Monoclonal antibody targeting of fibroblast growth factor receptor 1c ameliorates obesity and glucose intolerance via central mechanisms.

We have generated a novel monoclonal antibody targeting human FGFR1c (R1c mAb) that caused profound body weight and body fat loss in diet-induced obese mice due to decreased food intake (with energy expenditure unaltered), in turn improving glucose control. R1c mAb also caused weight loss in leptin-deficient ob/ob mice, leptin receptor-mutant db/db mice, and in mice lacking either the melanocortin 4 receptor or the melanin-concentrating hormone receptor 1. In addition, R1c mAb did not change hypothalamic mRNA expression levels of Agrp, Cart, Pomc, Npy, Crh, Mch, or Orexin, suggesting that R1c mAb could cause food intake inhibition and body weight loss via other mechanisms in the brain. Interestingly, peripherally administered R1c mAb accumulated in the median eminence, adjacent arcuate nucleus and in the circumventricular organs where it activated the early response gene c-Fos. As a plausible mechanism and coinciding with the initiation of food intake suppression, R1c mAb induced hypothalamic expression levels of the cytokines Monocyte chemoattractant protein 1 and 3 and ERK1/2 and p70 S6 kinase 1 activation

Defining and unpacking the core concepts of pharmacology : A global initiative

The authors acknowledge the contribution of the expert group members who contributed their expertise to the study and Professor Martin Kingsbury for his invaluable guidance on concept mapping.Peer reviewe

Impact of a hypomorphic Artemis disease allele on lymphocyte development, DNA end processing, and genome stability

Artemis was initially discovered as the gene inactivated in human radiosensitive T−B− severe combined immunodeficiency, a syndrome characterized by the absence of B and T lymphocytes and cellular hypersensitivity to ionizing radiation. Hypomorphic Artemis alleles have also been identified in patients and are associated with combined immunodeficiencies of varying severity. We examine the molecular mechanisms underlying a syndrome of partial immunodeficiency caused by a hypomorphic Artemis allele using the mouse as a model system. This mutation, P70, leads to premature translation termination that deletes a large portion of a nonconserved C terminus. We find that homozygous Artemis-P70 mice exhibit reduced numbers of B and T lymphocytes, thereby recapitulating the patient phenotypes. The hypomorphic mutation results in impaired end processing during the lymphoid-specific DNA rearrangement known as V(D)J recombination, defective double-strand break repair, and increased chromosomal instability. Biochemical analyses reveal that the Artemis-P70 mutant protein interacts with the DNA-dependent protein kinase catalytic subunit and retains significant, albeit reduced, exo- and endonuclease activities but does not undergo phosphorylation. Together, our findings indicate that the Artemis C terminus has critical in vivo functions in ensuring efficient V(D)J rearrangements and maintaining genome integrity

Identifying the core concepts of pharmacology education : a global initiative

Background and Purpose: In recent decades, a focus on the most critical and fundamental concepts has proven highly advantageous to students and educators in many science disciplines. Pharmacology, unlike microbiology, biochemistry or physiology, lacks a consensus list of such core concepts . Experimental approach: We sought to develop a research-based, globally relevant list of core concepts that all students completing a foundational pharmacology course should master. This two-part project consisted of exploratory and refinement phases. The exploratory phase involved empirical data mining of the introductory sections of five key textbooks, in parallel with an online survey of over 200 pharmacology educators from 17 countries across six continents. The refinement phase involved three Delphi rounds involving 24 experts from 15 countries across six continents. Key Results: The exploratory phase resulted in a consolidated list of 74 candidate core concepts. In the refinement phase, the expert group produced a consensus list of 25 core concepts of pharmacology. Conclusion and Implications: This list will allow pharmacology educators everywhere to focus their efforts on the conceptual knowledge perceived to matter most by experts within the discipline. Next steps for this project include defining and unpacking each core concept and developing resources to help pharmacology educators globally teach and assess these concepts within their educational contexts

Annotated Bibliography of Relative Sea Level Change

Source: https://erdc-library.erdc.dren.mil/jspui/This report summarizes 377 abstracts on the relative change of sea level that have been published through 1989. Articles cited in this bibliography include references to global, regional, and local sea level changes with emphasis on quantitative data analysis. Coastal and geological processes that affect sea level change are discussed in the background section. A crossreferenced keyword index and a subject index are included

Preface

The University of Pennsylvania Working Papers in Linguistics (PWPL) is an occasional series published by the Penn Linguistics Club. The series has included volumes of previously unpublished work, or work in progress, by linguists with an ongoing affiliation with the Department, as well as volumes of papers from NWAV and the Penn Linguistics Colloquium. This volume contains selected papers from NWAV 37, held from November 6-9, 2008 in Houston, TX hosted by Rice University and co-hosted by University of Texas-San Antonio. Thanks (alphabetically) to Dimka Atanassov, Jana Beck, Toni Cook, Lauren Friedman, Shane Jobber, Catherine Lai, Marielle Lerner, Jon Stevens, and Joshua Tauberer for help in editing, uploading, and general support. Thanks also to Stefanie Brody for her initial work in putting together this volume. Since Vol. 14.2, PWPL has been an internet-only publication. Since Vol. 13.2, PWPL has been published both in print and online gratis via ScholarlyCommons@Penn. Due to the large number of hits these online papers have received, and the time and expense of managing a back catalog of PWPL volumes, the editorial committee decided in 2008 to cease print publication in favor of wider-scale free online dissemination. Please continue citing PWPL papers or issues as you would a paper in a refereed collection, though you may also provide the URL of the manuscript. An example is below: Baker, Wendy, and David Bowie. 2010. Religious affiliation as a correlate of linguistic behavior. In U. Penn Working Papers in Linguistics 15.2: Proceedings of NWAV 37, ed. K. Gorman and L. MacKenzie, 1-10. URL http://repository.upenn.edu/pwpl/vol15/iss2/2 Ultimately, the entire back catalog will be digitized and made available on ScholarlyCommons@Penn. Publication in the University of Pennsylvania Working Papers in Linguistics (PWPL) does not preclude submission of papers elsewhere; copyright is retained by the author(s) of individual papers. The PWPL editors can be contacted at: U. Penn Working Papers in Linguistics 619 Williams Hall University of Pennsylvania Philadelphia, PA 19104–6305 [email protected] http://ling.upenn.edu/papers/pwpl.html Kyle Gorman and Laurel MacKenzie Issue Editor

Preface

The University of Pennsylvania Working Papers in Linguistics (PWPL) is an occasional series published by the Penn Linguistics Club. The series has included volumes of previously unpublished work, or work in progress, by linguists with an ongoing affiliation with the Department, as well as volumes of papers from NWAV and the Penn Linguistics Colloquium. This volume contains selected papers from NWAV 37, held from November 6-9, 2008 in Houston, TX hosted by Rice University and co-hosted by University of Texas-San Antonio. Thanks (alphabetically) to Dimka Atanassov, Jana Beck, Toni Cook, Lauren Friedman, Shane Jobber, Catherine Lai, Marielle Lerner, Jon Stevens, and Joshua Tauberer for help in editing, uploading, and general support. Thanks also to Stefanie Brody for her initial work in putting together this volume. Since Vol. 14.2, PWPL has been an internet-only publication. Since Vol. 13.2, PWPL has been published both in print and online gratis via ScholarlyCommons@Penn. Due to the large number of hits these online papers have received, and the time and expense of managing a back catalog of PWPL volumes, the editorial committee decided in 2008 to cease print publication in favor of wider-scale free online dissemination. Please continue citing PWPL papers or issues as you would a paper in a refereed collection, though you may also provide the URL of the manuscript. An example is below: Baker, Wendy, and David Bowie. 2010. Religious affiliation as a correlate of linguistic behavior. In U. Penn Working Papers in Linguistics 15.2: Proceedings of NWAV 37, ed. K. Gorman and L. MacKenzie, 1-10. URL http://repository.upenn.edu/pwpl/vol15/iss2/2 Ultimately, the entire back catalog will be digitized and made available on ScholarlyCommons@Penn. Publication in the University of Pennsylvania Working Papers in Linguistics (PWPL) does not preclude submission of papers elsewhere; copyright is retained by the author(s) of individual papers. The PWPL editors can be contacted at: U. Penn Working Papers in Linguistics 619 Williams Hall University of Pennsylvania Philadelphia, PA 19104–6305 [email protected] http://ling.upenn.edu/papers/pwpl.html Kyle Gorman and Laurel MacKenzie Issue Editor

Kings Bay Coastal and Estuarine Physical Monitoring and Evaluation Program: coastal studies. Volume 2, Appendices B-G

Source: https://erdc-library.erdc.dren.mil/jspui/The objective of this study was to assess the impacts of U.S. Navy-sponsored navigation channel modification and maintenance activities conducted from 1985-1992 on the shoreline in the vicinity of the traditionally called St. Marys Entrance. This inlet, separating Cumberland Island, Georgia, to the north and Amelia Island, Florida, to the south, contains a large estuary, a commercial and recreational port, Fernandina Harbor, Florida, and, since the 1970s, a U.S. Navy submarine base located at Kings Bay, Georgia. A study of the coastal area included the following components: (a.) Review of historical data and previous studies. (b.) Numerical simulation of waves and shoreline change. (c.) Monitoring of waves, water level, shoreline position, beach profile and sediments, and ebb-tidal bathymetry over the period 1988-1992. No adverse impact on the beaches of Cumberland Island and Amelia Island by U.S. Navy navigation channel modification and maintenance at St. Marys Entrance could be detected in any of the analyses or monitoring. NOTE: This file is large. Allow your browser several minutes to download the file