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

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

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)

Uveal Melanoma: A European Network to Face the Many Challenges of a Rare Cancer

Uveal melanoma (UM) is the most frequent primary ocular cancer in adults, accounting for 5% of all melanomas. Despite effective treatments for the primary tumour, up to 50% of UM patients will develop metastasis, leading to a very poor prognosis and a median overall survival of 6 to 12 months, with no major improvements in the last 30 years. There is no standard oncological treatment available for metastatic UM patients, and BRAF/MEK and immune checkpoint inhibitors show disappointing results when compared to cutaneous melanoma (CM). Recent advances in biology, however, identified specific gene and chromosome alterations, potentially permitting an actively tailored surveillance strategy, and dedicated clinical studies. Being a rare cancer, UM patients have to overcome issues such as identifying referral centres, having access to information, and partnering with oncologists for specific management strategies and research priorities. Here, we describe how the European Rare Adult solid Cancer Network (EURACAN) will help in addressing these challenges and accelerating international collaborations to enhance the development of innovative treatments in UM

Acute Human Self-Poisoning with Imidacloprid Compound: A Neonicotinoid Insecticide

Background: Deliberate self-poisoning with older pesticides such as organophosphorus compounds are commonly fatal and a serious public health problem in the developing world. The clinical consequences of self-poisoning with newer pesticides are not well described. Such information may help to improve clinical management and inform pesticide regulators of their relative toxicity. This study reports the clinical outcomes and toxicokinetics of the neonicotinoid insecticide imidacloprid following acute self-poisoning in humans. Methodology/Principal Findings: Demographic and clinical data were prospectively recorded in patients with imidacloprid exposure in three hospitals in Sri Lanka. Blood samples were collected when possible for quantification of imidacloprid concentration. There were 68 patients (61 self-ingestions and 7 dermal exposures) with exposure to imidacloprid. Of the self-poisoning patients, the median time to presentation was 4 hours (IQR 2.3–6.0) and median amount ingested was 15 mL (IQR 10–50 mL). Most patients only developed mild symptoms such as nausea, vomiting, headache and diarrhoea. One patient developed respiratory failure needing mechanical ventilation while another was admitted to intensive care due to prolonged sedation. There were no deaths. Median admission imidacloprid concentration was 10.58 ng/L; IQR: 3.84–15.58 ng/L, Range: 0.02–51.25 ng/L. Changes in the concentration of imidacloprid in serial blood samples were consistent with prolonged absorption and/or saturable elimination. Conclusions: Imidacloprid generally demonstrates low human lethality even in large ingestions. Respiratory failure and reduced level of consciousness were the most serious complications, but these were uncommon. Substitution of imidacloprid for organophosphorus compounds in areas where the incidence of self-poisoning is high may help reduce deaths from self-poisoning

RETRATO DE MUJER [Material gráfico]

Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte, 201

A versatile synthesis method of dendrites-free segmented nanowires with a precise size control

We report an innovative strategy to obtain cylindrical nanowires combining well established and low-cost bottom-up methods such as template-assisted nanowires synthesis and electrodeposition process. This approach allows the growth of single-layer or multi-segmented nanowires with precise control over their length (from few nanometers to several micrometers). The employed techniques give rise to branched pores at the bottom of the templates and consequently dendrites at the end of the nanowires. With our method, these undesired features are easily removed from the nanowires by a selective chemical etching. This is crucial for magnetic characterizations where such non-homogeneous branches may introduce undesired features into the final magnetic response. The obtained structures show extremely narrow distributions in diameter and length, improved robustness and high-yield, making this versatile approach strongly compatible with large scale production at an industrial level. Finally, we show the possibility to tune accurately the size of the nanostructures and consequently provide an easy control over the magnetic properties of these nanostructures