The emerging roles of phosphatases in Hedgehog pathway

Hedgehog signaling is evolutionarily conserved and plays a pivotal role in cell fate determination, embryonic development, and tissue renewal. As aberrant Hedgehog signaling is tightly associated with a broad range of human diseases, its activities must be precisely controlled. It has been known that several core components of Hedgehog pathway undergo reversible phosphorylations mediated by protein kinases and phosphatases, which acts as an effective regulatory mechanism to modulate Hedgehog signal activities. In contrast to kinases that have been extensively studied in these phosphorylation events, phosphatases were thought to function in an unspecific manner, thus obtained much less emphasis in the past. However, in recent years, increasing evidence has implicated that phosphatases play crucial and specific roles in the context of developmental signaling, including Hedgehog signaling. In this review, we present a summary of current progress on phosphatase studies in Hedgehog pathway, emphasizing the multiple employments of protein serine/threonine phosphatases during the transduction of morphogenic Hedgehog signal in both Drosophila and vertebrate systems, all of which provide insights into the importance of phosphatases in the specific regulation of Hedgehog signaling

Early Cretaceous high-Ti and low-Ti mafic magmatism in Southeastern Tibet: Insights into magmatic evolution of the Comei Large Igneous Province

The Dala diabase intrusion, at the southeastern margin of the Yardoi gneiss dome, is located within the outcrop area of the ~ 132 Ma Comei Large Igneous Province (LIP), the result of initial activity of the Kerguelen plume. We present new zircon U-Pb geochronology results to show that the Dala diabase was emplaced at ~ 132 Ma and geochemical data (whole-rock element and Sr-Nd isotope ratios, zircon Hf isotopes and Fe-Ti oxide mineral chemistry) to confirm that the Dala diabase intrusion is part of the Comei LIP. The Dala diabase can be divided into a high-Mg/low-Ti series and a low-Mg/high-Ti series. The high-Mg/low-Ti series represents more primitive mafic magma compositions that we demonstrate are parental to the low-Mg/high-Ti series. Fractionation of olivine and clinopyroxene, followed by plagioclase within the low-Mg series, lead to systematic changes in concentrations of mantle compatible elements (Cr, Co, Ni, and V), REEs, HFSEs, and major elements such as Ti and P. Some Dala samples from the low-Mg/high-Ti series contain large ilmenite clusters and show extreme enrichment of Ti with elevated Ti/Y ratios, likely due to settling and accumulation of ilmenite during the magma chamber evolution. However, most samples from throughout the Comei LIP follow the Ti-evolution trend of the typical liquid line of descent (LLD) of primary OIB compositions, showing strong evidence of control of Ti contents by differentiation processes. In many other localities, however, primitive magmas are absent and observed Ti contents of evolved magmas cannot be quantitatively related to source processes. Careful examination of the petrogenetic relationship between co-existing low-Ti and high-Ti mafic rocks is essential to using observed rock chemistry to infer source composition, location, and degree of melting

Isolation of a 2-picolinic acid-assimilating bacterium and its proposed degradation pathway

Burkholderia sp. ZD1, aerobically utilizes 2-picolinic acid as a source of carbon, nitrogen and energy, was isolated. ZD1 completely degraded 2-picolinic acid when the initial concentrations ranged from 25 to 300 mg/L. Specific growth rate (μ) and specific consumption rate (q) increased continually in the concentration range of 25–100 mg/L, and then declined. Based on the Haldane model and Andrew’s model, μmax and qmax were calculated as 3.9 and 16.5 h−1, respectively. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) was used to determine the main intermediates in the degradation pathway. Moreover, attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) was innovatively used to deduce the ring cleavage mechanism of N-heterocycle of 2-picolinic acid. To our knowledge, this is the first report on not only the utilization of 2-picolinic acid by a Burkholderia sp., but also applying FT-ICR-MS and ATR-FTIR for exploring the biodegradation pathway of organic compounds

Prenatal allergen and diesel exhaust exposure and their effects on allergy in adult offspring mice

Multiple studies have suggested that prenatal exposure to either allergens or air pollution may increase the risk for the development of allergic immune responses in young offspring. However, the effects of prenatal environmental exposures on adult offspring have not been well-studied. We hypothesized that combined prenatal exposure to Aspergillus fumigatus (A. fumigatus) allergen and diesel exhaust particles will be associated with altered IgE production, airway inflammation, airway hyperreactivity (AHR), and airway remodeling of adult offspring. Following sensitization via the airway route to A. fumigatus and mating, pregnant BALB/c mice were exposed to additional A. fumigatus and/or diesel exhaust particles. At age 9-10 weeks, their offspring were sensitized and challenged with A. fumigatus. We found that adult offspring from mice that were exposed to A. fumigatus or diesel exhaust particles during pregnancy experienced decreases in IgE production. Adult offspring of mice that were exposed to both A. fumigatus and diesel exhaust particles during pregnancy experienced decreases in airway eosinophilia. These results suggest that, in this model, allergen and/or diesel administration during pregnancy may be associated with protection from developing systemic and airway allergic immune responses in the adult offspring

Envisioning how the prototypic molecular machine TFIIH functions in transcription initiation and DNA repair

Critical for transcription initiation and bulky lesion DNA repair, TFIIH provides an exemplary system to connect molecular mechanisms to biological outcomes due to its strong genetic links to different specific human diseases. Recent advances in structural and computational biology provide a unique opportunity to re-examine biologically relevant molecular structures and develop possible mechanistic insights for the large dynamic TFIIH complex. TFIIH presents many puzzles involving how its two SF2 helicase family enzymes, XPB and XPD, function in transcription initiation and repair: how do they initiate transcription, detect and verify DNA damage, select the damaged strand for incision, coordinate repair with transcription and cell cycle through Cdk-activating-kinase (CAK) signaling, and result in very different specific human diseases associated with cancer, aging, and development from single missense mutations? By joining analyses of breakthrough cryo-electron microscopy (cryo-EM) structures and advanced computation with data from biochemistry and human genetics, we develop unified concepts and molecular level understanding for TFIIH functions with a focus on structural mechanisms. We provocatively consider that TFIIH may have first evolved from evolutionary pressure for TCR to resolve arrested transcription blocks to DNA replication and later added its key roles in transcription initiation and global DNA repair. We anticipate that this level of mechanistic information will have significant impact on thinking about TFIIH, laying a robust foundation suitable to develop new paradigms for DNA transcription initiation and repair along with insights into disease prevention, susceptibility, diagnosis and interventions

Insights into the adsorption of Pb(II) over trimercapto-s-triazine trisodium salt-modified lignin in a wide pH range

A novel fabrication method for modifying alkaline lignin (AL) was reported, in which trimercapto-s-triazine trisodium salt was used as a modifier to tune surface properties of AL. Molecular structure of modified AL (FAL) was determined by 3D-EEM, synchronous fluorescence, FTIR, 13C MAS NMR and XPS. Two-dimensional correlation spectroscopy and electron localization function demonstrated that both of electrostatic and coordinate bonds formed between these functional groups and Pb(II) at higher pH of 3.0 to 6.0 while only coordinate bond at lower pH of 0.2 to 1.2. The higher the solution pH was, the stronger the adsorption capacity of FAL had. The maximum adsorption capacity (qm) of Pb(II) was 20.0, 28.2, 65.1 and 73.7 mg/g at pH of 0.2, 1.2, 3.0 and 6.0 (T = 25 °C), respectively. The adsorption performance of FAL towards Pb(II) was better by comparing with other biomass-based materials via adsorption amount, equilibrium time as well as simplicity of the synthesized steps. These results improve the understanding of FAL-Pb(II) interaction at the molecular level and facilitate a comprehensive evaluation on the treatment efficiency of FAL

Driving Forces of the Bubble-Driven Tubular Micromotor Based on the Full Life-Cycle of the Bubble

Micromotors show many advantages in practical applications, including small size, large push-to-weight ratio, and low power consumption. Micromotors have been widely used in a variety of applications, including cell manipulation, payload delivery, and removal of toxic components. Among them, bubble-driven micromotors have received great attention due to their large driving force and high speed. The driving force of the bubble-driven micromotor movement comes from the four stages of the life cycle of the bubble: nucleation, growth, slip, and ejection. At present, investigators are still unclear about the driving mechanism of the bubble-driven micromotors, the source of the driving force being still especially controversial. In response to this problem, this paper combines the mass transfer model, hydrodynamic theory, and numerical simulation to explain the driving force generated by the various stages of the life-cycle of the bubble. A mass transfer model was used to calculate the driving force of the motor contributed by the bubble nucleation and slip stage. Based on equilibrium of force and conservation of energy, a theoretical model of the driving force of the tubular micromotor in the growth and ejection stage of the bubble was established. The results show that the driving force contributed by the bubble in the nucleation and the slip stage is rather small. However, the stage of bubble growth and ejection provide most of the driving force. On further evaluating the effect of the bubble driving force on the motor speed, it was found that the growth stage plays a major role in the motion of the bubble-driven micromotor. The micromotor velocity based on the driving forces of the full life-cycle of bubbles agrees well with the experimental results

Influence of sulfamethazine (SMT) on the adsorption of antimony by the black soil: Implication for the complexation between SMT and antimony

This paper reported when sulfamethazine (SMT) and antimony (Sb(V)) coexisted in aqueous solution at pH of 3.0, 5.0 and 7.0, the complexation between SMT and Sb(V) occurred. Such a complexation impeded the adsorption of Sb(V) on the black soil. The higher the solution pH value was, the more the amount of Sb(V) was prevented from adsorbing on the black soil. The maximum adsorption capacity (qm) of Sb(V) at the presence of SMT under pH of 3.0, 5.0 and 7.0was 5.28, 3.45 and 1.95 mg/g, respectively. -NH2, N-H, S = O and C-\N of pyrimidine ring carried by SMT acted as the complexation sites with Sb(V). The complexation constant K were- 3.15,-3.26 and- 3.48 at pH of 7.0, 5.0 and 3.0, respectively, indicating that the complexation strength between SMT and Sb(V) followed the order of pH 7.0 > pH 5.0 > pH 3.0. The binding energy between Sb(V) and the C-N group of pyrimidine ring was the highest (1.42 eV), and then followed by the groups of -NH (1.37 eV), S = O (0.66 eV) and -NH2 (0.39 eV). Besides S = O and C-N, Sb(V) tends to complex with N-H via coordination bond at pH of 7.0 while -NH2 via cation-p interaction at pH 3.0 and 5.0. Compared to pH of 5.0, the strength of cation-p interaction at pH of 3.0 weakened according to the molecular electrostatic potentialmap. These results demonstrated that different from the situation where Sb(V) exists in aqueous solution alone, the coexistence of SMT with Sb(V) affected the adsorption behavior of Sb(V) in soil and solution pH was also an influence factor. These findings in this paperwould be helpful for further understanding themobility, bioavailability and other environmental behavior of Sb(V) in soil when Sb(V) coexists with antibiotics even other organic compounds. (C) 2020 Elsevier B.V. All rights reserved

Effect of High Pressure Treatment on Poly(lactic acid)/Nano–TiO2 Composite Films

The microstructure, thermal properties, mechanical properties and oxygen and water vapor barrier properties of a poly(lactic acid) (PLA)/nano-TiO2 composite film before and after high pressure treatment were studied. Structural analysis showed that the functional group structure of the high pressure treated composite film did not change. It was found that the high pressure treatment did not form new chemical bonds between the nanoparticles and the PLA. The micro-section of the composite film after high pressure treatment became very rough, and the structure was depressed. Through the analysis of thermal and mechanical properties, high pressure treatment can not only increase the strength and stiffness of the composite film, but also increase the crystallinity of the composite film. Through the analysis of barrier properties, it is found that the barrier properties of composite films after high pressure treatment were been improved by the applied high pressure treatment