SigFlux: A novel network feature to evaluate the importance of proteins in signal transduction networks

BACKGROUND: Measuring each protein's importance in signaling networks helps to identify the crucial proteins in a cellular process, find the fragile portion of the biology system and further assist for disease therapy. However, there are relatively few methods to evaluate the importance of proteins in signaling networks. RESULTS: We developed a novel network feature to evaluate the importance of proteins in signal transduction networks, that we call SigFlux, based on the concept of minimal path sets (MPSs). An MPS is a minimal set of nodes that can perform the signal propagation from ligands to target genes or feedback loops. We define SigFlux as the number of MPSs in which each protein is involved. We applied this network feature to the large signal transduction network in the hippocampal CA1 neuron of mice. Significant correlations were simultaneously observed between SigFlux and both the essentiality and evolutionary rate of genes. Compared with another commonly used network feature, connectivity, SigFlux has similar or better ability as connectivity to reflect a protein's essentiality. Further classification according to protein function demonstrates that high SigFlux, low connectivity proteins are abundant in receptors and transcriptional factors, indicating that SigFlux candescribe the importance of proteins within the context of the entire network. CONCLUSION: SigFlux is a useful network feature in signal transduction networks that allows the prediction of the essentiality and conservation of proteins. With this novel network feature, proteins that participate in more pathways or feedback loops within a signaling network are proved far more likely to be essential and conserved during evolution than their counterparts

A nonparametric model for quality control of database search results in shotgun proteomics

<p>Abstract</p> <p>Background</p> <p>Analysis of complex samples with tandem mass spectrometry (MS/MS) has become routine in proteomic research. However, validation of database search results creates a bottleneck in MS/MS data processing. Recently, methods based on a randomized database have become popular for quality control of database search results. However, a consequent problem is the ignorance of how to combine different database search scores to improve the sensitivity of randomized database methods.</p> <p>Results</p> <p>In this paper, a multivariate nonlinear discriminate function (DF) based on the multivariate nonparametric density estimation technique was used to filter out false-positive database search results with a predictable false positive rate (FPR). Application of this method to control datasets of different instruments (LCQ, LTQ, and LTQ/FT) yielded an estimated FPR close to the actual FPR. As expected, the method was more sensitive when more features were used. Furthermore, the new method was shown to be more sensitive than two commonly used methods on 3 complex sample datasets and 3 control datasets.</p> <p>Conclusion</p> <p>Using the nonparametric model, a more flexible DF can be obtained, resulting in improved sensitivity and good FPR estimation. This nonparametric statistical technique is a powerful tool for tackling the complexity and diversity of datasets in shotgun proteomics.</p

Effect of the of remazolam toluenesulfonate and IPACK on postoperative rehabilitation and sedation in elderly patients undergoing knee arthroplasty

Purpose: To investigate the effect of the combination of remazolam toluenesulfonate and infiltration between the popliteal artery and capsule of the knee (IPACK) on the rehabilitation and sedation of elderly patients undergoing knee arthroplasty. Methods: A total of 84 elderly patients who underwent knee arthroplasty in Quzhou Affiliated Hospital of Wenzhou Medical University between January 2021 and December 2021 were given IPACK in combination with adductor canal block under ultrasound guidance. Forty (40) patients were given anesthesia with propofol + sufentanil + cis-benzene sulfonic acid atracurium (control group), while 44 patients received anesthesia with remazolam toluenesulfonate + sufentanil + cis-benzene sulfonic acid atracurium (study group). Various clinical indices in the patients were assessed Results: Relative to control, there were significantly lower visual analog scale (VAS) scores at 6 and 12 h after operation, lower frequency of post-operation pumping with PCA pump, lower frequency of remedial analgesia within 48 h after operation (p &lt; 0.05). Moreover, the time taken for spontaneous recovery of breathing, recovery time, and extubation time were similar in the two groups (p &gt; 0.05). The muscle strength of quadriceps femoris of the affected knee joint was higher in the study group than in the control group at 12, 24, and 48 h, after operation (p &lt; 0.05). Conclusion: The combination of remazolam toluenesulfonate with IPACK effectively alleviate pain in elderly patients undergoing knee arthroplasty and improves sedation without increasing cognitive dysfunction. This treatment strategy has potentials for further investigation for possible large-scale application

JMJD3 promotes survival of diffuse large B-cell lymphoma subtypes via distinct mechanisms.

JMJD3 (Jumonji domain containing-3), a histone H3 Lys27 (H3K27) demethylase, has been reported to be involved in the antigen-driven differentiation of germinal center B-cells. However, insight into the mechanism of JMJD3 in DLBCL (Diffuse large B-cell lymphoma) progression remains poorly understood. In this study, we investigated the subtype-specific JMJD3-dependent survival effects in DLBCL. Our data showed that in the ABC subtype, silencing-down of JMJD3 inhibited interferon regulatory factor 4 (IRF4) expression in a demethylase activity-dependent fashion. IRF4 reciprocally stimulated expression of JMJD3, forming a positive feedback loop that promoted survival in these cells. Accordingly, IRF4 expression was sufficient to rescue the pro-apoptotic effect of JMJD3 suppression in the ABC, but not in the GCB subtype. In contrast, ectopic overexpression of BCL-2 completely offset JMJD3-mediated survival in the GCB DLBCL cells. In vivo, treatment with siRNA to JMJD3 reduced tumor volume concordant with increased apoptosis in either subtype. This suggests it is a common target, though the distinctive signaling axes regulating DCBCL survival offer different strategic options for treating DLBCL subtypes

Theoretical Modeling on Chemical Composition and Mechanical Properties of Well Cement under Carbonation Reactions

This paper presents theoretical models of the phase transformation and the change of mechanical properties of oil well cement due to underground carbonation reactions. Application of oil well cement has become common practice in CO2 underground storage formations. However, the CO2 stored underground may leak through damaged well cement, and it can cause carbonation reactions which may significantly decrease the mechanical properties of well cement. Extensive research has been conducted by using experimental methods in laboratories to characterize the carbonation reactions of cement underground. However, no theoretical formulations have been developed considering the mechanical properties change due to the carbonation effect. In this paper, the CO2 profile was predicted first by the error function solution of a 1D CO2 diffusion equation and further the carbonation reaction rate was calculated. The phase transformation of well cement due to carbonation were then analyzed by using a stoichiometric model. After that, the changes of mechanical properties of well cement were modeled using a two-phase generalized self-consistent model at different scales. Specifically, the decrease of the elastic modulus of well cement during the carbonation process was used as an example application of the model. Finally, the modeling result was validated with published experimental results. &nbsp;</p

Alternate erosion and deposition in the Yangtze Estuary and its future change

The morphological changing trend of the Yangtze Estuary, the largest estuary of Asia, has become a focus of research in recent years. Based on a long series of topographic data from 1950 to 2015, this paper studied the erosion-deposition pattern of the entire Yangtze Estuary. An alternation between erosion and deposition was found during the past 65 years, which was in correspondence to the alternation between flood and dry periods identified by multi-year average duration days of high-level water flow (defined as discharge ≥ 60,000 m3/s, namely, D≥60,000) from the Yangtze River Basin. A quantitative relationship was further developed between the erosional/depositional rate of the Yangtze Estuary and the interpreting variables of yearly water discharge, D≥60,000 and yearly river sediment load, with contributing rates of 1%, 59% and 40%, respectively. Mechanism behind the alternate erosion and deposition pattern was analyzed by examining residual water surface slope and the corresponding capacity of sediment transport in flood and dry periods. In flood periods, a larger discharge results in steeper slope of residual water level which permits a greater capacity of sediment transport. Therefore, more bed materials can be washed to the sea, leading to erosion of the estuary. In contrast, flatter slope of residual water level occurs in dry periods, and deposition dominates the estuarine area due to the decreased capacity of sediment transport and the increased backwater effect of flood-tide. Coastal dynamics and estuarine engineering projects alter the local morphological changes, but slightly affect the total erosional/depositional rate of the whole estuarine region. Heavy sedimentation within the Yangtze Estuary after the impoundment of the Three Gorges Dam can be attributed to the reduced occurrence frequency of flood years due to water regulation by the dam, and largely (at least 36%–52%) sourced from the sea. Deposition is still possible to occur in the Yangtze Estuary in the future, because the multi-year average D≥60,000 is unlikely to exceed the critical value of 14 days/yr which corresponds to the future equilibrium state of the Yangtze Estuary, under the water regulation of the large cascade dams in the upper Yangtze. Nevertheless, the mean depositional rate will not surpass the peak value of the past years, since the total sediment load entering the Yangtze Estuary has presented a decreasing trend

Ambient air pollution and adverse birth outcomes: a natural experiment study

Background Radical regulations to improve air quality, including traffic control, were implemented prior to and during the 2008 Beijing Olympic Games. Consequently, ambient concentrations of nitrogen dioxide (NO 2 ) and particular matter 10 micrometers or less (PM 10 ), were reduced in a distinct and short window of time, which presented a natural experiment for testing the relationships between maternal exposure to PM 10 and NO 2 during pregnancy and adverse birth outcomes. Methods We estimated the effect of PM 10 and NO 2 exposure during each trimester of gestation on the risk of preterm birth among live births and the birth weight among term babies. The data were based on 50,874 live births delivered between January 1, 2006 and December 31, 2010 at the Beijing Haidian Maternal and Child Health Hospital. Air monitoring data for the same period were obtained from the Beijing Municipal Environmental Monitoring Center. Results Among full-term births, maternal exposure to NO 2 in the third trimester predicted birth weight, with each 10-unit increment (per 10 ug/m 3 ) in NO 2 concentration associated with a 13.78 g (95 % confidence interval: −21.12, −6.43; p \u3c 0.0001) reduction in birth weight. This association was maintained after adjusting for other pollutants, including carbon monoxide (CO), sulfur dioxide (SO 2 ), and PM 10 . No relationship was found between the concentration of PM 10 and low birth weight among full-term births. Neither PM 10 nor NO 2 concentrations predicted the risk of premature birth. Conclusions Exposure to ambient air pollution during certain periods of pregnancy may decrease birth weight, but the effect size is small