An Unusual Antagonistic Pleiotropy in the Penna Model for Biological Ageing

We combine the Penna Model for biological aging, which is based on the mutation-accumulation theory, with a sort of antagonistic pleiotropy. We show that depending on how the pleiotropy is introduced, it is possible to reproduce both the humans mortality, which increases exponentially with age, and fruitfly mortality, which decelerates at old ages, allowing the appearance of arbitrarily old Methuselah's.Comment: 8 pages, 3 figures, to appear in Physica

Effect of preoperative thoracic duct drainage on canine kidney transplantation

Chronic drainage of the thoracic duct to the esophagus was developed in dogs, and its efficacy in immunomodulation was tested using kidney transplantation. Compared to 9.7 days in the control, the mean animal survival was prolonged to 9.9 days, 17.8 days, and 18.5 days when TDD was applied preoperatively for 3 weeks, 6 weeks, and 9 weeks, respectively. Prolongation was significant after 6 weeks. Patency of the fistula was 93.5, 80.4, and 76.1% at respective weeks. Number of peripheral T-lymphocytes determined by a new monoclonal antibody diminished after 3 weeks. All animals were in normal health, requiring no special care for fluid, electrolyte, or protein replacement

Why Y chromosome is shorter and women live longer?

We have used the Penna ageing model to analyze how the differences in evolution of sex chromosomes depend on the strategy of reproduction. In panmictic populations, when females (XX) can freely choose the male partner (XY) for reproduction from the whole population, the Y chromosome accumulates defects and eventually the only information it brings is a male sex determination. As a result of shrinking Y chromosome the males become hemizygous in respect to the X chromosome content and are characterized by higher mortality, observed also in the human populations. If it is assumed in the model that the presence of the male is indispensable at least during the pregnancy of his female partner and he cannot be seduced by another female at least during the one reproduction cycle - the Y chromosome preserves its content, does not shrink and the lifespan of females and males is the same. Thus, Y chromosome shrinks not because of existing in one copy, without the possibility of recombination, but because it stays under weaker selection pressure; in panmictic populations without the necessity of being faithful, a considerable fraction of males is dispensable and they can be eliminated from the population without reducing its reproduction potential.Comment: 8 pages, 5 figure

A pace and shape perspective on fertility

Ageing is ubiquitous to all organisms, but ageing does not always mean senescence. Counter to most evolutionary theories of ageing, the patterns of mortality and reproduction may remain unchanged or improve with age, as well as deteriorate. Describing this diversity presents a challenge to eco‐evolutionary demography. The pace–shape framework of mortality tackled this challenge to qualify and quantify orthogonal components of ageing patterns in mortality. Here, we extend this framework to fertility. Analogous to the logic of the mortality framework, we define a perspective, a framework and novel methods for the pace and shape of fertility. These distinguish between orthogonal components of time‐scale (pace) and distribution (shape) of reproduction over adult life span. Our pace and shape framework mirrors that of mortality, through a shift of perspective from the mother giving birth, to the offspring being born. Our new measures overcome many problems associated with measuring natural fertility trajectories, have both a clear biological and mathematical interpretation, can be intuitively visualized and satisfy and extend important conditions of the pace–shape paradigm. A comprehensive framework of fertility pace–shape facilitates ecological and evolutionary research addressing interactions and trade‐offs between components of birth and death patterns, across the whole tree of life. The burgeoning emergence of large comparative demographic data sources across wide environmental, geographical, temporal and phylogenetic ranges, combined with pace–shape measures, opens the door to comparative analyses of ageing which were never possible before

Microguards and micromessengers of the genome

The regulation of gene expression is of fundamental importance to maintain organismal function and integrity and requires a multifaceted and highly ordered sequence of events. The cyclic nature of gene expression is known as ‘transcription dynamics’. Disruption or perturbation of these dynamics can result in significant fitness costs arising from genome instability, accelerated ageing and disease. We review recent research that supports the idea that an important new role for small RNAs, particularly microRNAs (miRNAs), is in protecting the genome against short-term transcriptional fluctuations, in a process we term ‘microguarding’. An additional emerging role for miRNAs is as ‘micromessengers’—through alteration of gene expression in target cells to which they are trafficked within microvesicles. We describe the scant but emerging evidence that miRNAs can be moved between different cells, individuals and even species, to exert biologically significant responses. With these two new roles, miRNAs have the potential to protect against deleterious gene expression variation from perturbation and to themselves perturb the expression of genes in target cells. These interactions between cells will frequently be subject to conflicts of interest when they occur between unrelated cells that lack a coincidence of fitness interests. Hence, there is the potential for miRNAs to represent both a means to resolve conflicts of interest, as well as instigate them. We conclude by exploring this conflict hypothesis, by describing some of the initial evidence consistent with it and proposing new ideas for future research into this exciting topic

Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro. In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research

Human factors and missed solutions to Enigma design weaknesses

The German World War II Enigma suffered from design weaknesses that facilitated its large-scale decryption by the British throughout the war. The author shows that the main technical weaknesses (self-coding and reciprocal coding) could have been avoided using simple contemporary technology, and therefore the true cause of the weaknesses is not technological but must be sought elsewhere. Specifically, human factors issues resulted in the persistent failure to seek out more effective designs. Similar limitations seem to beset the literature on the period, which misunderstands the Enigma weaknesses and therefore inhibits broader thinking about design or realising the critical role of human factors engineering in cryptography

Reinventing grounded theory: some questions about theory, ground and discovery

Grounded theory’s popularity persists after three decades of broad-ranging critique. In this article three problematic notions are discussed—‘theory,’ ‘ground’ and ‘discovery’—which linger in the continuing use and development of grounded theory procedures. It is argued that far from providing the epistemic security promised by grounded theory, these notions—embodied in continuing reinventions of grounded theory—constrain and distort qualitative inquiry, and that what is contrived is not in fact theory in any meaningful sense, that ‘ground’ is a misnomer when talking about interpretation and that what ultimately materializes following grounded theory procedures is less like discovery and more akin to invention. The procedures admittedly provide signposts for qualitative inquirers, but educational researchers should be wary, for the significance of interpretation, narrative and reflection can be undermined in the procedures of grounded theory

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Vital Rates from the Action of Mutation Accumulation

New models for evolutionary processes of mutation accumulation allow hypotheses about the age-specificity of mutational effects to be translated into predictions of heterogeneous population hazard functions. We apply these models to questions in the biodemography of longevity, including proposed explanations of Gompertz hazards and mortality plateaus