Cyclin K-containing kinase complexes maintain self-renewal in murine embryonic stem cells.

Protein phosphorylation plays an important role in the regulation of self-renewal and differentiation of embryonic stem cells. However, the responsible intracellular kinases are not well characterized. Here, we discovered that cyclin K protein was highly expressed in pluripotent embryonic stem cells but low in their differentiated derivatives or tissue-specific stem cells. Upon cell differentiation, the level of cyclin K protein was decreased. Furthermore, knockdown of cyclin K led to cell differentiation, which could be rescued by an expression construct resistant to RNA interference. Surprisingly, cyclin K did not interact with CDK9 protein in cells as thought previously. Instead, it associated with CrkRS (also known as CDK12) and CDC2L5 (also known as CDK13). Similar to cyclin K, both CDK12 and CDK13 proteins were highly expressed in murine embryonic stem cells and were decreased upon cell differentiation. Importantly, knockdown of either kinase resulted in differentiation. Thus, our studies have uncovered two novel protein kinase complexes that maintain self-renewal in embryonic stem cells.

Field Investigation of the Dynamic Response of Culvert-Embankment-Culvert Transitions in a High-Speed Railway.

The stiffnesses of embankments and culverts differ in the transition sections of high-speed railways (HSRs) due to their different supporting conditions. The dynamic irregularity caused by the different stiffnesses makes this transition area the weakest part of high-speed railways. Graded crushed stone combined with 5% cement is typically used to fill the subgrade in these transition areas. Thus, three different particle size ratios of crushed stone were matched and tested regarding the construction parameters to explore the most suitable materials to fill the roadbed in a transition section. Then, field dynamic tests were carried out on the culvert-embankment-culvert transition area where trains run at speeds of 5-360 km/h. A time-domain analysis of the test data was performed to obtain the laws of variation that cause the dynamic characteristics to change with the railway line and roadbed layer and the changes induced by a train's running speed, operating direction, and axle weight. The results indicate that (i) it is feasible to fill transition section roadbeds with well-graded crushed stone combined with 5% cement with optimal water contents; (ii) extreme dynamic responses in some special sections are observed, suggesting the value of taking special measures at the transition section. For example, the sections 14.5 m and 30 m from the 679 culvert and the bed layer should be specially stabilized; (iii) the train's axle load and driving direction show a great effect on corresponding sections and layers but present a small effect on the sections and layers nearby; and (iv) 260 km/h is a critical speed.

Vertical transmission of Salmonella Enteritidis with heterogeneous antimicrobial resistance from breeding chickens to commercial chickens in China.

Human salmonellosis caused by the consumption of eggs and chicken meat contaminated with Salmonella Enteritidis has become a continuing public health concern worldwide. In this study we adopted whole genome sequencing (WGS) to determine the genetic relationship and antimicrobial resistance of S. enterica strains isolated from a poultry breeding enterprise that consists of one breeding chicken farm, one egg hatchery and one commercial chicken farm. A total of 148 S. enterica including 147 S. Enteritidis strains were isolated from 2100 fecal swab samples, with 16 (5.3 %, 16/300) from breeding chicken farm, 38 (4.2 %, 38/900) from egg hatchery and 94 (10.4 %, 94/900) from commercial chicken farm. WGS revealed that all 147 S. Enteritidis strains belonged to ST11, and further divided into 4 different ribosomal STs and 64 core genome STs. Single nucleotide polymorphism typing suggested the presence of the vertical transmission of S. Enteritidis from breeding chicken to commercial chicken. Three different antimicrobial-resistant plasmids including one blaCTX-M-14-carrying plasmid and two virulence-resistance plasmids were characterized, resulting in the heterogeneous antimicrobial resistance of clonally related S. Enteritidis strains. Routine surveillance in breeding chicken farms is conducive to the control of S. Enteritidis from farm to fork.