bluuebunny/crossref_metadata_2025 huggingface dataset:
New insights into the regulation of iron homeostasis
Authors: Deicher R. , Hörl W. H.
Published: April 2006

Hepcidin evolves as a potent hepatocyte‐derived regulator of the body's iron distribution piloting the flow of iron via, and directly binding, to the cellular iron exporter ferroportin. The hepcidin‐ferroportin axis dominates the iron egress from all cellular compartments that are critical to iron homeostasis, namely placental syncytiotrophoblasts, duodenal enterocytes, hepatocytes and macrophages of the reticuloendothelial system. The gene that encodes hepcidin expression (HAMP) is subject to regulation by proinflammatory cytokines, such as IL‐6 and IL‐1; excessive hepcidin production explains the relative deficiency of iron during inflammatory states, eventually resulting in the anaemia of inflammation. The haemochromatosis genes HFE (the human leukocyte antigen‐related gene), TfR2 (the transferrin receptor‐2 gene) and HJV (the haemojuvelin gene) potentially facilitate the transcription of HAMP. Disruption of each of the four genes leads to a diminished hepatic release of hepcidin consistent with both a dominant role of hepcidin in hereditary haemochromatosis and an upstream regulatory role of HFE, TfR2 and HJV on HAMP expression. The engineered generation of hepcidin agonists, mimetics or antagonists could largely broaden current therapeutic strategies to redirect the flow of iron.
Stem cells in the lung parenchyma and prospects for lung injury therapy
Authors: Yen C. C. , Yang S. H. , Lin C. Y. , Chen C. M.
Published: April 2006

Until recently, it was thought that only embryonic stem cells were pluripotent and that adult stem cells were restricted in their differentiative and regenerative potential to become the tissues in which they reside. However, the discovery that adult stem cells in one tissue can contribute to the formation of other tissues, especially after injury or cell damage, implies that stem cells have developmental plasticity. For example, haematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) from bone marrow can be used to regenerate diverse tissues at distant sites, including the lung. This article reviews the character of stem cells in the lung parenchyma and focuses on the potential uses of adult stem cells in research of lung injury and lung disease therapies.
Effect of enzymatic and NaOCl treatments on acrylic roughness and on biofilm accumulation
Authors: LIMA E. M. C. X. , MOURA J. S. , DEL BEL CURY A. A. , GARCIA R. C. M. R. , CURY J. A.
Published: April 2006

summary  As denture cleansers should be able to reduce biofilm accumulation without changing the acrylic resin surface structure, this study evaluated the effect of denture cleansers on surface roughness of acrylic resin and on biofilm accumulation. It was conducted a crossover study of three phases of 4 days each and 13 volunteers wore palatal appliances containing four specimens of acrylic resin of known surface roughness which were extra‐orally submitted once a day to three groups of separated treatments: (i) negative control, (ii) enzymatic commercial solution (Ortoform) or (iii) 0·5% sodium hypochlorite (NaOCl).The appliances were immersed eight times a day in a 20% sucrose solution to enhance biofilm formation. On morning of the fifth day of each phase, the amount of biofilm formed on the specimens was estimated by the amount of protein extracted with alkali and the surface roughness of the specimens was again measured. New palatal appliances with new specimens were worn by the volunteers in the following phases, but the treatments were changed. The roughness of the resin increased after the treatments (P < 0·05) but the difference among the cleansers was not statistically significant (P = 0·85). The lowest amount of biofilm formed on acrylic resin specimens was found for the treatment with NaOCl (P < 0·05) but the enzymatic product did not differ from the negative control group (P > 0·05). The data suggest that the roughness of acrylic resin was not changed by the cleansers, but the ability to reduce biofilm accumulation depended on the product used.
Fracture resistance of single‐tooth implant‐supported all‐ceramic restorations after exposure to the artificial mouth
Authors: ATT W. , KURUN S. , GERDS T. , STRUB J. R.
Published: April 2006

summary  The purpose of this in vitro study was to evaluate the fracture resistance of single‐tooth implant‐supported all‐ceramic restorations, composed of zirconium dioxide all ceramic restorations on different implant abutments, and to identify the weakest component of the restorative system. Forty‐eight standardized maxillary central incisor zirconia crowns (Procera) were fabricated for two test groups and one control group (group Al: alumina abutments; group Zr: zirconia abutments; control group Ti: titanium abutments). All abutments were placed on the implants (Replace) using titanium screws. The crowns were adhesively luted using a resin luting agent (Panavia 21) and artificially aged through dynamic loading and thermal cycling. Afterwards, all specimens were tested for fracture resistance using compressive load on the palatal surfaces of the crowns. Pair‐wise Wilcoxon rank tests were performed to test for differences in fracture resistance values with a global significance level of 0·05. All test specimens survived aging in the artificial mouth. No screw loosening was recorded. The median fracture resistance was 1251, 241 and 457 N for groups Ti, Al and Zr respectively. Statistically significant differences were found for the comparisons of group Ti with groups Al and Zr (P < 0·00001), and for the comparison of group Al with Zr (P < 0·00001). Results of this study showed that all tested implant‐supported restorations have the potential to withstand physiological occlusal forces applied in the anterior region. Because of the low fracture resistance values of group Al, the combination of zirconia crowns and alumina abutments should carefully be considered before clinical application.
Predictors of gastric emptying in Parkinson's disease
Authors: Goetze O. , Nikodem A. B. , Wiezcorek J. , Banasch M. , Przuntek H. , Mueller T. , Schmidt W. E. , Woitalla D.
Published: April 2006

Abstract  Predictors of gastric emptying (GE) in patients with idiopathic Parkinson's disease (PD) of a solid and liquid meal are not well defined. For measurement of GE 80 patients with PD were randomly assigned to receive either a solid meal (250 kcal) containing 13C‐octanoate (n = 40) or a liquid meal (315 kcal) with 13C‐acetate (n = 40). All patient groups were off medication affecting motility and were matched for age, gender, body mass index, disease duration and severity, using Unified Parkinson's Disease Rating Scale (UPDRS). Gastric emptying was compared with a healthy control group (n = 40). Multiple regression analysis was used to determine predictors of gastric emptying. Exactly 88% and 38% of PD patients had delayed GE of solids and liquids respectively. Solid and liquid emptying was similar in women and men. There were no differences in GE in PD patients <65 years of age when compared with patients ≥65 years. Multiple regression analysis showed that motor handicaps such as rigour and action tremor are independent predictors of solid GE (r = 0.68, P < 0.001). The severity of motor impairment, but not any other neurological symptom, as assessed by UPDRS is associated with gastroparesis in PD and solid emptying is more likely to be delayed.
Decreased tongue mobility – an explanation for difficult endotracheal intubation?
Authors: Rosenstock C. , Kristensen M. S.
Published: April 2006

Established parameters predictive of difficulty in airway management were inconclusive in five ear, nose and throat (ENT) patients. All presented with degrees of tongue fixation – restriction of movement. Initially, experienced anaesthetists concluded that conventional endotracheal intubation would present no problems. Later, there were adjustments to this conclusion, with the ultimate being that four of the patients underwent fibre‐optic intubation: one electively, two after repeated failed conventional attempts and one after a failed attempt of retrograde intubation. The last patient underwent elective retrograde intubation. All intubations were performed uneventfully in anaesthetized or sedated patients under spontaneous respiration.

We found that tongue fixation was a direct cause of failed conventional endotracheal intubation, and recommend that a detailed tongue status investigation should be routine during Mallampati evaluation. Any abnormality should be seen as predictive of difficult/impossible conventional direct laryngoscopic intubation.
Improved resuscitation outcome in emergency medical systems with increased usage of sodium bicarbonate during cardiopulmonary resuscitation
Authors: Bar‐Joseph G. , Abramson N. S. , Kelsey S. F. , Mashiach T. , Craig M. T. , Safar P. ,   for the Brain Resuscitation Clinical Trial III (BRCT III) Study Group
Published: April 2006

Background:  The use of sodium bicarbonate (SB) in cardiopulmonary resuscitation (CPR) is controversial. This study analyzes the effects of SB use on CPR outcome in the Brain Resuscitation Clinical Trial III (BRCT III), which was a multicenter randomized trial comparing high‐dose to standard‐dose epinephrine during CPR. Sodium bicarbonate use in BRCT III was optional.

Methods:  The entire BRCT III database was reviewed. Analysis included only patients who arrested out of the hospital and whose time from collapse to initiation of ACLS was no longer than 30 min (total n = 2122 patients). Sodium bicarbonate use by the 16 participating study sites was analyzed. The study sites were divided according to their SB usage profile: ‘low SB user’ sites administered SB in less than 50% of CPRs and their first epinephrine to SB time exceeded 10 min; and ‘high SB user’ sites used SB in over 50% of CPRs and their first epinephrine to SB time was <10 min.

Results:  Sites' SB usage rates ranged between 3.1% and 98.2% of CPRs. Sodium bicarbonate usage rates correlated inversely with the sites' intervals from collapse (r = − 0.579 P = 0.018) from initiation of ACLS (r = − 0.685 P = 0.003) and from first epinephrine (r = − 0.611 P = 0.012) to SB administration.

Mean ROSC rate in the ‘high SB user’ sites was 33.5% (CI = 30.0–37.0) compared to 25.7% (CI = 23.1–28.4) in the ‘low SB user’ sites. In the ‘high SB user’ sites, hospital discharge rate was 5.3% (CI = 3.6–7.0) compared to 3% (CI = 2.0–4.0) in the ‘low SB user’ sites, and 5.3% (CI = 3.6–7.0) had a favorable neurological outcome compared to 2.1% (CI = 1.2–3.0) in the ‘low SB user’ sites. Collapse to ACLS interval was 8.5 min (CI = 8.1–9.0) in the ‘high SB user’ sites compared to 10.2 min (CI = 9.8–10.6) in the ‘low SB user’ sites, and their ACLS to first epinephrine interval was 7.0 min (CI = 6.5–7.5) compared to 9.7 min (CI = 9.3–10.2). Multivariate regression analysis found that belonging to ‘high SB user’ sites independently increased the chances for ROSC (OR 1.36, CI 1.08–1.7) and for achieving a good neurological outcome (OR 2.18, CI 1.23–3.86).

Conclusions:  Earlier and more frequent use of SB was associated with higher early resuscitability rates and with better long‐term outcome. Sodium bicarbonate may be beneficial during CPR, and it should be subjected to a randomized clinical trial.
Variation in the latitudinal reproductive patterns of the genus Didelphis (Didelphimorphia:Didelphidae)
Authors: RADEMAKER V. , CERQUEIRA R.
Published: April 2006

Abstract:  The data published on reproduction of the species of the genus Didelphis (Didelphimorphia, Didelphidae) were compiled and analysed to identify general patterns. The duration of the breeding season for the Didelphis species varied from 12 months near the Equator to 6 months at latitude 25°S and varied inversely with latitude and litter size. The mean litter size varied from 4.2 in Colombia to 9.4 in New York and was positively associated with latitude and negatively with the duration of breeding season. We propose that the higher investment in production at higher latitudes was compensated by increased mortality owing to the seasonal variation in food availability and environmental variables in theses latitudes.
Development of Displaced Speech in Early Mother–Child Conversations
Authors: Adamson Lauren B. , Bakeman Roger
Published: April 2006

This study documents the development of symbolic, spatial, and temporal displacement of toddler's speech. Fifty‐six children and their mothers were observed longitudinally 5 times from 18 to 30 months of age during a staged communication play while they engaged in scenes that encouraged interacting, requesting, and commenting and scenes that explicitly focused on the past and the future. Reliably coded transcripts revealed that toddlers highlighted symbols at a high and stable rate and that over time they became less focused on the here and now and more focused on internal states. The greatest expansion was into the near future. Only in scenes designed to discuss the past and future did conversations turn to the past and expand spatially beyond here.
Contact allergy to idoxuridine
Authors: Thormann J. , Wfldenhoff K. E.
Published: April 2006

A total of 45 of 60 patients with herpes zoster previously treated with topical idoxuridine 5–40% in dimethylsulfaxide were patch tested 2 years later with idoxuridine 0.5% and 5% in petrolatum. Three (7%) showed positive reactions. Idoxuridine is considered a weak sensitizer, but in strong concentrations and in active solvents, which increases absorption, there seems to be a risk of sensitization.
Comparative study of the density of particles in suspensions for patch testing*
Authors: Vanneste D. , Martin P. , Lachafelle J. M.
Published: April 2006

A simple and reliable method to evaluate the density of particles in patch test suspensions is described. The number of particles per unit volume has been found to vary significantly within a wide range of values. These variations have no relation to the concentration or the molecular weight of the substance, as far as particles larger than 10 μ are concerned. Because the presence of particles is one of the factors which can influence percutaneous penetration and since physical manipulations are able to modify the size of these particles, it is suggested that the kinetics of penetration of haptens through the skin should be reevaluated with regard to this special point.
Skin irritants of the sun spurge (Euphorbia helioscopia L)
Authors: Schmidt Richard J. , Evans Fred J.
Published: April 2006

Euphorbia helioscopia is a common herbaceous weed found in the British Isles and parts of Europe. It has been responsible for poisoning of livestock resulting in severe inflammation particularly of mucous membranes and the eyes. Four esters of 12‐deoxyphorbol were isolated from the fresh aerial parts of the plant and their irritant doses 50% (I.D.50) ascertained using female L.A.C.A. mice. 12‐Deoxyphorbol‐13‐phenylacetale‐20‐acetate was found to be the major component of the toxic fraction and occurred in yields of 0.0012 % w/w. This compound was also the most irritant substance isolated and exhibited an I.D.50 of 0.038μg, and is accordingly considered to be responsible for the major part of the toxicity of E. helioscopia. A high molecular weight aliphatic ester, 12‐deoxyphorbol‐13‐dodec‐dienoate‐20‐acetate, was also obtained in low yields. This compound exhibited an T.D‐no of 0.12μg. The final two esters obtained from the toxic fraction of the plant were the low molecular weight homologues, 12‐deoxyphorbol‐13‐[2‐methyl‐cis‐2‐butenoate].‐20‐acetate and 12‐deoxyphorbol‐13‐[2‐methyl‐cis‐2‐butenoate]. These compounds exhibited I.D.50 of 3.09 and 0.72 μg, respectively and were the least irritant of the series of compounds isolated.
Diagnosing drug‐seeking behaviour in an adult emergency department
Authors: McNabb Charley , Foot Carole , Ting Joseph , Breeze Katina , Stickley Mark
Published: April 2006

Objective:  The objective of the present study were to determine factors used by ED doctors to diagnose drug seeking and their attitude towards management of this patient group.

Methods:  Prospective, descriptive study, of doctors working in a tertiary hospital ED. Doctors voluntarily identified patients they suspected were drug seeking and completed a written survey.

Results:  Thirty‐seven surveys were completed for presentations involving 31 patients. A patient's specific request for narcotics, previous documented episodes of suspected drug seeking, an unwillingness to try simple analgesia and demanding or aggressive behaviour were the most frequently used factors for diagnosing drug seeking. These factors are similar to, but not the same, as the criteria in the literature. Doctors commonly found consultations involving drug seeking to be unsatisfying.

Conclusions:  Factors, such as those used by doctors in the present study, should not be used as diagnostic markers. Further study is warranted in order to improve the effectiveness of consultations involving drug seeking.
A simple Bayesian network to interpret the accuracy of armyworm outbreak forecasts
Authors: Holt J. , Mushobozi W. , Day R.K. , Knight J.D. , Kimani M. , Njuki J. , Musebe R.
Published: April 2006

Forecasting of outbreaks of armyworm (larvae of the moth Spodoptera exempta) employs information from rain gauges and moth traps. Rainfall is an independent variable, but moth catch is affected by rainfall, and outbreak risk is affected by both moth catch and rainfall. A simple Bayesian network was used to describe these relationships and so derive conditional probabilities. The data were from a new initiative, community‐based forecasting of armyworm in Tanzania, in which outbreak risk for a village is determined locally from a single moth trap and rain gauge located within the village. It was found that, following a positive forecast, an armyworm outbreak was approximately twice as likely to occur as would be expected by chance. If the forecast was negative because of insufficient moths, outbreaks were half as likely as would be expected by chance. If the forecast was negative because of insufficient rain, however, the outbreak probability remained similar to chance: an aspect of the forecast that requires improvement. Overall, a high forecasting accuracy can be achieved by village communities using simple rules to predict armyworm outbreaks.
DNA‐binding by Functionalized Gold Nanoparticles: Mechanism and Structural Requirements
Authors: Goodman Catherine M. , Chari Nandini S. , Han Gang , Hong Rui , Ghosh Partha , Rotello Vincent M.
Published: April 2006

A family of nanoparticles featuring surfaces of varying hydrophobicity was synthesized. The efficiency of DNA‐binding was determined, demonstrating in a fivefold modulation in binding a 37‐mer DNA strand. Nanoparticle‐binding causes a reversible conformational change in the DNA structure, as demonstrated by circular dichroism and fluorescence experiments. Furthermore, the affinity of the nanoparticle for the DNA can be regulated by external agents, though stability of the complex is observed at relatively high ionic strengths.
The Discovery of Tropane‐derived CCR5 Receptor Antagonists
Authors: Armour Duncan R. , De Groot Marcel J. , Price David A. , Stammen Blanda L. C. , Wood Anthony , Perros Manos , Burt Catherine
Published: April 2006

The development of compound 1, a piperidine‐based CCR5 receptor antagonist with Type I CYP2D6 inhibition, into the tropane‐derived analogue 5, is described. This compound, which is devoid of CYP2D6 liabilities, is a highly potent ligand for the CCR5 receptor and has broad‐spectrum activity against a range of clinically relevant HIV isolates. The identification of human ether a‐go‐go‐related gene channel inhibition within this series is described and the potential for QTc interval prolongation discussed. Furthermore, structure activity relationship (SAR) around the piperidine moiety is also described.
A QSAR Model of hERG Binding Using a Large, Diverse, and Internally Consistent Training Set
Authors: Seierstad Mark , Agrafiotis Dimitris K.
Published: April 2006

Over the past decade, the pharmaceutical industry has begun to address an addition to ADME/Tox profiling – the ability of a compound to bind to and inhibit the human ether‐a‐go‐go‐related gene (hERG)‐encoded cardiac potassium channel. With the compilation of a large and diverse set of compounds measured in a single, consistent hERG channel inhibition assay, we recognized a unique opportunity to attempt to construct predictive QSAR models. Early efforts with classification models built from this training set were very encouraging. Here, we report a systematic evaluation of regression models based on neural network ensembles in conjunction with a variety of structure representations and feature selection algorithms. The combination of these modeling techniques (neural networks to capture non‐linear relationships in the data, feature selection to prevent over‐fitting, and aggregation to minimize model instability) was found to produce models with very good internal cross‐validation statistics and good predictivity on external data.
The Mycobacterial 38-Kilodalton Glycolipoprotein Antigen Activates the Mitogen-Activated Protein Kinase Pathway and Release of Proinflammatory Cytokines through Toll-Like Receptors 2 and 4 in Human Monocytes
Authors: Jung Saet-Byel , Yang Chul-Su , Lee Ji-Sook , Shin A-Rum , Jung Sung-Soo , Son Ji Woong , Harding Clifford V. , Kim Hwa-Jung , Park Jeong-Kyu , Paik Tae-Hyun , Song Chang-Hwa , Jo Eun-Kyeong
Published: April 2006

Although the 38-kDa glycolipoprotein ofMycobacterium tuberculosisH37Rv is known to evoke prominent cellular and humoral immune responses in human tuberculosis (TB), little information is known about intracellular regulatory mechanisms involved in 38-kDa antigen (Ag)-induced host responses. In this study, we found that purified 38-kDa glycolipoprotein activates mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase 1/2 [ERK1/2] and p38) and induces tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in human monocytes. When the 38-kDa Ag was applied to monocytes from TB patients and healthy controls, the activation of ERK1/2 and p38 MAPK and the subsequent cytokine secretion were greater in the monocytes from the active pulmonary TB patients than in monocytes from the healthy controls. Additionally, neutralizing antibodies for Toll-like receptor 2 (TLR2) or TLR4 significantly reduced the ERK1/2 and p38 activation induced by the 38-kDa protein when the antibodies were applied to HEK293 cells overexpressing TLR2 or TLR4 as well as human primary monocytes. Furthermore, the inhibition of TLR2 significantly, and that of TLR4 partially, decreased the 38-kDa Ag-induced secretion of TNF-α and IL-6 in human monocytes. The intact protein moieties of the 38-kDa protein were responsible for biologic activities by this Ag. These data collectively demonstrate that the 38-kDa glycolipoprotein, acting through both TLR2 and TLR4, induces the activation of the ERK1/2 and p38 MAPK pathways, which in turn play an essential role in TNF-α and IL-6 expression during mycobacterial infection.
Protection by Meningococcal Outer Membrane Protein PorA-Specific Antibodies and a Serogroup B Capsular Polysaccharide-Specific Antibody in Complement-Sufficient and C6-Deficient Infant Rats
Authors: Toropainen Maija , Saarinen Leena , Vidarsson Gestur , Käyhty Helena
Published: April 2006

The relative contributions of antibody-induced complement-mediated bacterial lysis and antibody/complement-mediated phagocytosis to host immunity against meningococcal infections are currently unclear. Further, the in vivo effector functions of antibodies may vary depending on their specificity and Fc heavy-chain isotype. In this study, a mouse immunoglobulin G2a (mIgG2a) monoclonal antibody (MN12H2) to meningococcal outer membrane protein PorA (P1.16), its human IgG subclass derivatives (hIgG1 to hIgG4), and an mIgG2a monoclonal antibody (Nmb735) to serogroup B capsular polysaccharide (B-PS) were evaluated for passive protection against meningococcal serogroup B strain 44/76-SL (B:15:P1.7,16) in an infant rat infection model. Complement component C6-deficient (PVG/c
−
) rats were used to assess the importance of complement-mediated bacterial lysis for protection. The PorA-specific parental mIgG2a and the hIgG1 to hIgG3 derivatives all induced efficient bactericidal activity in vitro in the presence of human or infant rat complement and augmented bacterial clearance in complement-sufficient HsdBrlHan:WIST rats, while the hIgG4 was unable to do so. In C6-deficient PVG/c
−
rats, lacking complement-mediated bacterial lysis, the augmentation of bacterial clearance by PorA-specific mIgG2a and hIgG1 antibodies was impaired compared to that in the syngeneic complement-sufficient PVG/c
+
rat strain. This was in contrast to the case for B-PS-specific mIgG2a, which conferred similar protective activity in both rat strains. These data suggest that while anti-B-PS antibody can provide protection in the infant rats without membrane attack complex formation, the protection afforded by anti-PorA antibody is more dependent on the activation of the whole complement pathway and subsequent bacterial lysis.
Role of the
Porphyromonas gingivalis
InlJ Protein in Homotypic and Heterotypic Biofilm Development
Authors: Capestany Cindy A. , Kuboniwa Masae , Jung Il-Young , Park Yoonsuk , Tribble Gena D. , Lamont Richard J.
Published: April 2006

The oral pathogen
Porphyromonas gingivalis
expresses a homolog of the internalin family protein InlJ. Inactivation of
inlJ
reduced monospecies biofilm formation by
P. gingivalis
. In contrast, heterotypic
P. gingivalis
-
Streptococcus gordonii
biofilm formation was enhanced in the InlJ-deficient mutant. The results indicate a nuanced role for InlJ in regulating biofilm accumulations of
P. gingivalis
.
Plasmodium falciparum
Parasites Expressing Pregnancy-Specific Variant Surface Antigens Adhere Strongly to the Choriocarcinoma Cell Line BeWo
Authors: Haase Rikke N. , Megnekou Rosette , Lundquist Maja , Ofori Michael F. , Hviid Lars , Staalsoe Trine
Published: April 2006

Placenta-sequestering
Plasmodium falciparum
parasites causing pregnancy-associated malaria express pregnancy-specific variant surface antigens (VSA
PAM
). We report here that VSA
PAM
-expressing patient isolates adhere strongly to the choriocarcinoma cell line BeWo and that the BeWo line can be used to efficiently select for VSA
PAM
expression in vitro.
Thin Aggregative Fimbriae and Cellulose Enhance Long-Term Survival and Persistence ofSalmonella
Authors: White A. P. , Gibson D. L. , Kim W. , Kay W. W. , Surette M. G.
Published: April 2006

Salmonellaspp. are environmentally persistent pathogens that have served as one of the important models for understanding how bacteria adapt to stressful conditions. However, it remains poorly understood how they survive extreme conditions encountered outside their hosts. Here we show that the rdar morphotype, a multicellular phenotype characterized by fimbria- and cellulose-mediated colony pattern formation, enhances the resistance ofSalmonellato desiccation. When colonies were stored on plastic for several months in the absence of exogenous nutrients, survival of wild-type cells was increased compared to mutants deficient in fimbriae and/or cellulose production. Differences between strains were further highlighted upon exposure to sodium hypochlorite, as cellulose-deficient strains were 1,000-fold more susceptible. Measurements of gene expression using luciferase reporters indicated that production of thin aggregative fimbriae (Tafi) may initiate formation of colony surface patterns characteristic of the rdar morphotype. We hypothesize that Tafi play a role in the organization of different components of the extracellular matrix. Conservation of the rdar morphotype among pathogenicS. entericaisolates and the survival advantages that it provides collectively suggest that this phenotype could play a role in the transmission ofSalmonellabetween hosts.
Mutational Analysis of Intervening Sequences Connecting the Binding Sites for Integration Host Factor, PepA, PurR, and RNA Polymerase in the Control Region of the
Escherichia coli carAB
Operon, Encoding Carbamoylphosphate Synthase
Authors: Devroede Neel , Huysveld Nadine , Charlier Daniel
Published: April 2006

Transcription of the
carAB
operon encoding the unique carbamoylphosphate synthase of
Escherichia coli
reflects the dual function of carbamoylphosphate in the biosynthesis of arginine and pyrimidine nucleotides. The tandem pair of promoters is regulated by various mechanisms depending on the needs of both pathways and the maintenance of a pyrimidine/purine nucleotide balance. Here we focus on the linker regions that impose the distribution of target sites for DNA-binding proteins involved in pyrimidine- and purine-specific repression of the upstream promoter P1. We introduced deletions and insertions, and combinations thereof, in four linkers connecting the binding sites for integration host factor (IHF), PepA, PurR, and RNA polymerase and studied the importance of phasing and spacing of the targets and the importance of the nucleotide sequence of the linkers. The two PepA binding sites must be properly aligned and separated with respect to each other and to the promoter for both pyrimidine- and purine-mediated repression. Similarly, the phasing and spacing of the IHF and PEPA2 sites are strictly constrained but only for pyrimidine-specific repression. The IHF target is even dispensable for purine-mediated regulation. Thus, a correct localization of PepA within the higher-order nucleoprotein complex is a prerequisite for the establishment of pyrimidine-mediated repression and for the coupling between purine- and pyrimidine-dependent regulation. Our data also suggest the existence of a novel
cis
-acting pyrimidine-specific regulatory target located around position −60. Finally, the analysis of a P1 derivative devoid of its control region has led to a reappraisal of the effect of excess adenine on P1 and has revealed that P1 has no need for a UP element.
Mutation ofwaaC, Encoding Heptosyltransferase I inCampylobacter jejuni81-176, Affects the Structure of both Lipooligosaccharide and Capsular Carbohydrate
Authors: Kanipes Margaret I. , Papp-Szabo Erzsebet , Guerry Patricia , Monteiro Mario A.
Published: April 2006

Campylobacter jejuni81-176 lipooligosaccharide (LOS) is composed of two covalently linked domains: lipid A, a hydrophobic anchor, and a nonrepeating core oligosaccharide, consisting of an inner and outer core region. We report the isolation and characterization of the deepest roughC. jejuni81-176 mutant by insertional mutagenesis into thewaaCgene, encoding heptosyltransferase I that catalyzes the transfer of the firstl-glycero-d-manno-heptose residue to 3-deoxy-d-manno-octulosonic residue (Kdo)-lipid A. Tricine gel electrophoresis, followed by silver staining, showed that site-specific mutation in thewaaCgene resulted in the expression of a severely truncated LOS compared to wild-type strain 81-176. Gas-liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy showed that thewaaCLOS species lacked all sugars distal to Kdo-lipid A. Parallel structural studies of the capsular polysaccharides of the wild-type strain 81-176 andwaaCmutant revealed loss of the 3-O-methyl group in thewaaCmutant. Complementation of theC. jejunimutant by insertion of the wild-typeC. jejuni waaCgene into a chromosomal locus resulted in LOS and capsular structures identical to those expressed in the parent strain. We also report here the presence ofO-methyl phosphoramidate in wild-type strain 81-176 capsular polysaccharide.
Mutational Analysis of the Chemoreceptor-Coupling Domain of the
Escherichia coli
Chemotaxis Signaling Kinase CheA
Authors: Zhao Jinshi , Parkinson John S.
Published: April 2006

During chemotactic signaling by
Escherichia coli
, autophosphorylation of the histidine kinase CheA is coupled to chemoreceptor control by the CheW protein, which interacts with the C-terminal P5 domain of CheA. To identify P5 determinants important for CheW binding and receptor coupling control, we isolated and characterized a series of P5 missense mutants. The mutants fell into four phenotypic groups on the basis of in vivo behavioral and protein stability tests and in vitro assays with purified mutant proteins. Group 1 mutants exhibited autophosphorylation and receptor-coupling defects, and their CheA proteins were subject to relatively rapid degradation in vivo. Group 1 mutations were located at hydrophobic residues in P5 subdomain 2 and most likely caused folding defects. Group 2 mutants made stable CheA proteins with normal autophosphorylation ability but with defects in CheW binding and in receptor-mediated activation of CheA autophosphorylation. Their mutations affected residues in P5 subdomain 1 near the interface with the CheA dimerization (P3) and ATP-binding (P4) domains. Mutant proteins of group 3 were normal in all tests yet could not support chemotaxis, suggesting that P5 has one or more important but still unknown signaling functions. Group 4 mutant proteins were specifically defective in receptor-mediated deactivation control. The group 4 mutations were located in P5 subdomain 1 at the P3/P3′ interface. We conclude that P5 subdomain 1 is important for CheW binding and for receptor coupling control and that these processes may require substantial motions of the P5 domain relative to the neighboring P3 and P4 domains of CheA.
Structure of the Functional Form of the Mosquito Larvicidal Cry4Aa Toxin from
Bacillus thuringiensis
at a 2.8-Angstrom Resolution
Authors: Boonserm Panadda , Mo Min , Angsuthanasombat Chanan , Lescar Julien
Published: April 2006

The Cry4Aa δ-endotoxin from
Bacillus thuringiensis
is toxic to larvae of
Culex
,
Anopheles
, and
Aedes
mosquitoes, which are vectors of important human tropical diseases. With the objective of designing modified toxins with improved potency that could be used as biopesticides, we determined the structure of this toxin in its functional form at a resolution of 2.8 Å. Like other Cry δ-endotoxins, the activated Cry4Aa toxin consists of three globular domains, a seven-α-helix bundle responsible for pore formation (domain I) and the following two other domains having structural similarities with carbohydrate binding proteins: a β-prism (domain II) and a plant lectin-like β-sandwich (domain III). We also studied the effect on toxicity of amino acid substitutions and deletions in three loops located at the surface of the putative receptor binding domain II of Cry4Aa. Our results indicate that one loop is an important determinant of toxicity, presumably through attachment of Cry4Aa to the surface of mosquito cells. The availability of the Cry4Aa structure should guide further investigations aimed at the molecular basis of the target specificity and membrane insertion of Cry endotoxins.
Functional Characterization of
Escherichia coli
GlpG and Additional Rhomboid Proteins Using an
aarA
Mutant of
Providencia stuartii
Authors: Clemmer Katy M. , Sturgill Gwen M. , Veenstra Alexander , Rather Philip N.
Published: April 2006

The
Providencia stuartii
AarA protein is a member of the rhomboid family of intramembrane serine proteases and required for the production of an extracellular signaling molecule that regulates cellular functions including peptidoglycan acetylation, methionine transport, and cysteine biosynthesis. Additional
aarA-
dependent phenotypes include (i) loss of an extracellular yellow pigment, (ii) inability to grow on MacConkey agar, and (iii) abnormal cell division. Since these phenotypes are easily assayed, the
P. stuartii aarA
mutant serves as a useful host system to investigate rhomboid function. The
Escherichia coli
GlpG protein was shown to be functionally similar to AarA and rescued the above
aarA
-dependent phenotypes in
P. stuartii
. GlpG proteins containing single alanine substitutions at the highly conserved catalytic triad of asparagine (N154A), serine (S201A), or histidine (H254A) residues were nonfunctional. The
P. stuartii aarA
mutant was also used as a biosensor to demonstrate that proteins from a variety of diverse sources exhibited rhomboid activity. In an effort to further investigate the role of a rhomboid protein in cell physiology, a
glpG
mutant of
E. coli
was constructed. In phenotype microarray experiments, the
glpG
mutant exhibited a slight increase in resistance to the β-lactam antibiotic cefotaxime.
Systemic administration of IGF-I enhances oxidative status and reduces contraction-induced injury in skeletal muscles of mdx dystrophic mice
Authors: Schertzer Jonathan D. , Ryall James G. , Lynch Gordon S.
Published: April 2006

The absence of dystrophin and resultant disruption of the dystrophin glycoprotein complex renders skeletal muscles of dystrophic patients and dystrophic mdx mice susceptible to contraction-induced injury. Strategies to reduce contraction-induced injury are of critical importance, because this mode of damage contributes to the etiology of myofiber breakdown in the dystrophic pathology. Transgenic overexpression of insulin-like growth factor-I (IGF-I) causes myofiber hypertrophy, increases force production, and can improve the dystrophic pathology in mdx mice. In contrast, the predominant effect of continuous exogenous administration of IGF-I to mdx mice at a low dose (1.0–1.5 mg·kg−1·day−1) is a shift in muscle phenotype from fast glycolytic toward a more oxidative, fatigue-resistant, slow muscle without alterations in myofiber cross-sectional area, muscle mass, or maximum force-producing capacity. We found that exogenous administration of IGF-I to mdx mice increased myofiber succinate dehydrogenase activity, shifted the overall myosin heavy chain isoform composition toward a slower phenotype, and, most importantly, reduced contraction-induced damage in tibialis anterior muscles. The deficit in force-producing capacity after two damaging lengthening contractions was reduced significantly in tibialis anterior muscles of IGF-I-treated (53 ± 4%) compared with untreated mdx mice (70 ± 5%, P < 0.05). The results provide further evidence that IGF-I administration can enhance the functional properties of dystrophic skeletal muscle and, compared with results in transgenic mice or virus-mediated overexpression, highlight the disparities in different models of endocrine factor delivery.
Gefitinib Therapy in Advanced Bronchioloalveolar Carcinoma: Southwest Oncology Group Study S0126
Authors: West Howard L. , Franklin Wilbur A. , McCoy Jason , Gumerlock Paul H. , Vance Ralph , Lau Derick H.M. , Chansky Kari , Crowley John J. , Gandara David R.
Published: April 2006

Purpose

Advanced bronchioloalveolar carcinoma (BAC) is a distinct subtype of non–small-cell lung cancer (NSCLC) for which there is currently no optimal therapy. Based on preclinical and clinical data suggesting relevance of the epidermal growth factor receptor (EGFR) axis in BAC, the Southwest Oncology Group initiated a phase II trial (S0126) to evaluate the EGFR tyrosine kinase inhibitor gefitinib in chemotherapy-naïve and chemotherapy-pretreated patients with advanced BAC.

Methods

A total of 136 eligible and assessable patients (101 untreated, 35 previously treated) received gefitinib 500 mg daily until progression or prohibitive toxicity.

Results

The median age was 68.0 years (range, 34.3 to 88.6); 51% were female; 89% had a performance status (PS) of 0% or 1% and 11% had a PS of 2. The Response Evaluation Criteria in Solid Tumors response rate was 17%, with 6% complete responses (CRs) among 69 previously untreated patients with measurable disease, and 9% with no CRs among 22 pretreated patients. Median survival was 13 months for both chemo-naïve (95% CI, 8 to 18) and previously treated patients (95% CI, 6 to 17). Overall survival at 3 years was 23% (95% CI, 14% to 32%). Toxicity consisted mainly of rash and diarrhea, but 2% of patients died of presumed interstitial lung disease. Exploratory subset analyses revealed improved survival among women (P = .031), patients developing a rash (P = .003), never-smokers (P = .061), and patients with a PS of 0 or 1 (P = .015).

Conclusion

Gefitinib is an active agent in advanced stage BAC. Several subsets demonstrate significantly improved clinical outcomes.
Sensorineural Hearing Loss After Radiotherapy and Chemoradiotherapy: A Single, Blinded, Randomized Study
Authors: Low Wong Kein , Toh Song Tar , Wee Joseph , Fook-Chong Stephanie M.C. , Wang De Yun
Published: April 2006

Purpose

The synergistic ototoxicity of radiation and cisplatin (CDDP) has not been adequately studied. This study investigated whether the use of concurrent and postradiotherapy CDDP in patients with nasopharyngeal carcinoma (NPC) resulted in a difference in postradiotherapy sensorineural hearing when compared with the use of radiotherapy alone.

Patients and Methods

Newly diagnosed patients were randomly assigned to the radiotherapy or chemoradiotherapy groups. Bone conduction hearing thresholds were performed before treatment and at 1 week, 6 months, 1 year, and 2 years after completion of radiotherapy. Statistical analysis was performed using the Mann-Whitney U test.

Results

Hearing thresholds averaged over 0.5, 1, and 2 kHz were found to be poorer in the chemoradiotherapy group (58 patients) compared with the radiotherapy group (57 patients) at 1 year (P = .001) and 2 years (P = .03) after radiotherapy. Hearing thresholds at 4 kHz were significantly worse for patients in the chemoradiotherapy arm at all of the postradiotherapy time points studied and were more severely affected than the thresholds at lower speech frequencies. In the radiotherapy group, deterioration of median hearing thresholds, which occurred in the immediate post-treatment period, improved within the first year but deteriorated again at 2 years. In the chemoradiotherapy group, median hearing threshold deterioration, which started immediately after radiotherapy, stabilized by 1 year.

Conclusion

Patients with NPC who received radiotherapy and concurrent/adjuvant chemotherapy using CDDP experienced greater sensorineural hearing loss compared with patients treated with radiotherapy alone, especially to high-frequency sounds in the speech range. Normal inner ear tissue tolerance, which was once defined only for radiotherapy patients alone, should be redefined in chemoradiotherapy patients.
Size, strength and allometry of joints in the articulated corallineCalliarthron
Authors: Martone Patrick T.
Published: April 2006

Articulated coralline algae (Corallinales, Rhodophyta) dominate low-intertidal, wave-exposed habitats around the world, yet the mechanics of this diverse group of organisms has been almost completely unexplored. In contrast to fleshy seaweeds, articulated corallines consist of calcified segments (intergenicula) separated by uncalcified joints (genicula). This jointed construction makes calcified fronds as flexible as fleshy seaweeds,allowing them to `go with the flow' when struck by breaking waves. In addition to functioning as joints, genicula act as breakage points along articulated fronds. Here, I describe the allometric scaling of geniculum size, breaking force and tissue strength along articulated fronds in two species of Calliarthron. Genicular material is much stronger than tissue from fleshy macroalgae. Moreover, as fronds grow, genicula get bigger and their tissue strengthens, two processes that help them resist breakage. Within individual fronds, larger branches, which presumably experience greater drag force, are supported by bigger, stronger genicula. However, frond growth greatly outpaces genicular strengthening. As a result, Calliarthronfronds most likely break at their bases when critically stressed by incoming waves. Shedding fronds probably reduces the drag force that threatens to dislodge coralline crusts and may constitute a reproductive strategy.
Terrestrial locomotion of the New Zealand short-tailed batMystacina tuberculataand the common vampire batDesmodus rotundus
Authors: Riskin Daniel K. , Parsons Stuart , Schutt William A. , Carter Gerald G. , Hermanson John W.
Published: April 2006

Bats (Chiroptera) are generally awkward crawlers, but the common vampire bat (Desmodus rotundus) and the New Zealand short-tailed bat(Mystacina tuberculata) have independently evolved the ability to manoeuvre well on the ground. In this study we describe the kinematics of locomotion in both species, and the kinetics of locomotion in M. tuberculata. We sought to determine whether these bats move terrestrially the way other quadrupeds do, or whether they possess altogether different patterns of movement on the ground than are observed in quadrupeds that do not fly. Using high-speed video analyses of bats moving on a treadmill, we observed that both species possess symmetrical lateral-sequence gaits similar to the kinematically defined walks of a broad range of tetrapods. At high speeds, D. rotundus use an asymmetrical bounding gait that appears to converge on the bounding gaits of small terrestrial mammals, but with the roles of the forelimbs and hindlimbs reversed. This gait was not performed by M. tuberculata.

Many animals that possess a single kinematic gait shift with increasing speed from a kinetic walk (where kinetic and potential energy of the centre of mass oscillate out of phase from each other) to a kinetic run (where they oscillate in phase). To determine whether the single kinematic gait of M. tuberculata meets the kinetic definition of a walk, a run, or a gait that functions as a walk at low speed and a run at high speed, we used force plates and high-speed video recordings to characterize the energetics of the centre of mass in that species. Although oscillations in kinetic and potential energy were of similar magnitudes, M. tuberculata did not use pendulum-like exchanges of energy between them to the extent that many other quadrupedal animals do, and did not transition from a kinetic walk to kinetic run with increasing speed. The gait of M. tuberculata is kinematically a walk,but kinetically run-like at all speeds.
The geometry of isoparametric hypersurfaces with four distinct principal curvatures in spheres
Authors: Immervoll Stefan
Published: April 2006

In this paper, we address three problems in the theory of incidence structures associated with isoparametric hypersurfaces with four distinct principal curvatures in spheres. In [4], we showed that these isoparametric hypersurfaces and their focal manifolds yield Tits buildings of type C2. Here, we ﬁrst give a short proof for the description of point rows and line pencils in these incidence structures. Furthermore, we provide criteria which characterize intersecting lines (or points which can be joined by a line, respectively) and obtain a simple description of the intersection point (the joining line, respectively). Finally, we describe for each antiﬂag (p,L) the position of the uniquely determined ﬂag (q, K ) such that (p, K, q, L) is a 3-chain. In this paper, we make extensive use of the theory of isoparametric triple systems as developed in [1].
A lower bound for the second sectional geometric genus of polarized manifolds
Authors: Fukuma Yoshiaki
Published: April 2006

Let (X, L) be a polarized manifold deﬁned over ℂ with dim
X = n ≥ 3 and let (M, A ) be a reduction of
(X, L). In this paper, if X is not uniruled and
KM
 + (n - 2)A is nef
and (n - 2)-big, then we give a lower bound for
c
2(M )A

n - 2, which
improves a result in a previous paper. By using this bound, we prove that
g
2 (X, L) ≥ h
1(## add figure
'advg.5.3.431_01.gif' ##
x ) if n ≥ 3, X is not
uniruled, and KM
 + (n - 2)A is nef
and (n - 2)-big, where g
2 (X, L) is the second sectional geometric genus of (X, L). In
particular, if n ≥ 3 and κ (X ) ≥ 0, then
g
2 (X, L) ≥ h
1(## add figure
'advg.5.3.431_01.gif' ##
x ). Furthermore we prove that g
2 (X, L) ≥ 0 for any polarized 3-folds. For
n ≥ 3 we also study (X, L) with
g
2 (X, L) ≥ h
1(## add figure
'advg.5.3.431_01.gif' ##x ). Finally we consider a lower bound of
h
0(KX
 + L) for polarized
3-folds (X, L

).