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"Abbott, David"
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Animal Models to Understand the Etiology and Pathophysiology of Polycystic Ovary Syndrome
Abstract
More than 1 out of 10 women worldwide are diagnosed with polycystic ovary syndrome (PCOS), the leading cause of female reproductive and metabolic dysfunction. Despite its high prevalence, PCOS and its accompanying morbidities are likely underdiagnosed, averaging > 2 years and 3 physicians before women are diagnosed. Although it has been intensively researched, the underlying cause(s) of PCOS have yet to be defined. In order to understand PCOS pathophysiology, its developmental origins, and how to predict and prevent PCOS onset, there is an urgent need for safe and effective markers and treatments. In this review, we detail which animal models are more suitable for contributing to our understanding of the etiology and pathophysiology of PCOS. We summarize and highlight advantages and limitations of hormonal or genetic manipulation of animal models, as well as of naturally occurring PCOS-like females.
Graphical Abstract
Graphical Abstract
Journal Article
Epigenetic Mechanism Underlying the Development of Polycystic Ovary Syndrome (PCOS)-Like Phenotypes in Prenatally Androgenized Rhesus Monkeys
The pathogenesis of polycystic ovary syndrome (PCOS) is poorly understood. PCOS-like phenotypes are produced by prenatal androgenization (PA) of female rhesus monkeys. We hypothesize that perturbation of the epigenome, through altered DNA methylation, is one of the mechanisms whereby PA reprograms monkeys to develop PCOS. Infant and adult visceral adipose tissues (VAT) harvested from 15 PA and 10 control monkeys were studied. Bisulfite treated samples were subjected to genome-wide CpG methylation analysis, designed to simultaneously measure methylation levels at 27,578 CpG sites. Analysis was carried out using Bayesian Classification with Singular Value Decomposition (BCSVD), testing all probes simultaneously in a single test. Stringent criteria were then applied to filter out invalid probes due to sequence dissimilarities between human probes and monkey DNA, and then mapped to the rhesus genome. This yielded differentially methylated loci between PA and control monkeys, 163 in infant VAT, and 325 in adult VAT (BCSVD P<0.05). Among these two sets of genes, we identified several significant pathways, including the antiproliferative role of TOB in T cell signaling and transforming growth factor-β (TGF-β) signaling. Our results suggest PA may modify DNA methylation patterns in both infant and adult VAT. This pilot study suggests that excess fetal androgen exposure in female nonhuman primates may predispose to PCOS via alteration of the epigenome, providing a novel avenue to understand PCOS in humans.
Journal Article
Collaborative school leadership : managing a group of schools
\"Collaborative School Leadership investigates how and why more collaboration is taking place in a wide range of settings in the UK, South Africa, New Zealand, China, the USA, the Seychelles, Tanzania and Greece, and considers the implications for leadership and the overall effectiveness of schools. David Middlewood, Ian Abbott and Sue Robinson explore various models of collaboration, considering their strengths, weaknesses and how they affect school leadership, including: executive leadership, school-to-school collaboration, federations, alliances, academy chains. The supportive structure of each chapter, with bullet point introduction, case studies, points of reflection, further reading and summaries, guides the reader and supports learning. Drawing on research, the authors identify the key areas for consideration, addressing questions such as: Where does leadership reside in collaborating partnerships? Who exactly are the leaders? What impact does this leadership have on others -staff, parents, governors, learners? What kind of leadership development is desirable? They look at the fact that the skills and approaches used by leaders of single schools are not automatically transferable to the leadership of several schools and propose possible ways forward for leadership and consider potential implications for education systems as a whole. They provide both an invaluable insight and also a practical guide for the school leaders of tomorrow\" -- Provided by publisher.
Book
Early-to-Mid Gestation Fetal Testosterone Increases Right Hand 2D∶4D Finger Length Ratio in Polycystic Ovary Syndrome-Like Monkeys
A smaller length ratio for the second relative to the fourth finger (2D:4D) is repeatedly associated with fetal male-typical testosterone (T) and is implicated as a biomarker for a variety of traits and susceptibility to a number of diseases, but no experimental human studies have been performed. The present study utilizes the rhesus monkey, a close relative of humans, and employs discrete gestational exposure of female monkeys to fetal male-typical T levels for 15-35 days during early-to-mid (40-76 days; n = 7) or late (94-139 days; n = 7) gestation (term: 165 days) by daily subcutaneous injection of their dams with 10 mg T propionate. Such gestational exposures are known to enhance male-typical behavior. In this study, compared to control females (n = 19), only early-to-mid gestation T exposure virilizes female external genitalia while increasing 2D:4D ratio in the right hand (RH) by male-like elongation of RH2D. RH2D length and 2D:4D positively correlate with androgen-dependent anogenital distance (AG), and RH2D and AG positively correlate with duration of early-to-mid gestation T exposure. Male monkeys (n = 9) exhibit a sexually dimorphic 2D:4D in the right foot, but this trait is not emulated by early-to-mid or late gestation T exposed females. X-ray determined phalanx measurements indicate elongated finger and toe phalanx length in males, but no other phalanx-related differences. Discrete T exposure during early-to-mid gestation in female rhesus monkeys thus appears to increase RH2D:4D through right-side biased, non-skeletal tissue growth. As variation in timing and duration of gestational T exposure alter male-like dimensions of RH2D independently of RH4D, postnatal RH2D:4D provides a complex biomarker for fetal T exposure.
Journal Article
No rest for the dead : a novel
Christopher Thomas, a curator at San Francisco's McFall Art Museum is murdered and his wife, Rosemary, is tried, convicted, and executed. But ten years later, Detective Jon Nunn uncovers evidence that convinces him the wrong person was put to death, and as he tries to right the wrong, he realizes someone will stop at nothing to ensure that secrets stay buried. A serial novel featuring contributions by twenty-five masters of suspense.
Book
Randomized control trial of Tools of the Mind: Marked benefits to kindergarten children and their teachers
The kindergarten program, Tools of the Mind (Tools), has been shown to improve executive functions (as assessed by laboratory measures) and academic performance. The objective here was to see if Tools can improve executive functions in the real world (in the classroom), academic outcomes not previously investigated, reduce bullying and peer ostracism, and increase teachers' and students' joy in being in the classroom. This first randomized controlled trial of Tools in Canada included 351 kindergarten children (mean age 5.2 years at entry; 51% female) in 18 public schools. Stratified randomization resulted in teachers and students in both groups being closely matched. Teachers in both groups received the same number of training hours and same funds for new materials. Outcome measures were pre and post standardized academic skill assessments and teacher online survey responses. This study replicated that Tools improves reading and shows for the first time that it improves writing (far exceeding levels the school districts had seen before), self-control and attention-regulation in the real world (e.g., time on task without supervision), reduces teacher burnout and children being ostracized or excluded, and increases the joy students and teachers experience in school. By Spring, Tools teachers were still enthusiastic about teaching; control teachers were exhausted. These results were not only better than the control group but also better than Tools teachers experienced the year before Tools. Thus, children in a kindergarten curriculum that emphasized play, improving self-regulation, working together and helping one another, and hands-on learning performed better academically, showed less bullying and peer ostracism and more kindness and helping behavior than students in more traditional classes, and teacher enthusiasm for teaching soared. Tools reduced initial disparities separating children, schools, and teachers.
Journal Article
Batman '66 meets Wonder Woman '77
The world knows them as Bruce Wayne, his youthful ward Dick Grayson, and American agent Diana Prince. To grateful citizens and fearful villains, they're none other than Batman, Robin and Wonder Woman. But the paths of the Dynamic Duo and the Amazon Princess have never crossed... until now! The all-powerful enemy known as Ra's al Ghul and his League of Shadows are on the move, hunting for everlasting life and bent on world domination. Batman and Wonder Woman's quest to stop him will span the globe and the decades alike -- from the time a 10-year-old Bruce Wayne faced the Nazi hordes, to the first full-fledged team-up between the heroes in 1966, to their reunion in the seventies, when Batman's former protâegâes Robin and Batgirl have taken over their mentor's war on crime. Can these incredible guardians of goodness stop an immortal madman? Tune in -- er, we mean turn the page -- and find out!
Book
