Redox remodeling by dendritic cells protects antigen-specific T cells against oxidative stress

Microorganisms and microbial products induce the release of reactive oxygen species (ROS) from monocytes and other myeloid cells, which may trigger dysfunction and apoptosis of adjacent lymphocytes. Therefore, T cell-mediated immunity is likely to comprise mechanisms of T cell protection against ROS-inflicted toxicity. The present study aimed to clarify the dynamics of reduced sulfhydryl groups (thiols) in human T cells after presentation of viral and bacterial Ags by dendritic cells (DCs) or B cells. DCs, but not B cells, efficiently triggered intra- and extracellular thiol expression in T cells with corresponding Ag specificity. After interaction with DCs, the Ag-specific T cells acquired the capacity to neutralize exogenous oxygen radicals and resisted ROS-induced apoptosis. Our results imply that DCs provide Ag-specific T cells with antioxidative thiols during Ag presentation, which suggests a novel aspect of DC/T cell cross-talk of relevance to the maintenance of specific immunity in inflamed or infected tissue.     

Drug-induced ion channel opening tuned by the voltage sensor charge profile

Polyunsaturated fatty acids modulate the voltage dependence of several voltage-gated ion channels, thereby being potent modifiers of cellular excitability. Detailed knowledge of this molecular mechanism can be used in designing a new class of small-molecule compounds against hyperexcitability diseases. Here, we show that arginines on one side of the helical K-channel voltage sensor S4 increased the sensitivity to docosahexaenoic acid (DHA), whereas arginines on the opposing side decreased this sensitivity. Glutamates had opposite effects. In addition, a positively charged DHA-like molecule, arachidonyl amine, had opposite effects to the negatively charged DHA. This suggests that S4 rotates to open the channel and that DHA electrostatically affects this rotation. A channel with arginines in positions 356, 359, and 362 was extremely sensitive to DHA: 70 µM DHA at pH 9.0 increased the current >500 times at negative voltages compared with wild type (WT). The small-molecule compound pimaric acid, a novel Shaker channel opener, opened the WT channel. The 356R/359R/362R channel drastically increased this effect, suggesting it to be instrumental in future drug screening.     

Malignant cells derived from 3T3 fibroblast feeder layer in cell culture for nasopharyngeal carcinoma

In this study, we discovered a subpopulation of 3T3 feeder cells were malignantly transformed by nasopharyngeal carcinoma (NPC) tumor cells during co-culture. The transformed 3T3 cells acquired an accelerated growth rate, displayed loosely attached multilayer growth in vitro and highly tumorigenic in vivo. Most strikingly, instead of forming sarcomas, they developed into carcinoma-like tumors somewhat resembling the original NPC. We further demonstrated the transformation is not a single isolated event, rather a common reproducible, cell contact dispensable phenomena among NPC tumor cells. However, NPC tumor cells alone were not sufficient to confer the transformed characteristics onto normal human cells.     

Survey of chimeric IStron elements in bacterial genomes: multiple molecular symbioses between group I intron ribozymes and DNA transposons

IStrons are chimeric genetic elements composed of a group I intron associated with an insertion sequence (IS). The group I intron is a catalytic RNA providing the IStron with self-splicing ability, which renders IStron insertions harmless to the host genome. The IS element is a DNA transposon conferring mobility, and thus allowing the IStron to spread in genomes. IStrons are therefore a striking example of a molecular symbiosis between unrelated genetic elements endowed with different functions. In this study, we have conducted the first comprehensive survey of IStrons in sequenced genomes that provides insights into the distribution, diversity, origin and evolution of IStrons. We show that IStrons have a restricted phylogenetic distribution limited to two bacterial phyla, the Firmicutes and the Fusobacteria. Nevertheless, diverse IStrons representing two major groups targeting different insertion site motifs were identified. This taken with the finding that while the intron components of all IStrons belong to the same structural class, they are fused to different IS families, indicates that multiple intron–IS symbioses have occurred during evolution. In addition, introns and IS elements related to those that were at the origin of IStrons were also identified.     

Simplifying a life cycle assessment of a mobile phone

Purpose

The possibilities for full life cycle assessment (LCA) of new Information and Communication Technology (ICT) products are often limited, so simplification approaches are needed. The aim of this paper is to investigate possible simplifications in LCA of a mobile phone and to use the results to discuss the possibilities of LCA simplifications for ICT products in a broader sense. Another aim is to identify processes and data that are sensitive to different methodological choices and assumptions related to the environmental impacts of a mobile phone.

Methods

Different approaches to a reference LCA of a mobile phone was tested: (1) excluding environmental impact categories, (2) excluding life cycle stages/processes, (3) using secondary process data from generic databases, (4) using input-output data and (5) using a simple linear relationship between mass and embodied emissions.

Results and discussion

It was not possible to identify one or a few impact categories representative of all others. If several impact categories would be excluded, information would be lost. A precautionary approach of not excluding impact categories is therefore recommended since impacts from the different life cycle stages vary between impact categories. Regarding use of secondary data for an ICT product similar to that studied here, we recommend prioritising collection of primary (specific) data on energy use during production and use, key component data (primarily integrated circuits) and process-specific data regarding raw material acquisition of specific metals (e.g. gold) and air transport. If secondary data are used for important processes, the scaling is crucial. The use of input-output data can be a considerable simplification and is probably best used to avoid data gaps when more specific data are lacking.

Conclusions

Further studies are needed to provide for simplified LCAs for ICT products. In particular, the end-of-life treatment stage need to be further addressed, as it could not be investigated here for all simplifications due to data gaps.     

Non-Host Volatile Blend Optimization for Forest Protection against the European Spruce Bark Beetle,Ips typographus

Conifer feeding bark beetles (Coleoptera, Curculionidae, Scolytinae) pose a serious economic threat to forest production. Volatiles released by non-host angiosperm plants (so called non-host volatiles, NHV) have been shown to reduce the risk of attack by many bark beetle species, including the European spruce bark beetle, Ips typographus. However, the most active blend for I. typographus, containing three green leaf volatiles (GLVs) in addition to the key compounds trans-conophthorin (tC) and verbenone, has been considered too expensive for use in large-scale management. To lower the cost and improve the applicability of NHV, we aim to simplify the blend without compromising its anti-attractant potency. Since the key compound tC is expensive in pure form, we also tested a crude version: technical grade trans-conophthorin (T-tC). In another attempt to find a more cost effective substitute for tC, we evaluated a more readily synthesized analog: dehydro-conophthorin (DHC). Our results showed that 1-hexanol alone could replace the three-component GLV blend containing 1-hexanol, (3Z)-hexen-1-ol, and (2E)-hexen-1-ol. Furthermore, the release rate of tC could be reduced from 5 mg/day to 0.5 mg/day in a blend with 1-hexanol and (–)-verbenone without compromising the anti-attractant activity. We further show that T-tC was comparable with tC, whereas DHC was a less effective anti-attractant. DHC also elicited weaker physiological responses in the tC-responding olfactory receptor neuron class, providing a likely mechanistic explanation for its weaker anti-attractive effect. Our results suggest a blend consisting of (–)-verbenone, 1-hexanol and technical trans-conophthorin as a cost-efficient anti-attractant for forest protection against I. typographus.     

The Gut Microbiota Modulates Glycaemic Control and Serum Metabolite Profiles in Non-Obese Diabetic Mice

Islet autoimmunity in children who later progress to type 1 diabetes is preceded by dysregulated serum metabolite profiles, but the origin of these metabolic changes is unknown. The gut microbiota affects host metabolism and changes in its composition contribute to several immune-mediated diseases; however, it is not known whether the gut microbiota is involved in the early metabolic disturbances in progression to type 1 diabetes. We rederived non-obese diabetic (NOD) mice as germ free to explore the potential role of the gut microbiota in the development of diabetic autoimmunity and to directly investigate whether the metabolic profiles associated with the development of type 1 diabetes can be modulated by the gut microbiota. The absence of a gut microbiota in NOD mice did not affect the overall diabetes incidence but resulted in increased insulitis and levels of interferon gamma and interleukin 12; these changes were counterbalanced by improved peripheral glucose metabolism. Furthermore, we observed a markedly increased variation in blood glucose levels in the absence of a microbiota in NOD mice that did not progress to diabetes. Additionally, germ-free NOD mice had a metabolite profile similar to that of pre-diabetic children. Our data suggest that germ-free NOD mice have reduced glycaemic control and dysregulated immunologic and metabolic responses.     

Trapping in predator management: catching the profile of trap users in Sweden

Many populations of wildlife, including large- and medium-sized predators are increasing in Europe. Trapping can be one way to reduce negative impacts of predators on human interests, such as game species and threatened species, but there is little knowledge of trap usage and motivation behind it. We used a mail survey in Sweden (n?=?3,886 respondents) to compare predator trappers with hunters who used other methods to kill predators, and with other hunters who did not kill predators, in regard to sociodemographics, beliefs, behaviors, and constraints. During 12 months prior to the survey 19 % of respondents had trapped any small- or medium-sized predator, while 15 % of respondents had trapped and 55 % had hunted (without using traps) red fox (Vulpes vulpes), European badger (Meles meles), or corvid birds. Reducing predator numbers was an important reason for hunting predators with traps. Of predator trappers, 97 % had hunted species that were potentially prey of the targeted predators (e.g., roe deer [Capreolus capreolus], hare [Lepus spp.], and grouse), 94 % believed that there were too many red foxes, badgers, or corvids on their main hunting ground, and 64 % believed it to be very important to reduce predator numbers to benefit other game species. We conclude that the use of traps is widespread among Swedish hunters, and that increasing wildlife populations, increased presence of wildlife in urban areas, and management of invasive species calls for effective management actions, of which trapping can be one.