bluuebunny/crossref_metadata_2025 huggingface dataset:
The Application of hCG, CPH and Ovopel in Successful Artificial Reproduction of Goldfish (Carassius auratus auratus) Under Controlled Conditions
Authors: Targońska K , Kucharczyk D
Published: December 2010

Contents

Artificial reproduction of fish is one of the main goals of aquaculture production. The aim of this study is to optimize the method of goldfish reproduction under controlled conditions by comparing the effectiveness of carp pituitary homogenate (CPH), Ovopel and human chorionic gonadotropin (hCG), administered as a one‐off dose and inducing two spawns in the same fish within a short time period. Goldfish spawners were stimulated with hCG, CPH and Ovopel, and the results were compared to the fish from the control group, comprised of unstimulated fish. In another experiment, spawn were induced twice within an interval of 21 days with the same group of fish. The best results in the first experiment in terms of the percentage of ovulating females and survival to the eyed‐egg stage were achieved after administering hCG (100% and 88.7%, respectively). However, the highest fecundity was observed in fish stimulated with Ovopel (89 960 eggs/kg). It was shown in the second experiment that female goldfish produce higher weight of eggs during the first spawning, but the number of eggs/BW ratio was higher during the next reproduction process. Survival, both that of embryos to the eyed‐egg stage and that of spawners, is higher during the first reproduction act.
Early modulation of gene expression used as a biomarker for chemoprevention in a preclinical model of colon carcinogenesis
Authors: Bousserouel Souad , Lamy Virginie , Gossé Francine , Lobstein Annelise , Marescaux Jacques , Raul Francis
Published: December 2010

By using the rat azoxymethane (AOM)‐induced colon carcinogenesis model, which mirrors many clinical features of human colorectal cancer, we examined whether genetic changes occurring early in colonic mucosa are predictive of treatment efficacy. In the present study the administration of the chemopreventive agent lupulone over the course of 7 weeks postinitiation reduced the number of preneoplastic lesions in the colonic mucosa by 50%. At the molecular level we observed the downregulation of genes involved in the inflammatory response, including IL‐1β and TNF‐α, and of matrix metalloproteinase‐7 gene and protein expression. We also observed a substantial upregulation of components of the innate immune system, α‐defensin‐5 and lipocalin 2. Lupulone induced the expression of apoptosis‐related genes and caused a reversal of the B‐cell lymphoma/leukemia 2 (Bcl‐2; antiapoptotic) to Bcl‐2 associated X protein (Bax; proapoptotic) transcript and protein ratios (Bcl‐2/Bax > 1 in AOM controls and Bcl‐2/Bax < 1 in lupulone‐treated AOM rats). Here, we identify several target genes that could be considered early biomarkers of colon carcinogenesis and indicative of drug efficacy.
Vitamin D hormone: A multitude of actions potentially influencing the physical function decline in older persons
Authors: Cesari Matteo , Incalzi Raffaele Antonelli , Zamboni Valentina , Pahor Marco
Published: December 2010

Vitamin D, a secosteroid (pro)‐hormone, has been traditionally considered as a key regulator of bone metabolism, and calcium and phosphorous homeostasis through a negative feedback with the parathyroid hormone. However, during the last 20 years, the role played by vitamin D has been largely revised by recognizing its pleiotropic action on a wide spectrum of systems, apparatuses and tissues. Thus, vitamin D has growingly been involved as a primary determinant of biological modifications and specific clinical conditions. The effect of vitamin D on skeletal muscle and related outcomes (including physical function decline and disability) is surely one of the most relevant to study in the context of global aging. In the present review, the subclinical and clinical consequences of vitamin D deficiency/insufficiency, extremely frequent conditions in older age, are described. Special focus is given to skeletal muscle and physical function. Limitations of available scientific evidence on the topic are also discussed. Geriatr Gerontol Int 2011; 11: 133–142.
MODEL SELECTION CRITERIA FOR LOGLINEAR MODELS
Authors: Bedrick Edward J. , Crandall Winston K.
Published: December 2010

Considerable work has been devoted to developing model selection criteria for normal theory regression models. Less attention has been paid to discrete data. We develop two loglinear model selection criteria for Poisson counts. These criteria are based on an estimated bias adjustment of the Akaike information criterion. We observe in a simulation study that the corrected statistics provide good model choices and relatively accurate estimates of the mean structure.
A follow‐up study of the ABRACADABRA web‐based literacy intervention in Grade 1
Authors: Di Stasio Maria Rosaria , Savage Robert , Abrami Philip C.
Published: December 2010

This paper reports the follow‐up of a randomised control trial study of the ABRACADABRA web‐based literacy intervention that contrasted synthetic versus analytic phonics (Comaskey, Savage & Abrami, 2009) in kindergarten children from urban low‐SES backgrounds. Participants who received a ‘synthetic’ phonics+phoneme awareness training (n = 26) or an ‘analytic’ phonics+phoneme awareness training literacy intervention (n = 27) were tested on standard measures of literacy 1 year later. Results revealed a significant main effect (p < .01) for the analytic group performing better on passage reading comprehension. Modest advantages for children who received the analytic phonics programme were evident. We obtained an effect size favourably comparable with other studies, after adjusting for intervention duration (ES = .41). It is concluded that analytic phonics programmes may provide modest but significant sustained advantages in literacy for kindergarten children from low‐SES backgrounds.
Food habits of school pupils in Tromsø, Norway, in the transition from 13 to 15 years of age
Authors: Øvrebø Else Marie
Published: December 2010

The aim of this study was to investigate the development of food habits in adolescents in Tromsø, whether pupil behaviour regarding food habits had changed in tenth grade compared with eighth grade, and whether this was linked to pupils' Home Economics lessons in ninth grade.

A total of 606 adolescents (321 boys and 285 girls) were studied on two different occasions – 2002 and 2005. A food‐frequency questionnaire comprising 16 different food and beverage groups was used. The questionnaire also enquired about food habits, the amounts of some food items consumed and the socio‐economic conditions of the participants and their families.

The frequency of eating breakfast, lunch and dinner decreased from eighth to tenth graders. Tenth graders ate chocolate and snacks more often than eighth graders. Girls reported eating fruits and vegetables more often than boys. This applies to both eighth and tenth graders. Far more pupils from both groups need to eat more fruits and vegetables every day.

The conclusion of the study is that food habits change significantly from the eighth to the tenth grade. Further progress must be achieved in addressing the issue of translating the theory of nutritional education into practice. More studies and evidence are required to understand the potential of the Home Economics curricula to change the unhealthy eating trends seen in this and other studies.
TWENTY YEARS OF HUMAN RESEARCH ETHICS COMMITTEES IN THE BALTIC STATES
Authors: DRANSEIKA VILIUS , GEFENAS EUGENIJUS , CEKANAUSKAITE ASTA , HUG KRISTINA , MEZINSKA SIGNE , PEICIUS EIMANTAS , SILIS VENTS , SOOSAAR ANDRES , STROSBERG MARTIN
Published: December 2010

Two decades have passed since the first attempts were made to establish systematic ethical review of human research in the Baltic States. Legally and institutionally much has changed. In this paper we provide an historical and structural overview of ethical review of human research and identify some problems related to the role of ethical review in establishing quality research environment in these countries. Problems connected to (a) public availability of information, (b) management of conflicts of interest, (c) REC composition and motivation of REC members, and (d) differing levels of stringency of ethical review for different types of studies, are identified. Recommendations are made to strengthen cooperation among the Baltic RECs.
Multiple Cutaneous Angiomyxomas in a Child
Authors: MARTÍ NURIA , JORDÁ ESPERANZA , MONTEAGUDO CARLOS , GÁMEZ LUCÍA , REIG IRELA , CALDUCH LUÍS
Published: December 2010

Abstract:  Cutaneous myxomas are rare, benign, connective tissue tumors composed of stellate cells set in a loose mucoid stroma containing delicate reticulin fibers running in various directions. They are also called angiomyxomas to reinforce their vascular component. These lesions have been recognized as part of Carney complex. We report an 11‐year‐old boy affected by disseminated cutaneous angiomyxomas since the age of 2, without any other component of Carney complex.
Psoriasiform Type of Lichen Scrofulosorum: Clue to Disseminated Tuberculosis
Authors: Kumar Uttam , Sethuraman Gomathy , Verma Parul , Das Prasanjit , Sharma Vinod K.
Published: December 2010

Abstract:  We present a 16‐year‐old girl with tuberculosis of the lungs, lymph nodes, and liver, who had extensive inflammatory lesions with pustules, which resembled psoriasis. A skin biopsy showed extensive tuberculoid granulomas surrounding hair follicles, consistent with lichen scrofulosorum. Antitubercular therapy led to resolution of skin lesions. This severe inflammatory type of lichen scrofulosorum is extremely rare.
The NDR Family Kinase NdrA of Dictyostelium Localizes to the Centrosome and Is Required for Efficient Phagocytosis
Authors: Kastner Peter M. , Schleicher Michael , Müller‐Taubenberger Annette
Published: December 2010

Dictyostelium discoideum cells are professional phagocytes that provide an easily accessible system to gain insights into the mechanisms and the regulatory machinery controlling phagocytosis. Here, we describe a novel function for nuclear Dbf2‐related (NDR) family kinases in phagocytosis of D. discoideum. Deletion of one of the four NDR kinases of D. discoideum, NdrA, resulted in impaired cell growth caused by reduced phagocytosis rates. Detailed analysis of NdrA‐null cells revealed that the formation of phagocytic cups was delayed. Microscopic investigations showed that NdrA localizes to centrosomes, and NdrA was also identified in isolated centrosome preparations. The localization of NdrA is regulated during the cell cycle. In prophase, NdrA disappears from the centrosome and forms a cloud‐like structure around the spindle, which is totally absent during later stages until completion of mitosis. Our results suggest that a signal which originates from the NdrA kinase at the centrosome affects the efficiency of phagocytosis. We assume that in NdrA‐null cells the defects in phagocytosis may be caused by an impairment of vesicle trafficking, which is involved in providing new membrane at the sites of particle uptake.
The relevance of context in property law: a case for judicial restraint?
Authors: Hopkins Nicholas
Published: December 2010

A distinction between the domestic and commercial context is commonly drawn in property law discourse and has been brought into focus by three recent House of Lords’ decisions. The thesis of this paper is that while the distinction is a useful explanatory tool, it runs into difficulties when given legal effect by the courts. There is a definitional problem in understanding what is included within each context. Indeed, the distinction assumes the existence of a dichotomy when, in fact, the domestic and commercial spheres are better seen as a continuum. In Stack v Dowden, the majority of the House of Lords gave legal effect to context and considered that different rules should apply to determine ownership of the home. This paper locates its decision in the broader debate on judicial restraint and creativity. By analogy with current discussion of due deference in public law, it is suggested that, in light of the policy issues involved and the broader ramifications of the decision, insufficient justification was given for the approach adopted by the majority.
Use of microdebrider bronchoscopy for the treatment of endobronchial leiomyoma
Authors: Wahla Ali Saeed , Khan Irtaza , Bellinger Christina , Haponik Edward , Conforti John Frank
Published: December 2010

Aims:  Pulmonary leiomyomas are rare benign tumors that may cause symptoms when they spread endobronchially. Traditionally they were managed surgically or through interventional bronchoscopy with the aid of thermal modalities to assist in debulking of tumor. We report the novel use of microdebrider bronchoscopy to debulk an endobronchial leiomyoma in a symptomatic patient.

Method/Results:  The microdebrider successfully débrided the endobronchial leiomyoma.

Conclusion:  This modality can be successfully employed when oxygenation is an issue, preventing use of thermal modalities. In addition, use of microdebrider not only reduced procedure time but also decreased the risk of airway fire and damage to adjacent normal tissue in our patient.

Please cite this paper as: Wahla AS, Khan I, Bellinger C, Haponik E and Conforti JF. Use of microdebrider bronchoscopy for the treatment of endobronchial leiomyoma. Clin Respir J 2011; 5: e4–e7.
Stipa adamii sp. nov. (Poaceae) from the western Tian‐Shan, and some remarks on the taxa of the section Smirnovia occurring in Kazakhstan
Authors: Nobis Marcin
Published: December 2010

Stipa adamii M. Nobis sp. nov. (Poaceae), endemic to Kazakhstan, is described and illustrated. The species belongs to the section Smirnovia Tzvel. and is distributed in the central Karatau Mountains (western Tian‐Shan). It is morphologically close to Stipa karataviensis Roshev. but is easily distinguishable by longer glumes, lemmas, awns and the callus. The awn is scabrous in the lower part and the callus is bearded in S. adamii whereas both organs are glabrous in S. karataviensis. Characters distinguishing S. karataviensis and S. adamii are presented in a table, together with photographs of the callus. The analysis of morphological characters of the taxa provides new information on their variability. A key to the species of Stipa sect. Smirnovia occurring in Kazakhstan, typification of the name S. manrakica and synonymization of the name S. saurica as a syn. nov. are included.
Fluoride in still bottled water in Australia
Authors: Mills K , Falconer S , Cook C
Published: December 2010

Background:  This study measured the fluoride content in a range of still bottled waters available in Australia. Increasing decay rates in children have prompted speculation that bottled water consumption may be impacting on dental caries rates. International studies have demonstrated that the fluoride levels in bottled water are often negligible, however there is little information about the fluoride content of still bottled water in Australia.

Methods:  One hundred different brands (300 samples) of still bottled water were obtained in Australia and tested using ion chromatography and an ion‐selective electrode method.

Results:  The tested fluoride levels ranged from <0.1 to 1.6 mg/L. Nine per cent of the samples reported fluoride levels within the range recommended for reticulated water in Australia, providing a dental health benefit. One per cent of samples recorded fluoride values greater than this range, from 1.2 to 1.6 mg/L. The majority of samples (91%) recorded fluoride levels below 0.6 mg/L.

Conclusions:  Better information about the fluoride levels in bottled water is of value, particularly for communities lacking access to a fluoridated drinking water supply.
The University of Newcastle’s first cohort of Bachelor of Oral Health students: a social profile
Authors: Wallace LG , Cockrell DJ , Taylor JA
Published: December 2010

Background:  This paper reports on the socio‐demographic characteristics of the first year cohort of 52 students enrolled in the Bachelor of Oral Health programme at the University of Newcastle, New South Wales.

Methods:  Forty students completed paper‐based questionnaires.

Results:  Results show that the cohort is predominantly female (94%), the mean age of students was 26.3 years and 72.5% of students had worked as dental chairside assistants prior to enrolment as mature‐entry students.

Conclusions:  This study provided a unique opportunity to compare and contrast the socio‐demographic profile of first year BOH students with similar research on first year dentistry students at the University of Sydney. Aspects of the study included age, gender, type of school attended, post‐secondary qualifications and work experience, ethnicity, parents’ level of education and occupation, and career choice motivation.
Regenerative endodontics – biologically‐based treatment for immature permanent teeth: a case report and review of the literature
Authors: Thomson A , Kahler B
Published: December 2010

Background:  A paradigm shift in the treatment of immature, necrotic teeth has occurred with biologically‐based principles and regenerative endodontic protocols replacing traditional ‘apexification’ procedures. Preliminary research suggests that stem and progenitor cells from the pulp and/or periodontium contribute to continued root development when regenerative procedures are followed.

Methods:  A mandibular premolar tooth with a chronic periapical abscess was irrigated with sodium hypochlorite with minimal instrumentation and then dressed with tri‐antibiotic paste consisting of ciprofloxacin, metronidazole and amoxicillin. At a subsequent visit a blood clot was evoked in the canal by irritating periapical tissues and the canal sealed with mineral trioxide aggregate, glass ionomer cement and composite resin.

Results:  Resolution of apical periodontitis and the draining sinus, continued root maturation and apical closure occurred over an 18‐month period. The tooth became responsive to pulp sensibility testing.

Conclusions:  It is important that dentists recognize the potential of regenerative endodontics in the treatment of necrotic, immature teeth. Initial management should involve irrigation with sodium hypochlorite only. Intra‐canal medicaments, such as calcium hydroxide, are contraindicated as they inhibit further root growth. This report uses a variation of the tri‐antibiotic paste currently recommended for regenerative procedures that avoided the discolouration of the crown associated with current protocols. Regenerative endodontics with continued root growth may reduce the risk of fracture and premature tooth loss associated with traditional ‘apexification’ procedures where the root remains thin and weak.
Optimizing Customer Forecasts for Forecast‐Commitment Contracts
Authors: Durango‐Cohen Elizabeth J. , Yano Candace A.
Published: December 2010

We study a “Forecast‐Commitment” contract motivated by a manufacturer's desire to provide good service in the form of delivery commitments in exchange for reasonable forecasts and a purchase commitment from the customer. The customer provides a forecast for a future order and a guarantee to purchase a portion of it. In return, the supplier commits to satisfy some or all of the forecast. The supplier pays penalties for shortfalls of the commitment quantity from the forecast, and for shortfalls of the delivered quantity from the customer's final order (not exceeding the commitment quantity). These penalties allow differential service among customers.

In Durango‐Cohen and Yano (2006), we analyzed the supplier's problem for a given customer forecast. In this paper, we analyze the customer's problem under symmetric information, both when the customer is honest and when he strategically orders more than his demand when doing so is advantageous. We show that the customer gains little from lying, so the supplier can use his control over the contract parameters to encourage honesty. When the customer is honest, the contract achieves (near‐)coordination of the supply chain in a great majority of instances, and thus provides both excellent performance and flexibility in structuring contracts.
Gating behaviour of sodium currents in adult mouse muscle recorded with an improved two‐electrode voltage clamp
Authors: Fu Yu , Struyk Arie , Markin Vladislav , Cannon Stephen
Published: December 2010

Non‐technical summary

Muscle contraction is triggered by the spread of an action potential along the fibre. The ionic current to generate the action potential is conducted through voltage‐activated sodium channels, and mutations of these channels are known to cause several human muscle disorders. Mouse models have been created by introducing point mutations into the sodium channel gene. This achievement has created the need for a high‐fidelity technique to record sodium currents from intact mouse muscle fibres. We have optimized a two‐electrode voltage clamp, using sharp microelectrodes to preserve the myoplasmic contents. The voltage‐dependent behaviour of sodium channel activation, inactivation and slow‐inactivation were characterized. The voltage range for these gating behaviours was remarkably hyperpolarized, in comparison to studies in artificial expression systems. These results provide normative data for sodium channels natively expressed in mouse muscle and illustrate the need to modify model simulations of muscle excitability to account for the hyperpolarized shift.
Main Gas Ingestion in a Turbine Stage for Three Rim Cavity Configurations
Authors: Zhou D. W. , Roy R. P. , Wang C.-Z. , Glahn J. A.
Published: December 2010

Experiments were carried out in a model air turbine stage to study the influence of rotor-stator rim cavity configuration on the ingestion of mainstream gas into the cavity. The three rim cavity configurations differed in their aspect ratio (height/width); the rim seal geometry remained the same. The aspect ratio was changed from the baseline ratio by installing an inner shell on the stator at an appropriate radius; this effectively introduced an axial-gap seal between the rim cavity and the cavity radially inboard. The initial step in each experiment was the measurement of time-average static pressure distribution in the turbine stage to ascertain that proper flow condition had been established. Subsequently, tracer gas concentration and particle image velocimetry techniques were employed to measure the time-average but spatially local main gas ingestion and the instantaneous velocity field in the rim cavity. At low purge air flow, regions of ingestion and egress could be identified by inspecting the instantaneous radial velocity distribution near the rim seal obtained from cavity gas velocity maps close to the stator. While the tangential velocity tended to be slightly larger for the so determined ingested gas, a more clear-cut indicator of ingestion was the strong inward gas radial velocity. Information provided by ensemble-average velocity maps was not sufficient for identifying ingestion because the averaging smeared out flow details, which varied from instant to instant. Velocity fields obtained from three-dimensional, time-dependent numerical simulation of a rim seal-cavity sector with similar dimensions qualitatively showed similar characteristics in the outer part of the cavity and provided insight into the complex flow in the seal region.
Aerothermal Investigation of a Rib-Roughened Trailing Edge Channel With Crossing Jets—Part II: Heat Transfer Analysis
Authors: Coletti Filippo , Armellini Alessandro , Arts Tony , Scholtes Christophe
Published: December 2010

The present contribution addresses the aerothermal experimental and computational study of a trapezoidal cross-section model simulating a trailing edge cooling cavity with one rib-roughened wall and slots along two opposite walls. Highly resolved heat transfer distributions for the geometry with and without ribs are achieved using a steady state liquid crystals method in part II of this paper. The reference Reynolds number defined at the entrance of the test section is set at 67,500 for all the experiments. Comparisons are made with the flow field visualizations presented in part I of this paper. The results show the dramatic impact of the flow structures on the local and global heat transfer coefficients along the cavity walls. Of particular importance is the jet deflected by the rib-roughened wall and impinging on the opposite smooth wall. The experimental results are compared with the numerical predictions obtained using the finite volume, Reynolds-Averaged Navier–Stokes solver Calcul d'Écoulements Diphasiques Réactifs pour l'Énergétique (CEDRE).
Model Selection Under Limited Information Using a Value-of-Information-Based Indicator
Authors: Messer Matthias , Panchal Jitesh H. , Krishnamurthy Vivek , Klein Benjamin , Yoder P. Douglas , Allen Janet K. , Mistree Farrokh
Published: December 2010

Designers are continuously challenged by complexity, as well as by the excessive instantiation and execution times of models, particularly in the context of integrated product and materials design. In order to manage these challenges, a systematic strategy for evaluating and selecting models is presented in this paper. The systematic strategy is based on value-of-information for design decision making. It consists of a (i) process performance indicator (PPI) to quantify the impact of model refinement from a decision-centric perspective and (ii) a method involving model evaluation. Using this method, a least complex but valid model is evaluated, and, only if necessary, gradually refined it until the most appropriate one is selected. The systematic approach is particularly well suited for integrated product and materials design, and all other scenarios where the perfect knowledge of the true system behavior and bounds of error are not available throughout the design space. The proposed strategy is applied to the design of photonic crystal waveguides for use in a next-generation optoelectronic communication system. In this paper, it is shown that the systematic strategy based on the PPI is useful for evaluating and selecting models particularly when accuracy of the prediction or the associated error bounds are not known.
An Investigation Into the Decision Analysis of Design Process Decisions
Authors: Thompson Stephanie C. , Paredis Christiaan J. J.
Published: December 2010

Although recent work in decision-based design (DBD) recognizes the need for an enterprise perspective in which the expected profit is the primary driver of utility, for the overwhelming majority of contributions in the DBD literature, the emphasis in the problem formulation is exclusively on the design artifact. This formulation of DBD problems is too narrow in scope, because the use of resources during the design and development phase is overlooked, making it impossible to consider the tradeoffs between the quality of the design artifact and the cost of the design process. We aim to establish a new DBD perspective that more accurately represents the tradeoffs under consideration in an enterprise context by studying the design actions with decision analysis. As a first step toward establishing this new perspective, a simple example problem of material selection for a pressure vessel is introduced and analyzed in this paper. Although several simplifying assumptions are made, the intent of this work is to qualitatively explore the impact of relaxing some of the assumptions implicitly made in previous work in DBD, specifically the assumption of ignoring the costs of the design phase and the assumption that the value of a particular analysis is independent of the ability to gain additional information from subsequent analyses. This work confirms that an analysis is worth performing only when the cost is low, the quality is high, and the overlap in the predicted utility of the two concepts is significant. These insights are also compared with the related work in information economics. We show that the decision analysis of design process decisions provides a more comprehensive model of the problem when multiple information sources can sequentially be used.
ERKed About Lamin A
Authors: Adler Elizabeth M.
Published: December 2010

ERK can promote cell proliferation through a mechanism independent of its catalytic activity.
Pain in the Brain
Authors: Stern Peter R.
Published: December 2010

Nerve injury increases the activity of an enzyme in the brain and contributes to chronic pain–related cortical sensitization.
Live or Die with ErbB4
Authors: Gough Nancy R.
Published: December 2010

Alternative splice variants of the receptor tyrosine kinase ErbB4 trigger proliferation or death.
Deadly Trio
Authors: Ray L. Bryan
Published: December 2010

Proapoptotic proteins act directly on mitochondrial “gatekeeper” proteins to initiate apoptotic events during mouse development.
Focus Issue: Metabolic Signals
Authors: Wong Wei
Published: December 2010

Complementing the
Science
Special Issue, this issue highlights signaling pathways with roles in metabolism.
Dependence Receptors: The Trophic Theory Revisited
Authors: Mehlen Patrick
Published: December 2010

Some receptor tyrosine kinases can activate apoptotic pathways in the absence of ligand.
Planar Patch Clamp Approach to Characterize Ionic Currents from Intact Lysosomes
Authors: Schieder Michael , Rötzer Katrin , Brüggemann Andrea , Biel Martin , Wahl-Schott Christian
Published: December 2010

Glass chips and gentle isolation are the keys to recording channels from intracellular organelles.
In VitroandIn VivoEfficacies of Mefloquine-Based Treatment against Alveolar Echinococcosis
Authors: Küster Tatiana , Stadelmann Britta , Hermann Corina , Scholl Sabrina , Keiser Jennifer , Hemphill Andrew
Published: December 2010

Alveolar echinococcosis (AE) is caused by the metacestode stage of the fox tapewormEchinococcus multilocularisand causes severe disease in the human liver, and occasionally in other organs, that is fatal when treatment is unsuccessful. The present chemotherapy against AE is based on mebendazole and albendazole. Albendazole treatment has been found to be ineffective in some instances, is parasitostatic rather than parasiticidal, and usually involves the lifelong uptake of large doses of drugs. Thus, new treatment options are urgently needed. In this study we investigated thein vitroandin vivoefficacy of mefloquine againstE. multilocularismetacestodes. Treatment using mefloquine (20 μM) againstin vitrocultures of metacestodes resulted in rapid and complete detachment of large parts of the germinal layer from the inner surface of the laminated layer within a few hours. Thein vitroactivity of mefloquine was dependent on the dosage.In vitroculture of metacestodes in the presence of 24 μM mefloquine for a period of 10 days was parasiticidal, as determined by murine bioassays, while treatment with 12 μM was not. Oral application of mefloquine (25 mg/kg of body weight administered twice a week for a period of 8 weeks) inE. multilocularis-infected mice was ineffective in achieving any reduction of parasite weight, whereas treatment with albendazole (200 mg/kg/day) was highly effective. However, when the same mefloquine dosage was applied intraperitoneally, the reduction in parasite weight was similar to the reduction seen with oral albendazole application. Combined application of both drugs did not increase the treatment efficacy. In conclusion, mefloquine represents an interesting drug candidate for the treatment of AE, and these results should be followed up in appropriatein vivostudies.
Comparison of a Regulated Delayed Antigen Synthesis System withIn Vivo-Inducible Promoters for Antigen Delivery by Live AttenuatedSalmonellaVaccines
Authors: Wang Shifeng , Li Yuhua , Shi Huoying , Sun Wei , Roland Kenneth L. , Curtiss Roy
Published: December 2010

Induction of strong immune responses against a vectored antigen in hosts immunized with live attenuatedSalmonellavaccines is related in part to the amount of antigen delivered and the overall fitness of theSalmonellavector in relation to its ability to stimulate the host immune system. Constitutive high-level antigen synthesis causes a metabolic burden to the vaccine vector strain that can reduce the vaccine strain's ability to interact with host lymphoid tissues, resulting in a compromised immune response. A solution to this problem is the use of systems that regulate antigen gene expression, permitting high levels of antigen synthesis only after the vaccine strain has reached its target tissues.In vivo-inducible promoters (IVIPs) are often used to accomplish this. We recently developed an alternative strategy, a regulated delayed antigen synthesis (RDAS) system, in which the LacI-repressible Ptrcpromoter controls antigen gene expression by adding arabinose. In this paper, we compared the RDAS system with two commonly used IVIPs, PssaGand PpagC. Three nearly identical plasmids, differing only in the promoter used to direct transcription of the pneumococcalpspAgene, Ptrc, PssaG, or PpagC, were constructed and introduced into isogenicSalmonellavaccine strains with or without arabinose-inducible LacI synthesis. Mice immunized with the RDAS strain developed slightly higher titers of mucosal and serum anti-PspA antibodies than PpagC-immunized mice, while titers in mice immunized with the PssaGstrain were 100-fold lower. Both the RDAS and PpagCstrains conferred similar levels of protection againstStreptococcus pneumoniaechallenge, significantly greater than those for the PssaGstrain or controls. Thus, RDAS provides another choice for inclusion in the live vaccine design to increase immunogenicity.
Mouse Peptidoglycan Recognition Protein PGLYRP-1 Plays a Role in the Host Innate Immune Response againstListeria monocytogenesInfection
Authors: Osanai Arihiro , Sashinami Hiroshi , Asano Krisana , Li Sheng-Jun , Hu Dong-Liang , Nakane Akio
Published: December 2010

The role of mouse peptidoglycan recognition protein PGLYRP-1 in innate immunity againstListeria monocytogenesinfection was studied. The recombinant mouse PGLYRP-1 and a polyclonal antibody specific to PGLYRP-1 were prepared. The mouse PGLYRP-1 showed antibacterial activities againstL. monocytogenesand other Gram-positive bacteria. PGLYRP-1 mRNA expression was induced in the spleens and livers of mice infected withL. monocytogenes. The viable bacterial number increased, and the production of cytokines such as gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) was reduced in mice when mice had been injected with anti-PGLYRP-1 antibody before infection. The levels of IFN-γ and TNF-α titers in the organs were higher and the viable bacterial number was reduced in mice injected with recombinant mouse PGLYRP-1 (rmPGLYRP-1) before infection. PGLYRP-1 could directly induce these cytokines in spleen cell cultures. The elimination of intracellular bacteria was upregulated in NMuLi hepatocyte cells overexpressing PGLYRP-1. The enhancement of the elimination ofL. monocytogenesfrom the organs was observed in IFN-γ−/−mice by rmPGLYRP-1 administration but not in TNF-α−/−mice. These results suggest that PGLYRP-1 plays a role in innate immunity againstL. monocytogenesinfection by inducing TNF-α.
Native Properdin Binds toChlamydia pneumoniaeand Promotes Complement Activation
Authors: Cortes Claudio , Ferreira V. P. , Pangburn Michael K.
Published: December 2010

Activation of complement represents one means of natural resistance to infection from a wide variety of potential pathogens. Recently, properdin, a positive regulator of the alternative pathway of complement, has been shown to bind to surfaces and promote complement activation. Here we studied whether properdin-mediated complement activation occurs on the surface ofChlamydia pneumoniae, an obligate intracellular Gram-negative bacterium that causes 10 to 20% of community-acquired pneumonia. We have determined for the first time that the physiological P2, P3, and P4forms of human properdin bind to the surface ofChlamydia pneumoniaedirectly. The binding of these physiological forms accelerates complement activation on theChlamydia pneumoniaesurface, as measured by C3b and C9 deposition. Finally, properdin-depleted serum could not controlChlamydia pneumoniaeinfection of HEp-2 cells compared with normal human serum. However, after addition of native properdin, the properdin-depleted serum recovered the ability to control the infection. Altogether, our data suggest that properdin is a pattern recognition molecule that plays a role in resistance toChlamydiainfection.
Comments on the dilemma in the October issue: ‘To treat or not?’
Authors: Mullan Siobhan
Published: December 2010

The dilemma in the October issue concerned a vet who had been asked by their client to perform a radical surgical intervention on their pet (In Practice, October 2010, volume 32, pages 458–459). The vet was highly competent at the procedure, but unsure whether it would be overtreatment for that case. If the vet did not perform the treatment, the client had made it clear they would go to another local vet. James Yeates commented that veterinary treatment choices must be based on the interests of the animal. Treatment should first be compared to euthanasia and it should be considered whether the pain of surgery was worth the pleasure of future life. It was not acceptable to perform the surgery simply because another vet would do it otherwise. A possible way forward would be for the vet to advise euthanasia and give their reasons why. If this was unsuccessful, the vet could try to speak to the other vet if possible, as this might reveal that he or she was also not keen to perform the surgery. If both the owner and the other vet were immovable, then performing the operation was legitimate, as it was possible that the other vet was less skilled in the procedure. However, it might be better for the vet to maintain their moral integrity – if the client and the other vet proceeded nonetheless, the stain would be on their consciences.
Minimally invasive soft tissue surgery in dogs and cats
Authors: Moore Alasdair Hotston
Published: December 2010

Part 1 of this article, published in the October 2010 issue of In Practice (volume 32, pp 426–431), outlined the equipment required for minimally invasive soft tissue surgery in small animals and described its use for common abdominal procedures. This article discusses how similar techniques may be applied to the thorax, urethra and bladder. However, it is important to note that new applications are constantly being developed for this type of surgery, and it is likely that other body systems will benefit from further innovation in the future.
14-3-3σ Exerts Tumor-Suppressor Activity Mediated by Regulation of COP1 Stability
Authors: Su Chun-Hui , Zhao Ruiying , Zhang Fanmao , Qu Changju , Chen Bo , Feng Yin-Hsun , Phan Liem , Chen Jian , Wang Hua , Wang Huamin , Yeung Sai-Ching J. , Lee Mong-Hong
Published: December 2010

Constitutive photomorphogenic 1 (COP1) is a p53-targeting E3 ubiquitin ligase that is downregulated by DNA damage through mechanisms that remain obscure. Here, we report that COP1 is not downregulated following DNA damage in 14-3-3σ null cells, implicating 14-3-3σ as a critical regulator in the response of COP1 to DNA damage. We also identified that 14-3-3σ, a p53 target gene product, interacted with COP1 and controlled COP1 protein stability after DNA damage. Mechanistic studies revealed that 14-3-3σ enhanced COP1 self-ubiquitination, thereby preventing COP1-mediated p53 ubiquitination, degradation, and transcriptional repression. In addition, we found that COP1 expression promoted cell proliferation, cell transformation, and tumor progression, manifesting its role in cancer promotion, whereas 14-3-3σ negatively regulated COP1 function and prevented tumor growth in a mouse xenograft model of human cancer. Immunohistochemical analysis of clinical breast and pancreatic cancer specimens demonstrated that COP1 protein levels were inversely correlated with 14-3-3σ protein levels. Together, our findings define a mechanism for posttranslational regulation of COP1 after DNA damage that can explain the correlation between COP1 overexpression and 14-3-3σ downregulation during tumorigenesis. Cancer Res; 71(3); 884–94. ©2010 AACR.
Combination Therapy Targeting Both Tumor-Initiating and Differentiated Cell Populations in Prostate Carcinoma
Authors: Dubrovska Anna , Elliott Jimmy , Salamone Richard J. , Kim Sungeun , Aimone Lindsey J. , Walker John R. , Watson James , Sauveur-Michel Maira , Garcia-Echeverria Carlos , Cho Charles Y. , Reddy Venkateshwar A. , Schultz Peter G.
Published: December 2010

Purpose: The cancer stem cell hypothesis predicts that standard prostate cancer monotherapy eliminates bulk tumor cells but not a tumor-initiating cell population, eventually leading to relapse. Many studies have sought to determine the underlying differences between bulk tumor and cancer stem cells.

Experimental Design: Our previous data suggest that the PTEN/PI3K/AKT pathway is critical for the in vitromaintenance of CD133+/CD44+ prostate cancer progenitors and, consequently, that targeting PI3K signaling may be beneficial in treatment of prostate cancer.

Results: Here, we show that inhibition of PI3K activity by the dual PI3K/mTOR inhibitor NVP-BEZ235 leads to a decrease in the population of CD133+/CD44+ prostate cancer progenitor cells in vivo. Moreover, the combination of the PI3K/mTOR modulator NVP-BEZ235, which eliminates prostate cancer progenitor populations, and the chemotherapeutic drug Taxotere, which targets the bulk tumor, is significantly more effective in eradicating tumors in a prostate cancer xenograft model than monotherapy.

Conclusion: This combination treatment ultimately leads to the expansion of cancer progenitors with a PTEN E91D mutation, suggesting that the analysis of PTEN mutations could predict therapeutic response to the dual therapy. Clin Cancer Res; 16(23); 5692–702. ©2010 AACR.
Inherited Variants in the Chemokine CCL2 Gene and Prostate Cancer Aggressiveness in a Caucasian Cohort
Authors: Sun Tong , Mary Lee Gwo-Shu , Oh William K. , Freedman Matthew L. , Pomerantz Mark , Pienta Kenneth J. , Kantoff Philip W.
Published: December 2010

Purpose: Though C–C chemokine ligand 2 (CCL2) has been shown to play a pivotal role in prostate cancer tumorigenesis and invasion, the role of inherited variation in the CCL2 gene in prostate cancer progression and metastases remains unanswered. This study is aimed to determine the influence of CCL2 germline variants on prostate cancer aggressiveness.

Experimental Design: We performed an association study between six single nucleotide polymorphisms (SNP) in the CCL2 gene and prostate cancer clinicopathologic variables in a large hospital-based Caucasian patient cohort (N = 4,073).

Results: Genetic variation at CCL2 is associated with markers of disease aggressiveness. Three SNPs, each in strong linkage disequilibrium, are associated with a higher (>7) biopsy Gleason score: CCL2 −1811 A/G, −2835 A/C, and +3726 T/C (P = 0.01, 0.03, and 0.04, respectively). The CCL2 -1811 G allele is addionally associated with advanced pathologic stages in patients who underwent radical prostatectomy (P = 0.04). In haplotype analysis, we found that the frequency of a common haplotype, H5, was higher among patients with D'Amico good risk features (Ppermutation = 0.04).

Conclusions: These results support the influence of CCL2 variants on prostate cancer development and progression. Clin Cancer Res; 17(6); 1546–52. ©2010 AACR.
Fibroblast Growth Factor 23 in Chronic Kidney Disease: Bridging the Gap between Bone Mineral Metabolism and Left Ventricular Hypertrophy
Authors: Canziani M.E.F. , Tomiyama C. , Higa A. , Draibe S.A. , Carvalho A.B.
Published: December 2010

Background: Left ventricular hypertrophy (LVH) is a major cardiovascular complication in chronic kidney disease (CKD) patients. For a successful management of LVH, the comprehensive understanding of the classical and the new emerging factors associated with LVH is of paramount importance. The aim of the present study was to evaluate the clinical correlates of bone mineral metabolism with the occurrence of LVH in nondialyzed CKD patients. Methods: This cross-sectional study included 96 patients with stages 2–4 CKD. Demographic characteristics, clinical profiles, laboratory tests and transthoracic echocardiogram were performed. Results: LVH was observed in 36% of the patients. Patients with LVH were older, had a higher prevalence of hypertension, and higher levels of intact parathormone, fibroblast growth factor 23 and C-reactive protein. Serum phosphorus, alkaline phosphatase and vitamin D were not associated with the presence of LVH. In the multiple logistic regression analyses only FGF23 remained as a variable independently associated with LVH. Conclusion: We confirmed the high prevalence of LVH in nondialyzed CKD patients and showed that FGF23, an early marker of phosphorus load, was an important factor associated with LVH in these patients. Monitoring of FGF23 could be important for the management of LVH in this population.
Glue-Enhanced Excimer Laser-Assisted Nonocclusive Anastomosis: A Laboratory Investigation
Authors: Alfieri Alex , Reinert Michael
Published: December 2010

Background/Aims: The excimer laser-assisted nonocclusive anastomosis (ELANA) technique has been developed as a clinical effective technique to perform intracranial high-flow bypass without temporary occlusion of cerebral vessels in otherwise untreatable or high-risk cerebrovascular diseases. We experimentally tested the application of a nonabsorbable cyanoacrylate-based sealant with the ELANA technique. Methods: Three technical in vitro variations of the ELANA anastomosis technique using Omnex© glue and expanded polytetrafluoroethylene tube were compared with conventional sutured ELANA bypasses, resulting in 36 bypasses and 72 anastomoses. After that, the best resulting type was tested in 10 rabbits. Results: The ELANA bypass using Omnex and the expanded polytetrafluoroethylene tube technique offers better results in vitro in the retrieval of the arterial wall flap after arteriotomy, is faster, and the tensile strength of the bypasses performed with Omnex is comparable with those performed with conventional sutures. However, in 2 cases, we observed thrombosis of the vessel and considerable stiffness. Conclusions: The combining of the ELANA technique with 2-octyl cyanoacrylate and butyl lactoyl cyanoacrylate experimentally provides some advantages over the conventional ELANA technique. Further experimental studies should be performed in order to improve the safety and applicability of this technique.