An essential role for Ran GTPase in epithelial ovarian cancer cell survival

<p>Abstract</p> <p>Background</p> <p>We previously identified that Ran protein, a member of the Ras GTPase family, is highly expressed in high grade and high stage serous epithelial ovarian cancers, and that its overexpression is associated with a poor prognosis. Ran is known to contribute to both nucleocytoplasmic transport and cell cycle progression, but its role in ovarian cancer is not well defined.</p> <p>Results</p> <p>Using a lentivirus-based tetracycline-inducible shRNA approach, we show that downregulation of Ran expression in aggressive ovarian cancer cell lines affects cellular proliferation by inducing a caspase-3 associated apoptosis. Using a xenograft tumor assay, we demonstrate that depletion of Ran results in decreased tumorigenesis, and eventual tumor formation is associated with tumor cells that express Ran protein.</p> <p>Conclusion</p> <p>Our results suggest a role for Ran in ovarian cancer cell survival and tumorigenicity and suggest that this critical GTPase may be suitable as a therapeutic target.</p

CHRONIC PAIN SELF-EFFICACY AS A MEDIATOR OF THE LINK BETWEEN ROMANTIC ATTACHMENT INSECURITY, INDIVIDUAL FUNCTIONING, AND COUPLE SATISFACTION: A PRELIMINARY STUDYS

This preliminary study was inspired by the Attachment-Diathesis Model of Chronic Pain (ADMoCP) and examined pain self-efficacy as a mediator of the relation between people’s insecure romantic attachment and individual functioning, as well couple satisfaction. This study used a sample of 45 adults with chronic pain from the community who have been in couple relationships for at least 6 months. Participants completed self-report measures. Direct links were obtained between 1) insecure romantic attachment (anxiety over abandonment) and pain self-efficacy, 2) pain self-efficacy and individual functioning, 3) insecure romantic attachment and low individual functioning, and 4) insecure romantic attachment and lower couple satisfaction. Results also showed that pain self-efficacy significantly mediates the relation between anxiety over abandonment and individual functioning, thus adding to existing literature as well as providing more support for the ADMoCP. Future research directions are discussed along with clinical implications.Keywords: Chronic Pain. Romantic Attachment. Pain Self-Efficacy. Individual Functioning. RESUMOEste estudo preliminar foi inspirado no Attachment-Diathesis Model of Chronic Pain – ADMoCP e investigou a autoeficácia no manejo da dor como um mediador da ligação entre estilo de apego inseguro nas relações afetivas, funcionamento individual e satisfação conjugal. Este estudo utilizou uma amostra de 45 adultos da comunidade com dor crônica e que estavam em um relacionamento há pelo menos 6 meses. Participantes responderam a questionários de autorrelato. Foram obtidas relações diretas entre 1) estilo de apego inseguro nas relações afetivas (ansiedade de abandono) e autoeficácia no manejo da dor, 2) autoeficácia no manejo da dor e funcionamento individual, 3) estilo de apego inseguro nas relações afetivas e limitações no funcionamento individual e 4) estilo de apego inseguro nas relações afetivas e menor satisfação conjugal. Os resultados também mostraram que a autoeficácia no manejo da dor interfere significativamente na relação entre ansiedade de abandono e funcionamento individual, corroborando a literatura existente bem como fornecendo mais suporte para a ADMoCP. São discutidas futuras direções de pesquisa bem como implicações clínicas.Palavras-chave: Dor Crônica. Apego nas relações afetivas. Autoeficácia no manejo da dor. Funcionamento Individual

CHRONIC PAIN SELF-EFFICACY AS A MEDIATOR OF THE LINK BETWEEN ROMANTIC ATTACHMENT INSECURITY, INDIVIDUAL FUNCTIONING, AND COUPLE SATISFACTION: A PRELIMINARY STUDYS

This preliminary study was inspired by the Attachment-Diathesis Model of Chronic Pain (ADMoCP) and examined pain self-efficacy as a mediator of the relation between people’s insecure romantic attachment and individual functioning, as well couple satisfaction. This study used a sample of 45 adults with chronic pain from the community who have been in couple relationships for at least 6 months. Participants completed self-report measures. Direct links were obtained between 1) insecure romantic attachment (anxiety over abandonment) and pain self-efficacy, 2) pain self-efficacy and individual functioning, 3) insecure romantic attachment and low individual functioning, and 4) insecure romantic attachment and lower couple satisfaction. Results also showed that pain self-efficacy significantly mediates the relation between anxiety over abandonment and individual functioning, thus adding to existing literature as well as providing more support for the ADMoCP. Future research directions are discussed along with clinical implications. Keywords: Chronic Pain. Romantic Attachment. Pain Self-Efficacy. Individual Functioning.   RESUMO Este estudo preliminar foi inspirado no Attachment-Diathesis Model of Chronic Pain – ADMoCP e investigou a autoeficácia no manejo da dor como um mediador da ligação entre estilo de apego inseguro nas relações afetivas, funcionamento individual e satisfação conjugal. Este estudo utilizou uma amostra de 45 adultos da comunidade com dor crônica e que estavam em um relacionamento há pelo menos 6 meses. Participantes responderam a questionários de autorrelato. Foram obtidas relações diretas entre 1) estilo de apego inseguro nas relações afetivas (ansiedade de abandono) e autoeficácia no manejo da dor, 2) autoeficácia no manejo da dor e funcionamento individual, 3) estilo de apego inseguro nas relações afetivas e limitações no funcionamento individual e 4) estilo de apego inseguro nas relações afetivas e menor satisfação conjugal. Os resultados também mostraram que a autoeficácia no manejo da dor interfere significativamente na relação entre ansiedade de abandono e funcionamento individual, corroborando a literatura existente bem como fornecendo mais suporte para a ADMoCP. São discutidas futuras direções de pesquisa bem como implicações clínicas. Palavras-chave: Dor Crônica. Apego nas relações afetivas. Autoeficácia no manejo da dor. Funcionamento Individual

Why Is Aging a Risk Factor for Cognitive Impairment in Parkinson's Disease?—A Resting State fMRI Study

Using resting-state functional MRI (rsfMRI) data of younger and older healthy volunteers and patients with Parkinson's disease (PD) with and without mild cognitive impairment (MCI) and applying two different analytic approaches, we investigated the effects of age, pathology, and cognition on brain connectivity. When comparing rsfMRI connectivity strength of PD patients and older healthy volunteers, reduction between multiple brain regions in PD patients with MCI (PD-MCI) compared with PD patients without MCI (PD-non-MCI) was observed. This group difference was not affected by the number and location of clusters but was reduced when age was included as a covariate. Next, we applied a graph-theory method with a cost-threshold approach to the rsfMRI data from patients with PD with and without MCI as well as groups of younger and older healthy volunteers. We observed decreased hub function (measured by degree and betweenness centrality) mainly in the medial prefrontal cortex (mPFC) in older healthy volunteers compared with younger healthy volunteers. We also found increased hub function in the posterior medial structure (precuneus and the cingulate cortex) in PD-non-MCI patients compared with older healthy volunteers and PD-MCI patients. Hub function in these posterior medial structures was positively correlated with cognitive function in all PD patients. Together these data suggest that overlapping patterns of hub modifications could mediate the effect of age as a risk factor for cognitive decline in PD, including age-related reduction of hub function in the mPFC, and recruitment availability of the posterior medial structure, possibly to compensate for impaired basal ganglia function

Regional Brain Stem Atrophy in Idiopathic Parkinson's Disease Detected by Anatomical MRI

Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder characterized by the dysfunction of dopaminergic dependent cortico-basal ganglia loops and diagnosed on the basis of motor symptoms (tremors and/or rigidity and bradykinesia). Post-mortem studies tend to show that the destruction of dopaminergic neurons in the substantia nigra constitutes an intermediate step in a broader neurodegenerative process rather than a unique feature of Parkinson's disease, as a consistent pattern of progression would exist, originating from the medulla oblongata/pontine tegmentum. To date, neuroimaging techniques have been unable to characterize the pre-symptomatic stages of PD. However, if such a regular neurodegenerative pattern were to exist, consistent damages would be found in the brain stem, even at early stages of the disease. We recruited 23 PD patients at Hoenn and Yahr stages I to II of the disease and 18 healthy controls (HC) matched for age. T1-weighted anatomical scans were acquired (MPRAGE, 1 mm3 resolution) and analyzed using an optimized VBM protocol to detect white and grey matter volume reduction without spatial a priori. When the HC group was compared to the PD group, a single cluster exhibited statistical difference (p<0.05 corrected for false detection rate, 4287 mm3) in the brain stem, between the pons and the medulla oblongata. The present study provides in-vivo evidence that brain stem damage may be the first identifiable stage of PD neuropathology, and that the identification of this consistent damage along with other factors could help with earlier diagnosis in the future. This damage could also explain some non-motor symptoms in PD that often precede diagnosis, such as autonomic dysfunction and sleep disorders