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Full-Text Articles in Medicine and Health Sciences

Genotype-Specific Lesion Growth Rates In Stargardt Disease, Rachael C. Heath Jeffery, Jennifer A. Thompson, Johnny Lo, Tina M. Lamey, Terri L. Mclaren, Ian L. Mcallister, Ian J. Constable, John N. De Roach, Fred K. Chen Dec 2021

Genotype-Specific Lesion Growth Rates In Stargardt Disease, Rachael C. Heath Jeffery, Jennifer A. Thompson, Johnny Lo, Tina M. Lamey, Terri L. Mclaren, Ian L. Mcallister, Ian J. Constable, John N. De Roach, Fred K. Chen

Research outputs 2014 to 2021

Reported growth rates (GR) of atrophic lesions in Stargardt disease (STGD1) vary widely. In the present study, we report the longitudinal natural history of patients with confirmed bial-lelic ABCA4 mutations from five genotype groups: c.6079C > T, c.[2588G > C;5603A > T], c.3113C > T, c.5882G > A and c.5603A > T. Fundus autofluorescence (AF) 30◦ × 30◦ images were manually seg-mented for boundaries of definitely decreased autofluorescence (DDAF). The primary outcome was the effective radius GR across five genotype groups. The age of DDAF formation in each eye was calculated using the x-intercept of the DDAF effective radius against age. Discordance between age at DDAF …


Clinical Trial Of Abcb5+ Mesenchymal Stem Cells For Recessive Dystrophic Epidermolysis Bullosa, Dimitra Kiritsi, Kathrin Dieter, Elke Niebergall-Roth, Silvia Fluhr, Cristina Daniele, Jasmina Esterlechner, Samar Sadeghi, Seda Ballikaya, Leoni Erdinger, Franziska Schauer, Stella Gewert, Martin Laimer, Johann W. Bauer, Alain Hovnanian, Giovanna Zambruno, May El Hachem, Emmanuelle Bourrat, Maria Papanikolaou, Gabriela Petrof, Sophie Kitzmüller, Christen L. Ebens, Markus H. Frank, Natasha Y. Frank, Christoph Ganss, Anna E. Martinez, John A. Mcgrath, Jakub Tolar, Mark A. Kluth Nov 2021

Clinical Trial Of Abcb5+ Mesenchymal Stem Cells For Recessive Dystrophic Epidermolysis Bullosa, Dimitra Kiritsi, Kathrin Dieter, Elke Niebergall-Roth, Silvia Fluhr, Cristina Daniele, Jasmina Esterlechner, Samar Sadeghi, Seda Ballikaya, Leoni Erdinger, Franziska Schauer, Stella Gewert, Martin Laimer, Johann W. Bauer, Alain Hovnanian, Giovanna Zambruno, May El Hachem, Emmanuelle Bourrat, Maria Papanikolaou, Gabriela Petrof, Sophie Kitzmüller, Christen L. Ebens, Markus H. Frank, Natasha Y. Frank, Christoph Ganss, Anna E. Martinez, John A. Mcgrath, Jakub Tolar, Mark A. Kluth

Research outputs 2014 to 2021

BACKGROUND. Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, devastating, and lifethreatening inherited skin fragility disorder that comes about due to a lack of functional type VII collagen, for which no effective therapy exists. ABCB5+ dermal mesenchymal stem cells (ABCB5+ MSCs) possess immunomodulatory, inflammation-dampening, and tissue-healing capacities. In a Col7a1-/-mouse model of RDEB, treatment with ABCB5+ MSCs markedly extended the animals' lifespans. METHODS. In this international, multicentric, single-arm, phase I/IIa clinical trial, 16 patients (aged 4-36 years) enrolled into 4 age cohorts received 3 i.v. infusions of 2 × 106ABCB5+ MSCs/kg on days 0, 17, and 35. Patients were followed …


Multi-Response Surface Optimisation Of Extrusion Cooking To Increase Soluble Dietary Fibre And Polyphenols In Lupin Seed Coat, Liezhou Zhong, Zhongxiang Fang, Mark L. Wahlqvist, Jonathan M. Hodgson, Stuart K. Johnson May 2021

Multi-Response Surface Optimisation Of Extrusion Cooking To Increase Soluble Dietary Fibre And Polyphenols In Lupin Seed Coat, Liezhou Zhong, Zhongxiang Fang, Mark L. Wahlqvist, Jonathan M. Hodgson, Stuart K. Johnson

Research outputs 2014 to 2021

The seed coat of the legume lupin which is rich in insoluble dietary fibre is a major by-product in human food applications. Extrusion cooking has been demonstrated to increase desirable soluble dietary fibre in the Australian sweet lupin seed coat. In this study, processing condition of twin-screw extrusion cooking was optimised using a central composite rotatable design to increase soluble dietary fibre in lupin seed coat from 44.17 g/kg up to 113.69 g/kg dry basis. The high levels of polyphenols in the seed coat were retained. The optimal extrusion conditions which achieved maximum levels of soluble dietary fibre, total free …


Extraction And Quantitative Determination Of Bile Acids In Feces, Armaghan Shafaei, Joanna Rees, Claus T. Christophersen, Amanda Devine, David Broadhurst, Mary C. Boyce Mar 2021

Extraction And Quantitative Determination Of Bile Acids In Feces, Armaghan Shafaei, Joanna Rees, Claus T. Christophersen, Amanda Devine, David Broadhurst, Mary C. Boyce

Research outputs 2014 to 2021

© 2021 Elsevier B.V. With rapid advances in gut microbiome research, fecal bile acids are increasingly being monitored as potential biomarkers of diet related disease susceptibility. As such, rapid, robust and reliable methods for their analysis are of increasing importance. Herein is described a simple extraction method for the analysis of bile acids in feces suitable for subsequent quantification by liquid chromatography and tandem mass spectrometry. A C18 column separated the analytes with excellent peak shape and retention time repeatability maintained across 800 injections. The intra-day and inter-day precision and accuracy was greater than 80%. Recoveries ranged from 83.58 to …


The Effects Of Acute Exercise On Bone Turnover Markers In Middle-Aged And Older Adults: A Systematic Review, Cassandra Smith, Alexander Tacey, Jakub Mesinovic, David Scott, Xuzhu Lin, Tara C. Brennan-Speranza, Joshua R. Lewis, Gustavo Duque, Itamar Levinger Feb 2021

The Effects Of Acute Exercise On Bone Turnover Markers In Middle-Aged And Older Adults: A Systematic Review, Cassandra Smith, Alexander Tacey, Jakub Mesinovic, David Scott, Xuzhu Lin, Tara C. Brennan-Speranza, Joshua R. Lewis, Gustavo Duque, Itamar Levinger

Research outputs 2014 to 2021

© 2020 Elsevier Inc. Background: Bone turnover is the cellular machinery responsible for bone integrity and strength and, in the clinical setting, it is assessed using bone turnover markers (BTMs). Acute exercise can induce mechanical stress on bone which is needed for bone remodelling, but to date, there are conflicting results in regards to the effects of varying mechanical stimuli on BTMs. Objectives: This systematic review examines the effects of acute aerobic, resistance and impact exercises on BTMs in middle and older-aged adults and examines whether the responses are determined by the exercise mode, intensity, age and sex. Methods: We …


Changes In Plasma Hydroxyproline And Plasma Cell-Free Dna Concentrations After Higher- Versus Lower-Intensity Eccentric Cycling, Georgios Mavropalias, Leslie Calapre, Michael Morici, Tomoko Koeda, Wayne C. K. Poon, Oliver R. Barley, Elin Gray, Anthony J. Blazevich, Kazunori Nosaka Jan 2021

Changes In Plasma Hydroxyproline And Plasma Cell-Free Dna Concentrations After Higher- Versus Lower-Intensity Eccentric Cycling, Georgios Mavropalias, Leslie Calapre, Michael Morici, Tomoko Koeda, Wayne C. K. Poon, Oliver R. Barley, Elin Gray, Anthony J. Blazevich, Kazunori Nosaka

Research outputs 2014 to 2021

Purpose:

We examined changes in plasma creatine kinase (CK) activity, hydroxyproline and cell-free DNA (cfDNA) concentrations in relation to changes in maximum voluntary isometric contraction (MVIC) torque and delayed-onset muscle soreness (DOMS) following a session of volume-matched higher- (HI) versus lower-intensity (LI) eccentric cycling exercise.

Methods:

Healthy young men performed either 5 × 1-min HI at 20% of peak power output (n = 11) or 5 × 4-min LI eccentric cycling at 5% of peak power output (n = 9). Changes in knee extensor MVIC torque, DOMS, plasma CK activity, and hydroxyproline and cfDNA concentrations before, immediately after, and 24–72 …


Molecular Analyses Reveal Consistent Food Web Structure With Elevation In Rainforest Drosophila – Parasitoid Communities, Christopher T. Jeffs, J. Christopher D. Terry, Megan Higgie, Anna Jandová, Hana Konvičková, Joel J. Brown, Chia H. Lue, Michele Schiffer, Eleanor K. O'Brien, Jon Bridle, Jan Hrček, Owen T. Lewis Jan 2021

Molecular Analyses Reveal Consistent Food Web Structure With Elevation In Rainforest Drosophila – Parasitoid Communities, Christopher T. Jeffs, J. Christopher D. Terry, Megan Higgie, Anna Jandová, Hana Konvičková, Joel J. Brown, Chia H. Lue, Michele Schiffer, Eleanor K. O'Brien, Jon Bridle, Jan Hrček, Owen T. Lewis

Research outputs 2014 to 2021

The analysis of interaction networks across spatial environmental gradients is a powerful approach to investigate the responses of communities to global change. Using a combination of DNA metabarcoding and traditional molecular methods we built bipartite Drosophila – parasitoid food webs from six Australian rainforest sites across gradients spanning 850 m in elevation and 5°C in mean temperature. Our cost-effective hierarchical approach to network reconstruction separated the determination of host frequencies from the detection and quantification of interactions. The food webs comprised 5–9 host and 5–11 parasitoid species at each site, and showed a lower incidence of parasitism at high elevation. …


A Population-Specific Major Allele Reference Genome From The United Arab Emirates Population, Gihan Daw Elbait, Andreas Henschel, Guan K. Tay, Habiba S. Al Safar Jan 2021

A Population-Specific Major Allele Reference Genome From The United Arab Emirates Population, Gihan Daw Elbait, Andreas Henschel, Guan K. Tay, Habiba S. Al Safar

Research outputs 2014 to 2021

The ethnic composition of the population of a country contributes to the uniqueness of each national DNA sequencing project and, ideally, individual reference genomes are required to reduce the confounding nature of ethnic bias. This work represents a representative Whole Genome Sequencing effort of an understudied population. Specifically, high coverage consensus sequences from 120 whole genomes and 33 whole exomes were used to construct the first ever population specific major allele reference genome for the United Arab Emirates (UAE). When this was applied and compared to the archetype hg19 reference, assembly of local Emirati genomes was reduced by ∼19% (i.e., …


Hypogonadism Induced By Surgical Stress And Brain Trauma Is Reversed By Human Chorionic Gonadotropin In Male Rats: A Potential Therapy For Surgical And Tbi-Induced Hypogonadism?, Rastafa I. Geddes, Amita Kapoor, Kentaro Hayashi, Ryan Rauh, Marlyse Wehber, Quinn Bongers, Alex D. Jansen, Icelle M. Anderson, Gabrielle Farquhar, Sivan Vadakkadath-Meethal, Toni E. Ziegler, Craig S. Atwood Jan 2021

Hypogonadism Induced By Surgical Stress And Brain Trauma Is Reversed By Human Chorionic Gonadotropin In Male Rats: A Potential Therapy For Surgical And Tbi-Induced Hypogonadism?, Rastafa I. Geddes, Amita Kapoor, Kentaro Hayashi, Ryan Rauh, Marlyse Wehber, Quinn Bongers, Alex D. Jansen, Icelle M. Anderson, Gabrielle Farquhar, Sivan Vadakkadath-Meethal, Toni E. Ziegler, Craig S. Atwood

Research outputs 2014 to 2021

Introduction: Hypogonadotropic hypogonadism (HH) is an almost universal, yet underappreciated, endocrinological complication of traumatic brain injury (TBI). The goal of this study was to determine whether the developmental hormone human chorionic gonadotropin (hCG) treatment could reverse HH induced by a TBI. Methods: Plasma samples were collected at post-surgery/post-injury (PSD/PID) days -10, 1, 11, 19 and 29 from male Sprague-Dawley rats (5- to 6-month-old) that had undergone a Sham surgery (craniectomy alone) or CCI injury (craniectomy + bilateral moderate-to-severe CCI injury) and treatment with saline or hCG (400 IU/kg; i.m.) every other day. Results: Both Sham and CCI injury significantly decreased …


Atrophy Expansion Rates In Stargardt Disease Using Ultra-Widefield Fundus Autofluorescence, Rachael C. Heath-Jeffery, Jennifer A. Thompson, Johnny Lo, Tina M. Lamey, Terri L. Mclaren, Ian L. Mcallister, David A. Mackey, Ian J. Constable, John N. De Roach, Fred K. Chen Jan 2021

Atrophy Expansion Rates In Stargardt Disease Using Ultra-Widefield Fundus Autofluorescence, Rachael C. Heath-Jeffery, Jennifer A. Thompson, Johnny Lo, Tina M. Lamey, Terri L. Mclaren, Ian L. Mcallister, David A. Mackey, Ian J. Constable, John N. De Roach, Fred K. Chen

Research outputs 2014 to 2021

Purpose To investigate atrophy expansion rate (ER) using ultra-widefield (UWF) fundus autofluorescence (FAF) in Stargardt disease (STGD1). Design Retrospective, longitudinal study. Participants Patients with biallelic ABCA4 mutations who were evaluated with UWF FAF and Heidelberg 30° × 30° and 55° × 55° FAF imaging. Methods Patients with atrophy secondary to STGD1 were classified into genotype groups: group A, biallelic severe or null-like variants with early-onset disease; group B, 1 intermediate variant in trans with severe or null-like variant; and group C, 1 mild variant in trans with severe or null-like variant or late-onset disease. The boundaries of definitely decreased autofluorescence …


Development Of A Vitamin K Database For Commercially Available Food In Australia, Claire R. Palmer, Henrietta Koch, Sujata Shinde, Lauren C. Blekkenhorst, Joshua Lewis, Kevin D. Croft, Jonathan M. Hodgson, Marc Sim Jan 2021

Development Of A Vitamin K Database For Commercially Available Food In Australia, Claire R. Palmer, Henrietta Koch, Sujata Shinde, Lauren C. Blekkenhorst, Joshua Lewis, Kevin D. Croft, Jonathan M. Hodgson, Marc Sim

Research outputs 2014 to 2021

Vitamin K content of foods is known to vary substantially by geographical location. In Australia, no Vitamin K database of food exists, thereby creating ambiguity when trying to develop national dietary intake guidelines. This investigation aimed to develop a Vitamin K database for commonly consumed foods that are commercially available in Australian supermarkets. The Vitamin K1 (phylloquinone; PK) and K2 (menaquinone; MK4, MK7) content of 60 foods known to contain Vitamin K were assessed (e.g., vegetables fruits, oils, animal products, dairy and fermented foods). A liquid chromatography with tandem mass spectrometry (LCMS/MS) method was developed and used to measure PK …


Genome-Wide Association Study Of Hospitalized Covid-19 Patients In The United Arab Emirates, Mira Mousa, Hema Vurivi, Hussein Kannout, Maimunah Uddin, Nawal Alkaabi, Bassam Mahboub, Guan K. Tay, Habiba S. Alsafar Jan 2021

Genome-Wide Association Study Of Hospitalized Covid-19 Patients In The United Arab Emirates, Mira Mousa, Hema Vurivi, Hussein Kannout, Maimunah Uddin, Nawal Alkaabi, Bassam Mahboub, Guan K. Tay, Habiba S. Alsafar

Research outputs 2014 to 2021

Background: The heterogeneity in symptomatology and phenotypic profile attributable to COVID-19 is widely unknown. The objective of this manuscript is to conduct a trans-ancestry genome wide association study (GWAS) meta-analysis of COVID-19 severity to improve the understanding of potentially causal targets for SARS-CoV-2. Methods: This cross-sectional study recruited 646 participants in the UAE that were divided into two phenotypic groups based on the severity of COVID-19 phenotypes, hospitalized (n=482) and non-hospitalized (n=164) participants. Hospitalized participants were COVID-19 patients that developed acute respiratory distress syndrome (ARDS), pneumonia or progression to respiratory failure that required supplemental oxygen therapy or mechanical ventilation support …


Gut Microbiota Interplay With Covid-19 Reveals Links To Host Lipid Metabolism Among Middle Eastern Populations, Mohammad Tahseen Al Bataineh, Andreas Henschel, Mira Mousa, Marianne Daou, Fathimathuz Waasia, Hussein Kannout, Mariam Khalili, Mohd Azzam Kayasseh, Abdulmajeed Alkhajeh, Maimunah Uddin, Nawal Alkaabi, Guan K. Tay, Samuel F. Feng, Ahmed F. Yousef, Habiba S. Alsafar, Uae Covid-19 Collaborative Partnership Jan 2021

Gut Microbiota Interplay With Covid-19 Reveals Links To Host Lipid Metabolism Among Middle Eastern Populations, Mohammad Tahseen Al Bataineh, Andreas Henschel, Mira Mousa, Marianne Daou, Fathimathuz Waasia, Hussein Kannout, Mariam Khalili, Mohd Azzam Kayasseh, Abdulmajeed Alkhajeh, Maimunah Uddin, Nawal Alkaabi, Guan K. Tay, Samuel F. Feng, Ahmed F. Yousef, Habiba S. Alsafar, Uae Covid-19 Collaborative Partnership

Research outputs 2014 to 2021

The interplay between the compositional changes in the gastrointestinal microbiome, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility and severity, and host functions is complex and yet to be fully understood. This study performed 16S rRNA gene-based microbial profiling of 143 subjects. We observed structural and compositional alterations in the gut microbiota of the SARS-CoV-2-infected group in comparison to non-infected controls. The gut microbiota composition of the SARS-CoV-2-infected individuals showed an increase in anti-inflammatory bacteria such as Faecalibacterium (p-value = 1.72 × 10–6) and Bacteroides (p-value = 5.67 × 10–8). We also revealed a higher relative abundance of the highly …


Risk Factors For Gut Dysbiosis In Early Life, Kimberley Parkin, Claus T. Christophersen, Valerie Verhasselt, Matthew N. Cooper, David Martino Jan 2021

Risk Factors For Gut Dysbiosis In Early Life, Kimberley Parkin, Claus T. Christophersen, Valerie Verhasselt, Matthew N. Cooper, David Martino

Research outputs 2014 to 2021

Dysbiosis refers to a reduction in microbial diversity, combined with a loss of beneficial taxa, and an increase in pathogenic microorganisms. Dysbiosis of the intestinal microbiota can have a substantial effect on the nervous and immune systems, contributing to the onset of several inflammatory diseases. Epidemiological studies provided insight in how changes in the living environment have contributed to an overall loss of diversity and key taxa in the gut microbiome, coinciding with increased reports of atopy and allergic diseases. The gut microbiome begins development at birth, with major transition periods occurring around the commencement of breastfeeding, and the introduction …


Associations Between Genetic Variants In The Vitamin D Metabolism Pathway And Severity Of Covid-19 Among Uae Residents, Fatme Al-Anouti, Mira Mousa, Spyridon N. Karras, William B. Grant, Zainab Alhalwachi, Laila Abdel-Wareth, Maimunah Uddin, Nawal Alkaabi, Guan K. Tay, Bassam Mahboub, Habiba Alsafar Jan 2021

Associations Between Genetic Variants In The Vitamin D Metabolism Pathway And Severity Of Covid-19 Among Uae Residents, Fatme Al-Anouti, Mira Mousa, Spyridon N. Karras, William B. Grant, Zainab Alhalwachi, Laila Abdel-Wareth, Maimunah Uddin, Nawal Alkaabi, Guan K. Tay, Bassam Mahboub, Habiba Alsafar

Research outputs 2014 to 2021

Vitamin D has many effects on cells in the immune system. Many studies have linked low vitamin D status with severity of COVID-19. Genetic variants involved in vitamin D metabolism have been implicated as potential risk factors for severe COVID-19 outcomes. This study investigated how genetic variations in humans affected the clinical presentation of COVID-19. In total, 646 patients with SARS-CoV-2 infection were divided into two groups: noncritical COVID-19 (n = 453; 70.12%) and a critical group (n = 193; 29.87%). Genotype data on the GC, NADSYN1, VDR, and CYP2R1 genes along with data on serum 25-hydroxyvitamin D levels were …


Fecal Sample Collection Methods And Time Of Day Impact Microbiome Composition And Short Chain Fatty Acid Concentrations, Jacquelyn Jones, Stacey N. Reinke, Alishum Ali, Debra J. Palmer, Claus T. Christophersen Jan 2021

Fecal Sample Collection Methods And Time Of Day Impact Microbiome Composition And Short Chain Fatty Acid Concentrations, Jacquelyn Jones, Stacey N. Reinke, Alishum Ali, Debra J. Palmer, Claus T. Christophersen

Research outputs 2014 to 2021

Associations between the human gut microbiome and health outcomes continues to be of great interest, although fecal sample collection methods which impact microbiome studies are sometimes neglected. Here, we expand on previous work in sample optimization, to promote high quality microbiome data. To compare fecal sample collection methods, amplicons from the bacterial 16S rRNA gene (V4) and fungal (ITS2) region, as well as short chain fatty acid (SCFA) concentrations were determined in fecal material over three timepoints. We demonstrated that spot sampling of stool results in variable detection of some microbial members, and inconsistent levels of SCFA; therefore, sample homogenization …


Identifying Differences In Nutrition-Related Learning Interests Of Adolescent Students, Margaret Miller, Donna Barwood, Michael Furfaro, Julie Boston, Sandra Smith, Martin Masek Jan 2021

Identifying Differences In Nutrition-Related Learning Interests Of Adolescent Students, Margaret Miller, Donna Barwood, Michael Furfaro, Julie Boston, Sandra Smith, Martin Masek

Research outputs 2014 to 2021

© 2021 The Authors. Journal of School Health published by Wiley Periodicals LLC. on behalf of American School Health Association. BACKGROUND: In this study, we examined nutrition-related topics among adolescent students attending schools with different Indices of Community Socio-Educational Advantage (ICSEA). METHOD: Participating students (N = 206) from 5 schools in Western Australia completed a paper-based questionnaire on nutrition-related topics. Frequencies and independent chi-square tests were used to identify differences between sexes and school ICSEA. RESULTS: Of the participating students, 75% were interested in learning about 8 of 16 topics. We found statistically significant differences by sex (p < .01) for “Eating the right foods for preventing illness and disease,” “Eating the right food for being active” among girls, and “Reducing food waste” among boys. We also noted differences by school ICSEA. CONCLUSION: Acknowledging sex and socioeducational differences in teaching and learning may help teachers to engage adolescent students in nutrition education.


Identification And Characterisation Of Putative Drug Binding Sites In Human Atp-Binding Cassette B5 (Abcb5) Transporter, Lokeswari P. Tangella, Mahreen Arooj, Evelyne Deplazes, Elin S. Gray, Ricardo L. Mancera Jan 2021

Identification And Characterisation Of Putative Drug Binding Sites In Human Atp-Binding Cassette B5 (Abcb5) Transporter, Lokeswari P. Tangella, Mahreen Arooj, Evelyne Deplazes, Elin S. Gray, Ricardo L. Mancera

Research outputs 2014 to 2021

© 2020 The Author(s) The human ATP-binding cassette B5 (ABCB5) transporter, a member of the ABC transporter superfamily, is linked to chemoresistance in tumour cells by drug effluxion. However, little is known about its structure and drug-binding sites. In this study, we generated an atomistic model of the full-length human ABCB5 transporter with the highest quality using the X-ray crystal structure of mouse ABCB1 (Pgp1), a close homologue of ABCB5 and a well-studied member of the ABC family. Molecular dynamics simulations were used to validate the atomistic model of ABCB5 and characterise its structural properties in model cell membranes. Molecular …


Human Ips Cells Engender Corneal Epithelial Stem Cells With Holoclone-Forming Capabilities, Shinya Watanabe, Ryuhei Hayashi, Yuzuru Sasamoto, Motokazu Tsujikawa, Bruce R. Ksander, Markus H. Frank, Andrew J. Quantock, Natasha Y. Frank, Kohji Nishida Jan 2021

Human Ips Cells Engender Corneal Epithelial Stem Cells With Holoclone-Forming Capabilities, Shinya Watanabe, Ryuhei Hayashi, Yuzuru Sasamoto, Motokazu Tsujikawa, Bruce R. Ksander, Markus H. Frank, Andrew J. Quantock, Natasha Y. Frank, Kohji Nishida

Research outputs 2014 to 2021

Human induced pluripotent stem cells (hiPSCs) can generate a multiplicity of organoids, yet no compelling evidence currently exists as to whether or not these contain tissue-specific, holoclone-forming stem cells. Here, we show that a subpopulation of cells in a hiPSC-derived corneal epithelial cell sheet is positive for ABCB5 (ATP-binding cassette, sub-family B, member 5), a functional marker of adult corneal epithelial stem cells. These cells possess remarkable holoclone-forming capabilities, which can be suppressed by an antibody-mediated ABCB5 blockade. The cell sheets are generated from ABCB5+ hiPSCs that first emerge in 2D eye-like organoids around six weeks of differentiation and display …


Irf7-Associated Immunophenotypes Have Dichotomous Responses To Virus/Allergen Co-Exposure And Om-85-Induced Reprogramming, Emma De Jong, Jean-Francois Lauzon-Joset, Jonatan Leffler, Michael Serralha, Alexander N. Larcombe, Claus T. Christophersen, Patrick G. Holt, Deborah H. Strickland, Anthony Bosco Jan 2021

Irf7-Associated Immunophenotypes Have Dichotomous Responses To Virus/Allergen Co-Exposure And Om-85-Induced Reprogramming, Emma De Jong, Jean-Francois Lauzon-Joset, Jonatan Leffler, Michael Serralha, Alexander N. Larcombe, Claus T. Christophersen, Patrick G. Holt, Deborah H. Strickland, Anthony Bosco

Research outputs 2014 to 2021

High risk for virus-induced asthma exacerbations in children is associated with an IRF7loimmunophenotype, but the underlying mechanisms are unclear. Here, we applied aSystems Biology approach to an animal model comprising rat strains manifesting high(BN)versuslow susceptibility (PVG) to experimental asthma, induced by virus/allergencoexposure, to elucidate the mechanism(s)-of-action of the high-risk asthmaimmunophenotype. We also investigated potential risk mitigationviapretreatment withthe immune training agent OM-85. Virus/allergen coexposure in low-risk PVG rats resultedin rapid and transient airways inflammation alongside IRF7 gene network formation. Incontrast, responses in high-risk BN rats were characterized by severe airways eosinophiliaand exaggerated proinflammatory responses that failed to resolve, and complete absenceof …


Heritability Enrichment Of Immunoglobulin G N-Glycosylation In Specific Tissues, Xingang Li, Hao Wang, Yahong Zhu, Weijie Cao, Song Manshu, Youxin Wang, Haifeng Hou, Minglin Lang, Xiuhua Guo, Xuerui Tan, Jingdong J. Han, Wei Wang Jan 2021

Heritability Enrichment Of Immunoglobulin G N-Glycosylation In Specific Tissues, Xingang Li, Hao Wang, Yahong Zhu, Weijie Cao, Song Manshu, Youxin Wang, Haifeng Hou, Minglin Lang, Xiuhua Guo, Xuerui Tan, Jingdong J. Han, Wei Wang

Research outputs 2014 to 2021

Genome-wide association studies (GWAS) have identified over 60 genetic loci associated with immunoglobulin G (IgG) N-glycosylation; however, the causal genes and their abundance in relevant tissues are uncertain. Leveraging data from GWAS summary statistics for 8,090 Europeans, and large-scale expression quantitative trait loci (eQTL) data from the genotype-tissue expression of 53 types of tissues (GTEx v7), we derived a linkage disequilibrium score for the specific expression of genes (LDSC-SEG) and conducted a transcriptome-wide association study (TWAS). We identified 55 gene associations whose predicted levels of expression were significantly associated with IgG N-glycosylation in 14 tissues. Three working scenarios, i.e., tissue-specific, …


Therapeutic Potential Of Mitophagy-Inducing Microflora Metabolite, Urolithin A For Alzheimer’S Disease, Dona Pamoda W. Jayatunga, Eugene Hone, Harjot Khaira, Taciana Lunelli, Harjinder Singh, Gilles J. Guillemin, Binosha Fernando, Manohar L. Garg, Giuseppe Verdile, Ralph N. Martins Jan 2021

Therapeutic Potential Of Mitophagy-Inducing Microflora Metabolite, Urolithin A For Alzheimer’S Disease, Dona Pamoda W. Jayatunga, Eugene Hone, Harjot Khaira, Taciana Lunelli, Harjinder Singh, Gilles J. Guillemin, Binosha Fernando, Manohar L. Garg, Giuseppe Verdile, Ralph N. Martins

Research outputs 2014 to 2021

Mitochondrial dysfunction including deficits of mitophagy is seen in aging and neuro-degenerative disorders including Alzheimer’s disease (AD). Apart from traditionally targeting amyloid beta (Aβ), the main culprit in AD brains, other approaches include investigating impaired mitochondrial pathways for potential therapeutic benefits against AD. Thus, a future therapy for AD may focus on novel candidates that enhance optimal mitochondrial integrity and turnover. Bi-oactive food components, known as nutraceuticals, may serve as such agents to combat AD. Uro-lithin A is an intestinal microbe-derived metabolite of a class of polyphenols, ellagitannins (ETs). Urolithin A is known to exert many health benefits. Its antioxidant, …


Pd-L1 Expression On Circulating Tumor Cells May Be Predictive Of Response To Pembrolizumab In Advanced Melanoma: Results From A Pilot Study, Muhammad K. Khattak, Anna L. Reid, James Freeman, Michelle Pereira, Ashleigh Mcevoy, Johnny Lo, Markus Frank, Tarek Meniawy, Ali Didan, Isaac Spencer, Benhur Amanuel, Michael Millward, Mel Ziman, Elin Gray Dec 2020

Pd-L1 Expression On Circulating Tumor Cells May Be Predictive Of Response To Pembrolizumab In Advanced Melanoma: Results From A Pilot Study, Muhammad K. Khattak, Anna L. Reid, James Freeman, Michelle Pereira, Ashleigh Mcevoy, Johnny Lo, Markus Frank, Tarek Meniawy, Ali Didan, Isaac Spencer, Benhur Amanuel, Michael Millward, Mel Ziman, Elin Gray

Research outputs 2014 to 2021

BACKGROUND: PD-1 inhibitors are routinely used for the treatment of advanced melanoma. This study sought to determine whether PD-L1 expression on circulating tumor cells (CTCs) can serve as a predictive biomarker of clinical benefit and response to treatment with the PD-1 inhibitor pembrolizumab.

METHODS: Blood samples were collected from patients with metastatic melanoma receiving pembrolizumab, prior to treatment and 6-12 weeks after initiation of therapy. Multiparametric flow cytometry was used to identify CTCs and evaluate the expression of PD-L1.

RESULTS: CTCs were detected in 25 of 40 patients (63%). Patients with detectable PD-L1

CONCLUSION: Our results reveal the potential of …


Genetic Analysis Of Endometriosis And Depression Identifies Shared Loci And Implicates Causal Links With Gastric Mucosa Abnormality, Emmanuel Adewuyi, Divya Mehta, Yadav Sapkota, Asa Auta, Kosuke Yoshihara, Mette Nyegaard, Lyn R. Griffiths, Grant W. Montgomery, Daniel I. Chasman, Dale R. Nyholt Sep 2020

Genetic Analysis Of Endometriosis And Depression Identifies Shared Loci And Implicates Causal Links With Gastric Mucosa Abnormality, Emmanuel Adewuyi, Divya Mehta, Yadav Sapkota, Asa Auta, Kosuke Yoshihara, Mette Nyegaard, Lyn R. Griffiths, Grant W. Montgomery, Daniel I. Chasman, Dale R. Nyholt

Research outputs 2014 to 2021

Evidence from observational studies indicates that endometriosis and depression often co-occur. However, conflicting evidence exists, and the etiology as well as biological mechanisms underlying their comorbidity remain unknown. Utilizing genome-wide association study (GWAS) data, we comprehensively assessed the relationship between endometriosis and depression. Single nucleotide polymorphism effect concordance analysis (SECA) found a significant genetic overlap between endometriosis and depression (PFsig-permuted = 9.99 × 10−4). Linkage disequilibrium score regression (LDSC) analysis estimated a positive and highly significant genetic correlation between the two traits (rG = 0.27, P = 8.85 × 10−27). A meta-analysis of endometriosis and depression GWAS (sample size = …


What Is The Minimal Dose For Resistance Exercise Effectiveness In Prostate Cancer Patients? Systematic Review And Meta-Analysis On Patient-Reported Outcomes, Pedro Lopez, Dennis R. Taaffe, Robert U. Newton, Laurien M. Buffart, Daniel A. Galvão Jan 2020

What Is The Minimal Dose For Resistance Exercise Effectiveness In Prostate Cancer Patients? Systematic Review And Meta-Analysis On Patient-Reported Outcomes, Pedro Lopez, Dennis R. Taaffe, Robert U. Newton, Laurien M. Buffart, Daniel A. Galvão

Research outputs 2014 to 2021

© 2020, The Author(s). Background: Active treatments for prostate cancer are well known to result in several adverse effects such as fatigue, depression and anxiety symptoms, impacting the overall quality of life (QoL) and wellbeing of a considerable proportion of patients. Resistance-based exercise interventions have shown positive effects to reduce or mitigate these treatment-related side effects. However, the minimal dosage required to derive these benefits is unknown. We systematically reviewed the resistance training effects in prostate cancer patients to determine the minimal dosage regarding the exercise components (mode, duration, volume and intensity) on fatigue, QoL, depression and anxiety. Methods: Using …


The Effects Of Yam Gruel On Lowering Fasted Blood Glucose In T2dm Rats, Xinjun Lin, Zongting Luo, Shuqin Pang, Carol Chunfeng Wang, Li Ge, Yanling Dai, Jian Zhou, Fang Chen, Xuepei Hong, Jiahui Zhang Jan 2020

The Effects Of Yam Gruel On Lowering Fasted Blood Glucose In T2dm Rats, Xinjun Lin, Zongting Luo, Shuqin Pang, Carol Chunfeng Wang, Li Ge, Yanling Dai, Jian Zhou, Fang Chen, Xuepei Hong, Jiahui Zhang

Research outputs 2014 to 2021

© 2020 Xinjun Lin et al., published by De Gruyter 2020. There is increasing evidence of the linkage between type 2 diabetes mellitus (T2DM) and gut microbiota. Based on our previous studies, we investigated the hypoglycemic mechanisms of yam gruel to provide a scientific basis for its popularization and application. Wistar rats were randomly divided into control and T2DM model groups. Rats in the model group were stimulated by a high-sugar/high-fat diet combined with an intraperitoneal injection of streptozotocin to induce T2DM. The T2DM rats were further subdivided randomly into three groups: (1) DM, (2) DM + yam gruel, and …


Concordant Peripheral Lipidome Signatures In Two Large Clinical Studies Of Alzheimer’S Disease, Kevin Huynh, Wei Ling Florence Lim, Corey Giles, Kaushala S. Jayawardana, Agus Salim, Natalie A. Mellett, Adam Alexander T. Smith, Gavriel Olshansky, Brian G. Drew, Pratishtha Chatterjee, Ian Martins, Simon M. Laws, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Colin L. Masters, Matthias Arnold, Kwangsik Nho, Andrew J. Saykin, Rebecca Baillie, Xianlin Han, Rima Kaddurah-Daouk, Ralph N. Martins, Peter J. Meikle Jan 2020

Concordant Peripheral Lipidome Signatures In Two Large Clinical Studies Of Alzheimer’S Disease, Kevin Huynh, Wei Ling Florence Lim, Corey Giles, Kaushala S. Jayawardana, Agus Salim, Natalie A. Mellett, Adam Alexander T. Smith, Gavriel Olshansky, Brian G. Drew, Pratishtha Chatterjee, Ian Martins, Simon M. Laws, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Colin L. Masters, Matthias Arnold, Kwangsik Nho, Andrew J. Saykin, Rebecca Baillie, Xianlin Han, Rima Kaddurah-Daouk, Ralph N. Martins, Peter J. Meikle

Research outputs 2014 to 2021

© 2020, The Author(s). Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer’s disease (AD). Lipids are complex molecules comprising many isomeric and isobaric species, necessitating detailed analysis to enable interpretation of biological significance. Our expanded targeted lipidomics platform (569 species across 32 classes) allows for detailed lipid separation and characterisation. In this study we examined peripheral samples of two cohorts (AIBL, n = 1112 and ADNI, n = 800). We are able to identify concordant peripheral signatures associated with prevalent AD arising from lipid pathways including; ether lipids, sphingolipids (notably GM3 gangliosides) and lipid …


Eftilagimod Alpha, A Soluble Lymphocyte Activation Gene-3 (Lag-3) Protein Plus Pembrolizumab In Patients With Metastatic Melanoma, Victoria Atkinson, Adnan Khattak, Andrew Haydon, Melissa Eastgate, Amitesh Roy, Prashanth Prithviraj, Christian Mueller, Chrystelle Brignone, Frederic Triebel Jan 2020

Eftilagimod Alpha, A Soluble Lymphocyte Activation Gene-3 (Lag-3) Protein Plus Pembrolizumab In Patients With Metastatic Melanoma, Victoria Atkinson, Adnan Khattak, Andrew Haydon, Melissa Eastgate, Amitesh Roy, Prashanth Prithviraj, Christian Mueller, Chrystelle Brignone, Frederic Triebel

Research outputs 2014 to 2021

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. BACKGROUND: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of eftilagimod alpha (efti), a soluble lymphocyte activation gene-3 protein, in combination with the programmed cell death-1 (PD-1) antagonist pembrolizumab. METHODS: The study was divided into two parts; parts A and B, where part A was the dose escalation part and part B was an extension part of the study. Patients with metastatic melanoma were treated with efti plus the standard dose of pembrolizumab. Blood samples were assayed to determine …


Influence Of Strength Level On The Acute Post-Activation Performance Enhancement Following Flywheel And Free Weight Resistance Training, Borja Sañudo, Moisés De Hoyo, Guy Gregory Haff, Alejandro Muñoz-López Jan 2020

Influence Of Strength Level On The Acute Post-Activation Performance Enhancement Following Flywheel And Free Weight Resistance Training, Borja Sañudo, Moisés De Hoyo, Guy Gregory Haff, Alejandro Muñoz-López

Research outputs 2014 to 2021

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This study aimed to compare the post-activation potentiation performance enhancement (PAPE) response to the acute inertial flywheel (FW) and free weight resistance training (TRA) on subsequent countermovement jump (CMJ) and sprint performance (10 m sprint). This study used a randomized crossover design including twenty-eight healthy males that were divided into strong (relative one-repetition maximum (1RM) back squat > 2.0 × body mass) and weak (relative 1RM back squat < 2.0 × body mass) groups. All participants performed the following: (a) three reps at 90% of their 1RM back squat (TRA) and (b) three reps on an inertial FW (plus one repetition to initiate flywheel movement) with an intensity that generated a mean propulsive velocity equal to that achieved with 90% of the 1RM back squat. Before and after the conditioning activity, participants performed two CMJs and two 10 m sprints. Within-group analyses showed significantly greater CMJ (d > 0.9, p < 0.001) and sprint performance (d > 0.5, p < 0.05) in the FW and the TRA group. Between-group analysis showed that sprint changes were significantly greater in the FW-strong group when compared with the TRA (F1,18 = 5.11, p = 0.036, η2p = 0.221—large) group. These results suggest that using a squat activation protocol on a FW may lead to an acute positive effect on jump and sprint performance, especially in stronger individuals.


Contralateral Effects Of Unilateral Strength And Skill Training: Modified Delphi Consensus To Establish Key Aspects Of Cross-Education, A. Manca, T. Hortobágyi, T. J. Carroll, R. M. Enoka, J. P. Farthing, S. C. Gandevia, D. J. Kidgell, Janet L. Taylor, F. Deriu Jan 2020

Contralateral Effects Of Unilateral Strength And Skill Training: Modified Delphi Consensus To Establish Key Aspects Of Cross-Education, A. Manca, T. Hortobágyi, T. J. Carroll, R. M. Enoka, J. P. Farthing, S. C. Gandevia, D. J. Kidgell, Janet L. Taylor, F. Deriu

Research outputs 2014 to 2021

© 2020, The Author(s). Background: Cross-education refers to increased motor output (i.e., force generation, skill) of the opposite, untrained limb following a period of unilateral exercise training. Despite extensive research, several aspects of the transfer phenomenon remain controversial. Methods: A modified two-round Delphi online survey was conducted among international experts to reach consensus on terminology, methodology, mechanisms of action, and translational potential of cross-education, and to provide a framework for future research. Results: Through purposive sampling of the literature, we identified 56 noted experts in the field, of whom 32 completed the survey, and reached consensus (75% threshold) on 17 …