Publications by authors named "Barbara Fraser"

72 Publications

A novel approach to nonsurgical sterilization; application of menadione-modified gonocyte-targeting M13 bacteriophage for germ cell ablation in utero.

Pharmacol Res Perspect 2020 10;8(5):e00654

Priority Research Centre for Reproductive Science, The University of Newcastle, Callaghan, NSW, Australia.

There remains a compelling need for the development of nonsurgical sterilizing agents to expand the fertility management options for both domestic and feral animal species. We hypothesize that an efficacious sterilization approach would be to selectively ablate nonrenewable cell types that are essential for reproduction, such as the undifferentiated gonocytes within the embryonic gonad. Here, we report a novel strategy to achieve this goal centered on the use of a chemically modified M13 bacteriophage to effect the targeted delivery of menadione, a redox-cycling naphthoquinone, to mouse gonocytes. Panning of the M13 random peptide 'phage display library proved effective in the isolation of gonocyte-specific targeting clones. One such clone was modified via N-succinimidyl-S-acetylthioacetate (SATA) linkage to the N-terminus of the major PVIII capsid protein. Subsequent deacetylation of the SATA was undertaken to expose a thiol group capable of reacting with menadione through Michael addition. This chemical modification was confirmed using UV spectrophotometry. In proof-of-concept experiments we applied the modified 'phage to primary cultures of fetal germ cells and induced, an approximately, 60% reduction in the viability of the target cell population. These studies pave the way for in vivo application of chemically modified M13 bacteriophage in order to achieve the selective ablation of nonrenewable cell types in the reproductive system, thereby providing a novel nonsurgical approach the regulation of fertility in target species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/prp2.654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507010PMC
October 2020

Violent protests in Chile linked to health-care inequities.

Authors:
Barbara Fraser

Lancet 2019 11;394(10210):1697-1698

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(19)32720-5DOI Listing
November 2019

Providing care for trans women with HIV/AIDS in Peru.

Authors:
Barbara Fraser

Lancet 2019 Apr 4;393(10179):1399-1400. Epub 2019 Apr 4.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(19)30806-2DOI Listing
April 2019

Measles outbreak in the Americas.

Authors:
Barbara Fraser

Lancet 2018 08 2;392(10145):373. Epub 2018 Aug 2.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(18)31727-6DOI Listing
August 2018

China's lust for jaguar fangs imperils big cats.

Authors:
Barbara Fraser

Nature 2018 03;555(7694):13-14

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/d41586-018-02314-5DOI Listing
March 2018

China's lust for jaguar fangs imperils big cats.

Authors:
Barbara Fraser

Nature 2018 Mar;555(7694):13-14

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/d41586-018-02314-5DOI Listing
March 2018

Dams nudge Amazon's ecosystems off-kilter.

Authors:
Barbara Fraser

Science 2018 Feb 1;359(6375):508-509. Epub 2018 Feb 1.

Lima.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.359.6375.508DOI Listing
February 2018

Emergency response after Mexico's earthquakes.

Lancet 2017 Sep 28;390(10102):1575. Epub 2017 Sep 28.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(17)32547-3DOI Listing
September 2017

RNA binding protein Musashi-2 regulates PIWIL1 and TBX1 in mouse spermatogenesis.

J Cell Physiol 2018 04 4;233(4):3262-3273. Epub 2017 Oct 4.

Priority Research Centre in Reproductive Science, University of Newcastle, Callaghan, Australia.

RNA-binding proteins (RBP) are important facilitators of post-transcriptional gene regulation. We have previously established that nuclear overexpression of the RBP Musashi-2 (MSI2) during male germ cell maturation is detrimental to sperm cell development and fertility. Herein we determine the genes and pathways impacted by the upregulation of Msi2. Microarray analysis and qPCR confirmed differential gene expression in factors fundamental to the cell cycle, cellular proliferation, and cell death. Similarly, comparative protein expression analysis via iTRAQ, immunoblot, and immunolocalization, identified differential expression and localization of important regulators of transcription, translation, RNA processing, and spermatogenesis. Specifically, the testis-expressed transcription factor, Tbx1, and the piRNA regulator of gamete development, Piwil1, were both found to be targeted for translational repression by MSI2. This study provides key evidence to support a fundamental role for MSI2 in post-transcriptional regulation during male gamete development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.26168DOI Listing
April 2018

Data reveal state of Venezuelan health system.

Authors:
Barbara Fraser

Lancet 2017 May;389(10084):2095

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(17)31435-6DOI Listing
May 2017

Venezuela: aid needed to ease health crisis.

Lancet 2016 Sep 1;388(10048):947-9. Epub 2016 Sep 1.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(16)31523-9DOI Listing
September 2016

Peru's new health minister outlines priorities.

Authors:
Barbara Fraser

Lancet 2016 Aug;388(10046):745-6

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(16)31415-5DOI Listing
August 2016

Oil in the forest.

Authors:
Barbara Fraser

Science 2016 Aug;353(6300):641-3

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.353.6300.641DOI Listing
August 2016

Peru's transgender community: the battle for rights.

Authors:
Barbara Fraser

Lancet 2016 Jul;388(10042):324-325

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(16)31146-1DOI Listing
July 2016

Systematic Population Screening, Using Biomarkers and Genetic Testing, Identifies 2.5% of the U.K. Pediatric Diabetes Population With Monogenic Diabetes.

Diabetes Care 2016 Nov 6;39(11):1879-1888. Epub 2016 Jun 6.

Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, U.K.

Objective: Monogenic diabetes is rare but is an important diagnosis in pediatric diabetes clinics. These patients are often not identified as this relies on the recognition of key clinical features by an alert clinician. Biomarkers (islet autoantibodies and C-peptide) can assist in the exclusion of patients with type 1 diabetes and allow systematic testing that does not rely on clinical recognition. Our study aimed to establish the prevalence of monogenic diabetes in U.K. pediatric clinics using a systematic approach of biomarker screening and targeted genetic testing.

Research Design And Methods: We studied 808 patients (79.5% of the eligible population) <20 years of age with diabetes who were attending six pediatric clinics in South West England and Tayside, Scotland. Endogenous insulin production was measured using the urinary C-peptide creatinine ratio (UCPCR). C-peptide-positive patients (UCPCR ≥0.2 nmol/mmol) underwent islet autoantibody (GAD and IA2) testing, with patients who were autoantibody negative undergoing genetic testing for all 29 identified causes of monogenic diabetes.

Results: A total of 2.5% of patients (20 of 808 patients) (95% CI 1.6-3.9%) had monogenic diabetes (8 GCK, 5 HNF1A, 4 HNF4A, 1 HNF1B, 1 ABCC8, 1 INSR). The majority (17 of 20 patients) were managed without insulin treatment. A similar proportion of the population had type 2 diabetes (3.3%, 27 of 808 patients).

Conclusions: This large systematic study confirms a prevalence of 2.5% of patients with monogenic diabetes who were <20 years of age in six U.K. clinics. This figure suggests that ∼50% of the estimated 875 U.K. pediatric patients with monogenic diabetes have still not received a genetic diagnosis. This biomarker screening pathway is a practical approach that can be used to identify pediatric patients who are most appropriate for genetic testing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc16-0645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5018394PMC
November 2016

ANTHROPOLOGY. Deadly attack on isolated tribe.

Authors:
Barbara Fraser

Science 2015 Dec;350(6266):1304

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.350.6266.1304DOI Listing
December 2015

Knockout of RNA Binding Protein MSI2 Impairs Follicle Development in the Mouse Ovary: Characterization of MSI1 and MSI2 during Folliculogenesis.

Biomolecules 2015 Jun 26;5(3):1228-44. Epub 2015 Jun 26.

School of Environmental and Life Sciences, University of Newcastle, Callaghan NSW 2308, Australia.

Characterizing the mechanisms underlying follicle development in the ovary is crucial to understanding female fertility and is an area of increasing research interest. The RNA binding protein Musashi is essential for post-transcriptional regulation of oocyte maturation in Xenopus and is expressed during ovarian development in Drosophila. In mammals Musashi is important for spermatogenesis and male fertility, but its role in the ovary has yet to be characterized. In this study we determined the expression of mammalian Musashi proteins MSI1 and MSI2 during mouse folliculogenesis, and through the use of a MSI2-specific knockout mouse model we identified that MSI2 is essential for normal follicle development. Time-course characterization of MSI1 and MSI2 revealed distinct differences in steady-state mRNA levels and protein expression/localization at important developmental time-points during folliculogenesis. Using a gene-trap mouse model that inactivates Msi2, we observed a significant decrease in ovarian mass, and change in follicle-stage composition due to developmental blocking of antral stage follicles and pre-antral follicle loss through atresia. We also confirmed that hormonally stimulated Msi2-deficient mice produce significantly fewer MII oocytes (60.9% less than controls, p < 0.05). Furthermore, the majority of these oocytes are of poor viability (62.2% non-viable/apoptotic, p < 0.05), which causes a reduction in female fertility evidenced by decreased litter size in Msi2-deficient animals (33.1% reduction to controls, p < 0.05). Our findings indicate that MSI1 and MSI2 display distinct expression profiles during mammalian folliculogenesis and that MSI2 is required for pre-antral follicle development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom5031228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598749PMC
June 2015

Oxidative stress and human spermatozoa: diagnostic and functional significance of aldehydes generated as a result of lipid peroxidation.

Mol Hum Reprod 2015 Jun 2;21(6):502-15. Epub 2015 Apr 2.

Priority Research Centre in Reproductive Science, Discipline of Biological Sciences, Faculty of Science and IT, University of Newcastle, University Drive, Callaghan, New South Wales 2308, Australia Hunter Medical Research Institute (HMRI), Newcastle, New South Wales 2310, Australia CellOxess LLC, 15 Roszel Street, Princeton, NJ 08540, USA

Oxidative stress is known to compromise human sperm function and to activate the intrinsic apoptotic cascade in these cells. One of the key features of oxidatively stressed spermatozoa is the induction of a lipid peroxidation process that results in the formation of aldehydes potentially capable of disrupting sperm function through the formation of adducts with DNA and key proteins. In this study, we have examined the impact of a range of small molecular mass aldehydes generated as a consequence of lipid peroxidation on human sperm function and also compared the two most commonly formed compounds, 4-hydroxynonenal (4HNE) and malondialdehyde (MDA), for their relative ability to reflect a state of oxidative stress in these cells. Dramatic differences in the bioactivity of individual aldehydes were observed, that generally correlated with the second order rate constants describing their interaction with the model nucleophile, glutathione. Our results demonstrate that acrolein and 4HNE were the most reactive lipid aldehydes, inhibiting sperm motility while augmenting reactive oxygen species production, lipid peroxidation, oxidative DNA damage and caspase activation, in a dose-dependent manner (P < 0.001). In contrast, a variety of saturated aldehydes and the well-known marker of oxidative stress, MDA, were without effect on this cell type. While MDA was not cytotoxic per se, its generation did reflect the induction of oxidative stress in vivo and in vitro in a manner that was highly correlated with the bioactive lipid aldehyde, 4HNE. Despite such overall correlations, individual patient samples were observed in which either MDA or 4HNE predominated. Given the relative cytotoxicity of 4HNE, we propose that this aldehyde should be the preferred criterion for diagnosing oxidative stress in the male germ line.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/molehr/gav014DOI Listing
June 2015