2,550 research outputs found
Maximum principle and mutation thresholds for four-letter sequence evolution
A four-state mutation-selection model for the evolution of populations of
DNA-sequences is investigated with particular interest in the phenomenon of
error thresholds. The mutation model considered is the Kimura 3ST mutation
scheme, fitness functions, which determine the selection process, come from the
permutation-invariant class. Error thresholds can be found for various fitness
functions, the phase diagrams are more interesting than for equivalent
two-state models. Results for (small) finite sequence lengths are compared with
those for infinite sequence length, obtained via a maximum principle that is
equivalent to the principle of minimal free energy in physics.Comment: 25 pages, 16 figure
Practitionersâ understanding of barriers to accessing specialist support by family carers of people with dementia in distress
Distressing symptoms in dementia are hard to manage for many family carers. This article explores practitioners' perceptions of the barriers to accessing skilled behaviour management support encountered by carers. A survey of cases referred to the English National Health Service (n = 5,360) was followed by in-depth group discussions and practitioner interviews. Data revealed that practitioners focused on care home residents or older people with mental health problems other than dementia, rather than community-dwelling people with dementia and families. Barriers to access included misperceptions about the nature of distressing behaviour affecting carers and structural limitations in the capacity of specialist services to respond to carers
Kinetic theory of age-structured stochastic birth-death processes
Classical age-structured mass-action models such as the McKendrick-von Foerster equation have been extensively studied but are unable to describe stochastic fluctuations or population-size-dependent birth and death rates. Stochastic theories that treat semi-Markov age-dependent processes using, e.g., the Bellman-Harris equation do not resolve a population's age structure and are unable to quantify population-size dependencies. Conversely, current theories that include size-dependent population dynamics (e.g., mathematical models that include carrying capacity such as the logistic equation) cannot be easily extended to take into account age-dependent birth and death rates. In this paper, we present a systematic derivation of a new, fully stochastic kinetic theory for interacting age-structured populations. By defining multiparticle probability density functions, we derive a hierarchy of kinetic equations for the stochastic evolution of an aging population undergoing birth and death. We show that the fully stochastic age-dependent birth-death process precludes factorization of the corresponding probability densities, which then must be solved by using a Bogoliubov-âBornâ-Greenâ-Kirkwood-âYvon-like hierarchy. Explicit solutions are derived in three limits: no birth, no death, and steady state. These are then compared with their corresponding mean-field results. Our results generalize both deterministic models and existing master equation approaches by providing an intuitive and efficient way to simultaneously model age- and population-dependent stochastic dynamics applicable to the study of demography, stem cell dynamics, and disease evolution
The status of supergenes in the 21st century: Recombination suppression in Batesian 1 mimicry and sex chromosomes and other complex adaptations
I review theoretical models for the evolution of supergenes in the cases of Batesian mimicry in butterflies, distylous plants and sex chromosomes. For each of these systems, I outline the genetic evidence that led to the proposal that they involve multiple genes that interact during âcomplex adaptationsâ, and at which the mutations involved are not unconditionally advantageous, but show advantages that tradeâoff against some disadvantages. I describe recent molecular genetic studies of these systems and questions they raise about the evolution of suppressed recombination. Nonrecombining regions of sex chromosomes have long been known, but it is not yet fully understood why recombination suppression repeatedly evolved in systems in distantly related taxa, but does not always evolve. Recent studies of distylous plants are tending to support the existence of recombinationâsuppressed genome regions, which may include modest numbers of genes and resemble recently evolved sexâlinked regions. For Batesian mimicry, however, molecular genetic work in two butterfly species suggests a new supergene scenario, with a single gene mutating to produce initial adaptive phenotypes, perhaps followed by modifiers specifically refining and perfecting the new phenotype
Recombination dramatically speeds up evolution of finite populations
We study the role of recombination, as practiced by genetically-competent
bacteria, in speeding up Darwinian evolution. This is done by adding a new
process to a previously-studied Markov model of evolution on a smooth fitness
landscape; this new process allows alleles to be exchanged with those in the
surrounding medium. Our results, both numerical and analytic, indicate that for
a wide range of intermediate population sizes, recombination dramatically
speeds up the evolutionary advance
The purification and characterization of ATP synthase complexes from the mitochondria of four fungal species.
The ATP synthases have been isolated by affinity chromatography from the mitochondria of the fungal species Yarrowia lipolytica, Pichia pastoris, Pichia angusta and Saccharomyces cerevisiae. The subunit compositions of the purified enzyme complexes depended on the detergent used to solubilize and purify the complex, and the presence or absence of exogenous phospholipids. All four enzymes purified in the presence of n-dodecyl-ÎČ-D-maltoside had a complete complement of core subunits involved directly in the synthesis of ATP, but they were deficient to different extents in their supernumerary membrane subunits. In contrast, the enzymes from P. angusta and S. cerevisiae purified in the presence of n-decyl-ÎČ-maltose neopentyl glycol and the phospholipids 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine, cardiolipin (diphosphatidylglycerol) and 1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] had a complete complement of core subunits and also contained all of the known supernumerary membrane subunits, e, f, g, j, k and ATP8 (or Aap1), plus an additional new membrane component named subunit l, related in sequence to subunit k. The catalytic domain of the enzyme from P. angusta was more resistant to thermal denaturation than the enzyme from S. cerevisiae, but less stable than the catalytic domain of the bovine enzyme, but the stator and the integrity of the transmembrane proton pathway were most stable in the enzyme from P. angusta. The P. angusta enzyme provides a suitable source of enzyme for studying the structure of the membrane domain and properties associated with that sector of the enzyme complex.This work was funded by the intramural programme of the Medical Research Council (MRC). T.J.C was the recipient of an MRC graduate studentship
Strong polarization-induced reduction of addition energies in single-molecule nanojunctions
We address polarization-induced renormalization of molecular levels in
solid-state based single-molecule transistors and focus on an organic conjugate
molecule where a surprisingly large reduction of the addition energy has been
observed. We have developed a scheme that combines a self-consistent solution
of a quantum chemical calculation with a realistic description of the screening
environment. Our results indeed show a large reduction, and we explain this to
be a consequence of both (a) a reduction of the electrostatic molecular
charging energy and (b) polarization induced level shifts of the HOMO and LUMO
levels. Finally, we calculate the charge stability diagram and explain at a
qualitative level general features observed experimentally.Comment: 9 pages, 5 figure
Blood ties: ABO is a trans-species polymorphism in primates
The ABO histo-blood group, the critical determinant of transfusion
incompatibility, was the first genetic polymorphism discovered in humans.
Remarkably, ABO antigens are also polymorphic in many other primates, with the
same two amino acid changes responsible for A and B specificity in all species
sequenced to date. Whether this recurrence of A and B antigens is the result of
an ancient polymorphism maintained across species or due to numerous, more
recent instances of convergent evolution has been debated for decades, with a
current consensus in support of convergent evolution. We show instead that
genetic variation data in humans and gibbons as well as in Old World Monkeys
are inconsistent with a model of convergent evolution and support the
hypothesis of an ancient, multi-allelic polymorphism of which some alleles are
shared by descent among species. These results demonstrate that the ABO
polymorphism is a trans-species polymorphism among distantly related species
and has remained under balancing selection for tens of millions of years, to
date, the only such example in Hominoids and Old World Monkeys outside of the
Major Histocompatibility Complex.Comment: 45 pages, 4 Figures, 4 Supplementary Figures, 5 Supplementary Table
An Evolutionary Reduction Principle for Mutation Rates at Multiple Loci
A model of mutation rate evolution for multiple loci under arbitrary
selection is analyzed. Results are obtained using techniques from Karlin (1982)
that overcome the weak selection constraints needed for tractability in prior
studies of multilocus event models. A multivariate form of the reduction
principle is found: reduction results at individual loci combine topologically
to produce a surface of mutation rate alterations that are neutral for a new
modifier allele. New mutation rates survive if and only if they fall below this
surface - a generalization of the hyperplane found by Zhivotovsky et al. (1994)
for a multilocus recombination modifier. Increases in mutation rates at some
loci may evolve if compensated for by decreases at other loci. The strength of
selection on the modifier scales in proportion to the number of germline cell
divisions, and increases with the number of loci affected. Loci that do not
make a difference to marginal fitnesses at equilibrium are not subject to the
reduction principle, and under fine tuning of mutation rates would be expected
to have higher mutation rates than loci in mutation-selection balance. Other
results include the nonexistence of 'viability analogous, Hardy-Weinberg'
modifier polymorphisms under multiplicative mutation, and the sufficiency of
average transmission rates to encapsulate the effect of modifier polymorphisms
on the transmission of loci under selection. A conjecture is offered regarding
situations, like recombination in the presence of mutation, that exhibit
departures from the reduction principle. Constraints for tractability are:
tight linkage of all loci, initial fixation at the modifier locus, and mutation
distributions comprising transition probabilities of reversible Markov chains.Comment: v3: Final corrections. v2: Revised title, reworked and expanded
introductory and discussion sections, added corollaries, new results on
modifier polymorphisms, minor corrections. 49 pages, 64 reference
Who am I? Autobiographical retrieval improves access to self-concepts
It is considered that an individual's current self-concept plays a crucial role in guiding the retrieval of autobiographical memory. Using a novel fluency paradigm, the present research examined whether or not the reverse is also true, that is, does memory retrieval influence the description of the conceptual self? Specifically, this study examined the effect of prior autobiographical reverie on the subsequent retrieval of stored self-concepts. Participants wrote a description of a personally relevant memory or a control topic (of no relevance to the self), following which they had 60 seconds to generate as many self-defining statements as possible, each beginning with I am. Participants engaging in autobiographical retrieval generated significantly more statements than those in the control condition, suggesting that autobiographical retrieval increased access to self-concepts. Type of statement also varied according to group. Participants in the autobiographical memory condition were more likely to conceptualise themselves in relation to their psychological traits, and this was replicated in a second experiment conducted online. Findings support the idea that self and episodic memory are highly related constructs, and are discussed in relation to implications for individuals with autobiographical memory deficits
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