bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract A23: Identification of KJ-Pyr-9 as a potent MYC inhibitor
Authors: Hart Jonathan R. , Bister Klaus , Janda Kim D. , Vogt Peter K.
Published: October 2015

We have identified a novel small-molecule inhibitor of MYC, KJ-Pyr-9, from a Kröhnke pyridine library. KJ-Pyr-9 functions as an inhibitor of MYC in biochemical assays, in cells and in xenograft experiments. In vitro, KJ-Pyr-9 binds to MYC as well as MYC-MAX dimers and can disrupt binding of MYC-MAX dimers with E-box DNA. In cells, MYC-MAX dimerization can be disrupted in cells as demonstrated by protein fragment complementation assays. KJ-Pyr-9 disrupts the transcriptional targets of MYC. The P493-6 cell line has tetracycline regulatable MYC expression. For this cell line, the transcriptional targets of MYC can be readily observed upon the addition of 0.1 ug/mL doxycycline. Both doxycycline and KJ-Pyr-9 negatively regulate MYC transcriptional signatures as determined by GSEA. The growth of a variety of different MYC-dependent cell lines is inhibited, including MYC-translocated Burkitt's lymphoma cell lines expressing high levels of MYC as well as solid tumor cell lines expressing moderate amounts of MYC. In vivo, KJ-Pyr-9 effectively blocks the growth of a xenotransplant of MYC-amplified human cancer cells.

Acknowledgements: This work was supported by the National Cancer Institute under award number R01 CA078230 (PKV), The Skaggs Institute for Chemical Biology (KDJ) and by the Austrian Science Fund (FWF) grant P23652 (KB). This is manuscript 25089 of The Scripps Research Institute.

Citation Format: Jonathan R. Hart, Klaus Bister, Kim D. Janda, Peter K. Vogt. Identification of KJ-Pyr-9 as a potent MYC inhibitor. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr A23.
Abstract A27: Epigenomic and transcriptional analyses in a Tet-Myc driven mouse model of liver cancer
Authors: Kress Theresia , Bianchi Valerio , D'Artista Luana , Nicoli Paola , Doni Mirko , Radaelli Enrico , Amati Bruno
Published: October 2015

The c-myc proto-oncogene is frequently overexpressed in human hepatoblastoma due to gene amplification or constitutively active Wnt signaling. High Myc levels characterize an aggressive hepatoblastoma subtype, reproduced in mice with a liver-specific tetracyclin-regulated c-myc transgene (1, 2). Here, we used an analogous mouse model (tetO-MYC/Lap-tTA; ref. 3) to study the epigenomic and transcriptional mechanisms underlying tumor progression and maintenance. Tet-Myc induction in utero resulted in rapid and fully penetrant tumorigenesis by the age of six weeks. Pre-tumoral changes were detectable already at a late embryonic stage (E18.5) with increased liver size and hepatoblast fraction. As previously described (2), tumors remained dependent on the constitutive expression of the transgene. To study transcriptional changes during tumor progression and regression, we established RNA-seq profiles in control hepatoblasts, pre-tumoral Tet-Myc hepatoblasts and tumor nodules, in the latter before and after short-term inactivation of Tet-Myc. In parallel, we used ChIP-seq to profile the genome-wide distribution of Myc, RNAPII and several histone marks (H3K4me1, H3K4me3, H3K27ac), yielding comprehensive maps of Myc binding to regulatory elements (promoters and enhancers). This unique dataset is providing the basis for mechanistic studies addressing how Myc deregulates its target genes during liver tumorigenesis: comparison of differentially expressed mRNAs and Myc-binding profiles enables us to discriminate between directly and potentially indirectly regulated genes, for which we are currently investigating the underlying molecular basis. Furthermore, our genome-wide data are allowing us to unravel potentially druggable genes and pathways regulated by Myc during hepatoblastoma progression and maintenance. Our progress in characterizing this model will be presented at the meeting.

References:

1. Cairo S et al. 2008, Cancer Cell, 14:471-84

2. Shachaf CM et al. 2004, Nature, 431:1112-7

3. van Riggelen J et al. 2010, Genes Dev, 24:1281-94

Citation Format: Theresia Kress, Valerio Bianchi, Luana D'Artista, Paola Nicoli, Mirko Doni, Enrico Radaelli, Bruno Amati. Epigenomic and transcriptional analyses in a Tet-Myc driven mouse model of liver cancer. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr A27.
Abstract A35: MAX inactivation in small cell lung cancer disrupts the MYC-SWI/SNF programs and is synthetic lethal with BRG1
Authors: Torres-Diz Manuel , Romero Octavio A. , Pros Eva , Savola Suvi , Gomez Antonio , Moran Sebastian , Montuenga Luis M. , Yokota Jun , Sanchez-Cespedes Montse
Published: October 2015

Our knowledge of small cell lung cancer (SCLC) genetics is still very limited, amplification of L-MYC , N-MYC , and C-MYC being some of the well-established genealterations. Here, we report our discovery of tumor-specifi c inactivation of the MYC-associated factorX gene, MAX , in SCLC. MAX inactivation is mutually exclusive with alterations of MYC and BRG1 , thelatter coding for an ATPase of the switch/sucrose nonfermentable (SWI/SNF) complex. We demonstratethat BRG1 regulates the expression of MAX through direct recruitment to the MAX promoter, and thatdepletion of BRG1 strongly hinders cell growth, specifi cally in MAX-defi cient cells, heralding a syntheticlethal interaction. Furthermore, MAX requires BRG1 to activate neuroendocrine transcriptional programsand to upregulate MYC targets, such as glycolysis-related genes. Finally, inactivation of the MAXdimerization protein, MGA, was also observed in both non–small cell lung cancer and SCLC. Our resultsprovide evidence that an aberrant SWI/SNF–MYC network is essential for lung cancer development.

SIGNIFICANCE: We discovered that the MYC-associated factor X gene, MAX , is inactivated in SCLCs.Furthermore, we revealed a preferential toxicity of the inactivation of the chromatin remodeler BRG1in MAX-defi cient lung cancer cells, which opens novel therapeutic possibilities for the treatment ofpatients with SCLC with MAX-defi cient tumors.

Citation Format: Manuel Torres-Diz, Octavio A. Romero, Eva Pros, Suvi Savola, Antonio Gomez, Sebastian Moran, Luis M. Montuenga, Jun Yokota, Montse Sanchez-Cespedes. MAX inactivation in small cell lung cancer disrupts the MYC-SWI/SNF programs and is synthetic lethal with BRG1. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr A35.
Abstract A39: The mitochondrial translation machinery is a critical effector of Myc in lymphomagenesis
Authors: D'Andrea Aleco , Bianchi Valerio , Nicoli Paola , Amati Bruno
Published: October 2015

The Myc protein, encoded by the c-myc proto-oncogene, is a transcription factor that binds thousands of genomic loci. Based on genome-wide binding and expression profiles, we recently provided an exhaustive list of genes that are up- or down-regulated by Myc during B-cell lymphomagenesis in Eµ-myc transgenic mice (Sabò et al. 2014 Nature 511, 488-492). Which among those Myc-regulated genes are critical effectors in tumor progression and maintenance remained largely unknown. Here, we show that concerted activation by Myc of the mitochondrial translation machinery is critical for the maintenance of Myc-induced lymphomas. A majority of genes encoding for Mitochondrial Ribosomal Proteins (MRPs) and other associated polypeptides were directly up-regulated by Myc in Eµ-myc lymphomas. Among those was the gene encoding PTCD3, a Pentatricopeptide repeat protein involved in mitochondrial translation (Davies et al. 2009 FEBS Lett. 583, 1853-1858). RNAi-based knockdown of PTCD3 or several MRPs conferred a selective disadvantage in lymphoma cells, owing to impaired cell proliferation. As expected PTCD3 knockdown in lymphomas was also accompanied by a reduction in the levels of mitochondrial-encoded protein COX-I. Chemical inhibition of mitochondrial translation with Tigecycline led to rapid death of Eµ-myc lymphoma cells in vitro. We are currently testing the effect of Tigecycline on lymphoma growth in vivo.

Citation Format: Aleco D'Andrea, Valerio Bianchi, Paola Nicoli, Bruno Amati. The mitochondrial translation machinery is a critical effector of Myc in lymphomagenesis. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr A39.
Abstract A41: Shaping Myc-dependent transcriptional amplification
Authors: Lin Charles , Bradner James E.
Published: October 2015

Myc deregulation, resulting in the elevated and constitutive expression of the protein, is a common oncogenic event that gives rise to numerous tumorigenic phenotypes in multiple tumor types. When, elevated, Myc acts as a general transcriptional regulator, non-linearly amplifying the expression of most transcriptionally active genes in the tumor cell. However the gene specific contexts that shape this non-linear response are poorly understood. Here we report that in B-cells, transcriptional response at active genes is largely a function of the change in Myc occupancy at promoter regions, consistent with Myc dependent transcriptional amplification. To explore determinants of Myc binding affinity, changes in Myc promoter occupancy were compared to sequence, transcription, and chromatin features in cells prior to Myc elevation. Changes in Myc occupancy correlate most strongly with promoter GC content rather than with the density of Myc E-box binding motifs or any other analyzed promoter feature. The ability of GC rich promoters to garner increased Myc occupancy levels suggest that general structural sequence and regulatory features of the promoter play a role in shaping Myc binding affinity. Importantly, Myc binding affinity, although generally correlating with transcriptional response, fails to articulate much of the observed gene expression variance suggesting that additional regulatory layers, including Myc interacting co-regulators such as MIZ1, likely contribute to shaping Myc dependent transcriptional responses.

Citation Format: Charles Lin, James E. Bradner. Shaping Myc-dependent transcriptional amplification. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr A41.
Abstract B02: The role of the immune system in sustained tumor regression following oncogene inactivation
Authors: Casey Stephanie C. , Do Rachel K. , Felsher Dean W.
Published: October 2015

The MYC oncogene has been implicated in the pathogenesis of many types of human cancer. The Felsher laboratory uses a conditional Tet-off MYC mouse model to study the formation of tumors in multiple tissue types, such as lymphoma, and has demonstrated that MYC-induced tumorigenesis is reversible. We have found that many cancers are “oncogene addicted” to MYC. Our laboratory has shown that an adaptive T cell-mediated immune response is essential for sustained tumor regression upon MYC inactivation (Rakhra et al, Cancer Cell, 2010). Now, we have found evidence suggesting that upon MYC inactivation in tumors, B cells are activated and are critical to tumor regression. MYC inactivation in a tumor was associated with the induction of an antibody-mediated response against tumor cells. This humoral response could mediate the killing of tumor cells in an Antibody-Dependent Cellular Cytotoxicity (ADCC) assay. Our work suggests that MYC inactivation results in a B cell-mediated immune response and that ADCC may contribute to tumor regression.

Citation Format: Stephanie C. Casey, Rachel K. Do, Dean W. Felsher. The role of the immune system in sustained tumor regression following oncogene inactivation. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr B02.
Abstract B30: Regulation of the core pre-mRNA splicing machinery by MYC and PRMT5 is essential to sustain lymphomagenesis
Authors: Koh Cheryl , Bezzi Marco , Low Diana , Ang WeiXia , Teo ShunXie , Gay Florence , Haddawi Muthafar Al , Tan SooYong , Osato Motomi , Sabo' Arianna , Wee KengBoon , Amati Bruno , Guccione Ernesto
Published: October 2015

Deregulated expression of the MYC transcription factor occurs in a majority of human cancers and correlates with high proliferation, reprogrammed cellular metabolism and poor prognosis. Over-expressed MYC binds to virtually all active promoters within a cell, although with different binding affinities, and modulates the expression of distinct subsets of genes. However, the critical effectors of MYC in tumorigenesis remain largely unknown.

Here, we show that during lymphomagenesis in Eµ-myc transgenic mice, MYC directly up-regulates the transcription of the core snRNP assembly genes, including Prmt5, an arginine methyltransferase that methylates Sm proteins. This coordinated regulatory effect is critical for snRNP biogenesis, effective mRNA splicing, cell survival and proliferation. Indeed, Prmt5 haplo-insufficiency significantly delays lymphoma onset in Eµ-myc transgenic mice and the acute deletion of PRMT5 in established lymphomas enhances the survival of tumor-bearing animals. In human lymphomas and leukemias, the expression of core snRNP genes also correlates with that of MYC, and PRMT5 knockdown results in aberrant pre-mRNA splicing and loss of viability. In both human or mouse lymphomas cells, MYC knockdown also reduces the expression of core snRNP components, causing aberrant pre-mRNA splicing.

Finally, we identify pre-mRNAs that are particularly sensitive to perturbation of the MYC-PRMT5 axis, resulting in either intron retention or exon skipping. Using antisense oligonucleotides (ASOs), we mimic these splicing defects and demonstrate their individual contribution to the anti-proliferative/apoptotic phenotype observed in Eµ-myc B-cells.

Thus, coordinate regulation of the core snRNP assembly machinery and PRMT5 is critical for the maintenance of normal pre-mRNA splicing and cell survival upon oncogenic activation of c-myc, pointing to PRMT5 methyl-transferase activity as a potential therapeutic target in MYC-driven tumors.

Citation Format: Cheryl Koh, Marco Bezzi, Diana Low, WeiXia Ang, ShunXie Teo, Florence Gay, Muthafar Al Haddawi, SooYong Tan, Motomi Osato, Arianna Sabo', KengBoon Wee, Bruno Amati, Ernesto Guccione. Regulation of the core pre-mRNA splicing machinery by MYC and PRMT5 is essential to sustain lymphomagenesis. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr B30.
Abstract IA09: Dynamic regulation of MYC and MYCN ubiquitination
Authors: Aifantis Iannis
Published: October 2015

The Myc proto-oncogenes have a well-established role in cellular transformation as well as in the maintenance of stem cells. Although the majority of previous studies have focused on the transcriptional regulation of Myc, the observation that Myc proteins have exceptionally short half-lives and that small perturbations in their expression lead to vast physiological consequences has illuminated the considerable importance of their post-translational regulators. Accordingly, FBXW7, which encodes a crucial subunit of the E3 ligase complex that polyubiquitylates both c-myc and N-myc, is one of the most frequently mutated genes in human cancers, including T-cell acute lymphoblastic leukemia (T-ALL). To study the effects of such lesions, we generated animals carrying regulatable Fbxw7 mutant alleles. We haave demonstrated that these mutations specifically bolster tumor-initiating activity in collaboration with NOTCH1 oncogenes, but spare normal hematopoietic stem cell (HSC) function. Stabilization of c-myc defines leukemia-initiating cells (LIC) and we demonstrated that the LIC population can be specifically ablated in vivo by depletion of c-myc, genetically or pharmacologically. Finally, we uncover a novel role for the HECT-family E3 ligase Huwe1 in the maintenance of HSC self-renewal and show that it functions specifically by controlling the stability of N-myc, but not c-myc. Molecular targets and interplay between c-Myc and N-Myc will be also presented and discussed, with a focus on hematopoiesis and induction of leukemia.

Citation Format: Iannis Aifantis. Dynamic regulation of MYC and MYCN ubiquitination. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr IA09.
Abstract IA23: An ancient signaling mechanism mediates the response of cells to fitness differences arising during tissue growth
Authors: Johnston Laura A.
Published: October 2015

Much work indicates that cells in developing tissues and organs use conserved mechanisms that allow them to cooperate or compete with their neighbors. These mechanisms allow cells to sense and respond to growth changes in their immediate environment, help to promote appropriate size control and ensure optimal organ fitness. One such mechanism, called cell competition, monitors cellular fitness so that potentially unfit cells are prevented from contributing to the tissue. We have developed models to determine how cell competition is regulated. In one model, mosaic tissues that contain cells with increased activity of the Myc transcription factor “compete” with wild-type cells and instruct them to die. As a result the higher-Myc cells (“winners”) are stimulated to proliferate more to fill the space. In another, cells deficient in one copy of a ribosomal protein compete with wild-type cells for occupancy of the tissue. Our recent work reveals that both types of cell competition use specific cohorts of components of the evolutionarily ancient innate immune system to eliminate the weaker cells. We find that Toll-related receptors (TRRs) and the cytokine Spätzle lead to NFkB-dependent apoptosis in both “loser” cell populations. However, diverse “loser” cells require different TRRs and NFkB factors, and activate distinct pro-death genes. Our results imply that the particular response to cell fitness differences is stipulated by context, just as innate immune genes respond to a variety of microbial pathogens. Our findings demonstrate a functional repurposing of components of TRRs and NFkB signaling modules in an internal cell fitness surveillance system that operates during development.

Citation Format: Laura A. Johnston. An ancient signaling mechanism mediates the response of cells to fitness differences arising during tissue growth. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr IA23.
Abstract PR02: Dynamic epigenetic regulation of glioblastoma tumorigenicity through a LSD1-MYC-OLIG2 axis
Authors: Chen Clark , Kozono David , Li Jie , Nitta Masayuki , Sampetrean Oltea , Ng Kimberly , Gonda David , Kushwaha Deepa S. , Merzon Dmitry , Ramakrishnan Valya , Zhu Shan , Zhu Kaya , Matsui Hiroko , Harismendy Olivier , Hua Wei , Mao Ying , Kwon Chang-Hyuk , Ligon Keith L. , Saya Hideyuki , Carter Bob S. , Pizzo Donald P. , VandenBerg Scott R. , Furnari Frank , Cavenee Webster
Published: October 2015

Glioblastoma is one of the most devastating of human cancers, with near-uniform fatality within two years of diagnosis. Therapeutic failure is thought to be related to small subpopulation of cells that exhibit the properties of self-renewal and tumorigenicity. Understanding how such subpopulations attain and retain these properties remains a central question in oncology. One fundamental issue is whether tumorigenicity exists within a static population of elite cells or whether the capacity is stochastically acquired. To test these models, we assayed the tumorigenicity of single-cell subclones derived from long-terms passaged and primary patient-derived xenograft (PDX) glioblastoma lines. Our findings were best described by a hybrid model that is largely deterministic (elite) but with opportunities for dynamic (stochastic) interchange between non-tumorigenic and tumorigenic states. To identify molecular determinants of tumorigenicity, we performed gene expression profiling of the subclones. Analysis of the data suggested that tumorigenicity in glioblastoma is a dynamic property driven by variation in MYC expression, which in turn regulates Olig2 expression, a neural stem cell marker. Ectopic expression of MYC conferred tumorigenicty and MYC silencing abolished tumorigenicity in vitro and in vivo for multiple PDX and GEMM models. Transition between tumorigenic and non-tumorigenic cell states was associated with changes in histone modification at the MYC locus mediated by expression of lysine-specific demethylase 1 (LSD1). The model suggests a critical LSD1-MYC-OLIG2 axis that regulates the dynamic transition between glioblastoma cell states of differing tumorigenicity and unveils a novel framework for glioblastoma therapeutic development.

Citation Format: Clark Chen, David Kozono, Jie Li, Masayuki Nitta, Oltea Sampetrean, Kimberly Ng, David Gonda, Deepa S. Kushwaha, Dmitry Merzon, Valya Ramakrishnan, Shan Zhu, Kaya Zhu, Hiroko Matsui, Olivier Harismendy, Wei Hua, Ying Mao, Chang-Hyuk Kwon, Keith L. Ligon, Hideyuki Saya, Bob S. Carter, Donald P. Pizzo, Scott R. VandenBerg, Frank Furnari, Webster Cavenee. Dynamic epigenetic regulation of glioblastoma tumorigenicity through a LSD1-MYC-OLIG2 axis. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr PR02.
Femoral Access and Delivery of Continuous Renal Replacement Therapy Dose
Authors: Bellomo Rinaldo , Mårtensson Johan , Lo Serigne , Kaukonen Kirsi-Maija , Cass Alan , Gallagher Martin ,   for the RENAL study investigators and the Australian and New Zealand Intensive Care Clinical Trials Group
Published: October 2015

Aims: The study aims to describe the use of dialysis catheters in critically ill patients treated with continuous renal replacement therapy (CRRT) and to study the impact of femoral versus non-femoral access on CRRT dose. Methods: Statistical analysis and predictive modelling of data from the Randomized Evaluation of Normal vs. Augmented Level renal replacement therapy trial. Results: The femoral vein was the first access site in 937 (67%) of 1,399 patients. These patients had higher Acute Physiology and Chronic Health Evaluation and Sequential Organ Failure Assessment scores (p = 0.009) and lower pH (p < 0.001) but similar mortality to patients with non-femoral access (44 vs. 45%; p = 0.63). Lower body weight was independently associated with femoral access placement (OR 0.97, 95% CI 0.96-0.98). Femoral access was associated with a 1.03% lower CRRT dose (p = 0.05), but a 4.20% higher dose was achieved with 13.5 Fr catheters (p = 0.03). Conclusions: Femoral access was preferred in lighter and sicker patients. Catheter gauge had greater impact than catheter site in CRRT dose delivery. Video Journal Club “Cappuccino with Claudio Ronco” at http://www.karger.com/?doi=439581.
Phylogeography of the common toad (Bufo bufo, Lissamphibia: Anura) in Switzerland
Authors: Waser Lea E. , Schweizer Manuel , Schmidt Benedikt R. , Hertwig Stefan T.
Published: October 2015

WhileBufo bufois widespread in Europe, the closely relatedB. spinosusis parapatrically distributed in Western Europe and Northern Africa. The exact course of the contact zone between both taxa, however, is still unknown. 24 samples from Switzerland were analysed using mitochondrial and nuclear markers combined with 243 previously published samples from Europe and Asia. No haplotypes ofB. spinosuswere detected in Switzerland, only two mitochondrial haplotypes ofB. bufo: one north and south of the Alps, the other only north of the Alps. Both haplotypes are also widely distributed in Eastern and Central Europe. These results agree with a postglacial recolonisation of Central Europe from refugia on the Balkan Peninsula. The occurrence of one haplotype north and south of the Alps can be explained by colonisation either from the north by crossing the Alps or from the east along the southern edge of the Alps. The rapid postglacial recolonisation from Balkan refugia might have prevented the spread of southern haplotypes from Italy and ofB. spinosusfrom France.
An ethogram of the Humboldt squid Dosidicus gigas Orbigny (1835) as observed from remotely operated vehicles
Authors: Trueblood Lloyd A. , Zylinski Sarah , Robison Bruce H. , Seibel Brad A.
Published: October 2015

Many cephalopods can rapidly change their external appearance to produce multiple body patterns. Body patterns are composed of various components, which can include colouration, bioluminescence, skin texture, posture, and locomotion. Shallow water benthic cephalopods are renowned for their diverse and complex body pattern repertoires, which have been attributed to the complexity of their habitat. Comparatively little is known about the body pattern repertoires of open ocean cephalopods. Here we create an ethogram of body patterns for the pelagic squid,Dosidicus gigas. We used video recordings of squid made in situ via remotely operated vehicles (ROV) to identify body pattern components and to determine the occurrence and duration of these components. We identified 29 chromatic, 15 postural and 6 locomotory components forD. gigas, a repertoire rivalling nearshore cephalopods for diversity. We discuss the possible functional roles of the recorded body patterns in the behavioural ecology of this open ocean species.
Early Dynamics of Deep Blue XBT Probes
Authors: Bringas Francis , Goni Gustavo
Published: October 2015

Expendable bathythermographs (XBTs) are probes widely used to monitor global ocean heat content, variability of ocean currents, and meridional heat transports. In the XBT temperature profile, the depth is estimated from the time of descent in the water using a fall-rate equation. There are two main errors in these profiles: temperature and depth errors. The reduction of error in the estimates of the depth allows a corresponding reduction in the errors in the computations in which XBTs are used. Two experiments were carried out to study the effect of the deployment height on the depth estimates of Deep Blue XBT probes. During these experiments, XBTs were deployed from different heights. The motion of the probes after entering the water was analyzed to determine the position and the velocity of the probes as a function of time, which was compared to that obtained using the Hanawa et al. fall-rate equation. Results showed a difference or offset between the experimentally observed depths and those derived from Hanawa et al. This offset was found to be linked to the deployment height. To eliminate the offset in the fall-rate equation for XBTs deployed from different heights, a methodology is proposed here based on the initial velocities of the probes in the water (or deployment height). Results indicate that the depth estimates in the profiles need to be corrected for an offset, which in addition to having a launch height dependence is time dependent during the first 1.5 s of descent of the probe in the water, and constant after that.
Suppression of Tinnitus in Chinese Patients Receiving Regular Cochlear Implant Programming
Authors: Liu Ying , Wang Hong , Han Dong Xu , Li Ming Hua , Wang Yu , Xiao Yu Li
Published: October 2015

Objective:

To assess the clinical effect of cochlear implant programming on tinnitus.

Methods:

Tinnitus patients (n = 234) were divided into 3 groups: (1) preoperative tinnitus (n = 108), (2) postoperative tinnitus occurring before implant switch-on at week 4 (n = 88), and (3) tinnitus occurring more than 1 year postoperatively (n = 44). Patients in each group were randomly allocated into a programming subgroup that received programming for 12 weeks postoperatively or after tinnitus occurrence or a control subgroup. Impedance testing and the Tinnitus Handicap Inventory (THI) were performed preoperatively and at 4, 6, 8, and 12 weeks postoperatively (groups 1 and 2) or after tinnitus occurrence (group 3). Comparisons were performed using t tests and chi-square tests.

Results:

Impedance was significantly lower in the programming subgroup than in the control subgroup in groups 1 and 2 at 8 and 12 weeks and in group 3 at 12 weeks. The THI scores decreased in both programming and control subgroups in all groups. However, this decrease was pronounced in the programming subgroup, whereas in the control subgroup, it occurred slowly over time.

Conclusion:

Cochlear implant programming decreases impedance and improves tinnitus symptoms.
Treatment and Survival Trends in Glottic Carcinoma in Situ and Stage I Cancer From 1988 to 2012
Authors: Khaja Sobia F. , Hoffman Henry T. , Pagedar Nitin A.
Published: October 2015

Objective:

To identify trends in treatment and survival for patients with stage I glottic cancer and glottic carcinoma in situ (CIS).

Methods:

The 18-registry SEER data were analyzed for CIS and stage I glottic cancer. Treatment variables and observed and relative survival were assessed separately for stage I and glottic CIS.

Results:

Among 14 025 cases of stage I glottic cancer identified from 1988 to 2012, radiation was the most common treatment for all eras. An increase in surgical treatment occurred with a decline in combination therapy. There were 3169 cases of glottic CIS, with surgery the most common initial treatment but with radiotherapy increasing across the years. Relative survival was similar for treatment type and era of diagnosis. Among the 3738 patients with glottic CIS, 5.4% went on to develop invasive glottic carcinoma of any stage, with invasive cancer more common in patients treated by surgery alone compared to radiation or surgery with radiation.

Conclusions:

Despite changes in treatment modalities for CIS and stage I glottic cancer, there have not been significant changes in survival for CIS, with slightly improved survival for treatment with surgery alone. Patients treated with surgery alone had an increased rate of subsequent invasive cancer.
The development and preliminary evaluation of an education intervention to prevent driveway run-over incidents
Authors: Armstrong Kerry A , Watling Hanna , Davey Jeremy
Published: October 2015

Objective:

While driveway run-over incidents continue to be a cause of serious injury and deaths among young children in Australia, few empirically evaluated educational interventions have been developed which address these incidents. Addressing this gap, this study describes the development and evaluation of a paper-based driveway safety intervention targeting caregivers of children aged 5 years or younger.

Design:

Cross-sectional survey.

Method and setting:

Informed by previous research, the intervention targeted key caregiver safety behaviours that address driveway risks. To assess the impact of the intervention, 137 Queensland (Australia) caregivers (95.0% women; mean age = 34.97 years) were recruited. After receiving the intervention, changes to a number of outcomes such as caregiver risk perception, safety knowledge and behavioural intentions were measured.

Results:

Findings indicated that the intervention had increased general and specific situational risk awareness and safety knowledge among a substantial proportion of participants. Close to one-quarter of the sample strongly agreed that the intervention had increased these outcomes. In addition, 71.6% of the sample reported that they intended to make changes to their routine in and around the driveway, as a result of reading the intervention material and a further, quarter of the participants strongly agreed that the information provided would be a help both to themselves (26.5%) and other caregivers (33.8%) to keep their children safe in the driveway.

Conclusion:

While the educational intervention requires further validation, findings from this study suggest that intervention content and format increases driveway safety.
“She chose us to be your parents”
Authors: Hays Alexie H. , Horstman Haley K. , Colaner Colleen W. , Nelson Leslie R.
Published: October 2015

Guided by narrative theorizing, the current study investigated the content and process of telling adoption entrance narratives (AENs)—or the story of how the child was born, placed for adoption, and integrated into their family—in open adoptive families. Thematic analysis of 165 adoptive parents’ (mostly mothers) AENs revealed six emergent themes: birth parents as family, chosen parents, forever, rescue, fate, and adoption makes us family. Structural equation modeling demonstrated that adoptive mothers’ relational satisfaction with the birth parent relates to birth parent storytelling which in turn relates to adoptee–birth parent relational closeness. Findings illuminate the ways adoptive mothers incorporate birth parents into their conceptualization of family in light of cultural assumptions of “family” and become gatekeepers of family relationships.
How is mobile technology changing city planning? Developing a taxonomy for the future
Authors: Riggs William , Gordon Kayla
Published: October 2015

The emergence of web technology creates tremendous opportunity to advance good government, through increased information, interaction with the public, and cost-effective, efficient means of conducting public transactions. Some have proposed that e-government tools have two major roles: (1) receptive and (2) interactive. We argue that there is a third role for planning and e-government technology – the transactive. To evaluate this, we survey public sector planning officials on their professional use of mobile technology. Results confirm the recent trends in increased smartphone use, but indicated that only a limited amount of this increased use is for work purposes. We find that there are still planners who not only do not rely on web technologies at all, within even desktop computer access. Furthermore, our results suggest that the current use of mobile technology appears to be less transactive than the literature suggests. This finding provides room for growth in these transactive and more dynamic exchanges, especially with the increasing prevalence of mobile devices. To assist in this, we provide a taxonomy to help define how mobile technology can change planning and local governance. Such a tool can provide a roadmap for increasing transactive exchanges between local government and citizens in the future.
The corporal dimension of sports-based interventions: Understanding the role of embedded expectations and embodied knowledge in sport policy implementation
Authors: Fahlén Josef
Published: October 2015

The aim of this paper is to show how the corporal character of activities commonly provided in sports-based policy interventions has implications for the results of policy implementation. By employing the theoretical concepts of embedded expectations and embodied knowledge, this paper examines how expectations embedded in such activities interact with experiences embodied by the participants and combine in availing or restricting the possibilities for participation – thereby affecting the outcome of policies for increased participation in organised sport. The paper builds on data from a case study of a sports-based intervention that aimed to usher so-called un-associated youth in to participation in regular sport-club activities by offering ‘organised spontaneous sports’ in ‘drop-in’ sessions that focus on the intrinsic characteristics of non-competitive sports and participants’ wishes. Findings from interviews, the intervention’s internal documentation, and observations show how expectations embedded in these activities require a very specific embodied knowledge of the individual participant. Instead of challenging dominant notions of what sport ‘is’ and ‘can be’, the activities reproduce existing preconceptions and, in extension, existing patterns of sport participation instead of supporting the formation of new ones as aimed for by policy makers. The findings are discussed in relation to the wider discussion about policy implementation in sport and highlight the necessity for understanding the content of the activities offered in sports-based interventions relative to the previous experiences of the pronounced recipients.
Prospects for Creation of Cardioprotective Drugs Based on Cannabinoid Receptor Agonists
Authors: Maslov Leonid N. , Khaliulin Igor , Zhang Yi , Krylatov Andrey V. , Naryzhnaya Natalia V. , Mechoulam Raphael , De Petrocellis Luciano , Downey James M.
Published: October 2015

Cannabinoids can mimic the infarct-reducing effect of early ischemic preconditioning, delayed ischemic preconditioning, and ischemic postconditioning against myocardial ischemia/reperfusion. They do this primarily through both CB1 and CB2 receptors. Cannabinoids are also involved in remote preconditioning of the heart. The cannabinoid receptor ligands also exhibit an antiapoptotic effect during ischemia/reperfusion of the heart. The acute cardioprotective effect of cannabinoids is mediated by activation of protein kinase C, extracellular signal-regulated kinase, and p38 kinase. The delayed cardioprotective effect of cannabinoid anandamide is mediated via stimulation of phosphatidylinositol-3-kinase-Akt signaling pathway and enhancement of heat shock protein 72 expression. The delayed cardioprotective effect of another cannabinoid, Δ9-tetrahydrocannabinol, is associated with augmentation of nitric oxide (NO) synthase expression, but data on the involvement of NO synthase in the acute cardioprotective effect of cannabinoids are contradictory. The adenosine triphosphate-sensitive K+ channel is involved in the synthetic cannabinoid HU-210-induced cardiac resistance to ischemia/reperfusion injury. Cannabinoids inhibit Na+/Ca2+ exchange via peripheral cannabinoid receptor (CB2) activation that may also be related to the antiapoptotic and cardioprotective effects of cannabinoids. The cannabinoid receptor agonists should be considered as prospective group of compounds for creation of drugs that are able to protect the heart against ischemia–reperfusion injury in the clinical setting.
Exposure-Reducing Behaviors Among Residents Living Near a Coal Ash Storage Site
Authors: Zierold Kristina M. , Sears Clara G. , Brock Guy N.
Published: October 2015

Coal ash, a waste product generated from burning coal for energy, is composed of highly respirable particles containing heavy metals, radioactive elements, and polycylic aromatic hydrocarbons. Coal ash is stored in landfills and surface impoundments frequently located near neighborhoods. Fugitive dust from the storage sites exposes neighborhoods, affecting the health and welfare of residents. The research questions of interest were (1) are community members concerned about coal ash exposure from the storage site; (2) what, if any, behaviors do community members engage in to reduce exposure; and (3) do exposure reducing behaviors differ by level of concern about coal ash. A community-based mixed-methods approach was used. Focus groups ( n = 26) were conducted in 2012, and a cross-sectional survey was administered in 2013 ( n = 231). The majority of survey respondents (62%) worried “a lot” about being exposed to coal ash; however, most did not engage in exposure-reducing behaviors, such as wearing protective equipment when doing chores. Compared with respondents who worry “some, very little, or none,” or responded “I don’t know,” respondents who worried “a lot” about being exposed to coal ash did more exposure-reducing behaviors outdoors ( p < .001) and indoors ( p = .01). For people living near environmental hazards, reducing exposure is a priority. Although challenging because of the chronic nature of exposure, some behaviors can be useful in reducing exposure, such as wearing a particle-specific respirator when mowing the lawn. Communities at risk for chronic exposure to environmental toxins could benefit from education about exposure-reducing behaviors.
Cutaneous asthenia (Ehlers–Danlos-like syndrome) of Burmese cats
Authors: Hansen Naomi , Foster Susan F , Burrows Amanda K , Mackie John , Malik Richard
Published: October 2015

Summary of cases:

A 6-month-old Burmese kitten developed focal skin lesions following a routine ovariohysterectomy. These were eventually attributed to the patient struggling during catheter placement and induction of anaesthesia. The lesions were caused by fluid extravasation in the subcutis and ischaemic necrosis of the overlying dermis, giving rise to an eschar-like appearance. Such lesions have been seen previously in Burmese cats with cutaneous asthenia and it is thought that they arise due to poor collagenous support for dermal blood vessels. An increased skin extensibility index (>23%) supported a diagnosis of cutaneous asthenia (Ehlers–Danlos-like syndrome), which has been reported as an inherited condition of Burmese cats in Australia, New Zealand and Europe. An additional Burmese cat with cutaneous asthenia is presented in detail, with lifetime follow-up and further salient observations by the owner, a veterinarian. Photographs of three other affected Burmese cats are provided to illustrate the range of presentations encountered with this condition. All five affected cats were presented with eschars, atrophic alopecia and increased skin extensibility, while one cat also had skin ulcers. Routine histopathological examination, including use of special stains such as trichrome, was unhelpful in establishing the diagnosis.

Clinical review:

The clinical features of this genetic disease of Burmese cats are reviewed, especially in relation to the postulated ‘vasculopathy’ that gives rise to characteristic skin lesions. Long term management of this condition is discussed briefly.
From collection to community to collections again: Urban Indigenous women, material culture and belonging
Authors: Krmpotich Cara , Howard Heather , Knight Emma
Published: October 2015

First Story Toronto – a community organization dedicated to the Indigenous histories of Toronto, Canada – is steward to a collection of items mostly made and collected during the 20th century. With origins in the Anglican Church Women, the collection reflects a time when policies and actions of the state and churches internalized colonial processes within Canada. Yet the donation of the ACW material to a Native woman and housing advocate in 1976 hints at the shifting political and cultural contexts of this collection. Native crafts were used by Indigenous women in the city in displays of both Indigenous sovereignty and multiculturalism. Recently, the collection has been taken up by another group of Indigenous women in the Memory, Meaning-Making and Collections project. Handling sessions with artefacts and ‘talking circles’, initially designed to research the role of objects in collective memory and life-history processes, have been appropriated by the participating seniors toward their own goals. The collection has become a source of continuing education, sparking the women to teach and learn beadwork and quillwork; compare life experiences among urban Indigenous people; question history-making processes; and visit museum stores to handle collections and learn with curators. The histories intersecting with this collection thus push back against a range of tropes, provide more nuanced insights into the lives and values of urban Indigenous women in Canada, and the ways collections are used in articulations of belonging among Indigenous peoples.
Experimental and numerical studies on the thermal performance of ventilated BIPV curtain walls
Authors: Lai Chi-ming , Hokoi Shuichi
Published: October 2015

In this study, we integrated a photovoltaic (PV) system, a double-skin structure and a thermal flow mechanism to design ventilated building-integrated photovoltaic (BIPV) curtain walls that can autogenously control an environment using buoyant force. Full-scale experiments and computational fluid dynamics (CFD) simulations were conducted to investigate the flow pattern characteristics for the channel airflow and the thermal performance of the ventilated BIPV curtain walls under various heating conditions, wall thicknesses and types of openings. Channel flows for different channel widths under the same wall heating exhibited different flow patterns and therefore variations in thermal performance. The developed ventilated BIPV curtain walls effectively removed their solar heat gain while maintaining adequate wall thermal performance.
Development and evaluation of a controlled drug delivery wound dressing based on polymeric porous microspheres
Authors: Khurshid Muhammad Furqan , Hussain Tanveer , Masood Rashid , Hussain Nisar
Published: October 2015

The aim of the present work was to develop and evaluate a controlled drug delivery wound dressing based on polymeric porous microspheres, which are also termed as microsponge drug delivery system. For this purpose, turmeric (drug)-based polymeric porous microspheres formulations were developed by quasi-emulsion solvent diffusion method. The production yields, actual drug content, drug entrapment efficiency, particle size, formulation of the material, and in vitro release were studied. On the basis of maximum drug released, a formulation was selected to incorporate into wound dressings with the help of a binder by spraying technique. Finally, the selected formulation and samples of wound dressings containing microsponges were subjected to scanning electron microscopy and drug release analyses. The result of in vitro release shows that microsponge drug delivery system is a versatile tool that has a potential to convert any wound dressing into a controlled drug delivery wound dressing.
The Validity and Reliability of Health Belief Scale for Testicular Cancer Self-Examination
Authors: Avci Ilknur Aydin , Altinel Busra
Published: October 2015

This study aimed to create a measurement tool for the determination of university students’ health beliefs about testicular cancer (TC) and self-examination. This is a methodological and cross-sectional study. The study sample included 425 university students. Consents and approvals were obtained from the relevant institutions and the ethics committee prior to the research. The data were collected using an interview form that included questions about descriptive characteristics, family history of TC, and knowledge, beliefs, and practice of self-examination. The health belief model including 41 questions about self-examination and the interview form were administered to the students in their classrooms at a suitable time. Principal components analysis and varimax rotation were used for the examination of the structures of the factors. Accordingly, factor patterns, self-values, and the variance percentages they explained were evaluated. The average age of the participants is 22.2 ± 2.3 (min = 17; max = 40). Of them, 98.8% of the participants are single ( n = 420). Of them, 56.2% have heard about TC before, and 18.4% said they were informed about TC. Factor loading of the items in the first factor was 0.64 to 0.89, while it was 0.48 to 0.75 for the items in the second factor, 0.50 to 0.87 for the items in the third factor, 0.37 to 0.68 for the items in the fourth factor, 0.51 to 0.68 for the items in the fifth factor, and 0.65 to 0.79 for the items in the sixth factor. The health belief model scale may be used in TC screenings for males to measure susceptibility, seriousness, health motivation, barriers, benefits, and self-efficacy.