MARCO, TLR2, and CD14 Are Required for Macrophage Cytokine Responses to Mycobacterial Trehalose Dimycolate and Mycobacterium tuberculosis

Virtually all of the elements of Mycobacterium tuberculosis (Mtb) pathogenesis, including pro-inflammatory cytokine production, granuloma formation, cachexia, and mortality, can be induced by its predominant cell wall glycolipid, trehalose 6,6′-dimycolate (TDM/cord factor). TDM mediates these potent inflammatory responses via interactions with macrophages both in vitro and in vivo in a myeloid differentiation factor 88 (MyD88)-dependent manner via phosphorylation of the mitogen activated protein kinases (MAPKs), implying involvement of toll-like receptors (TLRs). However, specific TLRs or binding receptors for TDM have yet to be identified. Herein, we demonstrate that the macrophage receptor with collagenous structure (MARCO), a class A scavenger receptor, is utilized preferentially to “tether” TDM to the macrophage and to activate the TLR2 signaling pathway. TDM-induced signaling, as measured by a nuclear factor-kappa B (NF-κB)-luciferase reporter assay, required MARCO in addition to TLR2 and CD14. MARCO was used preferentially over the highly homologous scavenger receptor class A (SRA), which required TLR2 and TLR4, as well as their respective accessory molecules, in order for a slight increase in NF-κB signaling to occur. Consistent with these observations, macrophages from MARCO−/− or MARCO−/−SRA−/− mice are defective in activation of extracellular signal-related kinase 1/2 (ERK1/2) and subsequent pro-inflammatory cytokine production in response to TDM. These results show that MARCO-expressing macrophages secrete pro-inflammatory cytokines in response to TDM by cooperation between MARCO and TLR2/CD14, whereas other macrophage subtypes (e.g. bone marrow–derived) may rely somewhat less effectively on SRA, TLR2/CD14, and TLR4/MD2. Macrophages from MARCO−/− mice also produce markedly lower levels of pro-inflammatory cytokines in response to infection with virulent Mtb. These observations identify the scavenger receptors as essential binding receptors for TDM, explain the differential response to TDM of various macrophage populations, which differ in their expression of the scavenger receptors, and identify MARCO as a novel component required for TLR signaling

The SOLAS air-sea gas exchange experiment (SAGE) 2004

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part II: Topical Studies in Oceanography 58 (2011): 753-763, doi:10.1016/j.dsr2.2010.10.015.The SOLAS air-sea gas exchange experiment (SAGE) was a multiple-objective study investigating gas-transfer processes and the influence of iron fertilisation on biologically driven gas exchange in high-nitrate low-silicic acid low-chlorophyll (HNLSiLC) Sub-Antarctic waters characteristic of the expansive Subpolar Zone of the southern oceans. This paper provides a general introduction and summary of the main experimental findings. The release site was selected from a pre-voyage desktop study of environmental parameters to be in the south-west Bounty Trough (46.5°S 172.5°E) to the south-east of New Zealand and the experiment conducted between mid-March and mid-April 2004. In common with other mesoscale iron addition experiments (FeAX’s), SAGE was designed as a Lagrangian study quantifying key biological and physical drivers influencing the air-sea gas exchange processes of CO2, DMS and other biogenic gases associated with an iron-induced phytoplankton bloom. A dual tracer SF6/3He release enabled quantification of both the lateral evolution of a labelled volume (patch) of ocean and the air-sea tracer exchange at the 10’s of km’s scale, in conjunction with the iron fertilisation. Estimates from the dual-tracer experiment found a quadratic dependency of the gas exchange coefficient on windspeed that is widely applicable and describes air-sea gas exchange in strong wind regimes. Within the patch, local and micrometeorological gas exchange process studies (100 m scale) and physical variables such as near-surface turbulence, temperature microstructure at the interface, wave properties, and wind speed were quantified to further assist the development of gas exchange models for high-wind environments. There was a significant increase in the photosynthetic competence (Fv/Fm) of resident phytoplankton within the first day following iron addition, but in contrast to other FeAX’s, rates of net primary production and column-integrated chlorophyll a concentrations had only doubled relative to the unfertilised surrounding waters by the end of the experiment. After 15 days and four iron additions totalling 1.1 tonne Fe2+, this was a very modest response compared to the other mesoscale iron enrichment experiments. An investigation of the factors limiting bloom development considered co- limitation by light and other nutrients, the phytoplankton seed-stock and grazing regulation. Whilst incident light levels and the initial Si:N ratio were the lowest recorded in all FeAX’s to date, there was only a small seed-stock of diatoms (less than 1% of biomass) and the main response to iron addition was by the picophytoplankton. A high rate of dilution of the fertilised patch relative to phytoplankton growth rate, the greater than expected depth of the surface mixed layer and microzooplankton grazing were all considered as factors that prevented significant biomass accumulation. In line with the limited response, the enhanced biological draw-down of pCO2 was small and masked by a general increase in pCO2 due to mixing with higher pCO2 waters. The DMS precursor DMSP was kept in check through grazing activity and in contrast to most FeAX’s dissolved dimethylsulfide (DMS) concentration declined through the experiment. SAGE is an important low-end member in the range of responses to iron addition in FeAX’s. In the context of iron fertilisation as a geoengineering tool for atmospheric CO2 removal, SAGE has clearly demonstrated that a significant proportion of the low iron ocean may not produce a phytoplankton bloom in response to iron addition.SAGE was jointly funded through the New Zealand Foundation for Research, Science and Technology (FRST) programs (C01X0204) "Drivers and Mitigation of Global Change" and (C01X0223) "Ocean Ecosystems: Their Contribution to NZ Marine Productivity." Funding was also provided for specific collaborations by the US National Science Foundation from grants OCE-0326814 (Ward), OCE-0327779 (Ho), and OCE 0327188 OCE-0326814 (Minnett) and the UK Natural Environment Research Council NER/B/S/2003/00282 (Archer). The New Zealand International Science and Technology (ISAT) linkages fund provided additional funding (Archer and Ziolkowski), and the many collaborator institutions also provided valuable support

Meaning-Making Lenses in Counselling: Discursive, Hermeneutic-Phenomenological, and Autoethnographic Perspectives

Counselling can be seen as a context or process for meaning-making where clients and counsellors actively interpret and construct meaning. We examine meaning-making in counselling through the lenses of three research methods: (a) discourse analysis, (b) hermeneutic-phenomenology, and (c) autoethnography. Specifically, we relate the process and experience of counselling in ways consistent with how meaning-making is regarded by each of these research methods. In this regard, we describe each method as if it was a counselling theory. We conclude by reflecting upon how these lenses on meaning-making and counselling can inform counselling practice generally and generatively.Le counselling peut être vue comme un contexte ou un processus de construction de sens où les clients et les conseillers activement interprètent et construient la signification. La construction de sens en counselling est examiné à travers l’optique de trois méthodes de recherche : (a) l’analyse de discours, (b) la phénoménologie herméneutique, et (c) l’autoethnographie. Spécifiquement, le processus et l’expérience de counselling sont associés de manière consistente avec une perspective de construction de sens dans chacune de ces méthodes de recherche. Chaque méthode est décrite comme une théorie de counselling. La conclusion se veut une réfl exion sur la contribution potentielle de ces optiques pour la pratique du counselling de façon générale et générative

Community integration: showcasing the evidence for therapeutic recreation services

Community integration (CI) is an important aspect of therapeutic recreation services for many client groups. CI speaks to the full social, physical, and psychological presence of individuals with disabilities and/or illnesses in their communities, whether that may be their personal homes, group homes, halfway houses, or long-term care facilities. The benefits of CI are numerous and include physical, social, psychological, health, and quality of life related outcomes. The purpose of this paper is to review the recent research regarding CI for individuals with (a) cerebrovascular accidents and traumatic brain injury, (b) intellectual and/or developmental disabilities, (c) mental illnesses, and (d) spinal cord injuries, and for (e) aging individuals with chronic diseases and/or illnesses. Specific implications for therapeutic recreation practice from this research are highlighted

Grieving together and apart: Bereaved parents’ contradictions of marital interaction

The researchers adopted relational dialectics theory (Baxter & Montgomery, 1996) to examine the discourse of 40 bereaved parents following the death of a child. Research questions guiding the study were what dialectical contradictions do bereaved parents experience when communicating with each other after their child’s death and how do bereaved parents communicatively negotiate the dialectical contradictions they experience? Bereaved parents experienced two dialectical contradictions-the first between trying to grieve their child’s death together as a couple and apart as individuals and the second between being both open and closed when talking with one another about their deceased child. Results describe how parents negotiated these contradictions using Baxter and Montgomery’s (1996) praxical patterns. Implications for bereaved parents and practitioners are discussed

New development opportunities for the craft brewing segment: the case study of a micro-malthouse

In Italy in the past few years, the number of small breweries penetrating the craft beer sector has grown exponentially. Craft producers intend to give a strong added value and a local character to their production in different ways. One of these is the use of malt derived from small batches of local cereals and pseudo cereals. The aim of this study is the assessment of investment profitability, through a cost-benefit analysis (CBA), for a compact and a modular micro-malting plant in Sicily (Southern Italy). The CBA for a micro-malthouse was carried out considering both installation and operating costs. Net present value (NPV), discounted benefit-cost ratio (DBCR) and internal rate of return (IRR) highlight the feasibility of an investment in a compact 2-tonnes micro-malthouse. Sensitivity analysis shows positive results of the above financial indices up to a 15% increase in the raw material costs, while with a 10% reduction of malt selling price, the same indices start being negative