Feedback

THE PHILOSOPHICAL NEWTON Andrew Janiak, Newton as Philosopher (Cambridge: Cambridge University Press, 2008), ISBN 13 978-0-521-86286-8 (hardback), ISBN 13 978-0-511-41404-6 (eBook), pp. 196

Documento informativo
THE PHILOSOPHICAL NEWTON Andrew Janiak, Newton as Philosopher (Cambridge: Cambridge University Press, 2008), ISBN 13 978-0-521-86286-8 (hardback), ISBN 13 978-0-511-41404-6 (eBook), pp. 196 Grigore VIDA∗ When Newton is referring to his works, he usually speaks about “my Philosophy.” The reader who opens the third edition of the Principia is announced on the first page that he will learn about “Newtoni Principia Philosophiæ.” Moreover, eighteenth-century expositions of the Newtonian achievements – whether by Henry Pemberton, Colin MacLaurin or Voltaire – are always claiming to present “Newton’s Philosophy.”1 In those days, a title like Newton as Philosopher would have made little sense, since it was obvious that he was one, and not so obvious what else he could have been. Today, however, such a title can sound provocative. Newton is not a very familiar figure in most of the histories of philosophy. He gets to be mentioned in connection with the Leibniz-Clarke correspondence, as holding a conception of space that is usually so oversimplified that it has nothing to do with Newton’s original intention; this happens especially in the caricature view that the main problems of early modern philosophy found their solution in Kant. But here is someone who has arrived at Newton by studying Kant and now devotes a book to the strictly philosophical part of the author of the Principia; Andrew Janiak declares from the very beginning that “this is a work in the history of philosophy” (p. vii). He does this after a 2004 edition of Newton’s Philosophical Writings,2 where technicalities from mathematics or rational mechanics are carefully avoided. This type of approach is not a novelty; especially J. E. McGuire’s studies3 have shown that the ‘philosophical Newton’ can be extremely rich. But a monographic treatment of Newton’s philosophy such as Janiak’s is certainly something rare and to be welcomed, since it does justice to a side of Newton that has an important place among the various other sides (alchemy, scriptural theology etc.) that balance the usual ‘hero of science’ image. As it is evident from above and as Janiak writes, “[t]o treat Newton as a philosopher might simply be to avoid an [anachronism]” (p. 1), reflecting in this way Newton’s own self-conception. The problem is that Newton’s concept of philosophy is radically different from ours and Janiak tends to conflate them. Although sometimes Newton speaks distinctively (and in the same context) about ∗ University of Bucharest, Faculty of Philosophy, Department of Theoretical Philosophy, 204 Splaiul Independenţei, Bucureşti, e-mail: grigore.vida@gmail.com Grigore Vida - The philosophical Newton “philosophy” and “natural philosophy,” there is no clear-cut distinction between the two.4 As for today, it is hard to define what philosophy is, but it is certainly separated from physico-mathematical inquiries. Instead, natural philosophy could be lacking anything that would be labeled today as ‘philosophical’ and still be natural philosophy. Of course, natural philosophy could contain elements that we straightforwardly call metaphysical or epistemological, but not necessarily. My point is that taking Newton as a philosopher in our sense does not reflect the way he considered himself. This is worth emphasizing because one might get the impression that Janiak puts weight on historical accuracy; but this is largely an illusion. His analyses are conceptual, while historical considerations play little, if any, role. Such an approach is absolutely legitimate, but it has some limitations. For instance, Janiak constantly insists on the idea that Newton is “contesting the mechanical philosophy” (chapters 3 and 4 bear this expression in their title). He takes Newton to be using the word “mechanical” in a technical sense, namely as something operating only on the surfaces of bodies; consequently, the cause of gravity cannot be mechanical, since it is proportional to the whole quantity of matter in a body (pp. 75-76). But “mechanical” could mean a lot of things in the seventeenth century and the “mechanical philosophy” is something sufficiently vague so as to have Newton included within it (like Richard Westfall or the Halls did). 5 To be sure, Newton changed his mind so many times regarding the cause of gravity, that it is hard to ascribe him an overarching position; he was very cautious about committing himself and it seems that he always left the door open for a mechanical explanation. The ether-queries appended to the second English edition (1717) of the Opticks are his last words on this subject and they bear a strong ‘mechanical’ flavor. The technical meaning of “mechanical” also helps Janiak to argue that although Newton rejects the mechanical philosophy, he does not accept action at a distance: not all local action is impact or surface (i. e. mechanical) action, as Leibniz contended. For Janiak the denial of distant action as “unconceivable” in the famous letter to Bentley6 is fundamental. God’s actions are always local, since he is everywhere and, moreover, bodies do not encounter resistance from his presence; this makes God a serious candidate for the cause of gravity (although it should be noted that Newton oscillated on this topic). The way Janiak puts these things together certainly makes sense, but some recent critics of his interpretation (most notably John Henry and Eric Schliesser)7 hold that the letter to Bentley is not only overemphasized, but it can also be put upside down on a careful reading, so that Newton is in fact not denying that gravity acts at a distance – and this is how eighteenth-century readers understood Newtonian gravity. But Janiak makes another interesting point about action at a distance. Sometime in the final stages of editing the second edition of the Principia, Roger Cotes sent Newton a letter in which he pressed him to accept distant action, as being implied by the application of the third law of motion to bodies that are not 166 Society and Politics Vol. 5, No. 2(10)/November 2011 contiguous. In his reply, Newton avoided to answer Cotes’ objection. Usually Newton was persuaded by arguments from physical theory, but this case seems to be an exception. For Janiak, Newton’s reluctance is explained by his unwillingness to change his conception about God acting only locally. This means that Newton’s ideas about God, or what Janiak calls “divine metaphysics,” are immune to revisions determined by physical theory; such revisions are restricted only for the “mundane metaphysics” or “physical metaphysics.” The latter one was put forward by adepts of Newton “the radical empiricist” - like Howard Stein or Robert DiSalle, - and Janiak essentially agrees with them, except when it comes to God. It could be argued, however, that the interaction between Newton’s theology and his natural science is less static than Janiak presents it, especially if we think at Newtonian cosmology. Although debatable, Janiak’s theses are composing a coherent picture and they can also set up an agenda. References 1 Pemberton, H., A View of Sir Isaac Newton’s Philosophy (London, 1728); MacLaurin, C., An Account of Sir Isaac Newton’s Philosophical Discoveries (London, 1748 – posthumous); Voltaire, Elémens de la philosophie de Neuton (Amsterdam, 1738). 2 Newton, I., Philosophical Writings, ed. A. Janiak (Cambridge: Cambridge University Press, 2004). 3 An important part of them is collected in McGuire, J. E., Tradition and Innovation: Newton’s Metaphysics of Nature (Dordrecht: Kluwer Academic Publishers, 1995). 4 McGuire, J. E., “Newton’s «Principles of Philosophy»: An Intended Preface for the 1704 Opticks and a Related Draft Fragment”, British Journal for the History of Science 5 (1970): 178186. See also “Of Educating Youth in the Universities”, in Unpublished Scientific Papers of Isaac Newton, eds. A. Rupert Hall & Marie Boas Hall (Cambridge: Cambridge University Press, 1962), 369-373. 5 See Westfall, R. S., Force in Newton’s Physics: The Science of Dynamics in the Seventeenth Century (London: Macdonald; New York: American Elsevier, 1971); the comments by Hall & Hall in their edition of Newton’s Unpublished Scientific Papers. 6 The Correspondence of Isaac Newton, eds. H. W. Turnbull, J. F. Scott, A. R. Hall, L. Tilling (Cambridge: Cambridge University Press, 1959-1977), 7 vols., vol. III, 253-254. 7 Henry, J., “Gravity and De gravitatione: The Development of Newton’s Ideas on Action at a Distance”, Studies in History and Philosophy of Science 42 (2011): 11-27; Schliesser, E., “Without God. Gravity as a relational Quality of Matter in Newton’s Treatise”, in Vanishing Matter and the Laws of Motion: Descartes and Beyond, eds. D. Jalobeanu & P. R. Anstey (London: Routledge, 2011), 80-100. 167 equilibrium value of MeCpG steps (,+14 deg.) [31,44]. In comparison, methylation has a significantly lower stability cost when happening at major groove positions, such as 211 and 21 base pair from dyad (mutations 9 and 12), where the roll of the nucleosome bound conformation (+10 deg.) is more compatible with the equilibrium geometry of MeCpG steps. The nucleosome destabilizing effect of cytosine methylation increases with the number of methylated cytosines, following the same position dependence as the single methylations. The multiple-methylation case reveals that each major groove meth- PLOS Computational Biology | www.ploscompbiol.org 3 November 2013 | Volume 9 | Issue 11 | e1003354 DNA Methylation and Nucleosome Positioning ylation destabilizes the nucleosome by around 1 kJ/mol (close to the average estimate of 2 kJ/mol obtained for from individual methylation studies), while each minor groove methylation destabilizes it by up to 5 kJ/mol (average free energy as single mutation is around 6 kJ/mol). This energetic position-dependence is the reverse of what was observed in a recent FRET/SAXS study [30]. The differences can be attributed to the use of different ionic conditions and different sequences: a modified Widom-601 sequence of 157 bp, which already contains multiple CpG steps in mixed orientations, and which could assume different positioning due to the introduction of new CpG steps and by effect of the methylation. The analysis of our trajectories reveals a larger root mean square deviation (RMSD) and fluctuation (RMSF; see Figures S2– S3 in Text S1) for the methylated nucleosomes, but failed to detect any systematic change in DNA geometry or in intermolecular DNA-histone energy related to methylation (Fig. S1B, S1C, S4–S6 in Text S1). The hydrophobic effect should favor orientation of the methyl group out from the solvent but this effect alone is not likely to justify the positional dependent stability changes in Figure 2, as the differential solvation of the methyl groups in the bound and unbound states is only in the order of a fraction of a water molecule (Figure S5 in Text S1). We find however, a reasonable correlation between methylation-induced changes in hydrogen bond and stacking interactions of the bases and the change in nucleosome stability (see Figure S6 in Text S1). This finding suggests that methylation-induced nucleosome destabilization is related to the poorer ability of methylated DNA to fit into the required conformation for DNA in a nucleosome. Changes in the elastic deformation energy between methylated and un-methylated DNA correlate with nucleosomal differential binding free energies To further analyze the idea that methylation-induced nucleosome destabilization is connected to a worse fit of methylated DNA into the required nucleosome-bound conformation, we computed the elastic energy of the nucleosomal DNA using a harmonic deformation method [36,37,44]. This method provides a rough estimate of the energy required to deform a DNA fiber to adopt the super helical conformation in the nucleosome (full details in Suppl. Information Text S1). As shown in Figure 2, there is an evident correlation between the increase that methylation produces in the elastic deformation energy (DDE def.) and the free energy variation (DDG bind.) computed from MD/TI calculations. Clearly, methylation increases the stiffness of the CpG step [31], raising the energy cost required to wrap DNA around the histone octamers. This extra energy cost will be smaller in regions of high positive roll (naked DNA MeCpG steps have a higher roll than CpG steps [31]) than in regions of high negative roll. Thus, simple elastic considerations explain why methylation is better tolerated when the DNA faces the histones through the major groove (where positive roll is required) that when it faces histones through the minor groove (where negative roll is required). Nucleosome methylation can give rise to nucleosome repositioning We have established that methylation affects the wrapping of DNA in nucleosomes, but how does this translate into chromatin structure? As noted above, accumulation of minor groove methylations strongly destabilizes the nucleosome, and could trigger nucleosome unfolding, or notable changes in positioning or phasing of DNA around the histone core. While accumulation of methylations might be well tolerated if placed in favorable positions, accumulation in unfavorable positions would destabilize the nucleosome, which might trigger changes in chromatin structure. Chromatin could in fact react in two different ways in response to significant levels of methylation in unfavorable positions: i) the DNA could either detach from the histone core, leading to nucleosome eviction or nucleosome repositioning, or ii) the DNA could rotate around the histone core, changing its phase to place MeCpG steps in favorable positions. Both effects are anticipated to alter DNA accessibility and impact gene expression regulation. The sub-microsecond time scale of our MD trajectories of methylated DNAs bound to nucleosomes is not large enough to capture these effects, but clear trends are visible in cases of multiple mutations occurring in unfavorable positions, where unmethylated and methylated DNA sequences are out of phase by around 28 degrees (Figure S7 in Text S1). Due to this repositioning, large or small, DNA could move and the nucleosome structure could assume a more compact and distorted conformation, as detected by Lee and Lee [29], or a slightly open conformation as found in Jimenez-Useche et al. [30]. Using the harmonic deformation method, we additionally predicted the change in stability induced by cytosine methylation for millions of different nucleosomal DNA sequences. Consistently with our calculations, we used two extreme scenarios to prepare our DNA sequences (see Fig. 3): i) all positions where the minor grooves contact the histone core are occupied by CpG steps, and ii) all positions where the major grooves contact the histone core are occupied by CpG steps. We then computed the elastic energy required to wrap the DNA around the histone proteins in unmethylated and methylated states, and, as expected, observed that methylation disfavors DNA wrapping (Figure 3A). We have rescaled the elastic energy differences with a factor of 0.23 to match the DDG prediction in figure 2B. In agreement with the rest of our results, our analysis confirms that the effect of methylation is position-dependent. In fact, the overall difference between the two extreme methylation scenarios (all-in-minor vs all-in-major) is larger than 60 kJ/mol, the average difference being around 15 kJ/ mol. We have also computed the elastic energy differences for a million sequences with CpG/MeCpG steps positioned at all possible intermediate locations with respect to the position (figure 3B). The large differences between the extreme cases can induce rotations of DNA around the histone core, shifting its phase to allow the placement of the methylated CpG steps facing the histones through the major groove. It is illustrative to compare the magnitude of CpG methylation penalty with sequence dependent differences. Since there are roughly 1.5e88 possible 147 base pairs long sequence combinations (i.e., (4n+4(n/2))/2, n = 147), it is unfeasible to calculate all the possible sequence effects. However, using our elastic model we can provide a range of values based on a reasonably large number of samples. If we consider all possible nucleosomal sequences in the yeast genome (around 12 Mbp), the energy difference between the best and the worst sequence that could form a nucleosome is 0.7 kj/mol per base (a minimum of 1 kJ/mol and maximum of around 1.7 kJ/mol per base, the first best and the last worst sequences are displayed in Table S3 in Text S1). We repeated the same calculation for one million random sequences and we obtained equivalent results. Placing one CpG step every helical turn gives an average energetic difference between minor groove and major groove methylation of 15 kJ/ mol, which translates into ,0.5 kJ/mol per methyl group, 2 kJ/ mol per base for the largest effects. Considering that not all nucleosome base pair steps are likely to be CpG steps, we can conclude that the balance between the destabilization due to CpG methylation and sequence repositioning will depend on the PLOS Computational Biology | www.ploscompbiol.org 4 November 2013 | Volume 9 | Issue 11 | e1003354 DNA Methylation and Nucleosome Positioning Figure 3. Methylated and non-methylated DNA elastic deformation energies. (A) Distribution of deformation energies for 147 bplong random DNA sequences with CpG steps positioned every 10 base steps (one helical turn) in minor (red and dark red) and major (light and dark blue) grooves respectively. The energy values were rescaled by the slope of a best-fit straight line of figure 2, which is 0.23, to in the aquatic environment for long-term survival and for transmission to arthropod and mammalian hosts. References 1. Ray K, Marteyn B, Sansonetti PJ, Tang CM. Life on the inside: the intracellular lifestyle of cytosolic bacteria. Nature reviews. 2009; 7(5):333–40. doi: 10.1038/nrmicro2112 PMID: 19369949 2. Kingry LC, Petersen JM. Comparative review of Francisella tularensis and Francisella novicida. Frontiers in cellular and infection microbiology. 2014; 4:35. doi: 10.3389/fcimb.2014.00035 PMID: 24660164 3. Sjodin A, Svensson K, Ohrman C, Ahlinder J, Lindgren P, Duodu S, et al. Genome characterisation of the genus Francisella reveals insight into similar evolutionary paths in pathogens of mammals and fish. BMC genomics. 2012; 13:268. doi: 10.1186/1471-2164-13-268 PMID: 22727144 4. Ellis J, Oyston PC, Green M, Titball RW. Tularemia. Clinical microbiology reviews. 2002; 15(4):631–46. PMID: 12364373 5. Gurcan S. Epidemiology of tularemia. Balkan medical journal. 2014; 31(1):3–10. doi: 10.5152/ balkanmedj.2014.13117 PMID: 25207161 6. Petersen JM, Mead PS, Schriefer ME. Francisella tularensis: an arthropod-borne pathogen. Veterinary research. 2009; 40(2):7. doi: 10.1051/vetres:2008045 PMID: 18950590 7. Lundstrom JO, Andersson AC, Backman S, Schafer ML, Forsman M, Thelaus J. Transstadial transmission of Francisella tularensis holarctica in mosquitoes, Sweden. Emerging infectious diseases. 2011; 17(5):794–9. doi: 10.3201/eid1705.100426 PMID: 21529386 8. van Hoek ML. Biofilms: an advancement in our understanding of Francisella species. Virulence. 2013; 4(8):833–46. doi: 10.4161/viru.27023 PMID: 24225421 9. Ryden P, Sjostedt A, Johansson A. Effects of climate change on tularaemia disease activity in Sweden. Global health action. 2009; 2. PLOS Pathogens | DOI:10.1371/journal.ppat.1005208 December 3, 2015 6/8 10. Barker JR, Chong A, Wehrly TD, Yu JJ, Rodriguez SA, Liu J, et al. The Francisella tularensis pathogenicity island encodes a secretion system that is required for phagosome escape and virulence. Molecular microbiology. 2009; 74(6):1459–70. PMID: 20054881 11. de Bruin OM, Duplantis BN, Ludu JS, Hare RF, Nix EB, Schmerk CL, et al. The biochemical properties of the Francisella pathogenicity island (FPI)-encoded proteins IglA, IglB, IglC, PdpB and DotU suggest roles in type VI secretion. Microbiology (Reading, England). 2011; 157(Pt 12):3483–91. 12. Filloux A, Hachani A, Bleves S. The bacterial type VI secretion machine: yet another player for protein transport across membranes. Microbiology (Reading, England). 2008; 154(Pt 6):1570–83. 13. Nguyen JQ, Gilley RP, Zogaj X, Rodriguez SA, Klose KE. Lipidation of the FPI protein IglE contributes to Francisella tularensis ssp. novicida intramacrophage replication and virulence. Pathogens and disease. 2014; 72(1):10–8. doi: 10.1111/2049-632X.12167 PMID: 24616435 14. Hood RD, Singh P, Hsu F, Guvener T, Carl MA, Trinidad RR, et al. A type VI secretion system of Pseudomonas aeruginosa targets a toxin to bacteria. Cell host & microbe. 2010; 7(1):25–37. 15. Mougous JD, Cuff ME, Raunser S, Shen A, Zhou M, Gifford CA, et al. A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus. Science (New York, NY. 2006; 312 (5779):1526–30. 16. Pukatzki S, Ma AT, Revel AT, Sturtevant D, Mekalanos JJ. Type VI secretion system translocates a phage tail spike-like protein into target cells where it cross-links actin. Proceedings of the National Academy of Sciences of the United States of America. 2007; 104(39):15508–13. PMID: 17873062 17. Santic M, Molmeret M, Klose KE, Jones S, Kwaik YA. The Francisella tularensis pathogenicity island protein IglC and its regulator MglA are essential for modulating phagosome biogenesis and subsequent bacterial escape into the cytoplasm. Cellular microbiology. 2005; 7(7):969–79. PMID: 15953029 18. de Bruin OM, Ludu JS, Nano FE. The Francisella pathogenicity island protein IglA localizes to the bacterial cytoplasm and is needed for intracellular growth. BMC microbiology. 2007; 7:1. PMID: 17233889 19. Llewellyn AC, Jones CL, Napier BA, Bina JE, Weiss DS. Macrophage replication screen identifies a novel Francisella hydroperoxide resistance protein involved in virulence. PloS one. 2011; 6(9):e24201. doi: 10.1371/journal.pone.0024201 PMID: 21915295 20. Clemens DL, Lee BY, Horwitz MA. Virulent and avirulent strains of Francisella tularensis prevent acidification and maturation of their phagosomes and escape into the cytoplasm in human macrophages. Infection and immunity. 2004; 72(6):3204–17. PMID: 15155622 21. Moreau GB, Mann BJ. Adherence and uptake of Francisella into host cells. Virulence. 2013; 4(8):826– 32. doi: 10.4161/viru.25629 PMID: 23921460 22. Tamilselvam B, Daefler S. Francisella targets cholesterol-rich host cell membrane domains for entry into macrophages. J Immunol. 2008; 180(12):8262–71. PMID: 18523292 23. Chong A, Wehrly TD, Nair V, Fischer ER, Barker JR, Klose KE, et al. The early phagosomal stage of Francisella tularensis determines optimal phagosomal escape and Francisella pathogenicity island protein expression. Infection and immunity. 2008; 76(12):5488–99. doi: 10.1128/IAI.00682-08 PMID: 18852245 24. Celli J, Zahrt TC. Mechanisms of Francisella tularensis intracellular pathogenesis. Cold Spring Harbor perspectives in medicine. 2013; 3(4):a010314. doi: 10.1101/cshperspect.a010314 PMID: 23545572 25. Santic M, Asare R, Skrobonja I, Jones S, Abu Kwaik Y. Acquisition of the vacuolar ATPase proton pump and phagosome acidification are essential for escape of Francisella tularensis into the macrophage cytosol. Infection and immunity. 2008; 76(6):2671–7. doi: 10.1128/IAI.00185-08 PMID: 18390995 26. Jones CL, Napier BA, Sampson TR, Llewellyn AC, Schroeder MR, Weiss DS. Subversion of host recognition and defense systems by Francisella spp. Microbiol Mol Biol Rev. 2012; 76(2):383–404. doi: 10. 1128/MMBR.05027-11 PMID: 22688817 27. Pierini R, Juruj C, Perret M, Jones CL, Mangeot P, Weiss DS, et al. AIM2/ASC triggers caspase-8dependent apoptosis in Francisella-infected caspase-1-deficient macrophages. Cell death and differentiation. 2012; 19(10):1709–21. doi: 10.1038/cdd.2012.51 PMID: 22555457 28. Asare R, Kwaik YA. Exploitation of host cell biology and evasion of immunity by francisella tularensis. Frontiers in microbiology. 2011; 1:145. doi: 10.3389/fmicb.2010.00145 PMID: 21687747 29. Keim P, Johansson A, Wagner DM. Molecular epidemiology, evolution, and ecology of Francisella. Annals of the New York Academy of Sciences. 2007; 1105:30–66. PMID: 17435120 30. Asare R, Akimana C, Jones S, Abu Kwaik Y. Molecular bases of proliferation of Francisella tularensis in arthropod vectors. Environmental microbiology. 2010; 12(9):2587–612. doi: 10.1111/j.1462-2920. 2010.02230.x PMID: 20482589 PLOS Pathogens | DOI:10.1371/journal.ppat.1005208 December 3, 2015 7/8 31. Vonkavaara M, Telepnev MV, Ryden P, Sjostedt A, Stoven S. Drosophila melanogaster as a model for elucidating the pathogenicity of Francisella tularensis. Cellular microbiology. 2008; 10(6):1327–38. doi: 10.1111/j.1462-5822.2008.01129.x PMID: 18248629 32. Santic M, Akimana C, Asare R, Kouokam JC, Atay S, Kwaik YA. Intracellular fate of Francisella tularensis within arthropod-derived cells. Environmental microbiology. 2009; 11(6):1473–81. doi: 10.1111/j. 1462-2920.2009.01875.x PMID: 19220402 33. Read A, Vogl SJ, Hueffer K, Gallagher LA, Happ GM. Francisella genes required for replication in mosquito cells. Journal of medical entomology. 2008; 45(6):1108–16. PMID: 19058636 34. Ahlund MK, Ryden P, Sjostedt A, Stoven S. Directed screen of Francisella novicida virulence determinants using Drosophila melanogaster. Infection and immunity. 2010; 78(7):3118–28. doi: 10.1128/IAI. 00146-10 PMID: 20479082 35. Abd H, Johansson T, Golovliov I, Sandstrom G, Forsman M. Survival and growth of Francisella tularensis in Acanthamoeba castellanii. Applied and environmental microbiology. 2003; 69(1):600–6. PMID: 12514047 36. Santic M, Ozanic M, Semic V, Pavokovic G, Mrvcic V, Kwaik YA. Intra-Vacuolar Proliferation of F. Novicida within H. Vermiformis. Frontiers in microbiology. 2011; 2:78. doi: 10.3389/fmicb.2011.00078 PMID: 21747796 37. El-Etr SH, Margolis JJ, Monack D, Robison RA, Cohen M, Moore E, et al. Francisella tularensis type A strains cause the rapid encystment of Acanthamoeba castellanii and survive in amoebal cysts for three weeks postinfection. Applied and environmental microbiology. 2009; 75(23):7488–500. doi: 10.1128/ AEM.01829-09 PMID: 19820161 38. Lauriano CM, Barker JR, Yoon SS, Nano FE, Arulanandam BP, Hassett DJ, et al. MglA regulates transcription of virulence factors necessary for Francisella tularensis intraamoebae and intramacrophage survival. Proceedings of the National Academy of Sciences of the United States of America. 2004; 101 (12):4246–9. PMID: 15010524 PLOS Pathogens | DOI:10.1371/journal.ppat.1005208 December 3, 2015 8/8
THE PHILOSOPHICAL NEWTON Andrew Janiak, Newton as Philosopher (Cambridge: Cambridge University Press, 2008), ISBN 13 978-0-521-86286-8 (hardback), ISBN 13 978-0-511-41404-6 (eBook), pp. 196
RECENT ACTIVITIES
Autor
Documento similar
Tags

THE PHILOSOPHICAL NEWTON Andrew Janiak, Newton as Philosopher (Cambridge: Cambridge University Press, 2008), ISBN 13 978-0-521-86286-8 (hardback), ISBN 13 978-0-511-41404-6 (eBook), pp. 196

Livre