The evolutionary path to terminal differentiation and division of labor in cyanobacteria

A common trait often associated with multicellularity is cellular differentiation, which is a spatial separation of tasks through the division of labor. In principle, the division of labor does not necessarily have to be constrained to a multicellular setting. In this study, we focus on the possible evolutionary paths leading to terminal differentiation in cyanobacteria. We develop mathematical models for two developmental strategies. First, of populations of terminally differentiated single cells surviving by the exchange of common goods. Second, of populations exhibiting terminal differentiation in a multicellular setting. After testing the two strategies against the effect of disruptive mutations (i.e. “cheater” mutants), we assess the effects of selection on the optimization of the ratio of vegetative (carbon fixing) to heterocystous (nitrogen fixing) cells, which in turn leads to the maximization of the carrying capacity for the population density. In addition, we compare the performance of differentiated populations to undifferentiated ones that temporally separate tasks in accordance to a day/night cycle. We then compare some predictions of our model with phylogenetic relationships derived from analyzing 16S rRNA sequences of different cyanobacterial strains. In line with studies indicating that group or spatial structure are ways to evolve cooperation and protect against the spread of cheaters, our work shows that compartmentalization afforded by multicellularity is required to maintain the vegetative/heterocyst division in cyanobacteria. We find that multicellularity allows for selection to optimize the carrying capacity. These results and the phylogenetic analysis indicates that terminally differentiated cyanobacteria evolved after undifferentiated species. In addition, we show that, in regimes of short daylight periods, terminally differentiated species perform worse than undifferentiated species that follow the day/night cycle; indicating that undifferentiated species have an evolutionary advantage in regimes of short daylight periods.     

Protein N-Homocysteinylation Induces the Formation of Toxic Amyloid-Like Protofibrils

Previous works reported that a mild increase in homocysteine level is a risk factor for cardiovascular and neurodegenerative diseases in humans. Homocysteine thiolactone is a cyclic thioester, most of which is produced by an error-editing function of methionyl-tRNA synthetase, causing in vivo post-translational protein modifications by reacting with the ?-amino group of lysine residues. In cells, the rate of homocysteine thiolactone synthesis is strictly dependent on the levels of the precursor metabolite, homocysteine. In this work, using bovine serum albumin as a model, we investigated the impact of N-homocysteinylation on protein conformation as well as its cellular actions. Previous works demonstrated that protein N-homocysteinylation causes enzyme inactivation, protein aggregation, and precipitation. In addition, in the last few years, several pieces of evidence have indicated that protein unfolding and aggregation are crucial events leading to the formation of amyloid fibrils associated with a wide range of human pathologies. For the first time, our results reveal how the low level of protein N-homocysteinylation can induce mild conformational changes leading to the formation of native-like aggregates evolving over time, producing amyloid-like structures. Taking into account the fact that in humans about 70% of circulating homocysteine is N-linked to blood proteins such as serum albumin and hemoglobin, the results reported in this article could have pathophysiological relevance and could contribute to clarify the mechanisms underlying some pathological consequences described in patients affected by hyperhomocysteinemia.     

Surface roughness of denture base and reline materials after disinfection by immersion in chlorhexidine or microwave irradiation

doi: 10.1111/j.1741‐2358.2011.00484.x
Surface roughness of denture base and reline materials after disinfection by immersion in chlorhexidine or microwave irradiation Background: This study evaluated the effect of disinfection by immersion and microwave irradiation on the roughness of one denture base resin (Lucitone‐L) and five relining materials, three hard (Tokuyama Rebase II‐TR, New Truliner‐NT, Ufigel Hard‐UH) and two resilient (Trusoft‐T, Sofreliner‐S). Methods: Fifty specimens were made and divided into groups: CL2 specimens were brushed with 4% chlorhexidine (1 min), immersed in the same solution (10 min) and immersed in water (3 min); MW2 specimens were immersed in water and microwave irradiated (650W; 6 min); CL2 and MW2 specimens were disinfected twice; CL7 and MW7 specimens were submitted to seven cycles using chlorhexidine or microwave irradiation, respectively; W specimens were not disinfected and remained in water (37°C; 7 days). Results: Results were statistically analysed (p = 0.05) and revealed that, at baseline, the highest mean value was observed for T (p < 0.001). Material NT showed increase in roughness after the first (p = 0.003), second (p = 0.001), seventh (p = 0.000) cycles of microwave disinfection and after 7 days of immersion in water (p = 0.033). Conclusions: Resilient liner S presented significant increase in roughness after the second cycle of disinfection with chlorhexidine (p = 0.003). Material T exhibited significantly decreased roughness in group W (p = 0.010), while microwaving produced severe alterations on its surface.     

Advantages of the division of labour for the long-term population dynamics of cyanobacteria at different latitudes

A fundamental advancement in the evolution of complexity is division of labour. This implies a partition of tasks among cells, either spatially through cellular differentiation, or temporally via a circadian rhythm. Cyanobacteria often employ either spatial differentiation or a circadian rhythm in order to separate the chemically incompatible processes of nitrogen fixation and photosynthesis. We present a theoretical framework to assess the advantages in terms of biomass production and population size for three species types: terminally differentiated (heterocystous), circadian, and an idealized species in which nitrogen and carbon fixation occur without biochemical constraints. On the basis of real solar irradiance data at different latitudes, we simulate population dynamics in isolation and in competition for light over a period of 40 years. Our results show that in isolation and regardless of latitude, the biomass of heterocystous cyanobacteria that optimally invest resources is comparable to that of the idealized unconstrained species. Hence, spatial division of labour overcomes biochemical constraints and enhances biomass production. In the circadian case, the strict temporal task separation modelled here hinders high biomass production in comparison with the heterocystous species. However, circadian species are found to be successful in competition for light whenever their resource investment prevents a waste of fixed nitrogen more effectively than do heterocystous species. In addition, we show the existence of a trade-off between population size and biomass accumulation, whereby each species can optimally invest resources to be proficient in biomass production or population growth, but not necessarily both. Finally, the model produces chaotic dynamics for population size, which is relevant to the study of cyanobacterial blooms.     

Bone marrow-infiltrating human neuroblastoma cells express high levels of calprotectin and HLA-G proteins

Metastases in the bone marrow (BM) are grim prognostic factors in patients with neuroblastoma (NB). In spite of extensive analysis of primary tumor cells from high- and low-risk NB patients, a characterization of freshly isolated BM-infiltrating metastatic NB cells is still lacking. Our aim was to identify proteins specifically expressed by metastatic NB cells, that may be relevant for prognostic and therapeutic purposes. Sixty-six Italian children over 18 months of age, diagnosed with stage 4 NB, were included in the study. Metastatic NB cells were freshly isolated from patients' BM by positive immunomagnetic bead manipulation using anti-GD2 monoclonal antibody. Gene expression profiles were compared with those obtained from archived NB primary tumors from patients with 5 y-follow-up. After validation by RT-qPCR, expression/secretion of the proteins encoded by the up-regulated genes in the BM-infiltrating NB cells was evaluated by flow cytometry and ELISA. Compared to primary tumor cells, BM-infiltrating NB cells down-modulated the expression of CX3CL1, AGT, ATP1A2 mRNAs, whereas they up-regulated several genes commonly expressed by various lineages of BM resident cells. BM-infiltrating NB cells expressed indeed the proteins encoded by the top-ranked genes, S100A8 and A9 (calprotectin), CD177 and CD3, and secreted the CXCL7 chemokine. BM-infiltrating NB cells also expressed CD271 and HLA-G. We have identified proteins specifically expressed by BM-infiltrating NB cells. Among them, calprotectin, a potent inflammatory protein, and HLA-G, endowed with tolerogenic properties facilitating tumor escape from host immune response, may represent novel biomarkers and/or targets for therapeutic intervention in high-risk NB patients.