Enhancement of the activity of phenoxodiol by cisplatin in prostate cancer cells

Phenoxodiol is a novel isoflav-3-ene, currently undergoing clinical trials, that has a broad in vitro activity against a number of human cancer cell lines. Phenoxodiol alone inhibited DU145 and PC3 in a dose- and time-dependent manner with IC50 values of 8±1 and 38±9 μM, respectively. The combination of phenoxodiol and cisplatin was synergistic in DU145, and additive in PC3, as assessed by the Chou–Talalay method. Carboplatin was also synergistic in combination with phenoxodiol in DU145 cells. The activity of the phenoxodiol and cisplatin combination was confirmed in vivo using a DU145 xenograft model in nude mice. Pharmacokinetic data from these mice suggest that the mechanism of synergy may occur through a pharmacodynamic mechanism. An intracellular cisplatin accumulation assay showed a 35% (P<0.05) increase in the uptake of cisplatin when it was combined in a ratio of 1 μM: 5 μM phenoxodiol, resulting in a 300% (P<0.05) increase in DNA adducts. Taken together, our results suggest that phenoxodiol has interesting properties that make combination therapy with cisplatin or carboplatin appealing

Coxiella burnetii, the Agent of Q Fever, Replicates within Trophoblasts and Induces a Unique Transcriptional Response

Q fever is a zoonosis caused by Coxiella burnetii, an obligate intracellular bacterium typically found in myeloid cells. The infection is a source of severe obstetrical complications in humans and cattle and can undergo chronic evolution in a minority of pregnant women. Because C. burnetii is found in the placentas of aborted fetuses, we investigated the possibility that it could infect trophoblasts. Here, we show that C. burnetii infected and replicated in BeWo trophoblasts within phagolysosomes. Using pangenomic microarrays, we found that C. burnetii induced a specific transcriptomic program. This program was associated with the modulation of inflammatory responses that were shared with inflammatory agonists, such as TNF, and more specific responses involving genes related to pregnancy development, including EGR-1 and NDGR1. In addition, C. burnetii stimulated gene networks organized around the IL-6 and IL-13 pathways, which both modulate STAT3. Taken together, these results revealed that trophoblasts represent a protective niche for C. burnetii. The activation program induced by C. burnetii in trophoblasts may allow bacterial replication but seems unable to interfere with the development of normal pregnancy. Such pathophysiologocal processes should require the activation of immune placental cells associated with trophoblasts

Assessment of comfort traveling in buses public transport

W artykule przedstawiono wyniki badań przeprowadzonych przez autorów w kołowych pojazdach komunikacji miejskiej. Opisano przyczyny powstawania drgań w autobusach oraz zagrożenia wynikające z narażenia organizmu człowieka na ich ekspozycję. Przedstawiono rozwiązania konstrukcyjne stosowane w autobusach miejskich oraz dokonano analizy wpływu poszczególnych elementów na drgania występujące w przestrzeni transportowej pojazdu. Obiektami badań były autobusy Przedsiębiorstwa Komunikacji Miejskiej Sosnowiec, w których prowadzono badania w warunkach normalnej eksploatacji. Przeprowadzone wnioskowanie pozwoliło na ocenę komfortu podróżowania na wybranych miejscach pasażerskich, rozmieszczonych równomiernie w całym pojeździe.The article presents the results of research conducted by the authors of wheeled transport vehicles. Described the causes of vibration in the buses and the risks resulting from exposure of the human body on their exposure. Presented construction solutions used in city buses and an analysis of the impact of individual components for vibration occurring in passenger space. Research facilities were buses from Sosnowiec Public Transport Company in which the study was conducted in normal transport operation. Carried out to assess the inference allowed the comfort of traveling on selected passenger seats, evenly distributed throughout the vehicle

Accurate and predictive antibody repertoire profiling by molecular amplification fingerprinting

High-throughput antibody repertoire sequencing (Ig-seq) provides quantitative molecular information on humoral immunity. However, Ig-seq is compromised by biases and errors introduced during library preparation and sequencing. By using synthetic antibody spike-in genes, we determined that primer bias from multiplex polymerase chain reaction (PCR) library preparation resulted in antibody frequencies with only 42 to 62% accuracy. Additionally, Ig-seq errors resulted in antibody diversity measurements being overestimated by up to 5000-fold. To rectify this, we developed molecular amplification fingerprinting (MAF), which uses unique molecular identifier (UID) tagging before and during multiplex PCR amplification, which enabled tagging of transcripts while accounting for PCR efficiency. Combined with a bioinformatic pipeline, MAF bias correction led to measurements of antibody frequencies with up to 99% accuracy. We also used MAF to correct PCR and sequencing errors, resulting in enhanced accuracy of full-length antibody diversity measurements, achieving 98 to 100% error correction. Using murine MAF-corrected data, we established a quantitative metric of recent clonal expansion—the intraclonal diversity index—which measures the number of unique transcripts associated with an antibody clone. We used this intraclonal diversity index along with antibody frequencies and somatic hypermutation to build a logistic regression model for prediction of the immunological status of clones. The model was able to predict clonal status with high confidence but only when using MAF error and bias corrected Ig-seq data. Improved accuracy by MAF provides the potential to greatly advance Ig-seq and its utility in immunology and biotechnology.ISSN:2375-254

SEAMLESS Global Change and Ecosystems D6.2.3.3: Documentation of baseline and policy scenarios to be assessed with Prototypes 2 and 3

This deliverable describes the construction of baseline and policy scenarios in Test Case 1 and 2 for the second and third prototypes of SEAMLESS-IF. It provides details of the methodology used in SEAMLESS-IP to build scenarios, and the data and parameters needed for the implementation of these scenarios in SEAMLESS-IF. These scenarios will be used to test the second and third prototypes of the integrated framework and its individual tools, especially the two backbone model chains: Data-base-APES-FSSIM-Indicators and Databases- APES-FSSIM-EXPAMOD-CAPRI-Indicators. The report is divided in two parts. The first part gives an overview of what we, in the SEAMLESS integrated project, define as a scenario. It also identifies the main elements for defining scenarios in agreement with the literature. After this overview, the steps defining scenarios in SEAMLESS-IF are identified and explained. The last section of the first part applies this approach to four typical user's problems that SEAMLESS-IF is designed to address: i) Green intensification at regional scale in animal-based farming systems(Auvergne), ii) Nitrate Directive at regional scale in crop based farming systems (Midi-Pyrenees), iii) Trade liberalisation at EU scale and iv) WTO and cotton policies in a LDC country (Sikasso and Koutiala regions of Mali). The second part of the report details the scenarios used in SEAMLESS-IF for Test Case 1 and 2 at EU and regional scales. The scenarios that can be developed depend on the availability of data as well as the model chain used for assessing the impact of the different EU policies and technological innovations. It proposes a template for the baseline and the policy scenarios compatible with the SEAMLESS-IF structure. More details on the parameters (premiums and constraints) of scenarios to be implemented by WP6 with prototype 2 and 3 are given in three sets of annexes: Annex 1: Concrete description of a SEAMLESS-IF project for four examples using the concepts highlighted in the document Explanation of the project definition V0.7: EU, Midi-Pyrennes, Auvergne and Mali. Annex 2: Scenarios to be carried out throughout EU regions with the third prototype. Annex 3: Scenarios to be carried out throughout some detailed regions for Prototype 2 and 3: Midi-Pyrenees (France), Auvergne (France), Zachodniopomorskie (Poland) and Koutiala