Cellular ATP Levels Determine the Stability of a Nucleotide Kinase

The energy currency of the cell ATP, is used by kinases to drive key cellular processes. However, the connection of cellular ATP abundance and protein stability is still under investigation. Using Fast Relaxation Imaging paired with alanine scanning and ATP depletion experiments, we study the nucleotide kinase (APSK) domain of 3′-phosphoadenosine-5′-phosphosulfate (PAPS) synthase, a marginally stable protein. Here, we show that the in-cell stability of the APSK is determined by ligand binding and directly connected to cellular ATP levels. The observed protein stability change for different ligand-bound states or under ATP-depleted conditions ranges from ΔGf0 = -10.7 to +13.8 kJ/mol, which is remarkable since it exceeds changes measured previously, for example upon osmotic pressure, cellular stress or differentiation. The results have implications for protein stability during the catalytic cycle of APS kinase and suggest that the cellular ATP level functions as a global regulator of kinase activity.

Stability Analysis of Slope Based on Limit Equilibrium Method and Strength Reduction Method

Drawing on the theories of limit equilibrium and finite-element strength reduction, this paper explores the instability modes and stability change laws of the slope in zones E, W, and S of Jiajika spodumene mine, through rock mechanics tests, field survey, and numerical simulation. The results show that the sliding mode of the slope is circular arc sliding or circular arc + plane sliding. Overall, the final slope of the open-pit mine is generally stable under the current design, and the slope of the current steps is reasonable.

Evaluation of Dimensional Changes According to Aging Period and Postcuring Time of 3D-Printed Denture Base Prostheses: An In Vitro Study

During the three-dimensional (3D) printing process of a dental prosthesis, using photopolymer resin, partially polymerized resin is further cured through the postcuring process that proceeds after the printing, which improves the stability of the printed product. The mechanical properties of the end product are known to be poor if the postcuring time is insufficient. Therefore, this study evaluated the effect of the postcuring time of the 3D-printed denture base on its dimensional stability, according to the aging period. The 3D prints were processed after designing maxillary and mandibular denture bases, and after the following postcuring times were applied: no postcuring, and 5, 15, 30, and 60 min. The dimensional stability change of the denture base was evaluated and analyzed for 28 days after the postcuring process. The trueness analysis indicated that the mandibular denture base had lower output accuracy than the maxillary denture base, and the dimensional stability change increased as postcuring progressed. In the no postcuring group for the mandible, the error value was 201.1 ± 5.5 µm (mean ± standard deviation) after 28 days, whereas it was 125.7 ± 13.0 µm in the 60 min postcuring group. For both the maxilla and the mandible, shorter postcuring times induced larger dimensional stability changes during the aging process. These findings indicate that in order to manufacture a denture base with dimensional stability, a sufficient postcuring process is required during the processing stage.

Bioinformatics and wet laboratory analysis of rs1800562 to predict genetic aetiology of iron overload in Nigeria

Introduction/Objective The most reported single nucleotide polymorphism (SNP) of the HFE gene is rs1800562, representing the substitution of Adenine for Guanine at position 847 of the HFE gene. This has been widely implicated in hereditary haemochromatosis and other conditions like altered cholesterol balance, Alzheimer’s disease and cutaneous photosensitivity. Abnormal HFE protein resulting from the mutant HFE gene leads to formation of excess iron which has been postulated as likely mechanism for these diseases. Although there is evidence of iron overload in Africans, only few studies have explored possible genetic causes, and prevalence of rs1800562 is not known in West African population. Hence the need to determine the prevalence of rs1800562 in Nigeria using computational and wet laboratory approach. Methods/Case Report Details of rs1800562 were retrieved from Ensembl Genome Browser version 99. Severity of the consequences of this SNP on protein product was determined using bioinformatics tools including SIFT, Polyphen, Mutation Assessor, HOPE, I-mutant and MutPred2. Genotyping of rs1800562 was done In silico using restriction fragment length polymorphism (RFLP). Primer3plus was used for primer design, NCBI BLAST and SMS were used for primer validation. We used Webcutter 2.0 to determine suitable restriction enzymes. The genotyping was simulated using USCS virtual PCR and RestrictionMapper. Whole blood samples were obtained from 200 participants selected randomly from a pool of blood donors. DNA was extracted and flanking region of rs1800562 was amplified. The amplified product was digested by RSA1and fragments examined on agarose gel electrophoresis. Results (if a Case Study enter NA) The MAF was found to be 0.01 globally and 0.02 in Africa. In the two Nigerian population examined (Yoruba and Esan population), MAF was 0.00. Mutation Assessor and SIFT Polyphen consistently predicted the mutation to be of severe consequences. Analysis on HOPE, I-mutant and Mutpred2 revealed loss of protein stability, change in net charges affecting the HFE protein localization and its interaction with other proteins. All the participants in the wet laboratory analysis were homozygous for the wild type allele of rs1800562 (MAF=0). Conclusion This study confirmed the In silico prediction of the absence of rs1800562 in Nigeria. Future studies should focus on other SNPs of the HFE gene as well as other gene involved in iron metabolism.

Stability Analysis and Augmentation Design of a Bionic Multi-Section Variable-Sweep-Wing UAV Based on the Centroid Self-Trim Compensation Morphing

In this study, a design scheme for a high-aspect-ratio bionic multi-section variable-sweep wing unmanned aerial vehicle (UAV) that utilizes the reverse coordinated change in the sweep angle of the inner and outer wing sections is proposed, which improves the aerodynamic performance and realizes the self-trim compensation of the wing’s centroid. According to the layout characteristics of this type of UAV, a reasonable distribution design of the wingspan ratio of the inner and outer sections is explored, to reduce the impact of aerodynamic center movement and moment of inertia change. The calculation and analysis results show that the coordinated variable-sweep scheme can significantly improve the influence of sweep angle change on the longitudinal static stability margin of UAVs with a high aspect ratio. The coordinated sweep angle change in the inner and outer wing sections can not only reduce the drag during high-speed flight, but also play a significant role in improving the performance of the aircraft at different stages in the mission profile. Appropriately increasing the wingspan proportion of the inner section can reduce the trim resistance of the V-tail, reduce the thrust of the engine, and increase the range and duration of the UAV. From the perspective of stability change, the multi-section variable-sweep wing UAV with a wingspan ratio of the inner and outer sections that is between 1.41 and 1.78 has better dynamic stability performance. Among them, the UAV with a wingspan ratio of the inner and outer sections that is equal to 1.41 has better longitudinal stability performance, while the UAV with a wingspan ratio of the inner and outer sections that is equal to 1.78 has better lateral/directional stability performance.

Analysis of the SARS-CoV-2 envelope (E), nucleocapsid (N), and non-structural protein12 (nsp12) genes from COVID-19 patients in West Java

According to World Health Organization, as of January 2021, Indonesia is the only Southeast Asian country in which COVID-19 is still occurring in community transmission. West Java is one of the provinces holding the highest positive cases number. With the envelope (E), nucleocapsid (N), and non-structural protein 12 (nsp12) being the target genes of SARS-CoV-2 diagnostic kits and several antiviral drugs, the study of genetic variations has become relevant and greatly important. Out of 267 oro-nasopharyngeal swab specimens that were previously confirmed positive for COVID-19 in qPCR diagnostic test in Laboratorium Kesehatan Provinsi Jawa Barat, ten samples with acceptable qualities were selected and three samples were sequenced using Sanger sequencing. Nonsynonymous mutations were observed in the envelope gene (L21F) and in the nucleocapsid genes (R203K, G204R, A211S, and S193I). Phylogenetic analysis showed that samples were clustered with other sequences carrying identical mutations, but clustered non-discriminatively with all sequences when carrying no mutation. No pattern in geographical areas and clades, except for R203K-G204R for being a marker for the GR clade. Protein structure analysis showed that mutations observed did not change the hydrophobicity and the secondary structure of the nucleocapsid, while stability change (ΔΔG) showed that all mutations, aside from the R203K-G204R, have neutral effect on the protein stability. Therefore, it can be concluded that mutations observed in this experiment did not impart preference to disperse in certain geographical areas or cause any significant structural change in the protein.

Best templates outperform homology models in predicting the impact of mutations on protein stability

Motivation: Prediction of protein stability change upon mutation (∆∆G) is crucial for facilitating protein engineering and understanding of protein folding principles. Robust prediction of protein folding free energy change requires the knowledge of protein three-dimensional (3D) structure. Unfortunately, protein 3D structure is not always available. In this case, one can still predict the protein stability change by constructing a homology model of the protein; however, the accuracy of homology model-based ∆∆G predictions is unknown. The perspectives of using 3D structures of the best templates are also unclear. Results: To investigate these questions, we used the most popular and accurate publicly available tools: FoldX for stability change prediction and I-Tasser for homology modeling. We found that both homology models and best templates worsen the ∆∆G prediction, with best templates performing 1.5 times better than homology models. For AlphaFold models, we also found that the best templates seem to outperform protein models. Our findings imply using the 3D structures of the best templates for ∆∆G prediction if the 3D protein structure is unavailable.

The Development of Vocational Interests in Early Adolescence: Stability, Change, and State-Trait Components

Vocational interests predict major life outcomes such as job performance, college major choice, and life goals. It is therefore important to gain a better understanding of their development during the crucial years of late childhood and early adolescence, when trait-like interests are starting to develop. The present study investigated the development of vocational interests in a longitudinal sample, comprising N = 3,876 participants—assessed at four time points from ages 11 to 14. Stability, state-trait variance components, mean-level development, and gender differences in mean-levels of Realistic, Investigative, Artistic, Social, Enterprising, and Conventional (RIASEC) dimensions were examined. Stabilities were moderate for all dimensions, but Realistic, Investigative, Social, and Conventional interests became more stable over time. For Realistic, Artistic, Social, and Conventional interests, the trait variance increased over time. At age 14, all dimensions had substantial trait variance components. The mean-levels of Realistic, Investigative, Artistic, and Conventional interests decreased over the 3 years (–0.44 < d < –0.24). Initial gender differences—with girls having higher Artistic and Social interests and boys having higher Realistic and Investigative interests—increased over time. By investigating the development of vocational interests in late childhood and early adolescence, we complement previous findings and provide first insights about state-trait proportions in early adolescence.

Postural Stability Change Under Sleep Deprivation and Mental Fatigue Status

BACKGROUND: Based on posturography parameters during sleep deprivation (SD), a mental fatigue index (MFI) was constructed for healthy male cadets.METHODS: There were 37 young male subjects who volunteered for two successive days of SD. Their posturography balance, profile of mood status (POMS), and heart rate variability (HRV) were measured at four different times (10:00 and 22:00 of day 1, 10:00 and 22:00 of day 2). According to the methods used in our previous research, similar MFIs based on posturography parameters were computed. Then, correlations of MFIs with POMS scores and HRV values were evaluated by linear and nonlinear methods including quadratic, S-curve, growth, and exponential analyses.RESULTS: MFI continued to increase during SD and MFI as the independent variable had quadratic relationships with fluster (R2 0.057), depression (R2 0.067), and anger (R2 0.05) scores of POMS. A linear correlation was found between MFI and the depression score (R2 0.045) and MFI correlated linearly (R2 0.029) and nonlinearly (R2 0.03) with heart rate. Similarly, MFI reflected changes in the time and frequency domain parameters of HRV, with linear (R2range: 0.0290.082) or nonlinear (R2range: 0.0300.082) relationships.DISCUSSION: The increase of MFI was linked with amplification of personal negative moods and an imbalance of autonomic nervous system activity. The findings suggest that MFI might be a potential indicator of mental fatigue and provide a method to prevent driving fatigue and human errors.Cheng S, Yang J, Su M, Sun J, Xiong K, Ma J, Hu W. Postural stability change under sleep deprivation and mental fatigue status. Aerosp Med Hum Perform. 2021; 92(8):627632.

The Development of Vocational Interests in Early Adolescence: Stability, Change, and State-Trait Components

Vocational interests predict major life outcomes such as job performance, college major choice, and life goals. It is therefore important to gain a better understanding of their development during the crucial years of late childhood and early adolescence, when trait-like interests are starting to develop. The present study investigated the development of vocational interests in a longitudinal sample, comprising N = 3,876 participants—assessed at four time points from ages 11 to 14. Stability, state-trait variance components, mean-level development, and gender differences in mean-levels of Holland’s (1997) RIASEC dimensions were examined. Stabilities were moderate for all dimensions, but Realistic, Investigative, Social, and Conventional interests became more stable over time. For Realistic, Artistic, Social, and Conventional interests, the trait variance increased over time. At age 14, all dimensions had substantial trait variance components. The mean-levels of Realistic, Investigative, Artistic, and Conventional interests decreased over the 3 years (-0.44 &lt; d &lt; -0.24). Initial gender differences—with girls having higher Artistic and Social interests and boys having higher Realistic and Investigative interests—increased over time. By investigating the development of vocational interests in late childhood and early adolescence, we complement previous findings and provide first insights about state-trait proportions in early adolescence.