ZCCHC8, the nuclear exosome targeting component, is mutated in familial pulmonary fibrosis and is required for telomerase RNA maturation.

Short telomere syndromes manifest as familial idiopathic pulmonary fibrosis; they are the most common premature aging disorders. We used genome-wide linkage to identify heterozygous loss of function of ZCCHC8, a zinc-knuckle containing protein, as a cause of autosomal dominant pulmonary fibrosis. ZCCHC8 associated with TR and was required for telomerase function. In ZCCHC8 knockout cells and in mutation carriers, genomically extended telomerase RNA (TR) accumulated at the expense of mature TR, consistent with a role for ZCCHC8 in mediating TR 3' end targeting to the nuclear RNA exosome. We generated Zcchc8-null mice and found that heterozygotes, similar to human mutation carriers, had TR insufficiency but an otherwise preserved transcriptome. In contrast, Zcchc8-/- mice developed progressive and fatal neurodevelopmental pathology with features of a ciliopathy. The Zcchc8-/- brain transcriptome was highly dysregulated, showing accumulation and 3' end misprocessing of other low-abundance RNAs, including those encoding cilia components as well as the intronless replication-dependent histones. Our data identify a novel cause of human short telomere syndromes-familial pulmonary fibrosis and uncover nuclear exosome targeting as an essential 3' end maturation mechanism that vertebrate TR shares with replication-dependent histones.

Time perspectives and procrastination in university students: exploring the moderating role of basic psychological need satisfaction.

BACKGROUND: Research on procrastination, regarding time perspective factors and basic psychological need satisfaction (BPNS) has placed this problem at the meeting point of individual and contextual variables. The present study focused both on the individual, given that time perspectives can be defined as a person's attitude to an object (time) at three moments (present, past, future); and on contextual aspects, because the satisfaction of basic psychological needs (competence, autonomy, relatedness) is facilitated or made difficult by social contexts. Based on this, the aim of this study was to analyse the relationships between time perspectives and inter-subject procrastination variations, testing the moderating role of BPNS in this relationship. METHOD: A total of 1,188 undergraduate students, aged 17-50 years (M = 20.02, SD = 2.63), completed three questionnaires containing the variables of interest. RESULTS: Regression analyses showed significant negative (thus, potentially protective) association of future time perspective with all three procrastination dimensions (decisional procrastination, implemental delay, and lateness). Conversely, past-negative time perspective showed a positive (thus, potentially adverse) association with procrastination. Satisfaction of the need for competence also showed a negative (thus, potentially protective) association with all procrastination dimensions. On eight occasions, the relationships between time perspectives and procrastination dimensions were moderated by psychological need satisfaction. CONCLUSIONS: These findings show that BPNS may play relevant roles in the negative (favourable) relationships between procrastination dimensions and positive time perspectives, as well as in the positive (adverse) associations between negative time perspectives and procrastination dimensions. Contextual interventions fostering enhanced levels of perceived autonomy, competence, and relatedness, as well as future time perspective, are thus strong candidates to consider for use and evaluation by policy makers, pedagogues, teachers, coaches and other professionals interested in counteracting procrastination tendencies.

VERICIGUAT RESCUES CYCLIC GUANOSINE MONOPHOSPHATE PRODUCTION IN HUMAN AORTIC VASCULAR SMOOTH MUSCLE CELLS AND AUGMENTS VASORELAXATION IN AORTIC RINGS EXPOSED TO HIGH GLUCOSE.

Background: Normal endothelial cell dependent vascular smooth muscle cell function is mediated by nitric oxide (NO), which stimulates soluble guanylyl cyclase (sGC) production of the second messenger, cyclic guanosine monophosphate (cGMP) leading to increased protein kinase G (PKG) activity and vascular smooth muscle relaxation. NO bioavailability is impaired in inflammatory settings, such as high glucose (HG). We examined whether the direct sGC sensitizer/stimulator vericiguat, augments cGMP production in human vascular smooth muscle cells (HVSMC) exposed to high glucose and explored its effect on vasorelaxation. Methods: Aortic HVSMCs were exposed to HG for 24h. In the treatment group, cells also received 1uM vericiguat for 24h. After incubation, cGMP and PKG activity were measured. Additionally, thoracic murine aortas were exposed to HG or to normal glucose (NG) control. The rings were then placed in an organ chamber bath and dose response curves to increasing doses of acetylcholine (Ach) and sodium nitroprusside were constructed for three groups: control (normal glucose), HG alone, and HG + vericiguat. Results: HVSMCs exposed to HG produced significantly less cGMP than those exposed to NG. cGMP production in the presence of HG was rescued when treated with 1uM vericiguat. Additionally, PKG activity was impaired in the presence of HG and enzyme activity was restored with vericiguat. In isolated mouse aortic rings, ACh mediated relaxation was impaired following treatment with HG, but was improved when a HG group was treated with vericiguat. Conclusions: The sGC sensitizer/stimulator vericiguat restored cGMP production and PKG activity in the setting of HG. Vericiguat enhanced ACh-mediated vasorelaxation in the setting of HG. The findings suggest clinical studies are warranted to investigate the potential of sGC sensitization/stimulation as a therapeutic intervention to improve vascular endothelial-dependent function that is impaired in pro-inflammatory settings that are associated with the development of atherosclerotic disease.

Physical activity (PA) among middle-aged women: initial and current influences and patterns of participation.

This study investigated the initial and current influences for doing physical activity (PA), current levels of PA participation, and future plans for it. Participants were 200 women aged 45 to 64 years old. Factor loadings of influences were explored using Principal Components Analysis. Pearson bivariate correlations, t-test, and ANOVA were used to show the differences among the influences, sociodemographic characteristics, and present/future PA participation. Personal fulfillment was the main initial influence, while health benefits/self-care, and outdoor/family activities were the most important current influences. The results highlight the factors that best explain present PA participation and also plans for activity in the future.

The role of proprotein convertase subtillisin/kexin type 9 in placental salvage and lipid metabolism in women with preeclampsia.

INTRODUCTION: Preeclampsia is associated with decreased maternal low-density lipoprotein cholesterol (LDL-c), which is essential for fetal growth. The underlying mechanisms for decreased LDL-c in preeclampsia remain unknown. Proprotein convertase subtillisin/kexin type 9 (PCSK9) regulates serum LDL-c via LDL receptor (LDL-R) degradation. We describe the possible role of PCSK9 in lipid metabolism in all compartments of the parturient (maternal blood, placental tissue, and fetal blood) in pregnancies with and without preeclampsia. METHODS: This is an observational study examining PCSK9 levels in maternal sera, umbilical cord blood, and PCSK9 protein content in placental tissue in three different locations (maternal placental interface, fetal placental interface, and umbilical cord) in women with and without preeclampsia at >23 weeks gestation. RESULTS: 68 parturients with preeclampsia and 55 without preeclampsia were enrolled. Maternal serum LDL-c (116.6 ± 48.9 mg/dL vs 146.1 ± 47.1 mg/dL, p = 0.0045) and PCSK9 (83 [61.8127.6] ng/mL vs 105.3 [83.5142.9] ng/mL, p = 0.011) were also reduced in the preeclamptics versus controls. There were no differences in PCSK9 protein content between preeclamptics and controls at comparative placental interfaces. However, PCSK9 protein content increased between the preeclampsia maternal placental interface (1.87 ± 0.62) and the preeclampsia umbilical cord (2.67 ± 1.08, p = 0.0243). DISCUSSION: PCSK9 levels are lower in maternal sera in preeclampsia when compared to controls. Placental PCSK9 protein content in preeclampsia increases from the maternal interface to the umbilical cord; however, this is not seen in controls. This suggests a potential compensatory mechanism for PCSK9 which allows for higher circulating fetal LDL-c levels in preeclampsia.

Comparison of the pH- and thermally-induced fluctuations of a therapeutic antibody Fab fragment by molecular dynamics simulation.

Successful development of protein therapeutics depends critically on achieving stability under a range of conditions. A deeper understanding of the drivers of instability across different stress conditions, will enable the engineering of more robust protein scaffolds. We compared the impacts of low pH and high temperature stresses on the structure of a humanized antibody fragment (Fab) A33, using atomistic molecular dynamics simulations, using a recent 2.5 Å crystal structure. This revealed that low-pH induced the loss of native contacts in the domain CL. By contrast, thermal stress led to 5-7% loss of native contacts in all four domains, and simultaneous loss of >30% of native contacts in the VL-VH and CL-CH interfaces. This revealed divergent destabilising pathways under the two different stresses. The underlying cause of instability was probed using FoldX and Rosetta mutation analysis, and packing density calculations. These agreed that mutations in the CL domain, and CL-CH1 interface have the greatest potential for stabilisation of Fab A33. Several key salt bridge losses underpinned the conformational change in CL at low pH, whereas at high temperature, salt bridges became more dynamic, thus contributing to an overall destabilization. Lastly, the unfolding events at the two stress conditions exposed different predicted aggregation-prone regions (APR) to solvent, which would potentially lead to different aggregation mechanisms. Overall, our results identified the early stages of unfolding and stability-limiting regions of Fab A33, and the VH and CL domains as interesting future targets for engineering stability to both pH- and thermal-stresses simultaneously.

Exercise triggers CAPN1-mediated AIF truncation, inducing myocyte cell death in arrhythmogenic cardiomyopathy.

Myocyte death occurs in many inherited and acquired cardiomyopathies, including arrhythmogenic cardiomyopathy (ACM), a genetic heart disease plagued by the prevalence of sudden cardiac death. Individuals with ACM and harboring pathogenic desmosomal variants, such as desmoglein-2 (DSG2), often show myocyte necrosis with progression to exercise-associated heart failure. Here, we showed that homozygous Dsg2 mutant mice (Dsg2 mut/mut), a model of ACM, die prematurely during swimming and display myocardial dysfunction and necrosis. We detected calcium (Ca2+) overload in Dsg2 mut/mut hearts, which induced calpain-1 (CAPN1) activation, association of CAPN1 with mitochondria, and CAPN1-induced cleavage of mitochondrial-bound apoptosis-inducing factor (AIF). Cleaved AIF translocated to the myocyte nucleus triggering large-scale DNA fragmentation and cell death, an effect potentiated by mitochondrial-driven AIF oxidation. Posttranslational oxidation of AIF cysteine residues was due, in part, to a depleted mitochondrial thioredoxin-2 redox system. Hearts from exercised Dsg2 mut/mut mice were depleted of calpastatin (CAST), an endogenous CAPN1 inhibitor, and overexpressing CAST in myocytes protected against Ca2+ overload-induced necrosis. When cardiomyocytes differentiated from Dsg2 mut/mut embryonic stem cells (ES-CMs) were challenged with ß-adrenergic stimulation, CAPN1 inhibition attenuated CAPN1-induced AIF truncation. In addition, pretreatment of Dsg2 mut/mut ES-CMs with an AIF-mimetic peptide, mirroring the cyclophilin-A (PPIA) binding site of AIF, blocked PPIA-mediated AIF-nuclear translocation, and reduced both apoptosis and necrosis. Thus, preventing CAPN1-induced AIF-truncation or barring binding of AIF to the nuclear chaperone, PPIA, may avert myocyte death and, ultimately, disease progression to heart failure in ACM and likely other forms of cardiomyopathies.

Imbalances in the Study of the Relationship between Leisure and Self-Esteem: A Systematic Review.

This systematic review offers a comprehensive examination of the relationship between leisure and self-esteem. The different perspectives were analyzed according to a framework that includes the different approaches for defining and measuring leisure, and a similar one was proposed for self-esteem. Articles indexed in the Web of Science (WoS) up to the end of 2018 were reviewed, specifically those that contained the keywords "leisure", "self-esteem" or "self esteem" anywhere in the manuscript. Articles that did not present the qualitative or quantitative instruments needed to evaluate leisure or self-esteem were excluded. A total of 49 articles included the final quantitative synthesis. The overall findings showed that the prevailing methodology was objective (external). As regards content, the following combinations predominated: the behavioral approach to leisure with the unidimensional approach to self-esteem and the experiential approach to leisure with the unidimensional approach to self-esteem. Less studies were observed with the combination of mixed approaches and more comprehensive analyses: the behavioral-experiential combined with the multidimensional. To conclude, this study shows there is a demand for further empirical studies that explore the relationships between leisure and self-esteem. It also identified which approaches are most desirable to expand our understanding of the relationships between leisure and self-esteem.

Gender-differences in conservatoire music practice maladjustment. Can contextual professional goals and context-derived psychological needs satisfaction account for amotivation variations?

In music education, women are present in great numbers. In professional settings, however, women musicians are not as predominant. With some exceptions, such as Scandinavian countries, women still pursue gender equality in professional music practice. To inquire about the causes of this, we considered if gender-differences in amotivation in conservatoire instrument practice could be associated with aspects of learning environment. Self-determination theory (SDT) posits that learning environments may influence motivation, by satisfying or thwarting students' psychological needs and by selectively endorsing specific extrinsic goals. Thus, we analysed if-women and men-amotivation variations could be explained by differences in behavioural regulations and satisfaction of their psychological needs for competence and autonomy. Participants (67 women and 74 men, 18-47 years old) completed validated scales for amotivation, behavioural regulations, and needs satisfaction. Students exhibited high intrinsic and introjected regulations, and high autonomy and competence needs satisfaction. Students' identified regulation levels were modest, and external regulation and amotivation levels were low. Women students' perceived competence was lower, and their amotivation was higher than men's. Amotivation variations were explained positively by identified regulation and negatively by context-derived satisfaction of the psychological needs for competence (and autonomy, only among women). Results suggest that internalization of extrinsic goals can pose difficulties and that psychological needs satisfaction may counteract amotivation (autonomy being potentially more important for women musicians).

University Students' Motives-for-Physical-Activity Profiles: Why They Practise and What They Get in Terms of Psychological Need Satisfaction.

Physical activity (PA) is an important habit for overall health and quality of life, but it tends to recede as young adults transition from high school into university. The present study sought to understand, in the case of university students that still practice PA, their motives for PA and their relationships with psychological need satisfaction (PNS) and characteristics of practice regularity (frequency, duration, team, competitive, coach, league, federation, and type of day of the week for PA). Participants were 423 university students who reported to practice PA (203 identified as men, 191 as women, 29 did not report gender), with ages ranging from 18 to 30 years old (M = 19.91, SD = 1.97). Measures assessing motives for PA, PNS, and PA characteristics were completed. Hierarchical, followed by iterative, cluster analysis was used and four naturally occurring groupings of university students were identified based on their motives for PA: one extrinsic-motives cluster (with both extrinsic motives-fitness and appearance-above the mean), one all-motives cluster (with all five motives above the mean), one intrinsic-motives cluster (with all three intrinsic motives-enjoyment, competence, social-above the mean), and one low-motives cluster (with all motives below the mean). Groupings were compared in terms of the characteristics of their practice regularity (frequency, duration, competition, team, coach, league, federation, type of day of the week used for PA) and their levels of PNS (of the needs for autonomy, competence, and relatedness in PA). Significant between-group differences were observed in the duration of single principal PA sessions, minutes per week practicing main PA, total PA minutes per week, and type of day of the week used for PA. The number of days per week devoted to the principal PA and the number of total PAs practiced were similar across all four clusters. With regard to between-group differences in psychological need satisfaction in PA by cluster, these analyses showed the existence of four clearly distinguishable naturally occurring groupings based on motives for PA, which gives researchers and practitioners the possibility to analyze and implement tailored interventions aimed at promoting PA among university students.

Theatrical Performance as Leisure Experience: Its Role in the Development of the Self.

Theater has been used in psychological intervention and as a metaphor for social life, tendencies that affect the self, highlighting how influential theatrical performance can be for individuals. Their limitations - in terms of the empowerment of the self and its authenticity, respectively - can be overcome by treating theatrical performance as a leisure experience, which considers that freedom and satisfaction play a central role in a more comprehensive understanding and development of the self. With this in mind, we present the conceptual and empirical bases of the leisure experience as an alternative conception of theatrical performance. To do so, we organized a 20 h theater exercise workshop with 16 university students (15 women, one man), aged between 18 and 21 years old (M = 19.06 years; SD = 1.06). The instruments used were: the Time Budget Technique (questionnaire about the activities carried out in the workshop, valued in relation to two items: perceptions of freedom and satisfaction); the Twenty-Statement Test (where people list characteristics of themselves - self-descriptions - related in this case to the theatrical exercises); and, as a third instrument, a combination of the other two - specifying which exercises were more closely related to the self-descriptions. The results showed that group discussion was the activity with the highest perception of freedom, followed by obstacle exercises; as regards the perception of satisfaction, the highest value was observed in the relaxations. In the case of the self-descriptions, the acquisition of practical and intellectual skills was significant, as well as emotional outlook and the expression of self-esteem. In sum, this empirical support - using instruments that invite an exploration of the self - revealed, on the one hand, which specific characteristics of the self are manifested by doing theatrical exercises and, on the other hand, which exercises - when experienced as leisure - have a more decisive impact on the self. Thus, this paper shows what aspects must be taken into account when deciding which activities to include in a psychosocial intervention addressed to the development of the self from the standpoint of theatrical performance as a leisure activity.

Young University Students' Academic Self-Regulation Profiles and Their Associated Procrastination: Autonomous Functioning Requires Self-Regulated Operations.

Students' autonomous self-regulation requires not only self-motivation but also volition or transforming motivation into specific behavioral intentions and following through. Self-regulation includes self-motivation (i.e., goal setting, learning from mistakes) and volitional regulation (i.e., strategic decision making). Furthermore, individual differences, like trait-level perseverance, significantly influence both motivation and volition. Procrastination has been defined as a volitional self-regulation problem, which involves delaying what one had intended to do, in spite of being motivated, and regardless of anticipating adverse consequences. Thus, it is a tendency toward dysregulated behavior - which may stabilize with age - in which subpar self-regulation may lead to procrastination. As a form of dysregulation, procrastination adversely affects young people's autonomy and well-being by limiting their personal growth. Previous research has confirmed a negative relationship between self-regulation and procrastination. However, more precision is demanded in: (a) examining the intertwined roles of motivational and volitional aspects of self-regulation for procrastination, and (b) distinguishing between different medium, and between medium and high levels of self-regulation. Consequently, it has been suggested that this could be accomplished by means of person-centered analyses, aimed at identifying distinct naturally occurring students' self-regulation profiles. These profiles would inform differentiated pedagogical approaches to promote self-regulation strategies counteracting procrastination tendencies. We used cluster analysis to identify academic self-regulation profiles and analyze their relationships with procrastination. Participants were 994 young university students from one public and one private university in Catalonia (41.0% men, 58.4% women, and 0.5% non-binary gender). Their age ranged from 18 to 24 years (M = 19.69, SD = 1.41). Sampling method was intentional, with proportional quotas by sex, academic year, and area of knowledge. The instrument used for data collection incorporated the Short Spanish Self-Regulation Questionnaire (SSSRQ), which includes four dimensions: perseverance, learning from mistakes, goal setting, and decision making; and the Pure Procrastination Scale (PPS), which considers three dimensions: decisional procrastination, implemental delay and lateness. Results obtained by means of cluster analysis distinguished between high and low academic self-regulation profiles, and also between these and two different medium self-regulation profiles, each with specific emphases on particular volitional shortcomings (i.e., weaknesses in decision-making skills and perseverance). These profiles and their relations with procrastination dimensions allow a joint evaluation via structural equation modeling (SEM) to test cognitive motivational strategies (goal setting, decision making, learning from mistakes, and decisional procrastination) together with behavioral aspects (perseverance, implemental delay), considered in the constructs of academic self-regulation and pure procrastination. From this joint evaluation, guidelines are suggested for promoting autonomy among young university students to the detriment of procrastination, thereby - and in accordance with previous research - enhancing students' well-being and growth.

Procrastination at the Core of Physical Activity (PA) and Perceived Quality of Life: A New Approach for Counteracting Lower Levels of PA Practice.

Faced with the demonstrated need to engage in physical activity (PA), lack of time is the argument commonly used to justify low or non-existent levels of PA. Underlying this argument, the accomplishment of procrastination behaviour seems to be related to the less time dedicated to practicing PA and the low perception of the quality of life. With this in mind, the purpose of this study is to show that dedicating different amounts of time to PA affects the perceived quality of life and the widespread problem of procrastination. We hypothesise that greater time investment in PA is related to greater perceived quality of life and less procrastination. In all, 621 practitioners of PA (347 men, 274 women) between 18 and 83 years old (M = 35.43, SD = 14.45) filled out validated versions of the World Health Organization quality of life assessment (WHOQOL-BREF) and the Pure Procrastination Scale. Results showed that people who do enough PA have a more positive perception of the quality of life in the domains of physical and psychological health; this perception, in turn, is related to lower levels of procrastination. Likewise, socio-demographic characteristics such as gender and the main activity presented significant associations with various quality of life domains and procrastination. In sum, the benefits of improvements in quality of life and reductions in procrastination identified in this study are sensitive to the time spent on PA, which suggests that a strategy to promote the practice of PA would improve time management and, thus, counteract procrastination.

De novo design of ACE2 protein decoys to neutralize SARS-CoV-2.

There is an urgent need for the ability to rapidly develop effective countermeasures for emerging biological threats, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the ongoing coronavirus disease 2019 (COVID-19) pandemic. We have developed a generalized computational design strategy to rapidly engineer de novo proteins that precisely recapitulate the protein surface targeted by biological agents, like viruses, to gain entry into cells. The designed proteins act as decoys that block cellular entry and aim to be resilient to viral mutational escape. Using our novel platform, in less than ten weeks, we engineered, validated, and optimized de novo protein decoys of human angiotensin-converting enzyme 2 (hACE2), the membrane-associated protein that SARS-CoV-2 exploits to infect cells. Our optimized designs are hyperstable de novo proteins (∼18-37 kDa), have high affinity for the SARS-CoV-2 receptor binding domain (RBD) and can potently inhibit the virus infection and replication in vitro. Future refinements to our strategy can enable the rapid development of other therapeutic de novo protein decoys, not limited to neutralizing viruses, but to combat any agent that explicitly interacts with cell surface proteins to cause disease.

De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2.

We developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins to infect the cell. Our pipeline allowed the design, validation, and optimization of de novo human angiotensin-converting enzyme 2 (hACE2) decoys to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The best monovalent decoy, CTC-445.2, bound with low nanomolar affinity and high specificity to the receptor-binding domain (RBD) of the spike protein. Cryo-electron microscopy (cryo-EM) showed that the design is accurate and can simultaneously bind to all three RBDs of a single spike protein. Because the decoy replicates the spike protein target interface in hACE2, it is intrinsically resilient to viral mutational escape. A bivalent decoy, CTC-445.2d, showed ~10-fold improvement in binding. CTC-445.2d potently neutralized SARS-CoV-2 infection of cells in vitro, and a single intranasal prophylactic dose of decoy protected Syrian hamsters from a subsequent lethal SARS-CoV-2 challenge.

Time Matters Differently in Leisure Experience for Men and Women: Leisure Dedication and Time Perspective.

There are inequalities with respect to the amount of time men and women spend on leisure. Therefore, it can be assumed that these inequalities are also manifested in the experiences derived from leisure activities and in certain attitudes to life associated with the amount of time devoted to leisure, which emphasize time orientations towards the past, present and future. Based on these ideas, this study analyses the time spent on leisure activities, leisure experience (i.e., perceptions of freedom and satisfaction), and the five factors of the time perspective (hedonistic and fatalistic present; positive and negative past; and future orientation). Participants were 435 men and 434 women, ranging from 18 to 24 years (sample mean M = 21.14, standard deviation SD = 1.99). Two tools were used: a questionnaire about leisure experience, based on the time budget technique, and the Zimbardo Time Perspective Inventory. The results show significant gender differences: men have more leisure time, but women have a more positive leisure experience and time perspectives than men. It can be concluded that women enjoy themselves more with less available leisure time and are more positive with regard to time orientations.

Leisure and Procrastination, a Quest for Autonomy in Free Time Investments: Task Avoidance or Accomplishment?

The purpose of the research was to analyze procrastination - a problem of time management that negatively affects the autonomy of people - in relation to leisure as a domain of everyday life. Specifically, the dynamics between leisure (activities and time invested - weekly frequency and duration of activity) and procrastination factors were studied. A sample of 185 university students (118 men and 67 women: M age = 20.77 years, SD age = 2.53) answered a procrastination scale - validated for the Spanish population - which refers to four factors of procrastination (dilatory behaviors, indecision, lack of punctuality, and lack of planning) and an adaptation of the Time Budget (TB) (a table where the participants were asked to specify "the three activities that you prefer to do when you are not studying or doing a paid job"). Results show that leisure activities are associated with factors of procrastination. As a matter of fact, the different factors of procrastination were related to specific types of leisure activities, depending on the weekly frequency of the activity or its duration. In this sense, there are cases in which the greater frequency of leisure activities (hobbies and computing, social life and entertainment) seems to contain - control, inhibit - procrastination (specifically, affecting its component of indecision) variations in the weekly frequency and duration of certain type of activities result in higher or lower scores on certain factors of procrastination. In sum, the time invested in leisure can protect from or inhibit delaying tasks - which implies enhancing the autonomy of people - a deduction that opens up new lines of research to identify optimal time investments for coping with procrastination.

An Expanded Conformation of an Antibody Fab Region by X-Ray Scattering, Molecular Dynamics, and smFRET Identifies an Aggregation Mechanism.

Protein aggregation is the underlying cause of many diseases, and also limits the usefulness of many natural and engineered proteins in biotechnology. Better mechanistic understanding and characterization of aggregation-prone states is needed to guide protein engineering, formulation, and drug-targeting strategies that prevent aggregation. While several final aggregated states-notably amyloids-have been characterized structurally, very little is known about the native structural conformers that initiate aggregation. We used a novel combination of small-angle x-ray scattering (SAXS), atomistic molecular dynamic simulations, single-molecule Förster resonance energy transfer, and aggregation-prone region predictions, to characterize structural changes in a native humanized Fab A33 antibody fragment, that correlated with the experimental aggregation kinetics. SAXS revealed increases in the native state radius of gyration, Rg, of 2.2% to 4.1%, at pH 5.5 and below, concomitant with accelerated aggregation. In a cutting-edge approach, we fitted the SAXS data to full MD simulations from the same conditions and located the conformational changes in the native state to the constant domain of the light chain (CL). This CL displacement was independently confirmed using single-molecule Förster resonance energy transfer measurements with two dual-labeled Fabs. These conformational changes were also found to increase the solvent exposure of a predicted APR, suggesting a likely mechanism through which they promote aggregation. Our findings provide a means by which aggregation-prone conformational states can be readily determined experimentally, and thus potentially used to guide protein engineering, or ligand binding strategies, with the aim of stabilizing the protein against aggregation.

Being Conscious of One's Own Heroism: An Empirical Approach to Analyzing the Leadership Potential of Future CEOs.

From the disciplinary field of the science of heroism, there is a need to deepen the processes that this science comprises, and at the same time, to test methods of inquiry to account for the variety of processes associated with this science. Linked to this sensitivity, the objective of this contribution is to jointly analyze, in a sample of future CEOs, what they imagine about heroism, their psychological types, and their values orientation. The sample consisted of 45 students (21 men and 24 women) between 22 and 47 years old (M = 26.69, SD = 4.47), who were part of a master's program oriented toward training future CEOs to be leaders. The analytical instruments were the Myers-Briggs Type Indicator (MBTI), a story that each participant developed about him/herself as the main hero or heroine, and a questionnaire on personal values. In the psychological types observed, the functions of thinking and sensing predominated, with intuition and feeling residing at a lower level of consciousness. With regard to the stories, the majority of the sample offered tales in which the hero/heroine was confronted with a mystery to solve (or mission to fulfill), faced difficulties, and, finally, achieved harmony between the personal and the collective. Regarding the values, significant associations are observed between the gender, the characteristics of the psychological types, and the content of the story about their own hero / heroine. In sum, the research carried out offers an empirical approach to the study of the subjective elements of heroism, combining quantitative and qualitative aspects in an educational setting, and broadening the perspectives on the science of heroism.

Relations Between Student Procrastination and Teaching Styles: Autonomy-Supportive and Controlling.

Procrastination is a complex problem that can be defined as delaying an intended course of action (despite anticipating adverse consequences). Even when some students have equivalent motivation and skill levels, they tend to procrastinate more frequently than others. Approaches that analyze whether contextual influences may prevent or promote dysregulation processes associated with procrastination are scarce. According to Self-Determination Theory, contextual influences can facilitate self-regulated motivation (e.g., autonomous pursuit of interests or personal goals), if teaching style is autonomy-supportive and guarantees the satisfaction of students' basic psychological needs for perceived competence, autonomy, and relatedness. Contrariwise, school context can also impede the development of autonomous motivation if teachers frustrate the satisfaction of their students' psychological needs by recurring to controlling teaching behaviors, such as controlling use of rewards, negative conditional regard, excessive personal control, or intimidation. The goal of the present study was to assess the relations between controlling and autonomy-supportive teaching behaviors, psychological needs satisfaction (of the needs for competence, autonomy, and relatedness), and four distinct measures of procrastination: general procrastination, decisional procrastination, procrastination linked to task avoidance, and pure procrastination. Data based on public university undergraduate students (N = 672) shows that controlling teaching behaviors are associated negatively with psychological needs satisfaction and positively with procrastination. Contrariwise, autonomy-supportive teaching behaviors are positively associated with psychological needs satisfaction and negatively with procrastination. The data obtained is useful for suggesting new lines of research to study the link between contextual influences and the prevention of academic procrastination in view of Self-Determination Theory. Also, our results suggest new pedagogical approaches where teachers can create contextual conditions that help to prevent or reduce procrastinating tendencies.