Uniparental mitochondrial DNA inheritance is not affected in Ustilago maydis Δatg11 mutants blocked in mitophagy

Background: Maternal or uniparental inheritance (UPI) of mitochondria is generally observed in sexual eukaryotes, however, the underlying mechanisms are diverse and largely unknown. Recently, based on the use of mutants blocked in autophagy, it has been demonstrated that autophagy is required for strict maternal inheritance in the nematode Caenorhabditis elegans. Uniparental mitochondrial DNA (mtDNA) inheritance has been well documented for numerous fungal species, and in particular, has been shown to be genetically governed by the mating-type loci in the isogamous species Cryptococcus neoformans, Phycomyces blakesleeanus and Ustilago maydis. Previously, we have shown that the a2 mating-type locus gene lga2 is decisive for UPI during sexual development of U. maydis. In axenic culture, conditional overexpression of lga2 triggers efficient loss of mtDNA as well as mitophagy. To assess a functional relationship, we have investigated UPI in U. maydis Δatg11 mutants, which are blocked in mitophagy. Results: This study has revealed that Äatg11 mutants are not affected in pathogenic development and this has allowed us to analyse UPI under comparable developmental conditions between mating-compatible wild-type and mutant strain combinations. Explicitly, we have examined two independent strain combinations that gave rise to different efficiencies of UPI. We demonstrate that in both cases UPI is atg11-independent, providing evidence that mitophagy is not critical for UPI in U. maydis, even under conditions of strict UPI. Conclusions: Until now, analysis of a role of mitophagy in UPI has not been reported for microbial species. Our study suggests that selective autophagy does not contribute to UPI in U. maydis, but is rather a consequence of selective mtDNA elimination in response to mitochondrial damage. © 2015 Wagner-Vogel et al.; licensee BioMed Central

Spherical collapse of dark energy with an arbitrary sound speed

We consider a generic type of dark energy fluid, characterised by a constant equation of state parameter w and sound speed c_s, and investigate the impact of dark energy clustering on cosmic structure formation using the spherical collapse model. Along the way, we also discuss in detail the evolution of dark energy perturbations in the linear regime. We find that the introduction of a finite sound speed into the picture necessarily induces a scale-dependence in the dark energy clustering, which in turn affects the dynamics of the spherical collapse in a scale-dependent way. As with other, more conventional fluids, we can define a Jeans scale for the dark energy clustering, and hence a Jeans mass M_J for the dark matter which feels the effect of dark energy clustering via gravitational interactions. For bound objects (halos) with masses M >> M_J, the effect of dark energy clustering is maximal. For those with M << M_J, the dark energy component is effectively homogeneous, and its role in the formation of these structures is reduced to its effects on the Hubble expansion rate. To compute quantitatively the virial density and the linearly extrapolated threshold density, we use a quasi-linear approach which is expected to be valid up to around the Jeans mass. We find an interesting dependence of these quantities on the halo mass M, given some w and c_s. The dependence is the strongest for masses lying in the vicinity of M ~ M_J. Observing this M-dependence will be a tell-tale sign that dark energy is dynamic, and a great leap towards pinning down its clustering properties.Comment: 25 pages, 6 figures, matches version published in JCA

Understanding the core density profile in TCV H-mode plasmas

Results from a database analysis of H-mode electron density profiles on the Tokamak \`a Configuration Variable (TCV) in stationary conditions show that the logarithmic electron density gradient increases with collisionality. By contrast, usual observations of H-modes showed that the electron density profiles tend to flatten with increasing collisionality. In this work it is reinforced that the role of collisionality alone, depending on the parameter regime, can be rather weak and in these, dominantly electron heated TCV cases, the electron density gradient is tailored by the underlying turbulence regime, which is mostly determined by the ratio of the electron to ion temperature and that of their gradients. Additionally, mostly in ohmic plasmas, the Ware-pinch can significantly contribute to the density peaking. Qualitative agreement between the predicted density peaking by quasi-linear gyrokinetic simulations and the experimental results is found. Quantitative comparison would necessitate ion temperature measurements, which are lacking in the considered experimental dataset. However, the simulation results show that it is the combination of several effects that influences the density peaking in TCV H-mode plasmas.Comment: 23 pages, 12 figure

Modelling radiation-induced cell cycle delays

Ionizing radiation is known to delay the cell cycle progression. In particular after particle exposure significant delays have been observed and it has been shown that the extent of delay affects the expression of damage such as chromosome aberrations. Thus, to predict how cells respond to ionizing radiation and to derive reliable estimates of radiation risks, information about radiation-induced cell cycle perturbations is required. In the present study we describe and apply a method for retrieval of information about the time-course of all cell cycle phases from experimental data on the mitotic index only. We study the progression of mammalian cells through the cell cycle after exposure. The analysis reveals a prolonged block of damaged cells in the G2 phase. Furthermore, by performing an error analysis on simulated data valuable information for the design of experimental studies has been obtained. The analysis showed that the number of cells analyzed in an experimental sample should be at least 100 to obtain a relative error less than 20%.Comment: 19 pages, 11 figures, accepted for publication in Radiation and Environmental Biophysic

Stable lepton mass matrices

Abstract: We study natural lepton mass matrices, obtained assuming the stability of physical flavour observables with respect to the variations of individual matrix elements. We identify all four possible stable neutrino textures from algebraic conditions on their entries. Two of them turn out to be uniquely associated to specific neutrino mass patterns. We then concentrate on the semi-degenerate pattern, corresponding to an overall neutrino mass scale within the reach of future experiments. In this context we show that i) the neutrino and charged lepton mixings and mass matrices are largely constrained by the requirement of stability, ii) naturalness considerations give a mild preference for the Majorana phase most relevant for neutrinoless double-\u3b2 decay, \u3b1 3c \u3c0/2, and iii) SU(5) unification allows to extend the implications of stability to the down quark sector. The above considerations would benefit from an experimental determination of the PMNS ratio 1aU32/U31 1a, i.e. of the Dirac phase \u3b4. \ua9 2016, The Author(s)

Identification and characterization of secreted and pathogenesis-related proteins in Ustilago maydis

Interactions between plants and fungal pathogens require a complex interplay at the plant–fungus interface. Extracellular effector proteins are thought to play a crucial role in establishing a successful infection. To identify pathogenesis-related proteins in Ustilago maydis we combined the isolation of secreted proteins using a signal sequence trap approach with bioinformatic analyses and the subsequent characterization of knock-out mutants. We identified 29 secreted proteins including hydrophobins and proteins with a repetitive structure similar to the repellent protein Rep1. Hum3, a protein containing both, a hydrophobin domain and a repetitive Rep1-like region, is shown to be processed during passage through the secretory pathway. While single knock-outs of hydrophobin or repellent-like genes did not affect pathogenicity, we found a strong effect of a double knock-out of hum3 and the repetitive rsp1. Yeast-like growth, mating, aerial hyphae formation and surface hydrophobicity were unaffected in this double mutant. However, pathogenic development in planta stops early after penetration leading to a complete loss of pathogenicity. This indicates that Hum3 and Rsp1 are pathogenicity proteins that share an essential function in early stages of the infection. Our results demonstrate that focusing on secreted proteins is a promising way to discover novel pathogenicity proteins that might be broadly applied to a variety of fungal pathogens

Perioperative strategy in colonic surgery; LAparoscopy and/or FAst track multimodal management versus standard care (LAFA trial)

BACKGROUND: Recent developments in large bowel surgery are the introduction of laparoscopic surgery and the implementation of multimodal fast track recovery programs. Both focus on a faster recovery and shorter hospital stay. The randomized controlled multicenter LAFA-trial (LAparoscopy and/or FAst track multimodal management versus standard care) was conceived to determine whether laparoscopic surgery, fast track perioperative care or a combination of both is to be preferred over open surgery with standard care in patients having segmental colectomy for malignant disease. METHODS/DESIGN: The LAFA-trial is a double blinded, multicenter trial with a 2 × 2 balanced factorial design. Patients eligible for segmental colectomy for malignant colorectal disease i.e. right and left colectomy and anterior resection will be randomized to either open or laparoscopic colectomy, and to either standard care or the fast track program. This factorial design produces four treatment groups; open colectomy with standard care (a), open colectomy with fast track program (b), laparoscopic colectomy with standard care (c), and laparoscopic surgery with fast track program (d). Primary outcome parameter is postoperative hospital length of stay including readmission within 30 days. Secondary outcome parameters are quality of life two and four weeks after surgery, overall hospital costs, morbidity, patient satisfaction and readmission rate. Based on a mean postoperative hospital stay of 9 +/- 2.5 days a group size of 400 patients (100 each arm) can reliably detect a minimum difference of 1 day between the four arms (alfa = 0.95, beta = 0.8). With 100 patients in each arm a difference of 10% in subscales of the Short Form 36 (SF-36) questionnaire and social functioning can be detected. DISCUSSION: The LAFA-trial is a randomized controlled multicenter trial that will provide evidence on the merits of fast track perioperative care and laparoscopic colorectal surgery in patients having segmental colectomy for malignant disease

Structured models of cell migration incorporating molecular binding processes

The dynamic interplay between collective cell movement and the various molecules involved in the accompanying cell signalling mechanisms plays a crucial role in many biological processes including normal tissue development and pathological scenarios such as wound healing and cancer. Information about the various structures embedded within these processes allows a detailed exploration of the binding of molecular species to cell-surface receptors within the evolving cell population. In this paper we establish a general spatio-temporal-structural framework that enables the description of molecular binding to cell membranes coupled with the cell population dynamics. We first provide a general theoretical description for this approach and then illustrate it with two examples arising from cancer invasion