The enhanced contrast areas in the chromosome were ascribed to the presence of iodine contents from erythrosine dye. The presented labeling approach might be a powerful strategy to reveal the structural and dynamic changes in natural DNA replication including the relationship between newly synthesized in vivo nucleic acid and the physiological state of the cell. © 2020 Wiley Periodicals, Inc.Hydrogen sulfide (H2 S), a high-threat chemical agent, occurs naturally in a variety of settings. Despite multiple incidents of exposures and deaths, no FDA-approved antidote exists. A rapid-acting, easy to administer antidote is needed. We conducted a randomized control trial in swine comparing intramuscular administration of aminotetrazole cobinamide (2.9 mL, 18 mg/kg) to no treatment following inhalation of H2 S gas. We found that aminotetrazole cobinamide administered 2 min after the onset of respiratory depression-defined as a tidal volume of less than 3 mL/kg for 2 consecutive minutes-yielded 100% survival, while all control animals died. Respiratory depression resolved in the treatment group within 3.6 ± 1.5 min (mean ± SD) of cobinamide administration, whereas control animals had intermittent gasping until death. Blood pressure and arterial oxygen saturation (SO2 ) returned to baseline values within 5 and 10 min, respectively, of cobinamide treatment, and plasma lactate concentration decreased to less than 50% of the highest value by the end of the experiment. In control animals, plasma lactate rose continuously until death. We conclude that intramuscular aminotetrazole cobinamide is effective in a large animal, inhalational model of acute, severe H2 S poisoning. © 2020 New York Academy of Sciences.This study was undertaken to assess in vivo the corrosion in two commercial nickel-titanium (NiTi) orthodontic archwires removed from the oral cavity of patients using fluoride mouthwashes. Five volunteers took part in this study on the corrosion behavior of two brands of NiTi archwires (3M and AO (brand of archwire)) during use of two mouthwashes with neutral sodium fluoride 1.1%, one with acidulated fluoride 1.1%, and one with placebo and a control group. Each patient used one mouthwash in three different periods of time for 1 min a day for 30 days. The archwires were assessed with scanning electron microscopy and atomic force microscopy for qualitative and quantitative analysis. The values obtained with atomic force microscopy (AFM) were submitted to normality test, two-way analysis of variance, and Tukey’s test at a significance level of 5%. The AFM images showed a gradual qualitative increase in the roughness of both types of wire between the treatments control  less then  placebo  less then  neutral fluoride  less then  acidulated fluoride. The arithmetic average of the roughness and root mean square of the roughness were similar. As for 3M archwires, only the acidulated fluoride group differed statistically from the others. As for AO archwires, the control and placebo groups did not differ from each other, but differed from the other fluoride treatments. The group using neutral fluoride also differed significantly from the acidulated fluoride group. 3M archwires were not affected by daily oral challenges. AO archwires were not affected by daily oral challenges either; their association with fluoride, either neutral or acidulated, increased their roughness. © 2020 Wiley Periodicals, Inc.Anatomical study of leaf xylary vessel elements of Carthamus oxycantha under various intensities of lead (Pb) and nickel (Ni) stress (200, 400, 600, and 800 mg Pb(NO3 )2 , NiCl2 ·6H2 O/kg of the soil) was conducted. The deformations caused due to metal stress were detected using point-based image registration technique. Initially, a set of corresponding feature points called landmarks was selected for warping of two-dimensional microscopic images of deformed/source vessel (stressed) to its normal/target (unstressed) counterpart. The results show that the target registration error is less than 3 mm using real plant image datasets. The stress caused alterations mainly in diameter, size, and shape of the cells. Average cell diameter and average wall diameter of vessels were measured with „Image J.” The range of decrease in average cell diameter from 18.566 to 13.1 μm and the range of increase in average wall diameter was from 5.166 to 10.1 μm, with increase in stress factor through 200, 400, 600, and 800 mg Pb(NO3 )2 , NiCl2 ·6H2 O/kg of the soil. We noted large deformation in the form of shrinkage in cell size and diminution in its diameter. The diminution in diameter and the shrinkage in cell size of vessel cells may be due to the deposition of wall materials. It can be a possible strategy to limit the water flow to overcome the rapid mobility and transportation of the excess amount of metals to safeguard the cellular components from unpleasant consequences of metallic stress. © 2020 Wiley Periodicals, Inc.Methyl isocyanate (MIC, „Bhopal agent”) is a highly reactive, toxic industrial chemical. Inhalation of high levels (500-1000 ppm) of MIC vapor is almost uniformly fatal. No therapeutic interventions other than supportive care have been described that can delay the onset of illness or death due to MIC. Recently, we found that inhalation of MIC caused the appearance of activated tissue factor in circulation with subsequent activation of the coagulation cascade. Herein, we report that MIC exposure (500 ppm for 30 min, nose-only) caused deposition of fibrin-rich casts in the conducting airways resulting in respiratory failure and death within 24 h in a rat model (LC90-100 ). We thus investigated the effect of airway delivery of the fibrinolytic agent tissue plasminogen activator (tPA) on mortality and morbidity in this model. Intratracheal administration of tPA was initiated 11 h post MIC exposure and repeated every 4 h for the duration of the study. Treatment with tPA afforded nearly 60% survival at 24 h post MIC exposure and was associated with decreased airway fibrin casts, stabilization of hypoxemia and respiratory distress, and improved acidosis. This work supports the potential of airway-delivered tPA therapy as a useful countermeasure in stabilizing victims of high-level MIC exposure. © 2020 New York Academy of Sciences.A balance between the synthesis and degradation of active proteins governs diverse cellular processes in plants spanning from cell-cycle progression and circadian rhythm to the outcome of several hormone signaling pathways. Ubiquitin-mediated post-translational modification determines the degradative fate of the target proteins, thereby altering the output of the cellular processes. An equally-important and perhaps under-appreciated aspect of this pathway is the antagonistic process of de-ubiquitination. De-ubiquitinases (DUBs), a group of processive enzymes, play an important role in maintaining cellular ubiquitin homeostasis by hydrolyzing ubiquitin poly-proteins and free poly-ubiquitin chains into mono-ubiquitin. Further, DUBs rescue the cellular proteins from 26S proteasome-mediated degradation to their active form by cleaving the poly-ubiquitin chain from the target protein. Any perturbation in the DUB activity is likely to affect proteostasis and downstream cellular processes. This review illustrates the recent findings on the biological significance and the mechanism of action of the DUBs in Arabidopsis thaliana (Arabidopsis), with an emphasis on ubiquitin-specific proteases (UBPs), the largest family among the DUBs. We focus on the putative roles of various protein-protein interaction interfaces in DUBs and their generalized function in ubiquitin recycling along with their pre-eminent role in plant development. This article is protected by copyright. All rights reserved.Amyloid-β (Aβ) oligomers are implicated in Alzheimer disease (AD) pathogenesis. However, their unstable nature and heterogeneous state disrupts elucidation of their explicit role in AD progression, impeding the development of tools targeting soluble Aβ oligomers. To address such obstacles, we designed and synthesized parallel and anti-parallel variants of Aβ(1-40) dimers and characterized their pathogenic properties in AD models. We found anti-parallel dimers induced cognitive impairments with increased amyloidogenesis and cytotoxicity, and subsequently developed a screening platform by immobilizing this dimer variant on 96-well-plates. Through screening, we identified two FDA-approved drugs, Oxytetracycline and Sunitinib, which were able to dissociate Aβ oligomers and plaques to monomers in 5XFAD transgenic mice. In addition, we discovered a fluorescent chemical, Astrophloxine, that could detect aggregated Aβ in brain tissue and cerebrospinal fluid samples of AD mice. Our screening platform provides a stable and homogeneous environment permitting isolated observations of Aβ interactions with dimer-specific molecules. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.We provide a long-term evaluation of patients enrolled in the EORTC/GIMEMA AML-10 trial which included a total of 2157 patients, 15-60 years old, randomized to receive either daunorubicin (DNR, 50 mg/m2 ), mitoxantrone (MXR, 12 mg/m2 ), or idarubicin (IDA, 10 mg/m2 ) in addition to standard-dose cytarabine and etoposide for induction chemotherapy and intermediate dose cytarabine for consolidation. Younger patients who reached complete remission with complete (CR) or incomplete (CRi) recovery were then scheduled to receive an allogeneic hematopoietic stem cell transplantation (HSCT). That was if they had a HLA-identical sibling donor; in all other cases, an autologous HSCT had to be administered. At an 11-year median follow-up, the 5-year, 10-year and 15-year overall survival (OS) rates were 33.2%, 30.1% and 28.0%, respectively. No significant difference between the three randomized groups regarding OS was observed (P = .38). In young patients, 15-45 years old, no treatment difference (P = .89) regarding OS was observed, while in patients 46-60 years old, MXR and IDA groups had a trend for a longer OS as compared to the DNR group (P = .029). Among younger patients without a favorable MRC cytogenetic risk subgroup who achieved a CR/CRi after induction chemotherapy, those with a HLA-identical sibling donor had higher 10-year and 15-year OS rates than those without. In older patients who reached CR/CRi, the long-term outcomes of those with or without a donor was similar. In conclusion, long-term outcomes of the study confirmed similar OS in the three randomized groups in the whole cohort of patients. © 2020 Wiley Periodicals, Inc.Efficient methods to introduce bioorthogonal groups, such as terminal alkynes, into biomolecules are important tools for chemical biology. State-of-the-art approaches are based on the introduction of a linker between the targeted amino acid and the alkyne, and still present limitations of either reactivity, selectivity or adduct stability. Herein, we present an ethynylation method of cysteine residues based on the use of ethynylbenziodoxolone (EBX) reagents. In contrast to other approaches, the acetylene group is directly introduced onto the thiol group of cysteine and can be used in one-pot in a copper-catalyzed alkyne-azide cycloaddition (CuAAC) for further functionalization. Labeling proceeded with reaction rates comparable or higher than the most often used iodoacetamide on peptides or maleimide on the antibody trastuzumab. Under optimized conditions, high cysteine selectivity was observed. The reagents were also used in living cells for cysteine proteomic profiling and displayed an improved coverage of the cysteinome compared to previously reported iodoacetamide or hypervalent iodine-reagent based probes.