bluuebunny/crossref_metadata_2025 huggingface dataset:
Iron Metabolism in Man
Authors: von Drygalski Annette , Adamson John W.
Published: September 2012

Iron metabolism in man is a highly regulated process designed to provide iron for erythropoiesis, mitochondrial energy production, electron transport, and cell proliferation. The mechanisms of iron handling also protect cells from the deleterious effects of free iron, which can produce oxidative damage of membranes, proteins, and lipids. Over the past decade, several important molecules involved in iron homeostasis have been discovered, and their function has expanded our understanding of iron trafficking under normal and pathological conditions. Physiologic iron metabolism is strongly influenced by inflammation, which clinically leads to anemia. Although hepcidin, a small circulating peptide produced by the liver, has been found to be the key regulator of iron trafficking, molecular pathways of iron sensing that control iron metabolism and hepcidin production are still incompletely understood. With this review, we provide an overview of the current understanding of iron metabolism, the recently discovered regulators of iron trafficking, and a focus on the effects of inflammation on the process.
An Existential Approach to Adoptive Identity Development in Adulthood
Authors: Fall Kevin A. , Roaten Gail K. , Eberts Stephanie E.
Published: September 2012

As adoption in our society continues to increase, mental health professionals are faced with working with the coexisting intrapersonal, familial, and social issues. The formation of an adoptive identity is one of the more critical and complicated tasks facing adoptees. Existentialism is a counseling theory that is well suited to address the issues related to adoptive identity formation in adulthood. An overview of the philosophy of existentialism as well as a detailed exploration of how to use the givens of existence along with the authentic relationship is provided as a framework for helping adults explore and develop a healthy self in context.
Postadoption Services Utilization Among African American, Transracial, and White American Parents
Authors: Adkison-Bradley Carla , DeBose Cynthia Hawkins , Terpstra Jeffrey , Bilgic Yusuf Kenan
Published: September 2012

The utilization of postadoption services among adoptive families has been an emerging topic of discussion over the last decade. However, what is often not discussed is the utilization rate of services among African American and transracial families who have adopted children from foster care. The purpose of this study was to explore the extent of the use of nonfinancial support services (e.g., participation in support groups or individual/family counseling) by African American, transracial, and White American adoptive families. Implications for family counselors will be presented.
Culture and social representations: A continuing dialogue in search for heterogeneity in social developmental psychology
Authors: Psaltis Charis
Published: September 2012

In this commentary on Jahoda (2012) and Moghaddam (2012), I discuss the problem of the reification of culture from a social representations perspective and argue that social representations as a notion overcomes many of the shortcomings of the notion of culture, the main being reification. Whilst building this argument I show, by making reference to recent developments in the field of social representations and social developmental psychology, how weaknesses in social representations theory identified by Jahoda (1988) were addressed and how insights from this approach can be used for diversity management policies in education.
Pro-nuclear European discourses: Socio-semiotic observations
Authors: Catellani Andrea
Published: September 2012

This article is focused on some recent examples of ‘nuclear discourse’, with a specific reference to the civil use of nuclear power in order to produce energy. The basic aim of this article is dual-fold. From a methodological point of view, I want to show an example of the application of a specific form of semiotic analysis (linked to the ‘continental’ tradition of structural analysis) to contemporary communication forms and supports. In this way, semiotics appears as a specific form of qualitative analysis, aimed at the understanding of meaning production by social actors on the basis of ‘signs’ (significant objects such as paper and electronic texts) that are produced and exchanged. From the point of view of the subject under analysis, I want to present some observations on recent pro-nuclear rhetorical forms, which have emerged in Europe in the last two years, before and after the tragedy of Fukushima. I analyse different types of texts, in particular videos and websites. The analysis of the ‘internal’ organization of texts is combined with attention to the context of their production.
The Effect of Food on Cysteamine Bitartrate Absorption in Healthy Participants
Authors: Dohil Ranjan , Cabrera Betty L. , Gangoiti Jon , Rioux Patrice
Published: September 2012

Objectives: Treatment with cysteamine reduces the rate of progression to end‐stage kidney disease in cystinosis. Although food is often taken with cysteamine to reduce associated gastrointestinal symptoms, this may alter the bioavailability of cysteamine. Methods: This is a prospective, randomized, 3‐treatment study to determine the effects of fasting and high‐fat/calorie and high‐protein meals on cysteamine absorption in healthy adult controls. On 3 separate days, serial plasma cysteamine levels were measured after cysteamine bitartrate 500 mg was ingested while fasting and also 30 minutes after high‐fat/calorie and high‐protein diets. Gastrointestinal (GI) symptoms were also monitored. Results: Eight participants (5 men) were enrolled. Cysteamine absorption, as measured by area under the cysteamine concentration‐time curve (AUC0‐∞) while fasted and following high‐fat/calorie and high‐protein meals, was 3618 ± 372 min·μM, 2799 ± 405 min·μM (P = .04 vs fasted), and 2457 ± 353 min·μM (P = .005), respectively, and the mean Cmax values for participants were 26.3 ± 3.5 μM, 22.4 ± 5.6 μM (P = .16 vs fasted), and 17.2 ± 2.6 μM (P = .036 vs fasted), respectively. Mild GI symptoms were reported in 3 participants. Conclusions: Cysteamine absorption may be decreased by 30% when taken with food as compared with the fasting state. Food causes wide variation in tmax and Cmax for cysteamine.
Vancomycin: Predictive Performance of a Population Pharmacokinetic Model and Optimal Dose in Neonates and Young Infants
Authors: Marsot Amélie , Vialet Renaud , Boulamery Audrey , Bruguerolle Bernard , Simon Nicolas
Published: September 2012

Introduction: Model evaluation is an important issue in population pharmacokinetic analyses. The objectives were to evaluate the predictive performance of previously published pediatric population pharmacokinetic models for vancomycin in a new data set and to propose an optimal dose to obtain a vancomycin concentration target. Methods: External evaluation was conducted for all the published models of vancomycin in neonates and young infants with a new data set of 70 patients. Bias and accuracy were calculated. Advanced analyses were performed to evaluate the predictive performance of the best model. This population pharmacokinetic analysis was performed to simulate doses of vancomycin according to the appropriate target concentration. Results: All models gave almost the same results, except 2 that were not acceptable. Nevertheless, the model described by Oudin et al presented the best results with a bias and accuracy of 4.0% and 27.8%, respectively. Simulations showed that the maintenance dose should be adjusted more precisely to each neonate based on his or her weight and serum creatinine value. Conclusion: Simulations have allowed the authors to describe new dosage schedules, and a chart was created to help clinicians to adapt dosage of vancomycin. Because of pharmacokinetic variability, vancomycin still requires therapeutic drug monitoring.
Effect of heat treatment on microstructure and mechanical properties of extruded ZM61 magnesium alloy
Authors: Qi F G , Zhang D F , Zhu Z T , Xu X X , Shi G L
Published: September 2012

The effects of T5 and T6 heat treatments on the microstructure and mechanical properties of extruded Mg–6Zn–1M n alloy were investigated in the present study. The results showed that T5 and T6 treatments could markedly improve the strengths of extruded ZM61 alloy, and the precipitate strengthening effect of double aging was better than that of single aging. The precipitates formed in the T6 treatment were much finer and more dispersive than the ones in the T5 treatment, resulting in stronger precipitation strengthening effect. However, due to additional grain size refinement strengthening effect, the T5 treatment could improve ductility without sacrificing strength over the T6 treatment. Scanning electron microscopy observation and tensile test indicated that different cooling methods after extrusion, such as air cooling and water quenching, had no obvious influence on the microstructure and strengths of extruded and subsequent heat treated Mg–6Zn–1Mn alloys. In addition, the Mn element mainly existed as fine Mn phase particles, which were well dispersed in the matrix. Dispersed Mn particles could be found in rod-like [Formula: see text] precipitates, but not in the disc shaped [Formula: see text] precipitates.
Comparative genomic analysis of NAC transcriptional factors to dissect the regulatory mechanisms for cell wall biosynthesis
Authors: Yao Dongxia , Wei Qiang , Xu Wenying , Syrenne Ryan D , Yuan Joshua S , Su Zhen
Published: September 2012

Background

NAC domain transcription factors are important transcriptional regulators involved in plant growth, development and stress responses. Recent studies have revealed several classes of NAC transcriptional factors crucial for controlling secondary cell wall biosynthesis. These transcriptional factors mainly include three classes, SND, NST and VND. Despite progress, most current analysis is carried out in the model plant Arabidopsis. Moreover, many downstream genes regulated by these transcriptional factors are still not clear.

Methods

In order to identify the key homologue genes across species and discover the network controlling cell wall biosynthesis, we carried out comparative genome analysis of NST, VND and SND genes across 19 higher plant species along with computational modelling of genes regulated or co-regulated with these transcriptional factors.

Results

The comparative genome analysis revealed that evolutionarily the secondary-wall-associated NAC domain transcription factors first appeared in Selaginella moellendorffii. In fact, among the three groups, only VND genes appeared in S. moellendorffii, which is evolutionarily earlier than the other two groups. The Arabidopsis and rice gene expression analysis showed specific patterns of the secondary cell wall-associated NAC genes (SND, NST and VND). Most of them were preferentially expressed in the stem, especially the second internodes. Furthermore, comprehensive co-regulatory network analysis revealed that the SND and MYB genes were co-regulated, which indicated the coordinative function of these transcriptional factors in modulating cell wall biosynthesis. In addition, the co-regulatory network analysis revealed many novel genes and pathways that could be involved in cell wall biosynthesis and its regulation. The gene ontology analysis also indicated that processes like carbohydrate synthesis, transport and stress response, are coordinately regulated toward cell wall biosynthesis.

Conclusions

Overall, we provided a new insight into the evolution and the gene regulatory network of a subgroup of the NAC gene family controlling cell wall composition through bioinformatics data mining and bench validation. Our work might benefit to elucidate the possible molecular mechanism underlying the regulation network of secondary cell wall biosynthesis.
Demand for pneumococcal vaccination under subsidy program for the elderly in Japan
Authors: Kondo Masahide , Yamamura Mariko , Hoshi Shu-Ling , Okubo Ichiro
Published: September 2012

Background

Vaccination programs often organize subsidies and public relations in order to obtain high uptake rates and coverage. However, effects of subsidies and public relations have not been studied well in the literature. In this study, the demand function of pneumococcal vaccination among the elderly in Japan is estimated, incorporating effects of public relations and subsidy.

Methods

Using a data from a questionnaire survey sent to municipalities, the varying and constant elasticity models were applied to estimate the demand function. The response variable is the uptake rate. Explanatory variables are: subsidy supported shot price, operating years of the program, target population size for vaccination, shot location intensity, income and various public relations tools. The best model is selected by c-AIC, and varying and constant price elasticities are calculated from estimation results.

Results

The vaccine uptake rate and the shot price have a negative relation. From the results of varying price elasticity, the demand for vaccination is elastic at municipalities with a shot price higher than 3,708 JPY (35.7 USD). Effects of public relations on the uptake rate are not found.

Conclusions

It can be suggested that municipalities with a shot price higher than 3,708 JPY (35.7 USD) could subsidize more and reduce price to increase the demand for vaccination. Effects of public relations are not confirmed in this study, probably due to measurement errors of variables used for public relations, and studies at micro level exploring individual’s response to public relations would be required.
Economic evaluation of a weight control program with e-mail and telephone counseling among overweight employees: a randomized controlled trial
Authors: van Wier Marieke F , Dekkers J Caroline , Bosmans Judith E , Heymans Martijn W , Hendriksen Ingrid JM , Pronk Nicolaas P , van Mechelen Willem , van Tulder Maurits W
Published: September 2012

Background

Distance lifestyle counseling for weight control is a promising public health intervention in the work setting. Information about the cost-effectiveness of such interventions is lacking, but necessary to make informed implementation decisions. The purpose of this study was to perform an economic evaluation of a six-month program with lifestyle counseling aimed at weight reduction in an overweight working population with a two-year time horizon from a societal perspective.

Methods

A randomized controlled trial comparing a program with two modes of intervention delivery against self-help. 1386 Employees from seven companies participated (67% male, mean age 43 (SD 8.6) years, mean BMI 29.6 (SD 3.5) kg/m2). All groups received self-directed lifestyle brochures. The two intervention groups additionally received a workbook-based program with phone counseling (phone; n=462) or a web-based program with e-mail counseling (internet; n=464). Body weight was measured at baseline and 24 months after baseline. Quality of life (EuroQol-5D) was assessed at baseline, 6, 12, 18 and 24 months after baseline. Resource use was measured with six-monthly diaries and valued with Dutch standard costs. Missing data were multiply imputed. Uncertainty around differences in costs and incremental cost-effectiveness ratios was estimated by applying non-parametric bootstrapping techniques and graphically plotting the results in cost-effectiveness planes and cost-effectiveness acceptability curves.

Results

At two years the incremental cost-effectiveness ratio was €1009/kg weight loss in the phone group and €16/kg weight loss in the internet group. The cost-utility analysis resulted in €245,243/quality adjusted life year (QALY) and €1337/QALY, respectively. The results from a complete-case analysis were slightly more favorable. However, there was considerable uncertainty around all outcomes.

Conclusions

Neither intervention mode was proven to be cost-effective compared to self-help.

Trial registration

ISRCTN04265725
Exciton-related nonlinear optical properties in cylindrical quantum dots with asymmetric axial potential: combined effects of hydrostatic pressure, intense laser field, and applied electric field
Authors: Zapata Alejandro , Acosta Ruben E , Mora-Ramos Miguel E , Duque Carlos A
Published: September 2012

The exciton binding energy of an asymmetrical GaAs-Ga1−x
Al
x
As cylindrical quantum dot is studied with the use of the effective mass approximation and a variational calculation procedure. The influence on this quantity of the application of a direct-current electric field along the growth direction of the cylinder, together with that of an intense laser field, is particularly considered. The resulting states are used to calculate the exciton-related nonlinear optical absorption and optical rectification, whose corresponding resonant peaks are reported as functions of the external probes, the quantum dot dimensions, and the aluminum molar fraction in the potential barrier regions.
Multiplex array proteomics detects increased MMP-8 in CSF after spinal cord injury
Authors: Light Matthew , Minor Kenneth H , DeWitt Peter , Jasper Kyle H , Davies Stephen JA
Published: September 2012

Introduction

A variety of methods have been used to study inflammatory changes in the acutely injured spinal cord. Recently novel multiplex assays have been used in an attempt to overcome limitations in numbers of available targets studied in a single experiment. Other technical challenges in developing pre-clinical rodent models to investigate biomarkers in cerebrospinal fluid (CSF) include relatively small volumes of sample and low concentrations of target proteins. The primary objective of this study was to characterize the inflammatory profile present in CSF at a subacute time point in a clinically relevant rodent model of traumatic spinal cord injury (SCI). Our other aim was to test a microarray proteomics platform specifically for this application.

Methods

A 34 cytokine sandwich ELISA microarray was used to study inflammatory changes in CSF samples taken 12 days post-cervical SCI in adult rats. The difference between the median foreground signal and the median background signal was measured. Bonferroni and Benjamini-Hochburg multiple testing corrections were applied to limit the False Discovery Rate (FDR), and a linear mixed model was used to account for repeated measures in the array.

Results

We report a novel subacute SCI biomarker, elevated levels of matrix metalloproteinase-8 protein in CSF, and discuss application of statistical models designed for multiplex testing.

Conclusions

Major advantages of this assay over conventional methods include high-throughput format, good sensitivity, and reduced sample consumption. This method can be useful for creating comprehensive inflammatory profiles, and biomarkers can be used in the clinic to assess injury severity and to objectively grade response to therapy.
Microsatellite instability in Marek’s Disease Virus infected primary chicken embryo fibroblasts
Authors: Zhou Zhenlei , Yao Dawei , Qiu Yan , Yang Deji
Published: September 2012

Background

Marek’s disease virus (MDV), an oncogenic α-herpes virus, causes a devastating disease in chickens characterized by development of lymphoblastoid tumors in multiple organs. Microsatellite instability (MSI), a symptom of defect in DNA mismatch repair function, is a form of genomic instability frequently detected in many types of tumors. However, the involvement of MSI in MDV-infected cells has not been investigated. In this study, we determined the presence and frequency of MSI in primary chicken embryo fibroblasts infected with or without MDV strain in vitro.

Results

118 distinct microsatellite markers were analyzed by polymerase chain reaction (PCR) in 21 samples. MSI was found in 91 of 118 markers, and 12 out of 118 demonstrated frequency of MSI at ≥ 40%. 27 of 118 microsatellite loci did not show microsatellite instability.

Conclusions

These findings showed that MSI was a real event occurring in primary chicken embryo fibroblasts infected with MDV in vitro as evidenced by the high frequency of MSI, and may be specifically associated with genome alteration of host cells during MDV infected.
Expression of the Transient Receptor Potential Channels TRPV1, TRPA1 and TRPM8 in Mouse Trigeminal Primary Afferent Neurons Innervating the Dura
Authors: Huang Dongyue , Li Shuyang , Dhaka Ajay , Story Gina M , Cao Yu-Qing
Published: September 2012

Background:

Migraine and other headache disorders affect a large percentage of the population and cause debilitating pain. Activation and sensitization of the trigeminal primary afferent neurons innervating the dura and cerebral vessels is a crucial step in the “headache circuit”. Many dural afferent neurons respond to algesic and inflammatory agents. Given the clear role of the transient receptor potential (TRP) family of channels in both sensing chemical stimulants and mediating inflammatory pain, we investigated the expression of TRP channels in dural afferent neurons.

Methods:

We used two fluorescent tracers to retrogradely label dural afferent neurons in adult mice and quantified the abundance of peptidergic and non-peptidergic neuron populations using calcitonin gene-related peptide immunoreactivity (CGRP-ir) and isolectin B4 (IB4) binding as markers, respectively. Using immunohistochemistry, we compared the expression of TRPV1 and TRPA1 channels in dural afferent neurons with the expression in total trigeminal ganglion (TG) neurons. To examine the distribution of TRPM8 channels, we labeled dural afferent neurons in mice expressing farnesylated enhanced green fluorescent protein (EGFPf) from a TRPM8 locus. We used nearest-neighbor measurement to predict the spatial association between dural afferent neurons and neurons expressing TRPA1 or TRPM8 channels in the TG.

Results and conclusions:

We report that the size of dural afferent neurons is significantly larger than that of total TG neurons and facial skin afferents. Approximately 40% of dural afferent neurons exhibit IB4 binding. Surprisingly, the percentage of dural afferent neurons containing CGRP-ir is significantly lower than those of total TG neurons and facial skin afferents. Both TRPV1 and TRPA1 channels are expressed in dural afferent neurons. Furthermore, nearest-neighbor measurement indicates that TRPA1-expressing neurons are clustered around a subset of dural afferent neurons. Interestingly, TRPM8-expressing neurons are virtually absent in the dural afferent population, nor do these neurons cluster around dural afferent neurons. Taken together, our results suggest that TRPV1 and TRPA1 but not TRPM8 channels likely contribute to the excitation of dural afferent neurons and the subsequent activation of the headache circuit. These results provide an anatomical basis for understanding further the functional significance of TRP channels in headache pathophysiology.
Preclinical evaluation of sunitinib, a multi-tyrosine kinase inhibitor, as a radiosensitizer for human prostate cancer
Authors: Brooks Colin , Sheu Tommy , Bridges Kathleen , Mason Kathy , Kuban Deborah , Mathew Paul , Meyn Raymond
Published: September 2012

Background

Many prostate cancers demonstrate an increased expression of growth factor receptors such as vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor (PDGFR) which have been correlated with increased resistance to radiotherapy and poor prognosis in other tumors. Therefore, response to radiation could potentially be improved by using inhibitors of these abnormally activated pathways. We have investigated the radiosensitizing effects of sunitinib, a potent, multi-tyrosine kinase inhibitor of the VEGFR and PDGFR receptors, on human prostate cancer cells.

Methods

The radiosensitizing effects of sunitinib were assessed on human prostate cancer cell lines DU145, PC3 and LNCaP by clonogenic assay. Sunitinib’s ability to inhibit the activities of its key targets was determined by immunoblot analysis. The radiosensitizing effects of sunitinib in vivo were tested on human tumor xenografts growing in nude mice where response was assessed by tumor growth delay.

Results

Clonogenic survival curve assays for both DU145 and PC3 cells showed that the surviving fraction at 2 Gy was reduced from 0.70 and 0.52 in controls to 0.44 and 0.38, respectively, by a 24 hr pretreatment with 100 nM sunitinib. LNCaP cells were not radiosensitized by sunitinib. Dose dependent decreases in VEGFR and PDGFR activation were also observed following sunitinib in both DU145 and PC3 cells. We assessed the ability of sunitinib to radiosensitize PC3 xenograft tumors growing in the hind limb of nude mice. Sunitinib given concurrently with radiation did not prolong tumor growth delay. However, when animals were treated with sunitinib commencing the day after fractionated radiation was complete, tumor growth delay was enhanced compared to radiation alone.

Conclusions

We conclude, based on the in vivo results, that sunitinib and radiation do not interact directly to radiosensitize the PC3 tumor cells in vivo as they did in vitro. The fact that tumor growth delay was enhanced when sunitinib was given after radiotherapy was completed suggests that sunitinib may be acting on the irradiated tumor stroma and suppressing its ability to sustain regrowth of the irradiated tumor. Based on these preclinical findings, we suggest that the combination of sunitinib and radiation for the treatment of prostate cancer deserves further development.
Age-related Epstein-Barr virus-positive cutaneous ulcer arising after a self-limited subcutaneous abscess: a case report
Authors: Sadiku Shemsedin , Kurshumliu Fisnik , Krasniqi Xhevdet , Brovina Ahmet , Kryeziu Emrush , Rrudhani Ibrahim , Meqa Kastriot , Gashi-Luci Lumturije , Merz Hartmut
Published: September 2012

Introduction

Epstein-Barr virus-positive mucocutaneous ulcer is a newly recognized clinicopathologic entity in the spectrum of Epstein-Barr virus-positive lymphoproliferative disorders. This entity is characterized by a self-limited, indolent course.

Case presentation

We report the case of a 74-year-old, type 2 diabetic man who presented with an ulceroinfiltrative skin lesion on the left side of his neck. Histological examination showed that the lesion consisted of large atypical cells, some with Hodgkin-Reed-Sternberg-like morphology, in the midst of reactive lymphocytes, plasma cells, eosinophils and histiocytes. The atypical cells were partially positive for CD45, CD20, CD79a, CD30, B-cell lymphoma 2 and latent membrane protein 1 (CS.1-4), and negative for CD15, B-cell lymphoma 6 and CD10. In situ hybridization for Epstein-Barr virus-encoded ribonucleic acid was positive. Two years before, the patient had been diagnosed with a self-limited subcutaneous abscess in the same anatomic area that healed after antibiotic therapy.

Conclusion

Older patients with positive Epstein-Barr virus serology may develop B-cell lymphoproliferations due to age-related immune suppression. Epstein-Barr virus-encoded ribonucleic acid testing and clonality analysis, eventually complemented with close clinical follow-up, should be performed for suspicious inflammatory lesions in older patients.
Life cycle of Renylaima capensis, a brachylaimid trematode of shrews and slugs in South Africa: two-host and three-host transmission modalities suggested by epizootiology and DNA sequencing
Authors: Sirgel Wilhelm F , Artigas Patricio , Bargues M Dolores , Mas-Coma Santiago
Published: September 2012

Background

The life cycle of the brachylaimid trematode species Renylaima capensis, infecting the urinary system of the shrew Myosorex varius (Mammalia: Soricidae: Crocidosoricinae) in the Hottentots Holland Nature Reserve, South Africa, has been elucidated by a study of its larval stages, epizootiological data in local snails and mammals during a 34-year period, and its verification with mtDNA sequencing.

Methods

Parasites obtained from dissected animals were mounted in microscope slides for the parasitological study and measured according to standardized methods. The mitochondrial DNA cox 1 gene was sequenced by the dideoxy chain-termination method.

Results

The slugs Ariostralis nebulosa and Ariopelta capensis (Gastropoda: Arionidae) act as specific first and second intermediate hosts, respectively. Branched sporocysts massively develop in A. nebulosa. Intrasporocystic mature cercariae show differentiated gonads, male terminal duct, ventral genital pore, and usually no tail, opposite to Brachylaimidae in which mature cercariae show a germinal primordium and small tail. Unencysted metacercariae, usually brevicaudate, infect the kidney of A. capensis and differ from mature cercariae by only a slightly greater size. The final microhabitats are the kidneys and ureters of the shrews, kidney pelvis and calyces in light infections and also kidney medulla and cortex in heavy infections. Sporocysts, cercariae, metacercariae and adults proved to belong to R. capensis by analysis of a 437-bp-long cox 1 fragment, which was identical except for three mutations in metacercariae, of which only one silent. Epizootiological studies showed usual sporocyst infection in A. nebulosa and very rare metacercarial infection in A. capensis, which does not agree with high prevalences and intensities in the shrews.

Conclusions

The presence of monotesticular adult forms and larval prevalences and intensities observed suggest that R. capensis may use two transmission strategies, a two-host life cycle by predation of A. nebulosa harbouring intrasporocystic cercariae may be the normal pattern, whereas a second mollusc host is just starting to be introduced. In shrews, a tissue-traversing, intraorganic migration followed by an interorganic migration to reach and penetrate the outer surface of either of both kidneys should occur. For first slug infection, the fluke takes advantage of the phenomenon that M. varius always urinate during defaecation. Consequently, in Brachylaimidae, the second intermediate mollusc host should evolutionarily be seen as a last addition to the cycle and their present adult stage microhabitat restricted to digestive tract and related organs as a loss of the tissue-traversing capacity of the metacercaria.
Knockdown of clusterin sensitizes pancreatic cancer cells to gemcitabine chemotherapy by ERK1/2 inactivation
Authors: Tang Yong , Liu Fenghua , Zheng Chunning , Sun Shaochuan , Jiang Yingsheng
Published: September 2012

Objectives

To study the hypothesis that gemcitabine treatment augments the chemoresistance to gemcitabine by clusterin (sCLU) upregulation. Clusterin inhibition could augment the chemosensitivity of human pancreatic cancer cells by inhibition of clusterin-dependent pERK1/2 activation.

Methods

Clusterin was silenced by serial concentration of OGX-011 transfection in pancreatic cancer MIAPaCa-2 and BxPC-3 cell lines, then treated with serial concentration of gemcitabine. After the cells were treated with OGX-011 for 8 h, the cells were then treated with 5 μM ERK inhibitor PD98059 for 18 h or transfected with a wt-pERK-expressing plasmid into these cells for 24 h, after which the cells were treated with 1.0 uM gemcitabine for 24–72 h. Cell proliferation was determined by MTT. Apoptosis was quantified by flow cytometry,.sCLU and pERK1/2 production was analyzed by western blot, and sCLU mRNA was analyzed by RT-PCR. Xenograft of established tumors was used to evaluate primary tumor growth and apoptosis after treatment with gemcitabine alone or in combination with OGX-011. Phosphorylated ERK1/2 and sCLU levels in tumor tissues were measured by TUNEL analysis.

Results

As detected by MTT and FACS assay, a combination of gemcitabine + OGX-011 reflected the chemotherapeutic sensitivity and increased the gemcitabine -induced apoptosis in MIAPaCa-2 and BxPC-3 cells. Western blotting and RT-PCR analysis revealed that the expression of clusterin was higher in gemcitabine -resistant MIAPaCa-2 cells, however, decreased significantly after pretreatment with OGX-011. Furthermore, the OGX-011 or combination of gemcitabine + OGX-011 decreased the gemcitabine -induced activation of pERK1/2. wt-pERK-re-expression decreased OGX-011+ gemcitabine -induced apoptosis. Finally, OGX-011 in combination with gemcitabine substantially decreased the in vivo tumor growth and promoted apoptosis. Taken together, clusterin confers gmcitabine resistance in pancreatic cancer cells.

Conclusions

Knockdown of clusterin by OGX-011 transfection sensitizes pancreatic cancer cells to gemcitabine by inhibition of gemcitabine -induced clusterin-pERK1/2 activation.
Enforced effect of tk-MCP-1 fusion gene in ovarian cancer
Authors: Hong Shuhui , Zhang Ping , Zhang Hui , Jia Lin , Qu Xun , Yang Qifeng , Rong Fengnian , Kong Beihua
Published: September 2012

Objective

The efficiency of HSV-tk/GCV system is not high because of insufficient gene transfer and incompletely initiative of host antineoplastic potency. The present study was designed to assess the antitumor efficacy of tk-MCP-1 on ovarian cancer in vitro and vivo.

Methods

A novel bicistronic expression system can help to improve the expression level of a gene in a stable manner. pLXSN/tk-MCP-1 co-expressing tk and MCP-1 genes was constructed using a pLXSN retroviral vector and an internal ribosome entry site sequence by restriction enzyme. Western blot was performed to determine tk and MCP-1 expression in the infected SKOV3. The GCV-sensitively tumoricidal activities of SKOV3/tk-MCP-1 with or without monocytes were compared to those of SKOV3expressing HSV-tk or MCP-1. We investigated the growth of subcutaneous tumors in SCID mice immuno-reconstituted, and evaluated the antitumor effect of MCP-1 in conjunction with suicide gene.

Results

The significant GCV-sensitively tumoricidal activity of pLXSN/tk-MCP-1 was observed when compared with those of pLXSN/tk, pLXSN/MCP-1 and pLXSN/neo, especially when monocytes were added. The growth of subcutaneous tumors in SCID mice immuno-reconstituted was markedly suppressed by co-delivery of HSV-tk and MCP-1 genes, and the enhanced antitumor effect was associated with the recruitment of monocytes.

Conclusion

These results demonstrated pLXSN/tk-MCP-1 presented an enhanced antitumor effects on ovarian cancer by orchestration of immune responses.
Hierarchical super-structure identified by polarized light microscopy, electron microscopy and nanoindentation: Implications for the limits of biological control over the growth mode of abalone sea shells
Authors: Schneider Andreas S , Heiland Birgit , Peter Nicolas J , Guth Christina , Arzt Eduard , Weiss Ingrid M
Published: September 2012

Background

Mollusc shells are commonly investigated using high-resolution imaging techniques based on cryo-fixation. Less detailed information is available regarding the light-optical properties. Sea shells ofHaliotis pulcherinawere embedded for polishing in defined orientations in order to investigate the interface between prismatic calcite and nacreous aragonite by standard materialographic methods. A polished thin section of the interface was prepared with a defined thickness of 60 μm for quantitative birefringence analysis using polarized light and LC-PolScope microscopy. Scanning electron microscopy images were obtained for comparison. In order to study structural-mechanical relationships, nanoindentation experiments were performed.

Results

Incident light microscopy revealed a super-structure in semi-transparent regions of the polished cross-section under a defined angle. This super-structure is not visible in transmitted birefringence analysis due to the blurred polarization of small nacre platelets and numerous organic interfaces. The relative orientation and homogeneity of calcite prisms was directly identified, some of them with their optical axes exactly normal to the imaging plane. Co-oriented "prism colonies" were identified by polarized light analyses. The nacreous super-structure was also visualized by secondary electron imaging under defined angles. The domains of the super-structure were interpreted to consist of crystallographically aligned platelet stacks. Nanoindentation experiments showed that mechanical properties changed with the same periodicity as the domain size.

Conclusions

In this study, we have demonstrated that insights into the growth mechanisms of nacre can be obtained by conventional light-optical methods. For example, we observed super-structures formed by co-oriented nacre platelets as previously identified using X-ray Photo-electron Emission Microscopy (X-PEEM) [Gilbert et al., Journal of the American Chemical Society 2008, 130:17519–17527]. Polarized optical microscopy revealed unprecedented super-structures in the calcitic shell part. This bears, in principle, the potential for in vivo studies, which might be useful for investigating the growth modes of nacre and other shell types.
A Japanese case of chronic lymphocytic leukemia with t (1;6)
Authors: Harada Kayo , Ikeda Kazuhiko , Matsumoto Hayato , Furukawa Miki , Takahashi Hiroshi , Ohkawara Hiroshi , Noji Hideyoshi , Tasaki Kazuhiro , Abe Masafumi , Ogawa Kazuei , Takeishi Yasuchika
Published: September 2012

Chronic lymphocytic leukemia (CLL) rarely exhibits an aggressive clinical course and its patients often have chromosomal deletions or additions. Furthermore, reciprocal translocations are barely observed in CLL. There have only been a few reports of CLL with t(1;6), and here we report the first Asian case of CLL with reciprocal translocation t(1;6). Since our case and previously reported CLL patients with t(1;6) consistently showed aggressive clinical course, t(1;6) may define a distinct type of CLL.
Beyond Synergy: Corticosterone and Thyroid Hormone Have Numerous Interaction Effects on Gene Regulation in Xenopus tropicalis Tadpoles
Authors: Kulkarni Saurabh S. , Buchholz Daniel R.
Published: September 2012

Hormones play critical roles in vertebrate development, and frog metamorphosis has been an excellent model system to study the developmental roles of thyroid hormone (TH) and glucocorticoids. Whereas TH regulates the initiation and rate of metamorphosis, the actions of corticosterone (CORT; the main glucocorticoid in frogs) are more complex. In the absence of TH during premetamorphosis, CORT inhibits development, but in the presence of TH during metamorphosis, CORT synergizes with TH to accelerate development. Synergy at the level of gene expression is known for three genes in frogs, but the nature and extent of TH and CORT cross talk is otherwise unknown. Therefore, to examine TH and CORT interactions, we performed microarray analysis on tails from Xenopus tropicalis tadpoles treated with CORT, TH, CORT+TH, or vehicle for 18 h. The expression of 5432 genes was significantly altered in response to either or both hormones. Using Venn diagrams and cluster analysis, we identified 16 main patterns of gene regulation due to up- or down-regulation by TH and/or CORT. Many genes were affected by only one of the hormones, and a large proportion of regulated genes (22%) required both hormones. We also identified patterns of additive or synergistic, inhibitory, subtractive, and annihilatory regulation. A total of 928 genes (17%) were regulated by novel interactions between the two hormones. These data expand our understanding of the hormonal cross talk underlying the gene regulation cascade directing tail resorption and suggest the possibility that CORT affects not only the timing but also the nature of TH-dependent tissue transformation.
Use of ESI-MS to Determine Reaction Pathway for Hydrogen Sulphide Scavenging with 1,3,5-Tri-(2-Hydroxyethyl)-Hexahydro-s-Triazine
Authors: Madsen Henrik T. , Søgaard Erik G.
Published: September 2012

To study the reaction between hydrogen sulphide and 1,3,5-tri-(2-hydroxyethyl)-hexahydro- s-triazine, which is an often used hydrogen sulphide scavenger, electrospray ionisation mass spectrometry (ESI-MS) was used. The investigation was carried out in positive mode and tandem mass spectrometry was used to investigate the nature of unknown peaks in the mass spectra. The reaction was found to proceed as expected from theory with the triazine reacting with hydrogen sulphide to form the corresponding thiadiazine. This species subsequently reacted with a second hydrogen sulphide molecule to form the dithiazine species, thereby confirming previously obtained results and showing the ability of the ESI-MS method for studying the scavenging reaction. The final theoretical product s-trithiane was not detected. Furthermore, fragmentation products of thiadiazine and dithiazine were detected in the solution and possible pathways and structures were suggested to describe the observed fragments. In these, thiadiazine fragmented to 2-(methylidene amino)-ethanol and 2-(1,3-thiazetidin-3-yl)-ethanol and N-(2-hydroxyethyl)- N-(sulfanylmethyl)-ethaniminium, which underwent a further fragmentation to N-methyl- N-(2-oxoethyl)-methaniminium. Dithiazine fragmented to N-methyl- N-(2-oxoethyl)-methaniminium as well. The byproduct from this reaction is methanedithiol, which was not detected due to its low polarity.
Design and Performance of a Desktop Time-of-Flight Mass Spectrometer for Analyzing Metal Ions
Authors: Guo Changjuan , Gao Wei , Huang Zhengxu , Zhu Hui , Fu Zhong , Dong Junguo , Cheng Ping , Zhou Zhen
Published: September 2012

We have described a home-made desktop orthogonal-injection time-of-flight (O-ToF) mass spectrometer combining a collisional cooling system. This O-ToF consists of a simple electrospray ion source, an atmosphere–vacuum interface, an area of transmission, including a radio-frequency only quadrupole (RF-only quadrupole, RFQ) as a collisional cooling cell and an orthogonal ToF mass analyzer. In order to detect ions of small m/z value, such as small metal ions, the RFQ has been improved to weaken the mass discrimination effect against low mass ions. Metal salt solutions were used in the experiment. The system has shown a satisfactory resolving power in the spectra ( m/A m = 3500), a good mass stability, a limit of detection of 80 fg and a mass accuracy of 48 ppm. The dynamic range is found to be from 10−8 mol L−1 to 10−5 mol L−1, allowing the semi-quantitative analysis of metal ions.
A model for calculating the within-subject biological variation and likelihood ratios for analytes with a time-dependent change in concentrations; exemplified with the use of D-dimer in suspected venous thromboembolism in healthy pregnant women
Authors: Kristoffersen Ann-Helen , Petersen Per H , Sandberg Sverre
Published: September 2012

Background

Within-subject biological variation and reference change value (RCV) are difficult to calculate for an analyte with a changing concentration. The aim of this study was to develop a model to examine if it was possible to transform an analyte with a time-dependent change in concentration into a ‘steady -state’ situation by the use of ‘multiples of the median’ (MoM) and its natural logarithm (lnMoM). In addition, we wanted to extend the RCV concept, using likelihood and odds ratios, to calculate the post-test probabilities for disease. D-dimer in pregnancy is used as an example.

Methods

Blood samples from 18 healthy pregnant and 18 healthy non-pregnant women were collected every fourth week. MoM of the D-dimer concentrations was calculated for each four-week interval to obtain a ‘steady-state’ situation for the D-dimer concentrations. The ‘normalized’ values were then transformed to the lnMoM to obtain a Gaussian distribution, used for the estimation of biological variation.

Results

Median D-dimer concentrations increased six-fold during pregnancy. Within-subject variation (SD) of lnMoM D-dimer was 0.27 during pregnancy and 0.23 in non-pregnant women, with RCVs of 0.72 and 0.90, respectively.

Conclusions

By using the lnMoM model, an increasing concentration of an analyte can be transformed to a steady-state situation and the within-subject biological variation and its derived parameters can be calculated.
Failure and Rescue in an Interbank Network
Authors: Rogers L. C. G. , Veraart L. A. M.
Published: September 2012

This paper is concerned with systemic risk in an interbank market, modelled as a directed graph of interbank obligations. This builds on the modelling paradigm of Eisenberg and Noe [Eisenberg L, Noe TH (2001) Systemic risk in financial systems. Management Sci. 47(2):236–249] by introducing costs of default if loans have to be called in by a failing bank. This immediately introduces novel and realistic effects. We find that, in general, many different clearing vectors can arise, among which there is a greatest clearing vector, arrived at by letting banks fail in succession until only solvent banks remain. Such a collapse should be prevented if at all possible. We then study situations in which consortia of banks may have the means and incentives to rescue failing banks. This again departs from the conclusions of the earlier work of Eisenberg and Noe, where in the absence of default losses there would be no incentive for solvent banks to rescue failing banks. We conclude with some remarks about how a rescue consortium might be constructed.

This paper was accepted by Wei Xiong, finance.
Add-on Pricing by Asymmetric Firms
Authors: Shulman Jeffrey D. , Geng Xianjun
Published: September 2012

This paper uses an analytical model to examine the consequences of add-on pricing when firms are both horizontally and vertically differentiated and there is a segment of boundedly rational consumers who are unaware of the add-on fees at the time of initial purchase. We find that consumers who know the add-on fees can be penalized—and increasingly so—by the existence of boundedly rational consumers. Our consideration of quality asymmetries on base goods and add-ons, plus the inclusion of boundedly rational consumers, leads to several novel findings regarding firm profits. When quality asymmetry is on base goods only and with boundedly rational consumers, add-on pricing can diminish profit for a qualitatively superior firm and increase profit for an inferior firm (i.e., a lose–win result), compared to when add-on pricing is prohibited or infeasible. When quality asymmetries exist on both base goods and add-ons and without boundedly rational consumers, the opposite win–lose result prevails. When quality asymmetries exist on both base goods and add-ons and with boundedly rational consumers, the result can be win–win, win–lose, or lose–win, depending on the magnitude of quality differentiation on add-ons.

This paper was accepted by J. Miguel Villas-Boas, marketing.
Publicizing Performance
Authors: Strobl Günter , Van Wesep Edward D.
Published: September 2012

In most employment relationships, the employee's performance at the firm is privately, not publicly, observed. Firms can reward successful employees by publicizing their abilities, for example, via a job title, a glowing letter of recommendation, or a resume-worthy award. Firms that establish reputations for hiring young workers and promoting those who succeed lose good workers to competitors but can pay less to young, inexperienced workers in exchange. We find in a general equilibrium setting that firms with reputations for publicizing performance are able to pay less to employees at every level of tenure and thus earn economic profit, but that these firms will never be the most productive in the economy. For such equilibria to exist, the worker–firm match must be important, suggesting that this practice takes place only in human-capital-intensive industries.

This paper was accepted by Wei Xiong, finance.