BRCA1 Forms a Functional Complex with γ-H2AX as a Late Response to Genotoxic Stress

Following genotoxic stress, the histone H2AX becomes phosphorylated at serine 139 by the ATM/ATR family of kinases. The tumor suppressor BRCA1, also phosphorylated by ATM/ATR kinases, is one of several proteins that colocalize with phospho-H2AX (γ-H2AX) at sites of active DNA repair. Both the precise mechanism and the purpose of BRCA1 recruitment to sites of DNA damage are unknown. Here we show that BRCA1 and γ-H2AX form an acid-stable biochemical complex on chromatin after DNA damage. Maximal association of BRCA1 with γ-H2AX correlates with reduced global γ-H2AX levels on chromatin late in the repair process. Since BRCA1 is known to have E3 ubiquitin ligase activity in vitro, we examined H2AX for evidence of ubiquitination. We found that H2AX is ubiquitinated at lysines 119 and 119 in vivo and that blockage of 26S proteasome function stabilizes γ-H2AX levels within cells. When BRCA1 levels were reduced, ubiquitination of H2AX was also reduced, and the cells retained higher levels of phosphorylated H2AX. These results indicate that BRCA1 is recruited into stable complexes with γ-H2AX and that the complex is involved in attenuation of the γ-H2AX repair signal after DNA damage

Distócia de ombros e lesão do plexo braquial: revisão e casuística 2012

In this paper, we investigate the realization problem of a special class of positive-real admittances in a form similar to biquadratic functions but with an extra pole at s = 0, which is common in vehicle suspension designs. The number of inerters and dampers is restricted to one in each case and number of the springs is arbitrary. To solve the problem, we first convert a previous result by Chen & Smith, 2009 to a more direct form. A necessary and sufficient condition for realizability is then derived and explicit circuit arrangements are provided to cover the realizability conditions. © 2012 IEEE.published_or_final_versio

The constant-velocity highly collimated outflows of the planetary nebula He 2-90

We present high-dispersion echelle spectroscopic observations and a narrow-band [N II] image of the remarkable jet-like features of He 2-90. They are detected in the echelle spectra in the H-alpha and [N II] lines but not in other nebular lines. The [N II]/H-alpha ratio is uniformly high, ~1. The observed kinematics reveals bipolar collimated outflows in the jet-like features and shows that the southeast (northwest) component expands towards (away from) the observer at a remarkably constant line-of-sight velocity, 26.0+-0.5 km/s. The observed expansion velocity and the opening angle of the jet-like features are used to estimate an inclination angle of ~5 degrees with respect to the sky plane and a space expansion velocity of ~290 km/s. The spectrum of the bright central nebula reveals a profusion of Fe lines and extended wings of the H-alpha line, similar to those seen in symbiotic stars and some young planetary nebulae that are presumed to host a mass-exchanging binary system. If this is the case for He 2-90, the constant velocity and direction of the jets require a very stable dynamic system against precession and warping.Comment: 8 pages (emulate ApJ), 5 figure, 1 tabl

Chemically modified cellulose nanocrystals as polyanion for preparation of polyelectrolyte complex.

Bacterial cellulose nanocrystals (BCNCs) have hydrophilic surfaces due to hydroxyl groups but are water-insoluble. The carboxymethylation improves the solubility of cellulose in polar media through the insertion of carboxymethyl groups. This study aims to evaluate the use of two different alcoholic solvents in the carboxymethylation reaction of BCNCs: ethanol and isopropanol. BCNCs were obtained under two hydrolysis conditions: sulfuric acid (BCNC-S) and combination of sulfuric and hydrochloric acids (BCNC-S/Cl). Two techniques (NMR and titration) were used to determine the degree of substitution (DS) values. Carboxymethylation of BCNC-S/Cl led to high DS compared to BCNC-S and the use of isopropanol promoted an even greater DS. The thermal properties were not affected after the chemical modification. However, functionalization provided an increase in the negative charge density at the surface of nanostructures and a change in the crystal structure (cellulose type Ia for amorphous), making this material a potential polyanion for the synthesis of polyelectrolyte complexes (PECs). The micrographs showed that the nanocrystals became soluble after carboxymethylation. Carboxymethylated bacterial cellulose nanocrystals hydrolyzed through the mixture of inorganic acids and modified using isopropanol (CBCNC-S/Cl-IPA) was a suitable polyanion to produce PECs with chitosan. The PECs produced had particle size ranging from 276 to 588 nm and zeta potential ranging from - 24.3 to + 39.0 mV

Effectiveness of a cardiovascular risk management program in the incidence of cardiovascular events in a low-income population from the caribbean region of Colombia

Methods This was a retrospective cohort study. Patients with 20 to 76 years affiliated to insurer company and enrolled to the DTC program were considered as the study population. The data source was an administrative database of all 128,263 patients between Jan 2015 and Dec 2018. The main outcome was the reduction in the risk of a CVE (stroke, AMI or CHF) based in the time-person exposed to the intervention. Four different time thresholds were considered for stablishing exposure status: six months, one year, two years and four years. Propensity score-weighted Cox regression models were used to evaluate the association between exposure to the program and the incidence of CVE