Mathematical demography of the Cape vulture

The Cape Vulture Gyps coprotheres is one of the world's largest avian scavengers and was once widely distributed in southern Africa, to which it is endemic. It has suffered major changes of fortune in recorded history and has, at least twice, undergone large range contractions and expansions in the Cape Province. It has variously been classified as 'rare', 'vulnerable' or 'threatened'. It is currently thought, by some, to be in decline. The central aim of these researches is to answer the 'Grand Question': What is the probability that the Cape Vulture will survive well into the twenty-first century as a free-flying bird? This is followed by a secondary question: What is the stability of the population in space, time and age-structure

Pronounced state-level disparities in prescription of cannabinoids to medicaid patients

Introduction: Dronabinol is approved in the USA for chemotherapy-induced nausea as well as vomiting and HIV-induced anorexia, while cannabidiol is primarily ap- proved for childhood epileptic disorders Lennox-Gastaut and Dravet syndrome. The use pattern for these prescription cannabinoids in the USA is unknown. This study examined Medicaid claims for two FDA-approved prescription cannabinoids, dronabinol and cannabidiol, approved in 1985 and 2018, respectively, from 2016–2020 to better understand the pharmacoepidemiologic trends and distribution of these drugs in US Medicaid amidst the increasing use of non-pharmaceutical formulations of cannabis. Methods: The longitudinal study analyzed Medicaid prescription claims that were calculated by extracting the prescriptions on a state level from 2016 to 2020 for two cannabinoids, dronabinol and cannabidiol, where outcomes over each year were calculated. Outcomes were (1) the number of prescriptions for each state corrected for the number of Medicaid enrollees and (2) dronabinol and cannabidiol spending. Spending refers to the amount reimbursed by the state Medicaid program. Results: Dronabinol prescriptions per state decreased by 25.3% from 2016 to 2020, while cannabidiol prescriptions increased by 16,272.99% from 2018 to 2020. The spending on these drugs parallels that of their prescription trend with a 66.3% decrease in reimbursement for dronabinol ($5.7 million in 2020), whereas cannabidiol increased by +26,582.0$233.3 million in 2020). Dronabinol prescriptions, when corrected for the number of enrollees, in Connecticut were 136.4 times larger than in New Mexico, and seventeen states had zero prescriptions. Idaho’s prescriptions of cannabidiol (27.8/10,000 enrollees) were significantly elevated relative to the national average and were 15.4-fold higher than Washington, DC (1.8/10K enrollees). Conclusions: The prescriptions of pharmaceutical-grade tetrahydrocannabinol decreased while those of cannabidiol increased. This study also identified pronounced state-level variation in cannabinoid prescribing to Medicaid patients. State formularies and prescription drug list variation may contribute to the drug reimbursements in Medicaid, though further research is needed to identify the health policy or pharmacoeconomic origins of these disparities

Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria

Macrophages mediate crucial innate immune responses via caspase-1-dependent processing and secretion of interleukin 1β (IL-1β) and IL-18. Although infection with wild-type Salmonella typhimurium is lethal to mice, we show here that a strain that persistently expresses flagellin was cleared by the cytosolic flagellin-detection pathway through the activation of caspase-1 by the NLRC4 inflammasome; however, this clearance was independent of IL-1β and IL-18. Instead, caspase-1-induced pyroptotic cell death released bacteria from macrophages and exposed the bacteria to uptake and killing by reactive oxygen species in neutrophils. Similarly, activation of caspase-1 cleared unmanipulated Legionella pneumophila and Burkholderia thailandensis by cytokine-independent mechanisms. This demonstrates that activation of caspase-1 clears intracellular bacteria in vivo independently of IL-1β and IL-18 and establishes pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system

A requirement for filopodia extension toward Slit during Robo-mediated axon repulsion

Axons navigate long distances through complex 3D environments to interconnect the nervous system during development. Although the precise spatiotemporal effects of most axon guidance cues remain poorly characterized, a prevailing model posits that attractive guidance cues stimulate actin polymerization in neuronal growth cones whereas repulsive cues induce actin disassembly. Contrary to this model, we find that the repulsive guidance cue Slit stimulates the formation and elongation of actin-based filopodia from mouse dorsal root ganglion growth cones. Surprisingly, filopodia form and elongate toward sources of Slit, a response that we find is required for subsequent axonal repulsion away from Slit. Mechanistically, Slit evokes changes in filopodium dynamics by increasing direct binding of its receptor, Robo, to members of the actin-regulatory Ena/VASP family. Perturbing filopodium dynamics pharmacologically or genetically disrupts Slit-mediated repulsion and produces severe axon guidance defects in vivo. Thus, Slit locally stimulates directional filopodial extension, a process that is required for subsequent axonal repulsion downstream of the Robo receptor.National Institutes of Health (U.S.) (Grant F32-CA165700)National Institutes of Health (U.S.) (Grant R01-GM068678)National Institutes of Health (U.S.) (Grant P30-CA014051

Old English macian, Its Origin and Dissemination

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66612/2/10.1177_007542428601900105.pd

Extracellular Transglutaminase 2 Is Catalytically Inactive, but Is Transiently Activated upon Tissue Injury

Transglutaminase 2 (TG2) is a multifunctional mammalian protein with transamidase and signaling properties. Using selective TG2 inhibitors and tagged nucleophilic amine substrates, we show that the majority of extracellular TG2 is inactive under normal physiological conditions in cell culture and in vivo. However, abundant TG2 activity was detected around the wound in a standard cultured fibroblast scratch assay. To demonstrate wounding-induced activation of TG2 in vivo, the toll-like receptor 3 ligand, polyinosinic-polycytidylic acid (poly(I:C)), was injected in mice to trigger small intestinal injury. Although no TG2 activity was detected in vehicle-treated mice, acute poly(I:C) injury resulted in rapid TG2 activation in the small intestinal mucosa. Our findings provide a new basis for understanding the role of TG2 in physiology and disease

Rational Extension of the Ribosome Biogenesis Pathway Using Network-Guided Genetics

Gene networks are an efficient route for associating candidate genes with biological processes. Here, networks are used to discover more than 15 new genes for ribosomal subunit maturation, rRNA processing, and ribosomal export from the nucleus