A pyrene-armed hexahomotrioxacalix[3]arene as a multi-sensor via synergistic and demetallation effects

A new pyrene-armed hexahomotrioxacalix[3]arene L has been synthesized, which exhibits a pronounced fluorescence enhancement response toward Cu²⁺ ions via a Zn²⁺ or Cd²⁺ triggered synergistic effect. Additionally, the L·Cu²⁺+ complex can subsequently serve as a sensor for F⁻ via anion-induced demetallation. The fluorescence responses by the input of Cu²⁺, Zn²⁺/Cd²⁺ and F⁻ can be constructed as a combinational logic gate which mimics a set of molecular traffic signals

Meiotic association between Spo11 regulated by Rec102, Rec104 and Rec114

Meiotic recombination is initiated by DNA double-stranded break (DSB) formation catalyzed by Spo11, a type-II topoisomerase-like transesterificase, presumably via a dimerization-mediated mechanism. We demonstrate the existence of in vivo interactions between Spo11 proteins carrying distinct tags, and the chromatin-binding and DSB activity of tagged Spo11 at innate and targeted DSB sites upon fusion to the Gal4 DNA-binding domain. First we identified the interaction between Spo11-3FLAG and Gal4BD-Spo11 proteins, and established that this interaction specifically occurs at the time of DSB formation. We then observed that presence of the Gal4BD-spo11Y135F (nuclease-deficient) protein allows Spo11-3FLAG recruitment at the GAL2 locus, indicative of the formation of a hetero-complex near the GAL2 UAS sites, but no formation of double- or single-strand breaks. Spo11 self-interaction around the GAL2 DSB site depends on other proteins for DSB formation, in particular Rec102, Rec104 and Rec114. Together, these results suggest that in vivo self-association of Spo11 during meiosis is genetically regulated. The results are discussed in relation to possible roles of Spo11 self-interaction in the control of the cleavage activity

The ν\nuMSM, Dark Matter and Baryon Asymmetry of the Universe

We show that the extension of the standard model by three right-handed neutrinos with masses smaller than the electroweak scale (the $\nu$MSM) can explain simultaneously dark matter and baryon asymmetry of the universe and be consistent with the experiments on neutrino oscillations. Several constraints on the parameters of the $\nu$MSM are derived.Comment: 16 pages, 1 figure, revtex

Acute megakaryoblastic leukemia, unlike acute erythroid leukemia, predicts an unfavorable outcome after allogeneic HSCT

Acute erythroid leukemia (FAB-M6) and acute megakaryoblastic leukemia (FAB-M7) exhibit closely related properties in cells regarding morphology and the gene expression profile. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the mainstay of the treatment for both subtypes of leukemia due to their refractoriness to chemotherapy and high rates of relapse, it remains unclear whether allo-HSCT is curative in such cases due to their scarcity. We retrospectively examined the impact of allo-HSCT in 382 patients with M6 and 108 patients with M7 using nationwide HSCT data and found the overall survival (OS) and relapse rates of the M6 patients to be significantly better than those of the M7 patients after adjusting for confounding factors and statistically comparable with those of the patients with M0/M1/M2/M4/M5 disease. Consequently, the factors of age, gender, performance status, karyotype, disease status at HSCT and development of graft-vs.-host disease predicted the OS for the M6 patients, while the performance status and disease status at HSCT were predictive of the OS for the M7 patients. These findings substantiate the importance of distinguishing between M6 and M7 in the HSCT setting and suggest that unknown mechanisms influence the HSCT outcomes of these closely related subtypes of leukemia. © 2016 Elsevier Ltd.Embargo Period 12 month

Topical application of 5-fluorouracil on attic cholesteatoma results in downregulation of keratinocyte growth factor and reduction of proliferative activity.

To investigate the cell-biological effect of topically applied 5-fluorouracil (5-FU) on middle ear cholesteatoma, 12 attic cholesteatomas were treated with topical application of 5-FU cream, two to five times with an interval of 2 weeks (5-FU group). The control group comprised 65 cholesteatoma that were not treated with 5-FU. All lesions were later excised surgically and processed for immunohistochemical analyses of Ki-67, keratinocyte growth factor (KGF) and its receptor (KGFR). 5-FU significantly reduced the expression of KGF, did not change KGFR expression, and significantly reduced the Ki-67 labeling index, relative to the control group. The effect of 5-FU on cholesteatoma seems to be mediated, at least in part, through downregulation of KGF in stromal cells and reduction of the proliferative activity of epithelial cells

Keratinocyte growth factor accelerates compensatory growth in the remaining lung after trilobectomy in rats.

OBJECTIVE: In rats pulmonary resection is followed by lung compensatory growth. However, the molecular mechanism underlying lung compensatory growth remains unclear. Keratinocyte growth factor is expressed in lung tissue and is considered a possible mitogen for lung epithelial cells. The objectives of this study were to define the role of keratinocyte growth factor and its receptor in rat lung compensatory growth after trilobectomy and the effect of exogenous keratinocyte growth factor gene transfection. METHODS: Adult Lewis rats were used. Right trilobectomy was performed in the operation group and sham thoracotomy in the sham group. In the operation group, keratinocyte growth factor-FLAG or FLAG expression vector was transfected directly into the lung by means of electroporation. Expression of keratinocyte growth factor and its receptor and alveolar cell proliferation index based on proliferating cell nuclear antigen levels were measured in the right lung at day 14 after the operation. RESULTS: Proliferating cell nuclear antigen, keratinocyte growth factor, and keratinocyte growth factor receptor expression in lung epithelial cells was significantly increased at day 4 after trilobectomy. Transfection of keratinocyte growth factor-FLAG expression vector resulted in further significant enhancement of proliferating cell nuclear antigen at day 4 after trilobectomy; however, the transfection of FLAG expression vector did not alter the enhancement of proliferating cell nuclear antigen. Exogenous expression of keratinocyte growth factor in the remaining lung by means of electroporation significantly augmented epithelial proliferation and decreased the average airspace distance (mean linear intercept). CONCLUSION: Our results implicate keratinocyte growth factor in the induction of alveolar epithelial cell proliferation for compensatory lung growth and indicate that overexpression of keratinocyte growth factor in the remaining lung by means of electroporation significantly augmented lung epithelial proliferation

Macrophage Migration Inhibitory Factor Activates Hypoxia-Inducible Factor in a p53-Dependent Manner

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