Adaptor usage and Toll-like receptor signaling specificity

It is now well established that Toll-like receptors (TLRs) act as primary sensors of microbial compounds. Details of the molecular mechanisms governing TLR responses are emerging steadily and our understanding of the signaling pathways activated these receptors has improved greatly over the last few years. Differences in adaptor usage, cellular localisation and signaling cascades have been elucidated. In this review we will summarize the current understanding of TLR signaling and its regulation.     

Microbial degradation of styrene: biochemistry, molecular genetics, and perspectives for biotechnological applications

Large quantities of the potentially toxic compound styrene are produced and used annually by the petrochemical and polymer-processing industries. It is as a direct consequence of this that significant volumes of styrene are released into the environment in both the liquid and the gaseous forms. Styrene and its metabolites are known to have serious negative effects on human health and therefore, strategies to prevent its release, remove it from the environment, and understand its route of degradation were the subject of much research. There are a large number of microbial genera capable of metabolizing styrene as a sole source of carbon and energy and therefore, the possibility of applying these organisms to bioremediation strategies was extensively investigated. From the multitude of biodegradation studies, the application of styrene-degrading organisms or single enzymes for the synthesis of value-added products such as epoxides has emerged.     

Inhibition of TLR2 promotes graft function in a murine model of renal transplant ischemia-reperfusion injury

Toll-like receptors (TLRs) are important molecules involved in the activation of innate and subsequent development of adaptive immunity. TLRs are ligated by exogenous ligands from pathogens and by endogenous ligands released in inflammatory diseases. Activation of TLR leads to activation of NF-κB and release of proinflammatory cytokines, such as IL-6 and TNF-α. TLRs play an important role in the pathogenesis of renal diseases. Increased expression of TLRs have been associated with ischemic kidney damage, acute kidney injury, end-stage renal failure, acute renal transplant rejection, and delayed allograft function. OPN301 is a mouse anti-human TLR2 antibody that cross-reacts with mouse TLR2. We show that inhibition of TLR2 promotes graft function in an isograft model of renal transplantation. Recipient mice were treated intravenously with OPN301 before reperfusion of the transplanted kidney that had been subjected to 30 min of cold ischemia. After 5 d, the residual native kidney was removed, and renal transplant function was assessed 24 h later by measurement of blood urea nitrogen. Renal function in both saline- and isotype-treated mice was similar, with significant improvement in OPN301-treated mice (isotype-treated vs. OPN301-treated: 33.9±3.2 vs. 19.8±1.9 μM; P<0.01). The histopathological appearance corresponded with renal functional results. In OPN301-treated recipients, renal structure was well preserved, whereas in the saline-treated group, tubular injury was severe, with marked tubular thinning, epithelial shedding, cast formation and necrosis. Inhibition of TLR2 also leads to a decrease in C3d deposition, although it is unclear whether this is due directly to TLR2 inhibition or a decrease in renal inflammation. This study shows that inhibition of TLR2 with a therapeutic agent (OPN301) provides significant protection from ischemia/reperfusion injury in a model of kidney transplantation.     

Diversity and dynamics of the DNA and cDNA-derived bacterial compost communities throughout the <Emphasis Type="Italic">Agaricus bisporus</Emphasis> mushroom cropping process

The cultivation of Agaricus bisporus involves the conversion of agricultural materials via fermentation into utilisable simple sugars as a nutrient source for the fungal crop during mushroom cropping. However, little is currently known about the role of the bacterial community contributing to the fermentation process. In this investigation we characterised the composition and dynamics of the DNA and cDNA-derived bacterial populations throughout a commercial mushroom cropping process using MiSeq sequencing. Both methods indicated substantial changes in the bacterial community structure after the first flush of the mushroom crop. However, differences were observed between the composition of the bacterial community determined by each of the two methods. The cDNA-derived community indicated that thermotolerant genera with known sulphur-reducing characteristics were highly active up to the first flush. Activity of the phyla Actinobacteria and Firmicutes was observed to increase as fermentation progressed, indicating that the members of these phyla played prominent roles in the conversion of wheat straw into utilisable sugars. The cDNA-derived community comprised genera with roles in the nitrification process that became highly active at post flush 1. Subsequent chemical analysis of extractable nitrate indicated that substantial nitrification occurred up until the termination of the cropping process. This study has demonstrated that a highly dynamic bacterial community is present throughout the mushroom cropping process.     

Towards an understanding of semaphorin signalling in the spinal cord

Semaphorins are a large family of proteins that are classically associated with axon guidance. These proteins and their interacting partners, the neuropilins and plexins are now known to be key mediators in a variety of processes throughout the nervous system ranging from synaptic refinement to the correct positioning of neuronal and glial cell bodies. Recently, much attention has been given to the roles semaphorins play in other body tissues including the immune and vascular systems. This review wishes to draw attention back to the nervous system, specifically focusing on the role of semaphorins in the development of the spinal cord and their proposed roles in the adult. In addition, their functions in spinal cord injury at the glial scar are also discussed.     

Determinants of woody encroachment and cover in African savannas

Savanna ecosystems are an integral part of the African landscape and sustain the livelihoods of millions of people. Woody encroachment in savannas is a widespread phenomenon but its causes are widely debated. We review the extensive literature on woody encroachment to help improve understanding of the possible causes and to highlight where and how future scientific efforts to fully understand these causes should be focused. Rainfall is the most important determinant of maximum woody cover across Africa, but fire and herbivory interact to reduce woody cover below the maximum at many locations. We postulate that woody encroachment is most likely driven by CO₂ enrichment and propose a two-system conceptual framework, whereby mechanisms of woody encroachment differ depending on whether the savanna is a wet or dry system. In dry savannas, the increased water-use efficiency in plants relaxes precipitation-driven constraints and increases woody growth. In wet savannas, the increase of carbon allocation to tree roots results in faster recovery rates after disturbance and a greater likelihood of reaching sexual maturity. Our proposed framework can be tested using a mixture of experimental and earth observational techniques. At a local level, changes in precipitation, burning regimes or herbivory could be driving woody encroachment, but are unlikely to be the explanation of this continent-wide phenomenon.     

MutS�� and histone deacetylase complexes promote expansions of trinucleotide repeats in human cells

Trinucleotide repeat (TNR) expansions cause at least 17 heritable neurological diseases, including Huntington’s disease. Expansions are thought to arise from abnormal processing of TNR DNA by specific trans-acting proteins. For example, the DNA repair complex MutSβ (MSH2–MSH3 heterodimer) is required in mice for on-going expansions of long, disease-causing alleles. A distinctive feature of TNR expansions is a threshold effect, a narrow range of repeat units (∼30–40 in humans) at which mutation frequency rises dramatically and disease can initiate. The goal of this study was to identify factors that promote expansion of threshold-length CTG•CAG repeats in a human astrocytic cell line. siRNA knockdown of the MutSβ subunits MSH2 or MSH3 impeded expansions of threshold-length repeats, while knockdown of the MutSα subunit MSH6 had no effect. Chromatin immunoprecipitation experiments indicated that MutSβ, but not MutSα, was enriched at the TNR. These findings imply a direct role for MutSβ in promoting expansion of threshold-length CTG•CAG tracts. We identified the class II deacetylase HDAC5 as a novel promoting factor for expansions, joining the class I deacetylase HDAC3 that was previously identified. Double knockdowns were consistent with the possibility that MutSβ, HDAC3 and HDAC5 act through a common pathway to promote expansions of threshold-length TNRs.