A Drosophila Model for Clostridium difficile Toxin CDT Reveals Interactions with Multiple Effector Pathways.

Clostridium difficile infections (CDIs) cause severe and occasionally life-threatening diarrhea. Hyper-virulent strains produce CDT, a toxin that ADP-ribosylates actin monomers and inhibits actin polymerization. We created transgenic Drosophila lines expressing the catalytic subunit CDTa to investigate its interaction with host signaling pathways in vivo. When expressed in the midgut, CDTa reduces body weight and fecal output and compromises survival, suggesting severe impairment of digestive functions. At the cellular level, CDTa induces F-actin network collapse, elimination of the intestinal brush border, and disruption of intercellular junctions. We confirm toxin-dependent re-distribution of Rab11 to enterocytes' apical surface and observe suppression of CDTa phenotypes by a Dominant-Negative form of Rab11 or RNAi of the dedicated Rab11GEF Crag (DENND4). We also report that Calmodulin (Cam) is required to mediate CDTa activity. In parallel, chemical inhibition of the Cam/Calcineurin pathway by Cyclosporin A or FK506 also reduces CDTa phenotypes, potentially opening new avenues for treating CDIs

The Risk of Cancer from CT Scans and Other Sources of Low-Dose Radiation: A Critical Appraisal of Methodologic Quality

AbstractIntroduction: Concern exists that radiation exposure from computerized tomography (CT) will cause thousands of malignancies. Other experts share the same perspective regarding the risk from additional sources of low-dose ionizing radiation, such as the releases from Three Mile Island (1979; Pennsylvania USA) and Fukushima (2011; Okuma, Fukushima Prefecture, Japan) nuclear power plant disasters. If this premise is false, the fear of cancer leading patients and physicians to avoid CT scans and disaster responders to initiate forcedevacuations is unfounded.Study Objective: This investigation provides a quantitative evaluation of the methodologic quality of studies to determine the evidentiary strength supporting or refuting a causal relationshipbetween low-dose radiation and cancer. It will assess the number of higher qualitystudies that support or question the role of low-dose radiation in oncogenesis.Methods: This investigation is a systematic, methodologic review of articles published from 1975–2017 examining cancer risk from external low-dose x-ray and gamma radiation, defined as less than 200 millisievert (mSv). Following the PRISMA guidelines, the authors performed a search of the PubMed, Cochrane, Scopus, and Web of Science databases. Methodologies of selected articles were scored using the Newcastle Ottawa Scale (NOS) and a tool identifying 11 lower quality indicators. Manuscript methodologies were rankedas higher quality if they scored no lower than seven out of nine on the NOS and contained no more than two lower quality indicators. Investigators then characterized articles as supporting or not supporting a causal relationship between low-dose radiation and cancer.Results: Investigators identified 4,382 articles for initial review. A total of 62 articles met all inclusion/exclusion criteria and were evaluated in this study. Quantitative evaluation of the manuscripts’ methodologic strengths found 25 studies met higher quality criteria while 37 studies met lower quality criteria. Of the 25 studies with higher quality methods, 21 out of 25did not support cancer induction by low-dose radiation (P = .0003).Conclusions: A clear preponderance of articles with higher quality methods found no increased risk of cancer from low-dose radiation. The evidence suggests that exposure to multiple CT scans and other sources of low-dose radiation with a cumulative dose up to 100 mSv (approximately 10 scans), and possibly as high as 200 mSv (approximately 20 scans), does not increase cancer risk

Bombardier Enables Delivery of Short-Form Bomanins in the Drosophila Toll Response.

Toll mediates a robust and effective innate immune response across vertebrates and invertebrates. In Drosophila melanogaster, activation of Toll by systemic infection drives the accumulation of a rich repertoire of immune effectors in hemolymph, including the recently characterized Bomanins, as well as the classical antimicrobial peptides (AMPs). Here we report the functional characterization of a Toll-induced hemolymph protein encoded by the bombardier (CG18067) gene. Using the CRISPR/Cas9 system to generate a precise deletion of the bombardier transcriptional unit, we found that Bombardier is required for Toll-mediated defense against fungi and Gram-positive bacteria. Assaying cell-free hemolymph, we found that the Bomanin-dependent candidacidal activity is also dependent on Bombardier, but is independent of the antifungal AMPs Drosomycin and Metchnikowin. Using mass spectrometry, we demonstrated that deletion of bombardier results in the specific absence of short-form Bomanins from hemolymph. In addition, flies lacking Bombardier exhibited a defect in pathogen tolerance that we trace to an aberrant condition triggered by Toll activation. These results lead us to a model in which the presence of Bombardier in wild-type flies enables the proper folding, secretion, or intermolecular associations of short-form Bomanins, and the absence of Bombardier disrupts one or more of these steps, resulting in defects in both immune resistance and tolerance

The effects of infotainment on public reaction to North Korea using hybrid text mining: Content analysis, machine learning-based sentiment analysis, and co-word analysis

This study proposes alternative measures of infotainment’s effects on audience perception and reception of news on social media, focusing on infotainment coverage of North Korea. We determine the elements of framing strategies and narrative styles in facilitating public attention, positive and negative responses, and engagement in news content. We used the YouTube application programming interface to collect data from VideoMug, Korea’s most popular YouTube channel, run by the Seoul Broadcasting System. We examined 23,774 replies commenting on North Korea-related video clips from July 1, 2018, to May 17, 2019. The findings show that entertainment and human interest frames were effective in drawing public attention to news coverage about North Korea. Using humor and colloquial language facilitated public attention (both positive and negative) and public engagement. Over half (59.55%) of the comments generated positive emotions; less than one-third generated negative emotions (31.41%); and a few generated neutral ones (9.03%). The infotainment approach helped make South Koreans’ attitudes toward North Korea and inter-Korean relations more positive. A small number of users who served as top authorities were extremely partisan and conducted intense debates about infotainment practices. This study’s hybrid analytical framework using computerized text mining techniques offers both theoretical and methodological insights into the function of infotainment in the context of social media

Fight or Flight? Defending Against Sequential Attacks in the Game of Siege

This paper examines theory and behavior in a two-player game of siege, sequential attack and defense. The attacker’s objective is to successfully win at least one battle while the defender’s objective is to win every battle. Theoretically, the defender either folds immediately or, if his valuation is sufficiently high and the number of battles is sufficiently small, then he has a constant incentive to fight in each battle. Attackers respond to defense with diminishing assaults over time. Consistent with theoretical predictions, our experimental results indicate that the probability of successful defense increases in the defenders valuation and it decreases in the overall number of battles in the contest. However, the defender engages in the contest significantly more often than predicted and the aggregate expenditures by both parties exceed predicted levels. Moreover, both defenders and attackers actually increase the intensity of the fight as they approach the end of the contest.Colonel Blotto, conflict resolution, weakest-link, game of siege, multi-period resource allocation, experiments.

Reflective Experiential Learning: Using Active Video Watching for Soft Skills Training

Learning by watching videos has become the dominant way of learning for millennials. However, watching videos is a passive form of learning which usually results in a low level of engagement. As the result, video-based learning often results in poor learning outcomes. One of the proven strategies to increase engagement is to integrate interactive activities such as quizzes and assessment problems into videos. Although this strategy increases engagement, it requires changing existing videos and therefore substantial effort from the teacher. We have developed the Active Video Watching (AVW) system that enables the teacher to use existing videos from YouTube without modifications. The teacher is required to define a set of aspects for videos, which serve as reflective scaffolds in order to increase engagement and focus learners’ thinking. AVW provides a Personal Space for individual learners to link their personal experiences while watching videos. The comments collected can be used by the individuals to reflect on their own thoughts or to be shared with other learners in the Social Space. We conducted a study with postgraduate students on presentation skills. The results show that the level of engagement with AVW was high, and that the aspects were effective as reflection prompts. We plan to conduct further studies related to other types of soft skills, and also to further extend AVW to provide individualized feedback to students

Facilitating the transition to sustainable green chemistry

Sustainable green chemistry depends on technically feasible, cost-effective and socially acceptable decisions by regulators, industry and the wider community. The discipline needs to embrace a new suite of tools and train proponents in their use. We propose a set of tools that will bridge the gap between technical feasibility and efficiency on one hand, and social preferences and values on the other. We argue that they are indispensable in the next generation of regulators and chemistry industry proponents

The Attack and Defense of Weakest-Link Networks

This paper experimentally examines behavior in a two-player game of attack and defense of a weakest-link network of targets, in which the attacker's objective is to successfully attack at least one target and the defender's objective is diametrically opposed. We apply two benchmark contest success functions (CSFs): the auction CSF and the lottery CSF. Consistent with the theoretical prediction, under the auction CSF, attackers utilize a stochastic “guerilla warfare” strategy — in which a single random target is attacked — more than 80% of the time. Under the lottery CSF, attackers utilize the stochastic guerilla warfare strategy almost 45% of the time, contrary to the theoretical prediction of an equal allocation of forces across the targets.Colonel Blotto, conflict resolution, weakest-link, best-shot, multi-dimensional resource allocation, experiments.

Semantic variant primary progressive aphasia: Practical recommendations for treatment from 20 years of behavioural research

People with semantic variant primary progressive aphasia (svPPA) present with a char-acteristic progressive breakdown of semantic knowledge. There are currently no pharmacological interventions to cure or slow svPPA, but promising behavioural approaches are increasingly reported. This article offers an overview of the last two decades of research into interventions to support language in people with svPPA including recommendations for clinical practice and future research based on the best available evidence. We offer a lay summary in English, Spanish and French for education and dissemination purposes. This paper discusses the implications of right-versus left-predominant atrophy in svPPA, which naming therapies offer the best outcomes and how to capitalise on preserved long-term memory systems. Current knowledge regarding the maintenance and generalisation of language therapy gains is described in detail along with the development of compensatory approaches and educational and support group programmes. It is concluded that there is evidence to support an integrative framework of treatment and care as best practice for svPPA. Such an approach should combine rehabilitation interventions addressing the language impairment, compensatory approaches to support activities of daily living and provision of education and support within the context of dementia