Temporal and thermal evolution of extensional faulting in the central Gulf of Suez and detrital zircon (U-Th)/He constraints on the thermo-tectonic Paleozoic and Mesozoic history of the Sinai, Egypt

Many fundamental concepts of rifting have been influenced by observation made in the Gulf of Suez as a result of detailed structural and sedimentological studies. Although the three-dimensional structural geometry of the rift is well understood, the timing of faulting, the nature of faults linkage during progressive rifting and the influence on syn-rift sedimentation is poorly constrained. Despite ample fission track data from the Sinai rift flank, the lack of thermochronometric data from exhumed pre-rift sedimentary cover and crystalline basement blocks in a proper structural context within the rift limit the temporal and thermal reconstruction and the influence of pre-rift structures on the style of rifting. To elucidate the temporal and spatial evolution of extensional faulting and fault interaction in the central Gulf of Suez, this study presents new apatite (U-Th)/He (AHe) thermochronometric data from vertical transects and combines both surface and borehole sample arrays from normal fault blocks, integrated with structural block reconstruction of the central east margin of the Gulf of Suez. AHe data from the Sinai border fault complex at Gebel Samra (north) and Gebel Mutga (south) and surface and subsurface samples from the Hamman Faraun fault blocks explore the temporal progression of normal faulting and the evolution of fault hard linkage in the central Gulf of Suez in the early to middle Miocene after the onset of normal faulting at ~23 Ma. As a second aspect, zircon (U-Th)/He (ZHe) dating from pre-rift strata and basement samples were analyzed to better constrain the pre-Tertiary tectonic, detrital provenance and thermal evolution of the Gulf of Suez to shed light on the Paleozoic/Mesozoic tectonic evolution and its influence on Red Sea-Gulf of Suez rifting. ZHe data from pre-rift strata in the central Gulf of Suez record a detailed Paleozoic/Mesozoic tectonic history that is highly influenced by Carboniferous, Triassic/Jurassic, and Santonian tectonism. Carboniferous Abu Thora sandstone contain detrital ZHe ages that suggest very short lag time, indicative of late Paleozoic tectonism and rapid cooling. Similarly, Triassic Qiseib sandstones, exhibits detrital ZHe ages indistinguishable from its stratigraphic age, underlining the importance of Triassic/Jurassic Neo-Tethyan rifting. Cretaceous Matulla pre-rift sandstones are dominated by Santonian detrital ZHe ages, with very short lag times, associated with the Syrian arc inverted structures and folding. The combination of AHe and ZHe ages in a detailed stratigraphic and structural context elucidates both the Neogene Gulf of Suez rift evolution and the impact of Paleozoic/Mesozoic tectonism on the structural grain of the gulf allowing for a more detailed and spatially differentiated understanding of the timing of extensional faulting and nature of fault linkage during progressive early to middle Miocene rifting in the central Gulf of Suez

Neutralizing antibodies against porcine circovirus type 2 in liquid pooled plasma contribute to the biosafety of commercially manufactured spray-dried porcine plasma

Neutralizing antibodies (NA) inherently present in pooled plasma collected at commercial abattoirs may provide some protection against potential porcine circovirus type 2 (PCV2) infectivity of plasma. Moreover, these NA may also contribute to the biosafety of spray-dried porcine plasma (SDPP). The objective of the study was to characterize and quantify the PCV2 antibody neutralizing capacity in pooled liquid porcine plasma and SDPP samples collected from industrial spray-drying facilities located in the Southeast and Midwest regions of the United States and the Northeast region of Spain. In the United States, PCV2 NA was determined in 1 sample of pooled liquid plasma from commercial spray-drying plants in the Southeast and 1 from the Midwest region. Obtained results were compared with those of a plasma sample from a PCV2 vaccinated sow and 1 from a PCV2 antibody negative sow. In Spain, 15 pooled liquid porcine plasma samples and 10 SDPP samples were collected at a commercial spray-drying plant total and NA against PCV2 were determined. Results with pooled liquid porcine plasma from commercial spray-drying facilities in the United States indicated that NA titers against PCV2 in these samples (log2 8.33 ± 0.41 and 9.0 ± 0.0) were similar or greater than the plasma from the PCV2-vaccinated sow (log2 6.33 ± 0.41). The analysis of U.S. samples indicated that liquid plasma diluted to 1:256 (10–2.41) was able to neutralize between 100 to 200 PCV2 virus particles or about 4 logs10 median tissue culture infective dose (TCID50) per milliliter. Similarly, samples from the Spanish pooled liquid plasma and the SDPP samples indicated an increased amount of NA activity against PCV2. Specifically, a dilution of 10–2.47 ± 0.33 of plasma was able to inactivate 100 PCV2 virus particles; therefore, the inactivation capacity of commercial liquid plasma was greater than 104 TCID50/mL. The calculated 90% reduction in infected cells because of NA in pooled plasma samples (log2 8.2 ± 0.38) was less (P < 0.05) than in its concentrate form of SDPP (mean, log2 10.2 ± 0.85). In conclusion, PCV2 NA contained in liquid pooled plasma from market pigs was detected at greater concentrations than that from a vaccinated sow and that after spray-drying biological neutralizing activity was conserved, which implies that the inherent NA in liquid plasma may have an important role in the biosafety of commercially produced SDPP.info:eu-repo/semantics/publishedVersio

High-throughput screening methodology to identify alpha-synuclein aggregation inhibitors

An increasing number of neurodegenerative diseases are being found to be associated with the abnormal accumulation of aggregated proteins in the brain. In Parkinson’s disease, this process involves the aggregation of alpha-synuclein (a-syn) into intraneuronal inclusions. Thus, compounds that inhibit a-syn aggregation represent a promising therapeutic strategy as disease-modifying agents for neurodegeneration. The formation of a-syn amyloid aggregates can be reproduced in vitro by incubation of the recombinant protein. However, the in vitro aggregation of a-syn is exceedingly slow and highly irreproducible, therefore precluding fast high throughput anti-aggregation drug screening. Here, we present a simple and easy-to-implement in-plate method for screening large chemical libraries in the search for a-syn aggregation modulators. It allows us to monitor aggregation kinetics with high reproducibility, while being faster and requiring lower protein amounts than conventional aggregation assays. We illustrate how the approach enables the identification of strong aggregation inhibitors in a library of more than 14, 000 compounds

Schmallenberg virus detection in Culicoides biting midges in Spain: First laboratory evidence for highly efficient infection of Culicoides of the Obsoletus complex and Culicoides imicola

Since Schmallenberg disease was discovered in 2011, the disease rapidly spread across Europe. Culicoides biting midges have been implicated as putative Schmallenberg vectors in Europe. The detection of Schmallenberg virus (SBV) in field collected Culicoides was evaluated through retrospective (2011–2012) collections and captures performed in 2013. This study represents the first detection of SBV in field collected Culicoides in Spain. Infectious midges were detected at the foothills of Pyrenees, Aramunt, in the summer 2012. All the specimens infected with Schmallenberg were of the species Culicoides obsoletus s.s. confirming its putative vector status in Spain. Experimental infection on field collected Culicoides provided evidence of atypical high efficiency for SBV vector infection and transmission potential in local populations of Culicoides imicola and in Culicoides of the Obsoletus complex. However, captured individuals of C. imicola were more susceptible to SBV infection than C. obsoletus s.l. (p < .001), with an infection ratio of 0.94 and 0.63, respectively. In contrast, a Culicoides nubeculosus colony appeared to be refractory to SBV infection.info:eu-repo/semantics/acceptedVersio

Combined effects of spray‐drying conditions and postdrying storage time and temperature on Salmonella choleraesuis and Salmonella typhimurium survival when inoculated in liquid porcine plasma

The objective of this study was to determine the effectiveness of the spray-drying process on the inactivation of Salmonella choleraesuis and Salmonella typhimurium spiked in liquid porcine plasma and to test the additive effect of immediate postdrying storage. Commercial spray-dried porcine plasma was sterilized by irradiation and then reconstituted (1:9) with sterile water. Aliquots of reconstituted plasma were inoculated with either S. choleraesuis or S. typhimurium, subjected to spray-drying at an inlet temperature of 200°C and an outlet temperature of either 71 or 80°C, and each spray-drying temperature combinations were subjected to either 0, 30 or 60 s of residence time (RT) as a simulation of residence time typical of commercial dryers. Spray-dried samples were stored at either 4·0 ± 3·0°C or 23·0 ± 0·3°C for 15 days. Bacterial counts of each Salmonella spp., were completed for all samples. For both Salmonella spp., spray-drying at both outlet temperatures reduced bacterial counts about 3 logs at RT 0 s, while there was about a 5·5 log reduction at RT 60 s. Storage of all dried samples at either 4·0 ± 3·0°C or 23·0 ± 0·3°C for 15 days eliminate all detectable bacterial counts of both Salmonella spp.info:eu-repo/semantics/publishedVersio

Lung myofibroblasts are characterized by down-regulated cyclooxygenase-2 and its main metabolite, prostaglandin E2.

Background: Prostaglandin E2 (PGE2), the main metabolite of cyclooxygenase (COX), is a well-known anti-fibrotic agent. Moreover, myofibroblasts expressing a-smooth muscle actin (a-SMA), fibroblast expansion and epithelial-mesenchymal transition (EMT) are critical to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our aim was to investigate the expression of COX-2 and PGE2 in human lung myofibroblasts and establish whether fibroblast-myofibroblast transition (FMT) and EMT are associated with COX-2 and PGE2 down-regulation. Methods: Fibroblasts obtained from IPF patients (n = 6) and patients undergoing spontaneous pneumothorax (control,n = 6) and alveolar epithelial cell line A549 were incubated with TGF-b1 and FMT and EMT markers were evaluated. COX-2 and a-SMA expression, PGE2 secretion and cell proliferation were measured after IL-1b and PGE2 incubation. Results: Myofibroblasts from both control and IPF fibroblast cultures stimulated with IL-1b showed no COX-2 expression. IPF fibroblasts showed increased myofibroblast population and reduced COX-2 expression in response to IL-1b. TGF-b1 increased the number of myofibroblasts in a time-dependent manner. In contrast, TGF-b1 induced slight COX-2 expression at 4 h (without increase in myofibroblasts) and 24 h, but not at 72 h. Both IPF and control cultures incubated with TGF-b1 for 72 h showed diminished COX-2 induction, PGE2 secretion and a-SMA expression after IL-1b addition. The latter decreased proliferation in fibroblasts but not in myofibroblasts. A549 cells incubated with TGF-b1 for 72 h showed downregulated COX-2 expression and low basal PGE2 secretion in response to IL-1b. Immuno-histochemical analysis of IPF lung tissue showed no COX-2 immuno-reactivity in myofibroblast foci. Conclusions: Myofibroblasts are associated with COX-2 down-regulation and reduced PGE2 production, which could be crucial in IPF development and progression

UV-C irradiation is able to inactivate pathogens found in commercially collected porcine plasma as demonstrated by swine bioassay

Liquid porcine plasma is an animal origin raw material for the manufacturing process of spray-dried porcine plasma that is used in pig nutrition worldwide. In previous studies we found that the application of ultraviolet light C (UV-C) in liquid plasma that was inoculated with a variety of bacteria or viruses of importance in the swine industry can be considered as redundant safety steps because in general achieve around 4 logs reduction for most of these pathogens. However, the final validation of the UV-C light as safety feature should be conducted with commercial liquid plasma and using the pig bioassay model. As a first objective, the potential infectivity of a raw liquid plasma product collected from an abattoir was tested by means of a swine bioassay. We used Porcine circovirus 2 (PCV-2), a ubiquitous virus that has been systematically detected by PCR in porcine plasma at abattoirs as selection criteria for commercial liquid plasma lot. As a second aim of the study, the effects of different doses of UV-C irradiation on the selected raw liquid plasma were assayed in the animal bioassay. Moreover, other swine infecting agents, including Porcine reproductive and respiratory syndrome virus (PRRSV), were also determined in the original plasma and monitored in the inoculated animals. Pigs negative for PCV-2 and PRRSV genome and antibodies were allotted to one of five groups (6 to 8 pigs/ group) and injected intra-peritoneally with 10 mL of their assigned inoculum at 50 d of age. Negative control pigs (group 1) were injected with PBS. Positive control pigs (group 5) were injected with a PCV-2 inoculum. Groups 2, 3 and 4 were injected with liquid porcine plasma that had been subjected to 0 (raw plasma), 3000 or 9000 J/L UV-C irradiation, respectively. Group 2 pigs (0 J/L UV-C) got infection by PRRSV but no PCV-2 infection or seroconversion. However, one pig from group 2 seroconverted to Rotavirus A (RVA) and Hepatitis E virus (HEV) and three group 2 pigs seroconverted to Porcine parvovirus (PPV). Groups 1, 3 and 4 pigs showed no evidence of infection or seroconversion associated with the tested viruses or any other pathogens found in the liquid plasma before UV-C irradiation. Group 5 pigs developed PCV-2 infectivity as expected. UV-C irradiation of liquid plasma at 3000 and 9000 J/L was effective in preventing PRRSV and other pathogens transmission. Moreover, raw liquid plasma was non-infectious for PCV-2 in naïve pigs.info:eu-repo/semantics/publishedVersio

Low prostaglandin E2 and cyclooxygenase expression in nasal mucosa fibroblasts of aspirin-intolerant asthmatics.

Background and objective: Anomalies in the regulation of cyclooxygenase (COX)-1 and-2 have been described in nasal polyps of aspirin-induced asthma (AIA). Whether these anomalies are specific to nasal polyps or affect all the nasal mucosa (NM) of upper airways is still unclear. The objective of this study was to compare the COX pathway in NM of AIA patients with the NM of control subjects. Methods: Fibroblasts were isolated from NM of 5 AIA patients (AIA-NM) and 5 control subjects (control-NM). Cells were treated with 10 ng/ml IL-1b for up to 72 hours. Prostaglandin E2 (PGE2) production was measured by ELISA, expression of COX-1 protein by Western blot, and COX-2 protein by ELISA, Western blot and immunofluorescence techniques. Results: IL-1b increased PGE2 production and COX-1 protein expression in control-NM fibroblasts, but no changes were found in AIA-NM. IL-1b provoked a significant timedependent increase in COX-2 protein expression in control-NM fibroblasts but had a very mild effect on COX-2 protein expression in AIA-NM. Conclusions: Our data suggest that abnormalities in the COX pathway are not a phenomenon exclusive to nasal polyp mucosa as they are also present in all the nasal mucosa of AIA patients. These anomalies may be involved in the pathogenesis of airway inflammation and NSAID intolerance in asthma patients with chronic rhinosinusitis and nasal polyposis