In-vitro and in-vivo evaluation of the antistaphylococcal activity of S-5556, a new 16-membered macrolide

During recent years, a resurgence of interest in the macrolides had led to the discovery of new derivatives of erythromycin with improved antibacterial activity and pharmacokinetic properties. In this study the in-vitro and in-vivo antistaphylococcal activity of S-5556, a 16-membered macrolide, was evaluated. In vitro, S-5556 was slightly less active than erythromycin against methicillin-susceptible Staphylococcus aureus. In contrast, it had superior activity for methicillin-resistant S. aureus (MRSA); several of these strains with inducible resistance to the macrolides-lincosamides-streptogramins group were susceptible to S-5556 whereas erythromycin was inactive. The combination of S-5556 with oxatillin was synergic for most MRSA strains tested. In vivo, a single prophylactic dose of S-5556 prevented 75%-100% of the cases of acute staphylococcal subcutaneous foreign body infection in a guinea pig-model. In a rat-model of chronic implant infection due to a methicillin- and erythromycin-resistant S. aureus strain, S-5556 significantly decreased the bacteria] concentration around the foreign material, however resistant mutants emerge

Extensive remodeling of DC function by rapid maturation-induced transcriptional silencing.

The activation, or maturation, of dendritic cells (DCs) is crucial for the initiation of adaptive T-cell mediated immune responses. Research on the molecular mechanisms implicated in DC maturation has focused primarily on inducible gene-expression events promoting the acquisition of new functions, such as cytokine production and enhanced T-cell-stimulatory capacity. In contrast, mechanisms that modulate DC function by inducing widespread gene-silencing remain poorly understood. Yet the termination of key functions is known to be critical for the function of activated DCs. Genome-wide analysis of activation-induced histone deacetylation, combined with genome-wide quantification of activation-induced silencing of nascent transcription, led us to identify a novel inducible transcriptional-repression pathway that makes major contributions to the DC-maturation process. This silencing response is a rapid primary event distinct from repression mechanisms known to operate at later stages of DC maturation. The repressed genes function in pivotal processes--including antigen-presentation, extracellular signal detection, intracellular signal transduction and lipid-mediator biosynthesis--underscoring the central contribution of the silencing mechanism to rapid reshaping of DC function. Interestingly, promoters of the repressed genes exhibit a surprisingly high frequency of PU.1-occupied sites, suggesting a novel role for this lineage-specific transcription factor in marking genes poised for inducible repression

ARTEMIN Promotes De Novo Angiogenesis in ER Negative Mammary Carcinoma through Activation of TWIST1-VEGF-A Signalling

10.1371/journal.pone.0050098PLoS ONE711

Organic residue analysis of Egyptian votive mummies and their research potential

YesVast numbers of votive mummies were produced in Egypt during the Late Pharaonic, Ptolemaic, and Roman periods. Although millions remain in situ, many were removed and have ultimately entered museum collections around the world. There they have often languished as uncomfortable reminders of antiquarian practices with little information available to enhance their value as artefacts worthy of conservation or display. A multi-disciplinary research project, based at the University of Manchester, is currently redressing these issues. One recent aspect of this work has been the characterization of natural products employed in the mummification of votive bundles. Using gas chromatography–mass spectrometry and the well-established biomarker approach, analysis of 24 samples from 17 mummy bundles has demonstrated the presence of oils/fats, natural waxes, petroleum products, resinous exudates, and essential oils. These results confirm the range of organic materials employed in embalming and augment our understanding of the treatment of votives. In this first systematic initiative of its kind, initial findings point to possible trends in body treatment practices in relation to chronology, geography, and changes in ideology which will be investigated as the study progresses. Detailed knowledge of the substances used on individual bundles has also served to enhance their value as display items and aid in their conservation.RCB is supported by a PhD studentship from the Art and Humanities Research Council (43019R00209). L.M. and S.A.W. are supported by a Leverhulme Trust Research Project Award (RPG-2013-143)

Corrosion behaviour of porous Ti intended for biomedical applications

Porous Ti implants are being developed inorder to reduce the biomechanical mismatch between theimplant and the bone, as well as increasing the osseointegrationby improving the bone in-growth. Most of the focusin the literature has been on the structural, biological andmechanical characterization of porous Ti whereas there islimited information on the electrochemical characterization.Therefore, the present work aims to study the corrosionbehaviour of porous Ti having 30 and 50 % ofnominal porosity, produced by powder metallurgy routeusing the space holder technique. The percentage, size anddistribution of the pores were determined by image analysis.Electrochemical tests consisting of potentiodynamicpolarization and electrochemical impedance spectroscopywere performed in 9 g/L NaCl solution at body temperature.Electrochemical studies revealed that samples presenteda less stable oxide film at increased porosity, morespecifically, the complex geometry and the interconnectivityof the pores resulted in formation of less protectiveoxide film in the pores.This study was supported by FCT with the reference project UID/EEA/04436/2013, by FEDER funds through the COMPETE 2020 – Programa Operacional Competitividade e Internacionalizac¸a˜o (POCI) with the reference project POCI-01-0145- FEDER-006941, Programa de Acc¸o˜es Universita´rias Integradas LusoFrancesas’ (PAUILF TC-12_14), and The Calouste Gulbenkian Foundation through ‘‘Programa de Mobilidade Acade´mica para Professores’’. The authors would also like to acknowledge Prof. Ana Senos (University of Aveiro) and Prof. Jose´ Carlos Teixeira (University of Minho) for the provision of the characterization facilities.info:eu-repo/semantics/publishedVersio

Insight into trade‐off between wood decay and parasitism from the genome of a fungal forest pathogen

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91191/1/j.1469-8137.2012.04128.x.pd

Growth Hormone Promotes Hair Cell Regeneration in the Zebrafish (Danio rerio) Inner Ear following Acoustic Trauma

BACKGROUND: Previous microarray analysis showed that growth hormone (GH) was significantly upregulated following acoustic trauma in the zebrafish (Danio rerio) ear suggesting that GH may play an important role in the process of auditory hair cell regeneration. Our objective was to examine the effects of exogenous and endogenous GH on zebrafish inner ear epithelia following acoustic trauma. METHODOLOGY/PRINCIPAL FINDINGS: We induced auditory hair cell damage by exposing zebrafish to acoustic overstimulation. Fish were then injected intraperitoneally with either carp GH or buffer, and placed in a recovery tank for either one or two days. Phalloidin-, bromodeoxyuridine (BrdU)-, and TUNEL-labeling were used to examine hair cell densities, cell proliferation, and apoptosis, respectively. Two days post-trauma, saccular hair cell densities in GH-treated fish were similar to that of baseline controls, whereas buffer-injected fish showed significantly reduced densities of hair cell bundles. Cell proliferation was greater and apoptosis reduced in the saccules, lagenae, and utricles of GH-treated fish one day following trauma compared to controls. Fluorescent in situ hybridization (FISH) was used to examine the localization of GH mRNA in the zebrafish ear. At one day post-trauma, GH mRNA expression appeared to be localized perinuclearly around erythrocytes in the blood vessels of the inner ear epithelia. In order to examine the effects of endogenous GH on the process of cell proliferation in the ear, a GH antagonist was injected into zebrafish immediately following acoustic trauma, resulting in significantly decreased cell proliferation one day post-trauma in all three zebrafish inner ear end organs. CONCLUSIONS/SIGNIFICANCE: Our results show that exogenous GH promotes post-trauma auditory hair cell regeneration in the zebrafish ear through stimulating proliferation and suppressing apoptosis, and that endogenous GH signals are present in the zebrafish ear during the process of auditory hair cell regeneration