Chemical biology: Paper alert

A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in chemical biology.     

Proteinopathies, neurodegenerative disorders with protein aggregation-based pathology

A number of neurodegenerative disorders were recently coalesced into a group of proteinopathies based on the similarity of molecular mechanisms underlying their pathogenesis. A key step in the development of proteinopathies is a structural change that triggers aggregation of the proteins that are intrinsically prone to form aggregates owing to their physical and chemical properties. The review considers the recent progress in the field of proteinopathies with a special focus on the properties of aggregation-prone proteins, the main stages of the development of molecular pathology, and the role of cell clearance systems in the progression of neurodegeneration. Recent modifications made to the nomenclature of neurodegenerative diseases on the basis of the molecular mechanism of neurodegeneration are also addressed.     

Molecular cloning and expression pattern of rpr-1, a resiniferatoxin-binding, phosphotriesterase-related protein, expressed in rat kidney tubules

Bacterial phosphotriesterases are enzymes that hydrolyse phosphotriester-containing organophosphate pesticides. Resiniferatoxin is a vanilloid that desensitises nociceptive neurons. By screening a rat cDNA library with labelled resiniferatoxin, we unexpectedly isolated a novel rat phosphotriesterase homologue, here named rpr-1, that encodes a 349 amino acid, 39 kDa protein (confirmed by in vitro translation). Northern blotting and in situ hybridisation show expression primarily in proximal tubules of the kidney, in which rpr-1 distribution correlates with resiniferatoxin-binding activity. These results suggest an unsuspected link between the phosphotriesterase enzyme family and resiniferatoxin toxicity and pharmacology.     

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.     

Acclimation or stress symptom? An integrated study of intraspecific variation in the clonal plant Aechmea bromeliifolia,a widespread CAM tank‐bromeliad

The clonal tank-bromeliad Aechmea bromeliifolia (Rudge) Baker was found in four different habitats in a restinga (vegetation mosaic on sandy coastal plains), of south-eastern Brazil. These habitats (swamp forest, dry forest, dry shrubland and herbaceous marsh) lie within a few hundred metres of each other along a gradient extending inland from the coast, and differ markedly in terms of light and flood regime. We compared ramet morphology, leaf anatomy and physiology, and population parameters to examine the amplitude of trait variation of this widespread species in the studied restinga. This integrated approach allowed us to examine which variation conferred acclimation and which was merely a stress symptom. A . bromeliifolia showed site-specific differences in abundance, distribution, rosette size and shape, leaf anatomical arrangement and photochemical efficiency (potential quantum yield; F _v/ F _m) during the day. Most of the variation found seemed to be related to the interaction of light and flooding. The lowest number and size of ramets at the exposed, dry shrubland was matched by a marked leaf photoinhibition, which suggested poor acclimation to local levels of light intensity and limited water supply. In the other habitats, the morpho-physiological parameters measured suggested adequate foraging behaviour and site acclimation.  © 2002 The Linnean Society of London, Botanical Journal of the Linnean Society, 2002, 140 , 391-401.