Translocation direct evidence

Chromosomal translocations are frequently associated with specific types of cancer. This is direct evidence that genetic abnormalities can lead to cancer. 

Fusion proteins have been constructed from peptide epitopes from influenza A antigens and the binding and translocation domains of Pseudomonas exotoxin A (Donelly ef al., 1993). When target cells were incubated with these fusion proteins, and subsequently exposed to cytotoxic T lymphocytes (CTLs) specific for the relevant epitopes, a CTL mediate lysis of the target cells was observed. These experiments suggest that the translocation machinery supplied by protein toxins may be useful tools for bringing peptides into cells for presentation via the major histocompatibility class I (MHC I) system. It should be noted that no direct evidence was provided that the translocation occurred by the toxin pathway, and it cannot be excluded that the toxin was only instrumental in accumulating the peptide on the surface of the cells and in the endocytic pathway. 

Prochloraz, with a log P of around 4.0 and a very low vapour pressure, Is not very mobile In plant tissue and It Is probable that this contributes, to some extent, to the observed spectrum of activity. In particular, chemical reaching the stem base would not be translocated away from there, whereas less lipophilic azoles would move more readily to the leaves. In addition, the point has already been made that the unique structural features of the compound could also affect the pattern of activity, although there Is no direct evidence for this at present. 

JNK activation may be a mechanism that is associated with the initiation of mitochondrial permeability transition (MPT) (Hanawa et al. 2008 Latchoumycan-dane et al. 2006, 2007). As discussed above, both JNK activation (Matsumaru et al. 2003) and MPT (Lemasters 1998) are known to occur as a result of increased oxidative stress. MPT leads to additional oxidative stress with loss of mitochondrial membrane potential and loss of the ability of the hepatocyte to synthesize ATP. Latchoumycandane et al. (2006, 2007) found that leflunomide protected mice from mitochondrial permeabilization. Direct evidence for a role of JNK activation in acetaminophen-induced MPT was recently reported by Hanawa et al. (2008). A time course of events indicated GSH depletion by 1-2 h, JNK activation in liver homogenate by 2-4- h, JNK translocation to mitochondria by 4 h, and increased toxicity (serum ALT by 6 h). The JNK inhibitor did not alter GSH depletion but blocked JNK activation in homogenate, JNK translocation to mitochondria, and toxicity. Mitochondria from liver of acetaminophen-treated mice showed decreased State III respiration and decreased respiratory control ratios, whereas mice treated with acetaminophen plus JNK inhibitor were partially protected from these losses. Addition of activated JNKl or JNK2 to mitochondria from acetaminophen-treated mice plus JNK inhibitor showed a decrease in State 111 respiration and decreased respiratory control ratio. Addition of the MPT inhibitor cyclosporine A prevented these decreases. It was hypothesized that activated JNK is an important mediator of acetaminophen-induced MPT (Hanawa et al. 2008). 

In the U-tube, ion selectivities are easily determined by comparison of transport efficiencies for detectable series of cations or anions. Different picrate salts are best known to determine cation selectivity sequences. The comparison of velocities with safranin O or DPX against CF or HPTS can provide direct evidence for anion/cation selectivity of molecular recognition and translocation. ... 

There appears to be no restriction on the capacity of a F gene within a family to combine with any C gene belonging to the same family, but interactions between different families do not occur e.g., no L chain has been detected which comprises a and a Cx region. The most direct evidence for translocation, within a cell, of a K gene from one C gene to another, has so far been obtained for H chains its occurrence in L chains is inferred on the basis of data already discussed. 

A central tenet of the above scheme of O-side chain biosynthesis, is that oligosaccharides linked to lipid carriers traverse the cytoplasmic membrane. There is little direct evidence that this occurs it being difficult to localise such an intermediate state. Some support for the hypothesis comes from the observation that the antibiotic bacitracin, which specifically interacts with the lipid carrier, inhibits O-side chain polymerisation. However, many consider the transfer of the oligosaccharide from one leaflet of the membrane to the other to pose insurmountable problems. To overcome this difficulty it has been postulated that nucleotide sugars are translocated through the membrane into the periplasmic space, where... 

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