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Also genetic depletion of key players in the apoptotic and necroptotic pathway (BAK, BAX, and RIPK1) confirmed the pharmacological data. Interestingly however, electron microscopy of fenretinide-treated cells revealed an excessive accumulation of cytoplasmic vacuoles, which were distinct from autophagosomes. Further flow cytometry and fluorescence microscopy experiments suggested a hyperstimulation of macropinocytosis, leading to an accumulation of enlarged early and late endosomes. Surprisingly, pharmacological inhibition as well as genetic depletion of large dynamin GTPases completely abolished fenretinide-induced vesicle formation and subsequent cell death, suggesting a new form of dynamin-dependent programmed cell death. Taken together, our data identify a new form of cell death mediated through the production of ROS by fenretinide treatment, highlighting the value of this compound for treatment of sarcoma patients including FP-RMS.Salinity is a critical abiotic stress, which significantly impacts the agricultural yield worldwide. Identification of the molecular mechanisms underlying the salt tolerance in euhalophyte Suaeda salsa is conducive to the development of salt-resistant crops. In the present study, high-throughput RNA sequencing was performed after S. salsa leaves were exposed to 300 mM NaCl for 7 days, and 7,753 unigenes were identified as differently expressed genes (DEGs) in S. salsa, including 3,638 increased and 4,115 decreased unigenes. Moreover, hundreds of pathways were predicted to participate in salt stress response in S. salsa by Gene Ontology (GO), MapMan and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, including ion transport and sequestration as well as photoprotection of photosystem (PS) II. The GO enrichment analysis indicated that genes related to ion transport, reactive oxygen species (ROS) scavenging and transcriptional factors were highly expressed upon NaCl treatment. The excessive Na+ and Cl- ions were supposed to be absorbed into the vacuole for ion sequestration and balance adjustment by potassium transporters (such as KEA3) with high expressions. Moreover, we predicted that mutiple candidate genes associated with photosynthesis (such as PSB33 and ABA4), ROS (such as TAU9 and PHI8) and transcriptional regulation (HB-7 and MYB78) pathways could mitigate salt stress-caused damage in S. salsa.The continued use of pyrazinamide in the treatment of tuberculosis in the absence of a rapid, accurate and standardized pyrazinamide drug susceptibility assays is of great concern. While whole genome sequencing holds promise, it is not yet feasible option in low resource settings as it requires expensive instruments and bioinformatic analysis. We investigated the diagnostic performance of a closed-tube Linear-After-The-Exponential (LATE)-PCR assay for pyrazinamide susceptibility in Mycobacterium tuberculosis. Based on a set of 654 clinical Mycobacterium tuberculosis culture isolates with known mutations throughout the pncA gene as determined by Sanger sequencing, the assay displays excellent sensitivity of 96.9% (95% CI 95.2-98.6) and specificity of 97.9% (95% CI 96.1-99.7). In a subset of 384 isolates with phenotypic drug susceptibility testing, we also observed high sensitivity of 98.9% (95% CI 97.5-100) but lower specificity of 91.8% (95% CI 87.9-95.8) when compared to phenotypic drug susceptibility testing. We conclude that the LATE PCR assay offers both a rapid and accurate prediction of pyrazinamide susceptibility.BACKGROUND/OBJECTIVES The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE) study showed that individuals who are nonobese were able to undergo significant calorie restriction (CR), yet the time course changes in adherence, weight, and appetite are unknown. This analysis aimed to investigate the time course changes in adherence, body weight, and appetite during the CALERIE study. SUBJECTS/METHODS Overall, 143 participants (body mass index 21.9-28.0 kg/m2) were randomized to a CR group that aimed to achieve 25% CR for 2 years. Throughout the intervention, body weight was measured, and appetite was assessed through visual analogue scales. Algorithms were utilized with body weight measurements to calculate adherence percentile score. Participants targeted an adherence percentile score of 50, though being between 80 (lowest acceptable adherence) and 10 (highest acceptable adherence) was adequate. Polynomial regression analyses were used to assess time course changes. RESULTS Polynomials indicated that adherence percentile score increased above 50 after approximately week 20, although adherence remained acceptable (adherence percentile score less than 80) (R2 = 0.89; P  less then  0.001). Weight loss occurred until approximately week 60 and then plateaued (R2 ≥ 0.92; P  less then  0.001). Syk inhibitor Hunger and thirst increased (R2 ≥ 0.30; P  less then  0.001), but the total increase in scale scores were less then 10 mm throughout the intervention. CONCLUSIONS In individuals who are nonobese, adherence to 25% CR declines after 20 weeks, but 2 years of CR that stimulates a meaningful reduction in weight, promotes aging-related benefits and negligibly affects appetite is viable.Cereal/legume intercropping is likely to achieve the optimal exploitation of soil and atmospheric nitrogen (N) sources to maintain high production and quality levels with low N inputs, as an attempt to eliminate underlying environmental effects. Nevertheless, the extent of the effect of cereal/legume intercropping on nodulation and N fixation of intercropped legumes in root interaction requires extensive verification. In the present study, root interaction of alfalfa/triticale intercropping was simulated in pots with the use of root separation types (pot with no barrier (A-T), pot with nylon mesh barrier (NA-T), pot with plastic barrier (PA-T), and alfalfa alone (SA)) in pots. Moreover, the experiment was measured at a range of N levels (N21, N210) and growing stages (branching, budding and initial flowering stages) in growth chamber. As alfalfa was growing, the total nodule number (TNN), effective nodule number (ENN) and nitrogenase activity (NA) of alfalfa with A-T and other cropping systems more noticeably differed from each other at higher N levels, whereas their diversification was reduced at lower N levels.