Toward a hypothesis-free understanding of how phosphorylation dynamically impacts protein turnover

The turnover measurement of proteins and proteoforms has been largely facilitated by workflows coupling metabolic labeling with mass spectrometry (MS), including dynamic stable isotope labeling by amino acids in cell culture (dynamic SILAC) or pulsed SILAC (pSILAC). Very recent studies including ours have integrated themeasurement of post-translational modifications (PTMs) at the proteome level (i.e., phosphoproteomics) with pSILAC experiments in steady state systems, exploring the link between PTMs and turnover at the proteome-scale. An open question in the field is how to exactly interpret these complex datasets in a biological perspective. Here, we present a novel pSILAC phosphoproteomic dataset which was obtained during a dynamic process of cell starvation using data-independent acquisition MS (DIA-MS). To provide an unbiased “hypothesis-free” analysis framework, we developed a strategy to interrogate how phosphorylation dynamically impacts protein turnover across the time series data. With this strategy, we discovered a complex relationship between phosphorylation and protein turnover that was previously underexplored. Our results further revealed a link between phosphorylation stoichiometry with the turnover of phosphorylated peptidoforms. Moreover, our results suggested that phosphoproteomic turnover diversity cannot directly explain the abundance regulation of phosphorylation during cell starvation, underscoring the importance of future studies addressing PTM site-resolved protein turnover.     

Toward an individual-level understanding of vigilance: the role of social information

A gregarious lifestyle affords the benefit of collective detectionof predators through the many-eyes effect. Studies of vigilanceare generally concerned with exploring the relationship betweenvigilance rates and group size. However, a mechanistic understandingof the rules individual animals use to achieve this group-levelbehavior is lacking. Building on a previous modeling approach,we suggest that individuals reconcile their own private informationagainst the social information they receive from their groupmates in order to decide whether to feed or be vigilant at anyone time. We present a novel modeling approach utilizing a Markovchain Monte Carlo process to describe the transition betweenvigilant and nonvigilant states. Many of our assumptions arebased qualitatively on recently published experimental observations.We vary the amount of social information and the fidelity withwhich individuals process this information and show that thishas a profound effect on the individual vigilance rate, theindividual vigilant bout length, and the proportion of vigilantindividuals at any one time. A wide range of group-level vigilancepatterns can be obtained by varying simple behavioral characteristicsof individual animals. We find that generally, increasing theamount of, and sensitivity to, social information generatesa more cooperative vigilance behavior. This model potentiallyprovides a theoretical and conceptual framework for examiningspecific real-life systems. We propose analyzing individual-baseddata from real animals by considering their group to be a connectednetwork of individuals, with information transfer between them.     

Aspergillus fumigatus biofilms: Toward understanding how growth as a multicellular network increases antifungal resistance and disease progression

Aspergillus fumigatus is a saprophytic, filamentous fungus found in soils and compost and the causative agent of several pulmonary diseases in humans, birds, and other mammals. A. fumigatus and other filamentous fungi grow as networks of filamentous hyphae that have characteristics of a classic microbial biofilm. These characteristics include production of an extracellular matrix (ECM), surface adhesion, multicellularity, and increased antimicrobial drug resistance. A. fumigatus biofilm growth occurs in vivo at sites of infection, highlighting the importance of defining mechanisms underlying biofilm development and associated emergent properties. We propose that there are 3 distinct phases in the development of A. fumigatus biofilms: biofilm initiation, immature biofilm, and mature biofilm. These stages are defined both temporally and by unique genetic and structural changes over the course of development. Here, we review known mechanisms within each of these stages that contribute to biofilm structure, ECM production, and increased resistance to contemporary antifungal drugs. We highlight gaps in our understanding of biofilm development and function that when addressed are expected to aid in the development of novel antifungal therapies capable of killing filamentous fungal biofilms.     

Toward understanding dog evolutionary and domestication history

Dog domestication was probably started very early during the Upper paleolithic period (~35,000 BP), thus well before any other animal or plant domestication. This early process, probably unconscious, is called proto-domestication to distinguish it from the real domestication process that has been dated around 14,000 BC. Genomic DNA analyses have shown recently that domestication started in the Middle East and rapidly expanded into all human populations. Nowadays, the dog population is fragmented in several hundreds of breeds well characterized by their phenotypes that offer a unique spectrum of polymorphism. More recent studies detect genetic signatures that will be useful to highlight breed history as well as the impact of domestication at the DNA level.     

Action understanding: how, what and why

The mirror neuron system may help us understand how others act and what they do. A recent study has shown that consciously reflecting on their intentions additionally recruits mentalizing areas.     

Toward understanding the origin and evolution of cellular organisms

In this era of high‐throughput biology, bioinformatics has become a major discipline for making sense out of large‐scale datasets. Bioinformatics is usually considered as a practical field developing databases and software tools for supporting other fields, rather than a fundamental scientific discipline for uncovering principles of biology. The KEGG resource that we have been developing is a reference knowledge base for biological interpretation of genome sequences and other high‐throughput data. It is now one of the most utilized biological databases because of its practical values. For me personally, KEGG is a step toward understanding the origin and evolution of cellular organisms.     

Toward a mechanistic understanding and prediction of biotic homogenization

The widespread replacement of native species with cosmopolitan, nonnative species is homogenizing the global fauna and flora. While the empirical study of biotic homogenization is substantial and growing, theoretical aspects have yet to be explored. Consequently, the breadth of possible ecological mechanisms that can shape current and future patterns and rates of homogenization remain largely unknown. Here, we develop a conceptual model that describes 14 potential scenarios by which species invasions and/or extinctions can lead to various trajectories of biotic homogenization (increased community similarity) or differentiation (decreased community similarity); we then use a simulation approach to explore the model's predictions. We found changes in community similarity to vary with the type and number of nonnative and native species, the historical degree of similarity among the communities, and, to a lesser degree, the richness of the recipient communities. Homogenization is greatest when similar species invade communities, causing either no extinction or differential extinction of native species. The model predictions are consistent with current empirical data for fish, bird, and plant communities and therefore may represent the dominant mechanisms of contemporary homogenization. We present a unifying model illustrating how the balance between invading and extinct species dictates the outcome of biotic homogenization. We conclude by discussing a number of critical but largely unrecognized issues that bear on the empirical study of biotic homogenization, including the importance of spatial scale, temporal scale, and data resolution. We argue that the study of biotic homogenization needs to be placed in a more mechanistic and predictive framework in order for studies to provide adequate guidance in conservation efforts to maintain regional distinctness of the global biota.     

Invasive ants alter foraging and parental behaviors of a native bird

Introduced species can exert outsized impacts on native biota through both direct (predation) and indirect (competition) effects. Ants frequently become established in new areas after being transported by humans across traditional biological or geographical barriers, and a prime example of such establishment is the red imported fire ant (Solenopsis invicta). Introduced to North America in the 1930's, red imported fire ants are now firmly established throughout the southeastern United States. Although these invasive predators can dramatically impact native arthropods, their effect on vertebrates through resource competition is essentially unknown. Using a paired experimental design, we compared patterns of foraging and rates of provisioning for breeding eastern bluebirds (Sialia sialis) in unmanipulated (control) territories to those in adjacent (treated) territories where fire ants were experimentally reduced. Bluebirds inhabiting treated territories foraged nearer their nests and provisioned offspring more frequently than bluebirds inhabiting control territories with unmanipulated fire ant levels. Additionally, nestlings from treated territories were in better condition than those from control territories, though these differences were largely confined to early development. The elimination of significant differences in body condition towards the end of the nestling period suggests that bluebird parents in control territories were able to make up the food deficit caused by fire ants, potentially by working harder to adequately provision their offspring. The relationship between fire ant abundance and bluebird behavior hints at the complexity of ecological communities and suggests negative effects of invasive species are not limited to taxa with which they have direct contact.     

Wild chimpanzees can perform social grooming and social play behaviors simultaneously

Reliable evidence was obtained of the simultaneous performance of social grooming and social play behaviors by individuals among wild chimpanzees of the M group in Mahale Mountains National Park. I observed three cases of this performance: in an old female, a young female, and an adult male. While the agent was grooming the back of an adult bimanually, an infant or a juvenile approached the agent. The agent then started playing with the infant/juvenile using only the right hand, while simultaneously grooming the back of the adult with the left hand. In one case, an old female continued the simultaneous performance for about 1 min. Such performances probably occur at low frequency because they are not often required. The similarity in the neurobiological bases and the functions of social grooming and social play behaviors, both of which include repetitive contact with the body of another individual, may facilitate their simultaneous performance.     

Toward an understanding of structure and function of ion channels

The second half of the 1980s is certain to be considered a turning point in the study of ion channels. Within the last few years, monumental advances in the application of molecular biology, single-channel recording, and direct molecular characterization have been brought to bear on the problem of relating the molecular structure of the ion channel proteins to their function in the cell membrane. Structure-function relationships can now be studied at a level of detail that was unimagined a decade ago. Recently, advances made with the techniques of molecular biology appear to have dominated the literature in this field; however, innovative strategies of structural characterization and electrical measurements of functioning channels in native and artificial membranes continue to break new ground. This paper is a selective review of current progress in understanding structure-function relationships in ion channels. The relative usefulness of determining amino acid sequences of channel proteins together with the resulting deductions about 3-dimensional structure and function will be evaluated with respect to the potential importance of studying the channel molecules more directly by biochemical, immunological, and electrophysiological methods. A full understanding of the details of channel structure and its relationship to function may be realized in the near future as a result of the interdisciplinary application of biophysical, biochemical, and molecular biological techniques.     

Toward understanding the structure and interactions of microtubules and motor proteins

To obtain an overall three-dimensional picture of the interaction between microtubules and the motor proteins of the kinesin family it will be necessary to take account of both atomic resolution structures obtained by X-ray crystallography and medium resolution reconstructions obtained by electron cryomicroscopy. We examine the problems associated with obtaining the required structural information from electron micrographs of vitreous ice-embedded microtubules decorated with motor domains. We find that the minus-end directed motor, ncd, decorates microtubules with an 80 Å periodicity as for kinesin. Our theoretical analysis and experiments with ncd illustrate the difficulty in determining unambiguously the surface lattice organization by diffraction analysis of micrographs. 3D reconstructions of decorated microtubules are required to accurately locate the motor domains. Helical diffraction theory is not usually applicable because microtubules are cylindrical structures that rarely have complete helical symmetry. We propose using a back-projection method based on the long pitch helices formed by individual protofilaments. Model reconstructions show that this approach is feasible. © 1995 Wiley-Liss, Inc.     

Multiple chemical sensitivities: stigma and social experiences

Multiple Chemical Sensitivity (MCS), an intolerance to everyday chemical and biological substances in amounts that do not bother other people, is a medically contested condition. In addition to symptoms and the ongoing difficulties of living with this condition, this hidden and stigmatized disability strongly impacts social relationships and daily life. Based on an ethnographic study, this article introduces the context of MCS in terms of cultural themes, the media, and the economic power of industries that manufacture the products that make people with MCS sick. Participants' experiences with family members and friends, in work and school settings, and with physicians exemplify the difficulties of living with MCS. I dedicate this article to Joan Ablon, my professor and mentor, whose work has always inspired my thinking and research topics.     

The co-evolution of individual behaviors and social institutions

We present agent-based simulations of a model of a deme-structured population in which group differences in social institutions are culturally transmitted and individual behaviors are genetically transmitted. We use a standard extended fitness accounting framework to identify the parameter space for which this co-evolutionary process generates high levels of group-beneficial behaviors. We show that intergroup conflicts may explain the evolutionary success of both: (a) altruistic forms of human sociality towards unrelated members of one's group; and (b) group-level institutional structures such as food sharing which have emerged and diffused repeatedly in a wide variety of ecologies during the course of human history. Group-beneficial behaviors may evolve if (a) they inflict sufficient fitness costs on outgroup individuals and (b) group-level institutions limit the individual fitness costs of these behaviors and thereby attenuate within-group selection against these behaviors. Thus, the evolutionary success of individually costly but group-beneficial behaviors in the relevant environments during the first 90,000 years of anatomically modern human existence may have been a consequence of distinctive human capacities in social institution building.