Modeling synucleinopathies in genetically modified animals: Successes and failures

The synuclein family and particularly α-synuclein takes a central part in aetiology and pathogenesis of Parkinson’s disease—one of the most common human neurodegenerative diseases. The pathological changes in certain other neurodegenerative diseases are also linked to changes in the metabolism and function of α-synuclein, hence comprising a new group of diseases—synucleinopathies. The molecular and cellular mechanisms that are involved in the development of neurodegeneration in synucleinopathies are still largely unknown. As a result, the therapeutic approaches to the treatment of synucleinopathies are inadequately tampered. The development of models of neurodegenerative process in laboratory animals plays a crucial role in the study of these molecular mechanisms. Recently a special emphasis was placed on transgenic animal models with modified expression of genes, whose mutations are associated with inherited forms of human neurodegenerative diseases. The current review is devoted to the analysis of different models of synucleinopathies as a result of genetic modifications of α-synuclein expression.     

The allometry of saguaro height

The allometry of plant height H with respect to mean stem diameter D was determined based on 118 saguaro plants. The slope obtained for the reduced major axis regression analysis of the data was 2.36 ± 0.085, indicating that taller plants are disproportionately more slender than their shorter, presumably younger counterparts. The consequences of this positive, extremely anisometric relation on the elastic stability of stems were estimated by computing the critical buckling height H_crit for each of the 118 stems on the basis of the mean density-specific stiffness (i.e., the quotient of Young's elastic modulus E and bulk tissue density ρ) determined for a single section from a mature saguaro stem. E/ρ was nearly equivalent to that of tissue samples of sclerenchyma isolated from other plant species. Since the slope of H_crit vs. D equals ≈ 0.67 when E/ρ ≈ a constant, the safety-factor for saguaro stems (i.e., H_crit/H) appeared to be size-dependent such that it decreased with increasing plant height (i.e., H_crit/H ≈ D^-1.65). However, the mean safety-factor computed for the 118 saguaro specimens was 9.64, indicating that, on the average, plant height was well below H_crit. Additionally, circumstantial evidence suggests that saguaro stems become more stiff as they increase in size (and age) and that the rate of stem growth decelerates over time. The former would obtain a near size-independent safety-factor against elastic buckling while the latter protracts the time required to reach the critical buckling height. Comparisons among the allometries of H and H_crit for saguaro, other cacti, nonwoody, and highly branched tree species indicated that saguaro size overlaps with the lower size-range of the largest known dicot and gymnosperm tree specimens likely as a consequence of the high E/ρ of mature saguaro stems.