Based on correlative evidence, it was widely believed that phosphorylation of NFs along their carboxyl terminal domains regulates the slow axonal transport of NFs. In vivo slow axonal transport studies from NF-Hdeleted, NF-HtailD, and NF-MtailD optic nerves indicate that neither loss of the entire NF-H subunit, nor the loss of the tail domains of NF-H or NF-M, alters slow NF transport. Due to the possible functional redundancy of these tail domains, it was thought that an intact C-terminal domain on either subunit could preserve putative transport functions when the C-terminal domain is lost on the other subunit. By eliminating both C-terminal domains, we showed here that regardless of any functional redundancy, transport is not affected by combined loss of these domains. Although our evidence excludes a physiological role for Cterminal domains in regulating normal NF transport, it does not exclude the possible significant effect of pathological C-terminal tail phosphorylation in influencing NF transport. In vitro culture studies with GFP-labeled NF-H C-terminal KSP mutants that mimic hyperphosphorylation of NF-H C-terminal domain indicate that phosphorylation of NF-H KSP sites on the tail domain does slow the rate of axonal transport of NFs. These overexpressed NF-H mutants that mimic hyperphosphorylation may represent pathological conditions that are observed in multiple NF transgenic lines and ALS mouse models. Hyperphosphorylated C-terminal regions of both NF-H and NF-M are observed in human ALS patients and in mouse models that exhibit ALS-like disease symptoms after NF overexpression or overexpression of mutant SOD1. In these transgenic mouse models, NF transport rates were significantly Bortezomib reduced suggesting that defective axonal transport of NFs may contribute to NF accumulation and other ALS-related pathological symptoms. NF-M and NF-L head domains are also relatively highly phosphorylated but most of these phospho-residues are short lived, disappearing as soon as NFs enter into the axon. We speculate that some of the phosphorylation sites on these domains may regulate the NF axonal transport rate. Although phosphorylation on head domains is believed to prevent NF assembly in cell bodies, that head domain of NF-L partly regulates NF axonal transport. The results of this study, demonstrating dramatic non-uniform depletion of NF along NF-tailD axons despite unchanged transport rate, reinforce the notion that NF transport rate is not the principal determinant of NF content in mature axons, which is, instead the incorporation of transported NF into a large slowly turning over stationary NF network. We show here that the size of this stationary network is modulated at least in part by changes in the long half-lives of NF in this network, although the rate of incorporation of slowly transported NF into the stationary network cannot be excluded as an additional factor. The greater reduction of NFs at proximal levels is consistent with our original observations that degradation of the stationary NF cytoskeleton takes place locally in the axon although the relatively small fraction of newly synthesized NF protein reaching the nerve terminals may be degraded there as described previously. The global TB crisis is further convoluted by the presence of MDRand XDR-TB, being resistant to current antibiotics and hence hard to treat. It is a known fact that TB therapy has remained unchanged for nearly four decades now.