Age structure landscapes emerge from the equilibrium between aging and rejuvenation in bacterial populations.

The physiological asymmetry between daughters of a mother bacterium is produced by the inheritance of either old poles, carrying non-genetic damage, or newly synthesized poles. However, as bacteria display long-term growth stability leading to physiological immortality, there is controversy on whether asymmetry corresponds to aging. Here we show that deterministic age structure landscapes emerge from physiologically immortal bacterial lineages. Through single-cell microscopy and microfluidic techniques, we demonstrate that aging and rejuvenating bacterial lineages reach two distinct states of growth equilibria. These equilibria display stabilizing properties, which we quantified according to the compensatory trajectories of continuous lineages throughout generations. Finally, we show that the physiological asymmetry between aging and rejuvenating lineages produces complex age structure landscapes, resulting in a deterministic phenotypic heterogeneity that is neither an artifact of starvation nor a product of extrinsic damage. These findings indicate that physiological immortality and cellular aging can both be manifested in single celled organisms

The HSV-1 Latency-Associated Transcript Functions to Repress Latent Phase Lytic Gene Expression and Suppress Virus Reactivation from Latently Infected Neurons

open access articleHerpes simplex virus 1 (HSV-1) establishes life-long latent infection within sensory neurons, during which viral lytic gene expression is silenced. The only highly expressed viral gene product during latent infection is the latency-associated transcript (LAT), a non-protein coding RNA that has been strongly implicated in the epigenetic regulation of HSV-1 gene expression. We have investigated LAT-mediated control of latent gene expression using chromatin immunoprecipitation analyses and LAT-negative viruses engineered to express firefly luciferase or β-galactosidase from a heterologous lytic promoter. Whilst we were unable to determine a significant effect of LAT expression upon heterochromatin enrichment on latent HSV-1 genomes, we show that reporter gene expression from latent HSV-1 genomes occurs at a greater frequency in the absence of LAT. Furthermore, using luciferase reporter viruses we have observed that HSV-1 gene expression decreases during long-term latent infection, with a most marked effect during LAT-negative virus infection. Finally, using a fluorescent mouse model of infection to isolate and culture single latently infected neurons, we also show that reactivation occurs at a greater frequency from cultures harbouring LAT-negative HSV-1. Together, our data suggest that the HSV-1 LAT RNA represses HSV-1 gene expression in small populations of neurons within the mouse TG, a phenomenon that directly impacts upon the frequency of reactivation and the maintenance of the transcriptionally active latent reservoir

Large Eddy simulations of isolated and installed jet noise using the high-order discontinuous Galerkin method

A recently developed computational framework for jet noise is used to compute the noise generated by an isolated and installed jet. The framework consists of two parts. In the first part, the spectral/hp element framework Nektar++ is used to compute the near-field flow. Nektar++ solves the unfiltered Navier-Stokes equations on unstructured grids using the high-order discontinuous Galerkin method. The discrete equations are integrated in time using an implicit scheme based on the matrix-free Newton-GMRES method. In the second part, the Antares library is used to compute the far-field noise. Antares solves the Ffowcs Williams - Hawkings equation for a permeable integration surface in the time domain using a source-time dominant algorithm. The simulations are validated against experimental data obtained in the Doak Laboratory Flight Jet Rig, located at the University of Southampton. For the isolated jet, good agreement is achieved, both in terms of the flow statistics and the far-field noise. The discrepancies observed for the isolated jet are believed to be caused by an under-resolved boundary layer in the simulations. For the installed jet, the flow statistics are also well predicted. In the far-field, very good agreement is achieved for downstream observers. For upstream observers, some discrepancies are observed for very high and very low frequencies

Distinguishing nanowire and nanotube formation by the deposition current transients

AbstractHigh aspect ratio Ni nanowires (NWs) and nanotubes (NTs) were electrodeposited inside ordered arrays of self-assembled pores (approximately 50 nm in diameter and approximately 50 μm in length) in anodic alumina templates by a potentiostatic method. The current transients monitored during each process allowed us to distinguish between NW and NT formation. The depositions were long enough for the deposited metal to reach the top of the template and form a continuous Ni film. The overfilling process was found to occur in two steps when depositing NWs and in a single step in the case of NTs. A comparative study of the morphological, structural, and magnetic properties of the Ni NWs and NTs was performed using scanning electron microscopy, X-ray diffraction, and vibrating sample magnetometry, respectively.M. P. Proença and C. T. Sousa are thankful to FCT for the doctoral and postdoctoral grants SFRH/BD/43440/2008 and SFRH/BPD/82010/2011, respectively. J. Ventura acknowledges the financial support through FSE/POPH. M Vázquez thanks the Spanish Ministry of Economia y Competitividad, MEC, under project MAT2010-20798-C05-01. J. P. Araújo also thanks the Fundação Gulbenkian for its financial support within the ‘Programa Gulbenkian de Estímulo à Investigação Científica’. The authors acknowledge the funding from FCT through the Associated Laboratory - IN and project PTDC/FIS/105416/2008.Peer Reviewe

Magnetic behaviour of multisegmented FeCoCu/Cu electrodeposited nanowires

Understanding the magnetic behaviour of multisegmented nanowires (NWs) is a major key for the application of such structures in future devices. In this work, magnetic/non-magnetic arrays of FeCoCu/Cu multilayered NWs electrodeposited in nanoporous alumina templates are studied. Contrarily to most reports on multilayered NWs, the magnetic layer thickness was kept constant (30 nm) and only the non-magnetic layer thickness was changed (0 to 80 nm). This allowed us to tune the interwire and intrawire interactions between the magnetic layers in the NW array creating a three-dimensional (3D) magnetic system without the need to change the template characteristics. Magnetic hysteresis loops, measured with the applied field parallel and perpendicular to the NWs' long axis, showed the effect of the non-magnetic Cu layer on the overall magnetic properties of the NW arrays. In particular, introducing Cu layers along the magnetic NW axis creates domain wall nucleation sites that facilitate the magnetization reversal of the wires, as seen by the decrease in the parallel coercivity and the reduction of the perpendicular saturation field. By further increasing the Cu layer thickness, the interactions between the magnetic segments, both along the NW axis and of neighbouring NWs, decrease, thus rising again the parallel coercivity and the perpendicular saturation field. This work shows how one can easily tune the parallel and perpendicular magnetic properties of a 3D magnetic layer system by adjusting the non-magnetic layer thickness

Oropouche Virus Infection And Pathogenesis Are Restricted By Mavs, Irf-3, Irf-7, And Type I Interferon Signaling Pathways In Nonmyeloid Cells

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Oropouche virus (OROV) is a member of the Orthobunyavirus genus in the Bunyaviridae family and a prominent cause of insect-transmitted viral disease in Central and South America. Despite its clinical relevance, little is known about OROV pathogenesis. To define the host defense pathways that control OROV infection and disease, we evaluated OROV pathogenesis and immune responses in primary cells and mice that were deficient in the RIG-I-like receptor signaling pathway (MDA5, RIG-I, or MAVS), downstream regulatory transcription factors (IRF-3 or IRF-7), beta interferon (IFN-beta), or the receptor for type I IFN signaling (IFNAR). OROV replicated to higher levels in primary fibroblasts and dendritic cells lacking MAVS signaling, the transcription factors IRF-3 and IRF-7, or IFNAR than in wild-type (WT) cells. In mice, deletion of IFNAR, MAVS, or IRF-3 and IRF-7 resulted in uncontrolled OROV replication, hypercytokinemia, extensive liver damage, and death, whereas WT congenic animals failed to develop disease. Unexpectedly, mice with a selective deletion of IFNAR on myeloid cells (CD11c Cre(+) Ifnar(f/f) or LysM Cre(+) Ifnar(f/f)) did not sustain enhanced disease with OROV or a selective (flox/flox) deletion La Crosse virus, a closely related encephalitic orthobunyavirus. In bone marrow chimera studies, recipient irradiated Ifnar(-/-) mice reconstituted with WT hematopoietic cells sustained high levels of OROV replication and liver damage, whereas WT mice reconstituted with Ifnar(-/-) bone marrow were resistant to disease. Collectively, these results establish a dominant protective role for MAVS, IRF-3 and IRF-7, and IFNAR in restricting OROV infection and tissue injury and suggest that IFN signaling in nonmyeloid cells contributes to the host defense against orthobunyaviruses.89947204737National Institutes of Health [R01 AI104972, P30 DK52574]Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)University Research Committee grantConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CNPq [246513/2012-8

Interferon-regulatory Factor 5-dependent Signaling Restricts Orthobunyavirus Dissemination To The Central Nervous System

Interferon (IFN)-regulatory factor 5 (IRF-5) is a transcription factor that induces inflammatory responses after engagement and signaling by pattern recognition receptors. To define the role of IRF-5 during bunyavirus infection, we evaluated Oropouche virus (OROV) and La Crosse virus (LACV) pathogenesis and immune responses in primary cells and in mice with gene deletions in Irf3, Irf5, and Irf7 or in Irf5 alone. Deletion of Irf3, Irf5, and Irf7 together resulted in uncontrolled viral replication in the liver and spleen, hypercytokinemia, extensive liver injury, and an early-death phenotype. Remarkably, deletion of Irf5 alone resulted in meningoencephalitis and death on a more protracted timeline, 1 to 2 weeks after initial OROV or LACV infection. The clinical signs in OROV-infected Irf5(-/-) mice were associated with abundant viral antigen and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells in several regions of the brain. Circulating dendritic cell (DC) subsets in Irf5(-/-) mice had higher levels of OROV RNA in vivo yet produced lower levels of type I IFN than wild-type (WT) cells. This result was supported by data obtained in vitro, since a deficiency of IRF-5 resulted in enhanced OROV infection and diminished type I IFN production in bone marrow-derived DCs. Collectively, these results indicate a key role for IRF-5 in modulating the host antiviral response in peripheral organs that controls bunyavirus neuroinvasion in mice.90118920

Multiple voice disorders in the same individual: Investigating handcrafted features, multi-label classification algorithms, and base-learners

Non-invasive acoustic analyses of voice disorders have been at the forefront of current biomedical research. Usual strategies, essentially based on machine learning (ML) algorithms, commonly classify a subject as being either healthy or pathologically-affected. Nevertheless, the latter state is not always a result of a sole laryngeal issue, i.e., multiple disorders might exist, demanding multi-label classification procedures for effective diagnoses. Consequently, the objective of this paper is to investigate the application of five multi-label classification methods based on problem transformation to play the role of base-learners, i.e., Label Powerset, Binary Relevance, Nested Stacking, Classifier Chains, and Dependent Binary Relevance with Random Forest (RF) and Support Vector Machine (SVM), in addition to a Deep Neural Network (DNN) from an algorithm adaptation method, to detect multiple voice disorders, i.e., Dysphonia, Laryngitis, Reinke's Edema, Vox Senilis, and Central Laryngeal Motion Disorder. Receiving as input three handcrafted features, i.e., signal energy (SE), zero-crossing rates (ZCRs), and signal entropy (SH), which allow for interpretable descriptors in terms of speech analysis, production, and perception, we observed that the DNN-based approach powered with SE-based feature vectors presented the best values of F1-score among the tested methods, i.e., 0.943, as the averaged value from all the balancing scenarios, under Saarbrücken Voice Database (SVD) and considering 20% of balancing rate with Synthetic Minority Over-sampling Technique (SMOTE). Finally, our findings of most false negatives for laryngitis may explain the reason why its detection is a serious issue in speech technology. The results we report provide an original contribution, allowing for the consistent detection of multiple speech pathologies and advancing the state-of-the-art in the field of handcrafted acoustic-based non-invasive diagnosis of voice disorders

Cobalt ferrite thin films deposited by electrophoresis on p-doped Si substrates

The structural and magnetic properties of cobalt ferrite (CoFe2O4) thin films deposited by electrophoresis on p-doped Si(001) substrates have been characterized. The films were polycrystalline and composed by cobalt ferrite with the cubic spinnel structure. The observed decrease of the coercive field with the sixth power of the grain size was indicative of a competition between the magnetocrystalline anisotropy and the exchange coupling energy, on these randomly oriented nanosized grained films.J. Barbosa and M.P. Proenca gratefully acknowledge a PhD grant from Fundacao para a Ciencia e Tecnologia (SFRH/BD/41913/2007 and SFRH/BD/43440/2008, respectively)

Deterministic and time resolved thermo-magnetic switching in a nickel nanowire

[EN]Heating a ferromagnetic material is often perceived as detrimental for most applications. This is indeed the case for modern nano-scaled spintronic devices which are operated solely (at least ideally) by an electric current. Heat is a by-product of the current-driven operation and it deteriorates many functionalities of the device. A large scientific and technological effort is devoted these days to avoid heat in modern magnetic nano devices. Here we show that heat can be used to provide an additional and useful degree of freedom in the control of the local magnetization at the nanoscale. In a ferromagnetic nanowire, temperature is used to induce a magnetic switching through a perfectly deterministic mechanism. The nucleation of the magnetic domain walls that triggers the switching can be achieved at a field considerably smaller than the nucleation field and, importantly, the exact moment of the magnetic switching can be pre-determined with nanosecond precision by controlling the power delivered locally to the switching area. With the help of micromagnetic simulations and a theoretical model, we provide an accurate explanation of how this deterministic thermo-magnetic switching operates. The concepts described in this work may lead to an increased functionality in magnetic nano-devices based on magnetic domain walls.MAT2017-87072-C4-1-P,MAT2017-87072-C4-4-P and MAT2017-87072-C4-3-P from the Spanish government SA299P18 from the Junta de Castilla y Leon POCI-01-0145-FEDER-028676 from Portuguese FCT COMPETE 2020 (FEDER)