Reconstruction of ancestral protein sequences and its applications

BACKGROUND: Modern-day proteins were selected during long evolutionary history as descendants of ancient life forms. In silico reconstruction of such ancestral protein sequences facilitates our understanding of evolutionary processes, protein classification and biological function. Additionally, reconstructed ancestral protein sequences could serve to fill in sequence space thus aiding remote homology inference. RESULTS: We developed ANCESCON, a package for distance-based phylogenetic inference and reconstruction of ancestral protein sequences that takes into account the observed variation of evolutionary rates between positions that more precisely describes the evolution of protein families. To improve the accuracy of evolutionary distance estimation and ancestral sequence reconstruction, two approaches are proposed to estimate position-specific evolutionary rates. Comparisons show that at large evolutionary distances our method gives more accurate ancestral sequence reconstruction than PAML, PHYLIP and PAUP*. We apply the reconstructed ancestral sequences to homology inference and functional site prediction. We show that the usage of hypothetical ancestors together with the present day sequences improves profile-based sequence similarity searches; and that ancestral sequence reconstruction methods can be used to predict positions with functional specificity. CONCLUSIONS: As a computational tool to reconstruct ancestral protein sequences from a given multiple sequence alignment, ANCESCON shows high accuracy in tests and helps detection of remote homologs and prediction of functional sites. ANCESCON is freely available for non-commercial use. Pre-compiled versions for several platforms can be downloaded from

Fog and Cloud Computing Assisted IoT Model Based Personal Emergency Monitoring and Diseases Prediction Services

Along with the rapid development of modern high-tech and the change of people's awareness of healthy life, the demand for personal healthcare services is gradually increasing. The rapid progress of information and communication technology and medical and bio technology not only improves personal healthcare services, but also brings the fact that the human being has entered the era of longevity. At present, there are many researches focused on various wearable sensing devices and implant devices and Internet of Things in order to capture personal daily life health information more conveniently and effectively, and significant results have been obtained, such as fog computing. To provide personal healthcare services, the fog and cloud computing is an effective solution for sharing health information. The health big data analysis model can provide personal health situation reports on a daily basis, and the gene sequencing can provide hereditary disease prediction. However, the injury mortality and emergency diseases since long ago caused death and great pain for the family. And there are no effective rescue methods to save precious lives and no methods to predict the disease morbidity likelihood. The purpose of this research is to capture personal daily health information based on sensors and monitoring emergency situations with the help of fog computing and mobile applications, and disease prediction based on cloud computing and big data analysis. Through the comparison of test results it was proved that the proposed emergency monitoring based on fog and cloud computing and the diseases prediction model based on big data analysis not only gain more of the rescue time than the traditional emergency treatment method, but they also accumulate lots of different personal healthcare related experience. The Taian 960 hospital of PLA and the Yanbian Hospital as IM testbed were joined to provide emergency monitoring tests, and to ensure the CVD and CVA morbidity likelihood medical big data analysis, the people around Taian city participated in personal health tests. Through the project, the five network layers architecture and integrated MAPE-K Model based EMDPS platform not only made the cooperation between hospitals feasible to deal with emergency situations, but also the Internet medicine for the disease prediction was built

Switching Fuzzy Guaranteed Cost Control for Nonlinear Networked Control Systems

This paper deals with the problem of guaranteed cost control for a class of nonlinear networked control systems (NCSs) with time-varying delay. A guaranteed cost controller design method is proposed to achieve the desired control performance based on the switched T-S fuzzy model. The switching mechanism is introduced to handle the uncertainties of NCSs. Based on Lyapunov functional approach, some sufficient conditions for the existence of state feedback robust guaranteed cost controller are presented. Simulation results show that the proposed method is effective to guarantee system’s global asymptotic stability and quality of service (QoS)

The value of a novel percutaneous lung puncture clamp biopsy technique in the diagnosis of pulmonary nodules

Abstract Background: Computed tomography-guided percutaneous lung biopsy is a crucial method to determine pulmonary anomalies, and is highly accurate in detecting evidence of malignancies, allowing medical practitioners to identify the stage of malignancy and thus help to plan the treatment regimens of patients.Objective: To explore the clinical application of a new computed tomography-guided percutaneous lung puncture clamp biopsy technique in the diagnosis of pulmonary nodules, characterized by ground-glass opacity on chest computed tomography images.Methods: A unique instrument named ‘combined percutaneous lung biopsy forceps’, consisting of a biopsy forceps, a 15-gauge coaxial needle and needle core, was designed. The new tool was used to obtain specimens in nine patients with pulmonary ground-glass opacity. The specimen volumes and the safety of using the instrument were measured. The samples obtained were also assessed to see if they were sufficient for conducting histological tests.Result: Samples were obtained in all nine patients – a success rate of 100%. Consistently, the volume of each specimen was sufficient to make a histological diagnosis. No serious complications, such as pneumothorax – primary spontaneous pneumothorax or secondary spontaneous pneumothorax – occurred during the biopsy.Conclusions: The application of this new tool in obtaining tissue specimens in patients with pulmonary ground-glass opacity under the guidance of chest computed tomography was invaluable in terms of its high accuracy and safety. Moreover, its effect was better compared to using a fine-needle aspiration biopsy or a cutting-needle biopsy. Therefore, this instrument can be used for histological diagnosis. [Ethiop. J. Health Dev. 2021; 35(2):85-90]Key words: Ground-glass opacity; percutaneous lung puncture clamp biopsy; fine-needle aspiration biopsy; cutting-needle biops

A pathogenic UFSP2 variant in an autosomal recessive form of pediatric neurodevelopmental anomalies and epilepsy

Purpose: Neurodevelopmental disabilities are common and genetically heterogeneous. We identified a homozygous variant in the gene encoding UFM1-specific peptidase 2 (UFSP2), which participates in the UFMylation pathway of protein modification. UFSP2 variants are implicated in autosomal dominant skeletal dysplasias, but not neurodevelopmental disorders. Homozygosity for the variant occurred in eight children from four South Asian families with neurodevelopmental delay and epilepsy. We describe the clinical consequences of this variant and its effect on UFMylation.Methods: Exome sequencing was used to detect potentially pathogenic variants and identify shared regions of homozygosity. Immunoblotting assessed protein expression and post-translational modifications in patient-derived fibroblasts.Results: The variant (c.344T\u3eA; p.V115E) is rare and alters a conserved residue in UFSP2. Immunoblotting in patient-derived fibroblasts revealed reduced UFSP2 abundance and increased abundance of UFMylated targets, indicating the variant may impair de-UFMylation rather than UFMylation. Reconstituting patient-derived fibroblasts with wild-type UFSP2 reduced UFMylation marks. Analysis of UFSP2\u27s structure indicated that variants observed in skeletal disorders localize to the catalytic domain, whereas V115 resides in an N-terminal domain possibly involved in substrate binding.Conclusion: Different UFSP2 variants cause markedly different diseases, with homozygosity for V115E causing a severe syndrome of neurodevelopmental disability and epilepsy

Structural Basis for Functional Tetramerization of Lentiviral Integrase

Experimental evidence suggests that a tetramer of integrase (IN) is the protagonist of the concerted strand transfer reaction, whereby both ends of retroviral DNA are inserted into a host cell chromosome. Herein we present two crystal structures containing the N-terminal and the catalytic core domains of maedi-visna virus IN in complex with the IN binding domain of the common lentiviral integration co-factor LEDGF. The structures reveal that the dimer-of-dimers architecture of the IN tetramer is stabilized by swapping N-terminal domains between the inner pair of monomers poised to execute catalytic function. Comparison of four independent IN tetramers in our crystal structures elucidate the basis for the closure of the highly flexible dimer-dimer interface, allowing us to model how a pair of active sites become situated for concerted integration. Using a range of complementary approaches, we demonstrate that the dimer-dimer interface is essential for HIV-1 IN tetramerization, concerted integration in vitro, and virus infectivity. Our structures moreover highlight adaptable changes at the interfaces of individual IN dimers that allow divergent lentiviruses to utilize a highly-conserved, common integration co-factor

Disturbance Effect of Pipe Jacking Group Adjacent Excavation on Surrounding Soil

Under the modern and complicated urban environment, clarifying the interaction mechanism and mutual influence mechanism between the urban tunnel and the surrounding environment is of considerable significance to the construction and operation of the tunnel. To understand and grasp the excavation-induced disturbance range and mechanism of adjacent pipeline jacking group on surrounding soils, this paper carries out relevant researches. Based on a case history of a three-hole parallel adjacent jacking pipeline in shallow overburden, a field test and assessment are performed. By setting monitoring points around the monitoring section, the earth pressure and water pressure under different buried depths and different spacing are monitored. For further discussion, the general law of soil disturbance around single-hole, double-hole, and three-hole jacking is investigated, the calculation method of lateral disturbance range and overlapping area range of pipe jacking group is deduced, and the degree of soil disturbance is evaluated as well. The results show that there will be different degrees of disturbance superposition in parallel multihole jacking due to the influence of the spacing, and the disturbance intensity is greatly affected by the parallel distance and buried depth

Psychometric Evaluation of the Affective Reactivity Index Among Children and Adolescents in China: A Multi-Method Assessment Approach

The Affective Reactivity Index (ARI) is one of the most studied scales for assessing youth irritability, but little is known about its measurement performance in community populations. This study applied item response theory (IRT), network analysis, and classical test theory (CTT) to examine the psychometric properties of the ARI in a sample of n = 395 community-based children (M-age = 13.44, SD = 2.51) and n = 403 parents. In this sample, the ARI demonstrated good reliability, as well as convergent and concurrent validity. The one-factor structure was supported by both confirmatory factor analysis (CFA) and network analysis. IRT analysis revealed that the ARI effectively distinguished between various levels of irritability within the community population. Network analysis identified "Loses temper easily,""Gets angry frequently," and "Often loses temper" are central aspects of irritability. The findings support the ARI as a brief, reliable, and valid instrument to assess irritability in community children and adolescents

Factor structure and measurement invariance of the 8-item CES-D: a national longitudinal sample of Chinese adolescents

BackgroundThe 8-item Center for Epidemiologic Studies Depression Scale (CES-D 8) has been widely used to measure depressive symptoms in many large-scale surveys. Due to its brevity, it can lower costs, relieve respondent burdens, and ensure data quality. However, its factor structure and measurement invariance across gender and time among adolescents have not been adequately evaluated. This study investigated its factor structure and measurement invariance across gender and time among adolescents.MethodsThe data was drawn from the China Family Panel Studies (CFPS) conducted in 2018 and 2020, with 3099 participants (46.82% girls) aged 11 to 18 in 2018. First, exploratory and confirmatory factor analyses were used to examine the factor structure of the CES-D 8. Next, multi-group confirmatory factor analysis was conducted to test its measurement invariance across gender and time. Finally, a longitudinal cross-gender test was conducted to further confirm the stability of the scale.ResultsA two-factor structure was identified among the adolescents, including Negative Symptoms and Diminished Happiness Feeling. Measurement invariance across gender and time, as well as the longitudinal cross-gender invariance, was supported, with configural, factor loadings, thresholds and residual invariance.ConclusionsThe factor structure of the CES-D 8 remains stable across gender and time among adolescents, indicating that it is a promising instrument for measuring depressive symptoms, especially in large-scale and longitudinal surveys.</p