Rats distinguish between absence of events and lack of evidence in contingency learning.

The goal of three experiments was to study whether rats are aware of the difference between absence of events and lack of evidence. We used a Pavlovian extinction paradigm in which lights consistently signaling sucrose were suddenly paired with the absence of sucrose. The crucial manipulation involved the absent outcomes in the extinction phase. Whereas in the Cover conditions, access to the drinking receptacle was blocked by a metal plate, in the No Cover conditions, the drinking receptacle was accessible. The Test phase showed that in the Cover conditions, the measured expectancies of sucrose were clearly at a higher level than in the No Cover conditions. We compare two competing theories potentially explaining the findings. A cognitive theory interprets the observed effect as evidence that the rats were able to understand that the cover blocked informational access to the outcome information, and therefore the changed learning input did not necessarily signify a change of the underlying contingency in the world. An alternative associationist account, renewal theory, might instead explain the relative sparing of extinction in the Cover condition as a consequence of context change. We discuss the merits of both theories as accounts of our data and conclude that the cognitive explanation is in this case preferred

Lineage fate of ductular reactions in liver injury and carcinogenesis.

Ductular reactions (DRs) are observed in virtually all forms of human liver disease; however, the histogenesis and function of DRs in liver injury are not entirely understood. It is widely believed that DRs contain bipotential liver progenitor cells (LPCs) that serve as an emergency cell pool to regenerate both cholangiocytes and hepatocytes and may eventually give rise to hepatocellular carcinoma (HCC). Here, we used a murine model that allows highly efficient and specific lineage labeling of the biliary compartment to analyze the histogenesis of DRs and their potential contribution to liver regeneration and carcinogenesis. In multiple experimental and genetic liver injury models, biliary cells were the predominant precursors of DRs but lacked substantial capacity to produce new hepatocytes, even when liver injuries were prolonged up to 12 months. Genetic modulation of NOTCH and/or WNT/β-catenin signaling within lineage-tagged DRs impaired DR expansion but failed to redirect DRs from biliary differentiation toward the hepatocyte lineage. Further, lineage-labeled DRs did not produce tumors in genetic and chemical HCC mouse models. In summary, we found no evidence in our system to support mouse biliary-derived DRs as an LPC pool to replenish hepatocytes in a quantitatively relevant way in injury or evidence that DRs give rise to HCCs

Pathophysiology of acute experimental pancreatitis: Lessons from genetically engineered animal models and new molecular approaches

The incidence of acute pancreatitis is growing and worldwide population-based studies report a doubling or tripling since the 1970s. 25% of acute pancreatitis are severe and associated with histological changes of necrotizing pancreatitis. There is still no specific medical treatment for acute pancreatitis. The average mortality resides around 10%. In order to develop new specific medical treatment strategies for acute pancreatitis, a better understanding of the pathophysiology during the onset of acute pancreatitis is necessary. Since it is difficult to study the early acinar events in human pancreatitis, several animal models of acute pancreatitis have been developed. By this, it is hoped that clues into human pathophysiology become possible. In the last decade, while employing molecular biology techniques, a major progress has been made. The genome of the mouse was recently sequenced. Various strategies are possible to prove a causal effect of a single gene or protein, using either gain-of-function (i.e., overexpression of the protein of interest) or loss-of-function studies (i.e., genetic deletion of the gene of interest). The availability of transgenic mouse models and gene deletion studies has clearly increased our knowledge about the pathophysiology of acute pancreatitis and enables us to study and confirm in vitro findings in animal models. In addition, transgenic models with specific genetic deletion or overexpression of genes help in understanding the role of one specific protein in a cascade of inflammatory processes such as pancreatitis where different proteins interact and co-react. This review summarizes the recent progress in this field. Copyright (c) 2005 S. Karger AG, Basel

Gauging the Effectiveness of Educational Technology Integration in Education: What the Best-Quality Meta-Analyses Tell Us

This chapter examines quantitative research in the literature of technology integration in education from the perspective of the meta-analyses of primary studies conducted from 1982 to 2015. The intent is to identify and review the best of these meta-analyses. Fifty-two meta-analyses were originally identified and evaluated for methodological quality using the Meta-Analysis Methodological Quality Review Guide (MMQRG), and the best 20 were selected and are included for review here. Some describe the effects of technology integration within specific content areas and some are more general. Technology integration in education is one of the most fluid areas of research, reflecting the incredible pace of the evolution of computer-based tools and applications. Just navigating through the vast primary empirical literature presents a real challenge to those interested in evaluating the educational effectiveness of technology. Systematic reviews in the field are numerous and quite diverse in their methodological quality, introducing potential bias in the interpretation of findings (Bernard RM, Borokhovski E, Schmid RF, Tamim RM. J Comput High Educ 26(3):183–209, 2014), thus bringing into question their applied value. This chapter identifies and reviews the best of these meta-analyses. In addition to overall statistical analyses of this collection, the findings of six of the most recent and best meta-analyses (after 2010) are summarized in more detail. The discussion focuses on the interpretation of the current findings, considers future alternatives to primary research in this area, and examines how meta-analysts might address them