The E. coli Acetylome: Form and Function

Castaño-Cerezo et al. (2014) conducted a proteomic evaluation of the Escherichia coli acetylome under four different growth conditions.1 As a post-translational modification (PTM), acetylation of lysine residues contributes to regulation of cellular activity with activation or inactivation of key proteins such as enzymes and other signaling molecules. By modifying nutrition and growth conditions in vitro, the Read the rest of this article

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Efficacy and Safety of Novel Agent-Based Therapies for Multiple Myeloma: A Meta-Analysis

This study aimed at comparing bortezomib, thalidomide, and lenalidomide in patients with multiple myeloma (MM) for safety and efficacy using meta-analysis. This meta-analysis identified 17 randomized controlled trials (RCTs) including 6742 patients. These RCTs were separated according to the different agent-based regimens and to autologous stem-cell transplantation (ASCT). Complete response (CR), progression-free survival (PFS), overall survival (OS), and adverse events (AE) were combined. The total weighted risk ratio (RR) of CR was 3.29 [95% confidence interval (95% CI): 2.22–4.88] () for the novel agent-based regimens. These novel agent-based regimens showed greater benefit in terms of PFS of all subgroups irrespective of whether the patient received ASCT or not. The hazard ratio (HR) for PFS was 0.64 [95% CI: 0.60–0.69] (). Improvements of OS could be found only in the bortezomib- and thalidomide-based regimens without ASCT. The pooled HRs were 0.74 [95% CI: 0.65–0.86] () and 0.80 [95% CI: 0.70–0.90] (), respectively. Several AEs were shown more frequently in the novel agent-based regimens compared with controls such as hematologic events (neutropenia, anemia, and thrombocytopenia), gastrointestinal infection, peripheral neuropathy, thrombosis, and embolism events. In conclusion, in spite of the AEs, novel agent-based regimens are safe and effective for the treatment of MM.

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Higher Fitness Linked to Reduced Risk of Death after First Heart Attack

Researchers at Johns Hopkins and the Henry Ford Health System report evidence that higher levels of physical fitness may not only reduce risk of heart attacks and death from all causes, but also possibly improve the chances of survival after a first attack.

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7-(Benzofuran-2-yl)-7-deazadeoxyguanosine as a fluorescence turn-ON probe for single-strand DNA binding protein

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C5CC09700B, Communication

Munefumi Tokugawa, Yoshiaki Masaki, Jan Christian Canggadibrata, Kazuhei Kaneko, Takashi Shiozawa, Takashi Kanamori, Morten Grotli, L. Marcus Wilhelmsson, Mitsuo Sekine, Kohji Seio
7-(Benzofuran-2-yl)-7-deazadeoxyguanosine (BFdG) was synthesized and incorporated into an oligodeoxynucleotide (ODN). The single-stranded ODN containing BFdG shows 91-fold fluorescence enhancement upon binding of single-strand DNA binding protein.
The content of this RSS Feed (c) The Royal Society of Chemistry

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A Novel Copper-Rich Open-Framework Chalcogenide Constructed from Octahedral Cu4Se6 and Icosahedral Cu8Se13 Nanocluster

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC00183A, Communication

Huajun Yang, Le Wang, Dandan Hu, Jian Lin, Luo Li, Hongxiang Wang, Tao Wu
We demonstrated a unique copper-rich open-framework chalcogenide constructed from icosahedral Cu8Se13 and octahedral Cu4Se6 nanocluster connected each other through SnSe3(Se2) bridging unit. The specific copper-rich composition gives rise to a...
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Comparison of Histopathological Effects of Thymoquinone and Local Nasal Corticosteroids in Allergic Rhinitis in a Rabbit Model

Background/Aims: In this study, we aimed to evaluate the histopathological effects of thymoquinone treatment of the nasal mucosa in a rabbit model of allergic rhinitis, and we compared its effects with those of nasal mometasone furoate. Methods: A total of 24 male New Zealand rabbits were used. The animals were randomly assigned to one of four groups. Group 1 received no treatment, while group 2 underwent ovalbumin (OVA) sensitization only. Group 3 was the study group; after OVA sensitization, the rabbits were treated with intranasal thymoquinone. The group 4 rabbits received mometasone furoate for 7 days after OVA sensitization. Mucosal structures were stained with hematoxylin and eosin, while toluidine blue was used to stain mast cells. Apoptosis was evaluated using a TUNEL assay. Results: In the positive control groups, including the thymoquinone and intranasal mometasone furoate groups, intraepithelial and submucosal inflammation and goblet cell hypertrophy were significantly decreased compared to group 2 (p Conclusion: This is the first study to evaluate the histopathological effects of thymoquinone in an allergic rhinitis model. Thymoquinone reduced allergic inflammation and may be valuable for treating allergic rhinitis. However, additional studies are needed.
ORL 2016;78:55-60

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Mutations Affect Multiple Stages of CBL Activation Cycle

Oncogenic mutations in the monomeric Casitas B-lineage lymphoma (Cbl) gene have been found in many tumors, but their significance remains largely unknown. Several human c-Cbl (CBL) structures have recently been solved, depicting the protein at different stages of its activation cycle and thus providing mechanistic insight underlying how stability—activity tradeoffs in cancer-related proteins—may influence disease onset and progression. In this study, we computationally modeled the effects of missense cancer mutations on structures representing four stages of the CBL activation cycle to identify driver mutations that affect CBL stability, binding, and activity. We found that recurrent, homozygous, and leukemia-specific mutations had greater destabilizing effects on CBL states than random noncancer mutations. We further tested the ability of these computational models, assessing the changes in CBL stability and its binding to ubiquitin-conjugating enzyme E2, by performing blind CBL-mediated EGFR ubiquitination assays in cells. Experimental CBL ubiquitin ligase activity was in agreement with the predicted changes in CBL stability and, to a lesser extent, with CBL-E2 binding affinity. Two thirds of all experimentally tested mutations affected the ubiquitin ligase activity by either destabilizing CBL or disrupting CBL-E2 binding, whereas about one-third of tested mutations were found to be neutral. Collectively, our findings demonstrate that computational methods incorporating multiple protein conformations and stability and binding affinity evaluations can successfully predict the functional consequences of cancer mutations on protein activity, and provide a proof of concept for mutations in CBL. Cancer Res; 76(3); 561–71. ©2015 AACR.

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