bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

AbstractObjectiveThe 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.MethodsA 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.ResultsThe 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.ConclusionThese 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

AbstractBackgroundMollusc 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.ResultsIncident 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.ConclusionsIn 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

Abstract
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

AbstractHormones 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.
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.