PROGRAM and PROCEEDINGS the NEBRASKA ACADEMY of SCIENCES 1880-2017
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Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 9 April 2020 Peer-reviewed version available at Cells 2020, 9, 956; doi:10.3390/cells9040956 Review Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs Kenneth A. Jacobson1 and Marc L. Reitman2 1Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA 2Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA Abstract: Many ligands directly target adenosine receptors (ARs). Here we review the effects of noncanonical AR drugs on adenosinergic signaling. Non-AR mechanisms include raising adenosine levels by inhibiting adenosine transport (e.g. ticagrelor, ethanol, cannabidiol), affecting intracellular metabolic pathways (e.g. methotrexate, nicotinamide riboside, salicylate, 5‐ aminoimidazole‐4‐carboxamide riboside), or undetermined means (e.g. acupuncture). Yet other compounds bind ARs in addition to their canonical ‘on-target’ activity (e.g. mefloquine). The strength of experimental support for an adenosine-related role in a drug’s effects varies widely. AR knockout mice are the ‘gold standard’ method for investigating an AR role, but few drugs have been tested in these mice. Given the interest in AR modulation for treatment of cancer, CNS, immune, metabolic, cardiovascular, and musculoskeletal conditions, it is informative to consider AR and non-AR adenosinergic effects of approved drugs and conventional treatments. Keywords: adenosine receptor; nucleoside transport; CNS; inflammation; cardiovascular system; pain 1. Introduction Drugs can affect adenosine signaling in multiple ways. They can act directly as ligands for one or more of the four G protein-coupled receptors (GPCRs) for adenosine [1–3]. -
The Dissertation Committee for Alyssa D
Copyright by Alyssa D. Harad 2003 The Dissertation Committee for Alyssa D. Harad certifies that this is the approved version of the following dissertation: Ordinary Witnesses Committee: _________________________________ Ann Cvetkovich, Supervisor _________________________________ Mia Carter _________________________________ Evan Carton _________________________________ Phillip Barrish _________________________________ Kathleen Stewart Ordinary Witnesses by Alyssa D. Harad, B.A., M.A. Dissertation Presented to the Faculty of the Graduate School of the University of Texas at Austin in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy The University of Texas at Austin August, 2003 Acknowledgements This project had its genesis in the stories I heard in the halls of Intermountain Psychiatric Hospital from 1993-1995. The people I met there were the first to show me the everyday nature of trauma. They also taught me to always respect what seem to be delays, detours and failures. During my time at the University of Texas, the brains and hearts of my colleagues have dazzled and comforted me. In particular I would like to thank my first partner in the study of testimony and autobiography and dear friend, Traci Freeman; the members of my first dissertation group, Jennifer Mason, Paige Schilt, and Sandy Soto; and my later dissertation group members, especially my fellow mystic, Jonathan Ayres and the fabulous Chris Strickling, who not only read my drafts and challenged me always to be better and clearer, but who has been my stalwart friend and partner in stretching the narrower bounds of graduate school. Julie Sievers leant me her sharp attention at several crucial moments in the project’s final stages. -
Animal Abuse As a Sentinel for Human Violence: a Critique ∗ Emily G
Journal of Social Issues, Vol. 65, No. 3, 2009, pp. 589--614 Animal Abuse as a Sentinel for Human Violence: A Critique ∗ Emily G. Patterson-Kane American Veterinary Medical Association Heather Piper Manchester Metropolitan University It has been suggested that acts of violence against human and nonhuman an- imals share commonalities, and that animal abuse is a sentinel for current or future violence toward people. The popular and professional acceptance of strong connections between types of violence is beginning to be used to justify social work interventions and to influence legal decision making, and so requires greater scrutiny. Examination of the limited pool of empirical data suggests that animal abuse is relatively common among men, with violent offenders having an increased probability of reporting prior animal abuse—with the majority of violent offend- ers not reporting any animal abuse. Causal explanations for “the link,” such as empathy impairment or conduct disorder, suffer from a lack of validating research and, based on research into interhuman violence, the assumption that violence has a predominant, single underlying cause must be questioned. An (over)emphasis on the danger that animal abusers pose to humans serves to assist in achieving a consensus that animal abuse is a serious issue, but potentially at the cost of failing to focus on the most common types of abuse, and the most effective strategies for reducing its occurrence. Nothing in this review and discussion should be taken as minimizing the importance of animals as frequent victims of violence, or the co-occurrence of abuse types in “at-risk” households. -
The 2020 Investor Day Programming Fact Sheet
THE 2020 INVESTOR DAY PROGRAMMING FACT SHEET ©Disney Today at The Walt Disney Company’s Investor Day event, Lucasfilm President Kathleen Kennedy announced an impressive number of exciting Disney+ series and new feature films destined to expand theStar Wars galaxy like never before. Introducing the Disney+ slate, Kennedy said, “We have a vast and expansive timeline in the Star Wars mythology spanning over 25,000 years of history in the galaxy—with each era being a rich resource for storytelling. Now with Disney+, we can explore limitless story possibilities like never before and fulfill the promise that there is truly a Star Wars story for everyone.” Among the 10 projects announced for Disney+ is “Obi-Wan Kenobi,” starring Ewan McGregor, with Hayden Christensen returning as Darth Vader, in what Kennedy called, “the rematch of the century.” Also announced are two new series from Jon Favreau and Dave Filoni, off-shoots of the multiple Emmy®-winning “The Mandalorian.” “Rangers of the New Republic” and “Ahsoka,” a series featuring the fan-favorite character Ahsoka Tano, will take place in “The Mandalorian” timeline. Kennedy announced that the next Star Wars feature film, releasing in December 2023, will be “Rogue Squadron,” which will be directed by Patty Jenkins of the “Wonder Woman” franchise. In July 2022, the next installment of the “Indiana Jones” franchise premieres, starring Harrison Ford, who reprises his iconic role. The film is directed by James Mangold. Following are the announced projects, listed in announcement order under the Disney+ and feature film headers: DISNEY+ Ahsoka After making her long-awaited, live-action debut in “The Mandalorian,” Ahsoka Tano’s story, written by Dave Filoni, will continue in a limited series, Ahsoka, starring Rosario Dawson and executive produced by Dave Filoni and Jon Favreau. -
Mcgirt Ruling Continues to Bewilder Legal System
Rebekah Burnett named CMS Teacher of the Year LADONNA RHODES NSU, and Colten who is a Ju- be a teacher until I had chil- “I also love getting to watch STAFF WRITER nior at CHS. My parents, Roy dren of my own. Working re- all my students compete as Rebekah Burnett has been and Donna Matthews, are both tail was very demanding and I well. I believe we should always named the Checotah Middle CHS graduates too, along with wanted a schedule more suit- support our students so I stay School Teacher of the Year. my brother, Mark Matthews, able for my family. Funny how active in many booster activ- Burnett is the 7th grade Math and sister, Jennifer Campbell, things worked out, because ities for baseball, softball and teacher at CMS and has been who is the CHS principal. We now I can’t imagine doing any- football. teaching for ten years. are a Wildcat family and I am a thing else. “Teaching students is not just “I bleed blue!” Burnett said. Wildcat for life!” “I love watching my kids par- about ‘making the grade.’ Don’t “Not only did I attend Checo- Burnett attended Connors ticipate in everything. When get me wrong. I definitely want tah K -12 but I married a Wild- State College to receive her Sara was in school, I chased her my students to be successful cat, Michael Burnett, who went Associates Degree then North- around the state, cheering her on their educational journeys to CHS K-12 as well. Togeth- eastern State University to re- on in softball and track. -
Star Channels, August 8
AUGUST 8 - 14, 2021 staradvertiser.com PARADISE LOST Roselyn Sánchez stars as Elena Roarke, a sophisticated and insightful woman who welcomes guests looking to fulfi l their fantasies at a mysterious luxury resort in the premiere of Fantasy Island. Roarke is assisted by Ruby (Kiara Barnes), a woman whose own island experience gave her a new lease on life, and pilot Javier (John Gabriel Rodriguez). Airing Tuesday, Aug. 10, on Fox. Enjoy original songs performed live by up and coming local artists. Hosted by Jake ShimabukuroZg]Ûef^]Zm¶ũe^ehl Mele A‘e new soundstage, Studio 1122. A SHOWCASE FOR HAWAI¶I’S SUNDAY, AUGUST 22, 7PM | olelo.org/53 olelo.org | olelo.org ASPIRING ARTISTS 53 SPECTRUM 53 & 1053 HAWAIIAN TELCOM 590242_MeleAePremiere_2_withJake_Channels.indd 1 8/3/21 1:37 PM ON THE COVER | FANTASY ISLAND Welcome (back) to ‘Fantasy Island’ ‘Da plane’ brings iconic with the Golden Gun,” 1974) as his assistant, This isn’t the first time the show has been Tattoo. The original show kicked off with two revived. In 1998, ABC brought “Fantasy Island” series back to TV made-for-television movies and continued in back to television with Malcolm McDowell a series that ran on ABC in the late 1970s and (“A Clockwork Orange,” 1971) as Mr. Roarke. early 1980s. However, the ABC edition failed to enchant By Kyla Brewer The reboot is the brainchild of writing team viewers the way the original had, and it was TV Media Liz Craft and Sarah Fain, who have worked on canceled after just 13 episodes. More re- “Angel,” “The Shield” and “Women’s Murder cently, Blumhouse Productions brought the hat if you could have exactly what Club.” The new “Fantasy Island,” a co-pro- concept to the big screen in the horror film you’ve always wanted? What if your duction between Fox Entertainment, Sony adaptation “Fantasy Island” in 2020, but it was Wwildest fantasy were to come true? panned by critics. -
Anishinaabeg Today Wednesday, September 1, 2021
AAnniisshhiinnaaaabbeegg TTooddaayy A Monthly Chronicle of White Earth Reservation Vol. 26 No. 9 White Earth, Minn. [email protected] Wednesday, September 1, 2021 Photo by Vicki Gerdes/ Detroit Lakes Tribune White Earth Tribal Home Health received the Community Spirit award from United Way during a ceremony on Aug. 19 at the Holmes Theater in Detroit Lakes. Accepting the award from left are Deb Killian, Mina Spalla, Sally Simonson, Lindsi Darco, Lisa Braun and Shirley Holzgrove. WE Tribal Home Health honored at event The United Way of Becker County held its Since they first began offering the vaccines annual Celebration of Heroes on Aug. 19 at the to the public in 2020, White Earth Home Health Holmes Theater in Detroit Lakes. The annual has successfully vaccinated 16,458 people, and event honors the “everyday heroes” that work directly contributed to the high vaccination rates behind the scenes to make our communities a of the counties where the vaccines were offered. better place to live. “When the vaccine became available to The members of the White Earth Tribal White Earth, the tribal council made the call to Home Health organization were collectively offer the vaccine to non-Native residents of honored for their efforts in offering free doses of Mahnomen, Becker and Clearwater, as well as the COVID-19 vaccine to both Native American nearby Norman and Polk counties because the and non-Native residents of not only council believes, ‘We should be good neighbors Mahnomen, Becker and Clearwater counties, during these times of need and it is the right which all contain part of the 900,000-acre reser - thing to do,’” said 2020 United Way of Becker vation, but also the neighboring counties of County President Anna Schmitz, who presented Norman and Polk. -
January 29, 2021 Seminole Tribune
Durante Blais-Billie PECS students raise Seminoles step up to named to museum post money for S. Sudan help Haskell v COMMUNITY v 8A EDUCATION 1B SPORTS v 5B www.seminoletribune.org Free Volume XLV • Number 1 January 29, 2021 Hard Rock Tribe’s vaccine distribution in full swing Tejon moves BY DAMON SCOTT closer to Staff Reporter breaking HOLLYWOOD — The Seminole Tribe started its Covid-19 vaccine program in late December and has since administered ground the shot to hundreds of tribal members and BY DAMON SCOTT key personnel. Staff Reporter Some of the first to receive the vaccine were tribal leaders and public safety and A partnership between Hard Rock health care workers. Seminole Fire Rescue International and the Tejon Tribe to develop staff, which has been administering the a hotel and casino recently took a significant shots, then began to vaccinate health clinic step forward. patients, disabled elders and those with The Bureau of Indian Affairs (BIA) diabetes. signed off on the proposed project Jan. 8 – Vaccine availability has since been one of the last hurdles to clear before the Hard opened up to any tribal member 18 years Rock Hotel & Casino Tejon could eventually and older. After tribal members who wish move toward a construction timeline. to receive the vaccine have been given an The $600 million project is to be built on opportunity, including non-tribal spouses a site in Mettler, California – 14 miles south that live with tribal members, tribal of Bakersfield and 90 miles north of Los employees will be in line for the shot. -
Patrick Dwayne Murphy Found Guilty by Federal Jury
TUCCÊNENNATIVE AMERICAN JOURNALISM ASSOCIATION ANDTHE SOCIETY MVSKOKE OF PROFESSIONAL NEWS JOURNALIST AWARD WINNING PUBLICATIONPAGE 1 AUGUST 15, 2021 | “HIYO RAKKO” BIG HARVEST MONTH | VOL. 51, ISSUE 15 NAMING CEREMONY FOR FORMER CANCER CENTER HELD THE MUSCOGEE NATION HEALTH SYSTEM PURCHASED A NEW FACILITY TO SERVE THE TULSA AREA (L-R) Shianne Dill, Ailanee Hicks, and Taylan Starr at a meet and greet accepting donations. (Morgan Taylor/Reporter) MUSCOGEE SOFTBALLERS HEAD TO LITTLE LEAGUE WORLD SERIES TEAM OKLAHOMA’S MAJORITY NATIVE AMERICAN ROSTER TO PLAY FASTPITCH ON NATIONAL Secretary of Health Shawn Terry presents the newly named hospital and speaks of future plans for the facility. STAGE (Morgan Taylor/Reporter) Morgan Taylor ship game in Waco, Texas. OAK - 2 REPORTER Taylan Starr (short- stop) of Preston, Ailanee Hicks (first/third baseman) OKMULGEE, Oklahoma of Henryetta, and Shianne “DOGS” RUN THROUGH THE – Three Muscogee (Creek) Dill (centerfield) of Oktaha girls with a love for softball will be part of the first team are representing Oklahoma in history to represent the RESERVATION in the Little League World state at the Little League Series in North Carolina World Series. FX SERIES “RESERVATION DOGS” SCREENINGS after winning the South- HELD AT RIVER SPIRIT, CIRCLE CINEMA west Regional Champion- FAST PITCH - 2 PATRICK DWAYNE MURPHY FOUND GUILTY BY FEDERAL JURY FOR IMMEDIATE jury trial began with testi- RELEASE mony on Tuesday, August 3, 2021 and concluded on Thursday, August 5, MUSKOGEE, OKLA- 2021 with the guilty ver- HOMA - The United dicts. The defendant faces States Attorney’s Office imprisonment for life for for the Eastern District the crimes the jury found A red carpet event was held for the screening of “Reservation Dogs,” at Circle Cinema in Tulsa, Oklahoma. -
Diastereoselective Formal Synthesis of a Monoterpene Alkaloid, (-)-Incarvilline
Diastereoselective Formal Synthesis of a Monoterpene Alkaloid, (-)-Incarvilline Toshio Honda* and Kyosuke Kaneda Faculty of Pharmaceutical Sciences, Hoshi UniVersity, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan [email protected] ReceiVed May 9, 2007 Diastereoselective formal synthesis of a monoterpene alkaloid, (-)-incarvilline, the key intermediate for the synthesis of (-)-incarvillateine, was achieved by using an intramolecular Pauson-Khand reaction of (S)-N-[(E)-2-butenyl]-N-(3-butynyl-2-methoxymethoxy)-p-toluenesulfonamide as a key step. Introduction To the best our knowledge, two total syntheses4,6 and one synthetic approach7 for 3 have been reported to date. Recent investigations of the plant IncarVilla sinensis,1 which As part of our continuing effort to synthesize biologically has been used to treat rheumatism and relieve pain as a active natural products, we are also interested in a diastereo- traditional Chinese medicine, led to the isolation of a various selective synthesis of (-)-incarvilline. Our retrosynthetic analy- types of monoterpene alkaloids with a wide range of structural sis was depicted in Scheme 1, where we decided to exploit an and stereochemical features. Among them, incarvillateine 1 intramolecular Pauson-Khand reaction8 of (S)-N-[(E)-2-bute- carrying a characteristic cyclobutane ring has been recognized nyl]-N-(3-butynyl-2-methoxymethoxy)-p-toluenesulfonamide as to exhibit significant antinociceptive activity in a formalin- a key step, since the relative stereochemistry between the 7- induced pain model in mice.2 It is also suggested that the and 7a-positions should be controlled by employing E-olefin antinociceptive effect arose from the activation of µ- and as the starting material. -
Development of New Synthetic Methods and Its Application to Total Synthesis of Nitrogen-Containing Bioactive Natural Products
November 2005 Chem. Pharm. Bull. 53(11) 1375—1386 (2005) 1375 Review Development of New Synthetic Methods and Its Application to Total Synthesis of Nitrogen-Containing Bioactive Natural Products Chihiro KIBAYASHI School of Pharmacy, Tokyo University of Pharmacy and Life Science; Horinouchi, Hachioji, Tokyo 192–0392, Japan. Received June 20, 2005 A group of naturally occurring substances containing nitrogen is widely distributed in plants as well as in fungi, animal, marine organisms, and insects, and many exhibit significant biological activity. These natural products with a huge variety of chemical structures include antibiotics, antitumor agents, immunostimulants, drugs affecting the cardiovascular and central nervous systems, analgesics etc. The diverse activities and low nat- ural abundance of this group of natural products when coupled with their molecular complexity warrant devel- opment of new and efficient synthetic methods and strategy for the total synthesis of these products, in particular alkaloids. The purpose of this review is to describe some of our achievements in the total synthesis of the natu- rally-occurring bases including the Dendrobatid alkaloids pumiliotoxin B and allopumiliotoxin A, the anitibiotic streptazolin, the tricyclic marine alkaloids isolated from the ascidians such as fasicularin, lepadiformine, and cylindricine C, and the dimeric monoterpene alkaloid incarvillateine as well as the formal total synthesis of the spirocyclic marine alkaloids halichlorine and pinnaic acid, which are isolated from the Japanese -
Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 8 April 2020 doi:10.20944/preprints202004.0115.v1 Review Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs Kenneth A. Jacobson1 and Marc L. Reitman2 1Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA 2Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA Abstract: Many ligands directly target adenosine receptors (ARs). Here we review the effects on adenosinergic signaling of other drugs that are not typically identified as binding ARs. Non-AR mechanisms include raising adenosine levels by inhibiting adenosine transport (e.g. ticagrelor, ethanol, cannabidiol), affecting intracellular metabolic pathways (e.g. methotrexate, nicotinamide riboside, salicylate, AICA riboside), or undetermined means (e.g. acupuncture). Yet other compounds bind ARs, in addition to their canonical ‘on-target’ activity (e.g. mefloquine). The strength of experimental support varies widely. AR knockout mice are the ‘gold standard’ method for investigating an AR role, but few drugs have been tested in these mice. Given the interest in AR modulation for treatment of cancer, CNS, immune, metabolic, cardiovascular, and musculoskeletal conditions, it is informative to consider AR and non-AR adenosinergic effects of approved drugs and conventional treatments. Keywords: adenosine receptor; nucleoside transport; CNS; inflammation; cardiovascular system; pain 1. Introduction Drugs acting on adenosine signaling can do so in multiple ways. They can act directly as ligands on one or more of the four G protein-coupled receptors (GPCRs) for adenosine. Alternatively, they can stimulate or inhibit pathways of adenosine generation, degradation, or clearance.