High-potency ligands for DREADD imaging and activation in rodents and monkeys.

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are a popular chemogenetic technology for manipulation of neuronal activity in uninstrumented awake animals with potential for human applications as well. The prototypical DREADD agonist clozapine N-oxide (CNO) lacks brain entry and converts to clozapine, making it difficult to apply in basic and translational applications. Here we report the development of two novel DREADD agonists, JHU37152 and JHU37160, and the first dedicated 18F positron emission tomography (PET) DREADD radiotracer, [18F]JHU37107. We show that JHU37152 and JHU37160 exhibit high in vivo DREADD potency. [18F]JHU37107 combined with PET allows for DREADD detection in locally-targeted neurons, and at their long-range projections, enabling noninvasive and longitudinal neuronal projection mapping

High-potency ligands for DREADD imaging and activation in rodents and monkeys

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are a popular chemogenetic technology for manipulation of neuronal activity in uninstrumented awake animals with potential for human applications as well. The prototypical DREADD agonist clozapine N-oxide (CNO) lacks brain entry and converts to clozapine, making it difficult to apply in basic and translational applications. Here we report the development of two novel DREADD agonists, JHU37152 and JHU37160, and the first dedicated 18F positron emission tomography (PET) DREADD radiotracer, [18F]JHU37107. We show that JHU37152 and JHU37160 exhibit high in vivo DREADD potency. [18F]JHU37107 combined with PET allows for DREADD detection in locally-targeted neurons, and at their long-range projections, enabling noninvasive and longitudinal neuronal projection mapping

The Impact of War on U.S. Army Leader Self-Development Domain in the Early 21st Century

This qualitative research examines senior U.S. Army officer leaders’ propensity and appreciation to engage in self-devolvement and to develop their junior leaders. The research compares what the Army is prescribing to its leaders with what they are actually saying and doing. It focuses on the decade before the Global War on Terrorism, during the high-tempo war period, and the last ten years. We find that the past 19 years of war have impacted the U.S. Army in countless ways. One is arguably on its most precious capability—its active officer leaders. As the Army rose to war-related challenges, it did so at leader-development costs. Little time, focus, and a battle environment left developing others and oneself low on the list of priorities. Less officer nurturing in the past will have an amplified and harmful effect in the near and distant future; unless, of course, the Army understands its self-development state-of-affairs today and takes action to bolster adult learning. It is no longer a question of if the Army wants to develop its leadership seed-corn, but if they can

Would Prosecuting Russia Prolong the War in Ukraine?

Ukrainian President Volodymyr Zelensky is calling for the creation of a special international tribunal on aggression that could hold Russian President Vladimir Putin to account for starting an illegal war in Ukraine. Although the International Criminal Court is investigating the war crimes and crimes against humanity being committed in Ukraine, it has no jurisdiction to prosecute Russian leaders for the crime of aggression

Would Prosecuting Russia Prolong the War in Ukraine?

Ukrainian President Volodymyr Zelensky is calling for the creation of a special international tribunal on aggression that could hold Russian President Vladimir Putin to account for starting an illegal war in Ukraine. Although the International Criminal Court is investigating the war crimes and crimes against humanity being committed in Ukraine, it has no jurisdiction to prosecute Russian leaders for the crime of aggression

Phosphorus-32, a clinically available drug, inhibits cancer growth by inducing DNA double-strand breakage.

Radioisotopes that emit electrons (beta particles), such as radioiodine, can effectively kill target cells, including cancer cells. Aqueous 32P[PO4] is a pure beta-emitter that has been used for several decades to treat non-malignant human myeloproliferative diseases. 32P[PO4] was directly compared to a more powerful pure beta-emitter, the clinically important 90Y isotope. In vitro, 32P[PO4] was more effective at killing cells than was the more powerful isotope 90Y (P ≤ 0.001) and also caused substantially more double-stranded DNA breaks than did 90Y. In vivo, a single low-dose intravenous dose of aqueous elemental 32P significantly inhibited tumor growth in the syngeneic murine cancer model (P ≤ 0.001). This effect is exerted by direct incorporation into nascent DNA chains, resulting in double-stranded breakage, a unique mechanism not duplicatable by other, more powerful electron-emitting radioisotopes. 32P[PO4] should be considered for human clinical trials as a potential novel anti-cancer drug