Cancer evolution: Darwin and beyond

Clinical and laboratory studies over recent decades have established branched evolution as a feature of cancer. However, while grounded in somatic selection, several lines of evidence suggest a Darwinian model alone is insufficient to fully explain cancer evolution. First, the role of macroevolutionary events in tumour initiation and progression contradicts Darwin's central thesis of gradualism. Whole-genome doubling, chromosomal chromoplexy and chromothripsis represent examples of single catastrophic events which can drive tumour evolution. Second, neutral evolution can play a role in some tumours, indicating that selection is not always driving evolution. Third, increasing appreciation of the role of the ageing soma has led to recent generalised theories of age-dependent carcinogenesis. Here, we review these concepts and others, which collectively argue for a model of cancer evolution which extends beyond Darwin. We also highlight clinical opportunities which can be grasped through targeting cancer vulnerabilities arising from non-Darwinian patterns of evolution

Retractability of solutions to the Yang-Baxter equation and p-nilpotency of skew braces

Using Bieberbach groups, we study multipermutation involutive solutions to the Yang-Baxter equation. We use a linear representation of the structure group of an involutive solution to study the unique product property in such groups. An algorithm to find subgroups of a Bieberbach group isomorphic to the Promislow subgroup is introduced and then used in the case of structure group of involutive solutions. To extend the results related to retractability to non-involutive solutions, following the ideas of Meng, Ballester-Bolinches and Romero, we develop the theory of right p-nilpotent skew braces. The theory of left p-nilpotent skew braces is also developed and used to give a short proof of a theorem of Smoktunowicz in the context of skew braces.Fil: Acri, Emiliano Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Investigaciones Matemáticas "Luis A. Santaló". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Matemáticas "Luis A. Santaló"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Matemática; ArgentinaFil: Lutowski, R.. University Of Gdańsk; PoloniaFil: Vendramin, Claudio Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Investigaciones Matemáticas "Luis A. Santaló". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Matemáticas "Luis A. Santaló"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Matemática; Argentin

Protein Disulfide Isomerase and Host-Pathogen Interaction

Reactive oxygen species (ROS) production by immunological cells is known to cause damage to pathogens. Increasing evidence accumulated in the last decade has shown, however, that ROS (and redox signals) functionally regulate different cellular pathways in the host-pathogen interaction. These especially affect (i) pathogen entry through protein redox switches and redox modification (i.e., intra- and interdisulfide and cysteine oxidation) and (ii) phagocytic ROS production via Nox family NADPH oxidase enzyme and the control of phagolysosome function with key implications for antigen processing. The protein disulfide isomerase (PDI) family of redox chaperones is closely involved in both processes and is also implicated in protein unfolding and trafficking across the endoplasmic reticulum (ER) and towards the cytosol, a thiol-based redox locus for antigen processing. Here, we summarise examples of the cellular association of host PDI with different pathogens and explore the possible roles of pathogen PDIs in infection. A better understanding of these complex regulatory steps will provide insightful information on the redox role and coevolutional biological process, and assist the development of more specific therapeutic strategies in pathogen-mediated infections

Super-conservative interpretation of muon g-2 results applied to supersymmetry

The recent developments in theory and experiment related to the anomalous magnetic moment of the muon are applied to supersymmetry. We follow a very cautious course, demanding that the supersymmetric contributions fit within five standard deviations of the difference between experiment and the standard model prediction. Arbitrarily small supersymmetric contributions are then allowed, so no upper bounds on superpartner masses result. Nevertheless, non-trivial exclusions are found. We characterize the substantial region of parameter space ruled out by this analysis that has not been probed by any previous experiment. We also discuss some implications of the results for forthcoming collider experiments.Comment: 10 pages, latex, 3 fig

Assessing the genetic diversity of farmed and wild Rufiji tilapia (Oreochromis urolepis urolepis) populations using ddRAD sequencing

Rufiji tilapia (Oreochromis urolepis urolepis) is an endemic cichlid in Tanzania. In addition to its importance for biodiversity conservation, Rufiji tilapia is also attractive for farming due to its high growth rate, salinity tolerance, and the production of all-male hybrids when crossed with Nile tilapia (Oreochromis niloticus). The aim of the current study was to assess the genetic diversity and population structure of both wild and farmed Rufiji tilapia populations in order to inform conservation and aquaculture practices. Double-digest restriction-site-associated DNA (ddRAD) libraries were constructed from 195 animals originating from eight wild (Nyamisati, Utete, Mansi, Mindu, Wami, Ruaha, Kibasira, and Kilola) and two farmed (Bwawani and Chemchem) populations. The identified single nucleotide polymorphisms (SNPs;n = 2,182) were used to investigate the genetic variation within and among the studied populations. Genetic distance estimates (F-st) were low among populations from neighboring locations, with the exception of Utete and Chemchem populations (F-st = 0.34). Isolation-by-distance (IBD) analysis among the wild populations did not detect any significant correlation signal (r = .05;p-value = .4) between the genetic distance and the sampling (Euclidean distance) locations. Population structure and putative ancestry were further investigated using both Bayesian (Structure) and multivariate approaches (discriminant analysis of principal components). Both analysis indicated the existence of three distinct genetic clusters. Two cross-validation scenarios were conducted in order to test the efficiency of the SNP dataset for discriminating between farmed and wild animals or predicting the population of origin. Approximately 95% of the test dataset was correctly classified in the first scenario, while in the case of predicting for the population of origin 68% of the test dataset was correctly classified. Overall, our results provide novel insights regarding the population structure of Rufiji tilapia and a new database of informative SNP markers for both conservation management and aquaculture activities

Very light CP-odd scalar in the Two-Higgs-Doublet Model

We show that a general two-Higgs-doublet model (THDM) with a very light CP-odd scalar (A) can be compatible with the rho parameter, Br(b --> s\gamma), R_b, A_b, (g-2) of muon, Br(Upsilon --> A gamma), and the direct search via the Yukawa process at LEP. For its mass around 0.2 GeV, the muon (g-2) and Br(Upsilon --> A \gamma) data require tan(beta) to be about 1. Consequently, A can behave like a fermiophobic CP-odd scalar and predominantly decay into a photon pair ("gamma gamma"), which registers in detectors of high energy collider experiments as a single photon signature when the momentum of A is large. We compute the partial decay width of Z --> A A A and the production rate of f \bar{f} --> Z A A --> Z +"gamma gamma", f^' {\bar f} --> W^{\pm} A A --> W^\pm + "gamma gamma" and f \bar f --> H^+ H^- --> W^+ W^- A A --> W^+ W^- + "gamma gamma" at high energy colliders such as LEP, Tevatron, LHC, and future Linear Colliders. Other production mechanisms of a light A, such as gg --> h --> AA --> "gamma gamma", are also discussed.Comment: Some improvementes, references updated, 3 new figures, one new appendix, abstract and conclusions unchaged. Version to appear in Physical Review

Nordic Walking promoted weight loss in overweight and obese people: A systematic review for future exercise prescription

The aim of this systematic review was to analyze the effect of Nordic Walking (NW) on anthropometric parameters, body composition, cardiovascular parameters, aerobic capacity, blood sample, and glucose tolerance in overweight and obese subjects. The main keywords "Nordic Walking" or "Pole Walking", associated with either "obese", "obesity", "overweight", or "weight loss" were used on the online database MEDLINE, PubMed, SPORTDiscus and Scopus. Additionally, references of the studies included were screened to identify eligible articles. Applying the inclusion and exclusion criteria, ten manuscripts were considered as eligible for this review. The results of the studies were categorized in several domains with regard to "anthropometric parameters and body composition", "cardiovascular parameters and aerobic capacity", and "blood sample and glucose tolerance". The results showed positive effects on the anthropometric parameters, body composition, cardiovascular parameters, blood sample, and glucose tolerance. The greatest improvements were observed in supervised and high weekly frequency of NW interventions. NW could be considered as an effective modality through which to involve the obese in physical activity. For weight loss, NW should be prescribed 4-5 times per week, at least 60 min per session, preferably combined with diet control

Muon anomalous magnetic dipole moment in supersymmetric theories

We study the muon anomalous magnetic dipole moment in supersymmetric theories. The impact of the recent Brookhaven E821 experimental measurement on both model-independent and model-dependent supersymmetric parameter spaces is discussed in detail. We find that values of tan\beta as low as 3 can be obtained while remaining within the E821 one-sigma bound. This requires a light smuon; however, we show that, somewhat surprisingly, no model-independent bound can be placed on the mass of the lightest chargino for any tan\beta greater than or equal to 3. We also show that the maximum contributions to the anomalous magnetic moment are insensitive to CP-violating phases. We provide analyses of the supersymmetric contribution to the muon anomalous magnetic moment in dilaton-dominated supergravity models and gauge-mediated supersymmetry-breaking models. Finally, we discuss how other phenomena, such as $B(b\to s\gamma)$, relic abundance of the lightest superpartner, and the Higgs mass may be correlated with the anomalous magnetic moment, but do not significantly impact the viability of a supersymmetric explanation, or the mass limits obtainable on smuons and charginos.Comment: 28 page

Two-hadron semi-inclusive production including subleading twist

We extend the analysis of two-hadron fragmentation functions to the subleading twist, discussing also the issue of color gauge invariance. Our results can be used anywhere two unpolarized hadrons are semi-inclusively produced in the same fragmentation region, also at moderate values of the hard scale Q. Here, we consider the example of polarized deep-inelastic production of two hadrons and we give a complete list of cross sections and spin asymmetries up to subleading twist. Among the results, we highlight the possibility of extracting the transversity distribution with longitudinally polarized targets and also the twist-3 distribution e(x), which is related to the pion-nucleon sigma term and to the strangeness content of the nucleon.Comment: 16 pages, RevTeX4, 5 figures, revised notation of several formulae, added text in Secs. III-V, added reference