bluuebunny/crossref_metadata_2025 huggingface dataset:
My Relational Self Psychology
Authors: Teicholz Judith Guss
Published: April 2009

In this article, I suggest recent sources of influence on psychoanalysis and describe a contemporary relational self psychology that is my personal attempt at integration. Even with this integration, I struggle to find the right “therapeutic” balance between my essential but imperfect instrument for empathic listening, on the one hand, and the risks of authentic engagement, on the other. These dialectical tensions in me mirror those in the psychoanalytic community as a whole, poised between a scientifically based practice and a healing “art”—or between a complex but teachable methodology or discipline—and an ordinary (yet extraordinary) human relationship in which spontaneity and even improvisation play a role. Complicating this balancing act, there is new evidence from neuroscientists, attachment theorists, and infant–caregiver researchers that, from birth onward, bidirectional influences on brain and psychic development create contingent and unpredictable outcomes in every intimately related dyad. Thus, the contemporary analyst must expect to be changed by the work and—while taking full responsibility for his or her own contribution—must recognize patient and analyst as co‐creators of the psychoanalytic project. At the same time that we now recognize contingency, complexity, and chaos at the heart of human minds and relationships, we also acknowledge the central importance of a sense of continuity and coherence as the individual undertakes the pursuit of goals and relationships in life. What kind of relationship can facilitate these qualities in the sense of self? That is the question that this article undertakes to answer.
Relational Trauma and the Developing Right Brain
Authors: Schore Allan N.
Published: April 2009

Psychoanalysis, the science of unconscious processes, has recently undergone a significant transformation. Self psychology, derived from the work of Heinz Kohut, represents perhaps the most important revision of Freud's theory as it has shifted its basic core concepts from an intrapsychic to a relational unconscious and from a cognitive ego to an emotion‐processing self. As a result of a common interest in the essential, rapid, bodily based, affective processes that lie beneath conscious awareness, a productive dialogue is now occurring between psychoanalysis and neuroscience. Here I apply this interdisciplinary perspective to a deeper understanding of the nonconscious brain/mind/body mechanisms that lie at the core of self psychology. I offer a neuropsychoanalytic conception of the development and structuralization of the self, focusing on the experience‐dependent maturation of the emotion‐processing right brain in infancy. I then articulate an interdisciplinary model of attachment trauma and pathological dissociation, an early forming defense against overwhelming affect that is a cardinal feature of self‐psychopathologies. I end with some thoughts on the mechanism of the psychotherapeutic change process and suggest that self psychology is, in essence, a psychology of the unique functions of the right brain and that a rapprochement between psychoanalysis and neuroscience is now at hand.
Psychoanalytic Self Psychology and Its Conceptual Development in Light of Developmental Psychology, Attachment Theory, and Neuroscience
Authors: Hartmann Hans‐Peter
Published: April 2009

The chapter starts with a historical overview of the subject of narcissism in psychoanalysis. Some sociophilosophical definitions ofnarcissismare explained and the connection to self psychology is described. It is especially referred to Honneth'sStruggle for Recognition, which is related to the need for selfobject experiences. An outline of different concepts concerning narcissism, especially in the European psychoanalytic tradition, follows and leads to a clearer understanding of Kohut's conception of the self and its selfobjects. Because self psychology can often be understood as applied developmental psychology, useful links to attachment research are described and the move to the level of representation by mentalization is clarified. Further development of self psychology in the direction of intersubjectivity helps to supply connections to systems theory. Recently developed theories of empathy with reference to neurobiological findings provide a dynamic perspective of the activation of empathy. Thus, empathy seems to be better understood as a sort of contagion on which cognitive cortical processes are superimposed. Finally, the therapeutic process in psychoanalytic self psychology is portrayed. This process implies a disruption and repair process by which transmuting internalization can take place. More current theories of self psychology view this process in its essence intersubjectively as a co‐construction between patient and analyst. The paper concludes with some hints for a paradigm shift in the direction of a more holistic understanding of the self.
‘FORENSIC GROUP PSYCHOTHERAPY’: ESTELA WELLDON'S CONTRIBUTION TO WORKING WITH GROUPS AT THE PORTMAN CLINIC
Authors: Hakeem Az
Published: April 2009

abstract

In this paper the author gives a summary of the contributions made by Dr Estela Welldon to the Group Psychotherapy at The Portman Clinic. He describes how clinicians working at the Portman Clinic have evolved and adapted the principles and practices from group psychotherapy in order to work with perverse, violent, delinquent, transsexual and other specialist patient groups in what is described as ‘forensic group psychotherapy’. Attention is drawn to the selection of patients, composition of the group, particular differences of dynamic administration of the group, the style of the conductor, and the observed and expected group processes. The author describes his personal experience as a specialist registrar in forensic psychotherapy at the Portman Clinic working with Dr Welldon, and his continued work there as a consultant, and the continual development and evolution of forensic group psychotherapy.
The Kinematics of Biological Growth
Authors: Garikipati K.
Published: April 2009

The kinematic aspects of biological growth models are reviewed by paying attention to the handful of crucial ideas on which modern treatments rest. Both surface and volumetric growth are considered. A critical appraisal is presented of the geometric and physical features of the models. Links are made to the mathematical treatment of growth and evolving interface phenomena in other physical problems. Computational issues are pointed out wherever appropriate.
Diagnosis of Active Tuberculosis in China Using an In-House Gamma Interferon Enzyme-Linked Immunospot Assay
Authors: Chen Xinchun , Yang Qianting , Zhang Mingxia , Graner Michael , Zhu Xiuyun , Larmonier Nicolas , Liao Mingfeng , Yu Weiye , Deng Qunyi , Zhou Boping
Published: April 2009

Gamma interferon (IFN-γ) release assays have been proven to be useful in the diagnosis of
Mycobacterium tuberculosis
infection. Nevertheless, their specificity and sensitivity vary among the different populations studied. Here, we evaluate the value of an in-house IFN-γ enzyme-linked immunospot (ELISPOT) assay in the diagnosis of active tuberculosis (TB) in Shenzhen, China, where the prevalence of tuberculosis is severe and
Mycobacterium bovis
BCG vaccination is mandatory at birth. A total of 305 patients with active tuberculosis, 18 patients with nontuberculosis lung diseases, and 202 healthy controls were recruited in this study. Among them, 156 individuals were simultaneously tested for IFN-γ responses by the commercial QuantiFERON-TB Gold in-tube (QFT-IT) assay. Tuberculin skin tests (TST) were performed with 202 healthy controls. The overall sensitivities of the ELISPOT and QFT-IT assays for active tuberculosis were 83.60% and 80.85%, respectively; the specificities were 76.6% and 73.26%, respectively. The IFN-γ ELISPOT responses, but not those of the TST, were significantly correlated with TB exposure (
r
= −0.6040,
P
< 0.0001). The sensitivities of the ELISPOT assay varied for patients with different forms of tuberculosis, with the highest sensitivity for patients with sputum-positive pulmonary tuberculosis (89.89%) and the lowest for those with tuberculous meningitis (62.5%). In conclusion, the IFN-γ ELISPOT assay is a useful adjunct to current tests for diagnosis of active TB in China. The ELISPOT assay is more accurate than TST in identifying TB infections.
A new parareptile with temporal fenestration from the Middle Permian of South Africa
Authors: Modesto Sean P. , Scott Diane M. , Reisz Robert R.
Published: April 2009

The partial skeleton of a small reptile, from the Middle Permian Tapinocephalus Assemblage Zone of South Africa, is described as a new parareptile. Australothyris smithi gen. et sp. nov. is diagnosed by contact between the postfrontal and the supratemporal, a relatively large pineal foramen, a small interpterygoid vacuity, the presence of teeth on the ventral surfaces of the basipterygoid processes, and several other autapomorphies. Phylogenetic analysis of an augmented data matrix from the literature positions A. smithi basally within Parareptilia, as the sister taxon of Ankyramorpha. Our results indicate that the presence of a lateral temporal fenestra is synapomorphic for procolophonomorphs (as regarded in this paper) and that this structure was variously modified in procolophonians. Australothyris smithi is the phylogenetically youngest member of a grade of Gondwanan parareptiles that includes mesosaurids and millerosaurs, a topology intimating that parareptiles diversified first in Gondwana and then dispersed into Laurasia. This biogeographic scenario is at odds with observations that the bolosaurids of Laurasia predate mesosaurids and other Gondwanan parareptiles by approximately 15 million years.
Role of Nest Raiding and Egg Predation in Regulating Population Density of Threespine Sticklebacks (Gasterosteus aculeatus) in a Coastal British Columbia Lake
Authors: Hyatt Kim D. , Ringler Neil H.
Published: April 2009

The consequences of nest raiding and egg predation for population regulation of sticklebacks (Gasterosteus aculeatus) were studied in a British Columbia coastal lake. Stickleback eggs were present in the stomachs of 23 and 11% of all sticklebacks sampled from the field in 1982 and 1985 respectively. On average, males consumed more eggs than did females. Seasonal egg consumption increased with increases in stickleback density in breeding colonies. In experimental enclosure studies, nest densities varied between 0 and 3∙m−2 as stickleback numbers were manipulated from 1.5 to 12∙m−2. Peak nest densities occurred at 5.8 fish∙m−2. Stickleback density explained 70–86% of the variation in nest numbers in an application of a Ricker stock–recruit model and weekly rates of nest survival exhibited strong density dependence. Our evidence indicates that both nest raiding and egg cannibalism are important in limiting the production of stickleback fry as population density increases in scattered, lakeshore, breeding colonies of Kennedy Lake.
Relationship between Anaerobic Sediment Phosphorus Release Rates and Sedimentary Phosphorus Species
Authors: Ostrofsky M. L. , Osborne D. A. , Zebulske T. J.
Published: April 2009

Rates of anaerobic phosphorus release from the sediments of 57 lakes of varying trophy and sediment characteristics were measured under controlled laboratory conditions to test the hypothesis that internal phosphorus loading was a function of sediment phosphorus species. Simple regression analyses indicated that no single species can predict more than 18% of the variability in release rates. Multiple regression analysis using both water and sediment characteristics were able to explain 51% of the variation. A model based on stepwise multiple regression analysis suggests that lakes most prone to high rates of internal phosphorus loading will be alkaline with high concentrations of spring overturn total phosphorus, and with sediments characterized by high concentrations of iron-bound phosphorus, and low concentrations of organic matter.
Extinction of a Population of Anadromous Parasitic Lamprey, Lampetra tridentata, Upstream of an Impassable Dam
Authors: Beamish R. J. , Northcote T. G.
Published: April 2009

The construction of dams on the outlet of Elsie Lake, in British Columbia, prevented young adult Pacific lamprey (Lampetra tridentata) from going to sea and adult lamprey from spawning above the dams. This resulted in a high incidence of lamprey attacks on resident trout that was initially interpreted as indicating that the lamprey population was landlocked. This study showed that a landlocked population of lamprey was not established. The attacks on fish occurred for only a brief period each year. Attacks on trout stopped approximately 7 yr after dam construction. Because this was the average estimated age when ammocoetes metamorphosed and scarred fish or ammocoetes were no longer found, we concluded that metamorphosed lamprey were unable to survive to maturity. The inability to establish a landlocked population indicated that the transition from an anadromous parasitic life history type to a freshwater parasitic life history type did not occur as quickly or as easily as previously suggested. The study also provided evidence that the statolith method of age determination may provide accurate ages.
Gut Sediments in a Burrowing Mayfly (Ephemeroptera, Hexagenia limbata): Their Contribution to Animal Trace Element Burdens, Their Removal, and the Efficacy of a Correction for Their Presence
Authors: Hare Landis , Campbell Peter G. C. , Tessier André , Belzile Nelson
Published: April 2009

Nymphs of the burrowing mayfly Hexagenia limbata were collected in the field, returned to the laboratory, and dissected to remove the gut contents. Concentrations of four trace elements (As, Cd, Cu, Zn) were determined both for the gut contents and for the body. Trace elements in gut contents represented up to 22% of whole animal trace element burdens. Studies of depuration of H. limbata nymphs held in water for up to 48 h indicate that individuals vary substantially in the rate at which they egest gut contents and that 48 h is not sufficient to ensure a complete emptying of the gut. A model developed to compensate for the presence of gut contents in the determination of body trace element burdens was applied to H. limbata. Comparisons of model estimates with actual body burdens (without gut contents) show that the model accurately predicts As and Cu concentrations, but overestimates concentrations of Cd and Zn by as much as 20%. We suggest that the biases in the model result from assuming that: (a) trace element concentrations in gut sediments are equivalent to those in sediments sampled from the animal's surroundings, and (b) there is no weight loss of gut contents during sample digestion (a two-thirds weight loss of gut contents was in fact observed). These biases may be minimized by, respectively: (a) measuring trace element burdens of gut contents and (b) compensating for weight loss of gut contents during digestion.
Synthesis and binding characteristics of novel calix[4]arene(amidocrown) diquinones
Authors: Chawla Har Mohindra , Sahu Satya Narayan , Shrivastava Rahul
Published: April 2009

A series of new calix[4]arene(amidocrown) diquinones (3a–3d) have been synthesized, characterized, and evaluated for cation recognition. It has been observed that 3b interacts with alkali metal ions (Li+, Na+, and K+) and ammonium ions to induce an unprecedented downfield shift in the NH proton resonance, which can be attributed to polarization of the amidocrown ring of the calix[4]arene diquinone receptor. The observation has been confirmed by a significant anodic shift (Li+ > NH4+ > Na+> K+) of the corresponding amidocrown-diquinone redox couple in cyclic and square wave voltammetric experiments. Both NMR and electrochemical studies of the binding characteristics of 3b with alkali metal cations and ammonium ions revealed a 1:1 binding stoichiometry for all and exhibited the highest association constant for lithium ions. This indicated that the receptor 3b selectively binds the lithium ion in preference to other alkali metal cations and ammonium ions.
HYPERCHAOS GENERATED FROM QI SYSTEM AND ITS OBSERVER
Authors: WANG XINGYUAN , ZHANG YAOXIAN , GAO YONGFENG
Published: April 2009

This paper reports a novel four-dimensional hyperchaos generated from Qi system, obtained by adding nonlinear controller to Qi chaos system. The novel hyperchaos is studied by bifurcation diagram, Lyapunov exponent spectrum and phase diagram. Numerical simulations show that the new system's behavior can be periodic, chaotic and hyperchaotic as the parameter varies. Based on the time-domain approach, a simple observer for the hyperchaotic is proposed to guarantee the global exponential stability of the resulting error system. The scheme is easy to implement and different from the other observer design since it does not need to transmit all signals of the dynamical system.
Nociceptive Laser-Evoked Brain Potentials Do Not Reflect Nociceptive-Specific Neural Activity
Authors: Mouraux A. , Iannetti G. D.
Published: April 2009

Brief radiant laser pulses can be used to activate cutaneous Aδ and C nociceptors selectively and elicit a number of transient brain responses [laser-evoked potentials (LEPs)] in the ongoing EEG. LEPs have been used extensively in the past 30 years to gain knowledge about the cortical mechanisms underlying nociception and pain in humans, by assuming that they reflect at least neural activities uniquely or preferentially involved in processing nociceptive input. Here, by applying a novel blind source separation algorithm (probabilistic independent component analysis) to 124-channel event-related potentials elicited by a random sequence of nociceptive and non-nociceptive somatosensory, auditory, and visual stimuli, we provide compelling evidence that this assumption is incorrect: LEPs do not reflect nociceptive-specific neural activity. Indeed, our results indicate that LEPs can be entirely explained by a combination of multimodal neural activities (i.e., activities also elicited by stimuli of other sensory modalities) and somatosensory-specific, but not nociceptive-specific, neural activities (i.e., activities elicited by both nociceptive and non-nociceptive somatosensory stimuli). Regardless of the sensory modality of the eliciting stimulus, the magnitude of multimodal activities correlated with the subjective rating of saliency, suggesting that these multimodal activities are involved in stimulus-triggered mechanisms of arousal or attentional reorientation.
Viral Vector Induction of CREB Expression in the Periaqueductal Gray Induces a Predator Stress-Like Pattern of Changes in pCREB Expression, Neuroplasticity, and Anxiety in Rodents
Authors: Adamec Robert , Berton Olivier , Abdul Razek Waleed
Published: April 2009

Predator stress is lastingly anxiogenic. Phosphorylation of CREB to pCREB (phosphorylated cyclic AMP response element binding protein) is increased after predator stress in fear circuitry, including in the right lateral column of the PAG (periaqueductal gray). Predator stress also potentiates right but not left CeA-PAG (central amygdala-PAG) transmission up to 12 days after stress. The present study explored the functional significance of pCREB changes by increasing CREB expression in non-predator stressed rats through viral vectoring, and assessing the behavioral, electrophysiological and pCREB expression changes in comparison with handled and predator stressed controls. Increasing CREB expression in right PAG was anxiogenic in the elevated plus maze, had no effect on risk assessment, and increased acoustic startle response while delaying startle habituation. Potentiation of the right but not left CeA-PAG pathway was also observed. pCREB expression was slightly elevated in the right lateral column of the PAG, while the dorsal and ventral columns were not affected. The findings of this study suggest that by increasing CREB and pCREB in the right lateral PAG, it is possible to produce rats that exhibit behavioral, brain, and molecular changes that closely resemble those seen in predator stressed rats.
Development of CRTEIL and CETRIZ, Cre‐loxP‐Based Systems, Which Allow Change of Expression of Red to Green or Green to Red Fluorescence upon Transfection with a Cre‐Expression Vector
Authors: Ohtsuka Masato , Warita Takayuki , Sakurai Takayuki , Watanabe Satoshi , Inoko Hidetoshi , Sato Masahiro
Published: April 2009

We developed Cre‐loxP‐based systems, termed CRTEIL and CETRIZ, which allow gene switching in a noninvasive manner. Single transfection with pCRTEIL resulted in predominant expression of red fluorescence. Cotransfection with pCRTEIL and Cre‐expression plasmid (pCAG/NCre) caused switching from red to green fluorescence. Similarly, cotransfection with pCETRIZ and pCAG/NCre resulted in change of green to red fluorescence. These noninvasive systems will be useful in cell lineage analysis, since descendants of cells exhibiting newly activated gene expression can be continuously monitored in noninvasive fashion.
Epidermal Growth Factor Receptor/β-Catenin/T-Cell Factor 4/Matrix Metalloproteinase 1: A New Pathway for Regulating Keratinocyte Invasiveness after UVA Irradiation
Authors: Jean Christine , Blanc Amandine , Prade-Houdellier Naïs , Ysebaert Loïc , Hernandez-Pigeon Hélène , Al Saati Talal , Haure Marie-José , Coluccia Addolorata-Maria-Luce , Charveron Marie , Delabesse Eric , Laurent Guy
Published: April 2009

Previous studies have established that UV irradiation results in epidermal growth factor receptor (EGFR) activation in keratinocytes. However, the signaling pathways and cellular effects related to this process remain incompletely elucidated. Herein, we describe for the first time that UVA-mediated EGFR activation results in β-catenin tyrosine phosphorylation at the Y654 residue responsible for the dissociation of E-cadherin/α-catenin/β-catenin complexes. Moreover, UVA induces an EGFR-dependent, but Wnt-independent, β-catenin relocalization from the membrane to the nucleus followed by its association with T-cell factor 4 (TCF4). This newly formed β-catenin/TCF4 complex binds to a specific site on matrix metalloproteinase 1 (MMP1) promoter and governs MMP1 gene and protein expression, as well as cell migration in collagen and gelatin. Altogether, these results suggest that UVA stimulates keratinocyte invasiveness through two coordinated EGFR-dependent processes: loss of cell-to-cell contact due to β-catenin/E-cadherin/α-catenin dissociation and increased cell migration through extracellular matrix component degradation due to β-catenin/TCF4–dependent MMP1 regulation. These events may represent an important step in epidermis repair following UVA injury and their abnormal regulation could contribute to photoaging and photocarcinogenesis. [Cancer Res 2009;69(8):3291–9]
Atg5 Regulates Phenethyl Isothiocyanate–Induced Autophagic and Apoptotic Cell Death in Human Prostate Cancer Cells
Authors: Bommareddy Ajay , Hahm Eun-Ryeong , Xiao Dong , Powolny Anna A. , Fisher Alfred L. , Jiang Yu , Singh Shivendra V.
Published: April 2009

Phenethyl isothiocyanate (PEITC) is a promising cancer chemopreventive agent but the mechanism of its anticancer effect is not fully understood. We now show, for the first time, that PEITC treatment triggers Atg5-dependent autophagic and apoptotic cell death in human prostate cancer cells. Exposure of PC-3 (androgen independent, p53 null) and LNCaP (androgen responsive, wild-type p53) human prostate cancer cells to PEITC resulted in several specific features characteristic of autophagy, including appearance of membranous vacuoles, formation of acidic vesicular organelles, and cleavage and recruitment of microtubule-associated protein 1 light chain 3 (LC3) to autophagosomes. A normal human prostate epithelial cell line (PrEC) was markedly more resistant toward PEITC-mediated cleavage and recruitment of LC3 compared with prostate cancer cells. Although PEITC treatment suppressed activating phosphorylations of Akt and mammalian target of rapamycin (mTOR), which are implicated in regulation of autophagy by different stimuli, processing and recruitment of LC3 was only partially/marginally reversed by ectopic expression of constitutively active Akt or overexpression of mTOR-positive regulator Rheb. The PEITC-mediated apoptotic DNA fragmentation was significantly attenuated in the presence of a pharmacologic inhibitor of autophagy (3-methyl adenine). Transient transfection of LNCaP and PC-3 cells with Atg5-specific small interfering RNA conferred significant protection against PEITC-mediated autophagy as well as apoptotic DNA fragmentation. A xenograft model using PC-3 cells and Caenorhabditis elegans expressing a lgg-1:GFP fusion protein provided evidence for occurrence of PEITC-induced autophagy in vivo. In conclusion, the present study indicates that Atg5 plays an important role in regulation of PEITC-induced autophagic and apoptotic cell death. [Cancer Res 2009;69(8):3704–12]
Aldehyde Dehydrogenase 1 Is a Marker for Normal and Malignant Human Colonic Stem Cells (SC) and Tracks SC Overpopulation during Colon Tumorigenesis
Authors: Huang Emina H. , Hynes Mark J. , Zhang Tao , Ginestier Christophe , Dontu Gabriela , Appelman Henry , Fields Jeremy Z. , Wicha Max S. , Boman Bruce M.
Published: April 2009

Although the concept that cancers originate from stem cells (SC) is becoming scientifically accepted, mechanisms by which SC contribute to tumor initiation and progression are largely unknown. For colorectal cancer (CRC), investigation of this problem has been hindered by a paucity of specific markers for identification and isolation of SC from normal and malignant colon. Accordingly, aldehyde dehydrogenase 1 (ALDH1) was investigated as a possible marker for identifying colonic SC and for tracking them during cancer progression. Immunostaining showed that ALDH1+ cells are sparse and limited to the normal crypt bottom, where SCs reside. During progression from normal epithelium to mutant (APC) epithelium to adenoma, ALDH1+ cells increased in number and became distributed farther up the crypt. CD133+ and CD44+ cells, which are more numerous and broadly distributed in normal crypts, showed similar changes during tumorigenesis. Flow cytometric isolation of cancer cells based on enzymatic activity of ALDH (Aldefluor assay) and implantation of these cells in nonobese diabetic–severe combined immunodeficient mice (a) generated xenograft tumors (Aldefluor− cells did not), (b) generated them after implanting as few as 25 cells, and (c) generated them dose dependently. Further isolation of cancer cells using a second marker (CD44+ or CD133+ serially) only modestly increased enrichment based on tumor-initiating ability. Thus, ALDH1 seems to be a specific marker for identifying, isolating, and tracking human colonic SC during CRC development. These findings also support our original hypothesis, derived previously from mathematical modeling of crypt dynamics, that progressive colonic SC overpopulation occurs during colon tumorigenesis and drives CRC development. [Cancer Res 2009;69(8):3382–9]
Guanylyl Cyclase C Prevents Colon Cancer Metastasis by Regulating Tumor Epithelial Cell Matrix Metalloproteinase-9
Authors: Lubbe Wilhelm J. , Zuzga David S. , Zhou Zengyi , Fu Weili , Pelta-Heller Joshua , Muschel Ruth J. , Waldman Scott A. , Pitari Giovanni M.
Published: April 2009

Matrix metalloproteinase-9 (MMP-9) produced by colorectal cancer cells is a critical determinant of metastatic disease progression and an attractive target for antimetastatic strategies to reduce colon cancer mortality. Cellular signaling by cyclic GMP (cGMP) regulates MMP-9 dynamics in various cell systems, and the bacterial enterotoxin receptor guanylyl cyclase C (GCC), the principle source of cGMP in colonocytes, which is overexpressed in colorectal cancers, inhibits tumor initiation and progression in the intestine. Here, we show that ligand-dependent GCC signaling through cGMP induces functional remodeling of cancer cell MMP-9 reflected by a compartmental redistribution of this gelatinase, in which intracellular retention resulted in reciprocal extracellular depletion. Functional remodeling of MMP-9 by GCC signaling reduced the ability of colon cancer cells to degrade matrix components, organize the actin cytoskeleton to form locomotory organelles and spread, and hematogenously seed distant organs. Of significance, GCC effects on cancer cell MMP-9 prevented establishment of metastatic colonies by colorectal cancer cells in the mouse peritoneum in vivo. Because endogenous hormones for GCC are uniformly deficient in intestinal tumors, reactivation of dormant GCC signaling with exogenous administration of GCC agonists may represent a specific intervention to target MMP-9 functions in colon cancer cells. The notion that GCC-mediated regulation of cancer cell MMP-9 disrupts metastasis, in turn, underscores the unexplored utility of GCC hormone replacement therapy in the chemoprevention of colorectal cancer progression. [Cancer Res 2009;69(8):3529–36]
Regulation of RUNX3 Tumor Suppressor Gene Expression in Cutaneous Melanoma
Authors: Kitago Minoru , Martinez Steve R. , Nakamura Takeshi , Sim Myung-Shin , Hoon Dave S.B.
Published: April 2009

Purpose: RUNX3 is a known tumor suppressor gene in several carcinomas. Aberration in RUNX3 expression has not been described for cutaneous melanoma. Therefore, we assessed the expression of RUNX3 in cutaneous melanoma and its regulatory mechanisms relative to tumor progression.

Experimental Design: The expression of RUNX3 mRNA and miR-532-5p (microRNA) was assessed in melanoma lines and in primary and metastatic melanoma tumors.

Results: RUNX3 mRNA expression was down-regulated in 11 of 11 (100%) metastatic melanoma lines relative to normal melanocytes (P < 0.001). Among 123 primary and metastatic melanoma tumors and 12 normal skin samples, RUNX3 expression was significantly down-regulated in primary melanomas (n = 82; P = 0.02) and in melanoma metastasis (n = 41; P < 0.0001) versus normal skin (n = 12). This suggested that RUNX3 down-regulation may play a role in the development and progression of melanoma. RUNX3 promoter region hypermethylation was assessed as a possible regulator of RUNX3 expression using methylation-specific PCR. Assessment of RUNX3 promoter region methylation showed that only 5 of 17 (29%) melanoma lines, 2 of 52 (4%) primary melanomas, and 5 of 30 (17%) metastatic melanomas had hypermethylation of the promoter region. A microRNA (miR-532-5p) was identified as a target of RUNX3 mRNA sequences. miR-532-5p expression was shown to be significantly up-regulated in melanoma lines and metastatic melanoma tumors relative to normal melanocytes and primary melanomas, respectively. To investigate the relation between RUNX3 and miR-532-5p, anti–miR-532-5p was transfected into melanoma lines. Inhibition of miR-532-5p up-regulated both RUNX3 mRNA and protein expression.

Conclusions: RUNX3 is down-regulated during melanoma progression and miR-532-5p is a regulatory factor of RUNX3 expression.
Energy Homeostasis and Cancer Prevention: The AMP-Activated Protein Kinase
Authors: Fay Judith R. , Steele Vernon , Crowell James A.
Published: April 2009

Caloric restriction has long been recognized as an extremely effective cancer preventive. Current population demographics suggest that caloric excess and obesity will lead to increased cancer incidence, underscoring the need to elucidate the molecular mechanisms that couple dysregulated energy homeostasis to aberrant cell growth. The AMP-activated protein kinase (AMPK) is a critical monitor of cellular energy status, largely studied for its importance in metabolic regulation. AMPK also controls processes relevant to tumor development, including cell cycle progression, protein synthesis, cell growth, and survival. Several tumor suppressors impinge on AMPK signaling, and activation of the kinase inhibits tumor growth. However, AMPK can also promote cancer in some settings, necessitating a more complete understanding of the complexities of this signaling network. Because dysregulated energy balance is a nexus for multiple chronic diseases of aging, drugs that target these pathways may find broad utility in aging populations.
Phase I-II Trial of Weekly Bicalutamide in Men with Elevated Prostate-Specific Antigen and Negative Prostate Biopsies
Authors: Zanardi Silvia , Puntoni Matteo , Maffezzini Massimo , Bandelloni Roberto , Mori Marco , Argusti Alessandra , Campodonico Fabio , Turbino Laura , Branchi Daniela , Montironi Rodolfo , Decensi Andrea
Published: April 2009

Background: Men with elevated prostate-specific antigen (PSA) and negative prostate biopsies are at risk for prostate cancer. The antiandrogen bicalutamide has a prolonged half-life, thus potentially allowing an intermittent administration to retain activity while reducing toxicity. We conducted a phase I-II trial of weekly bicalutamide in men with PSA >4 ng/mL and negative biopsies.

Methods: Eighty subjects were nonrandomly assigned to a three-arm trial to either bicalutamide 50 mg/wk (n = 26) or 100 mg/wk (n = 28) or no treatment (n = 26) for 6 months. Blood samples were obtained at 0, 3, and 6 months, and prostate biopsies were repeated after 6 months. The outcome measures were 6-month changes of tissue Ki-67 (primary end point), high-grade prostatic intraepithelial neoplasia (HG-PIN), proliferative inflammatory atrophy, circulating PSA, and sex hormones.

Results: Ki-67 expression was higher in HG-PIN than in normal tissue (10% versus 3%; P < 0.01) but was not modulated by bicalutamide in normal luminal cells. A trend toward an improvement of HG-PIN status was found in treated subjects (26% improved, 60% had no change, 15% worsened) as compared with the no-treatment arm (4% improved, 83% had no change, 13% worsened; P = 0.07). Proliferative inflammatory atrophy prevalence was not reduced by bicalutamide. Bicalutamide reduced PSA by 50% in both arms and raised testosterone and estradiol levels. Asymptomatic breast swelling was noted in 40% of the treated cases.

Conclusions: A weekly administration of bicalutamide seems to be reasonably safe and shows an encouraging signal of activity on HG-PIN prevalence, supporting further studies of this schedule in men at high risk despite the negative primary end-point findings on Ki-67.
Liposomal Encapsulation of Deguelin: Evidence for Enhanced Antitumor Activity in Tobacco Carcinogen–Induced and Oncogenic K-ras–Induced Lung Tumorigenesis
Authors: Woo Jong K. , Choi Dong Soon , Tran Hai T. , Gilbert Brian E. , Hong Waun Ki , Lee Ho-Young
Published: April 2009

Deguelin has shown promising chemopreventive and therapeutic activities in diverse types of cancers. However, the potential side effect of deguelin over a certain dose could be the substantial hurdle in the practical application of the drug. One of the successful strategies for the use of deguelin in clinical trials could be lung-specific delivery of the drug. The present study evaluates the efficacy of liposome-encapsulated deguelin with a dose of 0.4 mg/kg, which is 10 times less than the dose (4 mg/kg) for preventive and therapeutic activities validated in previous in vivo studies. Liposomal deguelin revealed cytotoxic activity in vitro in premalignant and malignant human bronchial epithelial cells and non–small cell lung cancer cells through the same mechanistic pathway previously reported for deguelin (i.e., suppression of the heat shock protein 90 chaperone function and induction of apoptosis). Delivery of liposomal deguelin at a dose of 0.4 mg/kg by intranasal instillation resulted in markedly increased drug partitioning to the lungs compared with that of 4 mg/kg deguelin or 0.4 mg/kg liposomal deguelin administered by oral gavage. Lung-specific delivery of deguelin (0.4 mg/kg) via nasal or intratracheal instillation in a liposomal formulation also showed significant chemopreventive and therapeutic activities in 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone/benzo(a)pyrene–treated A/J mice and K-rasLAC57Bl6/129/sv F1 mice with no detectable toxicity. Our findings support the potential use of deguelin in a liposomal formulation via lung-specific delivery to improve efficacy and to reduce the potential side effects of the agent.
A Common Variant of the
FTO
Gene Is Associated With Not Only Increased Adiposity but Also Elevated Blood Pressure in French Canadians
Authors: Pausova Zdenka , Syme Catriona , Abrahamowicz Michal , Xiao Yongling , Leonard Gabriel T. , Perron Michel , Richer Louis , Veillette Suzanne , Smith George Davey , Seda Ondrej , Tremblay Johanne , Hamet Pavel , Gaudet Daniel , Paus Tomas
Published: April 2009

Background—

FTO
is the first gene established as contributing to common forms of obesity. The gene is highly expressed in the hypothalamus and is thought to mediate this effect through its influence on energy homeostasis. The hypothalamus, however, also regulates blood pressure (BP). Therefore, we investigated whether the
FTO
-risk variant is associated not only with increased adiposity but also with elevated BP and whether the latter may be mediated, in part, by increased sympathetic modulation of vasomotor tone.

Methods and Results—

The primary study was carried out in 485 adolescents recruited from a French Canadian founder population who underwent detailed body-composition and cardiovascular phenotyping. Body fat was examined with MRI, bioimpedance, and anthropometry. BP was recorded beat to beat at rest and during physical and mental challenges. Sympathetic modulation of vasomotor tone was assessed with power spectral analysis of BP. We found that individuals with the
FTO-
risk genotype compared with those without it demonstrate greater adiposity, including the amount of intra-abdominal fat (by 38%). They also showed higher systolic BP throughout the entire protocol, with a maximum difference during a mental stress (6.4 [1.5 to 11.3] mm Hg). The difference in BP was accompanied by elevated index of sympathetic modulation of vasomotor tone. A replication in an independent sample of adults from the same founder population confirmed the association between
FTO
and BP.

Conclusions—

These results suggest that, in a French Canadian founder population,
FTO
may increase not only risk for obesity, as demonstrated in other populations, but also for hypertension. The latter may be related, at least in part, to the regulation of sympathetic vasomotor tone.
"Teder" behaviour (tenderness) – an exploration into the neural pathways of mild touch perception in mammals and birds
Authors: Dubbeldam Jacob , Kortmulder Koenraad
Published: April 2009

A category of teder interaction is proposed as the main source of (mutual) mild touch stimuli in higher vertebrates. The somatosensory circuits for the perception of these stimuli in mammals and birds are discussed using data from the literature. In addition to the usual somatosensory areas of the brain, in mammals mild touch signals are also conducted to the insula, which is closely connected to the limbic system. This separate processing of mild touch stimuli lends more substance to the category of teder behaviour. The comparable neuroanatomy in birds is more difficult to interpret. There are some intriguing parallels between the relevant circuits of mammals and birds, though in the telencephalic parts in particular, conclusions are limited by uncertainties as to the homologies of the mammalian and avian brains.
Spatial and temporal variability of fish communities of the Upper Mississippi River, USA
Authors: Yildirim Ayhan , Pegg Mark
Published: April 2009

Fish community structure, morphological characteristics, functional composition, and life history attributes in relation to three aquatic habitats, backwater shoreline (BWS), main channel borders (MCB), and side channel borders (SCB) in Pool 4 of the Upper Mississippi River System (UMRS) were assessed. Fish communities were sampled annually using standardized electrofishing techniques from 1994 to 2004. We found significant differences in community composition and abundance, and the clearest pattern was that diversity and fish community structure in BWS were different from those in both MCB and SCB. We also found morphological characteristics, functional composition, and life-history differences among the habitats, with fish communities from BWS having a number of different characteristics from both MCB and SCB. Temporal changes in fish abundance, community structure, morphological, functional and life-history attributes from each habitat may reflect both human impact and environmental factors on the Upper Mississippi River System.
Serological characterization and confirmation of the taxonomic status of Montivipera albizona (Serpentes, Viperidae) with an additional new locality record and some phylogenetical comments
Authors: Göçmen Bayram , Arikan Hüseyin , Yildiz Mehmet Zülfü , Mermer Ahmet , Alpagut-Keskin Nursen
Published: April 2009

This is the first record of the presence of Montivipera albizona (Nilson, Andrén & Flärdh 1990), in Kahramanmaraş province, Mediterranean Region of Turkey. Here, one young male specimen was collected and is described. The present record of M. albizona extends its known distribution (Kulmac Mountain Range, Sivas) some 250 km to the south-west, where the Anatolian Diagonal exhibits a bifurcation. Our data based on the electropheoretic analysis of blood-sera, indicate that the M. xanthina populations from the western Anatolia and M. albizona distributed along the Anatolian Diagonal show significant differences, qualitatively and quantitatively. Accordingly, it is concluded that M. albizona should not be included within the polymorphic species M. xanthina which lives in western Anatolia and therefore, it should be accepted as a valid species. Moreover, the actual distributions of the related taxa in Anatolia and the geographic structure of the Anatolian Diagonal were discussed.
Hybridization behaviour between two common European cyprinid fish species – silver bream, Blicca bjoerkna and common bream, Abramis brama – in a controlled environment
Authors: Matondo Billy Nzau , Ovidio Michaël , Philippart Jean-Claude , Poncin Pascal
Published: April 2009

The egg release–mating comparison, heterospecific matings and mating success under two hybridization conditions – (i) mixing one sex per species and (ii) mixing both sexes from each species – were investigated to determine whether silver bream Blicca bjoerkna and common bream Abramis brama can hybridize in nature.The results revealed that non-matings in hybridization experiments of silver bream females × common bream males can be explained by territorial and aggressiveness activities observed in common bream. In common bream females × silver bream males, heterospecific matings were observed but their numbers were significantly lower than the spawning numbers, and in this experiment, a female mated with one to four heterospecific males. In mixing both sexes from both species, similar spawning – mating numbers were observed but heterospecific matings accounted for only 27% of the total matings, with 24% accounting for heterospecific matings between common bream females and silver bream males, directly or by opportunism. Mating success was characterized by the occurrence of fertilized eggs after matings.Natural hybridization occurred preferentially between common bream females and silver bream males.
Global Pharma in the Land of Snows: Tibetan Medicines, SARS, and Identity Politics Across Nations
Authors: Adams Vincanne , Craig Sienna
Published: April 2009

This article takes as its starting point the outbreak of the SARS epidemic in 2002–2003 in the People's Republic of China (PRC) to ask pertinent questions about the politics of identity in the Tibet Autonomous Region (TAR), and to connect these issues to the circulation of, as well as the social and economic value placed on, Tibetan medicines within China and abroad. We aim to connect the global pharmaceutical industry—including the ways it shapes science, disseminates knowledge, increases market demand, and influences clinical and social practice—to the production of Tibetan identities. We discuss dramatic increases in the production and sale of Tibetan medicinal products, specifically protective amulets, 'precious pills', and incense, during a particularly traumatic and widely publicised public health crisis in the PRC. These products clearly demand that we rethink the category 'medicine'. The popularity of these products during the SARS epidemic also points to the complicated positions of Tibetans and Tibetan cultural forms within contemporary China. What was it about these products that gave rise to the perception among Chinese and Tibetans alike they could 'save' or 'protect' people from contracting SARS. In more general terms, we ask if this exponential growth of the Tibetan medical industry in China—heightened during the SARS epidemic, but continuing apace since then—is allowing for cultural expression that highlights Tibetan uniqueness difference within otherwise contested social and political arenas. Or, is the global pharmaceutical industry in China in the process of encompassing and reformulating Tibetan medicine? Finally, we explore connections and distinctions between the rise in highly marketed Tibetan medicinals in China and their availability and appeal in the West.
Nourishing Life, Cultivation and Material Culture in the Late Ming: Some Thoughts on Zunsheng bajian (Eight Discourses on Respecting Life, 1591)
Authors: Hsiu-fen Chen
Published: April 2009

This article sets out to explore the ideas and practices of yangsheng (nourishing life or health preservation) in the late Ming, i.e. late sixteenth- and early seventeenth-century China. Yangsheng had long played a key role in the traditions of Chinese medicine, religions and court societies. Initially restricted to certain social classes and milieux, knowledge of yangsheng began to spread much more widely from the Song dynasty (960–1279) onwards, mostly owing to rapid social and economic change. In this context, the theories and practices of yangsheng attracted the attention and curiosity of many scholars. The popularisation of yangsheng peaked in the sixteenth and seventeenth centuries. Numerous literary works, essay collections and household encyclopaedias for everyday use have passages and sections on yangsheng. They describe various ideas and techniques of yangsheng by means of regulating the body in daily life, involving sleeping, exercising, washing, eating, drinking, etc. Through a survey of the most famous late Ming work on yangsheng, Zunsheng bajian (1591), this article attempts to highlight how yangsheng came to dominate the scholarly lifestyle. It will give a clear picture of the ideas of a late Ming literatus on prolonging life and replenishing the body, while showing how these practices were inspired by the flourishing material culture of the late Ming as a whole.
Spatial Variation of the Regional Wind Field with Land–Sea Contrasts and Complex Topography
Authors: Ha Kyung-Ja , Shin Sun-Hee , Mahrt Larry
Published: April 2009

This study examines the spatial variation of the wind field observed in the coastal zone of southeast Korea with its complex terrain, using measurements from a regional network 75 km across and centered about Busan. Results are compared with observations from an inland regional network centered around Daegu, Korea, with less dramatic, but still significant, surface heterogeneity. The coherency between stations is examined in terms of the between-station correlations of the wind components for all pairs of stations as a function of separation distance between stations. A mesovelocity scale is defined as a measure of the spatial variability of the wind field within the network. This variability is related to wind speed and cloud cover for the two contrasting regional networks. Additional comparisons are made with a homogenous rural network in Iowa. The results underscore the complexity of flow with topography, urban areas, and land–sea contrasts and demonstrate the inadequacy of existing network strategies.