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Amy M Gratton, Louie Ye, Fiona C Brownfoot, Natalie J Hannan, Clare Whitehead, Ping Cannon, Minh Deo, Peter J Fuller, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino
INTRODUCTION: Preeclampsia is a serious complication of pregnancy affecting 5% of pregnancies. Our team identified 137 genes highly expressed in placenta relative to other human tissues. Here, we have explored a role for steroid sulfatase (STS) in preeclampsia by characterising STS expression and the functional effects of STS on primary placental trophoblasts. METHODS: Characterisation of STS was performed on preterm preeclamptic and gestation-matched normotensive preterm controls who delivered at <34 weeks gestation...
December 2016: Placenta
Louie Ye, Amy Gratton, Natalie J Hannan, Ping Cannon, Minh Deo, Kirsten R Palmer, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino, Fiona C Brownfoot
INTRODUCTION: Preeclampsia is a serious complication affecting 5-8% of pregnancies. Central to its pathogenesis is placental hypoxia and inflammation which leads to secretion of soluble fms-like tyrosine kinase 1 (sFlt-1). sFlt-1 causes widespread endothelial dysfunction. The molecular mechanisms regulating sFlt-1 production remain poorly understood. Recently, a binding site for the nuclear factor activated T cells (NFAT) transcription factor has been found on fms-like tyrosine kinase 1 (FLT-1) promoter...
December 2016: Placenta
E J Denton, L M Hannan, M Hew
BACKGROUND: Pleural ultrasound guidance reduces complications of pleural procedures, and lung ultrasound can diagnose the cause of acute respiratory failure. Yet as recently as five years ago, many respiratory physicians lacked sufficient access, training and expertise to perform chest ultrasound. AIMS: This study examines whether progress has been achieved in chest ultrasound amongst respiratory physicians in Australia and New Zealand. METHODS: We conducted a web-based chest ultrasound survey of adult respiratory physicians across Australia and New Zealand...
November 16, 2016: Internal Medicine Journal
Grinu Mathew, Abdul Hannan, Kristina Hertzler-Schaefer, Fen Wang, Gen-Sheng Feng, Jian Zhong, Jean J Zhao, Julian Downward, Xin Zhang
Deficiency in PTEN (phosphatase and tensin homolog deleted on chromosome 10) is the underlying cause of PTEN hamartoma tumor syndrome and a wide variety of human cancers. In skin epidermis, we have previously identified an autocrine FGF signaling induced by loss of Pten in keratinocytes. In this study, we demonstrate that skin hyperplasia requires FGF receptor adaptor protein Frs2α and tyrosine phosphatase Shp2, two upstream regulators of Ras signaling. Although the PI3-kinase regulatory subunits p85α and p85β are dispensable, the PI3-kinase catalytic subunit p110α requires interaction with Ras to promote hyperplasia in Pten-deficient skin, thus demonstrating an important cross-talk between Ras and PI3K pathways...
October 31, 2016: Proceedings of the National Academy of Sciences of the United States of America
Valerie P O'Brien, Thomas J Hannan, Lu Yu, Jonathan Livny, Elisha D O Roberson, Drew J Schwartz, Spenser Souza, Cathy L Mendelsohn, Marco Colonna, Amanda L Lewis, Scott J Hultgren
Recurrent bacterial infections are a significant burden worldwide, and prior history of infection is often a significant risk factor for developing new infections. For urinary tract infection (UTI), a history of two or more episodes is an independent risk factor for acute infection. However, mechanistic knowledge of UTI pathogenesis has come almost exclusively from studies in naive mice. Here we show that, in mice, an initial Escherichia coli UTI, whether chronic or self-limiting, leaves a long-lasting molecular imprint on the bladder tissue that alters the pathophysiology of subsequent infections, affecting host susceptibility and disease outcome...
October 31, 2016: Nature Microbiology
Cheng-Shiu Chung, Hongwu Wang, Matthew J Hannan, Dan Ding, Annmarie R Kelleher, Rory A Cooper
OBJECTIVE: The objectives of this study were to evaluate the performance of commercially available assistive robotic manipulators (ARMs) user interfaces and to investigate the concurrent validity and sensitivity to change with task-oriented performance evaluation tools (TO-PETs) for ARMs. DESIGN: This was a nonblinded randomized controlled study with power-wheelchair users with upper-extremity impairments (N = 10). Participants were trained to use 2 ARMs with their respective original user interfaces (keypad and joystick) and evaluated the performance using TO-PET and the adapted Wolf Motor Function Test (WMFT-ARM)...
October 6, 2016: American Journal of Physical Medicine & Rehabilitation
Natalie K Binder, Jemma Evans, Lois A Salamonsen, David K Gardner, Tu'uhevaha J Kaitu'u-Lino, Natalie J Hannan
Embryo implantation requires synchronized dialogue between the receptive endometrium and activated blastocyst via locally produced soluble mediators. During the mid-secretory (MS) phase of the menstrual cycle, increased glandular secretion into the uterine lumen provides important mediators that modulate the endometrium and support the conceptus during implantation. Previously we demonstrated the importance of vascular endothelial growth factor (VEGF) in the human uterus, particularly with respect to embryo implantation...
2016: PloS One
Laurel Mydock-McGrane, Zachary Cusumano, Zhenfu Han, Jana Binkley, Maria Kostakioti, Thomas Hannan, Jerome S Pinkner, Roger Klein, Vasilios Kalas, Jan Crowley, Nigam P Rath, Scott J Hultgren, James W Janetka
Gram-negative uropathogenic Escherichia coli (UPEC) bacteria are a causative pathogen of urinary tract infections (UTIs). Previously developed antivirulence inhibitors of the type 1 pilus adhesin, FimH, demonstrated oral activity in animal models of UTI but were found to have limited compound exposure due to the metabolic instability of the O-glycosidic bond (O-mannosides). Herein, we disclose that compounds having the O-glycosidic bond replaced with carbon linkages had improved stability and inhibitory activity against FimH...
October 14, 2016: Journal of Medicinal Chemistry
A Daly, J M Redmond, M M Hannan
Traditionally, the modified Duke's criteria, based primarily on positive blood cultures, is used to diagnose Infective Endocarditis (IE). However, reports demonstrate that 31% of cases are diagnosed as Culture Negative Infective Endocarditis (CNIE)1. Consequently, empiric broad-spectrum antibiotics are prescribed to cover unidentified organisms and, as a result, antibiotic therapy may be compromised. Molecular diagnostic techniques aid with identifying causative organisms in cases of CNIE and we question if the increasing use of such technologies will change the local epidemiology of CNIE...
May 10, 2016: Irish Medical Journal
D Ishihara, K Louder, M Akter, C Ahn, V Margulis, Y Arriaga, K Courtney, R D Timmerman, J Brugarolas, R Hannan
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
G Maquilan, K D Westover, Z Wardak, R D Timmerman, R Hannan, P Iyengar, D L Schwartz, J J Meyer, R E Abdulrahman, M R Folkert, A M Laine, N B Desai, K V Albuquerque, H Choy, C Ahn, A S Rahimi
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Hotaka Matsui, Biljana Musicki, Nikolai A Sopko, Xiaopu Liu, Paula J Hurley, Arthur L Burnett, Trinity J Bivalacqua, Johanna L Hannan
OBJECTIVE: To assess neurite sprouting and gene expression of neurotrophic factors, nerve markers, and apoptosis in the major pelvic ganglia (MPGs) of rats with type 2 diabetes mellitus (T2DM) as it relates to erectile function. MATERIALS AND METHODS: Male rats were fed high-fat diet for 2 weeks followed by 2 low-dose injections of streptozotocin (20 mg/kg). In 3 groups (controls, 3-week, or 5-week T2DM), erectile function was measured by ratios of intracavernosal pressure to mean arterial pressure after cavernous nerve stimulation...
September 14, 2016: Urology
S McNicholas, A Fe Talento, J O'Gorman, M M Hannan, M Lynch, C M Greene, P J Conlon, A C Shore, D C Coleman, H Humphreys, D Fitzgerald-Hughes
Patients with end-stage renal failure undergo regular haemodialysis (HD) and often develop episodes of Staphylococcus aureus bloodstream infection (BSI), which can re-occur. However, clinically, patients on HD, with S. aureus BSI, respond well to treatment, rarely developing overt signs of sepsis. We investigated the contributions of bacterial virulence and cytokine responses to the clinical course of S. aureus BSI in HD and non-HD patients. Seventy patients were recruited, including 27 (38.6 %) patients on HD...
September 9, 2016: European Journal of Clinical Microbiology & Infectious Diseases
A Shepherd, S Tyebji, A J Hannan, E L Burrows
Cognitive dysfunction appears as a core feature of dementia, which includes its most prevalent form, Alzheimer's disease (AD), as well as vascular dementia, frontotemporal dementia, and other brain disorders. AD alone affects more than 45 million people worldwide, with growing prevalence in aging populations. There is no cure, and therapeutic options remain limited. Gene-edited and transgenic animal models, expressing disease-specific gene mutations, illuminate pathogenic mechanisms leading to cognitive decline in AD and other forms of dementia...
November 2016: Journal of Molecular Neuroscience: MN
Danielle M Bartlett, Travis M Cruickshank, Anthony J Hannan, Peter R Eastwood, Alpar S Lazar, Mel R Ziman
Huntington's disease (HD) is a fatal neurodegenerative disease caused by an extended polyglutamine tract in the huntingtin protein. Circadian, sleep and hypothalamic-pituitary-adrenal (HPA) axis disturbances are observed in HD as early as 15 years before clinical disease onset. Disturbances in these key processes result in increased cortisol and altered melatonin release which may negatively impact on brain-derived neurotrophic factor (BDNF) expression and contribute to documented neuropathological and clinical disease features...
September 13, 2016: Neuroscience and Biobehavioral Reviews
Anthony J Hannan
Is that a rumbling I feel in my stomach? Or perhaps it is the trillions of bacteria down there who are in revolt, fomenting (or fermenting!) a microbial revolution? No active biologist or medical researcher can easily ignore the revolution in gut microbiome research in recent years. It seems that the gut microbiome, the entire microbial ecosystem occupying the gastrointestinal ecological niche, can impact almost every organ in the human body, not least of which being the brain. The gut microbiome has been found to signal to both the developing and adult mammalian brain, modulating both health and disease states (Cryan and Dinan, 2012; Mayer et al...
September 13, 2016: European Journal of Neuroscience
Andrew J Colebatch, Leon Di Stefano, Stephen Q Wong, Ross D Hannan, Paul M Waring, Alexander Dobrovic, Grant A McArthur, Anthony T Papenfuss
Most cancer DNA sequencing studies have prioritized recurrent non-synonymous coding mutations in order to identify novel cancer-related mutations. Although attention is increasingly being paid to mutations in non-coding regions, standard approaches to identifying significant mutations may not be appropriate and there has been limited analysis of mutational clusters in functionally annotated non-coding regions. We sought to identify clustered somatic mutations (hotspot regions across samples) in functionally annotated regions in melanoma and other cutaneous malignancies (cutaneous squamous cell carcinoma, basal cell carcinoma and Merkel cell carcinoma)...
September 7, 2016: Oncotarget
Fabian Kreilaus, Adena S Spiro, Anthony J Hannan, Brett Garner, Andrew M Jenner
BACKGROUND: Huntington's disease (HD) is a progressive neurodegenerative disease with no effective treatment or cure. Environmental enrichment has been used to slow processes leading to ageing and neurodegenerative diseases including HD. Phenolic phytochemicals including anthocyanins have also been shown to improve brain function in ageing and neurodegenerative diseases. OBJECTIVE: This study examined the effects of anthocyanin dietary supplementation and environmental enrichment on behavioural phenotypes and brain cholesterol metabolic alterations in the R6/1 mouse model of HD...
October 1, 2016: Journal of Huntington's Disease
Keefe T Chan, Lassi Paavolainen, Katherine M Hannan, Amee J George, Ross D Hannan, Kaylene J Simpson, Peter Horvath, Richard B Pearson
Hyperactivation of the PI3K/AKT/mTORC1 signaling pathway is a hallmark of the majority of sporadic human cancers. Paradoxically, chronic activation of this pathway in nontransformed cells promotes senescence, which acts as a significant barrier to malignant progression. Understanding how this oncogene-induced senescence is maintained in nontransformed cells and conversely how it is subverted in cancer cells will provide insight into cancer development and potentially identify novel therapeutic targets. High-throughput screening provides a powerful platform for target discovery...
September 2016: Assay and Drug Development Technologies
M Carugati, C A Petti, C Arnold, J M Miro, J M Pericàs, C Garcia de la Maria, Z Kanafani, E Durante-Mangoni, J Baddley, D Wray, J L Klein, F Delahaye, N Fernandez-Hidalgo, M M Hannan, D Murdoch, A Bayer, V H Chu
The phenotypic expression of methicillin resistance among coagulase-negative staphylococci (CoNS) is heterogeneous regardless of the presence of the mecA gene. The potential discordance between phenotypic and genotypic results has led to the use of vancomycin for the treatment of CoNS infective endocarditis (IE) regardless of methicillin MIC values. In this study, we assessed the outcome of methicillin-susceptible CoNS IE among patients treated with antistaphylococcal β-lactams (ASB) versus vancomycin (VAN) in a multicenter cohort study based on data from the International Collaboration on Endocarditis (ICE) Prospective Cohort Study (PCS) and the ICE-Plus databases...
October 2016: Antimicrobial Agents and Chemotherapy
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