Medicine and Health Sciences Commons^™

Mice With Deficient Bk Channel Function Show Impaired Prepulse Inhibition And Spatial Learning, But Normal Working And Spatial Reference Memory, Marei Typlt, Magdalena Mirkowski, Erin Azzopardi, Lukas Ruettiger, Peter Ruth, Susanne Schmid

Anatomy and Cell Biology Publications

Genetic variations in the large-conductance, voltage- and calcium activated potassium channels (BK channels) have been recently implicated in mental retardation, autism and schizophrenia which all come along with severe cognitive impairments. In the present study we investigate the effects of functional BK channel deletion on cognition using a genetic mouse model with a knock-out of the gene for the pore forming α-subunit of the channel. We tested the F1 generation of a hybrid SV129/C57BL6 mouse line in which the slo1 gene was deleted in both parent strains.

We first evaluated hearing and motor function to establish the suitability of this …

Functional And Structural Changes Throughout The Auditory System Following Congenital And Early-Onset Deafness: Implications For Hearing Restoration, Blake E. Butler, Stephen G. Lombar

Brain and Mind Institute Researchers' Publications

The absence of auditory input, particularly during development, causes widespread changes in the structure and function of the auditory system, extending from peripheral structures into auditory cortex. In humans, the consequences of these changes are far-reaching and often include detriments to language acquisition, and associated psychosocial issues.Much of what is currently known about the nature of deafness-related changes to auditory structures comes from studies of congenitally deaf or early-deafened animal models. Fortunately, the mammalian auditory system shows a high degree of preservation among species, allowing for generalization from these models to the human auditory system. This review begins with a …

Bdnf In The Dentate Gyrus Is Required For Consolidation Of "Pattern-Separated" Memories., Pedro Bekinschtein, Brianne A Kent, Charlotte A Oomen, Gregory D Clemenson, Fred H Gage, Lisa M Saksida, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

Successful memory involves not only remembering information over time, but also keeping memories distinct and less confusable. The computational process for making representations for similar input patterns more distinct from each other has been referred to as "pattern separation." In this work, we developed a set of behavioral conditions that allowed us to manipulate the load for pattern separation at different stages of memory. Thus, we provide experimental evidence that a brain-derived neurotrophic factor (BDNF)-dependent pattern separation process occurs during the encoding/storage/consolidation, but not the retrieval stage of memory processing. We also found that a spontaneous increase in BDNF in …

Reduced Expression Of The Vesicular Acetylcholine Transporter And Neurotransmitter Content Affects Synaptic Vesicle Distribution And Shape In Mouse Neuromuscular Junction, Hermann A. Rodrigues, Matheus De C. Fonseca, Wallace L. Camargo, Patricia M. A. Lima, Patricia M. Martinelli, Ligia A. Naves, Vania F. Prado, Marco A. M. Prado, Cristina Guatimosim

Anatomy and Cell Biology Publications

In vertebrates, nerve muscle communication is mediated by the release of the neurotransmitter acetylcholine packed inside synaptic vesicles by a specific vesicular acetylcholine transporter (VAChT). Here we used a mouse model (VAChT KDHOM) with 70% reduction in the expression of VAChT to investigate the morphological and functional consequences of a decreased acetylcholine uptake and release in neuromuscular synapses. Upon hypertonic stimulation, VAChT KDHOM mice presented a reduction in the amplitude and frequency of miniature endplate potentials, FM 1-43 staining intensity, total number of synaptic vesicles and altered distribution of vesicles within the synaptic terminal. In contrast, under electrical stimulation or …

One, Two And Three-Dimensional Ultrasound Measurements Of Carotid Atherosclerosis Before And After Cardiac Rehabilitation: Preliminary Results Of A Randomized Controlled Trial., Tamas J Lindenmaier, Daniel N Buchanan, Damien Pike, Tim Hartley, Robert D Reid, J David Spence, Richard Chan, Michael Sharma, Peter L Prior, Neville Suskin, Grace Parraga

Medical Biophysics Publications

BACKGROUND: It is still not known how patients who are post-transient ischemic attack (TIA) or post-stroke might benefit from prospectively planned comprehensive cardiac rehabilitation (CCR). In this pilot evaluation of a larger ongoing randomized-controlled-trial, we evaluated ultrasound (US) measurements of carotid atherosclerosis in subjects following TIA or mild non-disabling stroke and their relationship with risk factors before and after 6-months of CCR.

METHODS: Carotid ultrasound (US) measurements of one-dimensional intima-media-thickness (IMT), two-dimensional total-plaque-area (TPA), three-dimensional total-plaque-volume (TPV) and vessel-wall-volume (VWV) were acquired before and after 6-months CCR for 39 subjects who had previously experienced a TIA and provided written informed …

Regulation Of Stress-Inducible Phosphoprotein 1 Nuclear Retention By Protein Inhibitor Of Activated Stat Pias1, Iaci N. Soares, Fabiana A. Caetano, Jordan Pinder, Bruna Roz Rodrigues, Flavio H. Beraldo, Valeriy G. Ostapchenko, Chantal Durette, Grace Schenatto Pereira, Marilene H. Lopes, Nicolle Queiroz-Hazarbassanov, Isabela W. Cunha, Paulo I. Sanematsu, Sergio Suzuki, Luiz F. Bleggi-Torres, Caroline Schild-Poulter, Pierre Thibault, Graham Dellaire, Vilma R. Martins, Vania F. Prado, Marco A. M. Prado

Anatomy and Cell Biology Publications

Stress-inducible phosphoprotein 1 (STI1), a cochaperone for Hsp90, has been shown to regulate multiple pathways in astrocytes, but its contributions to cellular stress responses are not fully understood. We show that in response to irradiation-mediated DNA damage stress STI1 accumulates in the nucleus of astrocytes. Also, STI1 haploinsufficiency decreases astrocyte survival after irradiation. Using yeast two-hybrid screenings we identified several nuclear proteins as STI1 interactors. Overexpression of one of these interactors, PIAS1, seems to be specifically involved in STI1 nuclear retention and in directing STI1 and Hsp90 to specific sub-nuclear regions. PIAS1 and STI1 co-immunoprecipitate and PIAS1 can function as …

The Centre Of The Brain: Topographical Model Of Motor, Cognitive, Affective, And Somatosensory Functions Of The Basal Ganglia, Marie Arsalidou, Emma G. Duerden, Margot J. Taylor

Paediatrics Publications

The basal ganglia have traditionally been viewed as motor processing nuclei; however, functional neuroimaging evidence has implicated these structures in more complex cognitive and affective processes that are fundamental for a range of human activities. Using quantitative meta-analysis methods we assessed the functional subdivisions of basal ganglia nuclei in relation to motor (body and eye movements), cognitive (working-memory and executive), affective (emotion and reward) and somatosensory functions in healthy participants. We document affective processes in the anterior parts of the caudate head with the most overlap within the left hemisphere. Cognitive processes showed the most widespread response, whereas motor processes …

Techniques For The Isolation Of High-Quality Rna From Cells Encapsulated In Chitosan Hydrogels, Claire Yu, Stuart Young, Valerio Russo, Brian G. Amsden, Lauren E. Flynn

Paediatrics Publications

Extracting high-quality RNA from hydrogels containing polysaccharide components is challenging, as traditional RNA isolation techniques designed for cells and tissues can have limited yields and purity due to physiochemical interactions between the nucleic acids and the biomaterials. In this study, a comparative analysis of several different RNA isolation methods was performed on human adipose-derived stem cells photo-encapsulated within methacrylated glycol chitosan hydrogels. The results demonstrated that RNA isolation methods with cetyl trimethylammonium bromide (CTAB) buffer followed by purification with an RNeasy® mini kit resulted in low yields of RNA, except when the samples were preminced directly within the buffer. In …

The Prion Protein Ligand, Stress-Inducible Phosphoprotein 1, Regulates Amyloid-Beta Oligomer Toxicity, Valeriy G. Ostapchenko, Flavio H. Beraldo, Amro H. Mohammad, Yu-Feng Xie, Pedro H. F. Hirata, Ana C. Magalhaes, Guillaume Lamour, Hongbin Li, Andrzej Maciejewski, Jillian C. Belrose, Bianca L. Teixeira, Margaret Fahnestock, Sergio T. Ferreira, Neil R. Cashman, Glaucia N. M. Hajj, Michael F. Jackson, Wing-Yiu Choy, John F. Macdonald, Vilma R. Martins, Vania F. Prado, Marco A. M. Prado

Anatomy and Cell Biology Publications

In Alzheimer's disease (AD), soluble amyloid-beta oligomers (A beta Os) trigger neurotoxic signaling, at least partially, via the cellular prion protein (PrPC). However, it is unknown whether other ligands of PrPC can regulate this potentially toxic interaction. Stress-inducible phosphoprotein 1 (STI1), an Hsp90 cochaperone secreted by astrocytes, binds to PrPC in the vicinity of the A beta O binding site to protect neurons against toxic stimuli. Here, we investigated a potential role of STI1 in A beta O toxicity. We confirmed the specific binding of A beta Os and STI1 to the PrP and showed that STI1 efficiently inhibited A …

Gsk-3Β Function In Bone Regulates Skeletal Development, Whole-Body Metabolism, And Male Life Span, J. R. Gillespie, J. R. Bush, G. I. Bell, L. A. Aubrey, H. Dupuis, F. Ferron, B. Kream, G. Dimattia, S. Patel, J. R. Woodgett, G. Karsenty, D. A. Hess, F. Beier

Paediatrics Publications

Glycogen synthase kinase 3 β (GSK-3β) is an essential negative regulator or “brake” on many anabolic-signaling pathways including Wnt and insulin. Global deletion of GSK-3β results in perinatal lethality and various skeletal defects. The goal of our research was to determine GSK-3β cell-autonomous effects and postnatal roles in the skeleton. We used the 3.6-kb Col1a1 promoter to inactivate the Gsk3b gene (Col1a1-Gsk3b knockout) in skeletal cells. Mutant mice exhibit decreased body fat and postnatal bone growth, as well as delayed development of several skeletal elements. Surprisingly, the mutant mice display decreased circulating glucose and insulin levels despite normal expression of …

The Touchscreen Operant Platform For Testing Learning And Memory In Rats And Mice., Alexa E Horner, Christopher J Heath, Martha Hvoslef-Eide, Brianne A Kent, Chi Hun Kim, Simon R O Nilsson, Johan Alsiö, Charlotte A Oomen, Andrew Holmes, Lisa M Saksida, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

An increasingly popular method of assessing cognitive functions in rodents is the automated touchscreen platform, on which a number of different cognitive tests can be run in a manner very similar to touchscreen methods currently used to test human subjects. This methodology is low stress (using appetitive rather than aversive reinforcement), has high translational potential and lends itself to a high degree of standardization and throughput. Applications include the study of cognition in rodent models of psychiatric and neurodegenerative diseases (e.g., Alzheimer's disease, schizophrenia, Huntington's disease, frontotemporal dementia), as well as the characterization of the role of select brain regions, …

The Touchscreen Operant Platform For Testing Working Memory And Pattern Separation In Rats And Mice., Charlotte A Oomen, Martha Hvoslef-Eide, Christopher J Heath, Adam C Mar, Alexa E Horner, Timothy J Bussey, Lisa M Saksida

Brain and Mind Institute Researchers' Publications

The automated touchscreen operant chamber for rats and mice allows for the assessment of multiple cognitive domains within the same testing environment. This protocol presents the location discrimination (LD) task and the trial-unique delayed nonmatching-to-location (TUNL) task, which both assess memory for location. During these tasks, animals are trained to a predefined criterion during ∼20-40 daily sessions. In LD sessions, touching the same location on the screen is rewarded on consecutive trials, followed by a reversal of location-reward contingencies. TUNL, a working memory task, requires animals to 'nonmatch' to a sample location after a delay. In both the LD and …

The Touchscreen Operant Platform For Assessing Executive Function In Rats And Mice., Adam C Mar, Alexa E Horner, Simon R O Nilsson, Johan Alsiö, Brianne A Kent, Chi Hun Kim, Andrew Holmes, Lisa M Saksida, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

This protocol details a subset of assays developed within the touchscreen platform to measure various aspects of executive function in rodents. Three main procedures are included: extinction, measuring the rate and extent of curtailing a response that was previously, but is no longer, associated with reward; reversal learning, measuring the rate and extent of switching a response toward a visual stimulus that was previously not, but has become, associated with reward (and away from a visual stimulus that was previously, but is no longer, rewarded); and the 5-choice serial reaction time (5-CSRT) task, gauging the ability to selectively detect and …

Scarpa's Fascia And Clinical Signs: The Role Of The Membranous Superficial Fascia In The Eponymous Clinical Signs Of Retroperitoneal Catastrophe., Shanoor Ullah, Robert Grant, Marjorie Johnson, Vivian Mcalister

Data and Test Instruments

This article deals with the history of membranous superficial fascia (Antonio Scarpa, Abraham Colles), the history of clinical signs that use discoloration of the torso (Cullen's sign, Grey Turner's sign, Fox's sign, Bryant's sign) and then describes anatomical dissection studies to link the two. INTRODUCTION: The membranous superficial fascia (MSF) was described early in the 19th century, as was its role in the clinical sign of urethral disruption. Clinical signs of haemorrhage or leakage of pancreatic and biliary fluid into the retroperitoneum, which were described throughout the 20th century, all relied on circumscribed discolouration of the skin of the torso. …

Quantification Of Stigma For Clinical Assessment In Psychiatric Practice’ - A Paradigm Shift In Anti-Stigma Intervention: Using Newly Developed Scale (Stigma Quantification Scale ‘Sqs’)., Amresh Srivastava

Data and Test Instruments

Purpose: Objective of the project was to develop a quantification tool for measurement of stigma in clinical practice for the purpose of identifying patients who have suffered severe stigma with the hopes of identifying and treating stigma related issues. Methods: Our tool which includes 49 items, quantifies four domains of stigma: (1) Personal; (2) Family; (3) Social; and (4) Illness. In addition, the items are distributed into three subscales: (a) self-experience; (b) illness related consequences; and (c) coping strategies. Results: In this pilot study conducted in India, we present the scale details and results. We found that as age increased …

Forebrain Deletion Of The Vesicular Acetylcholine Transporter Results In Deficits In Executive Function, Metabolic, And Rna Splicing Abnormalities In The Prefrontal Cortex, Benjamin Kolisnyk, Mohammed A. Al-Onaizi, Pedro H. F. Hirata, Monica S. Guzman, Simona Nikolova, Shahar Barbash, Hermona Soreq, Robert Bartha, Marco A. M. Prado, Vania F. Prado

Anatomy and Cell Biology Publications

One of the key brain regions in cognitive processing and executive function is the prefrontal cortex (PFC), which receives cholinergic input from basal forebrain cholinergic neurons. We evaluated the contribution of synaptically released acetylcholine (ACh) to executive function by genetically targeting the vesicular acetylcholine transporter (VAChT) in the mouse forebrain. Executive function was assessed using a pairwise visual discrimination paradigm and the 5-choice serial reaction time task (5-CSRT). In the pairwise test, VAChT-deficient mice were able to learn, but were impaired in reversal learning, suggesting that these mice present cognitive inflexibility. Interestingly, VAChT-targeted mice took longer to reach criteria in …

Stress-Inducible Phosphoprotein 1 Has Unique Cochaperone Activity During Development And Regulates Cellular Response To Ischemia Via The Prion Protein., Flavio H Beraldo, Iaci N Soares, Daniela F Goncalves, Jue Fan, Anu A Thomas, Tiago G Santos, Amro H Mohammad, Martin Roffé, Michele D Calder, Simona Nikolova, Glaucia N Hajj, Andre L Guimaraes, Andre R Massensini, Ian Welch, Dean H Betts, Robert Gros, Maria Drangova, Andrew J Watson, Robert Bartha, Vania F Prado, Vilma R Martins, Marco A M Prado

Obstetrics & Gynaecology Publications

Stress-inducible phosphoprotein 1 (STI1) is part of the chaperone machinery, but it also functions as an extracellular ligand for the prion protein. However, the physiological relevance of these STI1 activities in vivo is unknown. Here, we show that in the absence of embryonic STI1, several Hsp90 client proteins are decreased by 50%, although Hsp90 levels are unaffected. Mutant STI1 mice showed increased caspase-3 activation and 50% impairment in cellular proliferation. Moreover, placental disruption and lack of cellular viability were linked to embryonic death by E10.5 in STI1-mutant mice. Rescue of embryonic lethality in these mutants, by transgenic expression of the …

Endogenous Folate Accumulation In Oocytes And Preimplantation Embryos And Its Epigenetic Implications., Mellissa R W Mann, Andrew J Watson

Obstetrics & Gynaecology Publications

No abstract provided.

Development Of Uv/Hplc Methods For Quantitative Analysis Of Benznidazole In Human Plasma And Urine For Application In Pediatric Clinical Studies, María Elena Marsón, Diego Dante Dana, Jaime Altcheh, Facundo García-Bournissen, Guido Mastrantonio

Paediatrics Publications

Objective: Chagas disease constitutes a major public health problem in Latin America. Correctly designed pharmacokinetic, safety, and bioequivalence studies are desirable in order to fill the knowledge gaps that presently exist on available drugs. It is necessary to develop accurate, simple, reproducible, and sensitive high-performance liquid chromatography (HPLC)/UV methods for the quantization of benznidazole (BNZ) in human plasma and urine for clinical applications, specially in pediatric patients. Methods: Quantization of BNZ in human plasma involved freeze-drying and re-suspension in organic solvent followed by reverse phase HPLC with UV detection. Analysis of BNZ in urine involved liquid/liquid extraction followed by reverse …

Absence Of The Genicular Arterial Anastomosis As Generally Depicted In Textbooks., Maher Sabalbal, Marjorie Johnson, Vivian Mcalister

Data and Test Instruments

This article reviews the history of anatomical research, starting with John Hunter and Astley Cooper, into the arterial anastomosis at the knee and uses dissection to determine the reality. The final draft is available below. (Ann R Coll Surg Engl. 2013 Sep;95(6):405-9) INTRODUCTION Textbook representations of the genicular arterial anastomosis show a large direct communication between the descending branch of the lateral circumflex femoral artery (DBLCFA) and a genicular branch of the popliteal artery but this is not compatible with clinical experience. The aim of this study was to determine whether the arterial anastomosis at the knee is sufficient, in …

Adverse Outcome Of Early Recurrent Ischemic Stroke Secondary To Atrial Fibrillation After Repeated Systemic Thrombolysis, Luciano A. Sposato, Valeria Salutto, Diego E. Beratti, Paula Monti, Patricia M. Riccio, Claudio Mazia

Anatomy and Cell Biology Publications

Background. Recurrent ischemic stroke is associated with adverse neurological outcome in patients with atrial fibrillation. There is very scarce information regarding the neurological outcome of atrial fibrillation patients undergoing repeated systemic thrombolysis after early recurrent ischemic stroke. Clinical Case and Discussion. We describe a case of a 76-year-old woman with known paroxysmal atrial fibrillation who was admitted because of an acute right middle cerebral artery ischemic stroke and who underwent repeated systemic thrombolysis within 110 hours. The patient underwent systemic thrombolysis after the first ischemic stroke with almost complete neurological recovery. On the fourth day after treatment, an …

A Multivariate Method To Determine The Dimensionality Of Neural Representation From Population Activity., Jörn Diedrichsen, Tobias Wiestler, Naveed Ejaz

Brain and Mind Institute Researchers' Publications

How do populations of neurons represent a variable of interest? The notion of feature spaces is a useful concept to approach this question: According to this model, the activation patterns across a neuronal population are composed of different pattern components. The strength of each of these components varies with one latent feature, which together are the dimensions along which the population represents the variable. Here we propose a new method to determine the number of feature dimensions that best describes the activation patterns. The method is based on Gaussian linear classifiers that use only the first d most important pattern …

Skill Learning Strengthens Cortical Representations Of Motor Sequences., Tobias Wiestler, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

Motor-skill learning can be accompanied by both increases and decreases in brain activity. Increases may indicate neural recruitment, while decreases may imply that a region became unimportant or developed a more efficient representation of the skill. These overlapping mechanisms make interpreting learning-related changes of spatially averaged activity difficult. Here we show that motor-skill acquisition is associated with the emergence of highly distinguishable activity patterns for trained movement sequences, in the absence of average activity increases. During functional magnetic resonance imaging, participants produced either four trained or four untrained finger sequences. Using multivariate pattern analysis, both untrained and trained sequences could …

Dimensions Of Suicidality: Analyzing The Domains Of The Sis-Map Suicide Risk Assessment Instrument And The Development Of A Brief Screener, Megan Johnston, Charles Nelson, Amresh Shrivastava

Data and Test Instruments

This study aimed at validating the domains of suicidality assessed by the Scale for Impact of Suicidality—Management, Assessment and Planning of Care (SISMAP) and creating a brief screener based on the full scale. A total of 50 individuals with suicidal ideation were given the SIS-MAP interview. Support was found for these domains of suicide risk; in particular, the subscales of ideation and protective factors for suicide risk were highly reliable. For each domain of suicidality, items most predictive of total risk index scores were selected to create a brief screener aimed at expediting the assessment process. The screener was reliable, …

Progression Of Carotid Plaque Volume Predicts Cardiovascular Events, Thapat Wannarong, Grace Parraga, Daniel Buchanan, Aaron Fenster, Andrew A House, Daniel G Hackam, J David Spence

Medical Biophysics Publications

BACKGROUND AND PURPOSE: Carotid ultrasound evaluation of intima-media thickness (IMT) and plaque burden has been used for risk stratification and for evaluation of antiatherosclerotic therapies. Increasing evidence indicates that measuring plaque burden is superior to measuring IMT for both purposes. We compared progression/regression of IMT, total plaque area (TPA), and total plaque volume (TPV) as predictors of cardiovascular outcomes.

METHODS: IMT, TPA, and TPV were measured at baseline in 349 patients attending vascular prevention clinics; they had TPA of 40 to 600 mm(2) at baseline to qualify for enrollment. Participants were followed up for ≤5 years (median, 3.17 years) to …

Erps Reveal The Temporal Dynamics Of Auditory Word Recognition In Specific Language Impairment., Jeffrey G Malins, Amy S Desroches, Erin K Robertson, Randy Lynn Newman, Lisa M D Archibald, Marc F Joanisse

Brain and Mind Institute Researchers' Publications

We used event-related potentials (ERPs) to compare auditory word recognition in children with specific language impairment (SLI group; N=14) to a group of typically developing children (TD group; N=14). Subjects were presented with pictures of items and heard auditory words that either matched or mismatched the pictures. Mismatches overlapped expected words in word-onset (cohort mismatches; see: DOLL, hear: dog), rhyme (CONE -bone), or were unrelated (SHELL -mug). In match trials, the SLI group showed a different pattern of N100 responses to auditory stimuli compared to the TD group, indicative of early auditory processing differences in SLI. However, the phonological mapping …

Prognostic Factors For Male Breast Cancer: Similarity To Female Counterparts, Edward Yu, Larry Stitt, Olga Vujovic, Kurian Joseph, Avi Assouline, Joseph Au, Jawaid Younus, Francisco Perera, Patricia Tai

Data and Test Instruments

Objective: To assess whether prognostic factors in male breast cancer (MBC) and female breast cancer (FBC) have similar impact on survival. Patients and Methods: Charts for men and women diagnosed with breast cancer referred to the London Regional Cancer Program (LRCP) were reviewed. Patients with distant metastatic diseases were excluded. Data on prognostic factors including age, nodal status, resection margin, use of hormonal therapy, chemotherapy with/without hormone and radiation therapy (RT), overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were analyzed. Survival estimates were obtained using Kaplan-Meier methodology. The Cox regression interaction was used to compare male and …

Dynamic And Opposing Adjustment Of Movement Cancellation And Generation In An Oculomotor Countermanding Task., Brian D Corneil, Joshua C Cheng, Samanthi C Goonetilleke

Brain and Mind Institute Researchers' Publications

Adaptive adjustments of strategies help optimize behavior in a dynamic and uncertain world. Previous studies in the countermanding (or stop-signal) paradigm have detailed how reaction times (RTs) change with trial sequence, demonstrating adaptive control of movement generation. Comparatively little is known about the adaptive control of movement cancellation in the countermanding task, mainly because movement cancellation implies the absence of an outcome and estimates of movement cancellation require hundreds of trials. Here, we exploit a within-trial proxy of movement cancellation based on recordings of neck muscle activity while human subjects attempted to cancel large eye-head gaze shifts. On a subset …

Fellows Serving In Afghanistan Thank Royal College With Special Gift, Dialogue

Data and Test Instruments

In recognition of support given to Fellows serving in Afghanistan, a flag box was commissioned by officers and recently presented to the Royal College. Past-President Louis Francescutti, MD, FRCPC, himself an Honorary Colonel of 1 Field Ambulance Edmonton, accepted the gift on behalf of the organization. Crafted by the Udin brothers of Kabul, the flag box is engraved with the Royal College crest, as well as with the Canadian and Afghani national flags. It will be displayed in the Roddick Room — the Royal College’s library. For over a decade, many Fellows of the Royal College, both civilians and Canadian …

Β-Estradiol-Dependent Activation Of The Jak/Stat Pathway Requires P/Cip And Carm1, N. Coughlan, G. Thillainadesan, J. Andrews, M. Isovic, J. Torchia

Paediatrics Publications

The steroid receptor coactivator p/CIP, also known as SRC-3, is an oncogene commonly amplified in breast and ovarian cancers. p/CIP is known to associate with coactivator arginine methyltransferase 1 (CARM1) on select estrogen responsive genes. We have shown, using a ChIP-on-chip approach, that in response to stimulation with 17β-estradiol (E2), the p/CIP/CARM1 complex is recruited to 204 proximal promoters in MCF-7 cells. Many of the complex target genes have been previously implicated in signaling pathways related to oncogenesis. Jak2, a member of the Jak/Stat signaling cascade, is one of the direct E2-dependent targets of the p/CIP/CARM1 complex. Following E2-treatment, histone …