A Model of Extracellular Enzymes in Free-Living Microbes: Which Strategy Pays Off?

ABSTRACTAn initial modeling approach was applied to analyze how a single, nonmotile, free-living, heterotrophic bacterial cell may optimize the deployment of its extracellular enzymes. Free-living cells live in a dilute and complex substrate field, and to gain enough substrate, their extracellular enzymes must be utilized efficiently. The model revealed that surface-attached and free enzymes generate unique enzyme and substrate fields, and each deployment strategy has distinctive advantages. For a solitary cell, surface-attached enzymes are suggested to be the most cost-efficient strategy. This strategy entails potential substrates being reduced to very low concentrations. Free enzymes, on the other hand, generate a radically different substrate field, which suggests significant benefits for the strategy if free cells engage in social foraging or experience high substrate concentrations. Swimming has a slight positive effect for the attached-enzyme strategy, while the effect is negative for the free-enzyme strategy. The results of this study suggest that specific dissolved organic compounds in the ocean likely persist below a threshold concentration impervious to biological utilization. This could help explain the persistence and apparent refractory state of oceanic dissolved organic matter (DOM). Microbial extracellular enzyme strategies, therefore, have important implications for larger-scale processes, such as shaping the role of DOM in ocean carbon sequestration.

The “Multicellular Origin” of Cancer and the Clonal Evolution of Oncogenesis

Cancer cells are the result of the multi-step, multi-dimensional and multi-generational process of oncogenesis, but they are never the products of cellular transformation. When a stem cell divides, asymmetrically or symmetrically, it produces two new (new generation) cells, a differentiated daughter cell and a daughter which is a parent-identical stem-cell, or two identical daughter stem cells, respectively. In either case, the daughter cells, differentiated or parent-identical, have their own individuality and character. A daughter cell is not a transformed parent cell; it has its own cellular identity, genotype and phenotype although it carries its parent’s genotypical and phenotypical features. The term “Cellular Transformation” in today’s Medical Research Literature, which refers to neoplastic cellular changes, is unintentionally amiss, but scientifically delusive; it implies a solitary cellular reign that misleadingly suggests a “single cell” origin for oncogenesis. In any living multicellular organism, whose multicellular existence and functionality is totally based on intercellular subsistence, a multicellular act or happening is absolutely impossible to start with or from a solitary cell action. In multicellular organisms, in vivo, malignant neoplasms, including leukemias, which all are the products of highly organized cellular teamwork from the very beginning, never arise from single cells; they arise from groups of cells.

Contact inhibition of locomotion probabilities drive solitary versus collective cell migration

Contact inhibition of locomotion (CIL) is the process whereby cells collide, cease migrating in the direction of the collision, and repolarize their migration machinery away from the collision. Quantitative analysis of CIL has remained elusive because cell-to-cell collisions are infrequent in traditional cell culture. Moreover, whereas CIL predicts mutual cell repulsion and ‘scattering’ of cells, the same cells in vivo are observed to undergo CIL at some developmental times and collective cell migration at others. It remains unclear whether CIL is simply absent during collective cell migration, or if the two processes coexist and are perhaps even related. Here, we used micropatterned stripes of extracellular matrix to restrict cell migration to linear paths such that cells polarized in one of two directions and collisions between cells occurred frequently and consistently, permitting quantitative and unbiased analysis of CIL. Observing repolarization events in different contexts, including head-to-head collision, head-to-tail collision, collision with an inert barrier, or no collision, and describing polarization as a two-state transition indicated that CIL occurs probabilistically, and most strongly upon head-to-head collisions. In addition to strong CIL, we also observed ‘trains’ of cells moving collectively with high persistence that appeared to emerge from single cells. To reconcile these seemingly conflicting observations of CIL and collective cell migration, we constructed an agent-based model to simulate our experiments. Our model quantitatively predicted the emergence of collective migration, and demonstrated the sensitivity of such emergence to the probability of CIL. Thus CIL and collective migration can coexist, and in fact a shift in CIL probabilities may underlie transitions between solitary cell migration and collective cell migration. Taken together, our data demonstrate the emergence of persistently polarized, collective cell movement arising from CIL between colliding cells.

Solitary Confinement

Solitary confinement has long been part of the practice of imprisonment in the United States, the United Kingdom, and elsewhere. It has changed over time in terms of the underlying rationale, the enthusiasm with which it is embraced, and the identities of its most ardent advocates. In the early decades of the 19th century, religiously motivated prison reformers were at the forefront. Consensus was widespread about the need for prisoners to live by a rule of silence but disagreement as to whether this required separation at all times from their peers or whether silent association was acceptable (or, indeed, preferable). In the closing decades of the 20th century, there was renewed interest in solitary confinement, but without the concern for prisoner welfare and rehabilitation that had characterized earlier debates. Now the protagonists were prison administrators, and a discourse that had taken place outside the prison gates and featured many voices was replaced by one that was almost entirely internal and one-sided. Typically, there are four kinds of circumstances under which prisoners are isolated. First, there is protective custody, often at the prisoner’s request. A return to the general population can be difficult if a prisoner has been segregated because of vulnerability due to the nature of his or her offense, the accumulation of debts that cannot be discharged, or a perception that he or she has communicated information to staff. Second, there is disciplinary detention for breaking prison rules; generally the duration is relatively short. In some countries a court can impose solitary confinement as part of a sentence and the time period here can be lengthy. Third is administrative segregation. This can be short term (e.g., while an investigation is being carried out or pending transfer) or long term (if a prisoner is thought to present a threat to institutional order). Fourth, there are occasions when prisoners seek the respite of the solitary cell as a way of easing psychological pressures. In such cases the stay tends to be brief and prisoners return to their usual place of abode afterward. Long-term administrative segregation in the United States in facilities that have been described as offering “supermax” custody has generated concern on human rights grounds as well as for reasons of economy and efficacy.

THE CHILDREN OF READING GAOL: A Letter from Oscar Wilde, 1897

A boy used to come and play in these streets. Now he is alone. Held by stone walls of a solitary cell. Gray slits of life escape through bars immobilizing him with shadowy splints. He sits on the floor wet with cold fear. His face a white wedge of terror like a hunted animal. He receives bread and water. In burned out sockets there is wrath. He has been crying all day. He cannot understand prison. He cannot realize what society is. Darkness covers him with dreams of death.

The Bakerian lecture—On the organization of the fossil plants of the coal-measures.—Part IX. On the latest researches into the organization of the fossil plants of the British coal-measures, especially of the calamites and lepidodendra

The first plant noticed is one of which a transverse section was figured in the lecturer’s Memoir, Part I., under the belief that it was Calamitean. It now proves not to be so, but is a branching non-articulated plant, lacking the nodes and the longitudinal internodal canals so characteristic of the Calamites. It has a large parenchymatous medulla with radiating prolongations separating the very distinctly defined wedges of the vascular zone. From the peculiar shape thus given to transverse sections of the medulla the author has assigned to the plant the provisional name of Astromyelon . In the place of the canal of Calamites the thin medullary extremity of each vascular wedge is occupied by a few larger and often more conspicuous vessels than those forming the rest of the wedge. The medulla farther differs from that of Calamites in being rarely fistular. Each wedge consists of a series of regular radiating laminæ of barred vessels separated by numerous medullary rays—the latter varying in composition from a solitary cell to numerous cells arranged in single vertical series. Nearly all the stems and branches of this plant are found to be decorticated. One specimen found by Mr. Butterworth is surrounded by a very thin cortex consisting only of three or four layers of parenchymatous cells. Astromyelon forms another example of the numerous carboniferous plants whose vascular zone grew by exogenous additions, yet the exclusion of every modification of tissue, except barred vessels, from the vascular laminæ suggests Cryptogamic rathter than Gymnospermous aflinities. Astromyelon is the only distinct type of plant left undescribed in the lecturer’s previous Memoirs; but he has obtained a considerable amount of additional information respecting some of those previously examined.