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RNA helicase DDX20 as a surrogate marker of statin activity in invasive breast cancer

中国药理学与毒理学杂志 2015年第S1期29卷 84-84页

作者： ChaoWANG BeiyingQIU JeanPaulTHIERY GautamSETHI patrickj.casey CelestialT.YAP SooChinLEE VinayTERGAONKAR AlanPremKUMAR Cancer Science Institute of Singapore National University of Singapore Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Institute of Molecular and Cell Biology ASTAR Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore National University Cancer Institute of Singapore Duke-NUS Graduate Medical School Department of Physiology Yong Loo Lin School of Medicine National University of Singapore Department of Haematology-Oncology National University Hospital Singapore Department of Biological Sciences University of North Texas

OBJECTIVE To evaluate if RNA helicase DDX20,highly expressed in triple negative breast cancer(TNBC)cells,could serve as a surrogate marker for simvastatin treatment *** We first assessed correlation between 17 mevalonate pathway-related genes and expression of DDX20 in a cohort of 1325 breast cancer *** cells,MDA-MB-231,were then treated with simvastatin and mevalonate pathway intermediates to assess the alteration in DDX20 *** the mouse model,MDA-MB-231 cells were injected to tail veins of mice,groups of 8mice each were injected intraperioneally with vehicle or simvastatin 25mg·kg-1 3times a week for *** number of metastatic colonies formed was quantified and immunohistochemical(IHC)staining of DDX20 was carried out in the lung *** Among the 17 genes evaluated,positive correlation with DDX20 expression was observed in eight of them,with HMGCR having the highest *** in vitro experiments show exposure of breast cancer cells to simvastatin lead to a Rho-dependent decrease in gene expression of DDX20,leading to decreased tumor proliferation in a mevalonate pathway-dependent ***,ectopic overexpression of DDX20 significantly abrogated the anti-metastatic activity of simvastatin.A similar observation is seen in the mouse model,where simvastatin-injected mice show significantly fewer visible lung metastases compared to placebo-fed *** staining on these lung tissues showed decreased DDX20 expression in simvastatin-injected group,corroborating our observations in *** DDX20 is a potential surrogate marker for simvastatin treatment response in breast cancer and a long term implication of our findings is the possibility of an effective combinatorial therapeutic intervention using statins(to suppress DDX20 gene expression)and a suitable firstline agent″for the kill″of invasive breast cancer.

关键词： RNA helicase DDX20 surrogate marker simvastatin br

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Synchronous formation of the‘forearc’Bay of Islands ophiolite and its basal high-temperature metamorphic sole constrained by U-Pb zircon ages

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Geoscience Frontiers 2023年第6期14卷 234-272页

作者： Weiyao Yan John F.casey Department of Earth and Atmospheric Sciences University of HoustonHoustonTXUSA

The welded metamorphic sole at the base of the Bay of Islands Ophiolite Complex(BOIC)in the Northern Appalachians of Newfoundland shows a typical inverted pressure-temperature(P-T)metamorphic gradient from HT-MP granulite to LT-LP greenschist *** incorporates mafic volcanic/plutonic protoliths mixed with pelagic,hemi-pelagic and coarser epiclastic sedimentary *** LA-ICP-MS U–Pb concordia ages,trace elements,and Ti-in-zircon geothermometry for -250 zircon analyses from three metabasites of the upper HT sole amphibolites with N-MORB-like protoliths are *** samples collected within meters of the ophiolite peridotite-sole contact of the Blow Me Down Mountain and North Arm Mountain massifs yielded the oldest comparable concordia ages of 487.7±2.6 Ma and 489.1±3.1 Ma,respectively,that are both within error of the igneous age of 488.3±1.5 Ma of the directly overlying BOIC ophiolite,which formed at a supra-subduction zone(SSZ)forearc spreading center.A third slightly younger age of 484.2±2.4 Ma was obtained for an upper HT amphibolite sample with similar phase assemblages but collected30 m below the peridotite contact of the Table Mountain *** crystals analyzed have similar size and morphologies,subparallel rare earth element(REE)variation patterns,and steep heavy REE-enrichments((Lu/Gd)_(cn)>20),significant positive Ce anomalies(dominantly>5)and slight positive to dominantly negative Eu anomalies(1.2–0.4).Zircon shows Th/U mean values of 0.37–0.48 with little to no rim to core *** Ti-in-zircon mean crystallization temperatures range from764–787℃.These neocrystallized zircon crystals appear to be derived from thin leucosomes within the three *** other samples also from the upper HT sole show evidence of inherited detrital zircon with core dates spanning the Cambrian Notre Dame Arc through older Laurentian-like basement and rift age *** of the sole took place below a hot forearc asthenospheric wed

关键词： Ophiolite metamorphic sole U-Pb zircon ages Hot subduction interface Supra-subduction forearc spreading center Arc-continent collision Taconic Orogeny

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Fibronectin: Functional character and role in alcoholic liver disease

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World Journal of Gastroenterology 2011年第20期17卷 2482-2499页

作者： Razia S Aziz-Seible Carol A casey Department of Biomedical Sciences Creighton University Department of Biochemistry and Molecular Biology University of Nebraska Medical Center985870 Nebraska Medical Center Department of Internal Medicine University of Nebraska Medical Center 986350 Nebraska Medical Center The Liver Study Unit Omaha Veterans Affairs Medical Center

Fibronectins are adhesive glycoproteins that can be found in tissue matrices and circulating in various fluids of the body. The variable composition of fibronectin molecules facilitates a diversity of interactions with cell surface receptors that suggest a role for these proteins beyond the structural considerations of the extracellular matrix. These interactions implicate fibronectin in the regulation of mechanisms that also determine cell behavior and activity. The two major forms, plasma fibronectin (pFn) and cellular fibronectin (cFn), exist as balanced amounts under normal physiological conditions. However, during injury and/or disease, tissue and circulating levels of cFn become disproportionately elevated. The accumulating cFn, in addition to being a consequence of prolonged tissue damage, may in factstimulate cellular events that promote further damage. In this review, we summarize what is known regarding such interactions between fibronectin and cells that may influence the biological response to injury. We elaborate on the effects of cFn in the liver, specifically under a condition of chronic alcohol-induced injury. Studies have revealed that chronic alcohol consumption stimulates excess production of cFn by sinusoidal endothelial cells and hepatic stellate cells while impairing its clearance by other cell types resulting in the build up of this glycoprotein throughout the liver and its consequent increased availability to influence cellular activity that could promote the development of alcoholic liver disease. We describe recent findings by our laboratory that support a plausible role for cFn in the promotion of liver injury under a condition of chronic alcohol abuse and the implications of cFn stimulation on the pathogenesis of alcoholic liver disease. These findings suggest an effect of cFn in regulating cell behavior in the alcohol-injured liver that is worth further characterizing not only to gain a more comprehensive understanding of the role this r

关键词： Fibronectin Liver disease Alcoholic liver disease Endocytosis Cellular fibronectin

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STRUCTURAL EVOLUTION IN BIORENEWABLE SOY BASED POLYURETHANES

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Chinese Journal of Polymer Science 2009年第4期27卷 447-454页

作者： Deepa Puthanparambil casey Kimball Shaw Ling Hsu Polymer Science and Engineering Department and Materials Research Science and Engineering Center University of MassachusettsAmherstMA 01003USA Douglas McKinnon Hall Williston Northampton AcademyEasthamptonMA 01027USA Invited lecture presented at the International Symposium on Polymer Physics

Spectroscopic studies have revealed that the amount of polyureas formed and the kinetics of their formation in soy based polyurethane systems are considerably different from traditional systems employing ethylene oxide-propylene oxide (EO-PO) based *** aggregation of polyureas was characterized by the hydrogen bonds formed utilizing FTIR *** study offered the opportunity to assign the previously undefined infrared *** structural transformation is reflected in the segmental rel...

关键词： Spectroscopy Miscibility Polyurethanes

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Impact of asialoglycoprotein receptor deficiency on the development of liver injury

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World Journal of Gastroenterology 2009年第10期15卷 1194-1200页

作者： Serene ML Lee Carol A casey Benita L McVicker Departments of Internal Medicine and Biochemistry & Molecular Biology University of Nebraska Medical Center Omaha NE 68105 United States Liver Study Unit Department of Veterans Affairs Medical Center and Departments of Internal Medicine and Biochemistry & Molecular Biology University of Nebraska Medical Center Omaha NE 68105 United States

The asialoglycoprotein （ASGP） receptor is a wellcharacterized hepatic receptor that is recycled via the common cellular process of receptor-mediated endocytosis （RME）. The RME process plays an integral part in the proper trafficking and routing of receptors and ligands in the healthy cell. Thus, the missorting or altered transport of proteins during RME is thought to play a role in several diseases associated with hepatocyte and liver dysfunction. Previously, we examined in detail alterations that occur in hepatocellular RME and associated receptor functions as a result of one particular liver injury, alcoholic liver disease （ALD）. The studies revealed profound ethanol- mediated impairments to the ASGP receptor and the RME process, indicating the importance of this receptor and the maintenance of proper endocytic events in normal tissue. To further clarify these observations, studies were performed utilizing knockout mice （lacking a functional ASGP receptor） to which were administered several liver toxicants. In addition to alcohol, we examined the effects following administration of anti- Fas （CD95） antibody, carbon tetrachloride （CCh） and lipopolysaccharide （LPS）/galactosamine. The results of these studies demonstrated that the knockout mice sustained enhanced liver injury in response to all of the treatments, as shown by increased indices of liver damage, such as enhancement of serum enzyme levels, histopathological scores, as well as hepatocellular death. Overall, the work completed to date suggests a possible link between hepatic receptors and liver injury. In particular, adequate function and content of the ASGP receptor may provide protection against various toxinmediated liver diseases.

关键词： Asialoglycoprotein receptor Asialoglycoproteinreceptor deficient mice Receptor-mediatedendocytosis Alcohol Carbon tetrachloride Anti-Fas Lipopolysaccharide/galactosamine Toxicant-induced liverinjury

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Analysis of Capacity Decay, Impedance, and Heat Generation of Lithium-ionBatteries Experiencing Multiple Simultaneous Abuse Conditions

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Energy Engineering 2023年第12期120卷 2721-2740页

作者： casey Jones Meghana Sudarshan Vikas Tomar School of Aeronautics and Astronautics Purdue UniversityWest Lafayette47907USA

Abuse of Lithium-ion batteries,both physical and electrochemical,can lead to significantly reduced operational *** some instances,abuse can cause catastrophic failure,including thermal runaway,combustion,and *** different test standards that include abuse conditions have been developed,but these generally consider only one condition at a time and only provide go/no-go *** this work,different types of cell abuse are implemented concurrently to determine the extent to which simultaneous abuse conditions aggravate cell degradation and *** loading is chosen to be the consistent type of physical abuse,and the first group of cells is cycled at different vibrational *** next group of cells is cycled at the same frequencies,with multiple charge pulses occurring during each *** final group of cells is cycled at the same frequencies,with a partial nail puncture occurring near the beginning of *** results show that abusing cells with vibrational loading or vibrational loading with current pulses does not cause a significant decrease in operational capabilities while abusing cells with vibrational loading and a nail puncture drastically reduces operational *** cells with vibration only experience an increase in internal resistance by a factor of 1.09–1.26,the cells with vibration and current pulses experience an increase in internal resistance by a factor of 1.16–1.23,and all cells from each group reach their rated lifetime of 500 cycles without reaching their end-of-life ***,the cells with vibration and nail puncture experience an increase in internal resistance by a factor of 6.83–22.1,and each cell reaches its end-of-life capacity within 50 ***,the results show that testing multiple abuse conditions simultaneously provides a better representation of the extreme limitations of cell operation and should be considered for inclusion in reference test standards.

关键词： Lithium-ion batteries dynamic abuse testing electrochemical impedance spectroscopy incremental capacity analysis thermal profile analysis

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Numerical investigation into water entry problems of a flat plate with air pockets

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Journal of Ocean Engineering and Science 2023年第4期8卷 386-400页

作者： casey O’Connor Saeed Mohajernasab Nagi Abdussamie National Centre for Maritime Engineering and Hydrodynamics Australian Maritime CollegeUniversity of TasmaniaLauncestonTasmaniaAustralia

Computational Fluid Dynamics(CFD)investigations into water entry problems of a rigid flat plate with air pockets were systematically *** Volume of Fluid(VOF)model was utilised to capture localised slamming phenomena that occur during,and post-impact *** model’s geometry was modified to include a pocket on the slamming impact surface to investigate the effect of air entrapment on the magnitude and distribution of slamming forces and pressures.A parametric study was conducted on the geometric parameters of the modelled pocket by altering its area,depth,and volume to exam-ine the response of slamming force and pressure loading under several impact *** numerical results of slamming forces and pressures were in good agreement with experimental drop test measure-ments(with relative error of-6%and 7%for the magnitude of slamming force and pressure,respectively).The numerical results proved that the peak pressure is proportional to the magnitude of impact velocity squared(p maxαv^(2)).

关键词： Marine structures Slamming Air entrapment Computationalﬂuid dynamics Drop tests

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Effect of ethanol on pro-apoptotic mechanisms in polarizedhepatic cells

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World Journal of Gastroenterology 2007年第37期13卷 4960-4966页

作者： Benita L McVicker Dean J Tuma Carol A casey Liver Study Unit Department of Veterans Affairs Medical Center and Departments of Internal Medicine and Biochemistry & Molecular Biology University of Nebraska Medical Center Omaha NE 68105 United States

Chronic ethanol consumption is associated with serious and potentially fatal alcohol-related liver injuries such as hepatomegaly, alcoholic hepatitis and cirrhosis. Moreover, it has been documented that the clinical progression of alcohol-induced liver damage may be associated with an increase in hepatocellular death that involves apoptotic mechanisms. Although much information has been learned about the clinical manifestations associated with alcohol-related diseases, the search continues for a better understanding of the molecular and/or cellular mechanisms by which ethanol exerts its deleterious effects such as the induction of pro-apoptotic mechanisms and related cell damaging events. As part of the effort to enhance our understanding of those particular cellular pathways and mechanisms associated with ethanol toxicity, researchers over the years have utilized a variety of model systems. Recently, work has come forth demonstrating the utility of a hybrid cell line (WIF-B) as a cell culture model system for the study of alcohol-associated alterations in hepatocellular mechanisms. Success with such emerging model systems could aid in the development of potential therapeutic treatments for the prevention of alcohol- induced apoptotic cell death that may ultimately serve as a significant target in delaying the onset and/or progression of clinical symptoms of alcohol-mediated liver disease. This review article summarizes the current understanding of ethanol-mediated modifications in cell survival and thus the promotion of pro-apoptotic events with emphasis on analyses made in various experimental model systems, particularly the more recently characterized WIF-B cell system.

关键词： Hepatoma hybrid cells Ethanol Apoptosis Fas receptor Caspase

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Kinematic analysis of penile reflexes in a rat model of spinal cord injury

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Asian Journal of Andrology 2021年第1期23卷 30-35页

作者： casey J Steadman Sai S Vangoor Charles H Hubscher Department of Anatomical Sciences and Neurobiology University of LouisvilleLouisvilleKY 40202USA Kentucky Spinal Cord Injury Research Center LouisvilleKY 40202USA.

The ex-copula penile dorsiflexion reflex(PDFR)is an established measure of sexual dysfunction in male rat models of spinal cord *** the PDFR after complete spinal transection is well described,information regarding the more clinically relevant incomplete spinal contusion injury model is *** study examined,using two-dimensional(2D)kinematic analysis,the relationship between the PDFR and degree of white matter sparing(WMS).Male Wistar rats received a T9 contusion with varying degrees of impactor *** kinematic recordings of the PDFR were made 3-8 weeks *** reflex components examined included maximum angle of penile dorsiflexion,total penile event duration,and penile ascent *** hoc comparison between animals grouped based upon injury severity(moderate-severe:13.33%-17.15%WMS vs moderate:20.85%-33.50%WMS)ndicated PDFR ***,the numbers of animals with more moderate contusions having data points above the median n both maximum angle of penile dorsiflexion and penile ascent speed were significantly lower than animals with more severe *** penile event duration was also affected but only at more chronic time points(6-8 weeks).Thus,2D kinematic analysis of the PDFR allows for more consistent and quantifiable analysis of the subtle differences that can occur between injury severity groups in the rat contusion model.

关键词： erection penile sexual dysfunction spinal cord injury

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Providing primary care to transgender patients

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Family Medicine and Community Health 2019年第3期7卷 37-39页

作者： Catherine Frances casey Family Medicine University of VirginiaCharlottesvilleVirginiaUSA

Lara(not an actual patient),a 45-year-old transwoman,presents to your clinic for a yearly *** has no significant medical history except for *** surgical history includes appendectomy and breast *** history is significant for a mother who developed breast cancer at age 55 years and a brother with type 2 *** terms of her social history,she does not smoke,drinks 1-2 glasses of wine on the weekends and has been in a mutually monogamous relationship with a male partner for 2 *** medications include spironolactone,oestradiol and *** people-people who identify as a gender other than the one assigned at birth-have existed throughout human history and in multiple *** at no time have they received as much attention as they have in the last few *** validity of their identities and their corresponding legal rights are a political battleground in the *** the increasing prevalence of people coming out as transgender or gender-expansive,and despite the trend towards greater societal acceptance of non-binary gender identities,transgender patients face significant barriers to accessing basic medical *** schools and residencies have traditionally provided very little training on caring for transgender patients,a paradigm that is only now beginning to *** to popular belief,patients identifying as transgender or gender-expansive span the entire age range,with paediatric to geriatric patients choosing interventions that include pubertyblocking medications,hormone therapy and/or surgical *** care doctors find themselves learning,often from patients,how to provide sensitive,competent care to this underserved and marginalised population.

关键词： patients legal smoke

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