Mother's Milk: A Purposeful Contribution to the Development of the infant Microbiota and immunity

Breast milk is the perfect nutrition for infants, a result of millions of years of evolution. In addition to providing a source of nutrition, breast milk contains a diverse array of microbiota and myriad biologically active components that are thought to guide the infant’s developing mucosal immune system. It is believed that bacteria from the mother’s intestine may translocate to breast milk and dynamically transfer to the infant. Such interplay between mother and her infant is a key to establishing a healthy infant intestinal microbiome. These intestinal bacteria protect against many respiratory and diarrheal illnesses, but are subject to environmental stresses such as antibiotic use. Orchestrating the development of the microbiota are the human milk oligosaccharides (HMOs), the synthesis of which are partially determined by the maternal genotype. HMOs are thought to play a role in preventing pathogenic bacterial adhesion though multiple mechanisms, while also providing nutrition for the microbiome. Extracellular vesicles (EVs), including exosomes, carry a diverse cargo, including mRNA, miRNA, and cytosolic and membrane-bound proteins, and are readily detectable in human breast milk. Strongly implicated in cell–cell signaling, EVs could therefore may play a further role in the development of the infant microbiome. This review considers the emerging role of breast milk microbiota, bioactive HMOs, and EVs in the establishment of the neonatal microbiome and the consequent potential for modulation of neonatal immune system development

Towards micro-arcsecond spatial resolution with Air Cherenkov Telescope arrays as optical intensity interferometers

In this poster contribution we highlight the equivalence between an Imaging Air Cherenkov Telescope (IACT) array and an Intensity Interferometer for a range of technical requirements. We touch on the differences between a Michelson and an Intensity Interferometer and give a brief overview of the current IACT arrays, their upgrades and next generation concepts (CTA, AGIS, completion 2015). The latter are foreseen to include 30-90 telescopes that will provide 400-4000 different baselines that range in length between 50m and a kilometre. Intensity interferometry with such arrays of telescopes attains 50 micro-arcseconds resolution for a limiting V magnitude of ~8.5. This technique opens the possibility of a wide range of studies, amongst others, probing the stellar surface activity and the dynamic AU scale circumstellar environment of stars in various crucial evolutionary stages. Here we discuss possibilities for using IACT arrays as optical Intensity Interferometers.Comment: Appeared in the proceedings of "The Universe under the Microscope - Astrophysics at High Angular Resolution", Journal of Physics:Conference Series (IOP; http://www.iop.org/EJ/toc/1742-6596/131/1

Multiwavelength Observations of 1ES 1959+650, One Year After the Strong Outburst of 2002

In April-May 2003, the blazar 1ES 1959+650 showed an increased level of X-ray activity. This prompted a multiwavelength observation campaign with the Whipple 10 m gamma-ray telescope, the Rossi X-ray Timing Explorer, the Bordeaux Optical Observatory, and the University of Michigan Radio Astrophysical Observatory. We present the multiwavelength data taken from May 2, 2003 to June 7, 2003 and compare the source characteristics with those measured during observations taken during the years 2000 and 2002. The X-ray observations gave a data set with high signal-to-noise light curves and energy spectra; however, the gamma-ray observations did not reveal a major TeV gamma-ray flare. Furthermore, we find that the radio and optical fluxes do not show statistically significant deviations from those measured during the 2002 flaring periods. While the X-ray flux and X-ray photon index appear correlated during subsequent observations, the apparent correlation evolved significantly between the years 2000, 2002, and 2003. We discuss the implications of this finding for the mechanism that causes the flaring activity.Comment: 17 pages, 6 figures, 2 table

Mrk 421, Mrk 501, and 1ES 1426+428 at 100 GeV with the CELESTE Cherenkov Telescope

We have measured the gamma-ray fluxes of the blazars Mrk 421 and Mrk 501 in the energy range between 50 and 350 GeV (1.2 to 8.3 x 10^25 Hz). The detector, called CELESTE, used first 40, then 53 heliostats of the former solar facility "Themis" in the French Pyrenees to collect Cherenkov light generated in atmospheric particle cascades. The signal from Mrk 421 is often strong. We compare its flux with previously published multi-wavelength studies and infer that we are straddling the high energy peak of the spectral energy distribution. The signal from Mrk 501 in 2000 was weak (3.4 sigma). We obtain an upper limit on the flux from 1ES 1426+428 of less than half that of the Crab flux near 100 GeV. The data analysis and understanding of systematic biases have improved compared to previous work, increasing the detector's sensitivity.Comment: 15 pages, 14 figures, accepted to A&A (July 2006) August 19 -- corrected error in author lis

<i>Plasmodium </i>Condensin Core Subunits SMC2/SMC4 Mediate Atypical Mitosis and Are Essential for Parasite Proliferation and Transmission

Condensin is a multi-subunit protein complex regulating chromosome condensation and segregation during cell division. In Plasmodium spp., the causative agent of malaria, cell division is atypical and the role of condensin is unclear. Here we examine the role of SMC2 and SMC4, the core subunits of condensin, during endomitosis in schizogony and endoreduplication in male gametogenesis. During early schizogony, SMC2/SMC4 localize to a distinct focus, identified as the centromeres by NDC80 fluorescence and chromatin immunoprecipitation sequencing (ChIP-seq) analyses, but do not form condensin I or II complexes. In mature schizonts and during male gametogenesis, there is a diffuse SMC2/SMC4 distribution on chromosomes and in the nucleus, and both condensin I and condensin II complexes form at these stages. Knockdown of smc2 and smc4 gene expression reveals essential roles in parasite proliferation and transmission. The condensin core subunits (SMC2/SMC4) form different complexes and may have distinct functions at various stages of the parasite life cycle

Synthesis and characterisation of pyrene-labelled polydimethylsiloxane networks: towards the in situ detection of strain in silicone elastomers

Pyrene-substituted polyhydromethylsiloxanes (PHMS-Py-x) were synthesised by the hydrosilylation reaction of prop-3-enyloxymethylpyrene with polyhydromethylsiloxane (M-n = 3700). The ratio of pyrene substituent to Si-H unit was varied to afford a range of pyrene-functionalised polysiloxanes. These copolymers were subsequently incorporated into polydimethylsiloxane (PDMS) elastomers by curing via either Pt(0) catalysed hydrosilylation with divinyl-terminated PDMS (M-n = 186) and tetrakis(dimethylsiloxy) silane, or Sn(II) catalysed condensation with alpha,omega-dihydroxyPDMS (M-n = 26 000) and tetraethoxysilane. An alternative method involving the synthesis and integration of [3-(pyren-1-ylmethoxy)propyl]triethoxysilane (Py-TEOS) into PDMS elastomers was also investigated: a mixture of alpha,omega-dihydroxyPDMS (M-n = 26 000), tetraethoxysilane, and Py-TEOS was cured using an Sn( II) catalyst. Certain of the resulting fluorescent pyrene-labelled elastomers were studied by differential scanning calorimetry and dynamic mechanical analysis. No significant changes were observed in the thermal or mechanical properties of the elastomers containing pyrene when compared to otherwise identical samples not containing pyrene. All of the pyrene-containing elastomers were demonstrated to be fluorescent under suitable excitation in a photoluminescent spectrometer. Two of the elastomers were placed in a photoluminescence spectrometer and subjected to cycles of extension and relaxation (strain = 0-16.7%) while changes in the emission spectra were monitored. The resulting spectra of the elastomer containing the PHMS-Py-50 copolymers were variable and inconsistent. However, the emission peaks of elastomers containing Py-TEOS displayed clear and reproducible changes in fluorescence intensity upon stretching and relaxation. The intensity of the monomer and excimer emission peaks was observed to increase with elongation of the sample and decrease upon relaxation. Furthermore, the ratio of the intensities of the excimer : monomer peak decreased with elongation and increased with relaxation. In neither case was there appreciable hysteresis, suggesting that fluorescent labelling of elastomers is a valid approach for the non-invasive in situ monitoring of stress and strain in such materials

Cherenkov Telescopes as Optical Telescopes for Bright Sources: Today's Specialised Thirty Metre Telescopes?

Imaging Atmospheric Cherenkov Telescopes (IACTs) use large-aperture (~ 10 - 30 m) optical telescopes with arcminute angular resolution to detect TeV gamma-rays in the atmosphere. I show that IACTs are well-suited for optical observations of bright sources (V <= 8 - 10), because these sources are brighter than the sky background. Their advantages are especially great on rapid time-scales. Thus, IACTs are ideal for studying many phenomena optically, including transiting exoplanets and the brightest gamma-ray bursts. In principle, an IACT could achieve millimagnitude photometry of these objects with second-long exposures. I also consider the potential for optical spectroscopy with IACTs, finding that their poor angular resolution limits their usefulness for high spectral resolutions, unless complex instruments are developed. The high photon collection rate of IACTs is potentially useful for precise polarimetry. Finally, I briefly discuss the broader possibilities of extremely large, low resolution telescopes, including a 10" resolution telescope and spaceborne telescopes.Comment: 10 pages, 3 figures, accepted by MNRA

Multiwavelength Observations of the Blazar Mrk 421 in December 2002 and January 2003

We report on a multiwavelength campaign on the TeV gamma-ray blazar Markarian (Mrk) 421 performed during December 2002 and January 2003. These target of opportunity observations were initiated by the detection of X-ray and TeV gamma-ray flares with the All Sky Monitor (ASM) on board the Rossi X-ray Timing Explorer (RXTE) and the 10 m Whipple gamma-ray telescope.The campaign included observational coverage in the radio (University of Michigan Radio Astronomy Observatory), optical (Boltwood, La Palma KVA 0.6m, WIYN 0.9m), X-ray (RXTE pointed telescopes), and TeV gamma-ray (Whipple and HEGRA) bands. At TeV energies, the observations revealed several flares at intermediate flux levels, peaking between 1 and 1.5 times the flux from the Crab Nebula. While the time averaged spectrum can be fitted with a single power law of photon index Gamma =2.8, we find some evidence for spectral variability. Confirming earlier results, the campaign reveals a rather loose correlation between the X-ray and TeV gamma-ray fluxes. In one case, a very strong X-ray flare is not accompanied by a comparable TeV gamma-ray flare. Although the source flux was variable in the optical and radio bands, the sparse sampling of the optical and radio light curves does not allow us to study the correlation properties in detail. We present a simple analysis of the data with a synchrotron-self Compton model, emphasizing that models with very high Doppler factors and low magnetic fields can describe the data.Comment: Accepted for publication in the Astrophysical Journa

Photoactivated chemotherapy (PACT) : the potential of excited-state d-block metals in medicine

The fields of phototherapy and of inorganic chemotherapy both have long histories. Inorganic photoactivated chemotherapy (PACT) offers both temporal and spatial control over drug activation and has remarkable potential for the treatment of cancer. Following photoexcitation, a number of different decay pathways (both photophysical and photochemical) are available to a metal complex. These pathways can result in radiative energy release, loss of ligands or transfer of energy to another species, such as triplet oxygen. We discuss the features which need to be considered when developing a metal-based anticancer drug, and the common mechanisms by which the current complexes are believed to operate. We then provide a comprehensive overview of PACT developments for complexes of the different d-block metals for the treatment of cancer, detailing the more established areas concerning Ti, V, Cr, Mn, Re, Fe, Ru, Os, Co, Rh, Pt, and Cu and also highlighting areas where there is potential for greater exploration. Nanoparticles (Ag, Au) and quantum dots (Cd) are also discussed for their photothermal destructive potential. We also discuss the potential held in particular by mixed-metal systems and Ru complexes