Primary structure and tetrahydropteroylglutamate binding site of rabbit liver cytosolic 5,10-methenyltetrahydrofolate synthetase.

The primary sequence of 5,10-methenyltetrahydrofolate synthetase from rabbit liver was determined by amino acid sequencing of the purified enzyme. The enzyme contains 201 amino acid residues with a predicted mass of 22,779 Da. The enzyme is located in the cytosolic fraction of liver homogenates. Carbodiimide-activated 5-formyltetrahydropteroylmonoglutamate and the pentaglutamate form of the substrate both irreversibly inactivate the enzyme by forming a covalent bond to Lys-18. Non-activated 5-formyltetrahydropteroylpentaglutamate protected against this inactivation. Substrate specificity studies showed that increasing the number of glutamate residues from zero to five on 5-formyltetrahydropteroate results in a 2 order of magnitude increase in the affinity of the substrate for the enzyme but only a 3-fold increase in the value of Vmax

Interference of dibutylphthalate on human prostate cell viability

Dibutylphthalate (DBP) is an environmental pollutant widely used as plasticizer in a variety of industrial applications worldwide. This agent can be found in personal-care products, children's toy, pharmaceuticals, food products. Exposure to DBP can occur via ingestion and inhalation as well as intravenous or skin contact. DBP belongs to the family of endocrine disrupting chemicals (EDCs) and its effects on reproductive system were demonstrated both in vivo and in vitro. In the present study we evaluated the effects of DBP on human prostate adenocarcinoma epithelial cells (LNCaP) in order to highlight xenoestrogens influence on human prostate. Moreover, we have compared DBP effects with 17β-estradiol action in order to investigate possible mimetical behaviour. We have assessed the effects of both compounds on the cell viability. After then, we have evaluated the expression of genes and proteins involved in cell cycle regulation. Furthermore, we have observed the expression and the cell localization of estrogen (ERs) and androgen (AR) receptors. In conclusion, we have demonstrated that DBP interacts with estrogen hormonal receptor pathway but differently from E2. DBP alters the normal gland physiology and it is involved in the deregulation of prostate cell cycle

Nonylphenol induces proliferation of prostate epithelial cell line (PNT1a)

Nonylphenol (NP) belongs to Endocrine Disrupting Chemicals (EDCs) with xenoestrogenic activity, called xenoestrogens, abundantly present in the environment. NP is widely used as surfactants in industrial and agricultural applications and in plastic formulations. Its xenoestrogenic activity was demonstrated both in vitro and in vivo. However, there are only few studies on the NP effects on prostate cell lines. Estrogens play an important role in development and growth of the prostate and may cause some pathologies, including cancer. Since NP mimics endogenous estrogens, it could have a negative influence on prostate physiology. In this study we examined the effects of NP and 17β-estradiol (E2) on the proliferation of non tumorigenic prostate epithelial cell line (PNT1A) and their interaction with estrogen receptors. These effects were also studied in presence of selective estrogen receptor antagonist ICI182,780. We found that both NP and E2 stimulate PNT1A proliferation in a dose-dependent manner, but the NP effects were lower than E2. Immunofluorescence and western blot analyses revealed that both NP and E2 induce cytoplasm-nucleus translocation of ERα. The nuclear localization of ERα by E2 was already shown after 2h of treatment and only after 6h by NP. The inhibition of these effects by adding ICI182,780 was shown. Surprisingly, NP and E2 didn’t affect the localization of ERβ. These results suggest that NP stimulates PNT1A proliferation probably through the interaction with ERα that in turn is involved in the activation of some prostate cell cycle key regulators

Peptide gH625 enters into neuron and astrocyte cell lines and crosses the blood-brain barrier in rats.

Peptide gH625, derived from glycoprotein H of herpes simplex virus type 1, can enter cells efficiently and deliver a cargo. Nanoparticles armed with gH625 are able to cross an in vitro model of the blood-brain barrier (BBB). In the present study, in vitro experiments were performed to investigate whether gH625 can enter and accumulate in neuron and astrocyte cell lines. The ability of gH625 to cross the BBB in vivo was also evaluated. gH625 was administered in vivo to rats and its presence in the liver and in the brain was detected. Within 3.5 hours of intravenous administration, gH625 can be found beyond the BBB in proximity to cell neurites. gH625 has no toxic effects in vivo, since it does not affect the maximal oxidative capacity of the brain or the mitochondrial respiration rate. Our data suggest that gH625, with its ability to cross the BBB, represents a novel nanocarrier system for drug delivery to the central nervous system. These results open up new possibilities for direct delivery of drugs into patients in the field of theranostics and might address the treatment of several human disease

BLAST Observations of the South Ecliptic Pole field: Number Counts and Source Catalogs

We present results from a survey carried out by the Balloon-borne Large Aperture Submillimeter Telescope (BLAST) on a 9 deg^2 field near the South Ecliptic Pole at 250, 350 and 500 {\mu}m. The median 1{\sigma} depths of the maps are 36.0, 26.4 and 18.4 mJy, respectively. We apply a statistical method to estimate submillimeter galaxy number counts and find that they are in agreement with other measurements made with the same instrument and with the more recent results from Herschel/SPIRE. Thanks to the large field observed, the new measurements give additional constraints on the bright end of the counts. We identify 132, 89 and 61 sources with S/N>4 at 250, 350, 500 {\mu}m, respectively and provide a multi-wavelength combined catalog of 232 sources with a significance >4{\sigma} in at least one BLAST band. The new BLAST maps and catalogs are available publicly at http://blastexperiment.info.Comment: 25 pages, 6 figures, 4 tables, Accepted by ApJS. Maps and catalogs available at http://blastexperiment.info

Health Technological Supports to Detect Medication Errors: The Saniarp Case-Study

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A Monte Carlo Approach to Evolution of the Far-Infrared Luminosity Function with BLAST

We constrain the evolution of the rest-frame far-infrared (FIR) luminosity function out to high redshift, by combining several pieces of complementary information provided by the deep Balloon-borne Large-Aperture Submillimeter Telescope surveys at 250, 350 and 500 micron, as well as other FIR and millimetre data. Unlike most other phenomenological models, we characterise the uncertainties in our fitted parameters using Monte Carlo Markov Chains. We use a bivariate local luminosity function that depends only on FIR luminosity and 60-to-100 micron colour, along with a single library of galaxy spectral energy distributions indexed by colour, and apply simple luminosity and density evolution. We use the surface density of sources, Cosmic Infrared Background (CIB) measurements and redshift distributions of bright sources, for which identifications have been made, to constrain this model. The precise evolution of the FIR luminosity function across this crucial range has eluded studies at longer wavelengths (e.g., using SCUBA and MAMBO) and at shorter wavelengths (e.g., Spitzer), and should provide a key piece of information required for the study of galaxy evolution. Our adoption of Monte Carlo methods enables us not only to find the best-fit evolution model, but also to explore correlations between the fitted parameters. Our model-fitting approach allows us to focus on sources of tension coming from the combination of data-sets. We specifically find that our choice of parameterisation has difficulty fitting the combination of CIB measurements and redshift distribution of sources near 1 mm. Existing and future data sets will be able to dramatically improve the fits, as well as break strong degeneracies among the models. [abridged]Comment: 20 pages, 14 figures, accepted to MNRA

Learning the fundamental mid-infrared spectral components of galaxies with non-negative matrix factorization

The mid-infrared (MIR) spectra observed with the Spitzer Infrared Spectrograph (IRS) provide a valuable data set for untangling the physical processes and conditions within galaxies. This paper presents the first attempt to blindly learn fundamental spectral components of MIR galaxy spectra, using non-negative matrix factorization (NMF). NMF is a recently developed multivariate technique shown to be successful in blind source separation problems. Unlike the more popular multivariate analysis technique, principal component analysis, NMF imposes the condition that weights and spectral components are non-negative. This more closely resembles the physical process of emission in the MIR, resulting in physically intuitive components. By applying NMF to galaxy spectra in the Cornell Atlas of Spitzer/IRS sources, we find similar components amongst different NMF sets. These similar components include two for active galactic nucleus (AGN) emission and one for star formation. The first AGN component is dominated by fine structure emission lines and hot dust, the second by broad silicate emission at 10 and 18 μm. The star formation component contains all the polycyclic aromatic hydrocarbon features and molecular hydrogen lines. Other components include rising continuums at longer wavelengths, indicative of colder grey-body dust emission. We show an NMF set with seven components can reconstruct the general spectral shape of a wide variety of objects, though struggle to fit the varying strength of emission lines. We also show that the seven components can be used to separate out different types of objects. We model this separation with Gaussian mixtures modelling and use the result to provide a classification tool. We also show that the NMF components can be used to separate out the emission from AGN and star formation regions and define a new star formation/AGN diagnostic which is consistent with all MIR diagnostics already in use but has the advantage that it can be applied to MIR spectra with low signal-to-noise ratio or with limited spectral range. The seven NMF components and code for classification are available at https://github.com/pdh21/NMF_software/

Spectral Energy Distributions of type 2 QSOs: obscured star formation at high redshifts

We present new mid-infrared and submillimetre observations for a sample of eight high redshift type-2 QSOs located in the Chandra Deep Field South. The sources are X-ray absorbed with luminosities in excess of 10^44 erg/s. Two of the targets have robust detections, S/N > 4, while a further three targets are marginally detected with S/N > =2.5. All sources are detected in multiple mid-infrared bands with the Spitzer Space Telescope. The multiwavelength spectral energy distributions (SEDs) of the type-2 QSOs are compared to those of two local ultraluminous galaxies (Arp220 and IR22491) in order to assess contributions from a star-forming component in various parts of the SED. We suggest that their submillimetre emission is possibly due to a starburst while a large fraction of the mid-infrared energy is likely to originate in the obscured central quasar. Using the mid-infrared and submm observations we derive infrared luminosities which are found to be in excess of L>10^12Lsun. The submillimetre (850micron) to X-ray (2 keV) spectral indices (alpha_SX) span a wide range. About half of the type-2 QSOs have values typical for a Compton-thick AGN with only 1 per cent of the nuclear emission seen through scattering and, the remaining with values typical of submm-bright galaxies. Combining the available observational evidence we outline a possible scenario for the early stages of evolution of these sources.Comment: Accepted for publication in MNRA

Quest for COSMOS Submillimeter Galaxy Counterparts using CARMA and VLA: Identifying Three High-redshift Starburst Galaxies

We report on interferometric observations at 1.3 mm at 2"-3" resolution using the Combined Array for Research in Millimeter-wave Astronomy. We identify multi-wavelength counterparts of three submillimeter galaxies (SMGs; F_(1mm) > 5.5 mJy) in the COSMOS field, initially detected with MAMBO and AzTEC bolometers at low, ~10"-30", resolution. All three sources—AzTEC/C1, Cosbo-3, and Cosbo-8—are identified to coincide with positions of 20 cm radio sources. Cosbo-3, however, is not associated with the most likely radio counterpart, closest to the MAMBO source position, but with that farther away from it. This illustrates the need for intermediate-resolution (~2") mm-observations to identify the correct counterparts of single-dish-detected SMGs. All of our three sources become prominent only at NIR wavelengths, and their mm-to-radio flux based redshifts suggest that they lie at redshifts z ≳ 2. As a proof of concept, we show that photometric redshifts can be well determined for SMGs, and we find photometric redshifts of 5.6 ± 1.2, 1.9^(+0.9)_(–0.5), and ~4 for AzTEC/C1, Cosbo-3, and Cosbo-8, respectively. Using these we infer that these galaxies have radio-based star formation rates of ≳ 1000 M_☉ yr^(–1) and IR luminosities of ~10^(13) L_☉ consistent with properties of high-redshift SMGs. In summary, our sources reflect a variety of SMG properties in terms of redshift and clustering, consistent with the framework that SMGs are progenitors of z ~ 2 and today's passive galaxies