A Mechanistic Investigation of the Nickel-Catalyzed Negishi Coupling of Styrenyl Aziridines

The nickel-catalyzed cross coupling of styrenyl aziridines and organozinc nucleophiles constitutes a novel synthetic methodology, which enables carbon-carbon bond formation with a non-traditional electrophile and implements a unique class of ligands. In order to gain a better understanding of this reaction, a mechanistic investigation was conducted. Through reaction progress kinetic analysis, it was determined that the reaction has either a first- or a fractional-order dependence on [catalyst] and seems to be inhibited by the product. Dynamic NMR studies illustrated that the product exists in multiples forms in the reaction mixture and undergoes interchange. Given the unique reactivity imparted to nickel by the electron-deficient olefin ligand, the nature of the catalytic species was examined as well. The absence of nonlinear effects in the reaction system suggests that the active catalyst is likely mono-ligated. Interestingly, it was also discovered that the catalyst loading influences the chemoselectivity of the reaction. Initial rate studies further demonstrated that the rate dependence on [aziridine] and [nucleophile] changes over the tested concentration range. Thus, this investigation has provided a deeper understanding of the reaction system, yet has also raised new questions regarding the mechanism. We anticipate that these studies will provide direction for future mechanistic work and aid in the further development of this valuable synthetic methodology

Longevity and mortality in cats: A single institution necropsy study of 3108 cases (1989–2019)

Client-owned cats who underwent a post-mortem examination (n = 3,108) at a veterinary medical teaching hospital between 1989 and 2019 were studied to determine longevity and factors affecting mortality. Demographic factors, environmental factors, age, and causes of death were assessed. Sexes included 5.66% intact females, 39.86% spayed females, 6.95% intact males and 47.49% neutered males. 84.2% were mixed breed cats. Age at death was known for 2,974 cases with a median of 9.07 years. Cancer was the most common pathophysiologic cause of death (35.81%) and was identified in 41.3% of cats. When categorized by organ system, mortality was most attributed to multiorgan/systemic (21.72%). Renal histologic abnormalities were noted in 62.84% of cats but was considered the primary cause of death in only 13.06% of cats. Intact female and male cats had significantly shorter lifespans than their spayed or neutered counterparts. FeLV positive status was associated with decreased longevity (P<0.0001) while FIV status was not. This study reports on risk factors associated with mortality and highlights areas of research that may contribute to improved lifespan in cats

Inflammatory cytokines directly disrupt the bovine intestinal epithelial barrier.

The small intestinal mucosa constitutes a physical barrier separating the gut lumen from sterile internal tissues. Junctional complexes between cells regulate transport across the barrier, preventing water loss and the entry of noxious molecules or pathogens. Inflammatory diseases in cattle disrupt this barrier; nonetheless, mechanisms of barrier disruption in cattle are poorly understood. We investigated the direct effects of three inflammatory cytokines, TNFα, IFNγ, and IL-18, on the bovine intestinal barrier utilizing intestinal organoids. Flux of fluorescein isothiocyanate (FITC)-labeled dextran was used to investigate barrier permeability. Immunocytochemistry and transmission electron microscopy were used to investigate junctional morphology, specifically tortuosity and length/width, respectively. Immunocytochemistry and flow cytometry was used to investigate cellular turnover via proliferation and apoptosis. Our study shows that 24-h cytokine treatment with TNFα or IFNγ significantly increased dextran permeability and tight junctional tortuosity, and reduced cellular proliferation. TNFα reduced the percentage of G2/M phase cells, and IFNγ treatment increased cell apoptotic rate. IL-18 did not directly induce significant changes to barrier permeability or cellular turnover. Our study concludes that the inflammatory cytokines, TNFα and IFNγ, directly induce intestinal epithelial barrier dysfunction and alter the tight junctional morphology and rate of cellular turnover in bovine intestinal epithelial cells

Cause of death in all cats and cats ≥1 year of age at the time of death categorized by organ system, sex and spay neuter status.

Cause of death in all cats and cats ≥1 year of age at the time of death categorized by organ system, sex and spay neuter status.</p