Foxm1 modulates cell non-autonomous response in zebrafish skeletal muscle homeostasis

Foxm1 is a master regulator of the cell cycle, contributing to cell proliferation. Recent data have shown that this transcription factor also modulates gene networks associated with other cellular mechanisms, suggesting non-proliferative functions that remain largely unexplored. In this study, we used CRISPR/Cas9 to disrupt foxm1 in the zebrafish terminally differentiated fast-twitching muscle cells. foxm1 genomic disruption increased myofiber death and clearance. Interestingly, this contributed to non-autonomous satellite cell activation and proliferation. Moreover, we observed that Cas9 expression alone was strongly deleterious to muscle cells. Our report shows that foxm1 modulates a muscle non-autonomous response to myofiber death and highlights underreported toxicity to high expression of Cas9 in vivo.This study was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (ERC-2015-StG-680156-ZPR). FEDER (Fundo Europeu de Desenvolvimento Regional) funds through the COMPETE 2020—Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020 and by Portuguese funds through FCT (Fundação para a Ciência e a Tecnologia) in the framework of the project POCI-01-0145-FEDER-031120 (PTDC/BIA-CEL/31120/2017); and POCI-01-0145-FEDER-007274 i3S framework project co-funded by COMPETE 2020/PORTUGAL 2020 through FEDER. E.L. and J.B. are supported by FCT (J.B.: Grant CEECIND/03482/2018; E.L.: Grants CEECIND/00654/2020 and IF/00916/2014). F.J.F. (PD/BD/105745/2014) is a PhD fellow from FCT

Phase conversion in a weakly first-order quark-hadron transition

We investigate the process of phase conversion in a thermally-driven {\it weakly} first-order quark-hadron transition. This scenario is physically appealing even if the nature of this transition in equilibrium proves to be a smooth crossover for vanishing baryonic chemical potential. We construct an effective potential by combining the equation of state obtained within Lattice QCD for the partonic sector with that of a gas of resonances in the hadronic phase, and present numerical results on bubble profiles, nucleation rates and time evolution, including the effects from reheating on the dynamics for different expansion scenarios. Our findings confirm the standard picture of a cosmological first-order transition, in which the process of phase conversion is entirely dominated by nucleation, also in the case of a weakly first-order transition. On the other hand, we show that, even for expansion rates much lower than those expected in high-energy heavy ion collisions, nucleation is very unlikely, indicating that the main mechanism of phase conversion is spinodal decomposition. Our results are compared to those obtained for a strongly first-order transition, as the one provided by the MIT bag model.Comment: 12 pages, 10 figures; v2: 1 reference added, minor modifications, matches published versio

Pressure of massless hot scalar theory in the boundary effective theory framework

We use the boundary effective theory (BET) approach to thermal field theory in order to calculate the pressure of a system of massless scalar fields with quartic interaction. The method naturally separates the infrared physics, and is essentially non-perturbative. To lowest order, the main ingredient is the solution of the free Euler-Lagrange equation with non-trivial (time) boundary conditions. We derive a resummed pressure, which is in good agreement with recent calculations found in the literature, following a very direct and compact procedure.Comment: 10 pages, 4 figure

Effective potential in the BET formalism

We calculate the one-loop effective potential at finite temperature for a system of massless scalar fields with quartic interaction $\lambda\phi^4$ in the framework of the boundary effective theory (BET) formalism. The calculation relies on the solution of the classical equation of motion for the field, and Gaussian fluctuations around it. Our result is non-perturbative and differs from the standard one-loop effective potential for field values larger than $T/\sqrt{\lambda}$.Comment: 10 pages, 3 figure

Primate occurrence across a human-impacted landscape in Guinea-Bissau and neighbouring regions in West Africa: using a systematic literature review to highlight the next conservation steps

This is the final version of the article. Available from PeerJ via the DOI in this record.Background West African landscapes are largely characterised by complex agroforest mosaics. Although the West African forests are considered a nonhuman primate hotspot, knowledge on the distribution of many species is often lacking and out-of-date. Considering the fast-changing nature of the landscapes in this region, up-to-date information on primate occurrence is urgently needed, particularly of taxa such as colobines, which may be more sensitive to habitat modification than others. Understanding wildlife occurrence and mechanisms of persistence in these human-dominated landscapes is fundamental for developing effective conservation strategies. Methods In this paper, we aim to review current knowledge on the distribution of three threatened primates in Guinea-Bissau and neighbouring regions, highlighting research gaps and identifying priority research and conservation action. We conducted a systematic literature review of primate studies from 1976 to 2016 in Guinea-Bissau, southern Senegal and western Guinea (Boké Region). We mapped historical observation records of chimpanzee (Pan troglodytes verus), Temminck’s red colobus (Pilicolobus badius temminckii) and king colobus (Colobus polykomos), including our preliminary survey data from Dulombi, a newly established National Park (NP) in Guinea-Bissau. Results We found 151 documents, including 87 journal articles, that contained field data on primates in this region. In Guinea-Bissau, nearly all studies focussed south of the Corubal River, including mainly Cantanhez, Cufada, and Boé NP’s. In Senegal, most of the data came from Fongoli and Niokolo-Koba NP. In Boké (Guinea) studies are few, with the most recent data coming from Sangarédi. In Dulombi NP we recorded eight primate species, including chimpanzees, red colobus and king colobus. Across the selected region, chimpanzees, red colobus and king colobus were reported in eleven, twelve and seven protected areas, respectively. Discussion Our study demonstrates large geographical research gaps particularly for the two colobines. For the first time after more than two decades, we confirm the presence of red colobus and king colobus north of the Corubal River in Guinea-Bissau. The little information available from large parts of the red colobus range raises questions regarding levels of population fragmentation in this species, particularly in Casamance and across northern Guinea-Bissau. There are still no records demonstrating the occurrence of king colobus in Senegal, and the presence of a viable population in north-eastern Guinea-Bissau remains uncertain. While the occurrence of chimpanzees in Guinea-Bissau and Senegal is well documented, data from Boké (Guinea) are sparse and out-of-date. Our approach—the mapping of data gathered from a systematic literature review—allows us to provide recommendations for selecting future geographical survey locations and planning further research and conservation strategies in this region.This study was conducted under the FCT (Fundação para a Ciência e a Tecnologia, Portugal) funded project EXPL/IVC-ANT/0997/2013

A differential method for bounding the ground state energy

For a wide class of Hamiltonians, a novel method to obtain lower and upper bounds for the lowest energy is presented. Unlike perturbative or variational techniques, this method does not involve the computation of any integral (a normalisation factor or a matrix element). It just requires the determination of the absolute minimum and maximum in the whole configuration space of the local energy associated with a normalisable trial function (the calculation of the norm is not needed). After a general introduction, the method is applied to three non-integrable systems: the asymmetric annular billiard, the many-body spinless Coulombian problem, the hydrogen atom in a constant and uniform magnetic field. Being more sensitive than the variational methods to any local perturbation of the trial function, this method can used to systematically improve the energy bounds with a local skilled analysis; an algorithm relying on this method can therefore be constructed and an explicit example for a one-dimensional problem is given.Comment: Accepted for publication in Journal of Physics

Structural analysis of Ti1−xSixNy nanocomposite films prepared by reactive magnetron sputtering

Nanocomposite thin films consisting of both nanosized solid solutions or nanosized polycrystalline materials embedded in various amorphous matrix materials thus provide a grate potential for future mechanical devices. In this paper we report on the preparation of films resulting from additions of Si to TiN matrix by r.f. reactive magnetron sputtering. Structural properties such as growing characteristics (type of matrix, texture and grain size) will be analysed in some detail. Conventional transmission electron microscopy (TEM) and High-resolution transmission electron microscopy (HRTEM), together with both symmetric and asymmetric mode X-ray diffraction (XRD) experiments were used for this characterisation. The atomic composition of the samples was obtained by Rutherford Backscattering Spectrometry (RBS). The analysis will be carried out as a function of the Si content in the Ti1-xSixNy matrix and several relations will be made regarding important parameters such as texture evolution, grain sizes, but most specially by the type of matrix developed. Regarding the results, all samples develop a double fcc phase with lattice parameters of 4.30 Å and 4.17 Å, corresponding to cubic TiN and most likely to a cubic lattice of SiNx, respectively. Although no significant changes in texture were observed till Si compositions up to 10.6 at. %, the arrangement in atoms planes seem to vary. Results show that an asymmetric arrangement is developed in samples of small Si additions. This arrangement becomes more isotropic with the increase of Si contents, which we attribute to the increase in the SiNx content. In fact this increase leads also to the development of a small amorphous tissue of Si3N4 for large Si additions.The authors gratefully acknowledge the financial support of the ‘Fundação para a Ciência e Tecnologia’ (FCT) during the course of this research under project n PBICT/P/CTM/1962/95 and also the French CNRS Institution and the Portugese ICCTI Institution through CNRS/ICCTI Programs (N: 5522-1998 and 7087-1999)

FOXM1 repression increases mitotic death upon antimitotic chemotherapy through BMF upregulation

Inhibition of spindle microtubule (MT) dynamics has been effectively used in cancer treatment. Although the mechanisms by which MT poisons elicit mitotic arrest are fairly understood, efforts are still needed towards elucidating how cancer cells respond to antimitotic drugs owing to cytotoxicity and resistance side effects. Here, we identified the critical G2/M transcription factor Forkhead box M1 (FOXM1) as a molecular determinant of cell response to antimitotics. We found FOXM1 repression to increase death in mitosis (DiM) due to upregulation of the BCL-2 modifying factor (BMF) gene involved in anoikis, an apoptotic process induced upon cell detachment from the extracellular matrix. FOXM1 binds to a BMF intronic cis-regulatory element that interacts with both the BMF and the neighbor gene BUB1B promoter regions, to oppositely regulate their expression. This mechanism ensures that cells treated with antimitotics repress BMF and avoid DiM when FOXM1 levels are high. In addition, we show that this mechanism is partly disrupted in anoikis/antimitotics-resistant tumor cells, with resistance correlating with lower BMF expression but in a FOXM1-independent manner. These findings provide a stratification biomarker for antimitotic chemotherapy response.This work was supported by: FEDER (Fundo Europeu de Desenvolvimento Regional) funds through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020 and by Portuguese funds through FCT (Fundação para a Ciência e a Tecnologia) in the framework of the project POCI-01-0145-FEDER-031120 (PTDC/BIA-CEL/31120/ 2017); and POCI-01-0145-FEDER-007274 i3S framework project co-funded by COMPETE 2020/ PORTUGAL 2020 through FEDER. S.V. and F.F. were supported by FCT fellowships SFRH/BD/125017/2016 and PD/BD/105745/2014. E.L. was supported by an FCT Investigator Grant (IF/00916/2014). U.B-D. and G.L. were supported by the Azrieli Faculty Fellowship (to U.D.-D.) and the DoD CDMRP Career Development Award (CA191138 to U.B.-D.). J.B. was supported by an FCT Investigator Grant (CEECIND/03482/2018) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC-2015-StG-680156-ZPR)