Medicine and Health Sciences Commons^™

Randomised Placebo-Controlled Cross-Over Study Examining The Role Of Anamorelin In Mesothelioma (The Anthem Study): Rationale And Protocol, Siao Nge Hoon, Katrina Fyfe, Carolyn J. Peddle-Mcintyre, Samantha Bowyer, Felicity Hawkins, Emily Jeffery, Hui Jun Chih, Jenette Creaney, Anna Nowak, Fraser Brims

Research outputs 2014 to 2021

Introduction Cachexia is common in malignant mesothelioma (MM); half of patients have malnutrition and low skeletal muscle mass. Malnourished patients have worse quality of life (QoL). Weight loss is strongly associated with poor survival. Anamorelin is an oral ghrelin receptor agonist that improves appetite, body weight and QoL in advanced cancer. The aim of this study is to examine the efficacy of anamorelin in improving appendicular skeletal muscle mass (ASM) and patient-reported outcomes in patients with MM with cachexia. Methods and analysis A single-centre, phase II, randomised, placebo-controlled cross-over pilot study with 28-day treatment periods and 3-day washout. Forty patients …

Liquid Biopsy In Ovarian Cancer Using Circulating Tumor Dna And Cells: Ready For Prime Time?, Du-Bois Asante, Leslie Calapre, Melanie Ziman, Tarek M. Meniawy, Elin S. Gray

Research outputs 2014 to 2021

Liquid biopsies hold the potential to inform cancer patient prognosis and to guide treatment decisions at the time when direct tumor biopsy may be impractical due to its invasive nature, inaccessibility and associated complications. Specifically, circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) have shown promising results as companion diagnostic biomarkers for screening, prognostication and/or patient surveillance in many cancer types. In ovarian cancer (OC), CTC and ctDNA analysis allow comprehensive molecular profiling of the primary, metastatic and recurrent tumors. These biomarkers also correlate with overall tumor burden and thus, they provide minimally-invasive means for patient monitoring during clinical …

Elecsys Csf Biomarker Immunoassays Demonstrate Concordance With Amyloid-Pet Imaging, James A. Doecke, Larry Ward, Samantha C. Burnham, Victor L. Villemagne, Qiao-Xin Li, Steven Collins, Christopher J. Fowler, Ekaterina Manuilova, Monika Widmann, Stephanie R. Rainey-Smith, Ralph N. Martins, Colin L. Masters, Aibl Research Group

Research outputs 2014 to 2021

Background: β-amyloid (Aβ) positron emission tomography (PET) imaging is currently the only Food and Drug Administration-approved method to support clinical diagnosis of Alzheimer's disease (AD). However, numerous research studies support the use of cerebrospinal fluid (CSF) biomarkers, as a cost-efficient, quick and equally valid method to define AD pathology. Methods: Using automated Elecsys® assays (Roche Diagnostics) for Aβ (1-42) (Aβ42), Aβ (1-40) (Aβ40), total tau (tTau) and phosphorylated tau (181P) (pTau), we examined CSF samples from 202 participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing cohort, to demonstrate the concordance with pathological AD via PET imaging. …

The Effect Of Sleep Restriction, With Or Without High-Intensity Interval Exercise, On Myofibrillar Protein Synthesis In Healthy Young Men, Nicholas J. Saner, Matthew J. -C. Lee, Nathan W. Pitchford, Jujiao Kuang, Gregory D. Roach, Andrew Garnham, Tanner Stokes, Stuart M. Phillips, David J. Bishop, Jonathan D. Bartlett

Research outputs 2014 to 2021

Key points: Sleep restriction has previously been associated with the loss of muscle mass in both human and animal models. The rate of myofibrillar protein synthesis (MyoPS) is a key variable in regulating skeletal muscle mass and can be increased by performing high-intensity interval exercise (HIIE), although the effect of sleep restriction on MyoPS is unknown. In the present study, we demonstrate that participants undergoing a sleep restriction protocol (five nights, with 4 h in bed each night) had lower rates of skeletal muscle MyoPS; however, rates of MyoPS were maintained at control levels by performing HIIE during this period. …

Blood-Based Molecular Biomarkers For Alzheimer's Disease, Henrik Zetterberg, Samantha C. Burnham

Research outputs 2014 to 2021

A major barrier to the effective conduct of clinical trials of new drug candidates against Alzheimer's disease (AD) and to identifying patients for receiving future disease-modifying treatments is the limited capacity of the current health system to find and diagnose patients with early AD pathology. This may be related in part to the limited capacity of the current health systems to select those people likely to have AD pathology in order to confirm the diagnosis with available cerebrospinal fluid and imaging biomarkers at memory clinics. In the current narrative review, we summarize the literature on candidate blood tests for AD …

The Chest Australia Trial: A Randomised Controlled Trial Of An Intervention To Increase Consultation Rates In Smokers At Risk Of Lung Cancer, Jon D. Emery, Sonya R. Murray, Fiona M. Walter, Andrew Martin, Stephen Goodall, Danielle Mazza, Emily Habgood, Yvonne Kutzer, David John Barnes, Peter Murchie

Research outputs 2014 to 2021

Background: International research has focused on screening and mass media campaigns to promote earlier patient presentation and detect lung cancer earlier. This trial tested the effect of a behavioural intervention in people at increased risk of lung cancer on help-seeking for respiratory symptoms.

Methods: Parallel, individually randomised controlled trial. Eligible participants were long-term smokers with at least 20 pack-years, aged 55 and above. The CHEST intervention entailed a consultation to discuss and implement a self-help manual, followed by self-monitoring reminders to encourage help-seeking for respiratory symptoms. The control group received a brief discussion about lung health. Both groups had baseline …

Chemical Profile And In Vivo Toxicity Evaluation Of Unripe Citrus Aurantifolia Essential Oil, Christian K. Adokoh, Du-Bois Asante, Desmond O. Acheampong, Yohei Kotsuchibashi, Francis A. Armah, Ignatius H. Sirikyi, Keisuke Kimura, Edward Gmakame, Sey Abdul-Rauf

Research outputs 2014 to 2021

Citrus aurantifolia (Christm.) Swingle (syn. C. MEDICA var. ACIDA Brandis) (family: Rutaceae) essential oil is one of the cheapest oils found in local markets. Although, it is generally accepted as non-toxic to vital organs and cells, majority of people are cynical about it usage. Herein, the present study reports the chemical composition and in vivo oral toxicity study of unripe C. aurantifolia essential oil found in Ghana. The toxicity of C. aurantifolia essential oil extract was investigated via oral administration using two methods: The acute toxicity single dose study (SDS) and the repeated dose method. The oil exhibited no acute …

Rigor And Reproducibility In Research With Transcranial Electrical Stimulation: An Nimh-Sponsored Workshop, Marom Bikson, Andre Brunoni, Leigh Charvet, Vincent Clark, Leonardo Cohen, Zhi-De Deng, Jacek Dmochowski, Dylan Edwards, Flavio Frohlich, Emily Kappenman, Kelvin Lim, Colleen Loo, Antonio Mantovani, David Mcmullen, Lucas Parra, Michele Pearson, Jessica Richardson, Judith Rumsey, Pejman Sehatpour, David Sommers, Gozde Unal, Eric Wassermann, Adam Woods, Sarah Lisanby

Research outputs 2014 to 2021

Background

Neuropsychiatric disorders are a leading source of disability and require novel treatments that target mechanisms of disease. As such disorders are thought to result from aberrant neuronal circuit activity, neuromodulation approaches are of increasing interest given their potential for manipulating circuits directly. Low intensity transcranial electrical stimulation (tES) with direct currents (transcranial direct current stimulation, tDCS) or alternating currents (transcranial alternating current stimulation, tACS) represent novel, safe, well-tolerated, and relatively inexpensive putative treatment modalities.

Objective

This report seeks to promote the science, technology and effective clinical applications of these modalities, identify research challenges, and suggest approaches for addressing these …

Cruciferous And Allium Vegetable Intakes Are Inversely Associated With 15‐Year Atherosclerotic Vascular Disease Deaths In Older Adult Women, Lauren Blekkenhorst, Catherine P. Bondonno, Joshua Lewis, Amanda Devine, Kun Zhu, Wai Lim, Richard Woodman, Lawrence Beilin, Richard Prince, Jonathan M. Hodgson

Research outputs 2014 to 2021

Background

Higher vegetable intake is consistently associated with lower atherosclerotic vascular disease (ASVD) events. However, the components responsible and mechanisms involved are uncertain. Nonnutritive phytochemicals may be involved. The objective of this study was to investigate the associations of total vegetable intake and types of vegetables grouped according to phytochemical constituents with ASVD mortality.

Methods and Results

The cohort consisted of 1226 Australian women aged 70 years and older without clinical ASVD or diabetes mellitus at baseline (1998). Vegetable intakes were calculated per serving (75 g/d) and were also classified into prespecified types relating to phytochemical constituents. ASVD‐related deaths were …

Guidelines For The Standardization Of Preanalytic Variables For Blood-Based Biomarker Studies In Alzheimer's Disease Research, Sid O'Bryant, Veer Gupta, Kim Henriksen, Melissa Edwards, Andreas Jeromin, Simone Lista, Chantal Bazenet, Holly Soares, Simon Lovestone, Harald Hampel, Thomas Montine, Kaj Blennow, Tatiana Foroud, Maria Carrillo, Neill Graff-Radford, Christoph Laske, Monique Breteler, Leslie Shaw, John Q. Trojanowski, Nicole Schupf, Robert A. Rissman, Anne M. Fagan, Pankaj Oberoi, Robert Umek, Michael W. Weiner, Paula Grammas, Holly Posner, Ralph Martins

Research outputs 2014 to 2021

The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer's disease (AD). Blood-based biomarkers have potential to overcome access and cost barriers and greatly facilitate advanced neuroimaging and cerebrospinal fluid biomarker approaches. Despite the fact that preanalytical processing is the largest source of variability in laboratory testing, there are no currently available standardized preanalytical guidelines. The current international working group provides the initial starting point for such guidelines for standardized operating procedures (SOPs). It is anticipated that these guidelines will be updated as additional research findings become available. The statement …

The Effect Of Multidisciplinary Rehabilitation On Brain Structure And Cognition In Huntington's Disease: An Exploratory Study, Travis M. Cruickshank, Jennifer A. Thompson, Juan F. Dominguez D, Alvaro P. Reyes, Mike Bynevelt, Nellie Georgiou-Karistianis, Roger A. Barker, Mel R. Ziman

Research outputs 2014 to 2021

Background: There is a wealth of evidence detailing gray matter degeneration and loss of cognitive function over time in individuals with Huntington's disease (HD). Efforts to attenuate disease-related brain and cognitive changes have been unsuccessful to date. Multidisciplinary rehabilitation, comprising motor and cognitive intervention, has been shown to positively impact on functional capacity, depression, quality of life and some aspects of cognition in individuals with HD. This exploratory study aimed to evaluate, for the first time, whether multidisciplinary rehabilitation can slow further deterioration of disease-related brain changes and related cognitive deficits in individuals with manifest HD. Methods: Fifteen participants who …

Effects Of Ambient Coarse, Fine, And Ultrafine Particles And Their Biological Constituents On Systemic Biomarkers: A Controlled Human Exposure Study, Ling Liu, Bruce Urch, Raymond Poon, Mieczyslaw Szyszkowicz, Mary Speck, Diane R. Gold, Amanda J. Wheeler, James A. Scott, Jeffrey R. Brook, Peter S. Thorne, Frances S. Silverman

Research outputs 2014 to 2021

Background: Ambient coarse, fine, and ultrafine particles have been associated with mortality and morbidity. Few studies have compared how various particle size fractions affect systemic biomarkers. Objectives: We examined changes of blood and urinary biomarkers following exposures to three particle sizes. Methods: Fifty healthy nonsmoking volunteers, mean age of 28 years, were exposed to coarse (2.5–10 μm; mean, 213 μg/m3) and fine (0.15–2.5 μm; mean, 238 μg/m3) concentrated ambient particles (CAPs), and filtered ambient and/or medical air. Twenty-five participants were exposed to ultrafine CAP (< 0.3 μm; mean, 136 μg/m3) and filtered medical air. Exposures lasted 130 min, separated by ≥ 2 weeks. Blood/urine samples were collected preexposure and 1 hr and 21 hr postexposure to determine blood interleukin-6 and C-reactive protein (inflammation), endothelin-1 and vascular endothelial growth factor (VEGF; vascular mediators), and malondialdehyde (lipid peroxidation); as well as urinary VEGF, 8-hydroxy-deoxy-guanosine (DNA oxidation), and malondialdehyde. Mixed-model regressions assessed pre- and postexposure differences. results: One hour postexposure, for every 100-μg/m3 increase, coarse CAP was associated with increased blood VEGF (2.41 pg/mL; 95% CI: 0.41, 4.40) in models adjusted for O3, fine CAP with increased urinary malondialdehyde in single- (0.31 nmol/mg creatinine; 95% CI: 0.02, 0.60) and two-pollutant models, and ultrafine CAP with increased urinary 8-hydroxydeoxyguanosine in single- (0.69 ng/mg creatinine; 95% CI: 0.09, 1.29) and two-pollutant models, lasting < 21 hr. Endotoxin was significantly associated with biomarker changes similar to those found with CAPs. conclusions: Ambient particles with various sizes/constituents may influence systemic biomarkers differently. Endotoxin in ambient particles may contribute to vascular mediator changes and oxidative stress.

Abcb5 Identifies Immunoregulatory Dermal Cells, Tobias Schatton, Jun Yang, Sonja Kleffel, Mayuko Uehara, Steven R. Barthel, Christoph Schlapbach, Qian Zhan, Stephen Dudeney, Hansgeorg Mueller, Nayoung Lee, Juliane C. De Vries, Barbara Meier, Seppe Vander Beken, Mark M. Kluth, Christoph Ganss, Arlene H. Sharpe, Ana Maria Waaga-Gasser, Mohamed H. Sayegh, Reza Abdi, Karin Scharffetter-Kochanek, George F. Murphy, Thomas S. Kupper, Natasha Y. Frank, Markus H. Frank

Research outputs 2014 to 2021

Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, the paucity of markers for isolation of molecularly defined immunomodulatory cell populations poses a barrier to this field. Here, we show that ATP-binding cassette member B5 (ABCB5) identifies dermal immunoregulatory cells (DIRCs) capable of exerting therapeutic immunoregulatory functions through engagement of programmed cell death 1 (PD-1). Purified Abcb5+ DIRCs suppressed T cell proliferation, evaded immune rejection, homed to recipient immune tissues, and induced Tregs in vivo. In fully major-histocompatibility-complex-mismatched cardiac allotransplantation models, allogeneic DIRCs significantly prolonged allograft survival. Blockade of DIRC-expressed PD-1 reversed the inhibitory effects of …

Effective, Clinically Feasible And Sustainable: Key Design Features Of Psycho-Educational And Supportive Care Interventions To Promote Individualised Self-Management In Cancer Care, P. Schofield, Suzanne Chambers

Research outputs 2014 to 2021

As the global burden of cancer increases healthcare services will face increasing challenges in meet the complex needs of these patients, their families and the communities in which they live. This raises the question of how to meet patient need where direct clinical contact may be constrained or not readily available. Patients and families require resources and skills to manage their illness outside of the hospital setting within their own communities. Aim. To propose a framework for the development and delivery of psycho-educational and supportive care interventions drawing on theoretical principles of behaviour change and evidence-based interventions, and based on …

Follow-Up Plasma Apolipoprotein E Levels In The Australian Imaging, Biomarkers And Lifestyle Flagship Study Of Ageing (Aibl) Cohort, Veer B. Gupta, V.B, Andrea C. Wilson, Samantha Burnham, Eugene Hone, Steve Pedrini, Simon M. Laws, Wei L.F. Lim, Alan Rembach, Stephanie Rainey-Smith, David Ames, Lynne Cobiac, S L. Macaulay, Colin L. Masters, Christopher C. Rowe, Ashley I. Bush, Ralph Martins, Aibl Research Group

Research outputs 2014 to 2021

Introduction: Alzheimer's disease (AD) is a growing socioeconomic problem worldwide. Early diagnosis and prevention of this devastating disease have become a research priority. Consequently, the identification of clinically significant and sensitive blood biomarkers for its early detection is very important. Apolipoprotein E (APOE) is a well-known and established genetic risk factor for late-onset AD; however, the impact of the protein level on AD risk is unclear. We assessed the utility of plasma ApoE protein as a potential biomarker of AD in the large, well-characterised Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) cohort. Methods: Total plasma ApoE levels were …

Pax Genes: Regulators Of Lineage Specification And Progenitor Cell Maintenance, Judith A. Blake, Mel R. Ziman

Research outputs 2014 to 2021

Pax genes encode a family of transcription factors that orchestrate complex processes of lineage determination in the developing embryo. Their key role is to specify and maintain progenitor cells through use of complex molecular mechanisms such as alternate RNA splice forms and gene activation or inhibition in conjunction with protein co-factors. The significance of Pax genes in development is highlighted by abnormalities that arise from the expression of mutant Pax genes. Here, we review the molecular functions of Pax genes during development and detail the regulatory mechanisms by which they specify and maintain progenitor cells across various tissue lineages. We …

A Quantitative Analysis Of The Mass Media Coverage Of Genomics Medicine In China: A Call For Science Journalism In The Developing World, Feifei Zhao, Yan Chen, Siqi Ge, Xinwei Yu, Shuang Shao, Michael Black, Youxin Wang, Jie Zhang, Manshu Song, Wei Wang

Research outputs 2014 to 2021

Science journalism is a previously neglected but rapidly growing area of scholarship in postgenomics medicine and socio-technical studies of knowledge-based innovations. Science journalism can help evaluate the quantity and quality of information flux between traditional scientific expert communities and the broader public, for example, in personalized medicine education. Newspapers can play a crucial role in science and health communication, and more importantly, in framing public engagement. However, research on the role of newspaper coverage of genomics-related articles has not been readily available in resource-limited settings. As genomics is rapidly expanding worldwide, this gap in newspaper reportage in China is therefore …

Biomarkers Of Alzheimer's Disease Risk In Peripheral Tissues; Focus On Buccal Cells, Maxime François, Wayne Leifert, Ralph Martins, Philip Thomas, Michael Fenech

Research outputs 2014 to 2021

Alzheimer's disease (AD) is a progressive degenerative disorder of the brain and is the most common form of dementia. To-date no simple, inexpensive and minimally invasive procedure is available to confirm with certainty the early diagnosis of AD prior to the manifestations of symptoms characteristic of the disease. Therefore, if population screening of individuals is to be performed, more suitable, easily accessible tissues would need to be used for a diagnostic test that would identify those who exhibit cellular pathology indicative of mild cognitive impairment (MCI) and AD risk so that they can be prioritized for primary prevention. This need …

Factors That Contribute To Balance And Mobility Impairments In Individuals With Huntington's Disease, Travis Cruickshank, Alvaro Reyes, Luis Peñailillo, Jennifer Thompson, Mel Ziman

Research outputs 2014 to 2021

Mobility and balance problems are common and often debilitating features of Huntington's disease (HD). In this exploratory study we aimed to investigate the influence of disease severity, severity of motor deficits, lower limb muscle strength, cognition, executive function, lean muscle mass and reactivity on mobility and balance.Twenty-two individuals with HD were recruited from the North Metropolitan Area Mental Health Service, Perth, Australia. Pertinent demographic, genetic and disease progression information was recorded prior to testing. Balance was assessed using dynamic and static balance tasks. Mobility was assessed using self-paced and fast-paced mobility measures. Cognitive and executive measures were used to assess …

Markers Of Circulating Tumour Cells In The Peripheral Blood Of Patients With Melanoma Correlate With Disease Recurrence And Progression, Anna L. Reid, M Millward, Robert Pearce, M Lee, M Frank, A Ireland, L Monshizadeh, Tapan Rai, P Heenan, Sandra Medic, P Kumarasinghe, Melanie R. Ziman

Research outputs 2013

Background Multimarker quantitative real-time polymerase chain reaction (qRT-PCR) represents an effective method for detecting circulating tumour cells in the peripheral blood of patients with melanoma. Objectives To investigate whether the phenotype of circulating melanoma cells represents a useful indicator of disease stage, recurrence and treatment efficacy. Methods Peripheral blood was collected from 230 patients with melanoma and 152 healthy controls over a period of 3 years and 9 months. Clinical data and blood samples were collected from patients with primary melanoma (early stages, 0-II, n = 154) and metastatic melanoma (late stages, III-IV, n = 76). Each specimen was examined …

Neither Heavy Nor Light Load Resistance Exercise Acutely Exacerbates Lymphedema In Breast Cancer Survivor, Prue Cormie, Daniel A. Galvao, Nigel A. Spry, Robert Newton

Research outputs 2013

Resistance exercise has great potential to aid in the management of breast cancer-related lymphedema (BCRL), but little is known regarding the acute response of performing resistance exercises with the affected limb. Purpose. To examine the acute impact of upper body resistance exercise on the amount of swelling and severity of symptoms in women with BCRL and to compare these effects between resistance exercise involving high and low loads (heavier vs lighter weights). Methods. Seventeen women aged 61 ± 9 years with mild to severe BCRL participated in this study. Participants completed a high load (6-8 repetition maximum) and low load …

Multiplex Biomarkers In Blood, Veer Bala Bala Gupta, Ramani Sundaram, Ralph N. Martins

Research outputs 2013

Advances in the field of blood biomarker discovery will help in identifying Alzheimer's disease in its preclinical stage, allowing treatment to be initiated before irreversible damage occurs. This review discusses some recent past and current approaches being taken by researchers in the field. Individual blood biomarkers have been unsuccessful in defining the disease pathology, progression and thus diagnosis. This directs to the need for discovering a multiplex panel of blood biomarkers as a promising approach with high sensitivity and specificity for early diagnosis. However, it is a great challenge to standardize a worldwide blood biomarker panel due to the innate …

A Necrotic Stimulus Is Required To Maximize Matrix-Mediated Myogenesis In Mice, Drew Kuraitis, Maria Grazia Berardinelli, Erik J. Suuronen, Antonio Musaro

Research outputs 2013

Biomaterials that are similar to skeletal muscle extracellular matrix have been shown to augment regeneration in ischemic muscle. In this study, treatment with a collagen-based matrix stimulated molecular myogenesis in an mdx murine model of necrosis. Matrix-treated animals ran ≥ 40% further, demonstrating functional regeneration, and expressed increased levels of myogenic transcripts. By contrast, matrix treatment was unable to induce transcriptional or functional changes in an MLC/SOD1G93A atrophic mouse model. In vitro, satellite cells were cultured under standard conditions, on matrix, in the presence of myocyte debris (to simulate a necrotic-like environment) or with both matrix and necrotic stimuli. Exposure …

Scd1 Plays A Tumor-Suppressive Role In Survival Of Leukemia Stem Cells And The Development Of Chronic Myeloid Leukemia, H Zhang, H Li, N Ho, Dongguang Li, Shaoguang Li

Research outputs 2012

Chronic myeloid leukemia (CML) is derived from a stem cell, and it is widely accepted that the existence of leukemia stem cells (LSCs) is one of the major reasons for the relapse of CML treated with kinase inhibitors. Key to eradicating LSCs is to identify genes that play a critical role in survival regulation of these stem cells. Using BCR-ABL-induced CML mouse model, here we show that expression of the stearoyl-CoA desaturase 1 (Scd1) gene is downregulated in LSCs and that Scd1 plays a tumor-suppressive role in LSCs with no effect on the function of normal hematopoietic stem cells. Deletion …

Altered Expression Of Alzheimer's Disease-Related Proteins In Male Hypogonadal Mice, Eleanor S. Drummond, Ralph Martins, D J Handelsman, A R Harvey

Research outputs 2012

Age-related depletion of estrogens and androgens is associated with an increase in Alzheimer's disease (AD) brain pathology and diminished cognitive function. Here we investigated AD-associated molecular and cellular changes in brains of aged hypogonadal (hpg) male and female mice. hpg Mice have a spontaneous, inactivating genetic mutation in the GnRH gene resulting in lifelong deficiency of gonadotropins and gonadal sex hormones. Western blot analysis revealed low levels of amyloid precursor protein and high levels of presenilin 1, amyloid precursor protein C-terminal fragment, and β-amyloid 42 in brains of aged male, but not female, hpg mice. Changes were confined to the …

Clinical And Biomarker Changes In Dominantly Inherited Alzheimer's Disease, R J Bateman, C Xiong, T L Benzinger, A M Fagan, A Goate, N C Fox, D S Marcus, N J Cairns, X Xie, T M Blazey, D M Holtzman, A Santacruz, V Buckles, A Oliver, K Moulder, P M Aisen, B Ghetti, W M Klunk, E Mcdade, Ralph Martins, C M Masters, R Mayeux, J M Ringman, M M Rossor, P M Schofield, R M Sperling, S Salloway, J M Morris

Research outputs 2012

BACKGROUND: The order and magnitude of pathologic processes in Alzheimer's disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer's disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease. METHODS: In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We used the participant's age at baseline assessment and the parent's age at the onset of symptoms of Alzheimer's disease to …

The Hippo Pathway Member Yap Plays A Key Role In Influencing Fate Decisions In Muscle Satellite Cells, Robert Judson, Annie Tremblay, Paul Knopp, Robert White, Roby Urcia, Cosimo De Bari, Peter Zammit, Fernando Camargo, Henning Wackerhage

Research outputs 2012

Satellite cells are the resident stem cells of skeletal muscle. Mitotically quiescent in mature muscle, they can be activated to proliferate and generate myoblasts to supply further myonuclei to hypertrophying or regenerating muscle fibres, or self-renew to maintain the resident stem cell pool. Here, we identify the transcriptional co-factor Yap as a novel regulator of satellite cell fate decisions. Yap expression increases during satellite cell activation and Yap remains highly expressed until after the differentiation versus self-renewal decision is made. Constitutive expression of Yap maintains Pax7+ and MyoD+ satellite cells and satellite cell-derived myoblasts, promotes proliferation but prevents differentiation. In …