long term administration of low doses of mycotoxins in poultry 1 residues of ochratoxin a in broilers and laying hens

Abstract The occurrence and amount of residues of ochratoxin A (OA) in poultry tissues and organs were investigated in a trial aimed at measuring the effects of contamination approaching the patterns more frequently found in natural situations (i.e., small doses of OA in the diet for long periods). Hubbard male broilers and laying hens were treated with an OA-contaminated feed (50 ppb) from the 14th day of age onward. Both groups were further divided into subgroups, some of which underwent continual treatment (64 and 169 days, respectively) and others that were withdrawn from administration (maximum 28 and 82 days, respectively). Determination of residues was performed by high performance liquid chromatography. Residues in liver were higher in broilers (up to 11.0 ppb) than in hens (1.5 ppb), whereas the reverse occurred in kidney (up to .8 and 5.8 ppb, respectively). Residues (.8 ppb) were also in hen thigh muscle but not in breast muscle. Residues of OA in poultry appear to be of possible public health concern. Suggestions for monitoring are given

Picosecond Internal Dynamics of Lysozyme as Affected by Thermal Unfolding in Nonaqueous Environment

AbstractA neutron-scattering investigation of the internal picosecond dynamics of lysozyme solvated in glycerol as a function of temperature in the range 200–410K has been undertaken. The inelastic contribution to the measured intensity is characterized by the presence of a bump generally known as “boson peak”, clearly distinguishable at low temperature. When the temperature is increased the quasielastic component of the spectrum becomes more and more intrusive and progressively overwhelms the vibrational bump. This happens especially for T>345K when the protein goes through an unfolding process, which leads to the complete denaturation. The quasielastic term is the superposition of two components whose intensities and linewidths have been studied as a function of temperature. The slower component describes motions with characteristic times of ∼4ps corresponding to reorientations of polypeptide side chains. Both the intensity and linewidth of this kind of relaxations show two distinct regimes with a crossover in the temperature range where the melting process occurs, thus suggesting the presence of a dynamical transition correlated to the protein unfolding. Conversely the faster component might be ascribed to the local dynamics of hydrogen atoms caged by the nearest neighbors with characteristic time of ∼0.3ps

Electronically synthesized Nyquist pulses for photonic sampling of microwave signals

We report electronic generation of optical Nyquist pulses using an arbitrary waveform generator (AWG) followed by a Mach Zehnder modulator (MZM), providing a simple, highly stable and flexible technique to perform photonic sampling. Here, we demonstrate the generation of 10 GHz periodic optical Nyquist pulses by synthesizing both all-positive and alternate positive-negative electrical pulse trains using a 25 GHz bandwidth AWG. Biasing the MZM at null ensures the meeting of the Nyquist ISI-free criterion in the optical domain and allows for pulse compression. Moreover, we report the first photonic sampling and demodulation of 1 Gbaud 16- and 32-QAM signals up to 22.5 GHz using 10 GHz optical Nyquist sampling pulse trains

Electron paramagnetic resonance (EPR) in medical dosimetry

This paper describes the fundamentals of electron paramagnetic resonance (EPR) and its application to retrospective measurements of clinically significant doses of ionizing radiation. X-band is the most widely used in EPR dosimetry because it represents a good compromise between sensitivity, sample size and water content in the sample. Higher frequency bands (e.g., W and Q) provide higher sensitivity, but they are also greatly influenced by water content. L and S bands can be used for EPR measurements in samples with high water content but they are less sensitive than X-band. Quality control for therapeutic radiation facilities using X-band EPR spectrometry of alanine is also presented

SMN protein promotes membrane compartmentalization of ribosomal protein S6 transcript in human fibroblasts

Alterations of RNA homeostasis can lead to severe pathological conditions. The Survival of Motor Neuron (SMN) protein, which is reduced in Spinal Muscular Atrophy, impacts critical aspects of the RNA life cycle, such as splicing, trafficking, and translation. Increasing evidence points to a potential role of SMN in ribosome biogenesis. Our previous study revealed that SMN promotes membrane-bound ribosomal proteins (RPs), sustaining activity-dependent local translation. Here, we suggest that plasma membrane domains could be a docking site not only for RPs but also for their encoding transcripts. We have shown that SMN knockdown perturbs subcellular localization as well as translation efficiency of RPS6 mRNA. We have also shown that plasma membrane-enriched fractions from human fibroblasts retain RPS6 transcripts in an SMN-dependent manner. Furthermore, we revealed that SMN traffics with RPS6 mRNA promoting its association with caveolin-1, a key component of membrane dynamics. Overall, these findings further support the SMN-mediated crosstalk between plasma membrane dynamics and translation machinery. Importantly, our study points to a potential role of SMN in the ribosome assembly pathway by selective RPs synthesis/localization in both space and time

H3 histamine receptor-mediated activation of protein kinase calpha inhibits the growth of cholangiocarcinoma in vitro and in vivo

Histamine regulates functions via four receptors (HRH1, HRH2, HRH3, and HRH4). The D-myo-inositol 1,4,5-trisphosphate (IP(3))/Ca(2+)/protein kinase C (PKC)/mitogen-activated protein kinase pathway regulates cholangiocarcinoma growth. We evaluated the role of HRH3 in the regulation of cholangiocarcinoma growth. Expression of HRH3 in intrahepatic and extrahepatic cell lines, normal cholangiocytes, and human tissue arrays was measured. In Mz-ChA-1 cells stimulated with (R)-(alpha)-(-)-methylhistamine dihydrobromide (RAMH), we measured (a) cell growth, (b) IP(3) and cyclic AMP levels, and (c) phosphorylation of PKC and mitogen-activated protein kinase isoforms. Localization of PKC alpha was visualized by immunofluorescence in cell smears and immunoblotting for PKC alpha in cytosol and membrane fractions. Following knockdown of PKC alpha, Mz-ChA-1 cells were stimulated with RAMH before evaluating cell growth and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation. In vivo experiments were done in BALB/c nude mice. Mice were treated with saline or RAMH for 44 days and tumor volume was measured. Tumors were excised and evaluated for proliferation, apoptosis, and expression of PKC alpha, vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF receptor 2, and VEGF receptor 3. HRH3 expression was found in all cells. RAMH inhibited the growth of cholangiocarcinoma cells. RAMH increased IP(3) levels and PKC alpha phosphorylation and decreased ERK1/2 phosphorylation. RAMH induced a shift in the localization of PKC alpha expression from the cytosolic domain into the membrane region of Mz-ChA-1 cells. Silencing of PKC alpha prevented RAMH inhibition of Mz-ChA-1 cell growth and ablated RAMH effects on ERK1/2 phosphorylation. In vivo, RAMH decreased tumor growth and expression of VEGF and its receptors; PKC alpha expression was increased. RAMH inhibits cholangiocarcinoma growth by PKC alpha-dependent ERK1/2 dephosphorylation. Modulation of PKC alpha by histamine receptors may be important in regulating cholangiocarcinoma growth. (Mol Cancer Res 2009;7(10):1704-13

Quasi-simultaneous INTEGRAL, SWIFT, and NuSTAR Observations of the New X-Ray Clocked Burster 1RXS J180408.9-342058

We report the quasi-simultaneous INTEGRAL, SWIFT, and NuSTAR observations showing spectral state transitions in the neutron star low-mass X-ray binary 1RXS J180408.9−342058 during its 2015 outburst. We present results of the analysis of high-quality broad energy band (0.8–200 keV) data in three different spectral states: high/soft, low/very-hard, and transitional state. The broadband spectra can be described in general as the sum of thermal Comptonization and reflection due to illumination of an optically thick accretion disk. During the high/soft state, blackbody emission is generated from the accretion disk and the surface of the neutron star. This emission, measured at a temperature of kT_(bb) ~ 1.2 keV, is then Comptonized by a thick corona with an electron temperature of ~2.5 keV. For the transitional and low/very-hard state, the spectra are successfully explained with emission from a double Comptonizing corona. The first component is described by thermal Comptonization of seed disk/neutron star photons (kT_(bb) ~ 1.2 keV) by a cold corona cloud with kT_e ~ 8–10 keV, while the second one originates from lower temperature blackbody photons (kT_(bb) ≤ 0.1 keV) Comptonized by a hot corona (kT_e ~ 35 keV). Finally, from NuSTAR observations, there is evidence that the source is a new clocked burster. The average time between two successive X-ray bursts corresponds to ~7.9 and ~4.0 ks when the persistent emission decreases by a factor of ~2, moving from a very hard to transitional state. The accretion rate (~4 x 10⁻⁹ M⊙ yr ⁻¹) and the decay time of the X-ray bursts longer than ~30 s suggest that the thermonuclear emission is due to mixed H/He burning triggered by thermally unstable He ignition

Viral hepatitis and iron dysregulation: molecular pathways and the role of lactoferrin

The liver is a frontline immune site specifically designed to check and detect potential pathogens from the bloodstream to maintain a general state of immune hyporesponsiveness. One of the main functions of the liver is the regulation of iron homeostasis. The liver detects changes in systemic iron requirements and can regulate its concentration. Pathological states lead to the dysregulation of iron homeostasis which, in turn, can promote infectious and inflammatory processes. In this context, hepatic viruses deviate hepatocytes' iron metabolism in order to better replicate. Indeed, some viruses are able to alter the expression of iron-related proteins or exploit host receptors to enter inside host cells. Lactoferrin (Lf), a multifunctional iron-binding glycoprotein belonging to the innate immunity, is endowed with potent antiviral activity, mainly related to its ability to block viral entry into host cells by interacting with viral and/or cell surface receptors. Moreover, Lf can act as an iron scavenger by both direct iron-chelation or the modulation of the main iron-related proteins. In this review, the complex interplay between viral hepatitis, iron homeostasis, and inflammation as well as the role of Lf are outlined

Different iron-handling in inflamed small and large cholangiocytes and in small and large-duct type intrahepatic cholangiocarcinoma

Cholangiocarcinoma (CCA) represents the second most common primary hepatic malignancy and originates from the neoplastic transformation of the biliary cells. The intrahepatic subtype includes two morpho-molecular forms: large-duct type intrahepatic CCA (iCCA) and small-duct type iCCA. Iron is fundamental for the cellular processes, contributing in tumor development and progression. The aim of this study was to evaluate iron uptake, storage, and efflux proteins in both lipopolysaccharide-inflamed small and large cholangiocytes as well as in different iCCA subtypes. Our results show that, despite an increase in interleukin-6 production by both small and large cholangiocytes, ferroportin (Fpn) was decreased only in small cholangiocytes, whereas transferrin receptor-1 (TfR1) and ferritin (Ftn) did not show any change. Differently from in vitro models, Fpn expression was increased in malignant cholangiocytes of small-duct type iCCA in comparison to large-duct type iCCA and peritumoral tissues. TfR1, Ftn and hepcidin were enhanced, even if at different extent, in both malignant cholangiocytes in comparison to the surrounding samples. Lactoferrin was higher in large-duct type iCCA in respect to small-duct type iCCA and peritumoral tissues. These findings show a different iron handling by inflamed small and large cholangiocytes, and small and large-duct type iCCA. The difference in iron homeostasis by the iCCA subtypes may have implications for the tumor management