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Let me begin with an expression of gratitude to Verena Meyer, Thomas Hunter, Penny Edwards, Laurie Sears, Tom Patton and Kaja McGowan. It is a fare privilege to be read [...]

Multicenter international clinical trials demonstrated the clinical safety and efficacy by using stem cell educator therapy to treat type 1 diabetes (T1D) and other autoimmune diseases. Previous studies characterized the peripheral blood insulin-producing cells (PB-IPC) from healthy donors with high potential to give rise to insulin-producing cells. PB-IPC displayed the molecular marker glucose transporter 2 (GLUT2), contributing to the glucose transport and sensing. To improve the clinical efficacy of stem cell educator therapy in the restoration of islet β-cell function, we explored the GLUT2 expression on PB-IPC in recent onset and longstanding T1D patients. In the Food and Drug Administration (FDA)-approved phase 2 clinical studies, patients received one treatment with the stem cell educator therapy. Peripheral blood mononuclear cells (PBMC) were isolated for flow cytometry analysis of PB-IPC and other immune markers before and after the treatment with stem cell educator therapy. Flow cytometry revealed that both recent onset and longstanding T1D patients displayed very low levels of GLUT2 on PB-IPC. After the treatment with stem cell educator therapy, the percentages of GLUT2+CD45RO+ PB-IPC were markedly increased in these T1D subjects. Notably, we found that T1D patients shared common clinical features with patients with other autoimmune and inflammation-associated diseases, such as displaying low or no expression of GLUT2 on PB-IPC at baseline and exhibiting a high profile of the inflammatory cytokine interleukin (IL)-1β. Flow cytometry demonstrated that their GLUT2 expressions on PB-IPC were also markedly upregulated, and the levels of IL-1β-positive cells were significantly downregulated after the treatment with stem cell educator therapy. Stem cell educator therapy could upregulate the GLUT2 expression on PB-IPC and restore their function in T1D patients, leading to the improvement of clinical outcomes. The clinical data advances current understanding about the molecular mechanisms underlying the stem cell educator therapy, which can be expanded to treat patients with other autoimmune and inflammation-associated diseases. [ABSTRACT FROM AUTHOR]

A large collection of dentigerous jaws quarried from the Gao Mine locality, late Paleocene, Paskapoo Formation, central Alberta, Canada, documents a new species of the early Paleogene phenacodontid 'condylarth' Ectocion Cope, 1882. The new species, Ectocion stockeyae, the smallest of the genus, occurs well before the abrupt global warming at the Paleocene-Eocene Thermal Maximum, an event purportedly causing the rapid evolution of 'dwarfed' mammals, including a species of Ectocion; however, there is no evidence of increased temperatures at Gao Mine to account for the small size of Ectocion stockeyae, raising questions of the relationship between temperature and body size in Ectocion. Ectocion stockeyae also exhibits sexual dimorphism of the canines, a pattern in mammals often associated with a population structure in which the males are relatively few and polygynous, resulting in intense male rivalry for mating success. The sample of Ectocion stockeyae from Gao Mine includes a substantial majority of 'juvenile' individuals retaining deciduous posterior premolars, many even after eruption of the molars had been completed, suggesting short life spans, accelerated growth, and rapid dental development in this species as expressed in Schultz's Rule. Key words: Mammalia, Paleocene, phenacodontid, Ectocion stockeyae, paleobiology. Une imposante collection de machoires dentigeres prelevees de la localite de Gao Mine, dans la Formation de Paskapoo du Pleistocene tardif du centre de lAlberta (Canada), documente une nouvelle espece de phenacodontide << condylarthe >> Ectocion Cope, 1882 du Paleogene precoce. La nouvelle espece, Ectocion stockeyae, la plus petite du genre, apparait bien avant le rechauffement planetaire subit au maximum thermique du passage Paleocene-Eocene, un episode qui aurait cause l evolution rapide de mammiferes << nains>>, dont une espece d'Ectocion; aucun indice de temperatures elevees n'a toutefois ete releve a Gao Mine pour expliquer la petite taille d'Ectocion stockeyae, ce qui souleve des questions concernant la relation entre la temperature et la taille du corps chez les Ectocion. Ectocion stockeyae presente egalement un dimorphisme sexuel des canines, ce qui, chez les mammiferes, est souvent associe a une structure de la population dans laquelle les males sont relativement peu nombreux et polygynes, entrainant une intense rivalite entre males pour assurer leur succes de reproduction. L'echantillon d'Ectocion stockeyae de Gao Mine comprend une majorite substantielle de specimens <> qui conservent des premolaires posterieures lacteales meme, dans de nombreux cas, une fois l'eruption des molaires terminee, ce qui indiquerait une longevite faible, une croissance acceleree et un developpement rapide des dents chez cette espece, conformement a la regle de Schultz. Mots-cles: mammiferes, Paleocene, phenacodontide, Ectocion stockeyae, paleobiologie., Introduction Paleocene mammals from western Canada are presently known from over 50 localities, most of which occur in deposits of the Alberta Syncline, north from the Porcupine Hills (Fox 1990; [...]