Rapid evolution of adaptive niche construction in experimental microbial populations

Many species engage in adaptive niche construction: modification of the local environment that increases the modifying organism's competitive fitness. Adaptive niche construction provides an alternative pathway to higher fitness, shaping the environment rather than conforming to it. Yet, experimental evidence for the evolutionary emergence of adaptive niche construction is lacking, leaving its role in evolution uncertain. Here we report a direct observation of the de novo evolution of adaptive niche construction in populations of the bacteria Pseudomonas fluorescens. In a laboratory experiment, we allowed several bacterial populations to adapt to a novel environment and assessed whether niche construction evolved over time. We found that adaptive niche construction emerged rapidly, within approximately 100 generations, and became ubiquitous after approximately 400 generations. The large fitness effect of this niche construction was dominated by the low fitness of evolved strains in the ancestrally modified environment: evolved niche constructors were highly dependent on their specific environmental modifications. Populations were subjected to frequent resetting of environmental conditions and severe reduction of spatial habitat structure, both of which are thought to make adaptive niche construction difficult to evolve. Our finding that adaptive niche construction nevertheless evolved repeatably suggests that it may play a more important role in evolution than generally thought.     

Relationship between autoantibodies to erythropoietin receptor and renal outcome in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Abstract

Purpose: We examined the relationship between autoantibodies to erythropoietin receptor (EPOR) and renal outcome in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Materials and methods: Sixty-three Japanese patients with AAV were enrolled and followed for a median of 31.4?months. Patients were screened for serum anti-EPOR antibodies using an enzyme-linked immunosorbent assay. Associations of anti-EPOR antibodies with clinical parameters were analyzed using logistic-regression models.

Results: Anti-EPOR antibodies were detected in 7 (11%) of the 63 patients, and levels of the antibodies decreased with immunosuppressive therapy. The presence of anti-EPOR antibodies was associated with a higher Birmingham vasculitis activity score. In addition, anti-EPOR antibodies were more frequently observed in patients with renal outcomes, which was defined as a sustained 50% reduction in the estimated glomerular filtration rate from baseline, than in those without. Multiple logistic regression analysis revealed that presence of anti-EPOR antibodies, as well as age at disease onset, were as risk factors for the renal outcome.

Conclusion: Anti-EPOR antibodies were associated with the progression of renal dysfunction in patients with AAV.     

Synthesis of 6-Methyluridine via Palladium-Catalyzed Cross-Coupling Between A 6-Iodouridine Derivative and Tetramethylstannane

Abstract

6-Methyluridine can be synthesized from 5′-O-(tert-butyl-dimethylsilyl)-6-iodo-2′,3′-O-isopropylideneuridine via palladiumcatalyzed cross-coupling with Me₄Sn followed by deprotection. Application of this method for the synthesis of 6-phenyluridine was also carried out.     

RAG-heptamer interaction in the synaptic complex is a crucial biochemical checkpoint for the 12/23 recombination rule

In V(D)J recombination, the RAG1 and RAG2 protein complex cleaves the recombination signal sequences (RSSs), generating a hairpin structure at the coding end. The cleavage occurs only between two RSSs with different spacer lengths of 12 and 23 bp. Here we report that in the synaptic complex, recombination-activating gene (RAG) proteins interact with the 7-mer and unstack the adjacent base in the coding region. We generated a RAG1 mutant that exhibits reduced RAG-7-mer interaction, unstacking of the coding base, and hairpin formation. Mutation of the 23-RSS at the first position of the 7-mer, which has been reported to impair the cleavage of the partner 12-RSS, demonstrated phenotypes similar to those of the RAG1 mutant; the RAG interaction and base unstacking in the partner 12-RSS are reduced. We propose that the RAG-7-mer interaction is a critical step for coding DNA distortion and hairpin formation in the context of the 12/23 rule.     

The gefitinib-sensitizing mutant epidermal growth factor receptor enables transformation of a mouse fibroblast cell line

A specific inhibitor of the Epidermal Growth Factor Receptor (EGFR), Gefitinib, displays significant antitumor effects against non-small cell lung cancers (NSCLC) that express EGFR with mutations in their tyrosine kinase domain. Although previous reports have already demonstrated that oncogenic transformation can be induced by some mutant EGFR forms, the precise differences between mutant and wild-type EGFR in terms of mechanisms of transformation have not been fully elucidated. We show here that a murine fibroblast cell line, NR6 becomes transformed by an expression level of the mutant EGFR form lacking E746-A750 that is far less than that needed with transfected wild-type EGFR. However, the mutant EGFR was unable to transform NR6 in a ligand-independent manner, as was seen with the wild-type EGFR. The consequent biological features after transformation, including DNA synthesis or cell cycle progression and biochemical characteristics such as MAPK activation mediated by the mutant EGFR are comparable and equivalent to those mediated by wild-type EGFR. These data suggest that the mutant EGFR possesses greater ligand-dependent transformation when compared with wild-type EGFR, although the exact mechanisms to account for this characteristic remain to be defined.     

A newly isolatedBacillus stearotheromophilus K1041 and its transformation by electroporation

Summary Optimal conditions for the plasmid transformation of a newly isolatedBacillus stearothermophilus K1041 by electroporation were investigated. The optimal conditions allowed a transformation efficiency of 5.8×10⁵ transformants per μg plasmid pUB110.     

New Type of Puzzle-Task Finger Maze Learning in Macaca fascicularis

In order to easily estimate the global cognitive ability of nonhuman primates, we developed a 4-step noncorrection-method-type finger maze (4FM) based on the standard puzzle feeder. We tested 7 experimentally naïve long-tailed macaques (Macaca fascicularis) to assess the validity of the apparatus and the testing procedure. The most notable difference between the 4FM and the standard puzzle feeder is the presence of an error box. There is a hole at both ends of each step. One hole of each step is connected to the lower step or feeding box. The other hole of each step is connected to an error box. The monkey had to move the reward into the feeding box without dropping it into the error box and to retrieve the reward from the feeding box. Task difficulties could be controlled by deciding on which step to place the food reward at the beginning of the trial. All the monkeys could complete the tasks without food/water deprivation and pretraining. The results suggest that the 4FM is a suitable device to assess the cognitive ability of the monkeys simply, easily, and objectively.     

Mechanism for retardation of amyloid fibril formation by sugars in Vλ6 protein

Sugars, which function as osmolytes within cells, retard the amyloid fibril formation of the amyloidosis peptides and proteins. To examine the mechanism of this retardation in detail, we analyzed the effect of sugars (trehalose, sucrose, and glucose) on the polypeptide chains in 3Hmut Wil, which is formed by the mutation of three His residues in Wil mutant as a cause of amyloid light‐chain (AL) amyloidosis, at pH 2, a pH condition under which 3Hmut Wil was almost denatured. Sugars caused the folding of 3Hmut Wil so that its polypeptide chains adopted a native‐like rather than a denatured conformation, as suggested by tryptophan fluorescence, CD spectroscopy, and heteronuclear NMR. Furthermore, these sugars promoted the folding to a native‐like conformation according to the effect of preferential hydration rather than direct interaction. However, the type of sugar had no effect on the elongation of amyloid fibrils. Therefore, it was concluded that sugar affected the thermodynamic stability of 3Hmut Wil but not the elongation of amyloid fibrils.