OTULIN protects the intestinal epithelium from apoptosis during inflammation and infection

The intestinal epithelium is a single cell layer that is constantly renewed and acts as a physical barrier that separates intestinal microbiota from underlying tissues. In inflammatory bowel disease (IBD) in humans, as well as in experimental mouse models of IBD, this barrier is impaired, causing microbial infiltration and inflammation. Deficiency in OTU deubiquitinase with linear linkage specificity (OTULIN) causes OTULIN-related autoinflammatory syndrome (ORAS), a severe inflammatory pathology affecting multiple organs including the intestine. We show that mice with intestinal epithelial cell (IEC)-specific OTULIN deficiency exhibit increased susceptibility to experimental colitis and are highly sensitive to TNF toxicity, due to excessive apoptosis of OTULIN deficient IECs. OTULIN deficiency also increases intestinal pathology in mice genetically engineered to secrete excess TNF, confirming that chronic exposure to TNF promotes epithelial cell death and inflammation in OTULIN deficient mice. Mechanistically we demonstrate that upon TNF stimulation, OTULIN deficiency impairs TNF receptor complex I formation and LUBAC recruitment, and promotes the formation of the cytosolic complex II inducing epithelial cell death. Finally, we show that OTULIN deficiency in IECs increases susceptibility to Salmonella infection, further confirming the importance of OTULIN for intestinal barrier integrity. Together, these results identify OTULIN as a major anti-apoptotic protein in the intestinal epithelium and provide mechanistic insights into how OTULIN deficiency drives gastrointestinal inflammation in ORAS patients.</p

Metabolite-based inter-kingdom communication controls intestinal tissue recovery following chemotherapeutic injury

Cytotoxic chemotherapies have devastating side effects, particularly within thegastrointestinal tract. Gastrointestinal toxicity includes death and damage of the epitheliumand an imbalance in the intestinal microbiota, otherwise known as dysbiosis. Whetherdysbiosis is a direct contributor to tissue toxicity is a key area of focus. Here, from bothmammalian and bacterial perspectives, we uncover an intestinal epithelial celldeath-Enterobacteriaceae signaling axis that fuels dysbiosis. Specifically, our datademonstrate that chemotherapy-induced epithelial cell apoptosis, and the purine-containingmetabolites released from dying cells, drives the inter-kingdom transcriptional re-wiring of theEnterobacteriaceae, including fundamental shifts in bacterial respiration and promotion ofpurine utilization-dependent expansion, which in turn delays the recovery of the intestinal tract.Inhibition of epithelial cell death or restriction of the Enterobacteriaceae to homeostatic levelsreverses dysbiosis and improves intestinal recovery. These findings suggest that supportivetherapies that maintain homeostatic levels of Enterobacteriaceae may be useful in resolvingintestinal disease

How not to attack intelligent design creationism: philosophical misconceptions about methodological naturalism

In recent controversies about Intelligent Design Creationism (IDC), the principle of methodological naturalism (MN) has played an important role. In this paper, an often neglected distinction is made between two different conceptions of MN, each with its respective rationale and with a different view on the proper role of MN in science. According to one popular conception, MN is a self-imposed or intrinsic limitation of science, which means that science is simply not equipped to deal with claims of the supernatural (Intrinsic MN or IMN). Alternatively, we will defend MN as a provisory and empirically grounded attitude of scientists, which is justified in virtue of the consistent success of naturalistic explanations and the lack of success of supernatural explanations in the history of science (Provisory MN or PMN). Science does have a bearing on supernatural hypotheses, and its verdict is uniformly negative. We will discuss five arguments that have been proposed in support of IMN: the argument from the definition of science, the argument from lawful regularity, the science stopper argument, the argument from procedural necessity, and the testability argument. We conclude that IMN, because of its philosophical flaws, proves to be an ill-advised strategy to counter the claims of IDC. Evolutionary scientists are on firmer ground if they discard supernatural explanations on purely evidential grounds, instead of ruling them out by philosophical fiat

Cognitive attraction and online misinformation

© The Author(s) 2019. The spread of online misinformation has gained mainstream attention in recent years. This paper approaches this phenomenon from a cultural evolution and cognitive anthropology perspective, focusing on the idea that some cultural traits can be successful because their content taps into general cognitive preferences. This research involves 260 articles from media outlets included in two authoritative lists of websites known for publishing hoaxes and ‘fake news’, tracking the presence of negative content, threat-related information, presence of sexually related material, elements associated to disgust, minimally counterintuitive elements (and a particular category of them, i.e., violations of essentialist beliefs), and social information, intended as presence of salient social interactions (e.g., gossip, cheating, formation of alliances), and as news about celebrities. The analysis shows that these features are, to a different degree, present in most texts, and thus that general cognitive inclinations may contribute to explain the success of online misinformation. This account can elucidate questions such as whether and why misinformation online is thriving more than accurate information, or the role of ‘fake news’ as a weapon of political propaganda. Online misinformation, while being an umbrella term covering many different phenomena, can be characterised, in this perspective, not as low-quality information that spreads because of the inefficiency of online communication, but as high-quality information that spreads because of its efficiency. The difference is that ‘quality’ is not equated to truthfulness but to psychological appeal.The Netherlands Organisation for Scientific Research (NWO VIDI-grant 016.144312)

Grist to the Mill of Anti-evolutionism: The Failed Strategy of Ruling the Supernatural Out of Science by Philosophical Fiat

According to a widespread philosophical opinion, science is strictly limited to investigating natural causes and putting forth natural explanations. Lacking the tools to evaluate supernatural claims, science must remain studiously neutral on questions of metaphysics. This (self-imposed) stricture, which goes under the name of ‘methodological naturalism’, allows science to be divorced from metaphysical naturalism or atheism, which many people tend to associate with it. However, ruling the supernatural out of science by fiat is not only philosophically untenable, it actually provides grist to the mill of anti-evolutionism. The philosophical flaws in this conception of methodological naturalism have been gratefully exploited by advocates of Intelligent Design Creationism to bolster their false accusations of naturalistic bias and dogmatism on the part of modern science. We argue that it promotes a misleading view of the scientific endeavor and is at odds with the foremost arguments for evolution by natural selection. Reconciling science and religion on the basis of such methodological strictures is therefore misguided

Mafia State: The Evolving Threat of North Korean Narcotics Trafficking

The North Korean government has long been suspected of involvement in state-sponsored drug production and trafficking. Research in this field is hampered by the secrecy of the DPRK regime and the dearth of reliable sources. Nonetheless, using Chinese- and English-language sources, Peng Wang and Stephan Blancke look at developments over the past decade, intensified counter-narcotics co-operation between the Chinese and South Korean police forces, and the failure of the North Korean government to control private involvement in the illicit drug business, which has had an unexpected outcome: a crystal-meth epidemic. These trends expose a severe threat to Northeast Asia and the wider international community