Letter from [O. C. Haslett ?] to John Muir, 1907 Oct 18.

[illegible] Oct. 18, 1907.Mr. John Muir, Martinez, Cal. Dear Sir:- I wish to impose on your good nature to the extent of settling a little dispute. To begin with, I want to any that I feel as though I were acquainted with you through reading some of your works on California and its forests, more particularly our National Parks , and through the medium of an acquaintance with Miss Ellie Mosgrove who is a friend of my family\u27s and who has often told me of her trip with you. Also Mr. C. F. Some, our former bookkeeper and quite a student of botany, has often [illegible] to no about you.The matter in dispute came about in this manner. I recently made a trip over the Hcoloud River Limber Company\u27s property with come of their [illegible] owners and while going through the timber they and their Manager continually referred to the Red Fir. I remarked that I thought the trees in question were Douglas Spruce and their Manager Disputed me quite vigorously. Later on we drove down Soda Creek, which you may recall ompties into the Sacramento River at soda Springs, and while driving along there were comments on the amount of Red Fir in this particular tract, which was then under offer to some eastern parties. In passing one large tree in particular I said I am quite sure this is not Red Fir but is a genuine Douglas Spruce, a close relative, if not identical with, the Douglas spruce or Oregon Pine of Oregon and Washington. It had a heavy, black corrugated bark and very fine needles and was entirely similar in 2 - J. M.[illegible]many ways - even the lumber itself when manufactured has a strong resemblance. Again their Manager contradicted me emphatically, and so I determined to look it up. Later on another member of the party a California lumberman also with whom I was discussing the matter, was equally emphatic in contradicting me and even went so far as to claim that there was no such thing as Douglas spruce in the Sierra Revada Mountains, or in California for that matter. I told him that I was so positive of my position that I would bet him anything he wanted and leave it to any well known naturalist or botanist to determine, and mentioned your name as a good authority. Since then I returned home and referring to my library consulted your National Parks and find that you support my contention absolutely on a member of different pages. My contention is that the Red Fir does not grow at a lower altitude than about 5000 ft. and from that up to 8000, whereas the spruce grows from 5000 to 8000 ft. and it happened that we were at an altitude of less than 4000 when the discussion arose, and there is a very marked difference in both the bark and needles and in fact general appenrance of the tree closer and look something like the fronde of the palm, whereas the branches of the Spruce stand out much as they do on the Sugar Pine and the needles are smaller and tesselated. To me there is such a marked difference that I cannot see any room for dispute, but as it has arisen I will greatly appreciate it if you will be the means of settling it.In conclusion I want to any that while my business requires me to be a fallen of trees, I am nearly as much a lover of the forests as your good self and try to study them, whenever I am in them, largely as a result of your teachings. Thanking you in advance for this information, 5- J. M.I am, Yours very truly, Have you ever published anything of your trip to the Caucasus or do you intend to [illegible] I have been looking for it but so far have not heard whether you did or not

Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung

Phagocytes not only coordinate acute inflammation and host defense at mucosal sites, but also contribute to tissue damage. Respiratory infection causes a globally significant disease burden and frequently progresses to acute respiratory distress syndrome, a devastating inflammatory condition characterized by neutrophil recruitment and accumulation of protein-rich edema fluid causing impaired lung function. We hypothesized that targeting the intracellular protein myeloid cell leukemia 1 (Mcl-1) by a cyclin-dependent kinase inhibitor (AT7519) or a flavone (wogonin) would accelerate neutrophil apoptosis and resolution of established inflammation, but without detriment to bacterial clearance. Mcl-1 loss induced human neutrophil apoptosis, but did not induce macrophage apoptosis nor impair phagocytosis of apoptotic neutrophils. Neutrophil-dominant inflammation was modelled in mice by either endotoxin or bacteria (Escherichia coli). Downregulating inflammatory cell Mcl-1 had anti-inflammatory, pro-resolution effects, shortening the resolution interval (R(i)) from 19 to 7 h and improved organ dysfunction with enhanced alveolar–capillary barrier integrity. Conversely, attenuating drug-induced Mcl-1 downregulation inhibited neutrophil apoptosis and delayed resolution of endotoxin-mediated lung inflammation. Importantly, manipulating lung inflammatory cell Mcl-1 also accelerated resolution of bacterial infection (R(i); 50 to 16 h) concurrent with enhanced bacterial clearance. Therefore, manipulating inflammatory cell Mcl-1 accelerates inflammation resolution without detriment to host defense against bacteria, and represents a target for treating infection-associated inflammation

Differential responses of osteoblasts and macrophages upon Staphylococcus aureus infection

Background Staphylococcus aureus (S. aureus) is one of the primary causes of bone infections which are often chronic and difficult to eradicate. Bacteria like S. aureus may survive upon internalization in cells and may be responsible for chronic and recurrent infections. In this study, we compared the responses of a phagocytic cell (i.e. macrophage) to a non-phagocytic cell (i.e. osteoblast) upon S. aureus internalization. Results We found that upon internalization, S. aureus could survive for up to 5 and 7 days within macrophages and osteoblasts, respectively. Significantly more S. aureus was internalized in macrophages compared to osteoblasts and a significantly higher (100 fold) level of live intracellular S. aureus was detected in macrophages compared to osteoblasts. However, the percentage of S. aureus survival after infection was significantly lower in macrophages compared to osteoblasts at post-infection days 1–6. Interestingly, macrophages had relatively lower viability in shorter infection time periods (i.e. 0.5-4 h; significant at 2 h) but higher viability in longer infection time periods (i.e. 6–8 h; significant at 8 h) compared to osteoblasts. In addition, S. aureusinfection led to significant changes in reactive oxygen species production in both macrophages and osteoblasts. Moreover, infected osteoblasts had significantly lower alkaline phosphatase activity at post-infection day 7 and infected macrophages had higher phagocytosis activity compared to non-infected cells. Conclusions S. aureus was found to internalize and survive within osteoblasts and macrophages and led to differential responses between osteoblasts and macrophages. These findings may assist in evaluation of the pathogenesis of chronic and recurrent infections which may be related to the intracellular persistence of bacteria within host cells

Meta-analysis of muscle transcriptome data using the MADMuscle database reveals biologically relevant gene patterns

<p>Abstract</p> <p>Background</p> <p>DNA microarray technology has had a great impact on muscle research and microarray gene expression data has been widely used to identify gene signatures characteristic of the studied conditions. With the rapid accumulation of muscle microarray data, it is of great interest to understand how to compare and combine data across multiple studies. Meta-analysis of transcriptome data is a valuable method to achieve it. It enables to highlight conserved gene signatures between multiple independent studies. However, using it is made difficult by the diversity of the available data: different microarray platforms, different gene nomenclature, different species studied, etc.</p> <p>Description</p> <p>We have developed a system tool dedicated to muscle transcriptome data. This system comprises a collection of microarray data as well as a query tool. This latter allows the user to extract similar clusters of co-expressed genes from the database, using an input gene list. Common and relevant gene signatures can thus be searched more easily. The dedicated database consists in a large compendium of public data (more than 500 data sets) related to muscle (skeletal and heart). These studies included seven different animal species from invertebrates (<it>Drosophila melanogaster, Caenorhabditis elegans</it>) and vertebrates (<it>Homo sapiens, Mus musculus, Rattus norvegicus, Canis familiaris, Gallus gallus</it>). After a renormalization step, clusters of co-expressed genes were identified in each dataset. The lists of co-expressed genes were annotated using a unified re-annotation procedure. These gene lists were compared to find significant overlaps between studies.</p> <p>Conclusions</p> <p>Applied to this large compendium of data sets, meta-analyses demonstrated that conserved patterns between species could be identified. Focusing on a specific pathology (Duchenne Muscular Dystrophy) we validated results across independent studies and revealed robust biomarkers and new pathways of interest. The meta-analyses performed with MADMuscle show the usefulness of this approach. Our method can be applied to all public transcriptome data.</p

Endogenous TNF alpha orchestrates the trafficking of neutrophils into and within lymphatic vessels during acute inflammation

This work was supported by funds from Arthritis Research UK (19913 to M.-B.V.) and the Wellcome Trust (098291/Z/12/Z to S.N.). S. A. was supported by a QMUL Principal’s Award PhD Studentship

Evaluation of the anti-inflammatory effects of synthesised tanshinone I and isotanshinone I analogues in zebrafish

During inflammation, dysregulated neutrophil behaviour can play a major role in a range of chronic inflammatory diseases, for many of which current treatments are generally ineffective. Recently, specific naturally occurring tanshinones have shown promising anti-inflammatory effects by targeting neutrophils in vivo, yet such tanshinones, and moreover, their isomeric isotanshinone counterparts, are still a largely underexplored class of compounds, both in terms of synthesis and biological effects. To explore the anti-inflammatory effects of isotanshinones, and the tanshinones more generally, a series of substituted tanshinone and isotanshinone analogues was synthesised, alongside other structurally similar molecules. Evaluation of these using a transgenic zebrafish model of neutrophilic inflammation revealed differential anti-inflammatory profiles in vivo, with a number of compounds exhibiting promising effects. Several compounds reduce initial neutrophil recruitment and/or promote resolution of neutrophilic inflammation, of which two also result in increased apoptosis of human neutrophils. In particular, the methoxy-substituted tanshinone 39 specifically accelerates resolution of inflammation without affecting the recruitment of neutrophils to inflammatory sites, making this a particularly attractive candidate for potential pro-resolution therapeutics, as well as a possible lead for future development of functionalised tanshinones as molecular tools and/or chemical probes. The structurally related β-lapachones promote neutrophil recruitment but do not affect resolution. We also observed notable differences in toxicity profiles between compound classes. Overall, we provide new insights into the in vivo anti-inflammatory activities of several novel tanshinones, isotanshinones, and structurally related compounds