We are what we eat: how the diet of infants affects their gut microbiome

Simultaneous analysis of the gut microbiome and host gene expression in infants reveals the impact of diet (breastfeeding versus formula) on host-microbiome interactions.     

Darwinian selection of host and bacteria supports emergence of Lamarckian-like adaptation of the system as a whole

Background

The relatively fast selection of symbiotic bacteria within hosts and the potential transmission of these bacteria across generations of hosts raise the question of whether interactions between host and bacteria support emergent adaptive capabilities beyond those of germ-free hosts.

Results

To investigate possibilities for emergent adaptations that may distinguish composite host-microbiome systems from germ-free hosts, we introduce a population genetics model of a host-microbiome system with vertical transmission of bacteria. The host and its bacteria are jointly exposed to a toxic agent, creating a toxic stress that can be alleviated by selection of resistant individuals and by secretion of a detoxification agent (“detox”). We show that toxic exposure in one generation of hosts leads to selection of resistant bacteria, which in turn, increases the toxic tolerance of the host’s offspring. Prolonged exposure to toxin over many host generations promotes anadditional form of emergent adaptation due to selection of hosts based on detox produced by their bacterial community as a whole (as opposed to properties of individual bacteria).

Conclusions

These findings show that interactions between pure Darwinian selections of host and its bacteria can give rise to emergent adaptive capabilities, including Lamarckian-like adaptation of the host-microbiome system.

Reviewers

This article was reviewed by Eugene Koonin, Yuri Wolf and Philippe Huneman.

     

Implicit Racial Attitudes Influence Perceived Emotional Intensity on Other-Race Faces

An ability to accurately perceive and evaluate out-group members'' emotions plays a critical role in intergroup interactions. Here we showed that Chinese participants'' implicit attitudes toward White people bias their perception and judgment of emotional intensity of White people''s facial expressions such as anger, fear and sadness. We found that Chinese participants held pro-Chinese/anti-White implicit biases that were assessed in an evaluative implicit association test (IAT). Moreover, their implicit biases positively predicted the perceived intensity of White people''s angry, fearful and sad facial expressions but not for happy expressions. This study demonstrates that implicit racial attitudes can influence perception and judgment of a range of emotional expressions. Implications for intergroup interactions were discussed.     

Review: The development of the gastrointestinal tract microbiota and intervention in neonatal ruminants

The complex microbiome colonizing the gastrointestinal tract (GIT) of ruminants plays an important role in the development of the immune system, nutrient absorption and metabolism. Hence, understanding GIT microbiota colonization in neonatal ruminants has positive impacts on host health and productivity. Microbes rapidly colonize the GIT after birth and gradually develop into a complex microbial community, which allows the possibility of GIT microbiome manipulation to enhance newborn health and growth and perhaps induce lasting effects in adult ruminants. This paper reviews recent advances in understanding how host-microbiome interactions affect the GIT development and health of neonatal ruminants. Following initial GIT microbiome colonization, continuous exposure to host-specific microorganisms is necessary for GIT development and immune system maturation. Furthermore, the early GIT microbial community structure is significantly affected by early life events, such as maternal microbiota exposure, dietary changes, age and the addition of prebiotics, probiotics and synbiotics, supporting the idea of microbial programming in early life. However, the time window in which interventions can optimally improve production and reduce gastrointestinal disease as well as the role of key host-specific microbiota constituents and host immune regulation requires further study.     

Pan1 regulates transitions between stages of clathrin-mediated endocytosis

Endocytosis is a well-conserved process by which cells invaginate small portions of the plasma membrane to create vesicles containing extracellular and transmembrane cargo proteins. Dozens of proteins and hundreds of specific binding interactions are needed to coordinate and regulate these events. Saccharomyces cerevisiae is a powerful model system with which to study clathrin-mediated endocytosis (CME). Pan1 is believed to be a scaffolding protein due to its interactions with numerous proteins that act throughout the endocytic process. Previous research characterized many Pan1 binding interactions, but due to Pan1''s essential nature, the exact mechanisms of Pan1''s function in endocytosis have been difficult to define. We created a novel Pan1-degron allele, Pan1-AID, in which Pan1 can be specifically and efficiently degraded in <1 h upon addition of the plant hormone auxin. The loss of Pan1 caused a delay in endocytic progression and weakened connections between the coat/actin machinery and the membrane, leading to arrest in CME. In addition, we determined a critical role for the central region of Pan1 in endocytosis and viability. The regions important for endocytosis and viability can be separated, suggesting that Pan1 may have a distinct role in the cell that is essential for viability.     

The Receptor Concept in 3D: From Hypothesis and Metaphor to GPCR–Ligand Structures

The first mentioning of the word “receptor” for the structure with which a bioactive compound should react for obtaining its specific influence on a physiological system goes back to the years around 1900. The receptor concept was adapted from the lock and key theory for the enzyme substrate and blockers interactions. Through the years the concept, in the beginning rather being a metaphor, not a model, was refined and became reality in recent years. Not only the structures of receptors were elucidated, also the receptor machineries were unraveled. Following a brief historical review we will describe how the recent breakthroughs in the experimental determination of G protein-coupled receptor (GPCR) crystal structures can be complemented by computational modeling, medicinal chemistry, biochemical, and molecular pharmacological studies to obtain new insights into the molecular determinants of GPCR–ligand binding and activation. We will furthermore discuss how this information can be used for structure-based discovery of novel GPCR ligands that bind specific (allosteric) binding sites with desired effects on GPCR functional activity.     

Taxol-stabilized microtubules promote the formation of filaments from unmodified full-length Tau in vitro

Tau is a neuronal protein that stabilizes the microtubule (MT) network, but it also forms filaments associated with Alzheimer''s disease. Understanding Tau–MT and Tau–Tau interactions would help to establish Tau function in health and disease. For many years, literature reports on Tau–MT binding behavior and affinity have remained surprisingly contradictory (e.g., 10-fold variation in Tau–MT affinity). Tau–Tau interactions have also been investigated, but whether MTs might affect Tau filament formation is unknown. We have addressed these issues through binding assays and microscopy. We assessed Tau–MT interactions via cosedimentation and found that the measured affinity of Tau varies greatly, depending on the experimental design and the protein concentrations used. To investigate this dependence, we used fluorescence microscopy to examine Tau–MT binding. Strikingly, we found that Taxol-stabilized MTs promote Tau filament formation without characterized Tau-filament inducers. We propose that these novel Tau filaments account for the incongruence in Tau–MT affinity measurements. Moreover, electron microscopy reveals that these filaments appear similar to the heparin-induced Alzheimer''s model. These observations suggest that the MT-induced Tau filaments provide a new model for Alzheimer''s studies and that MTs might play a role in the formation of Alzheimer''s-associated neurofibrillary tangles.     

Topological constraints are major determinants of tRNA tertiary structure and dynamics and provide basis for tertiary folding cooperativity

Recent studies have shown that basic steric and connectivity constraints encoded at the secondary structure level are key determinants of 3D structure and dynamics in simple two-way RNA junctions. However, the role of these topological constraints in higher order RNA junctions remains poorly understood. Here, we use a specialized coarse-grained molecular dynamics model to directly probe the thermodynamic contributions of topological constraints in defining the 3D architecture and dynamics of transfer RNA (tRNA). Topological constraints alone restrict tRNA''s allowed conformational space by over an order of magnitude and strongly discriminate against formation of non-native tertiary contacts, providing a sequence independent source of folding specificity. Topological constraints also give rise to long-range correlations between the relative orientation of tRNA''s helices, which in turn provides a mechanism for encoding thermodynamic cooperativity between distinct tertiary interactions. These aspects of topological constraints make it such that only several tertiary interactions are needed to confine tRNA to its native global structure and specify functionally important 3D dynamics. We further show that topological constraints are conserved across tRNA''s different naturally occurring secondary structures. Taken together, our results emphasize the central role of secondary-structure-encoded topological constraints in defining RNA 3D structure, dynamics and folding.     

The polygenic system of cycloheximide inactivation inSchizophyllum commune

Resistant and sensitive strains ofSchizophyllum commune inactivate the fungicidal antibiotic cyeloheximide. This property is controlled by 3 – 4 genes. Intergenic interactions play an important role here. Heritability of the inactivation is high (0.8 – 0.9).     

Self-assembly,self-organization and division of labour

The prospect of generic principles of biological organization being uncovered through the increasingly broad use of the concepts of ''self-assembly'' and ''self-organization'' in biology will only be fulfilled if students of different levels of biological organization use the same terms with the same meanings. We consider the different ways the terms ''self-assembly'' and ''self-organization'' have been used, from studies of molecules to studies of animal societies. By linking ''self-assembly'' and ''self-organization'' with division of labour, we not only put forward a distinction between the underlying concepts but we are also able to relate them to the question: Why has a certain structure been favoured by natural selection? Using the particularly instructive case of social resilience in ant colonies, we demonstrate that the principle of self-organizing self-assembly may apply to higher levels of biological organization than previously considered. We predict that at the level of interactions among organisms within the most advanced animal societies, specialization through learning has a crucial role to play in re-assembly processes. This review may also help important commonalities and differences to be recognized between ordering mechanisms up to the social level and those further up the biological hierarchy, at the level of ecological communities.     

Embodied economics: how bodily information shapes the social coordination dynamics of decision-making

To date, experiments in economics are restricted to situations in which individuals are not influenced by the physical presence of other people. In such contexts, interactions remain at an abstract level, agents guessing what another person is thinking or is about to decide based on money exchange. Physical presence and bodily signals are therefore left out of the picture. However, in real life, social interactions (involving economic decisions or not) are not solely determined by a person''s inference about someone else''s state-of-mind. In this essay, we argue for embodied economics: an approach to neuroeconomics that takes into account how information provided by the entire body and its coordination dynamics influences the way we make economic decisions. Considering the role of embodiment in economics—movements, posture, sensitivity to mimicry and every kind of information the body conveys—makes sense. This is what we claim in this essay which, to some extent, constitutes a plea to consider bodily interactions between agents in social (neuro)economics.     

Shape and evolution of the fundamental niche in marine Vibrio

Hutchinson''s fundamental niche, defined by the physical and biological environments in which an organism can thrive in the absence of inter-species interactions, is an important theoretical concept in ecology. However, little is known about the overlap between the fundamental niche and the set of conditions species inhabit in nature, and about natural variation in fundamental niche shape and its change as species adapt to their environment. Here, we develop a custom-made dual gradient apparatus to map a cross-section of the fundamental niche for several marine bacterial species within the genus Vibrio based on their temperature and salinity tolerance, and compare tolerance limits to the environment where these species commonly occur. We interpret these niche shapes in light of a conceptual model comprising five basic niche shapes. We find that the fundamental niche encompasses a much wider set of conditions than those strains typically inhabit, especially for salinity. Moreover, though the conditions that strains typically inhabit agree well with the strains'' temperature tolerance, they are negatively correlated with the strains'' salinity tolerance. Such relationships can arise when the physiological response to different stressors is coupled, and we present evidence for such a coupling between temperature and salinity tolerance. Finally, comparison with well-documented ecological range in V. vulnificus suggests that biotic interactions limit the occurrence of this species at low-temperature—high-salinity conditions. Our findings highlight the complex interplay between the ecological, physiological and evolutionary determinants of niche morphology, and caution against making inferences based on a single ecological factor.     

Functional Domain Analysis of the Cell Division Inhibitor EzrA

The precise spatial and temporal control of bacterial cell division is achieved through the balanced actions of factors that inhibit assembly of the tubulin-like protein FtsZ at aberrant subcellular locations or promote its assembly at the future sites of division. In Bacillus subtilis, the membrane anchored cell division protein EzrA, interacts directly with FtsZ to prevent aberrant FtsZ assembly at cell poles and contributes to the inherently dynamic nature of the cytokinetic ring. Recent work suggests EzrA also serves as a scaffolding protein to coordinate lateral growth with cell wall biosynthesis through interactions with a host of proteins, a finding consistent with EzrA''s four extensive coiled-coil domains. In a previous study we identified a conserved patch of residues near EzrA''s C-terminus (the QNR motif) that are critical for maintenance of a dynamic cytokinetic ring, but dispensable for EzrA-mediated inhibition of FtsZ assembly at cell poles. In an extension of this work, here we report that EzrA''s two C-terminal coiled-coils function in concert with the QNR motif to mediate interactions with FtsZ and maintain the dynamic nature of the cytokinetic ring. In contrast, EzrA''s two N-terminal coiled-coils are dispensable for interaction between EzrA and FtsZ in vitro and in vivo, but required for EzrA mediated inhibition of FtsZ assembly at cell poles. Finally, chimeric analysis indicates that EzrA''s transmembrane anchor plays a generic role: concentrating EzrA at the plasma membrane where presumably it can most effectively modulate FtsZ assembly.     

Real Time Measurements of Membrane Protein:Receptor Interactions Using Surface Plasmon Resonance (SPR)

Protein-protein interactions are pivotal to most, if not all, physiological processes, and understanding the nature of such interactions is a central step in biological research. Surface Plasmon Resonance (SPR) is a sensitive detection technique for label-free study of bio-molecular interactions in real time. In a typical SPR experiment, one component (usually a protein, termed ''ligand'') is immobilized onto a sensor chip surface, while the other (the ''analyte'') is free in solution and is injected over the surface. Association and dissociation of the analyte from the ligand are measured and plotted in real time on a graph called a sensogram, from which pre-equilibrium and equilibrium data is derived. Being label-free, consuming low amounts of material, and providing pre-equilibrium kinetic data, often makes SPR the method of choice when studying dynamics of protein interactions. However, one has to keep in mind that due to the method''s high sensitivity, the data obtained needs to be carefully analyzed, and supported by other biochemical methods. SPR is particularly suitable for studying membrane proteins since it consumes small amounts of purified material, and is compatible with lipids and detergents. This protocol describes an SPR experiment characterizing the kinetic properties of the interaction between a membrane protein (an ABC transporter) and a soluble protein (the transporter''s cognate substrate binding protein).     

Subjects and Capital: A Fragment of a Documentary Ethnography

This paper considers the workings of various kinds of 'capital' in the early lives of one cohort, the Class of '58 of a U.S. High School. Bourdieu's valuable concept of capital as both material and cultural/symbolic is augmented with the idea of 'psychological' capital, a concept meant to begin to fill a gap in Bourdieu's framework concerning the complexity of desires, intentions, and 'personalities' in acting subjects. The paper also tackles some problems of ethnographic and ethnohistorical representation, suggesting the value of an analogy with several sub-genres of documentary films.     

Prevention of psychosocial problems in children with chronic illness.

Children with chronic illness and disability are at considerably increased risk of psychosocial problems, such as neurosis, attention deficit and poor adjustment to school. Health care professionals, especially primary care physicians, can do a great deal to prevent such problems in these children and their families. The approach outlined here is based on an understanding of the transactional model of development, in which the child interacts with--and to some extent creates--the social environment, and on a "noncategorical" concept in which common elements in chronic illness are recognized and emphasized. The physician''s role is to inform the family of the child''s condition as soon as possible, to offer hope, encouragement and guidance, to watch the child''s development, to maintain a shared view of the child and family, and, if possible, to ensure continuity of care.     

Investigating Protein-protein Interactions in Live Cells Using Bioluminescence Resonance Energy Transfer

Assays based on Bioluminescence Resonance Energy Transfer (BRET) provide a sensitive and reliable means to monitor protein-protein interactions in live cells. BRET is the non-radiative transfer of energy from a ''donor'' luciferase enzyme to an ''acceptor'' fluorescent protein. In the most common configuration of this assay, the donor is Renilla reniformis luciferase and the acceptor is Yellow Fluorescent Protein (YFP). Because the efficiency of energy transfer is strongly distance-dependent, observation of the BRET phenomenon requires that the donor and acceptor be in close proximity. To test for an interaction between two proteins of interest in cultured mammalian cells, one protein is expressed as a fusion with luciferase and the second as a fusion with YFP. An interaction between the two proteins of interest may bring the donor and acceptor sufficiently close for energy transfer to occur. Compared to other techniques for investigating protein-protein interactions, the BRET assay is sensitive, requires little hands-on time and few reagents, and is able to detect interactions which are weak, transient, or dependent on the biochemical environment found within a live cell. It is therefore an ideal approach for confirming putative interactions suggested by yeast two-hybrid or mass spectrometry proteomics studies, and in addition it is well-suited for mapping interacting regions, assessing the effect of post-translational modifications on protein-protein interactions, and evaluating the impact of mutations identified in patient DNA.     

Evolutionarily conserved linkage between enzyme fold, flexibility, and catalysis

Proteins are intrinsically flexible molecules. The role of internal motions in a protein''s designated function is widely debated. The role of protein structure in enzyme catalysis is well established, and conservation of structural features provides vital clues to their role in function. Recently, it has been proposed that the protein function may involve multiple conformations: the observed deviations are not random thermodynamic fluctuations; rather, flexibility may be closely linked to protein function, including enzyme catalysis. We hypothesize that the argument of conservation of important structural features can also be extended to identification of protein flexibility in interconnection with enzyme function. Three classes of enzymes (prolyl-peptidyl isomerase, oxidoreductase, and nuclease) that catalyze diverse chemical reactions have been examined using detailed computational modeling. For each class, the identification and characterization of the internal protein motions coupled to the chemical step in enzyme mechanisms in multiple species show identical enzyme conformational fluctuations. In addition to the active-site residues, motions of protein surface loop regions (>10 Å away) are observed to be identical across species, and networks of conserved interactions/residues connect these highly flexible surface regions to the active-site residues that make direct contact with substrates. More interestingly, examination of reaction-coupled motions in non-homologous enzyme systems (with no structural or sequence similarity) that catalyze the same biochemical reaction shows motions that induce remarkably similar changes in the enzyme–substrate interactions during catalysis. The results indicate that the reaction-coupled flexibility is a conserved aspect of the enzyme molecular architecture. Protein motions in distal areas of homologous and non-homologous enzyme systems mediate similar changes in the active-site enzyme–substrate interactions, thereby impacting the mechanism of catalyzed chemistry. These results have implications for understanding the mechanism of allostery, and for protein engineering and drug design.

Author''s Summary

Enzymes are nature''s molecular machines that catalyze biochemical reactions with remarkable efficiency. Recent evidence suggests that enzyme function may involve not only direct structural interactions between the enzyme and its substrate, but also internal motions of the enzyme itself. Here, we describe a computational investigation of three classes of enzymes that catalyze completely different biochemical reactions. Remarkably, the mobile enzyme regions and the nature of these motions are the same across species ranging from single-celled organisms to complex life-forms. Also surprisingly, non-homologous enzymes that catalyze the same chemical reaction but do not share sequence or structural similarity reveal a similar impact of enzyme motions on their reaction mechanisms. Flexible enzyme regions are found to be connected by conserved networks of coupled interactions that connect surface regions to active-site residues. These networks may provide a mechanism for the solvent on an enzyme''s surface to couple to the reaction catalyzed by the enzyme. These results have implications for understanding the mechanism of allostery (long-range effects), and for protein engineering and drug design.     

Cation-pi interactions at non-redundant protein-RNA interfaces

Cation-pi interactions have proved to be important in proteins and protein-ligand complexes. Here, cation-pi interactions are analyzed for 282 non-redundant protein-RNA interfaces. The statistical results show that this kind of interactions exists in 65% of the interfaces. The four RNA bases are ranked as Gua > Ade > Ura > Cyt according to their propensity to participate in cation-pi interactions. The corresponding ranking for the involved amino acid residues is: Arg > Lys > Asn > Gln. The same trends are obtained based on the empirical energy calculation. The Arg-Gua pairs have the greatest stability and are also most frequently observed. The number of cation-pi pairs involving unpaired bases is 2.5 times as many as those involving paired bases. Hence, cation-pi interactions show sequence and structural specificities. For the bicyclic bases, Gua and Ade, their 5-atom rings participate in cation-pi interactions somewhat more than the 6-atom rings, with percentages of 54 and 46%, respectively, which is due to the higher cation-pi participation proportion (63%) of 5-atom rings in the paired bases. These results give a general view of cation-pi interactions at protein-RNA interfaces and are helpful in understanding the specific recognition between protein and RNA.