Deep CRISPR mutagenesis characterizes the functional diversity of TP53 mutations.

The mutational landscape of TP53, a tumor suppressor mutated in about half of all cancers, includes over 2,000 known missense mutations. To fully leverage TP53 mutation status for personalized medicine, a thorough understanding of the functional diversity of these mutations is essential. We conducted a deep mutational scan using saturation genome editing with CRISPR-mediated homology-directed repair to engineer 9,225 TP53 variants in cancer cells.

Response of Fluorescent Boron Difluoride β-Diketonates to X-Rays.

This paper reports the results of a detailed study of the optical response of boron difluoride curcuminoids to radiation exposure. Two lines of the dyes fundamentally different in structure (namely, symmetrical and asymmetrical) were tested. If the absorption responses of their solutions in chloroform to X-rays turns out to be quite close quantitatively (note that it has a very indicative visual manifestation - a gradual discoloration is observed in the dose range up to 300 Gy), the fluorescence ones differ notably: among other things, the former demonstrate much more sensitive reactions (the corresponding limit of detection values ​​differ by up to 2.

Optical Polymorphism of Liquid-Crystalline Dispersions of DNA at High Concentrations of Crowding Polymer.

Optically active liquid-crystalline dispersions (LCD) of nucleic acids, obtained by polymer- and salt-induced (-) condensation, e.g., by mixing of aqueous saline solutions of low molecular weight DNA (≤10 Da) and polyethylene glycol (PEG), possess an outstanding circular dichroism (CD) signal (so-called -CD) and are of interest for sensor applications.

Autologous thrombin preparations: Biocompatibility and growth factor release.

Platelet-rich plasma (PRP) has been investigated to promote wound healing in a variety of tissues. Thrombin, another essential component of wound healing, is sometimes combined with PRP to generate a fibrin clot in order to retain the sample at the delivery site and to stimulate growth factor release. Using a fully autologous approach, autologous serum (AS) with thrombin activity can be prepared using a one-step procedure by supplementing with ethanol (E AS) to prolong room temperature stability or prepared ethanol free (E AS) by utilizing a two-step procedure to prolong stability.

Phosphorylation Control of p53 DNA-Binding Cooperativity Balances Tumorigenesis and Aging.

Posttranslational modifications are essential for regulating the transcription factor p53, which binds DNA in a highly cooperative manner to control expression of a plethora of tumor-suppressive programs. Here we show at the biochemical, cellular, and organismal level that the cooperative nature of DNA binding is reduced by phosphorylation of highly conserved serine residues (human S183/S185, mouse S180) in the DNA-binding domain. To explore the role of this inhibitory phosphorylation , new phosphorylation-deficient p53-S180A knock-in mice were generated.

Loss of p53 function at late stages of tumorigenesis confers ARF-dependent vulnerability to p53 reactivation therapy.

Cancer development is driven by activated oncogenes and loss of tumor suppressors. While oncogene inhibitors have entered routine clinical practice, tumor suppressor reactivation therapy remains to be established. For the most frequently inactivated tumor suppressor p53, genetic mouse models have demonstrated regression of p53-null tumors upon p53 reactivation.

An Ethanol-Free Autologous Thrombin System.

Thrombin is a coagulation protein of central importance to hemostasis and wound healing that can be sourced from human blood, bovine blood, and engineered cell lines. Only autologous thrombin lacks the risks of transmitting emergent pathogens or eliciting an immunogenic response. Previous commercial autologous thrombin devices require the use of high concentrations of ethanol to achieve thrombin stability, introducing cytotoxicity risks.

[A new approach to analysis of participation of oxidative processes in regulation of metabolism in animal tissues].

A new approach to the analysis of the oxidative processes participated in regulation of metabolism in norm and the assessment of the biological consequences under the action of damaging factors of different nature and intensity for animal groups is suggested using the analysis of interrelations between the different parameters of the physicochemical regulatory system of the lipid peroxidation in tissues of the laboratory mice (the phospholipid composition, amounts of the oxidation products in lipids). by changes of the scale and direction of interrelations between the reciprocal parameters of the lipid peroxidation system in norm.

[Change of the lipid parameters in the murine liver during one month after low intensity X-ray exposure at low doses].

Parameters of the physicochemical regulatory system of lipid peroxidation in the liver of white outbred mice (females) were studied before and during one month after X-ray exposure at the doses less than 1.5 mGy in the autumn and spring-summer seasons. The initial value of parameters is found to exert the most substantial influence on the liver relative mass, the phosphatidylcholine and lysoform relative content in the liver phospholipids of mice.

[Influence of the lipid characteristics on the age changes of the interrelation in the metabolic regulatory system of the laboratory murine tissues].

The age changes of the lipid physicochemical characteristics in tissues of the laboratory mice were studied. The reliable age changes of the phospholipid composition in the liver and brain of outbreed mice were revealed. The conclusion was done about the influence of the physicochemical characteristics of lipids on the regulation of the biochemical processes in the animal organism.

[Changes in the lipid peroxidation systems in tissues from various rodent species during aging].

The comparative investigation of parameters of the physicochemical regulatory system of the lipid peroxidation (LPO) in liver, spleen and blood components of laboratory rodents of 5 strains and species was carried out. The interrelation between the LPO intensity and the cell-free DNA content in the blood plasma of mice has been shown. The absence of the same type and direct changes of the LPO regulatory system parameters during aging was shown.