Augmenter of liver regeneration enhances the success rate of fetal pancreas transplantation in rodents

Background. Treatment of fetal pancreas (FP) isografts with insulin- like growth factor-I greatly improves the rate of conversion to euglycemia in diabetic rats. Complete knowledge of other factors that may facilitate the engraftment and function of FP in vivo is still embryonic. Augmenter of liver regeneration (ALR) is a newly described polypeptide growth factor found in weanling rat livers. ALR has trophic effects on regenerating liver. We studied the effects of in situ administration of this agent on FP isografts in rats. Methods. Streptozotocin-diabetic Lewis rats (blood glucose >300 mg/dl) received 16 FP isografts transplanted intramuscularly. ALR was delivered from day 1 through day 14, in doses of 40 or 400 ng/kg/d. Animals were followed for 3 months with serial weights and blood glucose monitoring. These animals were compared with those treated with vehicle alone. Results. Of the group treated with ALR at 40 ng/kg/day for 14 days, 89% (eight of nine) were euglycemic (P=0.0003). Of the group treated with ALR at 400 ng/kg/day for 14 days, 88% (seven of eight) were euglycemic (P=0.0007). Of the group treated with vehicle alone, none of the six were euglycemic. Euglycemia is defined here as glucose<200 mg/dl for 3 days. Pathology of the intramuscular transplant site showed patches of islet tissue embedded in fat. These patches demonstrated insulin immunoreactivity. Conclusions. Diabetes was reversed in a significantly greater proportion of FP + ALR-treated recipients than those animals treated with vehicle alone. Local delivery of growth factors my be used as an adjunct to FP transplantation to improve the rate of success. This in situ model may be useful to further evaluate other soluble factors

Detection of an Optical Counterpart to the ALFALFA Ultra-compact High Velocity Cloud AGC 249525

We report on the detection at $>$98% confidence of an optical counterpart to AGC 249525, an Ultra-Compact High Velocity Cloud (UCHVC) discovered by the ALFALFA blind neutral hydrogen survey. UCHVCs are compact, isolated HI clouds with properties consistent with their being nearby low-mass galaxies, but without identified counterparts in extant optical surveys. Analysis of the resolved stellar sources in deep $g$- and $i$-band imaging from the WIYN pODI camera reveals a clustering of possible Red Giant Branch stars associated with AGC 249525 at a distance of 1.64$\pm$0.45 Mpc. Matching our optical detection with the HI synthesis map of AGC 249525 from Adams et al. (2016) shows that the stellar overdensity is exactly coincident with the highest-density HI contour from that study. Combining our optical photometry and the HI properties of this object yields an absolute magnitude of $-7.1 \leq M_V \leq -4.5$, a stellar mass between $2.2\pm0.6\times10^4 M_{\odot}$ and $3.6\pm1.0\times10^5 M_{\odot}$, and an HI to stellar mass ratio between 9 and 144. This object has stellar properties within the observed range of gas-poor Ultra-Faint Dwarfs in the Local Group, but is gas-dominated.Comment: 9 pages, 4 figures; accepted to ApJ

Innovating Pedagogy 2015: Open University Innovation Report 4

This series of reports explores new forms of teaching, learning and assessment for an interactive world, to guide teachers and policy makers in productive innovation. This fourth report proposes ten innovations that are already in currency but have not yet had a profound influence on education. To produce it, a group of academics at the Institute of Educational Technology in The Open University collaborated with researchers from the Center for Technology in Learning at SRI International. We proposed a long list of new educational terms, theories, and practices. We then pared these down to ten that have the potential to provoke major shifts in educational practice, particularly in post-school education. Lastly, we drew on published and unpublished writings to compile the ten sketches of new pedagogies that might transform education. These are summarised below in an approximate order of immediacy and timescale to widespread implementation

A gene regulatory network armature for T lymphocyte specification

Choice of a T lymphoid fate by hematopoietic progenitor cells depends on sustained Notch–Delta signaling combined with tightly regulated activities of multiple transcription factors. To dissect the regulatory network connections that mediate this process, we have used high-resolution analysis of regulatory gene expression trajectories from the beginning to the end of specification, tests of the short-term Notch dependence of these gene expression changes, and analyses of the effects of overexpression of two essential transcription factors, namely PU.1 and GATA-3. Quantitative expression measurements of >50 transcription factor and marker genes have been used to derive the principal components of regulatory change through which T cell precursors progress from primitive multipotency to T lineage commitment. Our analyses reveal separate contributions of Notch signaling, GATA-3 activity, and down-regulation of PU.1. Using BioTapestry (www.BioTapestry.org), the results have been assembled into a draft gene regulatory network for the specification of T cell precursors and the choice of T as opposed to myeloid/dendritic or mast-cell fates. This network also accommodates effects of E proteins and mutual repression circuits of Gfi1 against Egr-2 and of TCF-1 against PU.1 as proposed elsewhere, but requires additional functions that remain unidentified. Distinctive features of this network structure include the intense dose dependence of GATA-3 effects, the gene-specific modulation of PU.1 activity based on Notch activity, the lack of direct opposition between PU.1 and GATA-3, and the need for a distinct, late-acting repressive function or functions to extinguish stem and progenitor-derived regulatory gene expression