Emerging diabetes therapies: Bringing back the β-cells

Stem cell therapies are finally coming of age as a viable alternative to pancreatic islet transplantation for the treatment of insulin-dependent diabetes. Several clinical trials using human embryonic stem cell (hESC)-derived β-like cells are currently underway, with encouraging preliminary results. Remaining challenges notwithstanding, these strategies are widely expected to reduce our reliance on human isolated islets for transplantation procedures, making cell therapies available to millions of diabetic patients. At the same time, advances in our understanding of pancreatic cell plasticity and the molecular mechanisms behind β-cell replication and regeneration have spawned a multitude of translational efforts aimed at inducing β-cell replenishment in situ through pharmacological means, thus circumventing the need for transplantation. We discuss here the current state of the art in hESC transplantation, as well as the parallel quest to discover agents capable of either preserving the residual mass of β-cells or inducing their proliferation, transdifferentiation or differentiation from progenitor cells. Stem cell-based replacement therapies in the mold of islet transplantation are already around the corner, but a permanent cure for type 1 diabetes will likely require the endogenous regeneration of β-cells aided by interventions to restore the immune balance. The promise of current research avenues and a strong pipeline of clinical trials designed to tackle these challenges bode well for the realization of this goal

The Genera of Pleurobemini (Bivalvia: Unionidae: Ambleminae)

The unionid tribe Pleurobemini is diverse but poorly-understood phylogenetically. Current classification recognizes two highly diverse genera, Elliptio Rafinesque, 1819 and Pleurobema Rafinesque, 1820, besides the moderately diverse Fusconaia Simpson, 1900, and several genera with one to three species. However, classification at the species and genus level has been problematic. Molecular data and re-examination of shell morphology and anatomy indicate new groupings of these taxa. Several genera proposed by early workers such as Rafinesque and Swainson are available, but are poorly-characterized and are often overlooked. We analyzed two mitochondrial genes, cox1 and nad1, for 50 species assigned to Pleurobemini, including the type species of each genus and as many other species as possible. Although the majority of studied species in Elliptio, Pleurobema, and Fusconaia show close affinities to the respective type species, the affinities of others are problematic. Genera or subgenera such as Eurynia Rafinesque, 1819, SintoxiaRafinesque, 1820, and Pleuronaia Frierson, 1927, generally regarded as subjective synonyms, apply to some clades. Other clades or unaffiliated species have no available name. Quincuncina burkei (Walker, 1922), the type of the genus Quincuncina Ortmann, 1922, is assigned to Fusconaia Simpson, 1900. Fusconaia apalachicola (Williams and Fradkin, 1999), F. ebenus (Lea, 1831), F. rotulata (Wright, 1899) (also listed as Obovaria rotulata), F. succissa (Lea, 1852), Cyclonaias tuberculatus (Rafinesque, 1820), Uniomerus Conrad, 1853, and the Quincuncina infucata (Conrad, 1834) complex are all excluded from Pleurobemini. The first three are placed in the new genus Reginaia Campbell and Lydeard; Uniomerus Conrad, 1853 is assigned to Quadrulini; and the remainder belong in the pustulosa Lea, 1831 group of Quadrulini (genus RotundariaRafinesque, 1820)