Activation of PyMT in β Cells Induces Irreversible Hyperplasia, but Oncogene-Dependent Acinar Cell Carcinomas When Activated in Pancreatic Progenitors

It is unclear whether the cellular origin of various forms of pancreatic cancer involves transformation or transdifferentiation of different target cells or whether tumors arise from common precursors, with tumor types determined by the specific genetic alterations. Previous studies suggested that pancreatic ductal carcinomas might be induced by polyoma middle T antigen (PyMT) expressed in non-ductal cells. To ask whether PyMT transforms and transdifferentiates endocrine cells toward exocrine tumor phenotypes, we generated transgenic mice that carry tetracycline-inducible PyMT and a linked luciferase reporter. Induction of PyMT in β cells causes β-cell hyperplastic lesions that do not progress to malignant neoplasms. When PyMT is de-induced, β cell proliferation and growth cease; however, regression does not occur, suggesting that continued production of PyMT is not required to maintain the viable expanded β cell population. In contrast, induction of PyMT in early pancreatic progenitor cells under the control of Pdx1 produces acinar cell carcinomas and β-cell hyperplasia. The survival of acinar tumor cells is dependent on continued expression of PyMT. Our findings indicate that PyMT can induce exocrine tumors from pancreatic progenitor cells, but cells in the β cell lineage are not transdifferentiated toward exocrine cell types by PyMT; instead, they undergo oncogene-dependent hyperplastic growth, but do not require PyMT for survival

Carnivore Translocations and Conservation: Insights from Population Models and Field Data for Fishers (Martes pennanti)

Translocations are frequently used to restore extirpated carnivore populations. Understanding the factors that influence translocation success is important because carnivore translocations can be time consuming, expensive, and controversial. Using population viability software, we modeled reintroductions of the fisher, a candidate for endangered or threatened status in the Pacific states of the US. Our model predicts that the most important factor influencing successful re-establishment of a fisher population is the number of adult females reintroduced (provided some males are also released). Data from 38 translocations of fishers in North America, including 30 reintroductions, 5 augmentations and 3 introductions, show that the number of females released was, indeed, a good predictor of success but that the number of males released, geographic region and proximity of the source population to the release site were also important predictors. The contradiction between model and data regarding males may relate to the assumption in the model that all males are equally good breeders. We hypothesize that many males may need to be released to insure a sufficient number of good breeders are included, probably large males. Seventy-seven percent of reintroductions with known outcomes (success or failure) succeeded; all 5 augmentations succeeded; but none of the 3 introductions succeeded. Reintroductions were instrumental in reestablishing fisher populations within their historical range and expanding the range from its most-contracted state (43% of the historical range) to its current state (68% of the historical range). To increase the likelihood of translocation success, we recommend that managers: 1) release as many fishers as possible, 2) release more females than males (55–60% females) when possible, 3) release as many adults as possible, especially large males, 4) release fishers from a nearby source population, 5) conduct a formal feasibility assessment, and 6) develop a comprehensive implementation plan that includes an active monitoring program

Reframing professional development through understanding authentic professional learning

Continuing to learn is universally accepted and expected by professionals and other stakeholders across all professions. However, despite changes in response to research findings about how professionals learn, many professional development practices still focus on delivering content rather than enhancing learning. In exploring reasons for the continuation of didactic practices in professional development, this article critiques the usual conceptualization of professional development through a review of recent literature across professions. An alternative conceptualization is proposed, based on philosophical assumptions congruent with evidence about professional learning from seminal educational research of the past two decades. An argument is presented for a shift in discourse and focus from delivering and evaluating professional development programs to understanding and supporting authentic professional learning

Copper complexes of the functionalised tripodal ligand tris(2-pyridyl)methylamine and its derivatives

The coordination chemistry of the new tripodal ligand tris(2-pyridyl)methylamine (tpm) with copper(I), copper(II) and zinc(II) has been investigated. The synthesis of tpm can readily be modified to access a variety of related tripodal ligands such as 2-(methylsulfanyl)-1,1-di(2-pyridyl)ethylamine (mde); in addition, the primary amine function can be derivatised to extend further the range of complexes obtained. tpm itself is a versatile ligand, showing three distinct coordination modes: bidentate (py, NH2), tridentate (2py, NH2) and tridentate (3py). Complexes of stoichiometries Cu(tpm)(n) (n=1-3) have been obtained. The (2py, NH2) coordination mode is illustrated by the crystal structure of [Cu(tpm)(2)][BF4](2). Me2CO, whilst (3py) coordination is found in the crystal structures of [Cu(SO4)(tpm)(H2O)]. 3H(2)O, [{Cu(tpm)}(2)Br-3]Br . 3MeOH and also the zinc complex [Zn(tpm)(H2O)(3)](2)[Zn(H2O)(6)][SO4](3). 3H(2)O. Amide derivatives of tpm give complexes of stoichiometry CuL2, and the crystal structures of [Cu(tpma)(2)][BF4](2) [tpma=tris(2-pyridyl)methylacetamide] and [Cu(tpms)(2)]. 8H(2)O {tpmsH=4-oxo-4-[tris(2-pyridyl)methylamino]butanoic acid} have been determined. The crystal structure of the sulfate-bridged dimeric complex [{Cu(SO4)(mde)}(2)]. 3H(2)O shows the mde ligand to be tridentate, with (2py, NH2) coordination

Shining light on the stability of metal thiosemicarbazonate complexes in living cells by FLIM

Complexes of Cu(ii), Ni(ii) and Zn(ii) have been prepared with bis(thiosemicarbazonate) ligands bearing a pendant Bodipy fluorophore both with (ATSMBodipy) and without (GTSBodipy) backbone methyl groups. Biophysical analysis using steady state confocal laser scanning fluorescence images and excited state fluorescence lifetime imaging microscopy (FLIM) data obtained from live cells under aerobic uptake conditions has uniquely allowed both the spatial distribution and degree of dissociation of the complexes to be assessed. The CuATSMBodipy complex is virtually intact after 20 min and 1 h whereas the corresponding CuGTSBodipy complex is totally dissociated. The complexes ZnATSMBodipy and NiATSMBodipy show little evidence for dissociation. The relevance of this data to the biomedical applications of bis(thiosemicarbazonate) complexes for imaging applications and implications for the treatment of disease such as Alzheimer's and the PET imaging of hypoxia are discussed. This journal is © The Royal Society of Chemistry 2013