The deubiquitinating enzyme USP4 regulates BRCA1 stability and function.

BRCA1 plays a suppressive role in breast tumorigenesis. Ubiquitin-dependent degradation is a common mechanism that regulates BRCA1 protein stability, and several ubiquitin ligases involved have been identified. However, the deubiquitinating enzyme for BRCA1 remains less defined. Here, we report that the deubiquitinase USP4 interacts with, deubiquitinates and stabilizes BRCA1, maintaining the protein level of BRCA1. USP4 knockdown results in a decreased BRCA1 protein level, impairment in homologous recombination mediated double-stranded break repair, and increased genome instability, and confers resistance to DNA damage-inducing agents and PARP inhibitors. Ectopic expression of USP4 stabilizes BRCA1 and reverse the effects caused by USP4 knockdown. Moreover, USP4 is low expressed in human breast cancer tissues and its low expression correlates with poorer survival of patients. Furthermore, we identified several loss-of-function mutations of USP4 in human gynecological cancers, the catalytic activity of which or their interaction with BRCA1 is disrupted. Together, we reveal that USP4 is a deubiquitinase for BRCA1. USP4 positively regulates the stability and function of BRCA1 through de-ubiquitination, and plays important role in the suppression of breast cancer.

Current and future distribution of the deciduous shrub Hydrangea macrophylla in China estimated by MaxEnt.

Climate change has a significant impact on the growth and distribution of vegetation worldwide. Hydrangea macrophylla is widely distributed and considered a model species for studying the distribution and responses of shrub plants under climate change. These results can inform decision-making regarding shrub plant protection, management, and introduction of germplasm resources, and are of great importance for formulating ecological countermeasures to climate change in the future. We used the maximum entropy model to predict the change, scope expansion/reduction, centroid movement, and dominant climate factors that restrict the growth and distribution of H. macrophylla in China under current and future climate change scenarios. It was found that both precipitation and temperature affect the distribution of suitable habitat for H. macrophylla. Akaike information criterion (AICc) was used to select the feature combination (FC) and the regularization multiplier (RM). After the establishment of the optimal model (FC = QP, RM = 0.5), the complexity and over-fitting degree of the model were low (delta AICc = 0, omission rate = 0.026, difference between training and testing area under the curve values = 0.0009), indicating that it had high accuracy in predicting the potential geographical distribution of H. macrophylla (area under the curve = 0.979). Overall, from the current period to future, the potential suitable habitat of this species in China expanded to the north. The greenhouse effect caused by an increase in CO2 emissions would not only increase the area of high-suitability habitat in Central China, but also expand the area of total suitable habitat in the north. Under the maximum greenhouse gas emission scenario (RCP8.5), the migration distance of the centroid was the longest (e.g., By 2070s, the centroids of total and highly suitable areas have shifted 186.15 km and 89.84 km, respectively).

Melatonin mediates monochromatic light-induced expression of somatostatin in the hypothalamus and pituitary of chicks.

Melatonin (MEL) plays an important role in regulating growth and development of organisms and the cellular metabolism. This study was conducted to explore the role of MEL in mediating monochromatic light-induced secretion of somatostatin (SST) in the hypothalamus and pituitary in chicks. Pinealectomy models of newly hatched broilers were exposed to white (WL), red (RL), green (GL), and blue (BL) lights. The results showed that SST immunoreactive neurons and fibers were distributed in the hypothalamus. SST and SST receptor 2 (SSTR2) mRNA and protein levels in the hypothalamus and pituitary were higher in chicks exposed to RL than in chicks exposed to GL and BL. However, after pinealectomy, the mRNA and protein levels of SST and SSTR2 in the hypothalamus and pituitary in the different light groups were increased, and the differences between the groups disapeared. The expression trend of SSTR5 mRNA in the pituitary was the idential to that of SSTR2 mRNA in the pituitary. In vitro, exogenous SST inhibited growth hormone (GH) secretion, and selective antogonists of SSTR2 and SSTR5 promoted GH secretion. Selective antogonists of the melatonin receptor 1b (Mel1b) and Mel1c increased the relative concentrations of SST in the adenohypophysis cells. These results indicated that monochromatic light affects the expression of SST in chick hypothalamus and pituitary. MEL, via Mel1b and Mel1c, decreased SST secretion under GL, which was associated with the inhibition of SST, SSTR2, and SSTR5 in adenohypophysis cells.

Preparation of polymyxin B-loaded gellan-polylysine polyion complex fibers with high affinity to endotoxin.

Endotoxemia, a life-threatening disease affecting people worldwide, can be treated by hemoperfusion alone. New hemoperfusion materials with high biocompatibility and endotoxin-combination ability are always in demand. Herein, polymyxin B (PMB), a specific endotoxin binding molecule, was loaded onto gellan-polylysine polyion complex, and the obtained material was used in preparing wet-spun fibers. The tensile strength of the as-spun yarns (100 fibers) ranged from 1.49 N to -1.58 N and that of the dried and rewetted yarns ranged from 1.45 N to 1.56 N. The adsorption ability of the fibers with lipopolysaccharides from E. coli was 2.784 ± 0.036 EU/mg in simulated human body fluid and 2.452 ± 0.107 EU/mg in mouse plasma. The fibers showed no cytotoxicity toward U2OS cells and no hemolysis toward mouse blood. The influence of the fibers on the clotting time of mouse blood was negligible, and the blood cells were not adhesive to the fibers. Thus, the PMB-loaded gellan-polylysine complex fiber and its derivate fabrics can be used in hemoperfusion.