Pathways of chaperone-mediated protein folding in the cytosol

Cells are faced with the task of folding thousands of different polypeptides into a wide range of conformations. For many proteins, the folding process requires the action of molecular chaperones. In the cytosol of prokaryotic and eukaryotic cells, molecular chaperones of different structural classes form a network of pathways that can handle substrate polypeptides from the point of initial synthesis on ribosomes to the final stages of folding.     

Dynamic stability of individuals with transtibial amputation walking in destabilizing environments

Lower limb amputation substantially disrupts motor and proprioceptive function. People with lower limb amputation experience considerable impairments in walking ability, including increased fall risk. Understanding the biomechanical aspects of the gait of these patients is crucial in improving their gait function and their quality of life. In the present study, 9 persons with unilateral transtibial amputation and 13 able-bodied controls walked on a large treadmill in a Computer Assisted Rehabilitation Environment (CAREN). While walking, subjects were either not perturbed, or were perturbed either by continuous mediolateral platform movements or by continuous mediolateral movements of the visual scene. Means and standard deviations of both step lengths and step widths increased significantly during both perturbation conditions (all p<0.001) for both groups. Measures of variability, local and orbital dynamic stability of trunk movements likewise exhibited large and highly significant increases during both perturbation conditions (all p<0.001) for both groups. Patients with amputation exhibited greater step width variability (p=0.01) and greater trunk movement variability (p=0.04) during platform perturbations, but did not exhibit greater local or orbital instability than healthy controls for either perturbation conditions. Our findings suggest that, in the absence of other co-morbidities, patients with unilateral transtibial amputation appear to retain sufficient sensory and motor function to maintain overall upper body stability during walking, even when substantially challenged. Additionally, these patients did not appear to rely more heavily on visual feedback to maintain trunk stability during these walking tasks.     

An incipient invasion of brown anole lizards (<Emphasis Type="Italic">Anolis sagrei</Emphasis>) into their own native range in the Cayman Islands: a case of cryptic back-introduction

Human-mediated dispersal has reshaped distribution patterns and biogeographic relationships for many taxa. Long-distance and over-water dispersal were historically rare events for most species, but now human activities can move organisms quickly over long distances to new places. A potential consequence of human-mediated dispersal is the eventual reintroduction of individuals from an invasive population back into their native range; a dimension of biological invasion termed “cryptic back-introduction.” We investigated whether this phenomenon was occurring in the Cayman Islands where brown anole lizards (Anolis sagrei) with red dewlaps (i.e., throat fans), either native to Little Cayman or invasive on Grand Cayman, have been found on Cayman Brac where the native A. sagrei have yellow dewlaps. Our analysis of microsatellite data shows strong population-genetic structure among the three Cayman Islands, but also evidence for non-equilibrium. We found some instances of intermediate multilocus genotypes (possibly 3–9% of individuals), particularly between Grand Cayman and Cayman Brac. Furthermore, analysis of dewlap reflectance data classified six males sampled on Cayman Brac as having red dewlaps similar to lizards from Grand Cayman and Little Cayman. Lastly, one individual from Cayman Brac had an intermediate microsatellite genotype, a red dewlap, and a mtDNA haplotype from Grand Cayman. This mismatch among genetic and phenotypic data strongly suggests that invasive A. sagrei from Grand Cayman are interbreeding with native A. sagrei on Cayman Brac. To our knowledge, this is the first evidence of cryptic back-introduction. Although we demonstrate this phenomenon is occurring in the Cayman Islands, assessing its frequency there and prevalence in other systems may prove difficult due to the need for genetic data in most instances. Cryptic back-introductions may eventually provide some insight into how lineages are changed by the invasion process and may be an underappreciated way in which invasive species impact native biodiversity.     

Planar cell polarity proteins differentially regulate extracellular matrix organization and assembly during zebrafish gastrulation

Zebrafish gastrulation cell movements occur in the context of dynamic changes in extracellular matrix (ECM) organization and require the concerted action of planar cell polarity (PCP) proteins that regulate cell elongation and mediolateral alignment. Data obtained using Xenopus laevis gastrulae have shown that integrin–fibronectin interactions underlie the formation of polarized cell protrusions necessary for PCP and have implicated PCP proteins themselves as regulators of ECM. By contrast, the relationship between establishment of PCP and ECM assembly/remodeling during zebrafish gastrulation is unclear. We previously showed that zebrafish embryos carrying a null mutation in the four-pass transmembrane PCP protein vang-like 2 (vangl2) exhibit increased matrix metalloproteinase activity and decreased immunolabeling of fibronectin. These data implicated for the first time a core PCP protein in the regulation of pericellular proteolysis of ECM substrates and raised the question of whether other zebrafish PCP proteins also impact ECM organization. In Drosophila melanogaster, the cytoplasmic PCP protein Prickle binds Van Gogh and regulates its function. Here we report that similar to vangl2, loss of zebrafish prickle1a decreases fibronectin protein levels in gastrula embryos. We further show that Prickle1a physically binds Vangl2 and regulates both the subcellular distribution and total protein level of Vangl2. These data suggest that the ability of Prickle1a to impact fibronectin organization is at least partly due to effects on Vangl2. In contrast to loss of either Vangl2 or Prickle1a function, we find that glypican4 (a Wnt co-receptor) and frizzled7 mutant gastrula embryos with disrupted non-canonical Wnt signaling exhibit the opposite phenotype, namely increased fibronectin assembly. Our data show that glypican4 mutants do not have decreased proteolysis of ECM substrates, but instead have increased cell surface cadherin protein expression and increased intercellular adhesion. These data indicate that Wnt/Glypican4/Frizzled signaling regulates ECM assembly through effects on cadherin-mediated cell cohesion. Together, our results demonstrate that zebrafish Vangl2/Prickle1a and non-canonical Wnt/Frizzled signaling have opposing effects on ECM organization underlying PCP and gastrulation cell movements.     

The superposition principle applied to grasping an object producing moments outside anatomically-defined axes

The superposition principle suggests that motor commands can be divided into individually controlled components that summate to produce complex motor actions. Previous studies have examined the validity of this principle in human grasping by changing moments acting on an object about a single anatomically-defined axis and asking subjects to hold the object while their forearm was constrained. Superposition was reflected as separate control of the grip force and moments required to prevent object slip and maintain orientation. The objective of this study was to examine the robustness of this principle by: 1) expanding the range of tasks to include those where moments act on an object with respect to moment arms not necessarily in line with the anatomically-defined axes; 2) asking subjects to hold the object in an unconstrained manner. Ten subjects were asked to lift and hold an object vertically under eighteen moment conditions. Force and moment data from all digits were analysed using principal components analysis (PCA). Different PCAs were run for variable sets corresponding to moments about the long axis of the forearm (M(x)), the vertical (M(y)) and grip (M(z)) axes, and for the entire dataset (M(3D)). The PCA showed grip force and moment variables on separate PCs for the M(x), M(y), and M(3D) variable sets. The M(3D) PCA also showed a separation of variables corresponding to moments about each anatomically-defined axis. Thus, the present results show that the superposition principle holds during natural manipulation of an object experiencing external moments outside the anatomically-defined axes.