Deducing topology of protein-protein interaction networks from experimentally measured sub-networks.

BackgroundProtein-protein interaction networks are commonly sampled using yeast two hybrid approaches. However, whether topological information reaped from these experimentally-measured sub-networks can be extrapolated to complete protein-protein interaction networks is unclear.ResultsBy analyzing various experimental protein-protein interaction datasets, we found that they are not random samples of the parent networks. Based on the experimental bait-prey behaviors, our computer simulations show that these non-random sampling features may affect the topological information. We tested the hypothesis that a core sub-network exists within the experimentally sampled network that better maintains the topological characteristics of the parent protein-protein interaction network. We developed a method to filter the experimentally sampled network to result in a core sub-network that more accurately reflects the topology of the parent network. These findings have fundamental implications for large-scale protein interaction studies and for our understanding of the behavior of cellular networks.ConclusionThe topological information from experimental measured networks network as is may not be the correct source for topological information about the parent protein-protein interaction network. We define a core sub-network that more accurately reflects the topology of the parent network

Characterization of the enzyme kinetics of EMP and HMP pathway in Corynebacterium glutamicum: reference for modeling metabolic networks

The model of intracellular metabolic network based on enzyme kinetics parameters plays an important role in understanding the intracellular metabolic process of Corynebacterium glutamicum, and constructing such a model requires a large number of enzymological parameters. In this work, the genes encoding the relevant enzymes of the EMP and HMP metabolic pathways from Corynebacterium glutamicum ATCC 13032 were cloned, and engineered strains for protein expression with E.coli BL21 and P.pastoris X33 as hosts were constructed. The twelve enzymes (GLK, GPI, TPI, GAPDH, PGK, PMGA, ENO, ZWF, RPI, RPE, TKT, and TAL) were successfully expressed and purified by Ni2+ chelate affinity chromatography in their active forms. In addition, the kinetic parameters (Vmax, Km, and Kcat) of these enzymes were measured and calculated at the same pH and temperature. The kinetic parameters of enzymes associated with EMP and the HMP pathway were determined systematically and completely for the first time in C.glutamicum. These kinetic parameters enable the prediction of key enzymes and rate-limiting steps within the metabolic pathway, and support the construction of a metabolic network model for important metabolic pathways in C.glutamicum. Such analyses and models aid in understanding the metabolic behavior of the organism and can guide the efficient production of high-value chemicals using C.glutamicum as a host

General Principles for the Validation of Proarrhythmia Risk Prediction Models: An Extension of the CiPA In Silico Strategy

This white paper presents principles for validating proarrhythmia risk prediction models for regulatory use as discussed at the In Silico Breakout Session of a Cardiac Safety Research Consortium/Health and Environmental Sciences Institute/US Food and Drug Administration–sponsored Think Tank Meeting on May 22, 2018. The meeting was convened to evaluate the progress in the development of a new cardiac safety paradigm, the Comprehensive in Vitro Proarrhythmia Assay (CiPA). The opinions regarding these principles reflect the collective views of those who participated in the discussion of this topic both at and after the breakout session. Although primarily discussed in the context of in silico models, these principles describe the interface between experimental input and model‐based interpretation and are intended to be general enough to be applied to other types of nonclinical models for proarrhythmia assessment. This document was developed with the intention of providing a foundation for more consistency and harmonization in developing and validating different models for proarrhythmia risk prediction using the example of the CiPA paradigm

Experimental Evaluation of the Usability of Cartogram for Representation of GlobeLand30 Data

GlobeLand30 is the world’s first global land cover dataset at 30 m resolution for two epochs, i.e., 2000 and 2010. On the official website, the data are represented by qualitative thematic maps which show the distribution of global land cover, and some proportional symbol maps which are quantitative representations of land cover data. However, researchers have also argued that the cartogram, a kind of value-by-area representation, has some advantages over these maps in some cases, while others doubt their usability because of the possible distortion in shape. This led us to conduct an experimental evaluation of the usability of the cartogram for the representation of GlobeLand30. This experimental evaluation is a comparative analysis between the cartogram and the proportional symbol map to examine which is more effective in various kinds of quantitative analyses. The results show that the thematic map is better than the cartogram for the representation of quantity (e.g., area size), but the cartogram performs better in the representation of tendency distribution and areas’ multiple relationships. The usability of the cartogram is notably affected by map projection and the irregularity in area shapes, but the equal-area projection does not necessarily perform better than equidistance projection, especially at high latitudes

Design and Analysis of Orthogonal Polarization Point Diffraction Pinhole Plate

The pinhole plate is a key component of the point diffraction interferometer (PDI). The reasonable improvement and simulation of this device would enhance the application of point diffraction interferometry technology during the measurement of wavefronts. The traditional point diffraction interferometry measurement method is easily disturbed by environmental noise, making it difficult to obtain high-precision dynamic measurements. This paper introduces a four-step phase-shift PDI that can be employed in a common optical path. By using the principle of the finite-difference time-domain method (FDTD), a simulation model of the orthogonal polarization point diffraction pinhole plate (OP-PDPP) structure is established. The results show that when Cr is used as the film material in the pinhole plate, the parameters include a film thickness of 150 nm, a pinhole diameter of 2 μm, a wire grid period of 150 nm, and a wire grid width of 100 nm; in addition, the comprehensive extinction ratio of the pinhole plate is the greatest and the diffraction wavefront error is the smallest. Finally, the constructed experimental system is used to test the wavefront of a flat sample with a 25.4 mm aperture, and the test results are compared with those of the ZYGO interferometer. The difference in the peak-to-valley (PV) value between the OP-PDI and the ZYGO interferometer measurement is 0.0028λ, with an RMS value difference of 0.0011λ; this verifies the feasibility of the scheme proposed in this paper. The experimental results show that the proposed OP-PDPP is an effective tool for high-precision dynamic measurement

Effect of Adding Pyrolysis Carbon Black (CBp) on Soft Friction and Metal Wear during Mixing

In the cracking process of waste tires, pyrolysis carbon black (CBp), as a solid product, accounts for about 35% of the total tire rubber content. Here, the treated CBp has been gradually applied to the tire formula to improve the recycling efficiency of waste tires. This study elucidated the influence of adding CBp during the tire mixing process on soft friction and metal wear. Compared with industrial carbon black (I-CB), the friction coefficient of CBp was smaller at different mixing stages, and the ripple caused by adhesion friction was not evident. After the modified CBp (M-CBp) was obtained by implementing the surface activation of common CBp (C-CBp), the friction coefficient between M-CBp and metal increased by 10%, while the filler dispersion and comprehensive mechanical properties showed an upward trend. The wear rate of metal was higher than that observed after adding I-CB during the same mixing mode; thus, it was necessary to strengthen the wear resistance of the inner-wall surface of the mixing chamber. The –OH group on the M-CBp surface can also participate in the silane coupling reaction and aggravate the metal wear of the mixer chamber wall. Through a comparison of results, the mixing friction coefficient can reflect the strength of filler–rubber interaction, which in turn can preliminarily represent the dispersion effect and comprehensive properties, reveal the reason behind the poor performance of CBp, and highlight the need for modification from the perspective of tribology

High expression of RUNX1 in colorectal cancer subtype accelerates malignancy by inhibiting HMGCR

Colorectal cancer (CRC) presents a complex landscape, characterized by both inter-tumor and intra-tumor heterogeneity. RUNX1, a gene implicated in modulating tumor cell growth, survival, and differentiation, remains incompletely understood regarding its impact on CRC prognosis. In our investigation, we discerned a positive correlation between elevated RUNX1 expression and aggressive phenotypes across various CRC subtypes. Notably, knockdown of RUNX1 demonstrated efficacy in restraining CRC proliferation both in vitro and in vivo, primarily through inducing apoptosis and impeding cell proliferation. Mechanistically, we unveiled a direct regulatory link between RUNX1 and cholesterol synthesis, mediated by its control over HMGCR expression. Knockdown of RUNX1 in CRC cells triggered HMGCR transcriptional activation, culminating in elevated cholesterol levels that subsequently hindered cancer progression. Clinically, heightened RUNX1 expression emerged as a prognostic marker for adverse outcomes in CRC patients. Our findings underscore the pivotal involvement of RUNX1 in CRC advancement and its potential as a therapeutic target. The unique influence of RUNX1 on cholesterol synthesis and HMGCR transcriptional regulation uncovers a novel pathway contributing to CRC progression

Drilling and completion technologies for deep carbonate rocks in the Sichuan Basin: Practices and prospects

The exploration and development of oil and gas resources in the Sichuan Basin is shifting to the deeper strata. The deep and ultra-deep wells in deep carbonate gas reservoirs are faced with many difficulties, such as multiple pressure systems, poor drillability, ultra-high pressure, ultra-high temperature and high sulfur content, which bring great challenges to drilling and completion engineering. In order to ensure the smooth exploration and development of deep carbonate oil and gas resources in the Sichuan Basin, the overall concept of combining field practice and technological research is followed. During the 13th Five-Year Plan, a batch of ultra-deep wells (well depth about 8000 m) have been drilled fast and safely (such as Well SYX133 in the Shuangyushi structure), and great progresses have been achieved in the experimental research of the support technologies in drilling and completion of deep and ultra-deep wells. And the achievements are as follows. First, the optimization of non-standard well structure, combined with the application of precisely managed pressure drilling technology and under-pressure plugging technology, lays a foundation for the optimized fast drilling and the safe reaching of geological targets. Second, a high-efficiency customized PDC drill bit is comprehensively optimized, popularized and applied, which effectively improves the average rate of penetration (ROP) in difficult-to-drill formations. Third, the development and application of drilling fluids (e.g. being resistant to high temperature of 200 °C and anti-composite brine) and active under-pressure plugging technology effectively reduces downhole complexities while drilling the complex formations, such as high temperature and high pressure brine and circulation loss. Fourth, when precisely managed pressure drilling and precisely managed pressure cementing methods are applied in the strata with a narrow density window, multiple pressure systems and pressure sensitivity, the average drilling and completion fluid loss is reduced by more than 90%, and the complexity treatment time is cut down by more than 85%, and the cementing quality pass rate is increased by more than 20%. Fifth, the integrated application of ROP improvement technologies and tools (e.g. air drilling) results in a great reduction of drilling cycle and cost. It is concluded that the experimental research achievements provide basic support for the fast development of natural gas resources in the Anyue Gas Field, Sichuan Basin, and the great discovery of the Permian and Devonian natural gas resources in the northwestern Sichuan Basin. What's more, in order to adapt to the development of the deep natural gas (over 9000 m) in the Sichuan Basin during the 14th Five-Year Plan, it is necessary to speed up researches on drilling and completion technologies in nine aspects, e.g. high-temperature downhole tools and working fluid

Toxicity, Behavioral Effects, and Chitin Structural Chemistry of Reticulitermes flaviceps Exposed to Cymbopogon citratus EO and Its Major Constituent Citral

Botanical pesticides are considered the most promising alternative to synthetic pesticides, considering their less negative impacts on the environment and human health. Here, we analyzed the components of lemongrass Cymbopogon citratus essential oil (EO) and evaluated its vapor activity against Reticulitermes flaviceps, in terms of the walking and gripping abilities of workers. In addition, the effects of lemongrass EO and its major component on the cuticular content and structure of chitin in termites were also observed. Our results indicate that cis-citral (36.51%) was the main constituent of lemongrass. In the vapor toxicity assay, the LC50 values of lemongrass EO and citral were 0.328 and 0.177 μL/L, respectively. When worker antennae were treated with lemongrass EO and citral, their walking and gripping capabilities were significantly inhibited. In addition, the cuticular content, thermal stability, and crystallinity of chitin in the termites were decreased after treatment with citral. Collectively, this study provides a basis for developing and utilizing lemongrass and citral as a new environment-friendly insecticide resource to control R. flaviceps