Kathryn Nixdorff

Toll-Like Receptor 4 and Toll-IL-1 Receptor Domain-Containing Adapter Protein (TIRAP)/Myeloid Differentiation Protein 88 Adapter-Like (Mal) Contribute to Maximal IL-6 Expression in Macrophages

Previous studies have shown that engagement of Toll-like receptors (TLR) 2 and 4 can induce macrophages to express a variety of proinflammatory cytokines. We have recently demonstrated that TLR2 agonists poorly induce a subset of TLR4-inducible proinflammatory genes (e.g., inducible protein (IP)-10, inducible NO synthase (iNOS), monocyte chemoattractant protein-5, IL-12p40), due in part to differential activation of IFN-β production and phosphorylation of the transcription factor STAT1. TLR4, but not TLR2, agonists can induce IFN-β expression via a mechanism that requires the adapter protein Toll-IL-1R domain-containing adapter protein (TIRAP)/myeloid differentiation protein 88 (MyD88) adapter-like (Mal), but not the adapter protein MyD88. Thus, the failure of TLR2 agonists to induce STAT1-dependent genes results, in part, from their failure to induce the expression of IFN-β. In this study, we show that IL-6 expression is also preferentially induced by activation of TLR4. TLR4-dependent induction of IL-6 expression did require Toll-IL-1R domain-containing adapter protein (TIRAP)/MyD88 adapter-like (Mal), but unlike iNOS and IP-10, it did not require the expression of IFN-β. Although exogenous IFN-β and IFN-γ could synergize with TLR2 agonists to restore high levels of iNOS expression and NO production, these IFNs could not synergize with TLR2 agonists to induce high levels of IL-6. Similarly, neutralizing anti-IFN Abs could block iNOS gene expression in LPS-stimulated murine macrophages, whereas these Abs had little effect on IL-6 gene expression in these cells. Together, these studies demonstrate that IL-6, like iNOS and IP-10, is differentially expressed in macrophages stimulated via TLR2 vs TLR4, although these differences appear to arise from distinct signaling mechanisms.

Ethics of university research, biotechnology and potential military spin-off

The paper provides a briefintroduction to the biotechnology revolutionand its impact upon biological researchrelevant to military uses. It describes thestatus of biological weapons today, and currentefforts to strengthen the Biological WeaponsConvention with a legally binding complianceprotocol. Specific modifications ofmicro-organisms that may be of military use arediscussed. Three examples of dual-use researchactivities are then used to highlight issuesand dilemmas in ethical decision making.

Preventing a biochemical arms race

Preventing a Biochemical Arms Race responds to a growing concern that changes in the life sciences and the nature of warfare could lead to a resurgent interest in chemical and biological weapons (CBW) capabilities. By bringing together a wide range of historical material and current literature in the field of CBW arms control, the book reveals how these two disparate fields might be integrated to precipitate a biochemical arms race among major powers, rogue states, or even non-state actors. It seeks to raise awareness among policy practitioners, the academic community, and the media that such an arms race may be looming if developments are left unattended, and to provide policy options on how it-and its devastating consequences-could be avoided. After identifying weaknesses in the international regime structures revolving around the Biological Weapons and Chemical Weapons Conventions, it provides policy proposals to deal with gaps and shortcomings in each prohibition regime individually, and then addresses the widening gap between them.

The Biotechnology Revolution: The Science and Applications

Biotechnology is a very old technology spanning a period of over 5000 years. In the earliest phases, it was concerned primarily with fermentation processes leading to bread-making as well as to the production of alcoholic beverages and cheese. With the recognition that microorganisms and their products were responsible for such processes and the establishment of microbiology as a science towards the end of the ninteenth century, biotechnology indeed acquired a scientific character. At this point the term biotechnology encompassed:1,2 “the use of living organisms or enzymes in the technically regulated production of organic substances.” Biotechnology has since been revolutionized by molecular biology and genetic engineering, and any modern account has to take these developments into consideration.

Education for life scientists on the dual-use implications of their research : commentary on "implementing biosecurity education: approaches, resources and programmes".

Abstract Advances in the life sciences are occurring with extreme rapidity and accumulating a great deal of knowledge about life’s vital processes. While this knowledge is essential for fighting disease in a more effective way, it can also be misused either intentionally or inadvertently to develop novel and more effective biological weapons. For nearly a decade civil-academic society as well as States Parties to the Biological and Toxin Weapons Convention have recognised the importance of dual-use biosecurity education for life scientists as a means to foster a culture of responsibility and prevent the potential misuse of advances in the life sciences for non-peaceful purposes. Nevertheless, the implementation of dual-use biosecurity education for life scientists has made little progress in institutions of higher learning. Professional societies and academic organizations have worked from the bottom-up in developing online dual-use biosecurity education modules that can be used for instruction. However, top-down help is needed from goverments if further progress is to be made in implementing biosecurity education for life scientists.

Advances in Targeted Delivery and the Future of Bioweapons

Biotechnology—and aerosol delivery specifically—is beginning to blur the line between solutions and threats. Could a cure for diabetes and a dangerous pathogen be delivered in the same way? Such a scenario isn’t far off.

Double Assault: Malign Manipulation of the Neuroendocrine-Immune System

Concerns about biological weapons and biological terrorism have increased over the last decade and, particularly since the events of 11 September 2001 in the United States. There has been a growing belief that large-scale biological weapons attacks are becoming more likely.1 The medical profession has been amongst those groups which have devoted more and more attention to what might need to be done in the event of an attack.

Molecular biological techniques for subspecies identification : immunological techniques ; a comparison

Immunological techniques have been used for decades to distinguish among and identify microorganisms and their products. These methods are all based on the ability of antibodies to bind with exquisite specificity to defined structures called antigen epitopes or antigen determinants characteristic of microbial components. The usefulness of immunological assays depends to a large extent on the binding affinity and specificity of the antibodies and how they are coupled to detection systems, which all together determine the sensitivity and facility of the procedures in identifying agents.

Strengthening BWC Prevention of State-Sponsored Bioweapons

The BWC needs to return to its core business: preventing state-level bioweapon programs. Enhancing the regime toward this end will also hinder the trickle down of bioweapon technologies to sub-state actors and individuals.

Science, Technology and the CW Prohibition Regime

This chapter will analyse the chemical weapons (CW) prohibition regime with a view to the impact that technological characteristics of and developments related to toxic chemicals as well as developments concerning chemical processes have on the control efforts by states parties to the regime. The analysis starts from the hypothesis that recent developments in modern biotechnology, especially the utilization of combinatorial chemistry in for example the pharmaceutical industries of developed countries pose a risk to the international regime set up for prohibiting chemical warfare agents. In order to prevent the CW prohibition regime from being undermined by these — and other — recent developments, a rethinking is needed of the interrelation between the scientific and technological basis of the issue area and the political-legal regime structure brought in place to control the dangers emanating from known chemical warfare agents and other toxic chemicals and biochemicals that could be misused for warfare or terrorist attacks.