Loureirin B, an essential component of Sanguis Draxonis, inhibits Kv1.3 channel and suppresses cytokine release from Jurkat T cells

Sanguis draxonis (SD), also known as “Dragon’s Blood”, is a traditional herb medicine that has been used to treat a variety of complications with unknown mechanisms. Recent studies show that SD displays immunosuppressive activities and improves symptoms of type I diabetes in animal models. However, the mechanisms underlying SD’s immunosuppressive actions are not completely understood. The voltage-gated Kv1.3 channel plays a critical role in the pathogenesis of autoimmune diseases by regulating the functions of both T cells and B cells. Here we investigated the effect of SD and one of its active components loureirin B (LrB) on Kv1.3. Both SD and LrB inhibited Kv1.3-mediated currents, produced a membrane depolarization, and reduced Ca(2+) influx in Jurkat T cells. In addition, application of LrB inhibited phytohemagglutinin (PHA)-induced IL-2 release from activated Jurkat T cells. Furthermore, point mutations in the selective filter region significantly reduced the inhibitory effect of LrB on Kv1.3. The results of these experiments provide evidence that LrB is a channel blocker of Kv1.3 by interacting with amino acid residues in its selective filter region. Direct inhibition of Kv1.3 in T cells by SD and LrB might be the cellular and molecular basis of SD-mediated immunosuppression

Small Screen, Big Tourism: The Role of Popular Korean Television Dramas in South Korean Tourism

This paper examines a popular cultural phenomenon originating in Korea which has assumed significance across Asia and beyond. This ‘Korean wave’ or Hallyu includes the circulation and consumption of Korean popular television dramas. An exploratory case study approach is presented to provide insights on the relationships between this phenomenon and patterns of tourism in Korea related to the wider concept of screen-tourism. The paper addresses the relative lack of attention to television programming within the film tourism literature, particularly in non-Western and non-English language settings. Some common assumptions in the film tourism literature are challenged here, including: the inter-changeability of large-screen films and programmes produced for the television; and the inter-cultural circulation of film and television programmes as catalysts for tourism. Our findings illustrate that the inter-cultural circulation of Hallyu television dramas, particularly in neighbouring countries in Asia, may be interpreted in relation to theories of cultural proximity. A need to understand the complex patterns and political economy of distribution, circulation and reception of television programmes is also identified. The paper argues for more research that links visitor flows with television audience research and which recognizes the organizational infrastructures that allow media productions to go beyond circulation in domestic TV markets. Professional expertise and networks, transnational business relationships, ownership and national media regulatory regimes are highlighted, as is the extent to which media professionals and organizations connect with the domestic and international tourism sector

Innovative Cardiac Resynchronization: Deployable Lead as an Anchor to Facilitate Guidewire Advancement.

An acutely angulated coronary sinus ostium coupled with a dilated right atrium presents technical challenges for cardiac resynchronization therapy (CRT) implantation. Innovative use of a deployable left ventricle lead as an anchor to support guidewire navigation within the cardiac venous system permits optimal CRT deployment. (Level of Difficulty: Advanced.)

From insect to man: Photorhabdus sheds light on the emergence of human pathogenicity

Photorhabdus are highly effective insect pathogenic bacteria that exist in a mutualistic relationship with Heterorhabditid nematodes. Unlike other members of the genus, Photorhabdus asymbiotica can also infect humans. Most Photorhabdus cannot replicate above 34°C, limiting their host-range to poikilothermic invertebrates. In contrast, P. asymbiotica must necessarily be able to replicate at 37°C or above. Many well-studied mammalian pathogens use the elevated temperature of their host as a signal to regulate the necessary changes in gene expression required for infection. Here we use RNA-seq, proteomics and phenotype microarrays to examine temperature dependent differences in transcription, translation and phenotype of P. asymbiotica at 28°C versus 37°C, relevant to the insect or human hosts respectively. Our findings reveal relatively few temperature dependant differences in gene expression. There is however a striking difference in metabolism at 37°C, with a significant reduction in the range of carbon and nitrogen sources that otherwise support respiration at 28°C. We propose that the key adaptation that enables P. asymbiotica to infect humans is to aggressively acquire amino acids, peptides and other nutrients from the human host, employing a so called “nutritional virulence” strategy. This would simultaneously cripple the host immune response while providing nutrients sufficient for reproduction. This might explain the severity of ulcerated lesions observed in clinical cases of Photorhabdosis. Furthermore, while P. asymbiotica can invade mammalian cells they must also resist immediate killing by humoral immunity components in serum. We observed an increase in the production of the insect Phenol-oxidase inhibitor Rhabduscin normally deployed to inhibit the melanisation immune cascade. Crucially we demonstrated this molecule also facilitates protection against killing by the alternative human complement pathway

Synthetic Nanoparticles for Vaccines and Immunotherapy

The immune system plays a critical role in our health. No other component of human physiology plays a decisive role in as diverse an array of maladies, from deadly diseases with which we are all familiar to equally terrible esoteric conditions: HIV, malaria, pneumococcal and influenza infections; cancer; atherosclerosis; autoimmune diseases such as lupus, diabetes, and multiple sclerosis. The importance of understanding the function of the immune system and learning how to modulate immunity to protect against or treat disease thus cannot be overstated. Fortunately, we are entering an exciting era where the science of immunology is defining pathways for the rational manipulation of the immune system at the cellular and molecular level, and this understanding is leading to dramatic advances in the clinic that are transforming the future of medicine.1,2 These initial advances are being made primarily through biologic drugs– recombinant proteins (especially antibodies) or patient-derived cell therapies– but exciting data from preclinical studies suggest that a marriage of approaches based in biotechnology with the materials science and chemistry of nanomaterials, especially nanoparticles, could enable more effective and safer immune engineering strategies. This review will examine these nanoparticle-based strategies to immune modulation in detail, and discuss the promise and outstanding challenges facing the field of immune engineering from a chemical biology/materials engineering perspectiveNational Institutes of Health (U.S.) (Grants AI111860, CA174795, CA172164, AI091693, and AI095109)United States. Department of Defense (W911NF-13-D-0001 and Awards W911NF-07-D-0004

Adapting an online guided self- help intervention for the management of binge eating in adults with type 2 diabetes: The POSE- D study

Aims People with type 2 diabetes (T2D) are more likely to experience binge eating than the general population, which may interfere with their diabetes management. Guided self-help (GSH) is the recommended treatment for binge-eating disorder, but there is currently a lack of evidenced treatment for binge eating in individuals living with T2D. The aims of the current study were to adapt an existing evidence-based GSH intervention using the principles of co-design to make it available online, suitable for remote delivery to address binge eating specifically in adults living with T2D. The Working to Overcome Eating Difficulties GSH intervention comprises online GSH materials presented in seven sections delivered over 12 weeks, supported by a trained Guide. Methods In order to adapt the intervention, we held four collaboration workshops with three expert patients recruited from diabetes support groups, eight healthcare professionals and an expert consensus group. We used thematic analysis to make sense of the data. Results and Conclusions The main themes included; keeping the GSH material generic, adapting Sam the central character, tailoring the dietary advice and eating diary. The length of Guidance sessions was increased to 60 min, and Guide training was focussed around working with people with diabetes

What caused extinction of the pleistocene megafauna of sahul?

2016 The Author(s) Published by the Royal Society. All rights reserved. During the Pleistocene, Australia and New Guinea supported a rich assemblage of large vertebrates. Why these animals disappeared has been debated for more than a century and remains controversial. Previous synthetic reviews of this problem have typically focused heavily on particular types of evidence, such as the dating of extinction and human arrival, and have frequently ignored uncertainties and biases that can lead to misinterpretation of this evidence. Here, we review diverse evidence bearing on this issue and conclude that, although many knowledge gaps remain, multiple independent lines of evidence point to direct human impact as the most likely cause of extinction

Corrigendum: Chronic Intra-Uterine Ureaplasma parvum infection induces injury of the enteric Nervous System in Ovine Fetuses

Michael L. Beeton was not included as an author in the published article. The corrected Author Contributions Statement appears below