George Williams is rightly honored for his contributions to basic biological theory. In addition, however, his thought and contribution paved the way for much needed integration of basic evolutionary theory and modern environmental problems. Specifically, his contributions to the levels of selection" debate, and his application of these contributions to the "Gaia" approach to ecological problems, may help us improve our ability to move past untested prescriptions to a thoughtful matching of the characteristics of the problem and solution, and thus improve our effectiveness.
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http://dx.doi.org/10.1086/431027 | DOI Listing |
J Med Chem
November 2024
Pfizer Research & Development, 558 Eastern Point Road, Groton, Connecticut 06340, United States.
Inhibition of branched-chain ketoacid dehydrogenase kinase (BDK or BCKDK), a negative regulator of branched-chain amino acid (BCAA) metabolism, is hypothesized to treat cardio-metabolic diseases. From a starting point with potential idiosyncratic toxicity risk, modification to a benzothiophene core and discovery of a cryptic pocket allowed for improved potency with 3-aryl substitution to arrive at PF-07328948, which was largely devoid of protein covalent binding liability. This BDK inhibitor was shown also to be a BDK degrader in cells and in vivo rodent studies.
View Article and Find Full Text PDFOphthalmol Retina
October 2024
Associated Retinal Consultants, Royal Oak, Michigan; Department of Ophthalmology, Oakland University William Beaumont School of Medicine, Rochester, Michigan.
J Cardiothorac Vasc Anesth
August 2024
Department of Anesthesiology, Perioperative Care & Pain Medicine, Neurology, Surgery and Medicine, New York University, New York, NY.
While considerable literature exists with respect to clinical aspects of critical care anesthesiology (CCA) practice, few publications have focused on how anesthesiology-based critical care practices are organized and the challenges associated with the administration and management of anesthesiology critical care units. Currently, numerous challenges are affecting the sustainability of CCA practice, including decreased applications to fellowship positions and decreased reimbursement for critical care work. This review describes what is known about the subspecialty of CCA and leverages the experience of administrative leaders in adult critical care anesthesiologists in the United States to describe potential solutions.
View Article and Find Full Text PDFBMJ Glob Health
February 2024
Health Emergencies, World Health Organization, Geneva, Switzerland
Chemistry
May 2024
School of Chemistry, University of Glasgow, Glasgow, G12 8QQ, UK.
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