. , Schneider‐Stock R.
Published: April 2008

Many studies aim at improving therapeutic efficacy by combining strategies with oxidative stress‐inducing drugs and histone deacetylase (HDAC) inhibitors in colorectal cancer. As p53 and p21WAF1 are essential in oxidative stress‐induced DNA damage, we investigated epigenetic regulation of p21WAF1 promoter. Firstly, HCT116 p53+/+ and p53−/− colorectal cancer cells were treated with H2O2 for 6 hrs and 24 hrs (early/late response). Chromatin immunoprecipitation revealed transcriptional transactivation of p21WAF1 in HCT116 p53+/+ cells as shown by increased binding of p53 and acetylated H4 around two p21WAF1 promoter sites, the responsible element (RE) and the Sp1 site, while both proteins bound preferentially on the RE. Interestingly, H3 was not involved, suggesting H4‐specific transactivation of the p21WAF1 promoter. H2O2 addition resulted in G2/M arrest of both HCT116 cell lines without significant cell death. To investigate whether a HDAC inhibitor strengthens G2/M arrest, we pretreated cells with Trichostatin A (TSA). In HCT116 p53+/+ cells, we found (i) remarkably increased acetylated H4 around both p21WAF1 promoter regions, especially at the Sp1 site; (ii) increased acetylation of p53 at lysines 320 and 382;(iii) displacement of HDAC1 from the Sp1 site, thus inhibiting its repression effect and increasing p53 binding.p53 seems to trigger H4‐acetylation around the p21WAF1 promoter because there was nearly no H4 acetylation in HCT116 p53−/− cells. For the first time we show that there is a time‐dependent TSA mode of action with increased p53‐dependent histone H4 acetylation at the p21WAF1 promoter in early response, and decreased acetylation in late response. Reduced p53‐triggered transactivation of p21WAF1 in late response allows cells to re‐enter cell cycle, and TSA causes p53 to simultaneously induce apoptosis.
Cell expression of GDAP1 in the nervous system and pathogenesis of Charcot‐Marie‐Tooth type 4A disease
Authors: Pedrola Laia , Espert Antonio , Valdés‐Sánchez Teresa , Sánchez‐Piris Maribel , Sirkowski Erich E. , Scherer Steven S. , Fariñas Isabel , Palau Francesc
Published: April 2008

Mutations in the mitochondrial protein GDAP1 are the cause of Charcot‐Marie‐Tooth type 4A disease (CMT4A), a severe form of peripheral neuropathy associated with either demyelinating, axonal or intermediate pheno‐types. GDAP1 is located in the outer mitochondrial membrane and it seems that may be related with the mitochondrial network dynamics. We are interested to define cell expression in the nervous system and the effect of mutations in mitochondrial morphology and pathogenesis of the disease. We investigated GDAP1 expression in the nervous system and dorsal root ganglia (DRG) neuron cultures. GDAP1 is expressed in motor and sensory neurons of the spinal cord and other large neurons such as cerebellar Purkinje neurons, hippocampal pyramidal neurons, mitral neurons of the olfactory bulb and cortical pyramidal neurons. The lack of GDAP1 staining in the white matter and nerve roots suggested that glial cells do not express GDAP1. In DRG cultures satellite cells and Schwann cells were GDAP1‐negative. Overexpression of GDAP1‐induced fragmentation of mitochondria suggesting a role of GDAP1 in the fission pathway of the mitochondrial dynamics. Missense mutations showed two different patterns: most of them induced mitochondrial fragmentation but the T157P mutation showed an aggregation pattern. Whereas null mutations of GDAP1 should be associated with loss of function of the protein, missense mutations may act through different pathogenic mechanisms including a dominant‐negative effect, suggesting that different molecular mechanisms may underlay the pathogenesis of CMT4A.
Ccr1 deficiency reduces inflammatory remodelling and preserves left ventricular function after myocardial infarction
Authors: Liehn E. A. , Merx M. W. , Postea O. , Becher S. , Djalali‐Talab Y. , Shagdarsuren E. , Kelm M. , Zernecke A. , Weber C.
Published: April 2008

Myocardial necrosis triggers inflammatory changes and a complex cytokine cascade that are only incompletely understood. The chemokine receptor CCR1 mediates inflammatory recruitment in response to several ligands released by activated platelets and up‐regulated after myocardial infarction (MI). Here, we assess the effect of CCR1 on remodelling after MI using Ccr1‐deficient (Ccr1−/−) mice. MI was induced in Ccr1−/− or wild‐type mice by proximal ligation of the left anterior descending (LAD). Mice were sacrificed and analysed at day 1, 4, 7, 14 and 21 after MI. While initial infarct areas and areas at risk did not differ between groups, infarct size increased to 20.6±8.4% of the left ventricle (LV) in wild‐type mice by day 21 but remained at 11.2±1.2% of LV (P<0.05) in Ccr1−/− mice. This attenuation in infarct expansion was associated with preserved LV function, as analysed by isolated heart studies according to Langendorff. Left ventricular developed pressure was 84.5±19.8 mmHg in Ccr1−/− mice compared to 49.0±19.7 mmHg in wild‐type mice (P<0.01) and coronary flow reserve was improved in Ccr1−/− mice. An altered post‐infarct inflammatory pattern was observed in Ccr1−/− mice characterized by diminished neutrophil infiltration, accelerated monocyte/lymphocyte infiltration, decreased apoptosis, increased cell proliferation and earlier myofibroblast population in the infarcted tissue. In conclusion, functional impairment and structural remodelling after MI is reduced in the genetic absence of Ccr1 due to an abrogated early inflammatory recruitment of neutrophils and improved tissue healing, thus revealing a potential therapeutic target.
Cancer stem cells: implications for the progression and treatment of metastatic disease
Authors: Croker A.K , Allan A.L
Published: April 2008

Introduction

The metastatic process

The cancer stem cell hypothesis

Parallels between stem cell behaviour and metastatic behaviour

Therapeutic implications

Conclusions and future directions

Metastasis is the major cause of death for cancer patients with solid tumours, due mainly to the ineffectiveness of current therapies once metastases begin to form. Further insight into the biology of metastasis is therefore essential in order to gain a greater understanding of this process and ultimately to develop better cancer therapies. Metastasis is an inefficient process, such that very few cells that leave a tumour successfully form macrometastases in distant sites. This suggests that only a small subset of cells can successfully navigate the metastatic cascade and eventually re‐initiate tumour growth to form life‐threatening metastases. Recently, there has been growing support for the cancer stem cell (CSC) hypothesis which stipulates that primary tumours are initiated and maintained by a small subpopulation of cancer cells that possess “stem‐like” characteristics. Classical properties of normal stem cells are strikingly reminiscent of the observed experimental and clinical behaviour of metastatic cancer cells, including an unlimited capacity for self renewal; the requirement for a specific ‘niche’or microenvironment to grow; use of the stromal cell‐derived factor 1 (SDF‐1)/chemokine receptor 4 (CXCR4) axis for migration; enhanced resistance to apoptosis and an increased capacity for drug resistance. Therefore, in addition to playing a role in primary tumour formation, we believe that CSCs are also key players in the metastatic process. We will review the current evidence supporting this idea and discuss the potential implications of the CSC hypothesis with regards to experimental investigation and treatment of metastatic disease.
Acetylcholinesterase‐R increases germ cell apoptosis but enhances sperm motility
Authors: Mor I. , Sklan E.H. , Podoly E. , Pick M. , Kirschner M. , Yogev L. , Bar‐Sheshet Itach S. , Schreiber L. , Geyer B. , Mor T. , Grisaru D. , Soreq H.
Published: April 2008

Changes in protein subdomains through alternative splicing often modify protein‐protein interactions, altering biological processes. A relevant example is that of the stress‐induced up‐regulation of the acetylcholinesterase (AChE‐R) splice variant, a common response in various tissues. In germ cells of male transgenic TgR mice, AChE‐R excess associates with reduced sperm differentiation and sperm counts. To explore the mechanism(s) by which AChE‐R up‐regulation affects spermatogenesis, we identified AChE‐R's protein partners through a yeast two‐hybrid screen. In meiotic spermatocytes from TgR mice, we detected AChE‐R interaction with the scaffold protein RACK1 and elevated apoptosis. This correlated with reduced scavenging by RACK1 of the pro‐apoptotic TAp73, an outcome compatible with the increased apoptosis. In contrast, at later stages in sperm development, AChE‐R's interaction with the glycolytic enzyme enolase‐α elevates enolase activity. In transfected cells, enforced AChE‐R excess increased glucose uptake and adenosine tri‐phosphate (ATP) levels. Correspondingly, TgR sperm cells display elevated ATP levels, mitochondrial hyperactivity and increased motility. In human donors' sperm, we found direct association of sperm motility with AChE‐R expression. Interchanging interactions with RACK1 and enolase‐α may hence enable AChE‐R to affect both sperm differentiation and function by participating in independent cellular pathways.
The alternative complement pathway revisited
Authors: Harboe Morten , Mollnes Tom Eirik
Published: April 2008

Introduction

Methods to study and modify the alternative pathway

Influence of AP amplification on the effect of specific activation of the other initial pathways

Properdin

Influence of AP in deficiency states

Complement in sepsis

Concluding remarks

Alternative pathway amplification plays a major role for the final effect of initial specific activation of the classical and lectin complement pathways, but the quantitative role of the amplification is insufficiently investigated. In experimental models of human diseases in which a direct activation of alternative pathway has been assumed, this interpretation needs revision placing a greater role on alternative amplification. We recently documented that the alternative amplification contributed to 80–90% of C5 activation when the initial activation was highly specific for the classical pathway. The recent identification of properdin as a recognition factor directly initiating alternative pathway activation, like C1q in the classical and mannose‐binding lectin in the lectin pathway, initiates a renewed interest in the reaction mechanisms of complement. Complement and Toll‐like receptors, including the CD14 molecule, are two main upstream recognition systems of innate immunity, contributing to the inflammatory reaction in a number of conditions including ischaemia‐reperfusion injury and sepsis. These systems act as ‘double‐edged swords’, being protective against microbial invasion, but harmful to the host when activated improperly or uncontrolled. Combined inhibition of complement and Toll‐like receptors/CD14 should be explored as a treatment regimen to reduce the overwhelming damaging inflammatory response during sepsis. The alternative pathway should be particularly considered in this regard, due to its uncontrolled amplification in sepsis. The alternative pathway should be regarded as a dual system, namely a recognition pathway principally similar to the classical and lectin pathways, and an amplification mechanism, well known, but quantitatively probably more important than generally recognized.
Nogo‐A and Nogo‐66 receptor in amyotrophic lateral sclerosis
Authors: Teng Felicia Yu Hsuan , Tang Bor Luen
Published: April 2008

Nogo/reticulon (RTN)‐4 has been strongly implicated as a disease marker for the motor neuron disease amyotrophic lateral sclerosis (ALS). Nogo isoforms, including Nogo‐A, are ectopically expressed in the skeletal muscle of ALS mouse models and patients and their levels correlate with the disease severity. The notion of a direct involvement of Nogo‐A in ALS aetiology is supported by the findings that Nogo‐A deletion in mice reduces muscle denervation and prolongs survival, whereas overexpression of Nogo‐A destabilizes motor nerve terminals and promotes denervation. Another intriguing, and somewhat paradoxical, recent finding revealed that binding of the Nogo‐66 receptor (NgR) by either agonistic or antagonistic Nogo‐66‐derived peptides protects against p75 neurotrophin receptor (p75NTR)‐dependent motor neuron death. Ligand binding by NgR could result in subsequent engagement of p75NTR, and this association could preclude pro‐apoptotic signalling by the latter. Understanding the intricate interplay among Nogo isoforms, NgR and p75NTR in ALS disease progression may provide important, therapeutically exploitable information.
Progressive recovery of osseoperception as a function of the combination of implant‐supported prostheses
Authors: Batista Mauro , Bonachela Wellington , Soares Janir
Published: April 2008

The extraction of teeth involves the elimination of extremely sensitive periodontal mechanoreceptors, which play an important role in oral sensory perception.

Objectives: The aim of this study was to evaluate the recovery of interocclusal sensory perception for micro‐thickness in individuals with different types of implant‐supported prostheses.

Materials and Methods: Wearers of complete dentures (CDs) comprised the negative control group (group A, n=17). The experimental group consisted of wearers of prostheses supported by osseointegrated implants (Group B, n=29), which was subsequently divided into 4 subgroups: B1 (n=5) – implant supported overdentures (ISO) occluding with CD; B2 (n=6) – implant‐supported fixed prostheses (ISFP) occluding with CD; B3 (n=8) – wearers of maxillary and mandibular ISFP, and B4 (n=10) – ISFP occluding with natural dentition (ND). Individuals with ND represented the positive control group (Group C, n=24). Aluminum foils measuring 10 μm, 24 μm, 30 μm, 50 μm, 80 μm, and 104 μm thickness were placed within the premolar area, adding up to 120 tests for each individual.

Results: The mean tactile thresholds of groups A, B1, B2, B3, B4, and C were 92 μm, 27 μm, 27 μm, 14 μm, 10 μm, and 10 μm, respectively. [Correction added after publication online 18 April 2008: in the preceding sentence 92 μm, 27 μm, 14 μm, 10 μm and 10 μm, was corrected to 92 μm, 27 μm, 27 μm, 14 μm, 10 μm and 10 μm.] The Kruskal‐Wallis test revealed significant difference among groups (P<0.05). The Dunn test revealed that group A was statistically different from groups C, B3, and B4, and that B1 and B2 were statistically different from group C.

Conclusion: Progressive recovery of osseoperception as a function of the combination of implant‐supported prostheses could be observed. Moreover, ISO and/or ISFP combinations may similarly maximize the recovery of osseoperception.
Spacing and crowding among African and Caucasian children
Authors: Mugonzibwa EA , Eskeli R , Laine‐Alava MT , Kuijpers‐Jagtman AM , Katsaros C
Published: April 2008

Structured Abstract

Authors –  Mugonzibwa EA, Eskeli R, Laine‐Alava MT, Kuijpers‐Jagtman AM, Katsaros C

Objective –  To determine spacing and crowding according to ethnic group, gender and dental emergence stage among Tanzanian African and Caucasian children.

Design –  Cross‐sectional epidemiological clinical study.

Setting –  A total of 869 African (428 boys, 441 girls) and 706 Caucasian (319 boys, 387 girls) school children, aged 3½–16 years.

Main Outcome Measures –  Comparison of spacing and crowding between African and Caucasian children according to gender and dental emergence stage.

Results –  Spacing was more often found in the maxilla, while crowding was more common in the mandible. Only during the transition of the maxillary permanent front teeth was there significantly more spacing in Caucasians. No gender differences were found. In both samples spacing decreased during later emergence stages. Crowding was more often found in Caucasian children than in African children. In Caucasian children the frequency of crowding increased with advanced emergence stages, while for Africans the trend was not consistent.

Conclusion –  When planning resources for orthodontic treatment for different populations as well as planning treatment for individuals, ethnic background and emergence stage of the dentition need to be considered.
The Story of Abraham and Models of Human Identity
Authors: Mills Mary
Published: April 2008

This paper explores the profiles of the women characters Sarah and Hagar as models of human identity. The two characters can only be explored through reading the over-arching narrative of the story of Abraham. Their profiles and narrated personalities have to be extracted from that narrative, but there is a two-sided nature of this necessity. If Sarah and Hagar cannot be separated from the biblical narrator's engagement with father Abraham, neither can Abraham function as father of the nations except through his interaction with these two women. The reader is thus led towards an understanding of how the stories of Genesis 12–24 deal with the issue of parenthood.

The body of the paper consists in a close reading of the biblical material following a method of reading which is rooted in the use of imagination as an exegetical tool – a style adopted by Paul in his allegorical approach to Sarah and Hagar in Galatians 4. This approach opens into narrative criticism with a focus on characterisation and on the interactions of Sarah, Hagar and Abraham, caught up in a Domestic Comedy. The women's characters are explored through the themes of parenthood as other, the other woman and woman as other. A final section explores some of the points of narrative ethics to be extracted from the close textual readings of the paper, with reference to the writings of Paul Ricoeur and Emmanuel Levinas. It is suggested that female as well as male characters may offer fruitful models for human identity.
Islam and Diversity: Alternative Voices within Contemporary Islam
Authors: Calderini Simonetta
Published: April 2008

Islam contains a greater plurality of theology than is often realised. Here two “alternative voices” are chosen as examples of how cultural accretions can be questioned to what is taken to be the original, pure voice of Islam. Amina Wadud has led a mixed congregation in prayer in New York and has demonstrated, not without opposition, that women can be imams. There follows a discussion of the historical debate about women as imams and reactions to Wadud's actions. The second voice is Hasan Askari, an Indian Muslim who has written widely on inter-faith dialogue. He maintains that to reduce differences between Judaism, Christianity and Islam, differences should be interpreted symbolically rather than literally. He questions all claims to finality in any religion and he believes that historical Islam has yet to be transformed to “universal Islam”. Religious differences can only be finally transcended at a level of mystical experience.
The Shakespeare Authorship Debate Revisited
Authors: Smith Emma
Published: April 2008

Who wrote Shakespeare? And does it matter? Since Delia Bacon's researches in the mid‐nineteenth century, writers have questioned whether Shakespeare of Stratford really did write the works attributed to him, and proposed numerous alternative authors including Francis Bacon, the Earl of Oxford and Christopher Marlowe. This article does not endorse this scepticism, but instead treats the sceptical phenomenon as a wayward contribution to Shakespearean studies, discussing the history and methodology of these anti‐Stratfordian claims, to assess their hold on generations of interested amateurs including Henry James, Nathaniel Hawthorne and Sigmund Freud. The authorship debate is conceptualised according to different paradigms: as a conspiracy theory, as a reaction against the growing professionalisation of literary studies within universities, and as a version of the child's wish for more glamorous parents, theorised by Freud in ‘Family Romances’. Its ideological force – both socially conservative – a nobleman must have written the plays – and hermeneutically radical – their messages are potentially dangerous so require the utmost secrecy – is discussed. Finally I relate the authorship debate to recent critical analyses of Shakespearean collaborations with other authors, and suggest that this is the direction in which its probing energies might most usefully be taken in future.
Innovations in Aged Care: The aged care pain chart: An innovative approach to assessing, managing and documenting pain in older people
Authors: Edvardsson David , Katz Benny , Nay Rhonda
Published: April 2008

This article presents the development and initial testing of a comprehensive pain chart for the assessment, management and documentation of pain in older people in subacute and residential aged care. The pain chart was developed from existing assessment scales and pain indicators, and is targeting needs of older people in residential care and geriatric hospital settings with high prevalence of cognitive impairments. The chart is based on self‐report of pain but allows for observation of pain‐related behaviours for those unable to report pain. The chart consists of one evaluative and one documentation dimension, and was evaluated by a group of clinicians in geriatric hospital care (n = 15) and residential aged care (n = 6). The chart was found to be content valid, informative and easy to use, facilitating clinical assessments and monitoring, and assisting visual readings of patients’ temporal pain trends.
Research: The challenges of clinical trials in the exclusion zone: The case of the frail elderly
Authors: Ridda Iman , Lindley Richard , MacIntyre Raina C
Published: April 2008

Frail older people have been systematically excluded from randomised controlled trials (RCT). We aim to recruit older, frail hospitalised patients in an RCT and evaluate the frailty index (FI) as a measure to describe the types of people included in the study. We recruited 315 hospitalised patients aged 65 years; age ranged from 60 to 102 years. Baseline assessment scores ranged as follow: Mini‐Mental Status Examination from 7 to 30, Barthel index from 5 to 100 and FI from 2 to 24. Total deaths were 20 (6%). We demonstrated that it is feasible to recruit frail older people into RCTs. The FI does not show any ‘floor’ or ‘ceiling’ effects. We can measure frailty in an RCT cohort, and we believe that clinical trials should include more frail older people and that the use of an FI can facilitate such trials and generate reliable data to guide future medical practice in a rapidly ageing society.
Biosynthesis of D‐arabinose in mycobacteria – a novel bacterial pathway with implications for antimycobacterial therapy
Authors: Wolucka Beata A.
Published: April 2008

Decaprenyl‐phospho‐arabinose (β‐d‐arabinofuranosyl‐1‐O‐monophosphodecaprenol), the only known donor of d‐arabinose in bacteria, and its precursor, decaprenyl‐phospho‐ribose (β‐d‐ribofuranosyl‐1‐O‐monophosphodecaprenol), were first described in 1992. En route to d‐arabinofuranose, the decaprenyl‐phospho‐ribose 2′‐epimerase converts decaprenyl‐phospho‐ribose to decaprenyl‐phospho‐arabinose, which is a substrate for arabinosyltransferases in the synthesis of the cell‐wall arabinogalactan and lipoarabinomannan polysaccharides of mycobacteria. The first step of the proposed decaprenyl‐phospho‐arabinose biosynthesis pathway in Mycobacterium tuberculosis and related actinobacteria is the formation of d‐ribose 5‐phosphate from sedoheptulose 7‐phosphate, catalysed by the Rv1449 transketolase, and/or the isomerization of d‐ribulose 5‐phosphate, catalysed by the Rv2465 d‐ribose 5‐phosphate isomerase. d‐Ribose 5‐phosphate is a substrate for the Rv1017 phosphoribosyl pyrophosphate synthetase which forms 5‐phosphoribosyl 1‐pyrophosphate (PRPP). The activated 5‐phosphoribofuranosyl residue of PRPP is transferred by the Rv3806 5‐phosphoribosyltransferase to decaprenyl phosphate, thus forming 5′‐phosphoribosyl‐monophospho‐decaprenol. The dephosphorylation of 5′‐phosphoribosyl‐monophospho‐decaprenol to decaprenyl‐phospho‐ribose by the putative Rv3807 phospholipid phosphatase is the committed step of the pathway. A subsequent 2′‐epimerization of decaprenyl‐phospho‐ribose by the heteromeric Rv3790/Rv3791 2′‐epimerase leads to the formation of the decaprenyl‐phospho‐arabinose precursor for the synthesis of the cell‐wall arabinans in Actinomycetales. The mycobacterial 2′‐epimerase Rv3790 subunit is similar to the fungal d‐arabinono‐1,4‐lactone oxidase, the last enzyme in the biosynthesis of d‐erythroascorbic acid, thus pointing to an evolutionary link between the d‐arabinofuranose‐ and l‐ascorbic acid‐related pathways. Decaprenyl‐phospho‐arabinose has been a lead compound for the chemical synthesis of substrates for mycobacterial arabinosyltransferases and of new inhibitors and potential antituberculosis drugs. The peculiar (ω,mono‐E,octa‐Z) configuration of decaprenol has yielded insights into lipid biosynthesis, and has led to the identification of the novel Z‐polyprenyl diphosphate synthases of mycobacteria. Mass spectrometric methods were developed for the analysis of anomeric linkages and of dolichol phosphate‐related lipids. In the field of immunology, the renaissance in mycobacterial polyisoprenoid research has led to the identification of mimetic mannosyl‐β‐1‐phosphomycoketides of pathogenic mycobacteria as potent lipid antigens presented by CD1c proteins to human T cells.
Molecular determinants of ligand specificity in family 11 carbohydrate binding modules – an NMR, X‐ray crystallography and computational chemistry approach
Authors: Viegas Aldino , Brás Natércia F. , Cerqueira Nuno M. F. S. A. , Fernandes Pedro Alexandrino , Prates José A. M. , Fontes Carlos M. G. A. , Bruix Marta , Romão Maria João , Carvalho Ana Luísa , Ramos Maria João , Macedo Anjos L. , Cabrita Eurico J.
Published: April 2008

The direct conversion of plant cell wall polysaccharides into soluble sugars is one of the most important reactions on earth, and is performed by certain microorganisms such asClostridium thermocellum(Ct). These organisms produce extracellular multi‐subunit complexes (i.e. cellulosomes) comprising a consortium of enzymes, which contain noncatalytic carbohydrate‐binding modules (CBM) that increase the activity of the catalytic module. In the present study, we describe a combined approach by X‐ray crystallography, NMR and computational chemistry that aimed to gain further insight into the binding mode of different carbohydrates (cellobiose, cellotetraose and cellohexaose) to the binding pocket of the family 11 CBM. The crystal structure ofC. thermocellumCBM11 has been resolved to 1.98 Å in the apo form. Since the structure with a bound substrate could not be obtained, computational studies with cellobiose, cellotetraose and cellohexaose were carried out to determine the molecular recognition of glucose polymers byCtCBM11. These studies revealed a specificity area at theCtCBM11 binding cleft, which is lined with several aspartate residues. In addition, a cluster of aromatic residues was found to be important for guiding and packing of the polysaccharide. The binding cleft ofCtCBM11 interacts more strongly with the central glucose units of cellotetraose and cellohexaose, mainly through interactions with the sugar units at positions 2 and 6. This model of binding is supported by saturation transfer difference NMR experiments and linebroadening NMR studies.
The role in the substrate specificity and catalysis of residues forming the substrate aglycone‐binding site of a β‐glycosidase
Authors: Mendonça Lúcio M. F. , Marana Sandro R.
Published: April 2008

The relative contributions to the specificity and catalysis of aglycone, of residues E190, E194, K201 and M453 that form the aglycone‐binding site of a β‐glycosidase from Spodoptera frugiperda (EC 3.2.1.21), were investigated through site‐directed mutagenesis and enzyme kinetic experiments. The results showed that E190 favors the binding of the initial portion of alkyl‐type aglycones (up to the sixth methylene group) and also the first glucose unit of oligosaccharidic aglycones, whereas a balance between interactions with E194 and K201 determines the preference for glucose units versus alkyl moieties. E194 favors the binding of alkyl moieties, whereas K201 is more relevant for the binding of glucose units, in spite of its favorable interaction with alkyl moieties. The three residues E190, E194 and K201 reduce the affinity for phenyl moieties. In addition, M453 favors the binding of the second glucose unit of oligosaccharidic aglycones and also of the initial portion of alkyl‐type aglycones. None of the residues investigated interacted with the terminal portion of alkyl‐type aglycones. It was also demonstrated that E190, E194, K201 and M453 similarly contribute to stabilize ES‡. Their interactions with aglycone are individually weaker than those formed by residues interacting with glycone, but their joint catalytic effects are similar. Finally, these interactions with aglycone do not influence glycone binding.
An alternative transcript from the death‐associated protein kinase 1 locus encoding a small protein selectively mediates membrane blebbing
Authors: Lin Yao , Stevens Craig , Hrstka Roman , Harrison Ben , Fourtouna Argyro , Pathuri Suresh , Vojtesek Borek , Hupp Ted
Published: April 2008

Death‐associated protein kinase 1 (DAPK‐1) is a multidomain protein kinase with diverse roles in autophagic, apoptotic and survival pathways. Bioinformatic screens were used to identify a small internal mRNA from the DAPK‐1 locus (named s‐DAPK‐1). This encodes a 295 amino acid polypeptide encompassing part of the ankyrin‐repeat domain, the P‐loop motifs, part of the cytoskeletal binding domain of DAPK‐1, and a unique C‐terminal ‘tail’ extension not present in DAPK‐1. Expression of s‐DAPK‐1 mRNA was detected in a panel of normal human tissues as well as primary colorectal cancers, indicating that its expression occurs in vivo. s‐DAPK‐1 gene transfection into cells produces two protein products: one with a denatured mass of 44 kDa, and a smaller product of 40 kDa. Double alanine mutation of the C‐terminal tail extension of s‐DAPK‐1 (Gly296/Arg297) prevented production of the 40 kDa fragment, suggesting that the smaller product is generated by in vivo proteolytic processing. The s‐DAPK‐1 gene cannot substitute for full‐length DAPK‐1 in an mitogen‐activated protein kinase kinase/extracellular signal‐regulated kinase‐dependent apoptotic transfection assay. However, the transfection of s‐DAPK‐1 was able to mimic full‐length DAPK‐1 in the induction of membrane blebbing. The 44 kDa protease‐resistant mutant s‐DAPK‐1G296A/R297A had very low activity in membrane blebbing, whereas the 40 kDa s‐DAPK‐1Δtail protein exhibited the highest levels of membrane blebbing. Deletion of the tail extension of s‐DAPK‐1 increased its half‐life, shifted the equilibrium of the protein from cytoskeletal to soluble cytosolic pools, and altered green fluorescent protein‐tagged s‐DAPK‐1 protein localization as observed by confocal microscopy. These data highlight the existence of an alternative product of the DAPK‐1 locus, and suggest that proteolytic removal of the C‐terminal tail of s‐DAPK‐1 is required to stimulate maximally its membrane‐blebbing function.
Insights into substrate and product traffic in the Drosophila melanogaster acetylcholinesterase active site gorge by enlarging a back channel
Authors: Nachon Florian , Stojan Jure , Fournier Didier
Published: April 2008

To test a product exit differing from the substrate entrance in the active site of acetylcholinesterase (EC 3.1.1.7), we enlarged a channel located at the bottom of the active site gorge in the Drosophila enzyme. Mutation of Trp83 to Ala or Glu widens the channel from 5 Å to 9 Å. The kinetics of substrate hydrolysis and the effect of ligands that close the main entrance suggest that the mutations facilitate both product exit and substrate entrance. Thus, in the wild‐type, the channel is so narrow that the ‘back door’ is used by at most 5% of the traffic, with the majority of traffic passing through the main entrance. In mutants Trp83Ala and Trp83Glu, ligands that close the main entrance do not inhibit substrate hydrolysis because the traffic can pass via an alternative route, presumably the enlarged back channel.
Midodrine Improves Orgasm in Spinal Cord-Injured Men: The Effects of Autonomic Stimulation
Authors: Soler Jean Marc , Previnaire Jean Gabriel , Plante Pierre , Denys Pierre , Chartier-Kastler Emmanuel
Published: April 2008

Introduction

Orgasm is less frequent in men with spinal cord injury (SCI) than in able-bodied subjects, and is poorly understood.

Aim

To assess the effect of autonomic stimulation on orgasm in SCI men using midodrine, an alpha1-adrenergic agonist agent.

Materials and Methods

Penile vibratory stimulation (PVS) was performed in 158 SCI men on midodrine as part of a treatment for anejaculation, after they failed a baseline PVS. A maximum of four trials were performed, weekly, with increasing doses of midodrine.

Main Outcome Measure

The presence and type of ejaculation, orgasm experiences, and cardiovascular data were collected.

Results

Ejaculation either antegrade or retrograde was obtained in 102 SCI men (65%). Orgasm without ejaculation was reported by 14 patients (9%) on baseline PVS. Ninety-three patients (59%) experienced orgasm during PVS on midodrine. Orgasm was significantly related to the presence of ejaculation in 86 patients (84%), and more strikingly to antegrade ejaculation (pure or mixed with retrograde), i.e., in 98% of 70 patients. Orgasm was significantly more frequent in patients with upper motor neuron and incomplete lesions who present somatic responses during PVS. There was no effect of the presence of psychogenic erection. There was a significant increase in both systolic and diastolic blood pressure. Sixteen patients, mainly tetraplegics, developed intense autonomic dysreflexia (AD) that required an oral nicardipine chlorhydrate.

Conclusion

Orgasm is the brain's cognitive interpretation of genital sensations and somatic responses, AD, and ejaculation. Intact sacral and T10-L2 cord segments are mandatory, allowing coordination between internal and external sphincters. Autonomic stimulation with midodrine enhances orgasm rate, mainly by creating antegrade ejaculation.
Profibrotic Role of Myostatin in Peyronie's Disease
Authors: Cantini Liliana P. , Ferrini Monica G. , Vernet Dolores , Magee Thomas R. , Qian Ansha , Gelfand Robert A. , Rajfer Jacob , Gonzalez-Cadavid Nestor F.
Published: April 2008

Introduction

The primary histologic finding in many urologic disorders, including Peyronie's disease (PD), is fibrosis, mainly mediated by the transforming growth factor β1 (TGFβ1).

Aim

To determine whether another member of the TGFβ family, myostatin, (i) is expressed in the human PD plaque and normal tunica albuginea (TA), their cell cultures, and the TGFβ1-induced PD lesion in the rat model; (ii) is responsible for myofibroblast generation, collagen deposition, and plaque formation; and (iii) mediates the profibrotic effects of TGFβ1 in PD.

Methods

Human TA and PD tissue sections, and cell cultures from both tissues incubated with myostatin and TGFβ1 were subjected to immunocytochemistry for myostatin and α-smooth muscle actin (ASMA). The cells were assayed by western blot, Real time-Polymerase chain reaction (RT-PCR), and ribonuclease protection. Myostatin cDNA and shRNA were injected, with or without TGFβ1, in the rat penile TA, and plaque size was estimated by Masson.

Main Outcome Measures

Myostatin expression in the human TA, the PD plaque, and their cell cultures, and myostatin effects on the PD-like plaque in the rat.

Results

A threefold overexpression of myostatin was found in the PD plaque as compared with the TA. In PD cells, myostatin expression was mainly in the myofibroblasts, and in the TA cells, it increased upon passage paralleling myofibroblast differentiation and was up-regulated by TGFβ1. Myostatin or its cDNA construct increased the myofibroblast number and collagen in TA cells. Myostatin was detected in the TGFβ1-induced PD-like plaque of the rat partly in the myofibroblasts, and in the TA. Myostatin cDNA injected in the TA induced a plaque and intensified the TGFβ1 lesion, which was not reduced by myostatin shRNA.

Conclusions

Myostatin is overexpressed in the PD plaque, partly because of myofibroblast generation. Although myostatin induces a plaque in the rat TA, it does not appear to mediate the one triggered by TGFβ1, thus suggesting that both proteins act concurrently and that therapy should target their common downstream effectors.