The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors

Pancreas development begins with the formation of buds at specific sites in the embryonic foregut endoderm. We used recombination-based lineage tracing in vivo to show that Ptf1a (also known as PTF1-p48) is expressed at these early stages in the progenitors of pancreatic ducts, exocrine and endocrine cells, rather than being an exocrine-specific gene as previously described. Moreover, inactivation of Ptf1a switches the character of pancreatic progenitors such that their progeny proliferate in and adopt the normal fates of duodenal epithelium, including its stem-cell compartment. Consistent with the proposal that Ptf1a supports the specification of precursors of all three pancreatic cell types, transgene-based expression of Pdx1, a gene essential to pancreas formation, from Ptf1a cis-regulatory sequences restores pancreas tissue to Pdx1-null mice that otherwise lack mature exocrine and endocrine cells because of an early arrest in organogenesis. These experiments provide evidence that Ptf1a expression is specifically connected to the acquisition of pancreatic fate by undifferentiated foregut endoderm.     

Urogastrone-epidermal growth factor is trophic to the intestinal epithelium of parenterally fed rats

Summary The weight of the stomach, small intestine and colon and the mucosal crypt cell production rate of these tissues were significantly decreased after 10 days on an isocaloric TPN diet when compared to orally fed controls. Continuous infusion of recombinant beta urogastrone, at a dose below that needed to inhibit gastric acid secretion, largely prevented this decrease in crypt cell production rate and gastrointestinal tissue weights.     

The invasion and growth of Babesia bovis in tick tissue culture.

Erythrocytic forms of Babesia bovis inoculated into cell cultures of the tick Boophilus microplus invaded the tick cells and showed multiplication for up to 48 h after inoculation.     

Peptides and epithelial growth regulation

There is now considerable evidence implicating several peptides in the control of gastrointestinal epithelial cell proliferation and cell renewal. While some of these may act directly, many may be involved in regulating the powerful trophic effects of the intake and digestion of food on the gut epithelium. Several peptides have been associated with the regulation of intestinal cell proliferation. There is little doubt that gastrin is trophic to the stomach, but, its role in the rest of the gastrointestinal tract is debatable. Enteroglucagon has often been associated with increased intestinal epithelial proliferation, but at the moment all the evidence for this is circumstantial. The effects of peptide YY and bombesin warrant further study. The availability of recombinant epidermal growth factor (EGF) has recently enabled us to demonstrate a powerful trophic response to infused EGF throughout the gastrointestinal tract. The increasing availability of peptides will eventually allow the rigorous in vivo evaluation of the trophic role of these potentially very important peptides.     

The consistency,coherence and calibration of holistic,decomposed and recomposed judgemental probability forecasts

In this paper we make an empirical investigation of the relationship between the consistency, coherence and validity of probability judgements in a real-world forecasting context. Our results indicate that these measures of the adequacy of an individual's probability assessments are not closely related as we anticipated. Twenty-nine of our thirty-six subjects were better calibrated in point probabilities than in odds and our subjects were, in general more coherent using point probabilities than odds forecasts. Contrary to our expectations we found very little difference in forecasting response and performance between simple and compound holistic forecasts. This result is evidence against the ‘divide-and-conquer’ rationale underlying most applications of normative decision theory. In addition, our recompositions of marginal and conditional assessments into compound forecasts were no better calibrated or resolved than their holistic counterparts. These findings convey two implications for forecasting. First, untrained judgemental forecasters should use point probabilities in preference to odds. Second, judgemental forecasts of complex compound probabilities may be as well assessed holistically as they are using methods of decomposition and recomposition. In addition, our study provides a paradigm for further studies of the relationship between consistency, coherence and validity in judgemental probability forecasting.     

The teachers/practitioners corner the effects of indexing ARMA series using the consumer price index

The authors demonstrate that indexing a time series with an ARMA representation using the Consumer Price Index does not materially alter the ARMA form of the model. They further demonstrate that the forecasting error of the indexed series and of the product of the forecasts of the index and the time series are, for practical purpose, the same. Simulation results are reported for five model classes.     

Sequence of human tissue inhibitor of metalloproteinases and its identity to erythroid-potentiating activity

Collagen fibres form the stable architecture of connective tissues and their breakdown is a key irreversible step in many pathological conditions. The destruction of collagen is usually initiated by proteinases, the best known of which is the metalloproteinase collagenase (EC 3.4.24). Collagenase and related metalloproteinases are regulated at the level of their synthesis and secretion, through the action of specific stimuli such as hormones and cytokines, and also at the level of their extracellular activity through the action of a specific inhibitor, TIMP (tissue inhibitor of metalloproteinases), which irreversibly forms inactive complexes with metalloproteinases. Although the mechanisms governing the production of TIMP are unknown, immunologically identical forms of this glycoprotein have been detected in a wide variety of human body fluids and cell and tissue culture media. We therefore suggested that under physiological conditions this ubiquitous inhibitor predominates over active metalloproteinases and that tissue destruction may arise when any perturbation of this controlling excess arises. However, further progress towards testing this theory has been hindered by a lack of knowledge about the structure of TIMP and insufficient material for studying it in model systems. Here we describe the structure of TIMP predicted from its complementary DNA, its synthesis in Escherichia coli and transfected animal cells, and the finding that it is identical to a protein recently reported to have erythroid-potentiating activity (EPA).