bluuebunny/crossref_metadata_2025 huggingface dataset:
Cannabidiol Induces Programmed Cell Death in Breast Cancer Cells by Coordinating the Cross-talk between Apoptosis and Autophagy
Authors: Shrivastava Ashutosh , Kuzontkoski Paula M. , Groopman Jerome E. , Prasad Anil
Published: May 2011

Cannabidiol (CBD), a major nonpsychoactive constituent of cannabis, is considered an antineoplastic agent on the basis of its in vitro and in vivo activity against tumor cells. However, the exact molecular mechanism through which CBD mediates this activity is yet to be elucidated. Here, we have shown CBD-induced cell death of breast cancer cells, independent of cannabinoid and vallinoid receptor activation. Electron microscopy revealed morphologies consistent with the coexistence of autophagy and apoptosis. Western blot analysis confirmed these findings. We showed that CBD induces endoplasmic reticulum stress and, subsequently, inhibits AKT and mTOR signaling as shown by decreased levels of phosphorylated mTOR and 4EBP1, and cyclin D1. Analyzing further the cross-talk between the autophagic and apoptotic signaling pathways, we found that beclin1 plays a central role in the induction of CBD-mediated apoptosis in MDA-MB-231 breast cancer cells. Although CBD enhances the interaction between beclin1 and Vps34, it inhibits the association between beclin1 and Bcl-2. In addition, we showed that CBD reduces mitochondrial membrane potential, triggers the translocation of BID to the mitochondria, the release of cytochrome c to the cytosol, and, ultimately, the activation of the intrinsic apoptotic pathway in breast cancer cells. CBD increased the generation of reactive oxygen species (ROS), and ROS inhibition blocked the induction of apoptosis and autophagy. Our study revealed an intricate interplay between apoptosis and autophagy in CBD-treated breast cancer cells and highlighted the value of continued investigation into the potential use of CBD as an antineoplastic agent. Mol Cancer Ther; 10(7); 1161–72. ©2011 AACR.
Hsp90 Inhibitor–Mediated Disruption of Chaperone Association of ATR with Hsp90 Sensitizes Cancer Cells to DNA Damage
Authors: Ha Kyungsoo , Fiskus Warren , Rao Rekha , Balusu Ramesh , Venkannagari Sreedhar , Nalabothula Narasimha Rao , Bhalla Kapil N.
Published: May 2011

Following DNA damage that results in stalled replication fork, activation of ATR-CHK1 signaling induces the DNA damage response (DDR) in transformed cells. In the present studies on human cervical and breast cancer cells, we determined the effects of hsp90 inhibition on the levels and accumulation of DNA damage/repair–associated proteins following exposure to γ-ionizing radiation (IR; 4 Gy). We show that hsp90 inhibition with 17-allylamino-demehoxygeldanamycin or the novel, nongeldanamycin analogue AUY922 (resorcinylic isoxazole amide; Novartis Pharma) dose-dependently reduced the levels of ATR and CHK1 without affecting ATM levels. AUY922-mediated depletion of ATR and CHK1 was associated with an increase in their polyubiquitylation and decreased binding to hsp90. Cotreatment with bortezomib partially restored AUY922-mediated depletion of ATR and CHK1 levels. Additionally, treatment with AUY922 reduced the accumulation of ATR, p53BP1, and CHK1 but not γ-H2AX to the sites of DNA damage. Following exposure to IR, AUY922 treatment abrogated IR-induced phospho (p)-ATR and p-CHK1 levels, but significantly enhanced γ-H2AX levels. AUY922 treatment also increased IR-induced accumulation of the cells in G2–M phase of the cell cycle, inhibited the repair of IR-induced DNA damage, and augmented IR-mediated loss of clonogenic survival. Short hairpin RNA–mediated depletion of ATR also inhibited IR-induced p-ATR and p-CHK1, but increased γ-H2AX levels, sensitizing cancer cells to IR-induced apoptosis and loss of clonogenic survival. These findings indicate that ATR is a bona fide hsp90 client protein and post-IR administration of AUY922, by inhibiting ATR-CHK1–mediated DDR, sensitizes cancer cells to IR. Mol Cancer Ther; 10(7); 1194–206. ©2011 AACR.
C-Raf Is Required for the Initiation of Lung Cancer by K-RasG12D
Authors: Karreth Florian A. , Frese Kristopher K. , DeNicola Gina M. , Baccarini Manuela , Tuveson David A.
Published: May 2011

The Ras/Raf/MEK/ERK (extracellular signal–regulated kinase) pathway is primarily responsible for mitogenesis in metazoans, and mutational activation of this pathway is common in cancer. A variety of selective chemical inhibitors directed against the mitogen-activated protein kinase pathway are now available for clinical investigation and thus the determination of the importance of each of the kinases in oncogenesis is paramount. We investigated the role of two Raf kinases, B-Raf and C-Raf, in Ras oncogenesis, and found that although B-Raf and C-Raf have overlapping functions in primary mesenchymal cells, C-Raf but not B-Raf is required for the proliferative effects of K-RasG12D in primary epithelial cells. Furthermore, in a lung cancer mouse model, C-Raf is essential for tumor initiation by oncogenic K-RasG12D, whereas B-Raf is dispensable for this process. Our findings reveal that K-RasG12D elicits its oncogenic effects primarily through C-Raf and suggest that selective C-Raf inhibition could be explored as a therapeutic strategy for K-Ras–dependent cancers.

Significance: Ras is one of the most prevalent oncogenes in human cancer; however, it is considered “undruggable.” Therefore, increasing our understanding of the importance of Ras effectors, including the Raf/MEK/ERK pathway, will create novel avenues for therapeutic intervention. Cancer Discovery; 1(2); 128–36. © 2011 AACR.

Read the Commentary on this article by Rebocho and Marais, p. 98

This article is highlighted in the In This Issue feature, p. 91
Exploratory Study on Domain-Specific Determinants of Opiate-Dependent Individuals’ Quality of Life
Authors: De Maeyer J. , Vanderplasschen W. , Lammertyn J. , van Nieuwenhuizen C. , Broekaert E.
Published: May 2011

Background/Aims: Studies on determinants of quality of life (QoL) among opiate-dependent individuals are scarce. Moreover, findings concerning the role of severity of drug use are inconsistent. This exploratory study investigates the association between domain-specific QoL and demographic, social, person, health and drug-related variables, and potential indirect effects of current heroin use on opiate-dependent individuals’ QoL. Methods: A cohort of opiate-dependent individuals who started outpatient methadone treatment at least 5 years previously (n = 159) were interviewed about their current QoL, psychological distress, satisfaction with methadone treatment and the severity of drug-related problems using the Lancashire Quality of Life Profile, the Brief Symptom Inventory, the Verona Service Satisfaction Scale for Methadone Treatment and the EuropASI. Results: None of the QoL domains were defined by the same compilation of determinants. No direct effect of current heroin use on QoL was retained, but path analyses demonstrated its indirect effects on the domains of ‘living situation’, ‘finances’ and ‘leisure and social participation’. Conclusion: These findings illustrate the particularity of each QoL domain and the need for a multidimensional approach to the concept. The relationship between current heroin use and various domains of opiate-dependent individuals’ QoL is complex, indirect and mediated by psychosocial and treatment-related variables.
Osteoclasts in the Dental Microenvironment: A Delicate Balance Controls Dental Histogenesis
Authors: Berdal A. , Castaneda B. , Aïoub M. , Néfussi J.R. , Mueller C. , Descroix V. , Lézot F.
Published: May 2011

The impact of osteoclast activity on dental development has been previously analyzed but in the context of severe osteopetrosis. The present study sought to investigate the effects of osteoclast hypofunction,present in Msx2 gene knockin mutant mice (Msx2–/–), and hyperfunction, in transgenic mice driving RANK over-expression in osteoclast precursors (RANKTg), on tooth development. In Msx2–/– mice, moderate osteopetrosis was observed, occurring exclusively in the periodontal region. Microradiographical and histological analyses revealed an abnormal dental epithelium histogenesis that gave rise to odontogenic tumor-like structures. This led to impaired tooth eruption, especially of the third mandibular molars. In RANKTg mice, root histogenesis showed site-specific upregulation of dental cell proliferation and differentiation rates. This culminated in roots with a reduced diameter and pulp size albeit of normal length. These two reverse experimental systems will enable the investigation of distinctive dental cell and osteoclast communication in normal growth and tumorigenesis.
Potential Role of the Amelogenin N-Terminus in the Regulation of Calcium Phosphate Formation in vitro
Authors: Le Norcy E. , Kwak S.-Y. , Wiedemann-Bidlack F.B. , Beniash E. , Yamakoshi Y. , Simmer J.P. , Margolis H.C.
Published: May 2011

N-terminal and C-terminal (CT) domains of amelogenin have been shown to be essential for proper enamel formation. Recent studies have also suggested that although the C-terminus plays an apparent role in protein-mineral interactions, other amelogenin structural domains are involved. The objective was to explore the role of the amelogenin N-terminus in the regulation of calcium phosphate formation in vitro. Spontaneous mineralization studies were carried out using the phosphorylated (+P) and nonphosphorylated (–P) N-terminus of the leucine-rich amelogenin peptide (LRAP) that lacks the hydrophilic CT domain. Mineralization progress was monitored via changes in solution pH. Mineral phases formed were characterized using TEM, selected area electron diffraction, and FT-IR. In controls, amorphous calcium phosphate was initially formed and subsequently transformed to randomly oriented hydroxyapatite (HA) plate-like crystals. In contrast to the control, LRAP(+P)-CT stabilized ACP formation for >1 day, while LRAP(–P)-CT accelerated the transformation of ACP to HA but had little effect on crystal shape or orientation. In conclusion, the N-terminal domain found in LRAP, as in amelogenins, appears to have the capacity to interact with forming calcium phosphate mineral phases. Results suggest that the N-terminal domain of amelogenin may play a direct role in early stages of enamel formation.
Phenotypic and Differentiation Stability of Human Embryonic Stem Cell-Derived Osteoblasts
Authors: Arpornmaeklong Premjit , Pressler Michael J. , Krebsbach Paul H.
Published: May 2011

Purpose: To ensure the efficiency and safety of transplanted human embryonic stem cell (hESC)-derived osteoblast-like cells (hESC-OS) for bone regeneration, this study was designed to determine the effects of continuous cell expansion on the osteoblastic differentiation stability, pluripotency, and tumorigenic potential of long-term expanded hESC-OS. Methods: hESCs manually harvested as cell aggregates or enzymatically dissociated as single cells were directly incubated in osteogenic medium and serially passaged to passage 25. Expression of osteoblast-related genes, pluripotent regulator genes, and genes related to tumorigenesis were examined at the primary passage and every 5 passages thereafter. hESC-OS were subcutaneously transplanted into nude mice for 4–24 weeks to test for teratoma formation. hESC-OS were recultivated in hESC culture conditions to evaluate the extent to which reverse differentiation back to the undifferentiated stage may occur. Results: hESC-OS derived from hESC aggregates and dissociated cells exhibited comparable osteoblast differentiation patterns. Expression levels of osteoblast-related genes reached plateau levels at passages 5–10 before declining in higher passages. Expression of tumor-associated genes was not significantly increased. Only hESC-OS at primary and first passages formed teratomas after 4 weeks in vivo. The hESC-OS were not able to revert to hESCs. Conclusions: Expanded hESC-OS demonstrated lineage-specific differentiation stability, did not maintain the pluripotency of hES cells, and were genetically stable. Thus, hESC-OS may be considered for large animal preclinical studies.
Human Umbilical Mesenchymal Stem Cells Promote Recovery After Ischemic Stroke
Authors: Lin Yu-Ching , Ko Tsui-Ling , Shih Yang-Hsin , Lin Maan-Yuh Anya , Fu Tz-Win , Hsiao Hsiao-Sheng , Hsu Jung-Yu C. , Fu Yu-Show
Published: May 2011

Background and Purpose—

Stroke is a cerebrovascular defect that leads to many adverse neurological complications. Current pharmacological treatments for stroke remain unclear in their effectiveness, whereas stem cell transplantation shows considerable promise. Previously, we have shown that human umbilical mesenchymal stem cells (HUMSCs) can differentiate into neurons in neuronal-conditioned medium. Here we evaluate the therapeutic potential of HUMSC transplantation for ischemic stroke in rats.

Methods—

Focal cerebral ischemia was produced by middle cerebral artery occlusion and reperfusion. The HUMSCs treated with neuronal-conditioned medium or not treated were transplanted into the ischemic cortex 24 hours after surgery.

Results—

Histology and MRI revealed that rats implanted with HUMSCs treated with neuronal-conditioned medium or not treated exhibited a trend toward less infarct volume and significantly less atrophy compared with the control group, which received no HUMSCs. Moreover, rats receiving HUMSCs showed significant improvements in motor function, greater metabolic activity of cortical neurons, and better revascularization in the infarct cortex. Implanted HUMSCs, treated or not treated, survived in the infarct cortex for at least 36 days and released neuroprotective and growth-associated cytokines, including brain-derived neurotrophic factor, platelet-derived growth factor-AA, basic fibroblast growth factor, angiopoietin-2, CXCL-16, neutrophil-activating protein-2, and vascular endothelial growth factor receptor-3.

Conclusions—

Our results demonstrate the therapeutic benefits of HUMSC transplantation for ischemic stroke, likely due to the ability of the cells to produce growth-promoting factors. Thus, HUMSC transplantation may be an effective therapy in the future.
Transient Ischemic Attack and Incident Depression
Authors: Luijendijk Hendrika J. , Stricker Bruno H.Ch. , Wieberdink Renske G. , Koudstaal Peter J. , Hofman Albert , Breteler Monique M. , Tiemeier Henning
Published: May 2011

Background and Purpose—

Depression after stroke is common. Like stroke, transient ischemic attack (TIA) is a manifestation of long-term atherosclerotic damage to the brain. However, the risk of depression developing after a TIA is uncertain. We studied whether TIA increases the risk of incident late-life depression.

Methods—

A cohort study of 5095 inhabitants of Rotterdam, the Netherlands, was performed between 1993 and 2005. Participants were aged 56 years or older and free of depression at baseline. TIA and depression were identified through regular standardized examinations and continuous monitoring of medical records. We estimated hazard ratios (HR) with time-varying Cox regression analyses, adjusting for sociodemographic and health-related factors.

Results—

During follow-up, 407 depressive syndromes occurred, of which 103 met criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM) for depressive disorders. TIA was significantly associated with the risk of incident depressive syndromes (HR, 1.68; 95% CI, 1.12–2.51) and DSM-defined depressive disorders (HR, 2.42; 95% CI, 1.26–4.67). The risk of depressive syndromes increased with the number of TIA a person had experienced (HR, 1.45; 95% CI, 1.17–1.81), as did the risk of depressive disorders (HR, 1.63; 95% CI, 1.18–2.24). In persons without a history of depression at baseline, we found an almost 3-fold increased risk of DSM-defined depressive disorders (HR, 2.91; 95% CI, 0.96–8.81).

Conclusions—

TIA was independently associated with an increased risk of incident depression. Our finding suggests that symptomatic cerebrovascular disease increases the vulnerability to late-life depression.
Outcomes of Intravenous Thrombolysis After Dissemination of the Stroke Code and Designation of New Referral Hospitals in Catalonia
Authors: Abilleira Sònia , Dávalos Antoni , Chamorro Ángel , Álvarez-Sabín José , Ribera Aida , Gallofré Miquel
Published: May 2011

Background and Purpose—

From 2006, the Stroke Code system operates throughout Catalonia with full coverage. The objective of this study was to determine safety and effectiveness of intravenous thrombolysis in routine practice through a monitored study (Catalan Stroke Code and Thrombolysis [Cat-SCT]) and to assess outcomes according to hospitals' previous experience.

Methods—

We conducted a prospective, multicenter, observational, monitored study of recombinant tissue plasminogen activator-treated patients declared to the Cat-SCT by all treating hospitals in Catalonia (n=13, of which 6 were newly designated) over a 12-month period. Consecutive recruitment and quality of data were assured through comprehensive quality control. We estimated rates of outcome measures for the potential final sample (after inclusion of undeclared cases) and compared them with those reported for the actual sample. Symptomatic intracranial hemorrhage, mortality, and favorable outcome (modified Rankin Scale score 0 to 1) at 3 months were also evaluated according to hospitals' previous experience using multilevel logistic regression.

Results—

We analyzed 488 patients with a median age of 72 years (interquartile range: 63, 77), 57.2% males, with a baseline National Institutes of Health Stroke Scale score of 13 (interquartile range: 8, 19), and stroke to treatment time of 150 minutes (interquartile range: 120, 180 minutes). Symptomatic intracranial hemorrhage (Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy definition) was observed in 3.3% patients. Ninety-day mortality was 16.6% and 38.5% showed a favorable outcome at 3 months. External monitoring set inclusion losses at <5%. A sensitivity analysis including undeclared cases did not show significant changes in main outcomes. Inexperienced hospitals achieved similar outcomes, except for a higher rate of favorable outcome at 3 months.

Conclusions—

Health planning applied to acute stroke care and based on dissemination of the Stroke Code system and designation of new referral hospitals showed intravenous thrombolysis safe and effective in routine practice, even among inexperienced hospitals.
Natural History, Predictors, and Associations of Depression 5 Years After Stroke
Authors: Ayerbe Luis , Ayis Salma , Rudd Anthony G. , Heuschmann Peter U. , Wolfe Charles D.A.
Published: May 2011

Background and Purpose—

The longer-term natural history of depression after stroke is poorly understood. We estimate frequency, predictors, and associations of depression up to 5 years after stroke in a population-based study.

Methods—

Data from 3689 patients registered in the South London Stroke Register 1995 to 2006 were used. Baseline data included age, sex, ethnicity, socioeconomic status, and stroke severity. At 3 months and at 1, 3, and 5 years, survivors were assessed for depression (Hospital Anxiety and Depression; depression subscale score >7 indicates depression), cognition, disability, activity, accommodation, employment, and social networks. Associations with depression were investigated with logistic regression. Data are reported with OR and 95% CI.

Results—

Depression frequencies were 33% (30%–36%), 28% (25%–30%), 32% (30%–35%), and 31% (27%–34%) at 3 months and at 1, 3, and 5 years after stroke, respectively. Forty-eight percent of patients were not depressed at any time point; 49% to 55% of depressed patients at 1 assessment remained depressed at follow-up; and 15% to 20% of patients at each assessment were new cases. Predictors of depression included stroke severity, inability to work, and impaired cognition. Associations with depression at follow-up included impaired cognition, lack of family support, institutionalization, inability to work, functional dependence, and low activity level.

Conclusions—

Frequency of depression up to 5 years after stroke is 30%; however, it is a dynamic situation with recovery and new cases diagnosed over time. These findings support the need for regular assessment of depression and its associated factors and for the development of effective interventions to reduce depression after stroke.
Are Distal Protection Devices ‘Protective’ During Carotid Angioplasty and Stenting?
Authors: Tallarita Tiziano , Rabinstein Alejandro A. , Cloft Harry , Kallmes David , Oderich Gustavo S. , Brown Robert D. , Lanzino Giuseppe
Published: May 2011

Background and Purpose—

To evaluate the periprocedural outcome after carotid artery stenting with embolic brain protection (EBP+) versus without embolic brain protection (EBP−).

Methods—

We retrospectively reviewed data from a prospective nonrandomized database of 357 patients who underwent carotid artery stenting in the neuroradiology division of our institution from 1999 to 2009. One hundred five patients underwent angioplasty and stenting without distal protection, whereas 252 were treated with distal protection. Patients were analyzed according to their EBP status (+ or −) for the primary end points of perioperative stroke, death, or myocardial infarction.

Results—

Unprotected stenting was mostly performed in the early years of this study and this is reflected in significant baseline differences between the two groups. In our earlier experience, carotid artery stenting was used in patients with more significant comorbidities. Diabetes mellitus (
P
=0.04), previous coronary artery disease (
P
=0.02) and myocardial infarction (
P
=0.04), and symptomatic lesion (
P
=0.01) were significantly more common in the EBP− cohort. Despite these baseline differences, there were no significant differences in the primary end points (2% in the EBP+ group and 4.8% in the EBP−,
P
=0.15). The incidence of ipsilateral stroke in the EBP− and in the EBP+ group was 3.8% versus 0.8%, respectively (
P
=0.6). There were 2 perioperative deaths (1 in each group) and 4 myocardial infarctions (3 in the EBP+ arm and 1 in the EBP− arm, all non-Q infarcts;
P
=nonsignificant).

Conclusions—

In accordance with recent literature, this series cast doubts as to the real effectiveness of distal embolic protection devices in reducing periprocedural complications.
Response to Psychosocial Treatment in Poststroke Depression Is Associated With Serotonin Transporter Polymorphisms
Authors: Kohen Ruth , Cain Kevin C. , Buzaitis Ann , Johnson Vicki , Becker Kyra J. , Teri Linda , Tirschwell David L. , Veith Richard C. , Mitchell Pamela H.
Published: May 2011

Background and Purpose—

The Living Well With Stroke study has demonstrated effectiveness of a brief psychosocial treatment in reducing depressive symptoms after stroke. The purpose of this analysis was to determine whether key variables associated with prevalence of poststroke depression also predicted treatment response.

Methods—

Response to a brief psychosocial/behavioral intervention for poststroke depression was measured with the Hamilton Rating Scale for Depression. Analysis of covariance models tested for interaction of potential predictor variables with treatment group on percent change in Hamilton Rating Scale for Depression from pre- to post-treatment as an outcome.

Results—

Initial depression severity, hemispheric location, level of social support, age, gender, and antidepressant adherence did not interact with the treatment with respect to percent change in Hamilton Rating Scale for Depression when considered 1 at a time. Participants who carried 1 or 2
s
-alleles at the 5-HTTLPR serotonin transporter polymorphism or 1 or 2 9- or 12-repeats of the STin2 VNTR polymorphism had significantly better response to psychosocial treatment than those with no
s
-alleles or no 9- or 12-repeats.

Conclusions—

Opposite to the effects of antidepressant drug treatment with selective serotonin reuptake inhibitors, the Living Well With Stroke psychotherapy intervention was most effective in 5-HTTLPR
s
-allele carriers and STin2 VNTR 9- or 12-repeat carriers.

Clinical Trial Registration—

URL:
www.clinicaltrials.gov/ct/show/NCT00194454?order_1
. Unique identifier: NCT00194454.
Sublingual Microvascular Changes in Patients With Cerebral Small Vessel Disease
Authors: Khalilzada Mostafa , Dogan Kemal , Ince Can , Stam Jan
Published: May 2011

Background and Purpose—

It is unknown whether changes in cerebral small vessel disease (SVD) are limited to the brain or part of a generalized vascular disorder.

Methods—

We examined the sublingual microcirculation of 10 healthy controls, 10 patients with large vessel disease, and 8 with SVD, with side-stream dark field imaging. We analyzed 146 video fragments masked to the origin of the videos. Imaging software measured the functional capillary density per tissue surface unit. We scored the percentage of blood vessels with abnormal flow (abnormal flow index) and the presence of extravascular erythrocyte material as presumed evidence of past microbleeds or obliterated vessels.

Results—

Functional capillary density differed between the 3 groups (SVD, large vessel disease, and controls; means, 14.8, 17.0, and 16.1 mm/mm
2
;
P
=0.01). Abnormal flow was more frequent in SVD patients compared with large vessel disease patients and controls (medians, 10.5%, 6.1%, 5.5%;
P
=0.04). Extravascular erythrocyte material was almost exclusively present in patients with SVD (
P
=0.004).

Conclusions—

We found evidence of pathological changes in the sublingual microcirculation in patients with cerebral small vessel disease, which suggests that cerebral SVD is part of a generalized vascular disorder.
Association Between Stroke and Patients With Pelvic Inflammatory Disease
Authors: Chen Po-Chih , Tseng Teng-chu , Hsieh Jui-Yang , Lin Hui-Wen
Published: May 2011

Background and Purpose—

The aim of this study is to estimate the risk of stroke in a 3-year period after pelvic inflammatory disease (PID) using a nationwide population-based study.

Methods—

Our study cohort consisted of all patients with a diagnosis of PID (N=64 515) between 2004 and 2005 with a control cohort (1:2) of age-matched controls (N=129 030). Each patient was tracked from hospitalization until the end of 2006. Cox regressions were performed to compute the 3-year stroke-free survival rates after adjusting for possible confounding factors.

Results—

We found that women with PID were more likely to have strokes than the control population. After adjusting for potential confounding factors, the adjusted hazard ratio of stroke was 1.63 (95% CI, 1.45–1.85) for PID patients as compared to the general population cohort. Sensitivity analysis using a bootstrap approach further ensured the validity of the results of our study.

Conclusions—

We concluded that patients with PID have an association with stroke. Further research is necessary to investigate the pathophysiology between PID and stroke.
Burn: The Radical Disappearance of Kathy Change
Authors: Shahadi Joseph
Published: May 2011

Kathy Change was a performance artist whose outrageous public performances and leftist politics were largely ignored by the University of Pennsylvania students she performed for, until she set herself on fire. Her 1996 self-immolation prompts an inquiry into the effectiveness of public suicide as a mode of political performance.
Before Us a Savage God: Self-Fashioning the Nation in Yorùbá Performance
Authors: Odom Glenn
Published: May 2011

The concept of identity is in a state of evolution in Yorùbá society, and this evolution works itself out in praise poetry. This poetry is performed in a variety of contexts, and each performance context contributes something distinctive to Yorùbá modernity.
Mirror, Mirror: Joanna Frueh as Fairy Stepmother
Authors: Buszek Maria Elena
Published: May 2011

For over 20 years, scholar and performance artist Joanna Frueh has been a pioneering force in feminist art and criticism. In homage to Frueh's “erotic scholarship,” Frueh's own writing and performances concerning relationships between women are interwoven with a biographical history of the author and the artist's own student/teacher relationship.
Ontology and Autobiographical Performance: Joanna Frueh's Aesthetics of Orgasm
Authors: O'Bryan Jill
Published: May 2011

Frueh's performance piece, The Aesthetics of Orgasm, begins with a primal scene — Frueh, as a child, walks in on her parents having sex. Weaving thinking into sex, orgasm, and the erotic, Frueh positions herself within feminist scholarship, performing language that enables a kind of heterosexual eroticism that does not objectify.
Krapp's First Tape: Okada Toshiki's Enjoy
Authors: Poulton Cody
Published: May 2011

The Play Company's production of Enjoy, Okada Toshiki's wry and tender portrait of 20-something slackers looking for love and meaning in contemporary Tokyo highlights the play's witty dialogue. The New York production of this English translation reveals that in our recession-ridden times, the anxieties of today's Japanese youth are not so different from our own.
Multiple Processes Underlying Dimensional Change Card Sort Performance: A Developmental Electrophysiological Investigation
Authors: Waxer Matthew , Morton J. Bruce
Published: May 2011

Cognitive flexibility follows a protracted developmental trajectory [Morton, J. B. Understanding genetic, neurophysiological, and experiential influences on the development of executive functioning: The need for developmental models. Wiley Interdisciplinary Reviews: Cognitive Science, 2010]. For example, performance and patterns of brain activity associated with the dimensional change card sort (DCCS) show continued age-related changes into early adolescence. According to many theoretical accounts, the DCCS places demands on a single underlying executive process. In the present study, we investigated the possibility that multiple processes unfold within the timeframe of a single DCCS trial through the use of ERPs. Children (n = 40), adolescents (n = 20), and adults (n = 20) performed a modified version of the DCCS with distinct instruction cue- and stimulus-related periods. On any particular trial, the sorting rule either changed (i.e., switch trials) or remained the same (i.e., repeat trials), and the imperative stimulus either embodied conflict (i.e., bivalent stimuli) or did not (i.e., univalent stimuli). Findings were consistent with the hypothesis that multiple distinct executive processes unfold within a single trial. First, for all age groups, rule switching and conflict processing made additive contributions to variability in RT. Second, ERPs time-locked to the instruction cue revealed a late frontal negativity whose amplitude was greater for switch trials relative to repeat trials and that was associated with the magnitude of the behavioral switch cost, whereas ERPs time-locked to the imperative stimulus revealed a fronto-central N2 whose amplitude was greater for bivalent than univalent stimuli and that was associated with the magnitude of the behavioral conflict cost. Finally, switch and conflict-related processes showed distinct developmental trajectories. Taken together, the findings suggest that multiple executive processes underlie DCCS performance and its development. Theoretical implications are discussed.
Functional Imaging Reveals Working Memory and Attention Interact to Produce the Attentional Blink
Authors: Johnston Stephen J. , Linden David E. J. , Shapiro Kimron L.
Published: May 2011

If two centrally presented visual stimuli occur within approximately half a second of each other, the second target often fails to be reported correctly. This effect, called the attentional blink (AB; Raymond, J. E., Shapiro, K. L., & Arnell, K. M. Temporary suppression of visual processing in an RSVP task: An attentional blink? Journal of Experimental Psychology, Human Perception and Performance, 18, 849–860, 1992], has been attributed to a resource “bottleneck,” likely arising as a failure of attention during encoding into or retrieval from visual working memory (WM). Here we present participants with a hybrid WM–AB study while they undergo fMRI to provide insight into the neural underpinnings of this bottleneck. Consistent with a WM-based bottleneck account, fronto-parietal brain areas exhibited a WM load-dependent modulation of neural responses during the AB task. These results are consistent with the view that WM and attention share a capacity-limited resource and provide insight into the neural structures that underlie resource allocation in tasks requiring joint use of WM and attention.
Serotonin Transporter Genotype Modulates Subgenual Response to Fearful Faces Using an Incidental Task
Authors: O'Nions Elizabeth J. P. , Dolan Raymond J. , Roiser Jonathan P.
Published: May 2011

This study assessed the impact of serotonin transporter genotype (5-HTTLPR) on regional responses to emotional faces in the amygdala and subgenual cingulate cortex (sgACC), while subjects performed a gender discrimination task. Although we found no evidence for greater amygdala reactivity or reduced amygdala–sgACC coupling in short variant 5-HTTLPR homozygotes (s/s), we observed an interaction between genotype and emotion in sgACC. Only long variant homozygotes (la/la) exhibited subgenual deactivation to fearful versus neutral faces, whereas the effect in s/s subjects was in the other direction. This absence of subgenual deactivation in s/s subjects parallels a recent finding in depressed subjects [Grimm, S., Boesiger, P., Beck, J., Schuepbach, D., Bermpohl, F., Walter, M., et al. Altered negative BOLD responses in the default-mode network during emotion processing in depressed subjects. Neuropsychopharmacology, 34, 932–943, 2009]. Taken together, the findings suggest that subgenual cingulate activity may play an important role in regulating the impact of aversive stimuli, potentially conferring greater resilience to the effects of aversive stimuli in la/la subjects. Using dynamic causal modeling of functional magnetic resonance imaging data, we explored the effects of genotype on effective connectivity and emotion-specific changes in coupling across a network of regions implicated in social processing. Viewing fearful faces enhanced bidirectional excitatory coupling between the amygdala and the fusiform gyrus, and increased the inhibitory influence of the amygdala over the sgACC, although this modulation of coupling did not differ between the genotype groups. The findings are discussed in relation to the role of sgACC and serotonin in moderating responses to aversive stimuli [Dayan, P., & Huys, Q. J., Serotonin, inhibition, and negative mood. PLoS Comput Biol, 4, e4, 2008; Mayberg, H. S., Liotti, M., Brannan, S. K., McGinnis, S., Mahurin, R. K., Jerabek, P. A., et al. Reciprocal limbic–cortical function and negative mood: Converging PET findings in depression and normal sadness. Am J Psychiatry, 156, 675–682, 1999].
The Effects of Attention on Age-related Relational Memory Deficits: fMRI Evidence from a Novel Attentional Manipulation
Authors: Kim So-Yeon , Giovanello Kelly S.
Published: May 2011

Numerous studies have documented that older adults (OAs) do not perform as well as young adults (YAs) when task demands require the establishment or retrieval of a novel link between previously unrelated information (relational memory: RM). Nonetheless, the source of this age-related RM deficit remains unspecified. One of the most widely investigated factors is an age-related reduction in attentional resources. To investigate this factor, previous researchers have tested whether dividing YAs' attention during encoding equated their RM performance to that of OAs. However, results from these studies failed to replicate the age-related RM impairment observed in aging. The current study investigated whether a reduction in attentional resources for processing of relational information (i.e., relational attention) underlies age-related RM deficits. Using fMRI, we examined whether the effect of reduced attentional resources for processing of relational information is similar to that observed in aging at both behavioral and neural levels. The behavioral results showed that reduced attentional resources for relational information during encoding equated YAs RM performance to that of OAs. Furthermore, the fMRI results demonstrated that both aging, as well as reductions in relational attention in YAs, significantly reduced activity in brain areas associated with successful RM formation, namely, the ventrolateral and dorsolateral PFC, superior and inferior parietal regions, and left hippocampus. Such converging evidence from behavioral and neuroimaging studies suggests that a reduction in attentional resources for relational information is a critical factor for the RM deficit observed in aging.
Memory-based Decision-making with Heuristics: Evidence for a Controlled Activation of Memory Representations
Authors: Khader Patrick H. , Pachur Thorsten , Meier Stefanie , Bien Siegfried , Jost Kerstin , Rösler Frank
Published: May 2011

Many of our daily decisions are memory based, that is, the attribute information about the decision alternatives has to be recalled. Behavioral studies suggest that for such decisions we often use simple strategies (heuristics) that rely on controlled and limited information search. It is assumed that these heuristics simplify decision-making by activating long-term memory representations of only those attributes that are necessary for the decision. However, from behavioral studies alone, it is unclear whether using heuristics is indeed associated with limited memory search. The present study tested this assumption by monitoring the activation of specific long-term-memory representations with fMRI while participants made memory-based decisions using the “take-the-best” heuristic. For different decision trials, different numbers and types of information had to be retrieved and processed. The attributes consisted of visual information known to be represented in different parts of the posterior cortex. We found that the amount of information required for a decision was mirrored by a parametric activation of the dorsolateral PFC. Such a parametric pattern was also observed in all posterior areas, suggesting that activation was not limited to those attributes required for a decision. However, the posterior increases were systematically modulated by the relative importance of the information for making a decision. These findings suggest that memory-based decision-making is mediated by the dorsolateral PFC, which selectively controls posterior storage areas. In addition, the systematic modulations of the posterior activations indicate a selective boosting of activation of decision-relevant attributes.
Functional Connectivity Separates Switching Operations in the Posterior Lateral Frontal Cortex
Authors: Stelzel Christine , Basten Ulrike , Fiebach Christian J.
Published: May 2011

Task representations consist of different aspects such as the representations of the relevant stimuli, the abstract rules to be applied, and the actions to be performed. To be flexible in our daily lives, we frequently need to switch between some or all aspects of a task. In the present study, we examined whether switching between abstract task rules and switching between response hands is associated with overlapping regions in the posterior lateral frontal cortex and whether switching between these two aspects of a task representation is neurally implemented by distinct functional brain networks. Subjects performed a cue-based task-switching paradigm where the location of the task cue additionally specified the response hand to be used. Overlapping activity for switching between abstract rules versus response hands was present in the inferior frontal junction area of the posterolateral frontal cortex. This region, however, showed very distinct patterns of functional connectivity depending on the content of the switch: Increased functional connectivity with anterior prefrontal, superior frontal, and hippocampal regions was present for abstract rule switching, whereas response hand switching led to increased coupling with motor regions surrounding the central sulcus. These results reveal that a rather general involvement of the posterior lateral frontal cortex in different switching contexts can be further characterized by highly specific functional interactions with other task-relevant regions, depending on the content of the switch.
The Brain Network for Deductive Reasoning: A Quantitative Meta-analysis of 28 Neuroimaging Studies
Authors: Prado Jérôme , Chadha Angad , Booth James R.
Published: May 2011

Over the course of the past decade, contradictory claims have been made regarding the neural bases of deductive reasoning. Researchers have been puzzled by apparent inconsistencies in the literature. Some have even questioned the effectiveness of the methodology used to study the neural bases of deductive reasoning. However, the idea that neuroimaging findings are inconsistent is not based on any quantitative evidence. Here, we report the results of a quantitative meta-analysis of 28 neuroimaging studies of deductive reasoning published between 1997 and 2010, combining 382 participants. Consistent areas of activations across studies were identified using the multilevel kernel density analysis method. We found that results from neuroimaging studies are more consistent than what has been previously assumed. Overall, studies consistently report activations in specific regions of a left fronto-parietal system, as well as in the left BG. This brain system can be decomposed into three subsystems that are specific to particular types of deductive arguments: relational, categorical, and propositional. These dissociations explain inconstancies in the literature. However, they are incompatible with the notion that deductive reasoning is supported by a single cognitive system relying either on visuospatial or rule-based mechanisms. Our findings provide critical insight into the cognitive organization of deductive reasoning and need to be accounted for by cognitive theories.
Where Are All the Women? Institutional Context and the Prevalence of Women on the Corporate Board of Directors
Authors: Grosvold Johanne
Published: May 2011

This dissertation abstract and the reflection commentary present the work of Dr. Johanne Grosvold. The dissertation addresses the influence of institutional context on the prevalence of women on corporate boards of directors. The dissertation abstract explains the research questions, setting, and methods.The reflection commentary discusses the author’s views of research process as a junior scholar.
Relationships Between Cattell–Horn–Carroll (CHC) Cognitive Abilities and Math Achievement Within a Sample of College Students With Learning Disabilities
Authors: Proctor Briley
Published: May 2011

This study examined the relationship between cognitive abilities and math achievement within a sample of college students with learning disabilities (LD). The cognitive abilities were seven areas identified by Stratum II of the Cattell–Horn–Carroll (CHC) theory of cognitive abilities, in addition to the eighth area of Working Memory. Math performance was assessed via math calculation and math reasoning tasks. Instruments include the Woodcock–Johnson III Tests of Cognitive Abilities and Tests of Achievement. Participants were 158 college students with a diagnosed LD in math. Multiple regression analyses found that Processing Speed and Working Memory were related to Math Calculation scores and that Comprehension-Knowledge, Fluid Reasoning, and Working Memory were related to Math Reasoning. Implications for the assessment of math LD in the college populations are discussed.
Dynamic and Static Assessment of Phonological Awareness in Preschool: A Behavior-Genetic Study
Authors: Coventry William L. , Byrne Brian , Olson Richard K. , Corley Robin , Samuelsson Stefan
Published: May 2011

The genetic and environmental overlap between static and dynamic measures of preschool phonological awareness (PA) and their relation to preschool letter knowledge (LK) and kindergarten reading were examined using monozygotic and dizygotic twin children (maximum N = 1,988). The static tests were those typically used to assess a child’s current level of PA such as blending and elision, and the dynamic test included instruction in phoneme identity to assess the child’s ability to respond to this instruction. Both forms were influenced by genes and by shared and nonshared environment. The static and dynamic versions were influenced by the same genes, and part of the total genetic influence was shared with LK. They were subject to both overlapping and independent shared environment influences, with the component in common also affecting LK. Nonshared environment influences were mostly independent. Scores from dynamic assessment added only minimally to variance explained in kindergarten reading after LK and static assessment had been factored in. Although one of the genetic factors that influenced both forms of PA also affected kindergarten reading, it was only the one shared with LK. The authors conclude that dynamic assessment of PA in preschool offers little advantage over the more commonly used static forms, especially if LK scores are available, although they acknowledge its potential in cases of preschool educational disadvantage.
The Use of a Dynamic Screening of Phonological Awareness to Predict Risk for Reading Disabilities in Kindergarten Children
Authors: Sittner Bridges Mindy , Catts Hugh W.
Published: May 2011

This study examined the usefulness and predictive validity of a dynamic screening of phonological awareness in two samples of kindergarten children. In one sample ( n = 90), the predictive validity of the dynamic assessment was compared to a static version of the same screening measure. In the second sample ( n = 96), the dynamic screening measure was compared to a commonly used screening tool, Dynamic Indicators of Basic Early Literacy Skills Initial Sound Fluency. Results showed that the dynamic screening measure uniquely predicted end-of-year reading achievement and outcomes in both samples. These results provide preliminary support for the usefulness of a dynamic screening measure of phonological awareness for kindergarten students.
Social capital building and new business formation
Authors: Audretsch David B. , Aldridge T. Taylor , Sanders Mark
Published: May 2011

The article tracks potential employees (team members), university scientists (advisors) and venture capitalists (investors) who participated in a two-day workshop at Stanford University. The three groups are identified as either having preexisting professional interactions with the other two groups prior to attending the initial workshop, or having met for the first time at the workshop. The groups are then tracked over time for entrepreneurial activity. Positive relationships are found for groups who had preexisting professional interactions for founding a firm after the workshop. The article argues that innovation accelerators, such as the Stanford University workshop, offer invaluable social capital building opportunities to accelerate needed trust and tacit knowledge requisite for new firm formation.
Rotation thromboelastography (ROTEM) parameters are influenced by age, gender, and oral contraception
Authors: Sucker C. , Tharra K. , Litmathe J. , Scharf RE , Zotz RB
Published: May 2011

Rotation thromboelastography (ROTEM) is a screening method that allows the rapid detection of plasma- and platelet-related haemostatic abnormalities. To use this procedure more efficiently, reference values depending on gender, age, and oral contraception are required. In this study, five cohorts of healthy subjects were examined by ROTEM upon activation of the extrinsic or intrinsic pathway of coagulation, or recalcification alone. The cohorts comprised male subjects below (1) and above (2) 45 years of age, female subjects below 45 years of age with (3) or without (4) oral contraception, and female subjects above 45 years (5) without hormone replacement therapy. A significant influence of gender, age, and oral contraception on parameters determined by ROTEM was observed. Thus, adjustment for age, gender, and oral contraception is required when ROTEM is used to screen for distinct abnormalities of haemostasis.