Reversibly Reactive Affinity Selection-Mass Spectrometry Enables Identification of Covalent Peptide Binders.

Covalent peptide binders have found applications as activity-based probes and as irreversible therapeutic inhibitors. Currently, there is no rapid, label-free, and tunable affinity selection platform to enrich covalent reactive peptide binders from synthetic libraries. We address this challenge by developing a reversibly reactive affinity selection platform termed ReAct-ASMS enabled by tandem high-resolution mass spectrometry (MS/MS) to identify covalent peptide binders to native protein targets.

Development of an α-Klotho Recognizing High-Affinity Peptide Probe from In-Solution Enrichment.

The kidney, parathyroid gland, and choroid plexus express the aging-related transmembrane protein α-Klotho, a coreceptor of the fibroblast growth factor 23 (FGF23) receptor complex. Reduced α-Klotho levels are correlated with chronic kidney disease and other age-related diseases, wherein they are released from membranes into circulation. Klotho's potential physiological action as a hormone is of current scientific interest.

Structure of the p53 degradation complex from HPV16.

Human papillomavirus (HPV) is a significant contributor to the global cancer burden, and its carcinogenic activity is facilitated in part by the HPV early protein 6 (E6), which interacts with the E3-ligase E6AP, also known as UBE3A, to promote degradation of the tumor suppressor, p53. In this study, we present a single-particle cryoEM structure of the full-length E6AP protein in complex with HPV16 E6 (16E6) and p53, determined at a resolution of ~3.3 Å.

Increasing exercise participation during the COVID-19 pandemic: the buffering role of nostalgia.

Introduction: Due to the coronavirus disease 2019 (COVID-19) pandemic, people faced difficulties engaging in exercise activities as usual. As a result, there has been an increase in the demand for home exercises and online sales. However, there is little research on individuals' buying and exercise behaviors during the pandemic.

Electrophile Scanning Reveals Reactivity Hotspots for the Design of Covalent Peptide Binders.

Protein-protein interactions (PPIs) are intriguing targets in drug discovery and development. Peptides are well suited to target PPIs, which typically present with large surface areas lacking distinct features and deep binding pockets. To improve binding interactions with these topologies and advance the development of PPI-focused therapeutics, potential ligands can be equipped with electrophilic groups to enable binding through covalent mechanisms of action.

Measuring educational leadership in Singapore: re-examining the psychometric properties of the Multifactor Leadership Questionnaire.

Introduction: The Multifactor Leadership Questionnaire (MLQ-5X) has been used frequently to assess leadership in different settings. Despite its popularity, there are many critiques of the MLQ-5X such as its questionable multidimensional structure, lack of connection to the theory and the different factor structures of the measurement tool. The purpose of this study was to re-examine the psychometric properties of the MLQ-5X in the Singapore educational context using two datasets.

Cryo-EM structure of human PAPP-A2 and mechanism of substrate recognition.

Pregnancy-Associated Plasma Protein A isoforms, PAPP-A and PAPP-A2, are metalloproteases that cleave insulin-like growth factor binding proteins (IGFBPs) to modulate insulin-like growth factor signaling. The structures of homodimeric PAPP-A in complex with IGFBP5 anchor peptide, and inhibitor proteins STC2 and proMBP have been recently reported. Here, we present the single-particle cryo-EM structure of the monomeric, N-terminal LG, MP, and the M1 domains (with the exception of LNR1/2) of human PAPP-A2 to 3.

Branched Multimeric Peptides as Affinity Reagents for the Detection of α-Klotho Protein.

α-Klotho, an aging-related protein found in the kidney, parathyroid gland, and choroid plexus, acts as an essential co-receptor with the fibroblast growth factor 23 receptor complex to regulate serum phosphate and vitamin D levels. Decreased levels of α-Klotho are a hallmark of age-associated diseases. Detecting or labeling α-Klotho in biological milieu has long been a challenge, however, hampering the understanding of its role.

High-Throughput Proteome Profiling of Plasma and Native Plasma Complexes Using Native Chromatography.

We describe a high-throughput method for co-fractionation mass spectrometry (CF-MS) profiling for native plasma protein profiling. CF-MS allows the profiling of endogenous protein complexes between samples. Proteins often interact with other proteins and form macromolecular complexes that are different in disease states as well as cell states and cell types.

Structure of the PAPP-A complex reveals mechanism of substrate recognition.

Insulin-like growth factor (IGF) signaling is highly conserved and tightly regulated by proteases including Pregnancy-Associated Plasma Protein A (PAPP-A). PAPP-A and its paralog PAPP-A2 are metalloproteases that mediate IGF bioavailability through cleavage of IGF binding proteins (IGFBPs). Here, we present single-particle cryo-EM structures of the catalytically inactive mutant PAPP-A (E483A) in complex with a peptide from its substrate IGFBP5 (PAPP-A) and also in its substrate-free form, by leveraging the power of AlphaFold to generate a high quality predicted model as a starting template.

Triple-threat quantitative multiplexed plasma proteomics analysis on immune complex disease MRL-lpr mice.

Systemic lupus erythematosus is a common autoimmune inflammatory disease which is associated with increases in autoantibodies and immune complexes that deposit in the kidney. The MRL-lpr mouse is a common mouse model used for the study of lupus and immune complex glomerulonephritis but very little is known about the plasma proteome changes in this model. We performed in-depth quantitative proteome profiling on MRL-lpr and control (strain MpJ) mice to investigate the changes in the proteome, immunoglobulins and their glycoproteome as well as protein and immune complexes.

Pathological gaming: a longitudinal study from the perspectives of mental health problems and social stress model.

Debates about pathological gaming continues in the wake of the World Health Organization's (WHO) decision to establish a gaming disorder diagnosis. Questions persist whether gaming disorder is best conceived as a stand-alone psychiatric disorder, or whether it heralds or accompanies other, more established conditions, such as depression or ADHD. We tested these hypotheses in a sample of 3,034 youth from Singapore.

Is Self-Determined Motivation a Useful Agent to Overcome Perceived Exercise Barriers in Patients With Type 2 Diabetes Mellitus?

: Devising a program to increase physical activity (PA)/exercise behavior in patients with type 2 diabetes mellitus (T2DM) can meet with limited effectiveness in real-world settings because of the variety of barriers to PA/exercise that individuals need to overcome. An alternative approach is to explore whether targeting motivation as a facilitator may be effective to increase PA/exercise. This study aimed to understand attitudes toward perceived barriers to PA/exercise by examining individual levels of motivation, grounded on self-determination theory, in patients with T2DM.

Aggressive Video Games are Not a Risk Factor for Future Aggression in Youth: A Longitudinal Study.

The issue of whether video games with aggressive or violent content (henceforth aggressive video games) contribute to aggressive behavior in youth remains an issue of significant debate. One issue that has been raised is that some studies may inadvertently inflate effect sizes by use of questionable researcher practices and unstandardized assessments of predictors and outcomes, or lack of proper theory-driven controls. In the current article, a large sample of 3034 youth (72.

Motivations for Volunteering and Its Associations with Time Perspectives and Life Satisfaction: A Latent Profile Approach.

This study aims to examine motivation for volunteering and its association with time perspective and life satisfaction among volunteers ( N = 221). Latent profile analysis was used to profile individuals based on their time perspectives and then to compare group differences in life satisfaction and volunteering motivation. Three profiles were identified.

Students' Motivational Profiles in the Physical Education Context.

The purpose of the current study is to test the self-determination theory (SDT) continuum hypothesis of motivation using latent profile analysis (LPA). A total of 3,220 school students took part in the study. We compared LPA solutions estimated using the four motivation types versus the two higher-order dimensions to assess their degree of correspondence to the SDT continuum hypothesis.

Chronic inhibition, self-control and eating behavior: test of a 'resource depletion' model.

The current research tested the hypothesis that individuals engaged in long-term efforts to limit food intake (e.g., individuals with high eating restraint) would have reduced capacity to regulate eating when self-control resources are limited.

Development of the talent development environment questionnaire for sport.

As sporting challenge at the elite level becomes ever harder, maximizing effectiveness of the talent development pathway is crucial. Reflecting this need, this paper describes the development of the Talent Development Environment Questionnaire, which has been designed to facilitate the development of sporting potential to world-class standard. The questionnaire measures the experiences of developing athletes in relation to empirically identified "key features" of effective talent development environments.

Evaluating the effects of implementation intention and self-concordance on behaviour.

The purpose of the present study was to investigate effects of implementation intentions on taking one multivitamin tablet, everyday, for 2 weeks, among individuals who endorsed self-concordant and self-discordant forms of motivation. A 2 (implementation intentions: yes, no) × 3 (motivation: self-concordance, self-discordance, control) experimental design was adopted with university students being exposed to manipulations of implementation intentions, self-concordance, and self-discordance (male = 110, female = 120, M age = 23.50 years, SD = 7.

Effects of a 12-week exercise training programme on aerobic fitness, body composition, blood lipids and C-reactive protein in adolescents with obesity.

Introduction: Developing effective exercise programmes for the paediatric population is a strategy for decreasing obesity and is expected to help in eventually limiting obesity-associated long-term health and societal impact. In this study, the effects of a 12-week twice weekly additional exercise training, which comprised a combination of circuit-based resistance training and aerobic exercises, in additional to typical physical education sessions, on aerobic fitness, body composition and serum C-reactive protein (CRP) and lipids were analysed in 13- to 14-year-old obese boys contrasted with a control group.

Materials And Methods: Both the exercise group (EG, n = 12) and control group (CG, n = 12) participated in the typical 2 sessions of 40-minute physical education (PE) per week in schools, but only EG participated in additional 2 sessions per week of 45 to 60 minutes per session of exercise training, which comprised a combination of circuit-based resistance training and aerobic exercises maintained at 65% to 85% maximum heart rate (HRmax = 220 - age).

Cross-cultural generalizability of the theory of planned behavior among young people in a physical activity context.

The present study tested the cross-cultural generalizability of the measurement and structural parameters of the theory of planned behavior (TPB) among youth in a physical activity context. Pupils from five cultural groups completed measures of attitudes, subjective norms, perceived behavioral control (PBC), and intentions for physical activity. Five weeks later, participants completed self-report measures of physical activity behavior.