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2013

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Full-Text Articles in Medicine and Health Sciences

Association Between In Utero Arsenic Exposure, Placental Gene Expression, And Infant Birth Weight: A Us Birth Cohort Study, Dennis Liang Fei, Devin C. Koestler, Zhigang Li, Camilla Giambelli, Avencia Sanchez-Mejias, Julie Gosse, Carmen J. Marsit, Margaret R. Karagas, David J. Robbins Dec 2013

Association Between In Utero Arsenic Exposure, Placental Gene Expression, And Infant Birth Weight: A Us Birth Cohort Study, Dennis Liang Fei, Devin C. Koestler, Zhigang Li, Camilla Giambelli, Avencia Sanchez-Mejias, Julie Gosse, Carmen J. Marsit, Margaret R. Karagas, David J. Robbins

Dartmouth Scholarship

Epidemiologic studies and animal models suggest that in utero arsenic exposure affects fetal health, with a negative association between maternal arsenic ingestion and infant birth weight often observed. However, the molecular mechanisms for this association remain elusive. In the present study, we aimed to increase our understanding of the impact of low-dose arsenic exposure on fetal health by identifying possible arsenic-associated fetal tissue biomarkers in a cohort of pregnant women exposed to arsenic at low levels.

Methods: Arsenic concentrations were determined from the urine samples of a cohort of 133 pregnant women from New Hampshire. Placental tissue samples collected from …


Serine/Threonine Kinase 17a Is A Novel Candidate For Therapeutic Targeting In Glioblastoma, Pingping Mao, Mary P. Hever-Jardine, Gilbert J. Rahme, Eric Yang, Janice Tam, Anita Kodali, Bijesh Biswal, Camilo E. Fadul, Arti Gaur, Mark A. Israel, Michael J. Spinella Nov 2013

Serine/Threonine Kinase 17a Is A Novel Candidate For Therapeutic Targeting In Glioblastoma, Pingping Mao, Mary P. Hever-Jardine, Gilbert J. Rahme, Eric Yang, Janice Tam, Anita Kodali, Bijesh Biswal, Camilo E. Fadul, Arti Gaur, Mark A. Israel, Michael J. Spinella

Dartmouth Scholarship

STK17A is a relatively uncharacterized member of the death-associated protein family of serine/threonine kinases which have previously been associated with cell death and apoptosis. Our prior work established that STK17A is a novel p53 target gene that is induced by a variety of DNA damaging agents in a p53-dependent manner. In this study we have uncovered an additional, unanticipated role for STK17A as a candidate promoter of cell proliferation and survival in glioblastoma (GBM). Unexpectedly, it was found that STK17A is highly overexpressed in a grade-dependent manner in gliomas compared to normal brain and other cancer cell types with the …


X-Linked Mtmr8 Diversity And Evolutionary History Of Sub-Saharan Populations, Damian Labuda, Vania Yotova, Jean-François Lefebvre, Claudia Moreau, Gerd Utermann, Scott M. Williams Nov 2013

X-Linked Mtmr8 Diversity And Evolutionary History Of Sub-Saharan Populations, Damian Labuda, Vania Yotova, Jean-François Lefebvre, Claudia Moreau, Gerd Utermann, Scott M. Williams

Dartmouth Scholarship

The genetic diversity within an 11 kb segment of the MTMR8 gene in a sample of 111 sub-Saharan and 49 non-African X chromosomes was investigated to assess the early evolutionary history of sub-Saharan Africans and the out-of-Africa expansion. The analyses revealed a complex genetic structure of the Africans that contributed to the emergence of modern humans. We observed partitioning of two thirds of old lineages among southern, west/central and east African populations indicating ancient population stratification predating the out of Africa migration. Age estimates of these lineages, older than coalescence times of uniparentally inherited markers, raise the question whether contemporary …


Clinical Phenotypes And Abcc6 Gene Mutations In Brazilian Families With Pseudoxanthoma Elasticum., Caroline Silvério Faria, Qiaoli Li, Haitao Guo, Jouni Uitto, Sylvia Satomi Takeno, Marilia De Arruda Cardoso Smith, Dertia Villalba Freire-Maia Nov 2013

Clinical Phenotypes And Abcc6 Gene Mutations In Brazilian Families With Pseudoxanthoma Elasticum., Caroline Silvério Faria, Qiaoli Li, Haitao Guo, Jouni Uitto, Sylvia Satomi Takeno, Marilia De Arruda Cardoso Smith, Dertia Villalba Freire-Maia

Department of Dermatology and Cutaneous Biology Faculty Papers

Pseudoxanthoma elasticum (PXE; OMIM 264800) manifests with characteristic skin lesions of yellowish papules which coalesce into plaques of inelastic and leathery skin on the predilection sites (1). The ocular findings consist of angioid streaks, choroidal neovascularization and subretinal hemorrhages resulting in loss of visual acuity and occasional blindness. Cardiovascular problems include hypertension, intermittent claudication, and occasional myocardial infarcts and stroke. The prevalence of PXE is estimated to be in the range of 1:50,000-70,000 and to be more frequent in females than in males. The diagnosis can be challenging to clinicians due to late-onset of clinical manifestations and considerable heterogeneity. PXE …


Patterning In Placental 11-B Hydroxysteroid Dehydrogenase Methylation According To Prenatal Socioeconomic Adversity, Allison A. Appleton, David A. Armstrong, Corina Lesseur, Joyce Lee, James F. Padbury, Barry M. Lester Sep 2013

Patterning In Placental 11-B Hydroxysteroid Dehydrogenase Methylation According To Prenatal Socioeconomic Adversity, Allison A. Appleton, David A. Armstrong, Corina Lesseur, Joyce Lee, James F. Padbury, Barry M. Lester

Dartmouth Scholarship

Background:

Prenatal socioeconomic adversity as an intrauterine exposure is associated with a range of perinatal outcomes although the explanatory mechanisms are not well understood. The development of the fetus can be shaped by the intrauterine environment through alterations in the function of the placenta. In the placenta, the HSD11B2 gene encodes the 11-beta hydroxysteroid dehydrogenase enzyme, which is responsible for the inactivation of maternal cortisol thereby protecting the developing fetus from this exposure. This gene is regulated by DNA methylation, and this methylation and the expression it controls has been shown to be susceptible to a variety of stressors from …


Cyclin D1 Determines Estrogen Signaling In The Mammary Gland In Vivo., Mathew C Casimiro, Chenguang Wang, Z Li, Gabriele Disante, Nicole E Willmart, Sankar Addya, Lei Chen, Yang Liu, Michael P. Lisanti, Richard Pestell Sep 2013

Cyclin D1 Determines Estrogen Signaling In The Mammary Gland In Vivo., Mathew C Casimiro, Chenguang Wang, Z Li, Gabriele Disante, Nicole E Willmart, Sankar Addya, Lei Chen, Yang Liu, Michael P. Lisanti, Richard Pestell

Department of Cancer Biology Faculty Papers

The CCND1 gene, which is frequently overexpressed in cancers, encodes the regulatory subunit of a holoenzyme that phosphorylates the retinoblastoma protein. Although it is known that cyclin D1 regulates estrogen receptor (ER)α transactivation using heterologous reporter systems, the in vivo biological significance of cyclin D1 to estrogen-dependent signaling, and the molecular mechanisms by which cyclin D1 is involved, are yet to be elucidated. Herein, genome-wide expression profiling conducted of 17β-estradiol-treated castrated virgin mice deleted of the Ccnd1 gene demonstrated that cyclin D1 determines estrogen-dependent gene expression for 88% of estrogen-responsive genes in vivo. In addition, expression profiling of 17β-estradiol-stimulated cyclin …


Integration Of Comprehensive Women’S Health Programmes Into Health Systems: Cervical Cancer Prevention, Care And Control In Rwanda, Agnes Binagwaho, Fidele Ngabo, Claire M. Wagner, Cathy Mugeni, Maurice Gatera, Cameron T. Nutt, Sabin Nsanzimana Sep 2013

Integration Of Comprehensive Women’S Health Programmes Into Health Systems: Cervical Cancer Prevention, Care And Control In Rwanda, Agnes Binagwaho, Fidele Ngabo, Claire M. Wagner, Cathy Mugeni, Maurice Gatera, Cameron T. Nutt, Sabin Nsanzimana

Dartmouth Scholarship

PROBLEM: Although it is highly preventable and treatable, cervical cancer is the most common and most deadly cancer among women in Rwanda.

APPROACH: By mobilizing a diverse coalition of partnerships, Rwanda became the first country in Africa to develop and implement a national strategic plan for cervical cancer prevention, screening and treatment.

LOCAL SETTING: Rwanda - a small, landlocked nation in East Africa with a population of 10.4 million - is well positioned to tackle a number of "high-burden" noncommunicable diseases. The country's integrated response to infectious diseases has resulted in steep declines in premature mortality over the past decade. …


Understanding The Pincer - The Importance Of Reference Plane Orientation On Acetabular Rim Evaluation, Anil K. Gupta, Nozomu Inoue, Michael D. Hellman, Joshua D. Harris, Frank M. Mccormick, Shane Nho Sep 2013

Understanding The Pincer - The Importance Of Reference Plane Orientation On Acetabular Rim Evaluation, Anil K. Gupta, Nozomu Inoue, Michael D. Hellman, Joshua D. Harris, Frank M. Mccormick, Shane Nho

Rothman Institute Faculty Papers

Objectives: Femoroacetabular impingement (FAI) is a common cause of young adult hip pain. FAI can result from an acetabular-sided bony lesion, or “pincer” lesion. A pincer lesion is defined as an area of linear contact between the acetabular rim and the femoral head-neck junction due to general or focal acetabular overcoverage. Three dimensional (3D) analysis of the acetabular rim morphology is essential to understand etiology and aciculate diagnosis of the of the pincer type FAI. A few studies have measured 3D geometry of the acetabular rim; in which the acetabular rim is described as a deviation from a reference plane. …


Sequential Sectioning Of The Ulnar Collateral Ligament Of The Elbow In Cadaveric Arms With Ulnohumeral Laxity Assessed By Dynamic Ultrasonography, Christopher C. Dodson, Levon N. Nazarian, Michael G. Ciccotti, Steven B. Cohen, Sommer Hammoud, Michael C. Ciccotti Sep 2013

Sequential Sectioning Of The Ulnar Collateral Ligament Of The Elbow In Cadaveric Arms With Ulnohumeral Laxity Assessed By Dynamic Ultrasonography, Christopher C. Dodson, Levon N. Nazarian, Michael G. Ciccotti, Steven B. Cohen, Sommer Hammoud, Michael C. Ciccotti

Rothman Institute Faculty Papers

Objectives: Injury of the ulnar collateral ligament (UCL), whether acute or chronic, is potentially career-threatening for elite overhead throwing athletes. Dynamic ultrasound (DUS) allows for rapid, cost-effective, non-invasive, and non-radiating evaluation of the UCL and elbow joint both at rest and with applied stress. The purpose of this study was to determine the amount of cadaveric elbow valgus laxity with sequential UCL sectioning using DUS. Our objective was to quantify which portions of the UCL must be injured to cause the varying levels of laxity seen clinically on DUS testing. No prior study has used DUS to quantify valgus joint …


A Joint Matrix Completion And Filtering Model For Influenza Serological Data Integration., Xiao-Tong Yuan, Tong Zhang, Xiu-Feng Wan Jul 2013

A Joint Matrix Completion And Filtering Model For Influenza Serological Data Integration., Xiao-Tong Yuan, Tong Zhang, Xiu-Feng Wan

College of Veterinary Medicine Publications and Scholarship

Antigenic characterization based on serological data, such as Hemagglutination Inhibition (HI) assay, is one of the routine procedures for influenza vaccine strain selection. In many cases, it would be impossible to measure all pairwise antigenic correlations between testing antigens and reference antisera in each individual experiment. Thus, we have to combine and integrate the HI tables from a number of individual experiments. Measurements from different experiments may be inconsistent due to different experimental conditions. Consequently we will observe a matrix with missing data and possibly inconsistent measurements. In this paper, we develop a new mathematical model, which we refer to …


Identification And Molecular Characterization Of A New Ovarian Cancer Susceptibility Locus At 17q21.31, Jennifer Permuth-Wey, Kate Lawrenson, Howard C. Shen, Aneliya Velkova, Jonathan P. Tyrer, Zhihua Chen, Hui-Yi Lin, Y. Ann Chen, Ya-Yu Tsai, Xiaotao Qu, Susan J. Ramus, Rod Karevan, Janet Lee, Nathan Lee, Melissa C. Larson, Katja K. Aben, Hoda Anton-Culver, Natalia Antonenkova, Antonis Antoniou, Sebastian M. Armasu, Australian Cancer Study, Queensland Institute Of Medical Research, Brisbane, Australian Ovarian Cancer Study, Queensland Institute Of Medical Research, Brisbane, François Bacot, Laura Baglietto, Elisa V. Bandera, Jill Barnholtz-Sloan, Matthias W. Beckmann, Michael J. Birrer, Greg Bloom, Natalia Bogdanova, Louise A. Brinton, Angela Brooks-Wilson, Robert Brown, Ralf Butzow, Qiuyin Cai, Ian Campbell, Jenny Change-Claude, Stephen Chanock, Georgia Chenevix-Trench, Jin Q. Cheng, Mine S. Cicek, Gerhard A. Coetzee, Consortium Of Investigators Of Modifiers Of Brca1/2, Linda S. Cook, Fergus J. Couch, Daniel W. Cramer, Julie M. Cunningham, Agnieszka Dansonka-Mieszkowska, Evelyn Despierre, Jennifer Doherty Jul 2013

Identification And Molecular Characterization Of A New Ovarian Cancer Susceptibility Locus At 17q21.31, Jennifer Permuth-Wey, Kate Lawrenson, Howard C. Shen, Aneliya Velkova, Jonathan P. Tyrer, Zhihua Chen, Hui-Yi Lin, Y. Ann Chen, Ya-Yu Tsai, Xiaotao Qu, Susan J. Ramus, Rod Karevan, Janet Lee, Nathan Lee, Melissa C. Larson, Katja K. Aben, Hoda Anton-Culver, Natalia Antonenkova, Antonis Antoniou, Sebastian M. Armasu, Australian Cancer Study, Queensland Institute Of Medical Research, Brisbane, Australian Ovarian Cancer Study, Queensland Institute Of Medical Research, Brisbane, François Bacot, Laura Baglietto, Elisa V. Bandera, Jill Barnholtz-Sloan, Matthias W. Beckmann, Michael J. Birrer, Greg Bloom, Natalia Bogdanova, Louise A. Brinton, Angela Brooks-Wilson, Robert Brown, Ralf Butzow, Qiuyin Cai, Ian Campbell, Jenny Change-Claude, Stephen Chanock, Georgia Chenevix-Trench, Jin Q. Cheng, Mine S. Cicek, Gerhard A. Coetzee, Consortium Of Investigators Of Modifiers Of Brca1/2, Linda S. Cook, Fergus J. Couch, Daniel W. Cramer, Julie M. Cunningham, Agnieszka Dansonka-Mieszkowska, Evelyn Despierre, Jennifer Doherty

Dartmouth Scholarship

Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3 ′ untranslated region at putative microRNA (miRNA) binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA binding site single nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (OR=1.12, P =10−8 ) mapping to an inversion polymorphism …


A Perspective On Multiple Waves Of Influenza Pandemics, Anna Mummert, Howard Weiss, Li-Ping Long, José M. Amigó, Xiu-Feng Wan Apr 2013

A Perspective On Multiple Waves Of Influenza Pandemics, Anna Mummert, Howard Weiss, Li-Ping Long, José M. Amigó, Xiu-Feng Wan

College of Veterinary Medicine Publications and Scholarship

BACKGROUND: A striking characteristic of the past four influenza pandemic outbreaks in the United States has been the multiple waves of infections. However, the mechanisms responsible for the multiple waves of influenza or other acute infectious diseases are uncertain. Understanding these mechanisms could provide knowledge for health authorities to develop and implement prevention and control strategies. MATERIALS AND METHODS: We exhibit five distinct mechanisms, each of which can generate two waves of infections for an acute infectious disease. The first two mechanisms capture changes in virus transmissibility and behavioral changes. The third mechanism involves population heterogeneity (e.g., demography, geography), where …


Mir203 Mediates Subversion Of Stem Cell Properties During Mammary Epithelial Differentiation Via Repression Of Δnp63Α And Promotes Mesenchymal-To-Epithelial Transition, A J. Decastro, K A. Dunphy, J Hutchinson, A L. Balboni, P Cherukuri, D J. Jerry, J Direnzo Feb 2013

Mir203 Mediates Subversion Of Stem Cell Properties During Mammary Epithelial Differentiation Via Repression Of Δnp63Α And Promotes Mesenchymal-To-Epithelial Transition, A J. Decastro, K A. Dunphy, J Hutchinson, A L. Balboni, P Cherukuri, D J. Jerry, J Direnzo

Dartmouth Scholarship

During reproductive life, the mammary epithelium undergoes consecutive cycles of proliferation, differentiation and apoptosis. Doing so relies on the retained proliferative capacity, prolonged lifespan and developmental potency of mammary stem cells (MaSCs). ΔNp63α, the predominant TP63 isoform in mammary epithelia, is robustly expressed in MaSCs and is required for preservation of self-renewing capacity in diverse epithelial structures. However, the mechanism(s) underlying subversion of this activity during forfeiture of self-renewing capacity are poorly understood. MicroRNAs (miRNAs) govern critical cellular functions including stem cell maintenance, development, cell cycle regulation and differentiation by disrupting translation of target mRNAs. Data presented here …


Hd-Cnv: Hotspot Detector For Copy Number Variants., Jenna L Butler, Marjorie Elizabeth Osborne Locke, Kathleen A Hill, Mark Daley Jan 2013

Hd-Cnv: Hotspot Detector For Copy Number Variants., Jenna L Butler, Marjorie Elizabeth Osborne Locke, Kathleen A Hill, Mark Daley

Brain and Mind Institute Researchers' Publications

SUMMARY: Copy number variants (CNVs) are a major source of genetic variation. Comparing CNVs between samples is important in elucidating their potential effects in a wide variety of biological contexts. HD-CNV (hotspot detector for copy number variants) is a tool for downstream analysis of previously identified CNV regions from multiple samples, and it detects recurrent regions by finding cliques in an interval graph generated from the input. It creates a unique graphical representation of the data, as well as summary spreadsheets and UCSC (University of California, Santa Cruz) Genome Browser track files. The interval graph, when viewed with other software …


Is The Reporting Timeliness Gap For Avian Flu And H1n1 Outbreaks In Global Health Surveillance Systems Associated With Country Transparency?, Feng-Jen Tsai, Eva Tseng, Chang-Chuan Chan, Hiko Tamashiro, Sandrine Motamed, André C Rougemont Jan 2013

Is The Reporting Timeliness Gap For Avian Flu And H1n1 Outbreaks In Global Health Surveillance Systems Associated With Country Transparency?, Feng-Jen Tsai, Eva Tseng, Chang-Chuan Chan, Hiko Tamashiro, Sandrine Motamed, André C Rougemont

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: This study aims to evaluate the length of time elapsed between reports of the same incidents related to avian flu and H1N1 outbreaks published by the WHO and ProMED-mail, the two major global health surveillance systems, before and after the amendment of the International Health Regulations in 2005 (IHR 2005) and to explore the association between country transparency and this timeliness gap.

METHODS: We recorded the initial release dates of each report related to avian flu or H1N1 listed on the WHO Disease Outbreak News site and the matching outbreak report from ProMED-mail, a non-governmental program for monitoring emerging …


Localization Of Pain-Related Brain Activation: A Meta-Analysis Of Neuroimaging Data, Emma G. Duerden, Marie Claire Albanese Jan 2013

Localization Of Pain-Related Brain Activation: A Meta-Analysis Of Neuroimaging Data, Emma G. Duerden, Marie Claire Albanese

Paediatrics Publications

A meta-analysis of 140 neuroimaging studies was performed using the activation-likelihood-estimate (ALE) method to explore the location and extent of activation in the brain in response to noxious stimuli in healthy volunteers. The first analysis involved the creation of a likelihood map illustrating brain activation common across studies using noxious stimuli. The left thalamus, right anterior cingulate cortex (ACC), bilateral anterior insulae, and left dorsal posterior insula had the highest likelihood of being activated. The second analysis contrasted noxious cold with noxious heat stimulation and revealed higher likelihood of activation to noxious cold in the subgenual ACC and the amygdala. …


Inhibition Of The Host Translation Shutoff Response By Herpes Simplex Virus 1 Triggers Nuclear Envelope-Derived Autophagy, Kerstin Radtke, Luc English, Christiane Rondeau, David Leib Jan 2013

Inhibition Of The Host Translation Shutoff Response By Herpes Simplex Virus 1 Triggers Nuclear Envelope-Derived Autophagy, Kerstin Radtke, Luc English, Christiane Rondeau, David Leib

Dartmouth Scholarship

Macroautophagy is a cellular pathway that degrades intracellular pathogens and contributes to antigen presentation. Herpes simplex virus 1 (HSV-1) infection triggers both macroautophagy and an additional form of autophagy that uses the nuclear envelope as a source of membrane. The present study constitutes the first in-depth analysis of nuclear envelope-derived autophagy (NEDA). We established LC3a as a marker that allowed us to distinguish between NEDA and macroautophagy in both immunofluorescence and flow cytometry. NEDA was observed in many different cell types, indicating that it is a general response to HSV-1 infection. This autophagic pathway is known to depend on the …


Developing Human Capital For Successful Implementation Of International Marine Scientific Research Projects, R J. Morrison, Jing Zhang, E R. Urban, J Hall, V Ittekkot, B Avril, L Hu, G H. Hong, S Kidwai, C B. Lange, V Lobanov, J Machiwa, M L. San Diego-Mcglone, T Oguz, F G. Plumley, T Yeemin, W Zhu, F Zuo Jan 2013

Developing Human Capital For Successful Implementation Of International Marine Scientific Research Projects, R J. Morrison, Jing Zhang, E R. Urban, J Hall, V Ittekkot, B Avril, L Hu, G H. Hong, S Kidwai, C B. Lange, V Lobanov, J Machiwa, M L. San Diego-Mcglone, T Oguz, F G. Plumley, T Yeemin, W Zhu, F Zuo

Faculty of Science, Medicine and Health - Papers: part A

The oceans play a crucial role in the global environment and the sustainability of human populations, because of their involvement in climate regulation and provision of living and non-living resources to humans. Maintenance of healthy oceans in an era of increasing human pressure requires a high-level understanding of the processes occurring in the marine environment and the impacts of anthropogenic activities. Effective protection and sustainable resource management must be based, in part, on knowledge derived from successful research. Current marine research activities are being limited by a need for high-quality researchers capable of addressing critical issues in broad multidisciplinary research …


Cay10593 Inhibits The Human P2x7 Receptor Independently Of Phospholipase D1 Stimulation, A Pupovac, L Stokes, R Sluyter Jan 2013

Cay10593 Inhibits The Human P2x7 Receptor Independently Of Phospholipase D1 Stimulation, A Pupovac, L Stokes, R Sluyter

Faculty of Science, Medicine and Health - Papers: part A

The P2X7 receptor is a trimeric ATP-gated cation channel important in health and disease. We have observed that the specific phospholipase D (PLD)1 antagonist, CAY10593 impairs P2X7-induced shedding of the 'low affinity' IgE receptor, CD23. The current study investigated the mode of action of this compound on P2X7 activation. Measurements of ATP-induced ethidium+ uptake revealed that CAY10593 impaired P2X7-induced pore formation in human RPMI 8226 B cells, P2X7-transfected HEK-293 cells and peripheral blood mononuclear cells. Concentration response curves demonstrated that CAY10593 impaired P2X7-induced pore formation in RPMI 8226 cells more potently than the PLD2 antagonist CAY10594 and the non-specific PLD …


Developing Galleria Mellonella As A Model Host For Human Pathogens, Simon M. Cook, Jason D. Mcarthur Jan 2013

Developing Galleria Mellonella As A Model Host For Human Pathogens, Simon M. Cook, Jason D. Mcarthur

Faculty of Science, Medicine and Health - Papers: part A

The larvae of Galleria mellonella (also known colloquially as the wax worm) is increasingly being used as an infection model to study virulence factors and pathogenesis of many prominent bacterial and fungal human pathogens. When compared with traditional mammalian model hosts, invertebrate infection models are cheaper to establish and maintain, are more amenable to high-throughput studies and are not subjected to the same ethical constraints as vertebrates. In addition to these benefits, G. mellonella larvae possess a number of other characteristics which make these organisms particularly useful for the study of human pathogens. Larvae are relatively large in size (12- …


Effect Of Nrf2 Activators On Release Of Glutathione, Cysteinylglycine And Homocysteine By Human U373 Astroglial Cells, Megan L. Steele, Stacey Fuller, Mili Patel, Cindy Kersaitis, Lezanne Ooi, Gerald Munch Jan 2013

Effect Of Nrf2 Activators On Release Of Glutathione, Cysteinylglycine And Homocysteine By Human U373 Astroglial Cells, Megan L. Steele, Stacey Fuller, Mili Patel, Cindy Kersaitis, Lezanne Ooi, Gerald Munch

Faculty of Science, Medicine and Health - Papers: part A

Neurons rely on the release and subsequent cleavage of GSH to cysteinylglycine (CysGly) by astrocytes in order to maintain optimal intracellular GSH levels. In neurodegenerative diseases characterised by oxidative stress, neurons need an optimal GSH supply to defend themselves against free radicals released from activated microglia and astroglia. The rate of GSH synthesis is controlled largely by the activity of γ-glutamyl cysteine ligase. Expression of γ-glutamyl cysteine ligase and of the Xc- system, which facilitates cystine uptake, is regulated by the redox-sensitive transcription factor, nuclear factor erythroid-2-related factor 2 (Nrf2). Compounds that can activate the Nrf2-ARE pathway, referred to as …


Human P2x7 Receptor Activation Induces The Rapid Shedding Of Cxcl16, Aleta Pupovac, Christopher M. Foster, Ronald Sluyter Jan 2013

Human P2x7 Receptor Activation Induces The Rapid Shedding Of Cxcl16, Aleta Pupovac, Christopher M. Foster, Ronald Sluyter

Faculty of Science, Medicine and Health - Papers: part A

Activation of the purinergic P2X7 receptor by extracellular ATP induces the shedding of cell-surface molecules including the low-affinity IgE receptor, CD23 from leukocytes. CD23 is a known substrate of a disintegrin and metalloprotease (ADAM)10. The aim of the current study was to determine if P2X7 activation induced the shedding of the chemokine CXCL16, an ADAM10 substrate. Using immunolabelling and flow cytometry we demonstrate that human RPMI 8226 multiple myeloma B cells, which have been previously shown to express P2X7, also express CXCL16. Flow cytometric and ELISA measurements of ATP-induced loss of cell-surface CXCL16 showed that ATP treatment of RPMI 8226 …


An Improved High-Throughput Lipid Extraction Method For The Analysis Of Human Brain Lipids, Sarah K. Abbott, Andrew M. Jenner, Todd W. Mitchell, Simon H. Brown, Glenda M. Halliday, Brett Garner Jan 2013

An Improved High-Throughput Lipid Extraction Method For The Analysis Of Human Brain Lipids, Sarah K. Abbott, Andrew M. Jenner, Todd W. Mitchell, Simon H. Brown, Glenda M. Halliday, Brett Garner

Illawarra Health and Medical Research Institute

We have developed a protocol suitable for high-throughput lipidomic analysis of human brain samples. The traditional Folch extraction (using chloroform and glass-glass homogenization) was compared to a high-throughput method combining methyl-tert-butyl ether (MTBE) extraction with mechanical homogenization utilizing ceramic beads. This high-throughput method significantly reduced sample handling time and increased efficiency compared to glass-glass homogenizing. Furthermore, replacing chloroform with MTBE is safer (less carcinogenic/toxic), with lipids dissolving in the upper phase, allowing for easier pipetting and the potential for automation (i.e., robotics). Both methods were applied to the analysis of human occipital cortex. Lipid species (including ceramides, sphingomyelins, choline glycerophospholipids, …


Age-Related Human Nuclear Cataract. Blindness Due To Inexorable Protein Deterioration, R Truscott Jan 2013

Age-Related Human Nuclear Cataract. Blindness Due To Inexorable Protein Deterioration, R Truscott

Illawarra Health and Medical Research Institute

Abstract from the 2013 European Association for Vision and Eye Research Conference, 18-21 September 2013, Nice, France.


Rapid Quantification Of Free Cholesterol In Tears Using Direct Insertion/Electron Ionization-Mass Spectrometry, Xiaojia Eric Wei, John Korth, Simon H. J Brown, Todd W. Mitchell, Roger J. W Truscott, Stephen J. Blanksby, Mark D. P Willcox, Zhenjun Zhao Jan 2013

Rapid Quantification Of Free Cholesterol In Tears Using Direct Insertion/Electron Ionization-Mass Spectrometry, Xiaojia Eric Wei, John Korth, Simon H. J Brown, Todd W. Mitchell, Roger J. W Truscott, Stephen J. Blanksby, Mark D. P Willcox, Zhenjun Zhao

Illawarra Health and Medical Research Institute

Purpose. To establish a simple and rapid analytical method, based on direct insertion/electron ionization–mass spectrometry (DI/EI-MS), for measuring free cholesterol in tears from humans and rabbits.

Methods. A stable-isotope dilution protocol employing DI/EI-MS in selected ion monitoring mode was developed and validated. It was used to quantify the free cholesterol content in human and rabbit tear extracts. Tears were collected from adult humans (n = 15) and rabbits (n = 10) and lipids extracted.

Results. Screening, full-scan (m/z 40–600) DI/EI-MS analysis of crude tear extracts showed that diagnostic ions located in the mass range m/z 350 to 400 were those …


The Ecology Of Medical Care In Beijing, Shuang Shao, Feifei Zhao, Jing Wang, Lei Feng, Xiaoqin Lu, Juan Du, Yuxiang Yan, Chao Wang, Yinghong Fu, Jingjing Wu, Xinwei Yu, Kaykeng Khoo, Youxin Wang, Wei Wang Jan 2013

The Ecology Of Medical Care In Beijing, Shuang Shao, Feifei Zhao, Jing Wang, Lei Feng, Xiaoqin Lu, Juan Du, Yuxiang Yan, Chao Wang, Yinghong Fu, Jingjing Wu, Xinwei Yu, Kaykeng Khoo, Youxin Wang, Wei Wang

Research outputs 2013

Background: We presented the pattern of health care consumption, and the utilization of available resources by describing the ecology of medical care in Beijing on a monthly basis and by describing the socio-demographic characteristics associated with receipt care in different settings. Methods: A cohort of 6,592 adults, 15 years of age and older were sampled to estimate the number of urbanresident adults per 1,000 who visited a medical facility at least once in a month, by the method of three-stage stratified and cluster random sampling. Separate logistic regression analyses assessed the association between those receiving care in different types of …


Health-Related Quality Of Life And Life Satisfaction In Colorectal Cancer Survivors: Trajectories Of Adjustment, Jeff Dunn, Shu Kay Ng, William Breitbart, Joanne Aitken, Pip Youl, Peter D. Baade, Suzanne K. Chambers Jan 2013

Health-Related Quality Of Life And Life Satisfaction In Colorectal Cancer Survivors: Trajectories Of Adjustment, Jeff Dunn, Shu Kay Ng, William Breitbart, Joanne Aitken, Pip Youl, Peter D. Baade, Suzanne K. Chambers

Research outputs 2013

Background: This longitudinal study describes the five year trajectories of health-related quality of life (HR-QOL) and life satisfaction in long term colorectal cancer survivors.Patients and methods: A population-based sample of 1966 colorectal cancer survivors were surveyed at six time points from five months to five years post-diagnosis. Predictor variables were: socio-demographic variables, optimism; cancer threat appraisal; perceived social support. Quality of life was assessed with the Functional Assessment of Cancer Therapy-Colorectal (HR-QOL); and the Satisfaction with Life Scale. Growth mixture models were applied to identify trajectory classes and their predictors.Results: Distinct adjustment trajectories were identified for HR-QOL and life satisfaction. …


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 Jan 2013

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 Jan 2013

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 Jan 2013

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 …