Cost of cooperation rules selection for cheats in bacterial metapopulations

Bacteria secrete a large variety of beneficial metabolites into the environment, which can be shared as public goods among producing bacteria, but also be exploited by nonproducing cheats. Here, we focus on cooperative production of iron-chelating molecules (siderophores) in the bacterium Pseudomonas aeruginosa to study how relevant ecological factors influence selection for cheating. We designed patch-structured metapopulations that allowed us introducing among-patch ecological variation. We found that cheating readily evolved in uniform iron-limited environments. This finding is explained by severe iron limitation demanding high siderophore-production efforts, which results in high metabolic costs accruing to cooperators, and thereby facilitates the spread of cheats. In contrast, we observed a significant reduction or even negation of selection for cheating in metapopulations where we introduced patches with increased iron availability and/or opportunities to recycle siderophores. These findings are compatible with the view that cheats are less likely to invade in environments that allow bacteria to reduce siderophore-production efforts, as this lowers the overall metabolic costs accruing to cooperators. Because we increased iron availability and siderophore recycling opportunities moderately, and only in some patches, our findings demonstrate that already-small local variations in ecological conditions as occurring in nature can significantly affect selection for public-goods secretion in microbes. In addition, we found that most (84.6%) of the evolved cheats were partially deficient for siderophore production and not loss-of-function mutants. Genetic considerations indicate that mutations leading to partial deficiency occur more frequent than mutations leading to loss of function, but also suggest that partially deficient mutants might often be the more competitive cheats.     

Anatomical connectivity influences both intra- and inter-brain synchronizations

Recent development in diffusion spectrum brain imaging combined to functional simulation has the potential to further our understanding of how structure and dynamics are intertwined in the human brain. At the intra-individual scale, neurocomputational models have already started to uncover how the human connectome constrains the coordination of brain activity across distributed brain regions. In parallel, at the inter-individual scale, nascent social neuroscience provides a new dynamical vista of the coupling between two embodied cognitive agents. Using EEG hyperscanning to record simultaneously the brain activities of subjects during their ongoing interaction, we have previously demonstrated that behavioral synchrony correlates with the emergence of inter-brain synchronization. However, the functional meaning of such synchronization remains to be specified. Here, we use a biophysical model to quantify to what extent inter-brain synchronizations are related to the anatomical and functional similarity of the two brains in interaction. Pairs of interacting brains were numerically simulated and compared to real data. Results show a potential dynamical property of the human connectome to facilitate inter-individual synchronizations and thus may partly account for our propensity to generate dynamical couplings with others.     

Modelling the ontogeny of ectotherms exhibiting indeterminate growth

Numerous growth functions exist to describe the ontogeny of animals. Such functions (e.g., von Bertalanffy's equation, thermal-unit growth coefficient) are currently applied to ectotherms even though they fail to provide analytical expressions that adapt to a wide range of fluctuating temperatures. The underlying mechanisms responsible for the ontogeny of ectotherms exhibiting indeterminate growth have not yet been summarised in terms of a simple but meaningful mathematical equation. Here, a growth function is developed, with parameters having physical or biological interpretation that accommodates indeterminate growth under fluctuating temperatures assuming the latter vary seasonally. The equation is derived as a special case of von Bertalanffy's equation providing realistic growth trajectories throughout the ontogeny of several groups of ectotherms (R²>0.90). The results suggest that the effect of temperature on growth trajectory supersedes that of reproduction in an environment with fluctuating temperature. Furthermore, values of the allometric weight exponent (0<b<0.75) indicate that the rules of body surface and body weight do not apply under certain circumstances. Finally, the growth function circumvents problems associated with models based on thermodynamic and chemical kinetic principles (e.g., inability to predict growth of organisms in which ontogeny exceeds 3 months) and on rule of thermal summation (e.g., reliable only in a certain range of temperature). The growth function can handle a wide range of temperature fluctuations, encompass life stages and apply to key organisms in ecology, fisheries and agriculture.     

Phylometabonomic patterns of adaptation to high fat diet feeding in inbred mice

Insulin resistance plays a central role in type 2 diabetes and obesity, which develop as a consequence of genetic and environmental factors. Dietary changes including high fat diet (HFD) feeding promotes insulin resistance in rodent models which present useful systems for studying interactions between genetic background and environmental influences contributing to disease susceptibility and progression. We applied a combination of classical physiological, biochemical and hormonal studies and plasma (1)H NMR spectroscopy-based metabonomics to characterize the phenotypic and metabotypic consequences of HFD (40%) feeding in inbred mouse strains (C57BL/6, 129S6, BALB/c, DBA/2, C3H) frequently used in genetic studies. We showed the wide range of phenotypic and metabonomic adaptations to HFD across the five strains and the increased nutrigenomic predisposition of 129S6 and C57BL/6 to insulin resistance and obesity relative to the other strains. In contrast mice of the BALB/c and DBA/2 strains showed relative resistance to HFD-induced glucose intolerance and obesity. Hierarchical metabonomic clustering derived from (1)H NMR spectral data of the strains provided a phylometabonomic classification of strain-specific metabolic features and differential responses to HFD which closely match SNP-based phylogenetic relationships between strains. Our results support the concept of genomic clustering of functionally related genes and provide important information for defining biological markers predicting spontaneous susceptibility to insulin resistance and pathological adaptations to fat feeding.     

7-Ketocholesterol favors lipid accumulation and colocalizes with Nile Red positive cytoplasmic structures formed during 7-ketocholesterol-induced apoptosis: analysis by flow cytometry, FRET biphoton spectral imaging microscopy, and subcellular fractionation.

BACKGROUND: Oxidized low-density lipoproteins play key roles in atherosclerosis. Their toxicity is at least in part due to 7-ketocholesterol (7KC), which is a potent inducer of apoptosis. In this study on human promonocytic U937 cells, we determined the effects and the interactions of 7KC with cellular lipids during 7KC-induced apoptosis. METHODS: Morphologic and functional changes were investigated by microscopic and flow cytometric methods after staining with propidium iodide, 3,3'-dihexyloxacarbocyanine iodide, and Hoechst 33342. Cellular lipid content was identified by using filipin to quantify free cholesterol and Nile Red (NR), which emit a yellow or orange-red fluorescence in the presence of neutral and polar lipids, respectively. After staining with NR, interactions of 7KC with cellular lipids were identified by fluorescence resonance energy transfer biphoton spectral imaging confocal microscopy and by subcellular fractionation, gas chromatography, and mass spectrometry. RESULTS: During 7KC-induced apoptosis the fluorescence from filipin and the ratio of measured (orange-red vs. yellow) fluorescence of NR were enhanced. Spectral analysis of images obtained in biphoton mode and resulting factor images demonstrated the occurrence of fluorescence resonance energy transfer between 7KC and NR and the subsequent colocalization of 7KC and NR. These data were in agreement with biochemical characterization and demonstrated that 7KC and neutral and polar lipids accumulate in NR-stained cytoplasmic structures. CONCLUSIONS: During 7KC-induced apoptosis, 7KC modifies the cellular content of neutral and polar lipids, favors free cholesterol accumulation, and colocalizes with neutral and polar lipids that are inside NR-stained cytoplasmic structures.     

Comparative Analysis of Extracellular and Intracellular Proteomes of Listeria monocytogenes Strains Reveals a Correlation between Protein Expression and Serovar

Listeria monocytogenes, the etiologic agent of listeriosis, remains a serious public health concern, with its frequent occurrence in food environments coupled with a high mortality rate. Among the 13 serovars, human listeriosis is mostly associated with the serovar 4b, 1/2b, and 1/2a strains. To investigate the diversity of L. monocytogenes, the intracellular and extracellular proteins of 12 strains were analyzed by two-dimensional gel electrophoresis. These strains had different origins, belonged to different serovars (4b, 1/2a, and 1/2b), and presented with different levels of virulence in chicken embryos. The clustering of the strains in two groups based on proteomic patterns is in agreement with the L. monocytogenes phylogenetic lineages. Statistical analysis did not allow for identification of proteins specific to the isolate origin or the virulence level of the strains, but 26 and 21 protein spots were shown to be significantly overexpressed and underexpressed, respectively, in the six strains of serovar 1/2a (lineage II) compared to strains of serovar 1/2b or 4b. Moreover, a penicillin-binding protein was specific for serovar 1/2b and two protein spots identified as a serine protease were specific to serovar 4b. These protein spots, identified through peptide mass fingerprinting using matrix-assisted laser desorption ionization-time of flight mass spectrometry, were essentially found in the extracellular proteome and may have uses as potential markers for serotyping and risk analysis.     

Discovery and parallel synthesis of a new class of cathepsin K inhibitors.

Peptidomimetic aminomethyl ketones have been identified as a new class of cathepsin K inhibitors. Traditional and high-speed parallel synthesis techniques were applied to investigate this series. Structure-activity relationships were established, and certain analogues were characterized with IC(50) values in the range 200-500 nM.     

Effects of the Racket Polar Moment of Inertia on Dominant Upper Limb Joint Moments during Tennis Serve

This study examined the effect of the polar moment of inertia of a tennis racket on upper limb loading in the serve. Eight amateur competition tennis players performed two sets of 10 serves using two rackets identical in mass, position of center of mass and moments of inertia other than the polar moment of inertia (0.00152 vs 0.00197 kg.m²). An eight-camera motion analysis system collected the 3D trajectories of 16 markers, located on the thorax, upper limbs and racket, from which shoulder, elbow and wrist net joint moments and powers were computed using inverse dynamics. During the cocking phase, increased racket polar moment of inertia was associated with significant increases in the peak shoulder extension and abduction moments, as well the peak elbow extension, valgus and supination moments. During the forward swing phase, peak wrist extension and radial deviation moments significantly increased with polar moment of inertia. During the follow-through phase, the peak shoulder adduction, elbow pronation and wrist external rotation moments displayed a significant inverse relationship with polar moment of inertia. During the forward swing, the magnitudes of negative joint power at the elbow and wrist were significantly larger when players served using the racket with a higher polar moment of inertia. Although a larger polar of inertia allows players to better tolerate off-center impacts, it also appears to place additional loads on the upper extremity when serving and may therefore increase injury risk in tennis players.