Nicholas Nathan tries to resist the current version of the causal argument for sense-data in two ... more Nicholas Nathan tries to resist the current version of the causal argument for sense-data in two ways. First he suggests that, on what he considers to be the correct re-construction of the argument, it equivocates on the sense of proximate cause. Second he defends a form of disjunctivism, by claiming that there might be an extra mechanism involved in producing veridical hallucination, that is not present in perception. I argue that Nathan’s reconstruction of the argument is not the appropriate one, and that, properly interpreted, the argument does not equivocate on proximate cause. Furthermore, I claim that his postulation of a modified mechanism for hallucinations is implausibly ad hoc.
Calreticulin has sequence homology with the molecular chaperone calnexin, which is known to contr... more Calreticulin has sequence homology with the molecular chaperone calnexin, which is known to control folding and assembly of nascent proteins in the endoplasmic reticulum in a calcium-dependent manner. We have investigated the interaction between human placental calreticulin and denatured placental and serum proteins under various incubation conditions. The interactions with denatured proteins differed significantly from the interactions with native proteins. The interactions were highly dependent on divalent metal ions or polyamines, but were not influenced by detergent and sulfhydryl agents. Our results indicate that calreticulin might have a similar role in protein folding as the chaperone calnexin.
Human Class III alcohol dehydrogenase (ADH), also known as glutathione-dependent formaldehyde deh... more Human Class III alcohol dehydrogenase (ADH), also known as glutathione-dependent formaldehyde dehydrogenase plays an important role in the formaldehyde detoxification and reduction of the nitric oxide metabolite s-nitrosoglutathione (GSNO). It follows a random bi bi kinetic mechanism and prefers bulkier substrates like long chain primary alcohols and glutathione adducts like s-hydroxymethylglutathione and GSNO over smaller alcohols like ethanol. The structure of the FDH.NAD(H) binary complex reported here, in conjunction with the other complexes of FDH, provide the structural basis of the kinetic observations. These structures show that the apoenzyme has a semi-open domain conformation that permits random random addition of alcohol or NAD(H). Moreover, there is no significant domain movement upon binding of the coenzyme or the substrate, 12-hydroxydodecanoic acid. Interestingly, two active site zinc coordination environments are observed in FDH. In the apoenzyme, the active site zinc is coordinated to Cys44, His66, Cys173 and a water molecule. In the FDH.NAD(H) binary complex reported here, Glu67 is added to the coordination environment of the active site zinc and the distance between the water molecule and zinc is increased. This change in the zinc coordination, brought about by the displacement of zinc of about 2 A towards Glu67 could promote substrate exchange at the active site metal during catalysis.
... Kim K. Heng, Jim Simpson, and Robin AJ Smith* Chemistry Department, University of Otago, Dune... more ... Kim K. Heng, Jim Simpson, and Robin AJ Smith* Chemistry Department, University of Otago, Dunedin, New Zealand Ward T. Robinson Chemistry Department, University ... 4) J. Mulzer, J. Segner, and G. Bruntrup, Tetrahedron Lett., 4651 (1977); A. I. Meyers and P. J. Reider, J. Am ...
Nicholas Nathan tries to resist the current version of the causal argument for sense-data in two ... more Nicholas Nathan tries to resist the current version of the causal argument for sense-data in two ways. First he suggests that, on what he considers to be the correct re-construction of the argument, it equivocates on the sense of proximate cause. Second he defends a form of disjunctivism, by claiming that there might be an extra mechanism involved in producing veridical hallucination, that is not present in perception. I argue that Nathan’s reconstruction of the argument is not the appropriate one, and that, properly interpreted, the argument does not equivocate on proximate cause. Furthermore, I claim that his postulation of a modified mechanism for hallucinations is implausibly ad hoc.
Calreticulin has sequence homology with the molecular chaperone calnexin, which is known to contr... more Calreticulin has sequence homology with the molecular chaperone calnexin, which is known to control folding and assembly of nascent proteins in the endoplasmic reticulum in a calcium-dependent manner. We have investigated the interaction between human placental calreticulin and denatured placental and serum proteins under various incubation conditions. The interactions with denatured proteins differed significantly from the interactions with native proteins. The interactions were highly dependent on divalent metal ions or polyamines, but were not influenced by detergent and sulfhydryl agents. Our results indicate that calreticulin might have a similar role in protein folding as the chaperone calnexin.
Human Class III alcohol dehydrogenase (ADH), also known as glutathione-dependent formaldehyde deh... more Human Class III alcohol dehydrogenase (ADH), also known as glutathione-dependent formaldehyde dehydrogenase plays an important role in the formaldehyde detoxification and reduction of the nitric oxide metabolite s-nitrosoglutathione (GSNO). It follows a random bi bi kinetic mechanism and prefers bulkier substrates like long chain primary alcohols and glutathione adducts like s-hydroxymethylglutathione and GSNO over smaller alcohols like ethanol. The structure of the FDH.NAD(H) binary complex reported here, in conjunction with the other complexes of FDH, provide the structural basis of the kinetic observations. These structures show that the apoenzyme has a semi-open domain conformation that permits random random addition of alcohol or NAD(H). Moreover, there is no significant domain movement upon binding of the coenzyme or the substrate, 12-hydroxydodecanoic acid. Interestingly, two active site zinc coordination environments are observed in FDH. In the apoenzyme, the active site zinc is coordinated to Cys44, His66, Cys173 and a water molecule. In the FDH.NAD(H) binary complex reported here, Glu67 is added to the coordination environment of the active site zinc and the distance between the water molecule and zinc is increased. This change in the zinc coordination, brought about by the displacement of zinc of about 2 A towards Glu67 could promote substrate exchange at the active site metal during catalysis.
... Kim K. Heng, Jim Simpson, and Robin AJ Smith* Chemistry Department, University of Otago, Dune... more ... Kim K. Heng, Jim Simpson, and Robin AJ Smith* Chemistry Department, University of Otago, Dunedin, New Zealand Ward T. Robinson Chemistry Department, University ... 4) J. Mulzer, J. Segner, and G. Bruntrup, Tetrahedron Lett., 4651 (1977); A. I. Meyers and P. J. Reider, J. Am ...
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