Entropy increase and information loss in Markov models of evolution

Markov models of evolution describe changes in the probability distribution of the trait values a population might exhibit. In consequence, they also describe how entropy and conditional entropy values evolve, and how the mutual information that characterizes the relation between an earlier and a later moment in a lineage’s history depends on how much time separates them. These models therefore provide an interesting perspective on questions that usually are considered in the foundations of physics—when and why does entropy increase and at what rates do changes in entropy take place? They also throw light on an important epistemological question: are there limits on what your observations of the present can tell you about the evolutionary past?     

Alterations in the morphology of ganglion cell dendrites in the adult rat retina after optic nerve transection and grafting of peripheral nerve segments

Summary Transected ganglion cell axons from the adult retina are capable of reinnervating their central targets by growing into transplanted peripheral nerve (PN) segments. Injury of the optic nerve causes various metabolic and morphological changes in the retinal ganglion cell (RGC) perikarya and in the dendrites. The present work examined the dendritic trees of those ganglion cells surviving axotomy and of those whose severed axons re-elongated in PN grafts to reach either the superior colliculus (SC), transplanted SC, or transplanted autologous thigh muscle. The elaboration of the dendritic trees was visualized by means of the strongly fluorescent carbocyanine dye DiI, which is taken up by axons and transported to the cell bodies and from there to the dendritic branches. Alternatively, retinofugal axons regrowing through PN grafts were anterogradely filled from the eye cup with rhodamine B-isothiocyanate. The transection of the optic nerve resulted in characteristic changes in the ganglion cell dendrites, particularly in the degeneration of most of the terminal and preterminal dendritic branches. This occurred within the first 1 to 2 weeks following axotomy. The different types of ganglion cells appear to vary in their sensitivity to axotomy, as reflected by a rapid degeneration of certain cell dendrites after severance of the optic nerve. The most vulnerable cells were those with small perikarya and small dendritic fields (type II), whereas larger cells with larger dendritic fields (type I and III) were slower to respond and less dramatically affected. Regrowth of the lesioned axons in peripheral nerve grafts and reconnection of the retina with various tissues did not result in a significant immediate recovery of ganglion cell dendrites, although it did prevent some axotomized cells from further progression toward posttraumatic cell death.     

Evidence Relating Cessation of Respiration, Cell Envelope Changes, and Death in Ultraviolet-Irradiated Escherichia coli B/r Cells

Ionic and nonionic detergents have little effect on respiring bacteria, but in cultures poisoned with KCN rapid solubilization of the cell membrane, as indicated by turbidity losses, takes place. Ultraviolet radiations cause Escherichia coli cells grown in minimal medium with glycerol as a carbon source to cease respiring and growing about 1 h after irradiation. We tested the effect of the nonionic detergent Triton X-100 on growth and cell membrane dissolution (both measured by turbidity changes), respiration, and viability of unirradiated and irradiated E. coli B/r cells. When the detergent was added to cells immediately after irradiation, a decrease in turbidity occurred only when respiration was about to cease; when it was added after cessation of respiration, the turbidity loss was immediate. In both cases the turbidity loss was about 60%, and disintegration of the cell walls did not take place. 5-Fluorouracil (FU) and thermal (42 C) treatments cause respiration of irradiated cells to be maintained and also cause viability increases. Irradiated cells treated with FU and detergent show no turbidity loss just prior to the time respiration normally ceases, but a loss does occur in irradiated cells incubated with detergent at 42 C. We conclude that FU maintains respiration for all of the cells, but that thermal treatment maintains respiration for only part of the cells. In all cases the detergent had only a negligible effect on the respiration and viability of unirradiated and irradiated cells. We conclude that Triton X-100 causes solubilization of cell membranes of only nonrespiring cells that are not destined to survive.     

Epigenetic gene regulation in stem cells and correlation to cancer

Through the classic study of genetics, much has been learned about the regulation and progression of human disease. Specifically, cancer has been defined as a disease driven by genetic alterations, including mutations in tumor-suppressor genes and oncogenes, as well as chromosomal abnormalities. However, the study of normal human development has identified that in addition to classical genetics, regulation of gene expression is also modified by ‘epigenetic’ alterations including chromatin remodeling and histone variants, DNA methylation, the regulation of polycomb group proteins, and the epigenetic function of non-coding RNA. These changes are modifications inherited during both meiosis and mitosis, yet they do not result in alterations of the actual DNA sequence. A number of biological questions are directly influenced by epigenetics, such as how does a cell know when to divide, differentiate or remain quiescent, and more importantly, what happens when these pathways become altered? Do these alterations lead to the development and/or progression of cancer? This review will focus on summarizing the limited current literature involving epigenetic alterations in the context of human cancer stems cells (CSCs). The extent to which epigenetic changes define cell fate, identity, and phenotype are still under intense investigation, and many questions remain largely unanswered. Before discussing epigenetic gene silencing in CSCs, the different classifications of stem cells and their properties will be introduced. This will be followed by an introduction to the different epigenetic mechanisms. Finally, there will be a discussion of the current knowledge of epigenetic modifications in stem cells, specifically what is known from rodent systems and established cancer cell lines, and how they are leading us to understand human stem cells.     

Charles Girard: Relationships and Representation in Nineteenth Century Systematics

Early nineteenth century systematists sought to describe what they called the Natural System or the Natural Classification. In the nineteenth century, there was no agreement about the basis of observed patterns of similarity between organisms. What did these systematists think they were doing, when they named taxa, proposed relationships between taxa, and arranged taxa into representational schemes? In this paper I explicate Charles Frederic Girard’s (1822–1895) theory and method of systematics. A student of Louis Agassiz, and subsequently (1850–1858) a collaborator with Spencer Baird, Girard claimed that natural classificatory methods do not presuppose either a special creationist or an evolutionary theory of the natural world. The natural system, in Girard’s view, comprises three distinct ways in which organisms can be related to each other. Girard analyzed these relationships, and justified his classificatory methodology, by appeal to his embryological and physiological work. Girard offers an explicit theoretical answer to the question, what characters are evidence for natural classificatory hypotheses? I show that the challenge of simultaneously depicting the three distinct types of relationship led Girard to add a third dimension to his classificatory diagrams.     

Wild justice and fair play: cooperation,forgiveness, and morality in animals

In this paper I argue that we can learn much about ‘wild justice’ and the evolutionary origins of social morality – behaving fairly – by studying social play behavior in group-living animals, and that interdisciplinary cooperation will help immensely. In our efforts to learn more about the evolution of morality we need to broaden our comparative research to include animals other than non-human primates. If one is a good Darwinian, it is premature to claim that only humans can be empathic and moral beings. By asking the question ‘What is it like to be another animal?’ we can discover rules of engagement that guide animals in their social encounters. When I study dogs, for example, I try to be a ‘dogocentrist’ and practice ‘dogomorphism.’ My major arguments center on the following ‘big’ questions: Can animals be moral beings or do they merely act as if they are? What are the evolutionary roots of cooperation, fairness, trust, forgiveness, and morality? What do animals do when they engage in social play? How do animals negotiate agreements to cooperate, to forgive, to behave fairly, to develop trust? Can animals forgive? Why cooperate and play fairly? Why did play evolve as it has? Does ‘being fair’ mean being more fit – do individual variations in play influence an individual's reproductive fitness, are more virtuous individuals more fit than less virtuous individuals? What is the taxonomic distribution of cognitive skills and emotional capacities necessary for individuals to be able to behave fairly, to empathize, to behave morally? Can we use information about moral behavior in animals to help us understand ourselves? I conclude that there is strong selection for cooperative fair play in which individuals establish and maintain a social contract to play because there are mutual benefits when individuals adopt this strategy and group stability may be also be fostered. Numerous mechanisms have evolved to facilitate the initiation and maintenance of social play to keep others engaged, so that agreeing to play fairly and the resulting benefits of doing so can be readily achieved. I also claim that the ability to make accurate predictions about what an individual is likely to do in a given social situation is a useful litmus test for explaining what might be happening in an individual's brain during social encounters, and that intentional or representational explanations are often important for making these predictions.     

Expression of the SOS system in Escherichia coli growing under nitrate respiration conditions

Induction of several SOS functions by mitomycin C, bleomycin or thermal treatment of a recA441 mutant growing under nitrate respiration conditions was studied in Escherichia coli. Mitomycin C caused inhibition of cell division, induction of prophages and expression of umuC gene but like in aerobically growing cells, it did not trigger the cessation of cell repiration. On the contrary, both recA⁺ and recA441 cultures either treated with bleomycin or incubated at 42°C failed to induce any of the different SOS functions cited above.Furthermore, after bleomycin addition or thermal treatment both recA⁺ and recA441 cultures did not present any variation in the cellular ATP level, contrary to what happens under aerobic growth. The blocking of the expression of some SOS functions under nitrate respiration conditions is not an irreversible process because cells incubated under these anaerobic conditions were able to induce the SOS system when changed to an aerobic medium 30 min after the SOS-inducing treatment had been applied.     

Troubled landscapes,troubling anthropology: co‐presence,necessity, and the making of ethnographic knowledge

If ‘co‐presence is a condition of [anthropological] inquiry’ (Fabian), what sort of knowledge does it produce? I explore this question through an ethnography of a ‘troubled landscape’ in Malaysian Borneo: a lush, hilly region that has been the site of a dam construction and resettlement project since the late 2000s. My article uses the notion of co‐presence as both a lens through which to explore the predicaments of the four small communities affected by the scheme and a reflexive device that underscores the embeddedness of the ethnographic encounter in a larger relational field – one characterized as much by chance and necessity as it is by anthropologists’ intellectual agendas. In the process, I seek to trouble some of the methodological and ethical issues posed by anthropology's recent ‘ontological turn’, notably the long‐standing questions of what it means to ‘take seriously’ and how ethnography and the ethnographer are implicated in this project.     

Tamoxifen and estradiol interact with the flavin mononucleotide site of complex I leading to mitochondrial failure

This study evaluated the action of tamoxifen and estradiol on the function of isolated liver mitochondria. We observed that although tamoxifen and estradiol per se did not affect mitochondrial complexes II, III, or IV, complex I is affected, this effect being more drastic (except for state 4 of respiration) when mitochondria were coincubated with both drugs. Furthermore, using two respiratory chain inhibitors, rotenone and diphenyliodonium chloride, we identified the flavin mononucleotide site of complex I as the target of tamoxifen and/or estradiol action(s). Tamoxifen (25 microm) per se induced a significant increase in hydrogen peroxide production and state 4 of respiration. Additionally, a significant decrease in respiratory control ratio, transmembrane, and depolarization potentials were observed. Estradiol per se decreased carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP)-stimulated respiration, state 3 of respiration, and respiratory control ratio and increased lag phase of repolarization. With the exception of state 4 of respiration whose increase induced by tamoxifen was reversed by the presence of estradiol, the effects of tamoxifen were highly exacerbated when estradiol was present. We observed that 10 microm tamoxifen in the presence of estradiol affected mitochondria significantly by decreasing FCCP-stimulated respiration, state 3 of respiration, respiratory control ratio, and ADP depolarization and increasing the lag phase of repolarization. All of the deleterious effects induced by 25 microm tamoxifen were highly exacerbated in the presence of estradiol. Furthermore, we observed that the effects of both compounds were independent of estrogen receptors because the pure estrogen antagonist ICI 182,780 did not interfere with tamoxifen and/or estradiol detrimental effects. Altogether, our data provide a mechanistic explanation for the multiple cytotoxic effects of tamoxifen including its capacity to destroy tamoxifen-resistant breast cancer cells in the presence of estradiol. This new piece of information provides a basis for the development of new and promising anticancer therapeutic strategies.     

“Targeting the absence” and therapeutic engineering for cancer therapy

The Gotham Prize was awarded to Alex Varshavsky for “Targeting the absence”, a strategy employing negative targets of cancer therapy. This is a brilliant example of therapeutic engineering: designing a sequence of events that leads to the selective killing of one type of cell, while sparing all others. A complex molecular device (Varshavsky’s Demon) examines DNA, recognizes the present target in normal cells and kills cancer cells. The strategy is limited by the delivery (transfection or infection) of DNA-based devices into each cell of our body. How can we overcome this limitation? Can therapeutic engineering be applied to small drugs? Can each small molecule reach a cell separately and, once in a cell, exert orchestrated action governed by cellular context? Here I describe how a combination of small drugs can acquire a demonic power to check, choose and selectively kill. The cytotoxicity is restricted to cells lacking (or having) one of the targets. For example, in the presence of a normal target, one drug can cancel the cytotoxic action of another drug. And by increasing a number of targets, we can increase the precision and power of such ‘restrictive’ combinations. Here I discuss restrictive combinations of currently available drugs that could be tested in clinical trials. Could then these combinations cure cancer today? And what does ‘cure’ really mean? This article suggests the answer.     

Stem cell competition: how speeding mutants beat the rest

How mutations lead to tumor formation is a central question in cancer research. Although cellular changes that follow the occurrence of common mutations are well characterized, much less is known about their effects on the population level. Now, two recent studies reveal in what way oncogenic aberrations alter stem cell dynamics to provide cells with an evolutionary advantage over their neighbors (Amoyel et al, 2014 ; Baker et al, 2014 ).     

Complex I dysfunction redirects cellular and mitochondrial metabolism in Arabidopsis

Mitochondrial complex I is a major avenue for reduced NAD oxidation linked to oxidative phosphorylation in plants. However, the plant enzyme has structural and functional features that set it apart from its counterparts in other organisms, raising questions about the physiological significance of this complex in plants. We have developed an experimental model in which rotenone, a classic complex I inhibitor, has been applied to Arabidopsis (Arabidopsis thaliana) cell suspension cultures in order to dissect early metabolic adjustments involved in cell acclimation to mitochondrial dysfunction. Rotenone induced a transitory decrease in cellular respiration (0-4 h after treatment). Cell respiration then progressively recovered and reached a steady state at 10 to 12 h after treatment. Complex I inhibition by rotenone did not induce obvious oxidative stress or cell death but affected longer term cell growth. Integrated analyses of gene expression, the mitochondrial proteome, and changes in primary metabolism indicated that rotenone treatment caused changes in mitochondrial function via alterations in specific components. A physical disengagement of glycolytic activities associated with the mitochondrial outer membrane was observed, and the tricarboxylic acid cycle was altered. Amino acid and organic acid pools were also modified by rotenone treatment, with a marked early decrease of 2-oxoglutarate, aspartate, and glutamine pools. These data demonstrate that, in Arabidopsis cells, complex I inhibition by rotenone induces significant remodeling of metabolic pathways involving the mitochondria and other compartments and point to early metabolic changes in response to mitochondrial dysfunction.     

Effects of catecholamines on hepatic and skeletal muscle mitochondrial respiration after prolonged exposure to faecal peritonitis in pigs

Use of norepinephrine to increase blood pressure in septic animals has been associated with increased efficiency of hepatic mitochondrial respiration. The aim of this study was to evaluate whether the same effect could be reproduced in isolated hepatic mitochondria after prolonged in vivo exposure to faecal peritonitis. Eighteen pigs were randomized to 27?h of faecal peritonitis and to a control condition (n?=?9 each group). At the end, hepatic mitochondria were isolated and incubated for one hour with either norepinephrine or placebo, with and without pretreatment with the specific receptor antagonists prazosin and yohimbine. Mitochondrial state 3 and state 4 respiration were measured for respiratory chain complexes I and II, and state 3 for complex IV using high-resolution respirometry, and respiratory control ratios were calculated. Additionally, skeletal muscle mitochondrial respiration was evaluated after incubation with norepinephrine and dobutamine with and without the respective antagonists (atenolol, propranolol and phentolamine for dobutamine). Faecal peritonitis was characterized by decreasing blood pressure and stroke volume, and maintained systemic oxygen consumption. Neither faecal peritonitis nor any of the drugs or drug combinations had measurable effects on hepatic or skeletal muscle mitochondrial respiration. Norepinephrine did not improve the efficiency of complex I- and complex II-dependent isolated hepatic mitochondrial respiration [respiratory control ratio (RCR) complex I: 5.6?±?5.3 (placebo) vs. 5.4?±?4.6 (norepinephrine) in controls and 2.7?±?2.1 (placebo) vs. 2.9?±?1.5 (norepinephrine) in septic animals; RCR complex II: 3.5?±?2.0 (placebo) vs. 3.5?±?1.8 (norepinephrine) in controls; 2.3?±?1.6 (placebo) vs. 2.2?±?1.1 (norepinephrine) in septic animals]. Prolonged faecal peritonitis did not affect either hepatic or skeletal muscle mitochondrial respiration. Subsequent incubation of isolated mitochondria with norepinephrine and dobutamine did not significantly influence their respiration.     

Immunocytochemical and immuno-electron-microscopical study of growth hormone cells in male and female rats of various ages

Summary Growth hormone (GH) secretory cells were identified by immunogold cytochemistry, and were classified on the basis of the size of secretory granules. Type I cells contained large secretory granules (250\2-350 nm in diameter). Type II cells contained the large secretory granules and small secretory granules (100\2-150 nm in diameter). Type III cells contained the small secretory granules. The percentages of each GH cell type changed with aging in male and female rats of the Wistar/Tw strain. Type I cells predominated throughout development; the proportion of type I cell was highest at 6 months of age, and decreased thereafter. The proportion of type II and type III cells decreased from 1 month to 6 months of age, but then increased at 12 and 18 months of age. The pituitary content of GH was highest at 6 months of age, and decreased thereafter. Estrogen and androgen, which are known to affect GH secretion, caused changes in the proportion of each GH cell type. The results suggest that when GH secretion is more active the proportion of type I GH cell increased, and when GH secretion is less active the proportion of type II and type III cells increased. The type III GH cell may therefore be an immature type of GH cell, and the type I cell the mature type of GH cell. Type II cells may be intermediate between type I and III cells.     

Infinite populations and counterfactual frequencies in evolutionary theory

One finds intertwined with ideas at the core of evolutionary theory claims about frequencies in counterfactual and infinitely large populations of organisms, as well as in sets of populations of organisms. One also finds claims about frequencies in counterfactual and infinitely large populations--of events--at the core of an answer to a question concerning the foundations of evolutionary theory. The question is this: to what do the numerical probabilities found throughout evolutionary theory correspond? The answer in question says that evolutionary probabilities are 'hypothetical frequencies' (including what are sometimes called 'long-run frequencies' and 'long-run propensities'). In this paper, I review two arguments against hypothetical frequencies. The arguments have implications for the interpretation of evolutionary probabilities, but more importantly, they seem to raise problems for biologists' claims about frequencies in counterfactual or infinite populations of organisms and sets of populations of organisms. I argue that when properly understood, claims about frequencies in large and infinite populations of organisms and sets of populations are not threatened by the arguments. Seeing why gives us a clearer understanding of the nature of counterfactual and infinite population claims and probability in evolutionary theory.     

Assessing root death and root system dynamics in a study of grape canopy pruning

Defining root death in studies of root dynamics is problematic because cell death occurs gradually and the resulting effects on root function are not well understood. In this study, metabolic activity of grape roots of different ages was assessed by excised root respiration and tetrazolium chloride reduction. We investigated changes in metabolic activity and patterns of cell death occurring with root age and changes in root pigmentation. Tetrazolium chloride reduction of roots of different ages was strongly correlated to respiration ( R ² = 0.786). As roots aged, respiration and tetrazolium chloride reduction declined similarly, with minimum metabolic activity reached at six weeks. Tetrazolium chloride reduction indicated that the onset of root browning corresponded to a 77% reduction in metabolic activity ( P < 0.001). Anatomical examination of roots at each pigmentation stage showed that even though some cells in brown roots were still alive, these roots were functionally dead. The effect of using different definitions of root death in relation to root survivorship was determined in a study of 'Concord' grapes with two pruning treatments, using three criteria for root death: browning, blackening or shriveling, and disappearance. There was no effect of vine pruning on root life span when life span was defined as the time from first appearance to the onset of browning. However, if death was judged as the point when roots either became black or shriveled or disappeared, vine pruning decreased root life span by 34% and 40%, respectively ( P < 0.001), and also increased the decay constant for root decomposition by about 45% ( P < 0.001). We conclude that the discrepancy among determinations of root life span assessed with different definitions of death might be partly caused by the latter evaluations of root life span incorporating a portion of root decomposition in definitions of root death.