ETS transcription factor Etsrp / Etv2 is required for lymphangiogenesis and directly regulates <i>vegfr3 / flt4</i> expression

Davis, Jennifer A.,Koenig, Andrew L.,Lubert, Allison,Chestnut, Brendan,Liu, Fang,Palencia Desai, Sharina,Winkler, Tamara,Pociute, Karolina,Choi, Kyunghee,Sumanas, Saulius Elsevier 2018 Developmental Biology Vol.440 No.1

<P><B>Abstract</B></P> <P>The molecular mechanisms initiating the formation of the lymphatic system, lymphangiogenesis, are still poorly understood. Here we have identified a novel role in lymphangiogenesis for an ETS transcription factor, Etv2/Etsrp, a known regulator of embryonic vascular development. Through the use of fully validated photoactivatable morpholinos we show that inducible Etv2 inhibition in zebrafish embryos at 1 day post-fertilization (dpf) results in significant inhibition of lymphangiogenesis, while development of blood vessels is unaffected. In Etv2-inhibited embryos and larvae, the number of lymphatic progenitors is greatly reduced, the major lymphatic vessel, the thoracic duct, is absent or severely fragmented, and lymphangiogenesis-associated marker expression, including <I>lyve1b</I>, <I>prox1a</I>, and <I>vegfr3/flt4</I>, is strongly downregulated. We also demonstrate that lymphatic progenitors in Etv2 deficient embryos fail to respond to Vegfc signaling. Chromatin immunoprecipitation and sequencing (ChIP-Seq) studies using differentiated mouse embryonic stem (ES) cells as well as luciferase reporter studies in the ES cells and in zebrafish embryos argue that Etv2 directly binds the promoter/enhancer regions of Vegfc receptor <I>Vegfr3/Flt4</I> and lymphatic marker <I>Lyve1</I>, and promotes their expression. Together these data support a model where Etv2 initiates lymphangiogenesis by directly promoting the expression of <I>flt4</I> within the posterior cardinal vein.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Etv2 expression is enriched in the vein during zebrafish lymphangiogenesis. </LI> <LI> Inducible Etv2 knockdown inhibits lymphangiogenesis. </LI> <LI> Blood vessels are not affected by Etv2 knockdown at 24 hpf. </LI> <LI> Vegfc fails to induce lymphangiogenesis in Etv2 knockdown embryos. </LI> <LI> Etv2 directly binds to Flt4 promoter and promotes its expression. </LI> </UL> </P>

Particle tracking acceleration via signed distance fields in direct-accelerated geometry Monte Carlo

Patrick C. Shriwise,Andrew Davis,Lucas J. Jacobson,Paul P.H. Wilson 한국원자력학회 2017 Nuclear Engineering and Technology Vol.49 No.6

Computer-aided design (CAD)-based Monte Carlo radiation transport is of value to the nuclear engineering community for its ability to conduct transport on high-fidelity models of nuclear systems, but it is more computationally expensive than native geometry representations. This work describes the adaptation of a rendering data structure, the signed distance field, as a geometric query tool for accelerating CAD-based transport in the direct-accelerated geometry Monte Carlo toolkit. Demonstrations of its effectiveness are shown for several problems. The beginnings of a predictive model for the data structure's utilization based on various problem parameters is also introduced.

Light Emission from Silicon Nanocrystals - Size Does Matter !

Robert G. Elliman,Andrew R. Wilkinson,Barry Luther-Davies,Marc G. Spooner,Marek Samoc,Max J. Lederer,Nathanael Smith,Tessica D.M. Weijers 한국물리학회 2004 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.45 No.3

A brief overview of two recent Si nanocrystal studies undertaken at the Australian National University is presented: recent work on hydrogen passivation of non-radiative defects and attempts to measure optical gain in waveguide structures. In the rst study, a generalized treatment of hydrogen passivation and desorption is employed to model the in uence of hydrogen on silicon nanocrystal luminescence. Values for reaction-rate parameters are determined from the model and found to be in excellent agreement with values previously determined for paramagnetic Si danglingbond defects (Pb-type centers) found at planar Si/SiO2 interfaces. In the second study, an attempt is made to measure optical gain in silicon nanocrystals by monitoring the intensity of a probe beam propagating in a waveguide structure containing silicon nanocrystals during photo-excitation of the nanocrystals. The probe beam is shown to be attenuated by the excitation demonstrating the dominance of absorptive processes. No gain was observed.

One-pot synthesis of hybrid TiO₂–polyaniline nanoparticles by self-catalyzed hydroamination and oxidative polymerization from TiO₂–methacrylic acid nanoparticles

Bae, Woo Jin,Davis, Andrew R.,Jung, Jaewoong,Jo, Won Ho,Carter, Kenneth R.,Coughlin, E. Bryan Royal Society of Chemistry 2011 Chemical communications Vol.47 No.38

<P>A simple self-catalyzed hydroamination method for creating hybrid TiO<SUB>2</SUB>-polyaniline core-shell nanoparticles (NP) has been shown. Hybrid NPs with a range of possible sizes are afforded in high yield under mild reaction conditions and simultaneously show improved charge transport and electrochromic behavior compared to either polyaniline alone or physically blended with TiO<SUB>2</SUB>.</P> <P>Graphic Abstract</P><P>A facile technique is presented for using methacrylic acid-functionalized TiO<SUB>2</SUB>nanoparticles to synthesize core-shell TiO<SUB>2</SUB>-Polyaniline (PANI) structures that display solvent dispersibility and improved electrochromic performance over PANI. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c1cc13137k'> </P>

TRAMP Prostate Tumor Growth Is Slowed by Walnut Diets Through Altered IGF-1 Levels, Energy Pathways, and Cholesterol Metabolism

김현숙,Wallace Yokoyama,Paul Andrew Davis 한국식품영양과학회 2014 Journal of medicinal food Vol.17 No.12

Dietary changes could potentially reduce prostate cancer morbidity and mortality. Transgenic adenocarcinoma of the mouse prostate (TRAMP) prostate tumor responses to a 100 g of fat/kg diet (whole walnuts, walnut oil, and other oils; balanced for macronutrients, tocopherols [a-and c]) for 18 weeks ad libitum were assessed. TRAMP mice (n = 17 per group) were fed diets with 100 g fat from either whole walnuts (diet group WW), walnut-like fat (diet group WLF, oils blended to match walnut’s fatty acid profile), or as walnut oil (diet group WO, pressed from the same walnuts as WW). Fasted plasma glucose was from tail vein blood, blood was obtained by cardiac puncture, and plasma stored frozen until analysis. Prostate (genitourinary intact [GUI]) was weighed and stored frozen at - 80 C. Plasma triglyceride, lipoprotein cholesterol, plasma multianalyte levels (Myriad RBM Rat Metabolic MAP), prostate (GUI), tissue metabolites (Metabolon, Inc., Durham, NC, USA), and mRNA (by Illumina NGS) were determined. The prostate tumor size, plasma insulin-like growth factor-1 (IGF-1), high density lipoprotein, and total cholesterol all decreased significantly (P< .05) in both WW and WO compared to WLF. Both WW and WO versus WLF showed increased insulin sensitivity (Homeostasis Model Assessment [HOMA]), and tissue metabolomics found reduced glucose-6-phosphate, succinylcarnitine, and 4-hydroxybutyrate in these groups suggesting effects on cellular energy status. Tissue mRNA levels also showed changes suggestive of altered glucose metabolism with WW and WO diet groups having increased PCK1 and CIDEC mRNA expression, known for their roles in gluconeogenesis and increased insulin sensitivity, respectively. WW and WO group tissues also had increased MSMB mRNa a tumor suppressor and decreased COX-2 mRNA, both reported to inhibit prostate tumor growth. Walnuts reduced prostate tumor growth by affecting energy metabolism along with decreased plasma IGF-1 andcholesterol. These effects are not due to the walnut’s N-3 fatty acids, but due to component(s) found in the walnut’s fat component.

An objective assessment of the impact of tendon retraction on sleep efficiency in patients with full-thickness rotator cuff tears: a prospective cohort study

Ashley E. MacConnell,William Davis,Rebecca Burr,Andrew Schneider,Lara R Dugas,Cara Joyce,Dane H. Salazar,Nickolas G. Garbis 대한견주관절의학회 2023 대한견주관절의학회지 Vol.26 No.2

Background: Sleep quality, quantity, and efficiency have all been demonstrated to be adversely affected by rotator cuff pathology. Previous measures of assessing the impact of rotator cuff pathology on sleep have been largely subjective in nature. This study was undertaken to objectively analyze this relationship through the use of activity monitors. Methods: Patients with full-thickness rotator cuff tears at a single institution were prospectively enrolled between 2018 and 2020. Waist-worn accelerometers were provided for the patients to use each night for 14 days. Sleep efficiency was calculated using the ratio of the time spent sleeping to the total amount of time that was spent in bed. Retraction of the rotator cuff tear was classified using the Patte staging system. Results: This study included 36 patients: 18 with Patte stage 1 disease, 14 with Patte stage 2 disease, and 4 patients with Patte stage 3 disease. During the study, 25 participants wore the monitor on multiple nights, and ultimately their data was used for the analysis. No difference in the median sleep efficiency was appreciated amongst these groups (P>0.1), with each cohort of patients demonstrating a generally high sleep efficiency. Conclusions: The severity of retraction of the rotator cuff tear did not appear to correlate with changes in sleep efficiency for patients (P>0.1). These findings can better inform providers on how to counsel their patients who present with complaints of poor sleep in the setting of full-thickness rotator cuff tears.

The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

The Cancer Genome Atlas Research Network,Davis, Caleb F.,Ricketts, C.J.,Wang, M.,Yang, L.,Cherniack, Andrew D.,Shen, H.,Buhay, C.,Kang, H.,Kim, S.,Fahey, Catherine C.,Hacker, Kathryn E.,Bhanot, G.,Gor Cell Press 2014 Cancer Cell Vol.26 No.3

We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations.

Are “Patellofemoral Symptoms” Truly Related to the Patellofemoral Joint?

( Rafik Yassa ),( Mahdi Yacine Khalfaoui ),( Andrew P. Davies ) 대한슬관절학회 2016 대한슬관절학회지 Vol.28 No.1

Purpose: The pattern of symptoms of knee osteoarthritis has been thought to be indicative of specific compartment involvement. This study investigated whether there was a true correlation between patellofemoral joint (PFJ) symptoms and unicompartmental patellofemoral arthritis. Materials and Methods: A prospective analysis of 34 patients rendered to be suffering from PFJ osteoarthritis and subsequently undergoing unicompartmental patellofemoral arthroplasty (PFA) was performed. A control cohort of 32 patients suffering from medial tibiofemoral joint (MTFJ) osteoarthritis was included in the analysis. Four questions derived from the Oxford knee score questionnaire, traditionally deemed to be indicative of PFJ osteoarthritis, were combined to create a PFJ subscore and statistically analyzed for their potential relationship with PFJ osteoarthritis and outcomes following PFA. Results: The PFJ subscore indicated slightly worse pathology in patients undergoing PFA compared to MTFJ replacement, but the difference was not significant (9.7 and 9.6, respectively; p=0.851). The improvement in PFJ symptoms was higher in those undergoing PFA compared to MTFJ surgery; however, the difference was not statistically significant (3.7 and 2.2 respectively, p=0.074). Conclusions: We were unable to prove that these symptoms were predictive of PFJ pathology in the preoperative setting, nor were they useful in interpreting which symptoms would likely improve following PFA.

7T Magnetic Resonance Imaging Quantification of Brain Glutamate in Acute Ischaemic Stroke

John-Paul Nicolo,Bradford Moffat,David K. Wright,Benjamin Sinclair,Andrew Neal,Elaine Lui,Patricia Desmond,Rebecca Glarin,Kathryn A. Davis,Ravinder Reddy,Bernard Yan,Terence J. O’Brien,Patrick Kwan 대한뇌졸중학회 2021 Journal of stroke Vol.23 No.2

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Bacterial Hash Function Using DNA-Based XOR Logic Reveals Unexpected Behavior of the LuxR Promoter

Pearson, Brianna,Lau, Kin H.,Allen, Alicia,Barron, James,Cool, Robert,Davis, Kelly,DeLoache, Will,Feeney, Erin,Gordon, Andrew,Igo, John,Lewis, Aaron,Muscalino, Kristi,Parra, Madeline,Penumetcha, Palla Korean Society for Bioinformatics 2011 Interdisciplinary Bio Central (IBC) Vol.3 No.3

Introduction: Hash functions are computer algorithms that protect information and secure transactions. In response to the NIST's "International Call for Hash Function", we developed a biological hash function using the computing capabilities of bacteria. We designed a DNA-based XOR logic gate that allows bacterial colonies arranged in a series on an agar plate to perform hash function calculations. Results and Discussion: In order to provide each colony with adequate time to process inputs and perform XOR logic, we designed and successfully demonstrated a system for time-delayed bacterial growth. Our system is based on the diffusion of ${\ss}$-lactamase, resulting in destruction of ampicillin. Our DNA-based XOR logic gate design is based on the op-position of two promoters. Our results showed that $P_{lux}$ and $P_{OmpC}$ functioned as expected individually, but $P_{lux}$ did not behave as expected in the XOR construct. Our data showed that, contrary to literature reports, the $P_{lux}$ promoter is bidirectional. In the absence of the 3OC6 inducer, the LuxR activator can bind to the $P_{lux}$ promoter and induce backwards transcription. Conclusion and Prospects: Our system of time delayed bacterial growth allows for the successive processing of a bacterial hash function, and is expected to have utility in other synthetic biology applications. While testing our DNA-based XOR logic gate, we uncovered a novel function of $P_{lux}$. In the absence of autoinducer 3OC6, LuxR binds to $P_{lux}$ and activates backwards transcription. This result advances basic research and has important implications for the widespread use of the $P_{lux}$ promoter.