Autonomous Role Research Articles

CRISPs Function to Boost Sperm Power Output and Motility

Fertilization requires sperm to travel long distances through the complex environment of the female reproductive tract. Despite the strong association between poor motility and infertility, the kinetics of sperm tail movement and the role individual proteins play in this process is poorly understood. Here, we use a high spatiotemporal sperm imaging system and an analysis protocol to define the role of CRISPs in the mechanobiology of sperm function. Each of CRISP1, CRISP2, and CRISP4 is required to optimize sperm flagellum waveform. Each plays an autonomous role in defining beat frequency, flexibility, and power dissipation. We thus posit that the expansion of the CRISP family from one member in basal vertebrates, to three in most mammals, and four in numerous rodents, represents an example of neofunctionalization wherein proteins with a common core function, boosting power output, have evolved to optimize different aspects of sperm tail performance.

Successfully Articulating National Constitutional Identity Claims: Strait Is the Gate and Narrow Is the Way

Article 4(2) Treaty of the European Union (TEU) has not played any autonomous role up to now. Cases involving that provision have not been handled differently by the Court than cases involving derogations to free movement. In this article, after an analysis of the existingcase law on Article 4(2) TEU, I make the case for a bolder and exceptional use of Article 4(2) TEU where genuine national constitutional identity claims (NCI claims) directly clash with provisions of EU law. I provide a normative framework of analysis to identify genuine NCI claims and determine how the Court should address them. ‘Strait is the gate and narrow is the way’ is certainly a relevant metaphor to capture the possibility for genuine NCI claims to be successful. In view of its own mission and constraints, the Court is only to accept well motivated, narrow claims that are strictly based on crucial and distinctive features of national law that are embedded in the national Constitution and do not run against the own constitutional identity of the Union. Member State constitutional identity, Article 4(2) TEU, Extraordinary function, Constitutional conflicts, Instructions for use, Constitutional courts, Court of Justice, Balancing between national identity and fundamental rights, European Union constitutional identity, National and European constitutionalism

Ketamine Infusion in an Outpatient Surgical Facility

<h3>Background Information</h3> Cancer and the treatment plans associated with its management has the potential to impact a patient physically and physiologically. With the common complication being chronic pain, management can be challenging and at times suboptimal. Ketamine in subanesthetic dose is a widely used phencyclidine derivative for the management of chronic pain when inadequate response to multimodal treatments such as opioid therapy occurs. The Josie Robertson Surgery Center (JRSC) has established a ketamine infusion program to manage chronic pain in our cancer population. <h3>Objectives of Project</h3> To provide ketamine intravenous infusions for the management of chronic cancer pain in conjunction with opioid and/or non-steroidal anti-inflammatory drugs in a controlled setting of a perianesthesia unit; to acquire an extended period of pain relief. <h3>Process of Implementation</h3> A core group of eight nurses were educated in implementing the program within a limited time frame, in partnership with an interdisciplinary team including the office practice pain service. Education included hands-on training of multiple equipment, electronic documentation in a training environment, review of the potential side effects to anticipate and how to navigate effectively the various healthcare technological systems available for monitoring patients during their individualized outpatient visit. Nurses use their perianesthesia clinical judgment in following the titration order of four-hour ketamine infusion in accordance with potential side effects that patients might exhibit. Nursing competency for this program is accomplished by maintaining BLS and ACLS certifications, evaluation of knowledge of moderate sedation through a yearly examination and frequent re-evaluation of workflow created to provide an efficient service. <h3>Statement of Successful Practice</h3> Centered on patient's self-reporting of pain relief as evident by vocalizing improvement in their quality of life through reduction of pain intensity, increase in their ability to perform ADLs and repeat infusions based on long-lasting effect. <h3>Implications for Advancing the Practice of Perianesthesia Nursing</h3> Provides perianesthesia nurses with an autonomous role to translate their perianesthesia skills for an outpatient pain service.

What do cardiac surgical assistants in the Kingdom of Saudi Arabia think about their job? A cross-sectional survey of job and work characteristics.

Concerns about job design of the cardiac surgical assistant workforce such as role autonomy and job dissatisfaction have been outlined in the literature, although scant empirical research has examined these concerns from the perspective of cardiac surgical assistants themselves. This study surveyed the job design of cardiac surgical assistants in the Kingdom of Saudi Arabia using Morgeson and Humphrey’s Work Design Questionnaire. All scalable items within the questionnaire were reported as satisfactory except for ‘autonomy’, ‘task identity’, ‘feedback from the job’, ‘job complexity’, ‘social support’, ‘feedback from others’, ‘ergonomic’ and ‘work condition’. The results provide insight into aspects of cardiac surgical assistants’ role characteristics and contribute to the body of knowledge about their organisational psychology. Given the growth of cardiothoracic operations, the role of the surgical care assistant needs to be further developed to address the job design issues raised.

Shared Decision-Making and Role Preference Among Patients With Schizophrenia in Malaysia: A Cross-Sectional Study.

Introduction: Shared decision-making (SDM) is recognized as a promising strategy for improving collaboration between clinicians and their patients in achieving recovery. In Malaysia, SDM among people with schizophrenia is still lacking both in practice and in research. This study aimed to determine the level of SDM and role preference and their associated factors among patients with schizophrenia in Malaysia.Methods: A cross-sectional study was conducted on 86 outpatient attendees with schizophrenia at a teaching hospital in Kuala Lumpur, Malaysia. The nine-item Shared Decision Making Questionnaire and Control Preference Scale were used to assess perceived SDM experience and role preference, respectively. Linear and logistic regression models were used to analyze the factors associated with SDM and role preference, respectively. Factors with a p <0.25 from the simple regression analyses were controlled as the covariates in the multiple regression analyses.Results: The study respondents were predominantly female, single, and unemployed, with a mean age of 44 years. Only 35% of the participants reported having high SDM experiences, even though the majority (56%) preferred autonomous role preference. Among the participants who preferred autonomous roles, only 40% experienced high SDM. High SDM was found to be significantly associated with being younger (B = −0.33, 95% CI = −0.67 to −0.003) and being non-clozapine users (B = 19.90, 95% CI = 9.39–30.41), while autonomous role preference was significantly associated with a lower level of insight [adjusted odds ratio (AOR) = 0.84, 95% CI = 0.72–0.99] and being on oral antipsychotic drugs only (AOR = 2.94, 95% CI = 1.10–7.82).Conclusion: The practice of SDM is still lacking in the treatment of patients with schizophrenia in Malaysia, even though many of them preferred to be involved in the decision-making pertaining to their treatment. This study indicates the need for clinicians to improve their patients' involvement in the treatment process. More research is needed on how SDM can be implemented in patients with schizophrenia, especially in Asian population settings.

Women’s Health Nursing in Turkey and in The World

Nursing, as a community service, is a profession that has existed since ancient times, with the desire to make people healthy, to ensure the comfort of people, to take care of the patient and to provide the patient with a sense of safety. Due to the impact of technology on healthcare, and with the increase in knowledge, many nurses today are seeking to work in an expanding, specialized or advanced practitioner role. Women's health nursing undertakes the roles of education, counseling, evidence-based work, research and scientific knowledge production, reducing the cost of care and increasing community satisfaction, with a woman-centered holistic approach at each life stage of women, in order to prevent diseases, and to protect and improve health. In developed countries in the field of Women's Health Nursing, such as the USA, England and Thailand, women's health nursing is a very special field of advanced nursing practices, which provides a woman-centered holistic approach, in the delivery of primary healthcare services, requiring master or PhD level expertise, and has dynamic&amp;highly autonomous roles. Considering the developing countries, it is seen that women's health nursing is not really developed and it is carried out under the name of community-based nursing or "midwifery" in these countries. In 2011, women's health nursing roles and responsibilities were announced in our country, but its special fields were not included. In this context, it is necessary to develop special fields such as urogynecology, infertility, perinatology, gynecology and gynecological oncology, sexual health, menopause, as well as reorganize the roles and responsibilities of specialist nurses and all these should be supported within the scope of legal regulation.

Acceptability of Physiotherapists in the Emergency Department for the Care of Adults With Musculoskeletal Disorders

Purpose: Over the past decades, pressure on emergency departments (EDs) has been increasing. New ED models of care including physiotherapists in more autonomous roles, often called advanced practice physiotherapy (APP) care, are emerging to improve access to care, especially for patients with musculoskeletal disorders (MSKDs). As such, the purpose of this study was to assess patient' acceptability of APP ED care for patients with MSKDs. Methods: Patients consulting for an MSKD were recruited in 1 Canadian ED and completed a 13-question survey assessing their acceptability of ED APP care. Descriptive analyses as well as χ2 and Fisher's exact tests, with associated 95% confidence interval, were performed. Results: Forty-one patients completed the survey. A majority of respondents (56%) trusted APPs to provide accurate diagnoses for MSKD in the ED, and 80.5% were confident they would provide safe care. Most participants felt confident that APPs would appropriately order medical imaging tests (73%) or prescribe medication (66%) when necessary. Sixty-six percent of participants agreed that seeing only a physiotherapist without the intervention of a physician would reduce their length of ED stay. Conclusions: Within this exploratory survey, participants were favorable to ED APP for the care of MSKD, suggesting that implementation of such models would be accepted by patients with MSKD presenting to an ED.

The autonomous side of EO and firm performance: the role of professional experience and entrepreneurial engagement

PurposeThe purpose of this study is to investigate the direct and indirect role of autonomy on firm performance. It also determines the role of professional experience in the relationship.Design/methodology/approachThe authors analyzed data collected from 124 small firms in Addis Ababa city using the ordinary least square (OLS) regression and hierarchical regression analysis.FindingsThe result of the OLS regression revealed that autonomy directly and indirectly (through entrepreneurial engagement) influences the firm's performance. Besides, professional experience moderates the relationship between autonomy and performance, as well as the relationship between autonomy and entrepreneurial engagement.Practical implicationsEntrepreneurs should tend to engage in the works that they have professional experience than involving in jobs that they have no experience.Originality/valueThis study examines the relationship between autonomy and firm performance in established firms. It is among the first studies that tested the moderation influence in the relationship. That is, determining the role of professional experience is a novel contribution of this study, which is forgotten previously.

Autonomy and control in the wish to die in terminally ill patients: A systematic integrative review.

Personal autonomy and control are major concepts for people with life-limiting conditions. Patients who express a wish to die (WTD) are often thought of wanting it because of loss of autonomy or control. The research conducted so far has not focused on personal beliefs and perspectives; and little is known about patients' understanding of autonomy and control in this context. The aim of this review was to analyze what role autonomy and control may play in relation to the WTD expressed by people with life-limiting conditions. A systematic integrative review was conducted. The search strategy used MeSH terms in combination with free-text searching of the EBSCO Discovery Service (which provides access to multiple academic library literature databases, including PubMed and CINAHL), as well as the large PsycINFO, Scopus, and Web of Science library literature databases from their inception until February 2019. The search was updated to January 2021. After the screening process, 85 full texts were included for the final analysis. Twenty-seven studies, recording the experiences of 1,824 participants, were identified. The studies were conducted in Australia (n = 5), Canada (n = 5), USA (n = 5), The Netherlands (n = 3), Spain (n = 2), Sweden (n = 2), Switzerland (n = 2), Finland (n = 1), Germany (n = 1), and the UK (n = 1). Three themes were identified: (1) the presence of autonomy for the WTD, (2) the different ways in which autonomy is conceptualized, and (3) the socio-cultural context of research participants. Despite the importance given to the concept of autonomy in the WTD discourse, only a few empirical studies have focused on personal interests. Comprehending the context is crucial because personal understandings of autonomy are shaped by socio-cultural-ethical backgrounds and these impact personal WTD attitudes.

Work-family conflict and firefighters' satisfaction with life: The autonomous motivation role.

Using the Conservation of Resources Theory and the Self-Determination Theory1-3 as theoretical frameworks, a model for this study was tested, which considers firefighters' autonomous motivation, work-family conflict, and well-being. The hypothesized model was tested using a sample of 201 firefighters from the Special Civil Protection Force in Portugal. Results revealed that autonomous work motivation was significantly related to both work-family conflict and satisfaction with life. In addition, work-family conflict was negatively related to satisfaction with life. More interestingly, the results showed that work-family conflict acted as a mechanism that helped to explain the relationship between autonomous motivation and satisfaction with life. These results underline the importance of understanding the mechanisms through which higher satisfaction with life occurs, with a view to the creation of appropriate -interventions.

Rgs4 is a regulator of mTOR activity required for motoneuron axon outgrowth and neuronal development in zebrafish

The Regulator of G protein signaling 4 (Rgs4) is a member of the RGS proteins superfamily that modulates the activity of G-protein coupled receptors. It is mainly expressed in the nervous system and is linked to several neuronal signaling pathways; however, its role in neural development in vivo remains inconclusive. Here, we generated and characterized a rgs4 loss of function model (MZrgs4) in zebrafish. MZrgs4 embryos showed motility defects and presented reduced head and eye sizes, reflecting defective motoneurons axon outgrowth and a significant decrease in the number of neurons in the central and peripheral nervous system. Forcing the expression of Rgs4 specifically within motoneurons rescued their early defective outgrowth in MZrgs4 embryos, indicating an autonomous role for Rgs4 in motoneurons. We also analyzed the role of Akt, Erk and mechanistic target of rapamycin (mTOR) signaling cascades and showed a requirement for these pathways in motoneurons axon outgrowth and neuronal development. Drawing on pharmacological and rescue experiments in MZrgs4, we provide evidence that Rgs4 facilitates signaling mediated by Akt, Erk and mTOR in order to drive axon outgrowth in motoneurons and regulate neuronal numbers.

Defective Notch Activation in Mesenchymal Cells Contributes to Myeloproliferative Neoplasm in Aged Mice

Increasing evidence supports important roles of the bone marrow (BM) microenvironment in the development of hematological malignancies. Recently, the non-cell autonomous role of Notch signaling has emerged as one of the key regulators of normal and malignant hematopoiesis. By using a Mx1 - Cre -mediated Rbpj gene deletion in mice (Mx1 - Cre ; R bpjf/f) as a genetic model of Notch loss-of function, we have previously discovered that loss of Rbpj in microenvironment leads to a myeloproliferative neoplasm (MPN)-like disease, which is driven by increased miR-155 expression, NF-kB activation, and inflammatory cytokine production (Wang et al . Cell Stem Cell, 2014). The Mx1 promoter is active in hematopoietic cells as well as in non-hematopoietic cells. In vitro analysis of the impact of Mx1 - Cre -induced R bpj gene deletion on BM endothelial cells (EC), mesenchymal stem cells (MSC), bone cells, andhematopoietic cells showed a greater increase of miR-155 expression in EC and MSC compared to other cell types, leading to higher production of inflammatory cytokines, in particular G-CSF and TNF-a. Comparative in vivo studies showed that EC-specific R bpj knockout mice (Tie2 - CreER ;Rbpjf/f) developed an inflammation and MPN-like disease like Mx1 - Cre ; R bpjf/f mice. However, the disease affected 80% of Tie2 - CreER ;Rbpjf/f mice (compared to 100% of Mx1 - Cre ; R bpjf/f), took longer time to develop (8-12 months vs. 4 months), and was less aggressive than in Mx1 - Cre ; R bpjf/f mice.To further dissect the individual contribution of different stromal cell types to the regulation of myelopoiesis, we used an Osterix (Osx)-Cre -mediated loss-of-function approach to inactivate Rbpj in mesenchymal cells in vivo . We found that the impact of Osx -driven Notch loss-of-function in mice is age-dependent. 5-month-old Osx-Cre ; Rbpjf/f mice showed no abnormal hematologic features compared to controls, as they exhibited similar numbers and percentages of white blood cells (WBC), lymphocytes, neutrophils, red blood cells, and platelets, and comparable percentages of Gr-1+CD11b+ granulocytes, B220+ B cells, and CD3+ T cells in their BMs and spleens. Age-dependent myeloid skewing was shown in wild-type (WT) control mice, but interestingly, was more accentuated in Osx-Cre ; Rbpjf/f mice. Osx-Cre ; Rbpjf/f mice between 11 and 18 months of age showed significantly increased WBC counts in their blood due to increases in neutrophils, lymphocytes and monocytes, but exhibited similar percentages of hematopoietic populations in their BMs and spleens. However, 2 out of 7 mice in the oldest cohort between 17 and 18 months of age showed significant hematological differences in terms of numbers and percentages of hematopoietic cells in their blood, BMs and spleens compared to age-matched controls. Detailed analysis of individual mice revealed that the 2 mutant mice showed an MPN-like disease with circulating myeloid progenitors, splenomegaly and increased granulocyte-macrophage progenitors (GMP) in the BM. In summary, the deletion of Rb pj induced a MPN-like disease in 15% of Osx-Cre ; Rbpjf/f mice and was age-dependent.Cytokine analysis revealed an overall increase of inflammatory cytokines in WT mice during aging; G-GSF and GM-CSF were detected only in the blood of aged (11- to 18-month-old) mice but not young (5-month-old), and C5/C5a was 14-fold increased. Interestingly, in the young Osx-Cre ; Rbpjf/f mice, the levels of many cytokines, such as TIMP-1, IL-16, TNF-a, M-CSF, C5/C5a, IP-10/CXCL10, and CCL2/MCP-1, were already more elevated (1.5- to 20-fold) than in age-matched controls. Importantly, the Osx-Cre ; Rbpjf/f mice that developed MPN showed specific increases of CXCL13/BCA-1, IL-1RA, IL-16, and TIMP-1, which were approximately 2- to 5-fold higher than in age-matched WT control and non-MPN mutant mice, indicating that these cytokines are strongly associated with the MPN phenotype. These data suggest that changes in the BM niche and inflammatory cytokines due to loss of Notch signaling in mesenchymal cells may cooperate with the physiological increase of inflammation occurring during aging in the development of MPN. Collectively, these observations show that loss of Notch signaling leads to different levels of inflammation and has a different biological impact depending on the specific niche cell type. DisclosuresNo relevant conflicts of interest to declare.

Autonomy and developing physicians: Reimagining supervision using self-determination theory.

In this article, we address the question, 'What is the role of autonomy in physician development?' Medical education is a developmental process, and autonomy plays a motivational role in physician development. Calls for increased supervision of residents have raised concerns that the resulting decreased autonomy might interfere with resident development, leading the authors to explore the relationship between supervision and autonomy. The medical education literature posits a simple inverse relationship between supervision and autonomy. Within competency frameworks, autonomy is operationalised as independence and viewed as the end goal of training. Alternatively, there is emerging empirical literature describing autonomy and supervision as dynamic and developmental constructs and point towards more complex relationship between supervision and autonomy. Self-determination theory (SDT) presents a framework for understanding this dynamic relationship and the role of autonomy in physician development. Within SDT, autonomy is a fundamental psychological need, associated with motivation for learning, self-regulation and an internal locus of control. Supporting learner autonomy can afford learners the opportunity to internalise the values and norms of the profession, leading to an integrated regulation of their behaviours and actions. Conceptualising autonomy through the lens of SDT provides an avenue for education interventions and future research on supervision and autonomy. Educators can integrate supervision and autonomy support in the clinical setting, seeking to motivate learner development by balancing optimal challenge and support and integrating autonomy support with 'hands-on' approaches to supervision. SDT also provides a theoretical framework relevant to current discussions regarding feedback conversations and coaching in medical education. Lastly, conceptualising autonomy using SDT opens new avenues for investigation, exploring the complex relationship between supervision and autonomy and developing efforts to integrate autonomy support with clinical supervision.

Pursuing Higher-Purpose Education in a Globalized Society

Education serves the role of preserving and passing down to future generations’ valuable aspects of traditions and cultures, forming the building blocks for advanced civilizations. The world is culturally diverse, yet bonds can be created through cultural exchanges, and found a global peaceful coexistence. The transmission of a variety of cultures can be inhibited or promoted by governments, yet civil society has an autonomous and important role. The author discusses examples from her personal experience in teaching music in a variety of cultural and socio-economic settings, and the impact of governmental policies on artistic teaching. The author also establishes why education in the humanities, conscience, music and fine arts form the structural underpinnings of an advanced society and culture that is sustainable and respects human rights for all.

A Novel Screen for Expression Regulators of the Telomeric Protein TRF2 Identified Small Molecules That Impair TRF2 Dependent Immunosuppression and Tumor Growth.

Simple SummaryThe telomeric protein TRF2 (Telomeric repeat-binding factor 2) is upregulated in human cancers and associated with poor prognosis. TRF2 oncogenic properties rely on its intrinsic telomere protective role, but also on cell extrinsic effects through immunosuppressive and angiogenic activities. Therefore, targeting TRF2 appears as a promising therapeutic anti-cancer strategy. In this study, we developed a cell-based method to screen for TRF2 inhibitors allowing us to identify two compounds that blunt the TRF2 pro-oncogenic properties in vivo.Telomeric repeat-binding factor 2 (TRF2) is a subunit of the shelterin protein complex, which binds to and protects telomeres from unwanted DNA damage response (DDR) activation. TRF2 expression plays a pivotal role in aging and cancer, being downregulated during cellular senescence and overexpressed during oncogenesis. Cancers overexpressing TRF2 often exhibit a poor prognosis. In cancer cells, TRF2 plays multiple functions, including telomere protection and non-cell autonomous roles, promoting neo-angiogenesis and immunosuppression. We present here an original screening strategy, which enables identification of small molecules that decrease or increase TRF2 expression. By screening a small library of Food and Drug Agency (FDA)-approved drugs, we identified two molecules (AR-A014418 and alexidine·2HCl) that impaired tumor growth, neo-angiogenesis and immunosuppression by downregulating TRF2 expression in a mouse xenograft model. These results support the chemotherapeutic strategy of downregulating TRF2 expression to treat aggressive human tumors and validate this cell-based assay capable of screening for potential anti-cancer and anti-aging molecules by modulating TRF2 expression levels.

Chromatin remodeler CHD7 is critical for cochlear morphogenesis and neurosensory patterning

Epigenetic regulation of gene transcription by chromatin remodeling proteins has recently emerged as an important contributing factor in inner ear development. Pathogenic variants in CHD7, the gene encoding Chromodomain Helicase DNA binding protein 7, cause CHARGE syndrome, which presents with malformations in the developing ear. Chd7 is broadly expressed in the developing mouse otocyst and mature auditory epithelium, yet the pathogenic effects of Chd7 loss in the cochlea are not well understood. Here we characterized cochlear epithelial phenotypes in mice with deletion of Chd7 throughout the otocyst (using Foxg1Cre/+ and Pax2Cre), in the otic mesenchyme (using TCre), in hair cells (using Atoh1Cre), in developing neuroblasts (using NgnCre), or in spiral ganglion neurons (using ShhCre/+). Pan-otic deletion of Chd7 resulted in shortened cochleae with aberrant projections and axonal looping, disorganized, supernumerary hair cells at the apical turn and a narrowed epithelium with missing hair cells in the middle region. Deletion of Chd7 in the otic mesenchyme had no effect on overall cochlear morphology. Loss of Chd7 in hair cells did not disrupt their formation or organization of the auditory epithelium. Similarly, absence of Chd7 in spiral ganglion neurons had no effect on axonal projections. In contrast, deletion of Chd7 in developing neuroblasts led to smaller spiral ganglia and disorganized cochlear neurites. Together, these observations reveal dosage-, tissue-, and time-sensitive cell autonomous roles for Chd7 in cochlear elongation and cochlear neuron organization, with minimal functions for Chd7 in hair cells. These studies provide novel information about roles for Chd7 in development of auditory neurons.

Oligodendrocyte progenitor cell maturation is dependent on dual function of MCT8 in the transport of thyroid hormone across brain barriers and the plasma membrane.

Inactivating mutations in the thyroid hormone (TH) transporter monocarboxylate transporter 8 (MCT8) causes a rare and debilitating form of X-linked psychomotor disability known as Allan Herndon Dudley syndrome (AHDS). One of the most prominent pathophysiological symptoms of MCT8-deficiency is hypomyelination. Here, patient-derived induced pluripotent stem cells (iPSCs) were used to study the role of MCT8 and TH on the maturation of oligodendrocytes. Interestingly, neither MCT8 mutations nor reduced TH affected the in vitro differentiation of control or MCT8-deficient iPSCs into oligodendrocytes. To assess whether patient-derived iPSC-derived oligodendrocyte progenitor cells (iOPCs) could provide myelinating oligodendrocytes in vivo, cells were transplanted into the shiverer mouse corpus callosum where they survived, migrated, and matured into myelinating oligodendrocytes, though the myelination efficiency was reduced compared with control cells. When MCT8-deficient and healthy control iOPCs were transplanted into a novel hypothyroid immunodeficient triple knockout mouse (tKO, mct8-/- ; oatp1c1-/- ; rag2-/- ), they failed to provide behavioral recovery and did not mature into oligodendrocytes in the hypothyroid corpus callosum, demonstrating the critical role of TH transport across brain barriers in oligodendrocyte maturation. We conclude that MCT8 plays a cell autonomous role in oligodendrocyte maturation and that functional TH transport into the central nervous system will be required for developing an effective treatment for MCT8-deficient patients.

Autonomous Non Antioxidant Roles for Fasciola hepatica Secreted Thioredoxin-1 and Peroxiredoxin-1.

Trematode parasites of the genus Fasciola are the cause of liver fluke disease (fasciolosis) in humans and their livestock. Infection of the host involves invasion through the intestinal wall followed by migration in the liver that results in extensive damage, before the parasite settles as a mature egg-laying adult in the bile ducts. Genomic and transcriptomic studies revealed that increased metabolic stress during the rapid growth and development of F. hepatica is balanced with the up-regulation of the thiol-independent antioxidant system. In this cascade system thioredoxin/glutathione reductase (TGR) reduces thioredoxin (Trx), which then reduces and activates peroxiredoxin (Prx), whose major function is to protect cells against the damaging hydrogen peroxide free radicals. F. hepatica expresses a single TGR, three Trx and three Prx genes; however, the transcriptional expression of Trx1 and Prx1 far out-weighs (>50-fold) other members of their family, and both are major components of the parasite secretome. While Prx1 possesses a leader signal peptide that directs its secretion through the classical pathway and explains why this enzyme is found freely soluble in the secretome, Trx1 lacks a leader peptide and is secreted via an alternative pathway that packages the majority of this enzyme into extracellular vesicles (EVs). Here we propose that F. hepatica Prx1 and Trx1 do not function as part of the parasite’s stress-inducible thiol-dependant cascade, but play autonomous roles in defence against the general anti-pathogen oxidative burst by innate immune cells, in the modulation of host immune responses and regulation of inflammation.

Engrailed-2 is a cell autonomous regulator of neurogenesis in cultured hippocampal neural stem cells.

Abnormalities in genes that regulate early brain development are known risk factors for neurodevelopmental disorders. Engrailed-2 (En2) is a homeodomain transcription factor with established roles in cerebellar patterning. En2 is highly expressed in the developing mid-hindbrain region, and En2 knockout (KO) mice exhibit major deficits in mid-hindbrain structures. However, En2 is also expressed in forebrain regions including the hippocampus, but its function is unknown. Previous studies have shown that the hippocampus of En2-KO mice exhibits reductions in its volume and cell numbers due to aberrant neurogenesis. Aberrant neurogenesis is due, in part, to noncell autonomous effects, specifically, reductions of innervating norepinephrine fibers from the locus coeruleus. In this study, we investigate possible cell autonomous roles of En2 in hippocampal neurogenesis. We examine proliferation, survival, and differentiation using cultures of hippocampal neurospheres of P7 wild-type (WT) and En2-KO hippocampal neural progenitor cells (NPCs). At 7days, En2-KO neurospheres were larger on average than WT spheres and exhibited 2.5-fold greater proliferation and 2-fold increase in apoptotic cells, similar to in vivo KO phenotype. Further, En2-KO cultures exhibited 40% less cells with neurite projections, suggesting decreased differentiation. Lastly, reestablishing En2 expression in En2-KO NPCs rescued excess proliferation. These results indicate that En2 functions in hippocampal NPCs by inhibiting proliferation and promoting survival and differentiation in a cell autonomous manner. More broadly, this study suggests that En2 impacts brain structure and function in diverse regions outside of the mid-hindbrain.

Portraits of UK Black and South Asian headteachers five years on: Leadership retention in the age of academization

This article analyzes the career trajectories of eight Black and South Asian headteachers who were part of a larger study of three generations of Black, Asian, and Minority Ethnic (BAME) headteachers (28) interviewed in 2015 (Johnson, 2017). Using a longitudinal life history approach and portraiture, it seeks to answer the question, “How do Black and South Asian headteachers narrate their career progression and leadership values over time?” In particular, I explore the growth of academization and the formation of Multi-Academy Trusts (MATs) on the work lives of Black and South Asian headteachers and the role of autonomy, value alignment, and professional support on their leadership retention.