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Cambrian-Devonian sedimentary rocks of the northern Canadian Cordillera record both the establishment and demise of the Great American Carbonate Bank, a widespread carbonate platform system that fringed the ancestral continental margins of North America (Laurentia). Here, we present a new examination of the deep-water Road River Group of the Richardson Mountains, Yukon, Canada, which was deposited in an intra-platformal embayment or seaway within the Great American Carbonate Bank called the Richardson trough. Eleven detailed stratigraphic sections through the Road River Group along the upper canyon of the Peel River are compiled and integrated with geological mapping, facies analysis, carbonate and organic carbon isotope chemostratigraphy, and new biostratigraphic results to formalize four new formations within the type area of the Richardson Mountains (Cronin, Mount Hare, Tetlit, and Vittrekwa). We recognize nine mixed carbonate and siliciclastic deep-water facies associations in the Road River Group and propose these strata were deposited in basin-floor to slope environments. New biostratigraphic data suggest the Road River Group spans the late Cambrian (Furongian) - Middle Devonian (Eifelian), and new chemostratigraphic data record multiple global carbon isotopic events, including the late Cambrian Steptoean positive carbon isotope excursion, the Late Ordovician Guttenberg excursion, the Silurian Aeronian, Valgu, Mulde (mid-Homerian), Ireviken (early Sheinwoodian), and Lau excursions, and the Early Devonian Klonk excursion. Together, these new data not only help clarify nomenclatural debate centered around the Road River Group, but also provide critical new sedimentological, biostratigraphic, and isotopic data for these widely distributed rocks of the northern Canadian Cordillera. Key words: Road River Group, Yukon, stratigraphy, chemostratigraphy, biostratigraphy. Des roches sedimentaires du Cambrien au Devonien du nord de la Cordillere canadienne temoignent de l'etablissement et de la fin du grand banc de carbonates americain, un vaste systeme de plateformes carbonatees qui bordait les marges continentales ancestrales de l'Amerique du Nord (Laurentie). Nous presentons les resultats d'un nouvel examen du Groupe de Road River, une unite d'eau profonde, des monts Richardson (Yukon, Canada), qui a ete depose dans un enfoncement ou un bras de mer intra-plateforme au sein du grand banc de carbonates americain appele la fosse de Richardson. Onze coupes stratigraphiques detaillees a travers le Groupe de Road River le long du canyon superieur de la riviere Peel sont compilees et integrees a la cartographie geologique, l'analyse des facies, la chimiostratigraphie des carbonates et des isotopes de carbone organique et de nouveaux resultats de biostratigraphie, permettant de definir quatre nouvelles formations dans la region type des monts Richardson (Cronin, Mount Hare, Tetlit et Vittrekwa). Nous relevons neuf associations de facies mixtes carbonates et silicoclastiques d'eau profonde dans le groupe de Road River et proposons que ces strates ont ete deposees dans des milieux allant de fonds de bassin a des talus. De nouvelles donnees biostratigraphiques donnent a penser que le Groupe de Road River s'etalerait du Cambrien tardif (Furongien) au Devonien moyen (Eifelien), et de nouvelles donnees chimiostratigraphiques font ressortir plusieurs episodes d'envergure planetaire du registre des isotopes du carbone, dont l'excursion isotopique positive steptoeenne au Cambrien tardif, l'excursion de Guttenberg a l'Ordovicien tardif, les excursions aeronien, de Valgu, de Mulde (Homerien intermediaire), d'Ireviken (Sheinwoodien precoce) et de Lau au Silurien et l'excursion de Klonk au Devonien precoce. Collectivement, ces nouvelles donnees aident non seulement a eclairer des debats relatifs a la nomenclature centres sur le Groupe de Road River, mais fournissent aussi de nouvelles donnees sedimentologiques, bio stratigraphiques et isotopiques cles sur ces roches largement repandues du nord de la Cordillere canadienne. [Traduit par la Redaction] Mots-cles: Groupe de Road River, Yukon, stratigraphie, chimiostratigraphie, biostratigraphie., Introduction The early Paleozoic witnessed major evolutionary radiations and biotic crises that dramatically altered animal ecosystems (Bambach et al. 2002; Alroy et al. 2008; Servais et al. 2008; Erwin et [...]

Exosomes, as functional paracrine units of therapeutic cells, can partially reproduce the reparative properties of their parental cells. The constitution of exosomes, as well as their biological activity, largely depends on the cells that secrete them. We isolated exosomes from explant-derived cardiac stromal cells from patients with heart failure (FEXO) or from normal donor hearts (NEXO) and compared their regenerative activities in vitro and in vivo. Patients in the FEXO group exhibited an impaired ability to promote endothelial tube formation and cardiomyocyte proliferation in vitro. Intramyocardial injection of NEXO resulted in structural and functional improvements in a murine model of acute myocardial infarction. In contrast. FEXO therapy exacerbated cardiac function and left ventricular remodeling. microRNA array and PCR analysis revealed dysregulation of miR-21-5p in FEXO. Restoring miR-21-5p expression rescued FEXO's reparative function, whereas blunting miR-21-5p expression in NEXO diminished its therapeutic benefits. Further mechanistic studies revealed that miR-21-5p augmented Akt kinase activity through the inhibition of phosphatase and tensin homolog. Taken together, the heart failure pathological condition altered the miR cargos of cardiac-derived exosomes and impaired their regenerative activities. miR-21-5p contributes to exosome-mediated heart repair by enhancing angiogenesis and cardiomyocyte survival through the phosphatase and tensin homolog/Akt pathway., Introduction Mounting lines of evidence, including that from our laboratory (1-4), have demonstrated that cell-based therapy holds great promise for the regeneration of injured heart muscle (5-12). Cell-based products must [...]

Previous reports have indicated the reciprocal effects of nicotine and ethanol on their rewarding and reinforcing properties, but studies using methodological approaches resembling substance use in vulnerable populations are lacking. In our study, rats first self-administered ethanol, and their sensitivity to ethanol's reinforcing effects was assessed using a reinforcer demand modeling approach. Subsequently, rats were equipped with intravenous catheters to self-administer nicotine, and their sensitivity to nicotine's reinforcing effects was evaluated using the same approach. In the final phase, rats were allowed to self-administer ethanol and nicotine concurrently, investigating the influence of one substance on the rate of responding for the other substance. Group analyses revealed notable differences in demand among sucrose, sweetened ethanol, and ethanolalone, with sucrose demonstrating the highest demand and ethanol-alone exhibiting greater sensitivity to changes in cost. At the individual level, our study finds significant correlations between rats' demand for sucrose and sweetened ethanol, suggesting parallel efforts for both substances. Our individual data also suggest interconnections in the elasticity of demand for sweetened ethanol and ethanol-alone, as well as a potential relationship in price response patterns between ethanol and nicotine. Furthermore, concurrent self-administration of ethanol and nicotine at the group level displayed reciprocal effects, with reduced responding for nicotine in the presence of ethanol and increased responding for ethanol in the presence of nicotine. This study provides valuable insights into modeling the co-use of ethanol and nicotine and assessing their interaction effects using reinforcer demand modeling and concurrent self-administration or noncontingent administration tests. These findings contribute to our understanding of the complex interplay between ethanol and nicotine and have implications for elucidating the underlying mechanisms involved in polydrug use. [ABSTRACT FROM AUTHOR]