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Mutations of the haematopoietic master regulator RUNX1 are associated with acute myeloid leukaemia, familial platelet disorder and other haematological malignancies whose phenotypes and prognoses depend upon the class of the RUNX1 mutation. The biochemical behaviour of these oncoproteins and their ability to cause unique diseases has been well studied, but the genomic basis of their differential action is unknown. To address this question we compared integrated phenotypic, transcriptomic, and genomic data from cells expressing four types of RUNX1 oncoproteins in an inducible fashion during blood development from embryonic stem cells. We show that each class of mutant RUNX1 deregulates endogenous RUNX1 function by a different mechanism, leading to specific alterations in developmentally controlled transcription factor binding and chromatin programming. The result is distinct perturbations in the trajectories of gene regulatory network changes underlying blood cell development which are consistent with the nature of the final disease phenotype. The development of novel treatments for RUNX1-driven diseases will therefore require individual consideration.Liver radioembolization (RE) is an emerging treatment against liver primary and secondary tumours. The whole procedure of RE involves different health care specialists with different expertise. During the fractionation and infusion phases, the personnel manipulates high activities of 90Y. In our centre, the number of RE treatments per year is increasing; the aim of this study is to monitor the dose to the operators and to estimate the radiological risk for the operators involved in the RE. At present, two medical devices are approved Sir-Sphere® and Therasphere™, both loaded with 90Y. The dosimeters used were TLD placed over the fingertips, for a total of four dosimeters for each phase; the selected dose descriptor was Hp0.07. The study concerned 17 patients affected by malignant hepatic lesions, treated from September 2017 to March 2018. We performed 27 procedures 10 fractionations (with Sir-Sphere®) and 17 infusions to the patients (10 with Sir-Spheres®, seven with Theraspheres™). For fractionation phase, the average activity of each preparation was 3.34 GBq, the average value of Hp0.07 was 0.50 mSv. For infusion phase, the average activity was 1.51 GBq for Sir-Sphere® and 2.10 GBq for Theraspheres™, the average value of Hp0.07 was 0.10 mSv. No significant differences were found between senior (Hp0.07 = 0.08 mSv) and young operators (Hp0.07 = 0.09 mSv), respectively. Similarly, no significant differences were found between the right and left hand, with the same average value of Hp0.07 (0.01 mSv). In conclusion, the results are encouraging, since fingertips reported doses very low. The handling of 90Y microspheres and the RE procedure can be carried out under safe conditions.Intellectual disabilities (ID) are a type of neurodevelopmental disorder (NDD). They can have a genetic cause, including an emerging class of ID centring around Rho GTPases, such as Ras-related C3 botulinum toxin substrate 1 (RAC1). Guidelines for establishing genetic causality include the use of cellular models, which often have morphological aberrations, a long-standing hallmark of ID. Disease cellular models can facilitate high-throughput screening (HTS) of chemical or genetic perturbations, which can provide translatable biological insight. Here, we discuss a class of IDs centring around RAC1. We review novel and established cellular models of ID, including mouse and human primary cells and reprogrammed or induced neurons. Finally, we review progress and remaining challenges in the adoption of HTS methodologies by the community studying neurological disorders.Fungal contamination is a concern for the food industry. Fungal spores resist food sterilization treatments and produce mycotoxins that are toxic for animals and humans. Technologies that deactivate spores and toxins without impacting food quality are desirable. This study demonstrates the efficiency of a high voltage atmospheric cold plasma (HVACP) technology using air to generate reactive oxygen (ROS) and nitrogen (RNS) species for the degradation of Aspergillus flavus cultures and the deoxynivalenol (DON) mycotoxin. Optical emission and absorption spectroscopy demonstrate ionization of hydroxyl groups, atomic oxygen and nitrogen, and confirm production of ROS and RNS, e.g. O3, NO2, NO3, N2O4, and N2O5. Fungal cultures show a depletion in pigmentation and an ~50% spore inactivation after 1-min treatments. Treated spores show surface ablation and membrane degradation by scanning electron microscopy. Twenty-minute direct HVACP treatments of 100 μg of DON in one mL aqueous suspensions resulted in a greater than 99% reduction in DON structure and rescued over 80% of Caco-2 cell viability; however, the same treatment on 100 μg of powdered DON toxin only showed a 33% reduction in DON and only rescued 15% of cell viability. In summary, HVACP air treatment can inactivate both fungal spores and toxins in minutes.Spores from 21 strains from different genera were heat-treated and stored in different sets of process conditions (4 temperatures and 3 pH levels) defined to prevent growth. In these conditions, spores surviving the heat treatment progressively lost viability during storage. Different inactivation curve shapes (linear, shoulder and tailing) and different sensitivities to storage were observed. B. coagulans showed the fastest inactivation kinetics, with more than 4-log reduction of spore population within 24 h after heating and G. stearothermophilus displayed slower inactivation kinetics, whereas all the anaerobic strains studied (M. thermoacetica and Thermoanaerobacterium spp.) proved resistant to storage conditions, with no destruction detected during 90 days in most cases. Inactivation rates were relatively unaffected by sub-lethal pH but sharply accelerated by temperature Inactivation became faster as temperature increased (in the 8 °C-55 °C temperature range), with growth blocked by low pH in sub-lethal temperatures. There were changes in surviving spore numbers after the heat-treatment phase. This has implications and applications in canned food industries, as the probability of a retorted sample testing as non-stable, meaning possible spoilage, may decrease with time. In simple terms, a batch of low-acid canned food that tests as non-shelf-stable after an incubation test i.e. positive growth conditions, may later become negative if stored at room temperature (below the minimal growth temperature for thermophilic spores), which may change the marketability of the batch.The objective of this study was to compare the effect of current (10 °C for 10 h followed by 0 °C with a low fan speed) versus four alternative beef carcass chilling regimes, ranging from -6 °C to 0 °C and wind speeds between 1.5 and 6 m/s on the microbiology of beef carcasses. NHWD-870 cost The temperature and relative humidity (RH) in the chillers, the carcass core and surface temperature, pH, water activity (aw) and carcass weight (drip) loss were recorded. Bacterial concentrations (total viable counts (TVC), total Enterobacteriaceae counts (TEC), Pseudomonas spp., lactic acid bacteria (LAB) and Brochothrix thermosphacta) were also monitored. Similar pH, aw and drip loss (2%) values were obtained regardless of chilling regime. For the most part, bacterial concentrations were also similar and, where statistically significant (P less then 0.05) counts occurred, the reductions were low (≤1 log10 cfu/cm2). It was concluded that the current chilling regime was as effective as the tested alternatives in terms of the bacterial quality of the carcasses.To investigate the persistence of acid tolerance response (ATR) and the regulatory mechanism during chilled storage, Salmonella ATCC 14028 and the △phoP mutant were acid adapted and then incubated in meat extract at 4 °C for 24 days as simulated beef storage. The bacterial population, D values and expression of PhoP/PhoQ linked genes of both strains were determined at 6-day intervals. Although a mild suppression effect on the D values of adapted Salmonella was found during the long-time storage in meat extract at 4 °C, the D value of adapted strains was significantly higher than non-adapted strains, indicating the persistence of ATR during the whole aging and distribution of beef posing a threat to food safety. The fact that low temperature inhibits the formation of ATR at the early adapted stage emphasizes the importance of keeping a low-temperature environment during slaughter. An interaction between the acidic adaptation and phoP gene on D values was found and the expression levels of adiA, adiY, cadA and cadB genes was significantly reduced in the △phoP mutant, suggesting that PhoP/Q system plays an important role in the ATR by sensing the pH and regulating lysine and arginine decarboxylation directly or indirectly.The objective of this study was the characterization of the microbiota associated with spoilage of vanilla cream pudding during storage at different temperatures. Commercial cream samples were stored aerobically at 4, 8, 12 and 15 °C for a maximum time period of 40 days. At appropriate time intervals, cream samples were subjected to (i) microbiological analyses, and (ii) high-performance liquid chromatography (HPLC). Furthermore, the spoilage microbiota was identified through repetitive extragenic palindrome-PCR, while selected isolates were further characterized based on sequencing of the V1-V3 region of the 16S rRNA gene. Microbial growth was observed only during storage of cream samples at 12 and 15 °C, with the applied genotypic analysis demonstrating that Bacillus subtilis subsp. subtilis was the dominant spoilage microorganism of this product. Based on the HPLC analysis results, citric acid and sucrose were the most abundant organic acid and sugar, respectively throughout storage of cream pudding, whereas notable changes mainly included (i) increase in the concentration of lactic acid and to a lesser extent of formic and acetic acids, and (ii) increase in the concentration of glucose and fructose at the expense of sucrose and lactose. The results of this study should be useful for the dairy industry in detecting and controlling microbiological spoilage in cream pudding and other chilled, neutral-pH dairy desserts.Higher alcohols are important flavor substance in alcoholic beverages. The content of α-amino nitrogen (α-AN) in the fermentation system affects the formation of higher alcohols by Saccharomyces cerevisiae. In this study, the effect of α-AN concentration on the higher alcohol productivity of yeast was explored, and the mechanism of this effect was investigated through metabolite and transcription sequence analyses. We screened 12 most likely genes and constructed the recombinant strain to evaluate the effect of each gene on high alcohol formation. Results showed that the AGP1, GDH1, and THR6 genes were important regulators of higher alcohol metabolism in S. cerevisiae. This study provided knowledge about the metabolic pathways of higher alcohols and gave an important reference for the breeding of S. cerevisiae with low-yield higher alcohols to deal with the fermentation system with different α-AN concentrations in the brewing industry.
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