Silencing Mist1 gene expression is essential for recovery from acute pancreatitis

Acinar cells of the exocrine pancreas are tasked with synthesizing, packaging and secreting vast quantities of pro-digestive enzymes to maintain proper metabolic homeostasis for the organism. Because the synthesis of high levels of hydrolases is potentially dangerous, the pancreas is prone to acute pancreatitis (AP), a disease that targets acinar cells, leading to acinar-ductal metaplasia (ADM), inflammation and fibrosis-events that can transition into the earliest stages of pancreatic ductal adenocarcinoma. Despite a wealth of information concerning the broad phenotype associated with pancreatitis, little is understood regarding specific transcriptional regulatory networks that are susceptible to AP and the role these networks play in acinar cell and exocrine pancreas responses. In this study, we examined the importance of the acinar-specific maturation transcription factor MIST1 to AP damage and organ recovery. Analysis of wild-type and Mist1 conditional null mice revealed that Mist1 gene transcription and protein accumulation were dramatically reduced as acinar cells underwent ADM alterations during AP episodes. To test if loss of MIST1 function was primarily responsible for the damaged status of the organ, mice harboring a Cre-inducible Mist1 transgene (iMist1) were utilized to determine if sustained MIST1 activity could alleviate AP damage responses. Unexpectedly, constitutive iMist1 expression during AP led to a dramatic increase in organ damage followed by acinar cell death. We conclude that the transient silencing of Mist1 expression is critical for acinar cells to survive an AP episode, providing cells an opportunity to suppress their secretory function and regenerate damaged cells. The importance of MIST1 to these events suggests that modulating key pancreas transcription networks could ease clinical symptoms in patients diagnosed with pancreatitis and pancreatic cancer. © 2015 Karki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

The genome of the jellyfish Aurelia and the evolution of animal complexity

We present the genome of the moon jellyfish Aurelia, a genome from a cnidarian with a medusa life stage. Our analyses suggest that gene gain and loss in Aurelia is comparable to what has been found in its morphologically simpler relatives—the anthozoan corals and sea anemones. RNA sequencing analysis does not support the hypothesis that taxonomically restricted (orphan) genes play an oversized role in the development of the medusa stage. Instead, genes broadly conserved across animals and eukaryotes play comparable roles throughout the life cycle. All life stages of Aurelia are significantly enriched in the expression of genes that are hypothesized to interact in protein networks found in bilaterian animals. Collectively, our results suggest that increased life cycle complexity in Aurelia does not correlate with an increased number of genes. This leads to two possible evolutionary scenarios: either medusozoans evolved their complex medusa life stage (with concomitant shifts into new ecological niches) primarily by re-working genetic pathways already present in the last common ancestor of cnidarians, or the earliest cnidarians had a medusa life stage, which was subsequently lost in the anthozoans. While we favour the earlier hypothesis, the latter is consistent with growing evidence that many of the earliest animals were more physically complex than previously hypothesized

Gender disparities in colloquium speakers at top universities

Colloquium talks at prestigious universities both create and reflect academic researchers' reputations. Gender disparities in colloquium talks can arise through a variety of mechanisms. The current study examines gender differences in colloquium speakers at 50 prestigious US colleges and universities in 2013-2014. Using archival data, we analyzed 3,652 talks in six academic disciplines. Men were more likely than women to be colloquium speakers even after controlling for the gender and rank of the available speakers. Eliminating alternative explanations (e.g., women declining invitations more often than men), our follow-up data revealed that female and male faculty at top universities reported no differences in the extent to which they (i) valued and (ii) turned down speaking engagements. Additional data revealed that the presence of women as colloquium chairs (and potentially on colloquium committees) increased the likelihood of women appearing as colloquium speakers. Our data suggest that those who invite and schedule speakers serve as gender gatekeepers with the power to create or reduce gender differences in academic reputations

Molecular profiling of multiplexed gene markers to assess viability of ex vivo human colon explant cultures

© Janice E. Drew et al. 2015; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. Acknowledgments The authors would like to thank the patients who kindly donated tissue samples, Sally Chalmers of the Tayside Tissue Bank for her help with collecting of the tissue donor samples, Emma Moss for advice on human colon dissection and explant culture, and Claus Dieter Mayer, Biomathematics and Statistics Scotland, for advice on statistical analysis. This work was supported by the Scottish Government (GT403), Scottish Universities Life Science Alliance, and TENOVUS Scotland.Peer reviewedPublisher PD

Latrepirdine: Molecular mechanisms underlying potential therapeutic roles in Alzheimer’s and other neurodegenerative diseases

Latrepirdine (DimebonTM) was originally marketed as a non-selective antihistamine in Russia. It was repurposed as an effective treatment for patients suffering from Alzheimer’s disease (AD) and Huntington’s disease (HD) following preliminary reports showing its neuroprotective functions and ability to enhance cognition in AD and HD models. However, latrepirdine failed to show efficacy in phase III trials in AD and HD patients following encouraging phase II trials. The failure of latrepirdine in the clinical trials has highlighted the importance of understanding the precise mechanism underlying its cognitive benefits in neurodegenerative diseases before clinical evaluation. Latrepirdine has shown to affect a number of cellular functions including multireceptor activity, mitochondrial function, calcium influx and intracellular catabolic pathways; however, it is unclear how these properties contribute to its clinical benefits. Here, we review the studies investigating latrepirdine in cellular and animal models to provide a complete evaluation of its mechanisms of action in the central nervous system. In addition, we review recent studies that demonstrate neuroprotective functions for latrepirdine-related class of molecules including the β-carbolines and aminopropyl carbazoles in AD, Parkinson’s disease and amyotrophic lateral sclerosis models. Assessment of their neuroprotective effects and underlying biological functions presents obvious value for developing structural analogues of latrepirdine for dementia treatment

Ohio Economic Insects and Related Anthropods

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Expansion of a single transposable element family is associated with genome-size increase and radiation in the genus Hydra

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Transposable elements are one of the major contributors to genome-size differences in metazoans. Despite this, relatively little is known about the evolutionary patterns of element expansions and the element families involved. Here we report a broad genomic sampling within the genus Hydra, a freshwater cnidarian at the focal point of diverse research in regeneration, symbiosis, biogeography, and aging. We find that the genome of Hydra is the result of an expansion event involving long interspersed nuclear elements and in particular a single family of the chicken repeat 1 (CR1) class. This expansion is unique to a subgroup of the genus Hydra, the brown hydras, and is absent in the green hydra, which has a repeat landscape similar to that of other cnidarians. These features of the genome make Hydra attractive for studies of transposon-driven genome expansions and speciation

Self-Affirmation Improves Problem-Solving under Stress

High levels of acute and chronic stress are known to impair problem-solving and creativity on a broad range of tasks. Despite this evidence, we know little about protective factors for mitigating the deleterious effects of stress on problem-solving. Building on previous research showing that self-affirmation can buffer stress, we tested whether an experimental manipulation of self-affirmation improves problem-solving performance in chronically stressed participants. Eighty undergraduates indicated their perceived chronic stress over the previous month and were randomly assigned to either a self-affirmation or control condition. They then completed 30 difficult remote associate problem-solving items under time pressure in front of an evaluator. Results showed that self-affirmation improved problem-solving performance in underperforming chronically stressed individuals. This research suggests a novel means for boosting problem-solving under stress and may have important implications for understanding how self-affirmation boosts academic achievement in school settings. © 2013 Creswell et al