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Abstract This study delved into the complex effects of work schedules on the well-being of healthcare professionals, spotlighting Nigeria’s medical landscape. A diverse cohort of 387 participants, spanning doctors, nurses, pharmacists, and laboratory technicians or scientists, formed the research base, with the majority being women (67.7%), with a mean age of 34.67 years. Professionals self-reported their predominant schedules to gauge work patterns, classifying them as day or night shifts. The World Health Organization Quality of Life Brief Version (WHOQOL-BREF) tool assessed the quality of life across the physical, psychological, social relationship, and environmental domains. Psychological distress was measured using the Depression, Anxiety, and Stress Scales (DASS), and perceived social support was evaluated via the Multidimensional Scale of Perceived Social Support (MSPSS). A cross-sectional design was adopted, and the study employed moderated mediation analysis using SmartPLS 4.0. The results underscored the significant ramifications of night shifts on environmental and physical well-being. Psychological health and social relationships were better among day shift than night shift workers. There was a pronounced correlation between night shifts and heightened levels of anxiety, stress, and depression. The mediating role of psychological distress and the moderating influence of social support in these relationships were evident. This study offers invaluable insights into the role of work schedules in shaping the well-being of healthcare professionals, emphasising the protective role of social support and the unique challenges faced by migrant health workers.

BackgroundThe CAPS-5 is a reliable instrument for assessing PTSD symptoms, demonstrating strong consistency, validity, and reliability after a traumatic event. However, further research is warranted to explore the divergent validity of the CAPS-5 and its adaptation to diverse cultural contexts.ObjectiveIn this meta-analysis, we endeavoured to comprehensively evaluate the reliability generalization of the CAPS-5 across diverse populations and clinical contexts.MethodsA reliability generalization meta-analysis on the psychometric properties of CAPS-5 was conducted, encompassing 15 studies. The original versions’ psychometric properties were systematically retrieved from databases including PubMed, PsychNet, Medline, CHAHL, ScienceDirect, Scopus, Web of Science, and Google Scholar, with a focus on studies published between 2013 and 2023. Two independent investigators evaluated study quality using QUADAS-2 and COSMIN RB, pre-registering the protocol in the Prospero database for transparency and minimizing bias risk.ResultsMeta-analysis reveals CAPS-5 global reliability (α = 0.92, 95% CI [0.90, 0.94]), z = 99.44, p

Abstract The aim to examine the link between diabetes distress and depression in individuals with diabetes, assess the mediating role of psychological resilience in this relationship, and analyses if these relationships differ between Type 1 and Type 2 diabetes. The study utilized a cross-sectional design. A total of 181 (age 33–72 years, mean = 54.76 years, and SD = 9.05 years) individuals diagnosed with diabetes who were receiving treatment from State Specialist Hospitals in Okitipupa were selected for the study using the convenient sampling technique. The data were analysed using Pearson Multiple correlation and multi-group mediation analysis. The analyses were carried out with Smartpls and IBM/SPSS Version 28.0. The results revealed a significant positive correlation between diabetes distress and depression (r = .80, p

Integrating work and family life is a relevant concern, especially for women in the banking industry. While the impact of job characteristics on work-family conflict is well-documented, the moderating role of core self-evaluations (CSE) remains underexplored. This study aimed to investigate the role of CSE in moderating the relationship between job characteristics and work-family conflict among married female bank employees in Nigeria. A cross-sectional survey was conducted with 245 married female bank employees in Enugu state. Participants were assessed using the Core Self-Evaluation, Job Characteristics, and Work-Family Conflict Scales. Pearson correlation analysis and path coefficient evaluation were utilised to test the study's hypotheses. Job characteristics, notably autonomy, feedback, skill variety, task identity, and task significance, influence work-family conflict across three dimensions: behaviour-based, strain-based, and time-based. Notably, CSE emerged as a significant moderator, with its influence varying depending on the job characteristics. The findings highlight the importance of considering both job characteristics and individual psychological attributes in addressing work-family conflicts. Organisations should adopt a multidimensional, individual-centred approach, recognising the intertwined roles of job factors and personal evaluations in shaping employees' work-life balance experiences.

Abstract Background This study aims to provide researchers and practitioners with a more elaborate instrument to measure turnover intentions based on the planned behaviour theory model. The questionnaire assesses 5 distinct aspects of turnover intentions (i.e., subjective social status, organisational culture, personal orientation, expectations, and career growth). Methods In this cross-sectional study (comprise of 2 studies in one) a wave survey design was applied to a large diversity of workers drawn from the staff of universities, banks, hospitals, factories, and telecommunication companies. Exploratory factor analysis (EFA) was applied the identify the sub-dimensions and Cronbach’s alpha to assess the reliability of the first study. In the second study, for the Confirmatory factor analysis to establishing structural model of the dimensions. Results We demonstrate the reliability, factor structure, and validity evidence based on internal structure and relationship with other variables of the new measure among two samples (N1 = 622; N2 = 433). Twenty-five items with 5 factors were extracted to represent a broader perspective of turnover intention scale. Conclusions In total, the study indicates that the assessment can be used to reliably assess several major indicators of turnover intentions. Therefore, improved employees’ evaluations and reduced loss of valuable staff as a result of avoidable measures in considering the interests of workers.

BackgroundThe General Health Questionnaire (GHQ-12) is widely used for detecting psychiatric disorders, but its reliability across different populations remains to be determined.ObjectiveThis meta-analysis aims to evaluate the reliability of GHQ-12 across varied cultural and demographic settings.MethodThis meta-analysis evaluates the reliability of General Health Questionnaire [GHQ-12]' across diverse populations, employing a systematic search strategy and rigorous inclusion criteria. This meta-analysis evaluates the General Health Questionnaire (GHQ-12) using a pre-registered protocol (CRD42023488436) to ensure unbiased results. Data from 20 studies published between 2016-2023 were analysed using a random-effects model, with quality assessment guided by COSMIN Risk of Bias and QUADAS-2. This study enhances our understanding of GHQ-12's psychometric properties.ResultsFor the GHQ-12 subscales, Cronbach's alpha coefficients were 0.72 (90% CI [0.68, 0.75]) for anxiety and depression, 0.82 (90% CI [0.79, 0.86]) for social dysfunction, and 0.72 (90% CI [0.68, 0.76]) for loss of confidence. However, the analysis showed substantial heterogeneity (I2 = 90.04%), with significant variability in reliability estimates across different studies. The overall Cronbach's alpha was 0.84 (95% Cl [0.810, 0.873]) with SE = 0.016 (90% CI [0.68, 0.82], p < .05), indicating moderate to high internal consistency. Quantifying heterogeneity revealed a substantial level (se = 0.0016, I2 = 96.7%), signifying considerable variability in the reliability estimate among the studies. Results further show Cronbach's alpha coefficients range from 0.82 to 0.85 (95% Cl [0.77, 0.86 to 0.81, 0.90]) for the GHQ 12 items.ConclusionWhile reaffirming the GHQ-12's utility in mental health assessment, our findings urge a more cautious and context-aware application of the questionnaire. The substantial heterogeneity and variability in reliability scores indicate a need for further research. Future studies should explore the reasons behind this variability, focusing on cultural, socio-economic, and methodological factors that might influence the GHQ-12's reliability. This critical analysis underscores the need for a deeper understanding of the GHQ-12's applicability and the importance of tailoring mental health assessment tools to specific population characteristics.

Retirement is a pivotal life transition that often changes routines, identity, and objectives. With increasing life expectancies and evolving societal norms, examining the interplay between retirement anxiety and life satisfaction is vital. This study delves into this relationship, recognising the complexities of retirement. A systematic review and meta-analysis followed PRISMA guidelines. Research from 2003 to 2023 was sourced from databases like CINAHL, PubMed/Medline, PsycINFO, ERIC, and Google Scholar, focusing on diverse methodologies and outcomes related to retirement registered in Prospero database (CRD42023427949). The quality assessment used an eight-criterion risk of bias scale, and analyses included qualitative and quantitative approaches, such as random-effects meta-analysis and moderator analyses. After reviewing 19 studies with varied geographical and demographic scopes, a mixed relationship between retirement and life satisfaction emerged: 32% of studies reported a positive relationship, 47% were negative, and 21% found no significant correlation. Meta-analysis indicated high heterogeneity and non-significant mean effect size, suggesting no consistent impact of retirement on life satisfaction. Moderator analyses highlighted the influence of measurement tools on outcomes. The findings reveal a complex interplay between retirement anxiety and life satisfaction, stressing the need for holistic retirement policies that encompass mental health, social integration, and adaptability, focusing on cultural sensitivity. Challenges include potential biases in data sources, methodological diversity, the scarcity of longitudinal studies, and difficulties in addressing recent societal shifts, like the COVID-19 pandemic. Variability in measurement tools and possible publication bias may have also influenced results. This study contributes to understanding retirement, emphasising the relationship between retirement anxiety and life satisfaction. It advocates for ongoing, detailed, culturally informed research to grasp retirement's multifaceted aspects fully.

Social media use has been linked to adverse health outcomes such as depression. To facilitate interventions, understanding the varied causes of depression is necessary. The authors developed a social media-induced depression tendency (SMIDT) scale for use with young people and aimed to validate it for young people in Nigeria. The study was conducted in three parts using an online survey (Google Forms) with purposive sampling targeting young people. Study 1 was an exploratory study that developed the SMIDT scale with 361 young people aged 16 to 26 years (mean age=22.81). A concise measure of SMIDT was obtained. In study 2, confirmatory factor analysis was performed on the SMIDT with young people aged 17 to 25 years (mean age=23.61). Construct, discriminant, and concurrent validities were established, and three factors were identified (sensitivity/attention seeking, worthlessness, and escapism/reality avoidance), which explained 55.87% of the variance. Study 3 tested the predictive validity of the scale. The results showed that the 15-item SMIDT scale had high internal consistency and satisfactory validity. The SMIDT scale can enable the assessment of factors associated with social media-induced depression tendency. The three factors identified in the scale provide insight into the factors contributing to depression associated with social media use. The SMIDT scale has the potential to help identify at-risk individuals and in-developing interventions to prevent or reduce social media-induced depression tendencies. However, this study only focused on young people in Nigeria. Additional studies using the SMIDT scale are required to assess its generalizability and applicability in evaluating other factors, such as quality of life among young people. Moreover, while social media use has been associated with adverse health outcomes, it is crucial to recognize that it can also positively affect mental health. Further research is necessary to explore the complex relationships between social media use and mental health outcomes.

The psychological implication of retirement is underemphasised. This study examined the relationship between proactive personality, social comparison, and retirement anxiety among Nigerian civil servants. The study is a cross-sectional design, using proactive personality, social comparison orientation, and Nigerian pre-retirement anxiety scales. Five hundred and eight staff members in government-owned tertiary institutions with five years or less to go until retirement, and at a mean age of 57.47 (SD = 3.02), were surveyed. The study established that a proactive personality negatively predicted retirement anxiety and that civil servants engage in diverse forms of intrapreneurship/entrepreneurship to augment their savings. The study also revealed that social comparison (opinion) mediated the relationship between proactive personality and retirement anxiety (financial preparedness and social alienation). In addition, the study found that social comparison (opinion and ability) mediated the relationship between proactive personality and retirement anxiety (financial preparedness) in a sequential order. The findings suggest that retirees in Nigeria face complex challenges, including financial unpreparedness, social alienation, and uncertainty. The study highlights the importance of understanding the relationship between personality traits, social comparison, and retirement anxiety in order to develop effective interventions and policies that support retirees in Nigeria.

The main objective of this paper is to investigate the mediating role of subjective career success (SCS) in the relationship between proactive personality, social support (SS), and pre-retirement anxiety. Using a two-wave longitudinal design, 624 pre-retirees were sampled (M = 56.49 years; SD = 4.56); of these, 237 (37.98%) were males and 387 (62.02%) were females. Measurement model and mediation test were performed using the SmartPLS and IBM SPSS Amos software. The result indicated that proactive personality, SS, and SCS showed negative relationships with the dimensions of pre-retirement anxiety (financial preparedness, social obligation, and social alienation). Subjective career success mediated the relationship between proactive personality and pre-retirement anxiety.

Conditional reasoning premises can be systematically manipulated to elicit specific response patterns. This is useful for investigating the reasoning style of people who report clinical symptoms. We administered a standardized conditional reasoning task to 16 participants with a diagnosis of Asperger's syndrome (AS), 16 participants with a diagnosis of depersonalization disorder (DPD), and 32 intelligence-quotient-matched controls. Premises were manipulated for a) context, with some being embedded within extra statements, and b) content, neutral or emotional. Both the AS and DPD participants were less likely to incorporate exceptions to the given premises than the controls, indicating difficulties with mental flexibility, although this effect was less marked in the DPD group. It seems the AS participants were also less influenced than the controls by statements that highlight possible alternative consequences. However, this effect was less robust than that observed with statements detailing exceptions, suggesting it may be because of general problems with executive function rather than difficulties in processing contextual information. We did not observe the expected difference between the DPD participants and the controls when reasoning with emotional premises. Overall, these data suggest that the DPD and AS participants have distinct reasoning styles, which may be of use for interventions based on cognitive change. [ABSTRACT FROM AUTHOR]

Large for gestational age (LGA) is another designation used to assess and monitor growth throughout the pregnancy and after delivery. Large for gestational age is an abnormal growth descriptor that assists in anticipating neonatal needs pre-and postnatally.Careful monitoring for abnormal growth trends in the fetus is imperative prenatally. The relative size of a neonate affects many aspects of prenatal and postnatal surveillance. Nursing care is guided by the maternal history and the delivery room complications that may occur. Anticipating complications in the delivery room is vital to the survival of LGA neonates.Nursing care for LGA neonates requires knowledge based on these potential complications. A thorough physical assessment with appropriate glucose monitoring and parental education is required.Size matters when it comes to the health and welfare of all sizes of neonates. Anticipatory guidance with prenatal monitoring and education can improve outcomes in the neonate at risk for WA complications at birth. [ABSTRACT FROM AUTHOR]

The relative size of a neonate impacts many aspects of prenatal and postnatal surveillance and care. The designations of appropriate for gestational age, small-for-gestational age, intrauterine growth restriction, and large-for-gestational age are systematic categorizations used to assess and monitor growth throughout pregnancy and delivery. Each abnormal growth descriptor aids in anticipating neonatal needs after birth because each has the potential for complications related to feeding, glucose utilization, short- and long-term growth, and development. Maternal risk factors that impact the neonate's size-related can have immediate implications in the delivery room as well as significant effects postnatally. Caring for neonates at risk for size complications requires knowledge based on prenatal and postnatal complications. Neonates must be carefully measured and plotted on growth charts to confirm a visual assessment of size. Each growth complication requires individual attention to detail and careful planning to maximize adequate postnatal growth and nutrition. Size matters when it comes to the health and welfare of neonates. Anticipatory guidance can improve outcomes in the neonate at risk for failure to thrive from size complications at birth. Part 1 of this article provides an overview of the size classifications and a discussion of clinical factors that are associated with or contribute to small-for-gestational age births. Once the neonate's size for gestational age is calculated, a focused physical assessment is described along with nursing care and prognostic implications. Part 2 will focus on the physical assessment, nursing care, prognosis, and complications associated with large-for-gestational-age neonates. [ABSTRACT FROM AUTHOR]

BACKGROUND: Empathy plays a key role in social understanding, but its empirical measurement has proved difficult. The Empathy Quotient (EQ) is a self-report scale designed to do just that. This series of four studies examined the reliability and validity of the EQ and determined its factor structure. METHOD: In Study 1, 53 people completed the EQ, Social Desirability Scale (SDS) and a non-verbal mental state inference test, the Eyes Task. In Study 2, a principal components analysis (PCA) was conducted on data from 110 healthy individuals and 62 people reporting depersonalisation (DPD). Approximately 1 year later, Study 3, involved the re-administration of the EQ (n = 24) along with the Interpersonal Reactivity Index (IRI; n = 28). In the last study, the EQ scores of those with DPD, a condition that includes a subjective lack of empathy, were examined in depth. RESULTS: An association was found between the Eyes task and EQ, and only three EQ items correlated with the SDS. PCA revealed three factors: (1) 'cognitive empathy'; (2) 'emotional reactivity', and (3) 'social skills'. Test-retest reliability was good and moderate associations were found between the EQ and IRI subscales, suggesting concurrent validity. People with DPD did not show a global empathy deficit, but reported less social competence. CONCLUSIONS: The EQ is a valid, reliable scale and the different subscales may have clinical applications. [ABSTRACT FROM AUTHOR]

Estimating the incidence and the prevalence of psychotic disorders in the province of Quebec has been the object of some interest in recent years as a contribution to the epidemiological study of the causes of psychotic disorders being carried out primarily in the UK and Scandinavia. A number of studies have used administrative data from the Régie de l’assurance maladie du Québec (RAMQ) that includes nearly all Quebec citizens to obtain geographical and temporal prevalence estimates for the illness. However, there has been no investigation of the validity of RAMQ diagnoses for psychotic disorders, and without a measure of the sensitivity and the specificity of these diagnoses, it is impossible to be confident in the accuracy of the estimates obtained. This paper proposes the use of latent class analysis to ascertain the validity of a diagnosis of schizophrenia using RAMQ data.

The purpose of this study was to examine variations in endogenous oxytocin levels in pregnancy and postpartum state. We also explored the associations between delivery variables and oxytocin levels. A final sample of 272 mothers in their first trimester of pregnancy were included for the study. Blood samples were drawn during the 1st trimester and 3rd trimester of pregnancy and at 8 weeks postpartum. Socio-demographic data were collected at each time point and medical files were consulted for delivery details. In most women, levels of circulating oxytocin increased from the 1st to 3rd trimester of pregnancy followed by a decrease in the postpartum period. Oxytocin levels varied considerably between individuals, ranging from 50 pg/mL to over 2000 pg/mL. Parity was the main predictor of oxytocin levels in the 3rd trimester of pregnancy and of oxytocin level changes from the 1st to the 3rd trimester of pregnancy. Oxytocin levels in the 3rd trimester of pregnancy predicted a self-reported negative labor experience and increased the chances of having an epidural. Intrapartum exogenous oxytocin was positively associated with levels of oxytocin during the postpartum period. Our exploratory results suggest that circulating oxytocin levels during the 3rd trimester of pregnancy may predict the type of labor a woman will experience. More importantly, the quantity of intrapartum exogenous oxytocin administered during labor predicted plasma oxytocin levels 2 months postpartum, suggesting a possible long-term effect of this routine intervention, the consequences of which are largely unknown.

Mucopolysaccharidosis type IIIA (MPS IIIA) is characterized by neurological and skeletal pathologies caused by reduced activity of the lysosomal hydrolase, sulfamidase, and the subsequent primary accumulation of undegraded heparan sulfate (HS). Respiratory pathology is considered secondary in MPS IIIA and the mechanisms are not well understood. Changes in the amount, metabolism, and function of pulmonary surfactant, the substance that regulates alveolar interfacial surface tension and modulates lung compliance and elastance, have been reported in MPS IIIA mice. Here we investigated changes in lung function in 20-wk-old control and MPS IIIA mice with a closed and open thoracic cage, diaphragm contractile properties, and potential parenchymal remodeling. MPS IIIA mice had increased compliance and airway resistance and reduced tissue damping and elastance compared with control mice. The chest wall impacted lung function as observed by an increase in airway resistance and a decrease in peripheral energy dissipation in the open compared with the closed thoracic cage state in MPS IIIA mice. Diaphragm contractile forces showed a decrease in peak twitch force, maximum specific force, and the force-frequency relationship but no change in muscle fiber cross-sectional area in MPS IIIA mice compared with control mice. Design-based stereology did not reveal any parenchymal remodeling or destruction of alveolar septa in the MPS IIIA mouse lung. In conclusion, the increased storage of HS which leads to biochemical and biophysical changes in pulmonary surfactant also affects lung and diaphragm function, but has no impact on lung or diaphragm structure at this stage of the disease. NEW & NOTEWORTHY Heparan sulfate storage in the lungs of mucopolysaccharidosis type IIIA (MPS IIIA) mice leads to changes in lung function consistent with those of an obstructive lung disease and includes an increase in lung compliance and airway resistance and a decrease in tissue elastance. In addition, diaphragm muscle contractile strength is reduced, potentially further contributing to lung function impairment. However, no changes in parenchymal lung structure were observed in mice at 20 wk of age.

Supravalvular aortic stenosis (SVAS) has been well described in Williams-Beuren Syndrome and non-syndromic elastin (ELN) mutations. Non-syndromic ELN mutations are inherited in an autosomal dominant pattern with incomplete penetrance and variable expressivity. ELN haploinsufficiency leads to progressive arteriopathy, typically affecting the aortic sinotubular junction. Multi-level pulmonary stenosis has also been reported and biventricular obstruction may portend a worse prognosis. Fetal presentation of ELN mutation with SVAS has not been previously reported in the literature. We present a case of fetal diagnosis of SVAS and multi-level pulmonary stenosis in a family with a known pathogenic ELN mutation (Exon 6, c.278del [p.Pro93Leufs*29]). On the fetus' initial fetal echo, there was only mild flow acceleration through the aortic outflow tract, however, she went on to develop progressive bilateral obstruction. In the early post-natal period, the child was clinically asymptomatic and showed similar mild SVAS and mild valvar and supravalvular pulmonary stenosis. Our case highlights the need for serial monitoring of fetuses with suspected or confirmed ELN arteriopathy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: The process of being admitted to a hospital is widely recognised as a distressing encounter for children, frequently resulting in notable levels of anxiety. The main aim was to assess the effectiveness of bibliotherapy in reducing anxiety and to associate anxiety levels with demographic and clinical variables., Methods: This study was conducted at a paediatric ward in a tertiary care hospital located in Tamil Nadu, India, for 3 months from 1 August 2023-30 October 2023. In this study, a one-group pre-test and post-test design was employed. A sample of 60 children, aged between 5 and 12 years, was recruited using a convenience sampling method. Spence Children Anxiety Scale was used for assessing anxiety levels., Results: The mean age of the participants was 8.46 ± 1.91 years, and the majority, comprising 57%, were male. Following bibliotherapy, 72% of children showed mild anxiety, 28% showed moderate anxiety and no individual had considerable anxiety. Anxiety scores dropped 27%. Significant associations were found between anxiety reduction and variables such as age, educational status, and type of family., Conclusion: Bibliotherapy was notably effective in substantially reducing anxiety levels among children aged 5-12 years who were admitted to hospitals., (© 2024 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Microtubules are dynamic cytoskeletal filaments that undergo stochastic switching between phases of polymerization and depolymerization-a behavior known as dynamic instability. Many important cellular processes, including cell motility, chromosome segregation, and intracellular transport, require complex spatiotemporal regulation of microtubule dynamics. This coordinated regulation is achieved through the interactions of numerous microtubule-associated proteins (MAPs) with microtubule ends and lattices. Here, we review the recent advances in our understanding of microtubule regulation, focusing on results arising from biochemical in vitro reconstitution approaches using purified multiprotein ensembles. We discuss how the combinatory effects of MAPs affect both the dynamics of individual microtubule ends, as well as the stability and turnover of the microtubule lattice. In addition, we highlight new results demonstrating the roles of protein condensates in microtubule regulation. Our overall intent is to showcase how lessons learned from reconstitution approaches help unravel the regulatory mechanisms at play in complex cellular environments., Competing Interests: Conflict of interest The authors declare no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Congenital left ventricular aneurysm, pseudoaneurysm, and diverticulum are rare entities. These diagnoses can be made pre- and/or postnatally. Although these entities overlap clinically and morphologically, important distinctions can allow for accurate diagnoses. Appropriate diagnosis can be imperative for risk stratification and guidance of prenatal and postnatal management. The case described in the present report highlights a challenging case of a fetal left ventricular aneurysm, management during the prenatal and postnatal periods, and important differentiating features from a ventricular diverticulum and pseudoaneurysm., (Copyright © 2023 by the American Academy of Pediatrics.)

Cytoplasmic linker-associated proteins (CLASPs) regulate microtubules in fundamental cellular processes. CLASPs stabilize dynamic microtubules by suppressing microtubule catastrophe and promoting rescue, the switch-like transitions between growth and shrinkage. How CLASPs specifically modulate microtubule transitions is not understood. Here, we investigate the effects of CLASPs on the pre-catastrophe intermediate state of microtubule dynamics, employing distinct microtubule substrates to mimic the intermediate state. Surprisingly, we find that CLASP1 promotes the depolymerization of stabilized microtubules in the presence of GTP, but not in the absence of nucleotide. This activity is also observed for CLASP2 family members and a minimal TOG2-domain construct. Conversely, we find that CLASP1 stabilizes unstable microtubules upon tubulin dilution in the presence of GTP. Strikingly, our results reveal that CLASP1 drives microtubule substrates with vastly different inherent stabilities into the same slowly depolymerizing state in a nucleotide-dependent manner. We interpret this state as the pre-catastrophe intermediate state. Therefore, we conclude that CLASPs suppress microtubule catastrophe by stabilizing the intermediate state between growth and shrinkage., (© 2023 Lawrence et al.)

Coordination between the microtubule and actin networks is essential for cell motility, neuronal growth cone guidance, and wound healing. Members of the CLASP (cytoplasmic linker-associated protein) family of proteins have been implicated in the cytoskeletal cross-talk between microtubules and actin networks; however, the molecular mechanisms underlying the role of CLASP in cytoskeletal coordination are unclear. Here, we investigate CLASP2α's cross-linking function with microtubules and F-actin. Our results demonstrate that CLASP2α cross-links F-actin to the microtubule lattice in vitro. We find that the cross-linking ability is retained by L-TOG2-S, a minimal construct containing the TOG2 domain and serine-arginine-rich region of CLASP2α. Furthermore, CLASP2α promotes the accumulation of multiple actin filaments along the microtubule, supporting up to 11 F-actin landing events on a single microtubule lattice region. CLASP2α also facilitates the dynamic organization of polymerizing actin filaments templated by the microtubule network, with F-actin forming bridges between individual microtubules. Finally, we find that depletion of CLASPs in vascular smooth muscle cells results in disorganized actin fibers and reduced coalignment of actin fibers with microtubules, suggesting that CLASP and microtubules contribute to higher-order actin structures. Taken together, our results indicate that CLASP2α can directly cross-link F-actin to microtubules and that this microtubule-CLASP-actin interaction may influence overall cytoskeletal organization in cells.

Microtubules (MTs) are cytoskeletal fibers that undergo dynamic instability (DI), a remarkable process involving phases of growth and shortening separated by stochastic transitions called catastrophe and rescue. Dissecting DI mechanism(s) requires first characterizing and quantifying these dynamics, a subjective process that often ignores complexity in MT behavior. We present a S tatistical T ool for A utomated D ynamic I nstability A nalysis (STADIA) that identifies and quantifies not only growth and shortening, but also a category of intermediate behaviors that we term "stutters." During stutters, the rate of MT length change tends to be smaller in magnitude than during typical growth or shortening phases. Quantifying stutters and other behaviors with STADIA demonstrates that stutters precede most catastrophes in our in vitro experiments and dimer-scale MT simulations, suggesting that stutters are mechanistically involved in catastrophes. Related to this idea, we show that the anticatastrophe factor CLASP2γ works by promoting the return of stuttering MTs to growth. STADIA enables more comprehensive and data-driven analysis of MT dynamics compared with previous methods. The treatment of stutters as distinct and quantifiable DI behaviors provides new opportunities for analyzing mechanisms of MT dynamics and their regulation by binding proteins.

Sjögren's syndrome nuclear autoantigen-1 (SSNA1/NA14) is a microtubule-associated protein with important functions in cilia, dividing cells, and developing neurons. However, the direct effects of SSNA1 on microtubules are not known. We employed in vitro reconstitution with purified proteins and TIRF microscopy to investigate the activity of human SSNA1 on dynamic microtubule ends and lattices. Our results show that SSNA1 modulates all parameters of microtubule dynamic instability-slowing down the rates of growth, shrinkage, and catastrophe, and promoting rescue. We find that SSNA1 forms stretches along growing microtubule ends and binds cooperatively to the microtubule lattice. Furthermore, SSNA1 is enriched on microtubule damage sites, occurring both naturally, as well as induced by the microtubule severing enzyme spastin. Finally, SSNA1 binding protects microtubules against spastin's severing activity. Taken together, our results demonstrate that SSNA1 is both a potent microtubule-stabilizing protein and a novel sensor of microtubule damage; activities that likely underlie SSNA1's functions on microtubule structures in cells., Competing Interests: EL, GA, CA, MZ No competing interests declared, (© 2021, Lawrence et al.)

Mucopolysaccharidosis IIIA (MPS IIIA) is a lysosomal storage disease with significant neurological and skeletal pathologies. Respiratory dysfunction is a secondary pathology contributing to mortality in MPS IIIA patients. Pulmonary surfactant is crucial to optimal lung function and has not been investigated in MPS IIIA. We measured heparan sulphate (HS), lipids and surfactant proteins (SP) in pulmonary tissue and bronchoalveolar lavage fluid (BALF), and surfactant activity in healthy and diseased mice (20 weeks of age). Heparan sulphate, ganglioside GM3 and bis(monoacylglycero)phosphate (BMP) were increased in MPS IIIA lung tissue. There was an increase in HS and a decrease in BMP and cholesteryl esters (CE) in MPS IIIA BALF. Phospholipid composition remained unchanged, but BALF total phospholipids were reduced (49.70%) in MPS IIIA. There was a reduction in SP-A, -C and -D mRNA, SP-D protein in tissue and SP-A, -C and -D protein in BALF of MPS IIIA mice. Captive bubble surfactometry showed an increase in minimum and maximum surface tension and percent surface area compression, as well as a higher compressibility and hysteresis in MPS IIIA surfactant upon dynamic cycling. Collectively these biochemical and biophysical changes in alveolar surfactant are likely to be detrimental to lung function in MPS IIIA.

During meiosis, DNA double-strand breaks undergo interhomolog repair to yield crossovers between homologous chromosomes. To investigate how interhomolog sequence polymorphism affects crossovers, we sequenced multiple recombinant populations of the model plant Arabidopsis thaliana. Crossovers were elevated in the diverse pericentromeric regions, showing a local preference for polymorphic regions. We provide evidence that crossover association with elevated diversity is mediated via the Class I crossover formation pathway, although very high levels of diversity suppress crossovers. Interhomolog polymorphism causes mismatches in recombining molecules, which can be detected by MutS homolog (MSH) mismatch repair protein heterodimers. Therefore, we mapped crossovers in a msh2 mutant, defective in mismatch recognition, using multiple hybrid backgrounds. Although total crossover numbers were unchanged in msh2 mutants, recombination was remodelled from the diverse pericentromeres towards the less-polymorphic sub-telomeric regions. Juxtaposition of megabase heterozygous and homozygous regions causes crossover remodelling towards the heterozygous regions in wild type Arabidopsis, but not in msh2 mutants. Immunostaining showed that MSH2 protein accumulates on meiotic chromosomes during prophase I, consistent with MSH2 regulating meiotic recombination. Our results reveal a pro-crossover role for MSH2 in regions of higher sequence diversity in A. thaliana., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)

Microtubule network remodeling is essential for fundamental cellular processes including cell division, differentiation, and motility. Microtubules are active biological polymers whose ends stochastically and independently switch between phases of growth and shrinkage. Microtubule treadmilling, in which the microtubule plus end grows while the minus end shrinks, is observed in cells; however, the underlying mechanisms are not known. Here, we use a combination of computational and in vitro reconstitution approaches to determine the conditions leading to robust microtubule treadmilling. We find that microtubules polymerized from tubulin alone can treadmill, albeit with opposite directionality and order-of-magnitude slower rates than observed in cells. We then employ computational simulations to predict that the combinatory effects of four microtubule-associated proteins (MAPs), namely EB1, XMAP215, CLASP2, and MCAK, can promote fast and sustained plus-end-leading treadmilling. Finally, we experimentally confirm the predictions of our computational model using a multi-MAP, in vitro microtubule dynamics assay to reconstitute robust plus-end-leading treadmilling, consistent with observations in cells. Our results demonstrate how microtubule dynamics can be modulated to achieve a dynamic balance between assembly and disassembly at opposite polymer ends, resulting in treadmilling over long periods of time. Overall, we show how the collective effects of multiple components give rise to complex microtubule behavior that may be used for global network remodeling in cells., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

CLIP-associating proteins (CLASPs) form an evolutionarily conserved family of regulatory factors that control microtubule dynamics and the organization of microtubule networks. The importance of CLASP activity has been appreciated for some time, but until recently our understanding of the underlying molecular mechanisms remained basic. Over the past few years, studies of, for example, migrating cells, neuronal development, and microtubule reorganization in plants, along with in vitro reconstitutions, have provided new insights into the cellular roles and molecular basis of CLASP activity. In this Cell Science at a Glance article and the accompanying poster, we will summarize some of these recent advances, emphasizing how they impact our current understanding of CLASP-mediated microtubule regulation., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Syntenin-1 is an essential multi-functional adaptor protein, which has multiple roles in membrane trafficking and exosome biogenesis, as well as scaffolding interactions with either the actin cytoskeleton or focal adhesions. However, how this functional multiplicity relates to syntenin-1 distribution in different endosome compartments or other intracellular locations and its underlying involvement in cancer pathogenesis have yet to be fully defined. To help facilitate the investigation of syntenin-1 biology, we developed two specific monoclonal antibodies (Synt-2C6 and Synt-3A11) to spatially distinct linear sequence epitopes on syntenin-1, which were each designed to be unique at the six-amino acid level. These antibodies produced very different intracellular staining patterns, with Synt-2C6 detecting endosomes and Synt-3A11 producing a fibrillar staining pattern suggesting a cytoskeletal localisation. Treatment of cells with Nocodazole altered the intracellular localisation of Synt-3A11, which was consistent with the syntenin-1 protein interacting with microtubules. In prostate tissue biopsies, Synt-3A11 defined atrophy and early-stage prostate cancer, whereas Synt-2C6 only showed minimal interaction with atrophic tissue. This highlights a critical need for site-specific antibodies and a knowledge of their reactivity to define differential protein distributions, interactions and functions, which may differ between normal and malignant cells., Competing Interests: The authors declare that they have no competing interests. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Meiotic crossover frequency varies within genomes, which influences genetic diversity and adaptation. In turn, genetic variation within populations can act to modify crossover frequency in cis and trans. To identify genetic variation that controls meiotic crossover frequency, we screened Arabidopsis accessions using fluorescent recombination reporters. We mapped a genetic modifier of crossover frequency in Col × Bur populations of Arabidopsis to a premature stop codon within TBP-ASSOCIATED FACTOR 4b (TAF4b), which encodes a subunit of the RNA polymerase II general transcription factor TFIID. The Arabidopsis taf4b mutation is a rare variant found in the British Isles, originating in South-West Ireland. Using genetics, genomics, and immunocytology, we demonstrate a genome-wide decrease in taf4b crossovers, with strongest reduction in the sub-telomeric regions. Using RNA sequencing (RNA-seq) from purified meiocytes, we show that TAF4b expression is meiocyte enriched, whereas its paralog TAF4 is broadly expressed. Consistent with the role of TFIID in promoting gene expression, RNA-seq of wild-type and taf4b meiocytes identified widespread transcriptional changes, including in genes that regulate the meiotic cell cycle and recombination. Therefore, TAF4b duplication is associated with acquisition of meiocyte-specific expression and promotion of germline transcription, which act directly or indirectly to elevate crossovers. This identifies a novel mode of meiotic recombination control via a general transcription factor., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

We herein explore whether tris(aryl)borane Lewis acids are capable of cleaving H 2 outside of the usual Lewis acid/base chemistry described by the concept of frustrated Lewis pairs (FLPs). Instead of a Lewis base we use a chemical reductant to generate stable radical anions of two highly hindered boranes: tris(3,5-dinitromesityl)borane and tris(mesityl)borane. NMR spectroscopic characterization reveals that the corresponding borane radical anions activate (cleave) dihydrogen, whilst EPR spectroscopic characterization, supported by computational analysis, reveals the intermediates along the hydrogen activation pathway. This radical-based, redox pathway involves the homolytic cleavage of H 2 , in contrast to conventional models of FLP chemistry, which invoke a heterolytic cleavage pathway. This represents a new mode of chemical reactivity for hydrogen activation by borane Lewis acids., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Introduction: In a pilot study of chronic maternal hyperoxygenation (CMH) in left heart hypoplasia (LHH), we sought to determine effect estimates of CMH on head size, vascular resistance indices, and neurodevelopment compared to controls., Material and Methods: Nine gravidae meeting the inclusion criteria (fetal LHH, ≥25.9 weeks' gestation, and ≥10% increase in percent aortic flow after acute hyperoxygenation) were prospectively enrolled. Controls were 9 contemporary gravidae with fetal LHH without CMH. Brain growth and Doppler-derived estimates of fetal cerebrovascular and placental resistance were blindly evaluated and compared using longitudinal regression. Postnatal anthropomorphic and neurodevelopmental assessments were compared., Results: There was no difference in baseline fetal measures between groups. There was significantly slower biparietal diameter (BPD) growth in the CMH group (z-score change -0.03 ± 0.02 vs. +0.09 ± 0.05 units/week, p = 0.02). At 6 months postnatal age, the mean head circumference z-score in the CMH group was smaller than that of controls (-0.20 ± 0.58 vs. +0.85 ± 1.11, p = 0.048). There were no differences in neurodevelopmental testing at 6 and 12 months., Discussion: In this pilot study, relatively diminished fetal BPD growth and smaller infant head circumference z-scores at 6 months were noted with in utero CMH exposure., (© 2018 S. Karger AG, Basel.)

Lipids are important cellular components which can be significantly altered in a range of disease states including prostate cancer. Here, a unique systematic approach has been used to define lipid profiles of prostate cancer cell lines, using quantitative mass spectrometry (LC-ESI-MS/MS), FTIR spectroscopy and fluorescent microscopy. All three approaches identified significant difference in the lipid profiles of the three prostate cancer cell lines (DU145, LNCaP and 22RV1) and one non-malignant cell line (PNT1a). Specific lipid classes and species, such as phospholipids (e.g., phosphatidylethanolamine 18:1/16:0 and 18:1/18:1) and cholesteryl esters, detected by LC-ESI-MS/MS, allowed statistical separation of all four prostate cell lines. Lipid mapping by FTIR revealed that variations in these lipid classes could also be detected at a single cell level, however further investigation into this approach would be needed to generate large enough data sets for quantitation. Visualisation by fluorescence microscopy showed striking variations that could be observed in lipid staining patterns between cell lines allowing visual separation of cell lines. In particular, polar lipid staining by a fluorescent marker was observed to increase significantly in prostate cancer lines cells, when compared to PNT1a cells, which was consistent with lipid quantitation by LC-ESI-MS/MS and FTIR spectroscopy. Thus, multiple technologies can be employed to either quantify or visualise changes in lipid composition, and moreover specific lipid profiles could be used to detect and phenotype prostate cancer cells., Competing Interests: CONFLICTS OF INTEREST Authors declare no conflicts of interest.

Cytoplasmic linker-associated proteins (CLASPs) are microtubule-associated proteins essential for microtubule regulation in many cellular processes. However, the molecular mechanisms underlying CLASP activity are not understood. Here, we use purified protein components and total internal reflection fluorescence microscopy to investigate the effects of human CLASP2 on microtubule dynamics in vitro. We demonstrate that CLASP2 suppresses microtubule catastrophe and promotes rescue without affecting the rates of microtubule growth or shrinkage. Strikingly, when CLASP2 is combined with EB1, a known binding partner, the effects on microtubule dynamics are strongly enhanced. We show that synergy between CLASP2 and EB1 is dependent on a direct interaction, since a truncated EB1 protein that lacks the CLASP2-binding domain does not enhance CLASP2 activity. Further, we find that EB1 targets CLASP2 to microtubules and increases the dwell time of CLASP2 at microtubule tips. Although the temporally averaged microtubule growth rates are unaffected by CLASP2, we find that microtubules grown with CLASP2 display greater variability in growth rates. Our results provide insight into the regulation of microtubule dynamics by CLASP proteins and highlight the importance of the functional interplay between regulatory proteins at dynamic microtubule ends.

Meiosis is a specialized cell division that produces haploid gametes required for sexual reproduction. During the first meiotic division, homologous chromosomes pair and undergo reciprocal crossing over, which recombines linked sequence variation. Meiotic recombination frequency varies extensively both within and between species. In this review, we will examine the molecular basis of meiotic recombination rate variation, with an emphasis on plant genomes. We first consider cis modification caused by polymorphisms at the site of recombination, or elsewhere on the same chromosome. We review cis effects caused by mismatches within recombining joint molecules, the effect of structural hemizygosity, and the role of specific DNA sequence motifs. In contrast, trans modification of recombination is exerted by polymorphic loci encoding diffusible molecules, which are able to modulate recombination on the same and/or other chromosomes. We consider trans modifiers that act to change total recombination levels, hotspot locations, or interactions between homologous and homeologous chromosomes in polyploid species. Finally, we consider the significance of genetic variation that modifies meiotic recombination for adaptation and evolution of plant species., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

During meiosis, homologous chromosomes undergo crossover recombination, which creates genetic diversity and balances homolog segregation. Despite these critical functions, crossover frequency varies extensively within and between species. Although natural crossover recombination modifier loci have been detected in plants, causal genes have remained elusive. Using natural Arabidopsis thaliana accessions, we identified two major recombination quantitative trait loci ( rQTL s) that explain 56.9% of crossover variation in Col×Ler F 2 populations. We mapped rQTL1 to semidominant polymorphisms in HEI10 , which encodes a conserved ubiquitin E3 ligase that regulates crossovers. Null hei10 mutants are haploinsufficient, and, using genome-wide mapping and immunocytology, we show that transformation of additional HEI10 copies is sufficient to more than double euchromatic crossovers. However, heterochromatic centromeres remained recombination-suppressed. The strongest HEI10 -mediated crossover increases occur in subtelomeric euchromatin, which is reminiscent of sex differences in Arabidopsis recombination. Our work reveals that HEI10 naturally limits Arabidopsis crossovers and has the potential to influence the response to selection., (© 2017 Ziolkowski et al.; Published by Cold Spring Harbor Laboratory Press.)

Objective: Acute maternal hyperoxygenation (AMH) results in increased fetal left heart blood flow. Our aim was to perform a pilot study to determine the safety, feasibility and direction and magnitude of effect of chronic maternal hyperoxygenation (CMH) on mitral and aortic valve annular dimensions in fetuses with left heart hypoplasia (LHH) after CMH., Methods: Gravidae with fetal LHH were eligible for inclusion in a prospective evaluation of CMH. LHH was defined as: sum of aortic and mitral valve annuli Z-scores < -4.5, arch flow reversal and left-to-right or bidirectional atrial level shunting without hypoplastic left heart syndrome or severe aortic stenosis. Gravidae with an affected fetus and with ≥ 10% increase in aortic/combined cardiac output flow after 10 min of AMH at 8 L/min 100% fraction of inspired oxygen were offered enrollment. Nine gravidae were enrolled from February 2014 to January 2015. The goal therapy was ≥ 8 h daily CMH from enrollment until delivery. Gravidae who were cared for from July 2012 to October 2014 with fetal LHH and no CMH were identified as historical controls (n = 9). Rates of growth in aortic and mitral annuli over the final trimester were compared between groups using longitudinal regression., Results: There were no significant maternal or fetal complications in the CMH cohort. Mean gestational age at study initiation was 29.6 ± 3.2 weeks for the intervention group and 28.4 ± 1.8 weeks for controls (P = 0.35). Mean relative increase in aortic/combined cardiac output after AMH was 35.3% (range, 18.1-47.9%). Median number of hours per day on CMH therapy was 9.3 (range, 6.5-14.6) and median duration of CMH was 48 (range, 33-84) days. Mean mitral annular growth was 0.19 ± 0.05 mm/week compared with 0.14 ± 0.05 mm/week in CMH vs controls (mean difference 0.05 ± 0.05 mm/week, P = 0.33). Mean aortic annular growth was 0.14 ± 0.03 mm/week compared with 0.13 ± 0.03 mm/week in CMH vs controls (mean difference 0.01 ± 0.03 mm/week, P = 0.75). More than 9 h CMH daily (n = 6) was associated with better growth of the aortic annulus in intervention fetuses (0.16 ± 0.03 vs 0.08 ± 0.02 mm/week, P = 0.014)., Conclusions: CMH is both safe and feasible for continued research. In this pilot study, the effect estimates of annular growth, using the studied method of delivery and dose of oxygen, were small. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

We herein report the synthesis of novel "Janus" calix[4]arenes bearing four "molecular tethering" functional groups on either the upper or lower rims of the calixarene. These enable facile multipoint covalent attachment to electrode surfaces with monolayer coverage. The other rim of the calixarenes bear either four azide or four ethynyl functional groups, which are easily modified by the copper(I)-catalyzed azide-alkyne cycloaddition reaction (CuAAC), either pre- or postsurface modification, enabling these conical, nanocavity reactor sites to be decorated with a wide range of substrates to impart desired chemical properties. Redox active species decorating the peripheral rim are shown to be electrically connected by the calixarene to the electrode surface in either "up" or "down" orientations of the calixarene.

Whilst hydrogen is a potentially clean fuel for energy storage and utilisation technologies, its conversion to electricity comes at a high energetic cost. This demands the use of rare and expensive precious metal electrocatalysts. Electrochemical-frustrated Lewis pairs offer a metal-free, CO tolerant pathway to the electrocatalysis of hydrogen oxidation. They function by combining the hydrogen-activating ability of frustrated Lewis pairs (FLPs) with electrochemical oxidation of the resultant hydride. Here we present an electrochemical-FLP approach that utilises two different Lewis acids - a carbon-based N -methylacridinium cation that possesses excellent electrochemical attributes, and a borane that exhibits fast hydrogen cleavage kinetics and functions as a "hydride shuttle". This synergistic interaction provides a system that is electrocatalytic with respect to the carbon-based Lewis acid, decreases the required potential for hydrogen oxidation by 1 V, and can be recycled multiple times.