Tumor promoter TPA activates Wnt/β-catenin signaling in a casein kinase 1-dependent manner.

The tumor promoter 12-O-tetra-decanoylphorbol-13-acetate (TPA) has been defined by its ability to promote tumorigenesis on carcinogen-initiated mouse skin. Activation of Wnt/β-catenin signaling has a decisive role in mouse skin carcinogenesis, but it remains unclear how TPA activates Wnt/β-catenin signaling in mouse skin carcinogenesis. Here, we found that TPA could enhance Wnt/β-catenin signaling in a casein kinase 1 (CK1) ε/δ-dependent manner. TPA stabilized CK1ε and enhanced its kinase activity. TPA further induced the phosphorylation of LRP6 at Thr1479 and Ser1490 and the formation of a CK1ε-LRP6-axin1 complex, leading to an increase in cytosolic β-catenin. Moreover, TPA increased the association of β-catenin with TCF4E in a CK1ε/δ-dependent way, resulting in the activation of Wnt target genes. Consistently, treatment with a selective CK1ε/δ inhibitor SR3029 suppressed TPA-induced skin tumor formation in vivo, probably through blocking Wnt/β-catenin signaling. Taken together, our study has identified a pathway by which TPA activates Wnt/β-catenin signaling

Evolution of the patellar sesamoid bone in mammals

The patella is a sesamoid bone located in the major extensor tendon of the knee joint, in the hindlimb of many tetrapods. Although numerous aspects of knee morphology are ancient and conserved among most tetrapods, the evolutionary occurrence of an ossified patella is highly variable. Among extant (crown clade) groups it is found in most birds, most lizards, the monotreme mammals and almost all placental mammals, but it is absent in most marsupial mammals as well as many reptiles. Here, we integrate data from the literature and first-hand studies of fossil and recent skeletal remains to reconstruct the evolution of the mammalian patella. We infer that bony patellae most likely evolved between four and six times in crown group Mammalia: in monotremes, in the extinct multituberculates, in one or more stem-mammal genera outside of therian or eutherian mammals and up to three times in therian mammals. Furthermore, an ossified patella was lost several times in mammals, not including those with absent hindlimbs: once or more in marsupials (with some re-acquisition) and at least once in bats. Our inferences about patellar evolution in mammals are reciprocally informed by the existence of several human genetic conditions in which the patella is either absent or severely reduced. Clearly, development of the patella is under close genomic control, although its responsiveness to its mechanical environment is also important (and perhaps variable among taxa). Where a bony patella is present it plays an important role in hindlimb function, especially in resisting gravity by providing an enhanced lever system for the knee joint. Yet the evolutionary origins, persistence and modifications of a patella in diverse groups with widely varying habits and habitats—from digging to running to aquatic, small or large body sizes, bipeds or quadrupeds—remain complex and perplexing, impeding a conclusive synthesis of form, function, development and genetics across mammalian evolution. This meta-analysis takes an initial step toward such a synthesis by collating available data and elucidating areas of promising future inquiry

On Sliding Mode Control for Singular Fractional-Order Systems with Matched External Disturbances

In this paper, we investigate the problem of sliding mode control for singular fractional-order systems that have matched uncertainties. We design an innovative integral sliding mode function and controller based on the normalizable condition. A strict linear matrix inequality-based sufficient condition is obtained for the system’s stability. The normalizable condition is eliminated by updating and developing the control method, and a sufficient and necessary condition is developed for the admissibility of the system. Lastly, verification of our method’s effectiveness is numerically conducted in two instances

Quantifying the Income-Increasing Effect of Digital Agriculture: Take the New Agricultural Tools of Smartphone as an Example

Smartphones are increasingly used in rural areas and have become indispensable new farming tools in farmers’ production and their lives. Based on data from the 2018 China Household Tracking Survey, this study uses ordinary least squares regression with two-stage least squares as a benchmark regression to investigate the impact of the extent of smartphone use on farm household income. Our findings are as follows. ① The degree of use of new smartphone farming tools has a significant income-increasing effect on farm households. ② There is variability in the impact of the use of new smartphone farming tools on the income of farmers in different regions. The highest income-generating effects on the use of smartphone tools were found in the western region, followed by the eastern region, with the smallest effects found in the central region. ③ Low-income farmers have the highest income effects from using new smartphone farming tools. We therefore recommend further improving the digital infrastructure in rural areas to give full play to the driving force of digital technology

Quantifying the Income-Increasing Effect of Digital Agriculture: Take the New Agricultural Tools of Smartphone as an Example

Smartphones are increasingly used in rural areas and have become indispensable new farming tools in farmers’ production and their lives. Based on data from the 2018 China Household Tracking Survey, this study uses ordinary least squares regression with two-stage least squares as a benchmark regression to investigate the impact of the extent of smartphone use on farm household income. Our findings are as follows. ① The degree of use of new smartphone farming tools has a significant income-increasing effect on farm households. ② There is variability in the impact of the use of new smartphone farming tools on the income of farmers in different regions. The highest income-generating effects on the use of smartphone tools were found in the western region, followed by the eastern region, with the smallest effects found in the central region. ③ Low-income farmers have the highest income effects from using new smartphone farming tools. We therefore recommend further improving the digital infrastructure in rural areas to give full play to the driving force of digital technology

Modeling the Coordinated Operation between Bus Rapid Transit and Bus

The coordination between bus rapid transit (BRT) and feeder bus service is helpful in improving the operational efficiency and service level of urban public transport system. Therefore, a coordinated operation model of BRT and bus is intended to develop in this paper. The total costs are formulated and optimized by genetic algorithm. Moreover, the skip-stop BRT operation is considered when building the coordinated operation model. A case of the existing bus network in Beijing is studied, the proposed coordinated operation model of BRT and bus is applied, and the optimized headway and costs are obtained. The results show that the coordinated operation model could effectively decrease the total costs of the transit system and the transfer time of passengers. The results also suggest that the coordination between the skip-stop BRT and bus during peak hour is more effective than non-coordination operation