Therapeutic intranasal vaccine HB-ATV-8 prevents atherogenesis and non-alcoholic fatty liver disease in a pig model of atherosclerosis

BACKGROUND AND AIMS: Atherosclerosis as an inflammatory disease involved in the etiology of cardiovascular disease worldwide, in our days demands an array of different therapeutic approaches in order to soon be able to visualize an effective prevention. Based on an immunotherapeutic approach, we designed a non-invasive vaccine (HB-ATV-8), contained in a micellar nanoparticle composed of lipids and a peptide segment derived from the C-terminus of the cholesterol-ester transfer protein (CETP). Now we extend our successful proof of concept from the rabbit to a porcine model and investigated its effect in an attempt to undoubtedly establish the efficacy of vaccination in a model closer to the human. METHODS: A preclinical trial was designed to study the efficacy of vaccine HB-ATV-8 in pigs (Large White × Landrace). Male experimental animals were fed with standard diet (control), high fat diet (HFD) or the same HFD but treated with HB-ATV-8 (HFD + Vaccine) applied nasally for up to 7 months. All biochemical and enzymatic analyses were performed in peripheral venous blood and thoracic aorta and liver samples examined using conventional, two-photon excitation and second harmonic generation microscopy to identify atherosclerotic and hepatic lesions. mRNA concentrations for KLF2, ACTA2, SOD1, COL1A1 genes and protein levels for PPARα and ABCA1 were quantified in aorta and liver respectively using qPCR and Western blot analysis. RESULTS: The administration of vaccine HB-ATV-8 induced anti-CETP IgG antibodies and reduced atherosclerotic and hepatic lesions promoted by the high fat diet. In addition, plasma triglyceride levels of vaccine treated pigs fed the HFD were similar to those of control group, in contrast to high concentrations reached with animals exclusively fed with HFD. Moreover, HFD promotes a tendency to decreased hepatic PPARα levels and increase in aorta gene expression of KLF2, ACTA2, SOD1 and COL1A1, while vaccine application promotes recovery close to control values. CONCLUSIONS: Vaccine HB-ATV-8 administration constitutes a promissory preventive approach useful in the control of atherogenesis and fatty liver disease. The positive results obtained, the non-invasive characteristics of the vaccine, the simple design employed in its conception and its low production cost, support the novelty of this therapeutic strategy designed to prevent the process of atherogenesis and control the development of fatty liver disease

Refuerzo de fustes de columna en la arquitectura monumental de Italica (prov. Baetica). Aplicación de nuevas tecnologías para la reconstrucción de una práctica singular

The pieces under study presented in this paper come from the already well known “Traianeum” of Italica (prov. Baetica, present Santiponce, Seville), a huge complex area, formed by a wide open square with a main central temple, built according to the extension of the city with a new quarter in Hadrian times. Most of them, fragments of column shafts, offer very peculiar technical features: canals for metallic dowels, cavities for marble tasselli and holes for also metallic staples or cramps. All these systems had the aim of reinforce a valuable material with potential structure problems. The ensemble is unique because of the preservation of a sufficient amount of fragments that allows their complete restitution with the help of photogrammetric techniques in order to obtain three-dimensional models of the pieces and to understand the ancient technologic solutions. Even more, the practices make us reflect about technical skills and economy and organization of constructions.Esta investigación tiene por objeto presentar los trabajos en curso en torno a un conjunto de fustes procedente de los órdenes arquitectónicos del conocido como Traianeum de Itálica (provincia Baetica, actual Santiponce, Sevilla), complejo de templo central y pórtico perimetral levantado en la ciudad a comienzos del siglo II d. C. En ellos se observan las huellas dejadas por toda una serie de recursos técnicos tales como grapas, espigas metálicas y cavidades para parches marmóreos, asociada con medidas preventivas de refuerzo de piedra eventualmente quebradiza. Para ello, dado su estado fragmentado y fragmentario, se ha recurrido a la aplicación de técnicas fotogramétricas que permitan la obtención de modelos tridimensionales de las piezas, con el fin de reconstruir el funcionamiento y finalidad mecánica de los citados recursos. En último término, se trata de profundizar en aspectos relacionados con una singular capacidad tecnológica selectiva y con la economía y organización de las obras

The central region of M83: Massive star formation, kinematics, and the location and origin of the nucleus

We report new near-IR integral field spectroscopy of the central starburst region of the barred spiral galaxy M83 obtained with CIRPASS on Gemini-S, which we analyse in conjunction with GHaFaS Fabry-Perot data, an AAT IRIS2 Ks-band image, and near- and mid-IR imaging from the Hubble and Spitzer space telescopes. The bulk of the current star formation activity is hidden from optical view by dust extinction, but is seen in the near- and mid-IR to the north of the nucleus. This region is being fed by inflow of gas through the bar of M83, traced by the prominent dust lane entering into the circumnuclear region from the north. An analysis of stellar ages confirms that the youngest stars are indeed in the northwest. A gradual age gradient, with older stars further to the south, characterises the well-known star-forming arc in the central region of M83. Detailed analyses of the Pa beta ionised gas kinematics and near-IR imaging confirm that the kinematic centre coincides with the photometric centre of M83, and that these are offset significantly, by about 3 arcsec or 60 pc, from the visible nucleus of the galaxy. We discuss two possible options, the first of which postulates that the kinematic and photometric centre traces a galaxy nucleus hidden by a substantial amount of dust extinction, in the range A_V=3-10 mag. By combining this information with kinematic results and using arguments from the literature, we conclude that such a scenario is, however, unlikely, as is the existence of other "hidden" nuclei in M83. We thus concur with recent authors and favour a second option, in which the nucleus of the galaxy is offset from its kinematic and photometric centre. This is presumably a result of some past interaction, possibly related to the event which lies at the origin of the disturbance of the outer disk of the galaxy. (Abridged)Comment: MNRAS, in press; 16 pages latex, 15 figure

Utilising the Intel RealSense camera for measuring health outcomes in clinical research

Applications utilising 3D Camera technologies for the measurement of health outcomes in the health and wellness sector continues to expand. The Intel® RealSense™ is one of the leading 3D depth sensing cameras currently available on the market and aligns itself for use in many applications, including robotics, automation, and medical systems. One of the most prominent areas is the production of interactive solutions for rehabilitation which includes gait analysis and facial tracking. Advancements in depth camera technology has resulted in a noticeable increase in the integration of these technologies into portable platforms, suggesting significant future potential for pervasive in-clinic and field based health assessment solutions. This paper reviews the Intel RealSense technology’s technical capabilities and discusses its application to clinical research and includes examples where the Intel RealSense camera range has been used for the measurement of health outcomes. This review supports the use of the technology to develop robust, objective movement and mobility-based endpoints to enable accurate tracking of the effects of treatment interventions in clinical trials

Operations of and Future Plans for the Pierre Auger Observatory

Technical reports on operations and features of the Pierre Auger Observatory, including ongoing and planned enhancements and the status of the future northern hemisphere portion of the Observatory. Contributions to the 31st International Cosmic Ray Conference, Lodz, Poland, July 2009.Comment: Contributions to the 31st ICRC, Lodz, Poland, July 200

Atmospheric effects on extensive air showers observed with the Surface Detector of the Pierre Auger Observatory

Atmospheric parameters, such as pressure (P), temperature (T) and density, affect the development of extensive air showers initiated by energetic cosmic rays. We have studied the impact of atmospheric variations on extensive air showers by means of the surface detector of the Pierre Auger Observatory. The rate of events shows a ~10% seasonal modulation and ~2% diurnal one. We find that the observed behaviour is explained by a model including the effects associated with the variations of pressure and density. The former affects the longitudinal development of air showers while the latter influences the Moliere radius and hence the lateral distribution of the shower particles. The model is validated with full simulations of extensive air showers using atmospheric profiles measured at the site of the Pierre Auger Observatory.Comment: 24 pages, 9 figures, accepted for publication in Astroparticle Physic

The Fluorescence Detector of the Pierre Auger Observatory

The Pierre Auger Observatory is a hybrid detector for ultra-high energy cosmic rays. It combines a surface array to measure secondary particles at ground level together with a fluorescence detector to measure the development of air showers in the atmosphere above the array. The fluorescence detector comprises 24 large telescopes specialized for measuring the nitrogen fluorescence caused by charged particles of cosmic ray air showers. In this paper we describe the components of the fluorescence detector including its optical system, the design of the camera, the electronics, and the systems for relative and absolute calibration. We also discuss the operation and the monitoring of the detector. Finally, we evaluate the detector performance and precision of shower reconstructions.Comment: 53 pages. Submitted to Nuclear Instruments and Methods in Physics Research Section

Histopathological alterations in Senegal sole, Solea Senegalensis, from a polluted Huelva estuary (SW, Spain)

As a component of a large research project to evaluate the effects of contaminants on fish health in the field, histopathological studies have been conducted to help establish causal relationship between pollutants (heavy metals and aromatic polycyclic hydrocarbons—PAHs) and histopathological responses in Senegal sole, Solea senegalensis, from an estuary of SW Spain. Heavy metals (As, Zn, Cd, Pb, Cu and Fe) and 16 PAHs (proprietary USEPA) concentrations in water, sediment and tissues (liver and gills) and histopathological alterations in S. senegalensis from three sampling sites of Ria de Huelva estuary during 2004–2006 years have been analysed. The histopathological studies revealed seasonal and spatial differences in the lesion grade of alterations observing the highest lesion grades in fish from Odiel River and autumn season. No significant differences were observed in the alterations prevalence between sampling sites, but significant differences were observed between seasons observing the highest prevalence in autumn season. However, calculated IPAT demonstrated a low–moderate impact of pollutants on health fish. Correlations between histopathological alterations and pollutants analysed were observed being heavy metals the group that presented a major number of correlations with alterations in several organs of S. senegalensis. In evaluating the general health of fish, the use of histopathological studies in recommended for making more reliable assessment of biochemical responses in fish exposed to a variety of environmental stressors. Statistical analysis using semiquantitative data on pathological lesions can help to establish correlation between cause (stressor) and effect (biomarker)

The first myriapod genome sequence reveals conservative arthropod gene content and genome organisation in the centipede Strigamia maritima.

Myriapods (e.g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.This work was supported by the following grants: NHGRIU54HG003273 to R.A.G; EU Marie Curie ITN #215781 “Evonet” to M.A.; a Wellcome Trust Value in People (VIP) award to C.B. and Wellcome Trust graduate studentship WT089615MA to J.E.G; Marine rhythms of Life” of the University of Vienna, an FWF (http://www.fwf.ac.at/) START award (#AY0041321) and HFSP (http://www.hfsp.org/) research grant (#RGY0082/2010) to KT-­‐R; MFPL Vienna International PostDoctoral Program for Molecular Life Sciences (funded by Austrian Ministry of Science and Research and City of Vienna, Cultural Department -­‐Science and Research to T.K; Direct Grant (4053034) of the Chinese University of Hong Kong to J.H.L.H.; NHGRI HG004164 to G.M.; Danish Research Agency (FNU), Carlsberg Foundation, and Lundbeck Foundation to C.J.P.G.; U.S. National Institutes of Health R01AI55624 to J.H.W.; Royal Society University Research fellowship to F.M.J.; P.D.E. was supported by the BBSRC via the Babraham Institute;This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pbio.100200