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This article reports on a study analysing changes in the use of digital technologies and working from home during the COVID-19 crisis and the impact of these changes on the wellbeing of five female university lecturers from Australia and Sweden. Applying collaborative autoethnographical methods, this study employed Weick's sensemaking framework to explore how the academics made sense of these sudden changes. The Positive emotion, Engagement, Relationships, Meaning, and Accomplishment (PERMA) wellbeing framework was also employed to explore the effect of these changes on the academics' wellbeing. Findings from the reflective narratives show that after the initial experiences of stress, each university lecturer was able to adapt and navigate the online teaching environment during the pandemic. However, the time constraints in preparing and adapting to online teaching, and working from home, were experienced by some of the university lecturers as highly stressful and isolating which impacted their sense of wellbeing. Even so, working from home was recognized as a positive experience, providing time for research, hobbies, and time with family. This study addresses a gap in current knowledge by examining the impact of the sudden transition to online teaching and learning had on academic wellbeing as conceptualised through the PERMA framework. In addition, by applying Weick's sensemaking framework, this study provides a unique perspective around how academics made sense of the sudden switch to online teaching and learning during COVID-19.

The use of social media in initial teacher education offers connection to a community of learners. As teacher educators we planned to use Twitter with pre-service teachers (PSTs). But at the end of the semester it was revealed that PSTs insisted on using a different platform; offering valuable perspectives and insights into the boundaries that are set by PSTs when moving from personal to professional use of social media. Through this paper we share our voices as initial teacher educators who valued the voices of PSTs in navigating the integration of Twitter into a semester of study. Revealed are insights into knowing where your students are when integrating social media to support the growth of a community. [Note: The month (Oct) and issue number (10) shown on the PDF is incorrect.]

Evolution can occur over ecological timescales, suggesting a potentially important role for rapid evolution in shaping community trait distributions. However, evidence of concordant eco-evolutionary dynamics often comes from in vitro studies of highly simplified communities, and measures of ecological and evolutionary dynamics are rarely directly comparable. Here, we quantified how ecological species sorting and rapid evolution simultaneously shape community trait distributions by tracking within- and between-species changes in a key trait in a complex bacterial community. We focused on the production of siderophores; bacteria use these costly secreted metabolites to scavenge poorly soluble iron and to detoxify environments polluted with toxic nonferrous metals. We found that responses to copper-imposed selection within and between species were ultimately the same--intermediate siderophore levels were favored--and occurred over similar timescales. Despite being a social trait, this level of siderophore production was selected regardless of whether species evolved in isolation or in a community context. Our study suggests that evolutionary selection can play a pivotal role in shaping community trait distributions within natural, highly complex, bacterial communities. Furthermore, trait evolution may not always be qualitatively affected by interactions with other community members. [ABSTRACT FROM AUTHOR]

This article reports on a qualitative case study with families of young English as an additional language (EAL) children in year 3-4 classrooms in metropolitan Melbourne, Australia. In the context of this inquiry, developmental bibliotherapy, which uses books to "heal the mind," was operationalized as a social-emotional learning (SEL) tool, using a transactional reader response approach. In this SEL approach, children made life-to-text and text-to-life connections that focused on three topic areas: body image, resilience, and self-esteem through the reading encounter. Findings shed light on the pedagogical implications of developmental bibliotherapy as an SEL tool and an eudaimonic factor in young EAL children's life worlds. [ABSTRACT FROM AUTHOR]

Targeting cell-surface molecules important for Wnt–β-catenin signaling using blocking antibodies is a promising therapeutic strategy in various cancers, but on-target inhibition of the pathway in healthy tissue leads to toxicity, limiting clinical development. Selective targeting of cell-surface Wnt receptor(s) responsible for disease initiation or progression could be a safer approach than therapies leading to broad inhibition of Wnt–β-catenin signaling in all tissues. Potent and selective activation of Wnt signaling using antibody modalities represents a significant advance in regenerative medicine drug development. Antibodies designed to activate Wnt–β-catenin signaling are in clinical development for the treatment of various ailments including colitis, liver diseases, and retinopathies. Since the recognition that mutations in components of the Wnt–β-catenin pathway underlie some human cancers, considerable attention has been dedicated to developing therapeutic modalities to block its activity. Despite numerous efforts, no drug directly inhibiting Wnt signaling is currently clinically available. Conversely, activating the Wnt pathway in a specific manner has recently been made possible with new molecules mimicking the activity of Wnt proteins, thus offering new possibilities for controlling tissue stem cell activity and for the rational treatment of various degenerative conditions. We describe the landscape of antibody modalities that modulate the Wnt–β-catenin pathway, and detail the advances and challenges in both cancer and regenerative medicine drug development. [ABSTRACT FROM AUTHOR]

The global pandemic significantly affected teacher training programs, specifically professional experience in schools. The past two years of teacher education have necessitated the innovation and adaption of traditional programs to ensure pre-service teachers' preparation and readiness to enter schools as graduates in Australia. This case report explores the creation and implementation of three innovations that were used to support pre-service teachers who undertook a remote and flexible learning placement due to school closures. The report presents the process implemented to best support the pre-service teachers and school mentors to deal with the disruption to professional experience caused. [ABSTRACT FROM AUTHOR]

FBXW7, which encodes a substrate‐specific receptor of an SCF E3 ligase complex, is a frequently mutated human tumor suppressor gene known to regulate the post‐translational stability of various proteins involved in cellular proliferation. Here, using genome‐wide CRISPR screens, we report a novel synthetic lethal genetic interaction between FBXW7 and CCNL1 and describe CCNL1 as a new substrate of the SCF‐FBXW7 E3 ligase. Further analysis showed that the CCNL1–CDK11 complex is critical at the G2‐M phase of the cell cycle since defective CCNL1 accumulation, resulting from FBXW7 mutation, leads to shorter mitotic time. Cells harboring FBXW7 loss‐of‐function mutations are hypersensitive to treatment with a CDK11 inhibitor, highlighting a genetic vulnerability that could be leveraged for cancer treatment. Synopsis: The candidate oncogene CCNL1 is regulated by FBXW7 through ubiquitination and degradation in a Cul1‐dependent manner. FBXW7‐mutant cells depend on CCNL1 for growth, sensitizing them to OTS964, an inhibitor of CCNL1 kinase partner CDK11. FBXW7‐mutant cells depend on CCNL1 for growth.CCNL1 is a novel substrate of FBXW7.CCNL1 mediates mitotic progression and reliance on this signalling axis sensitizes cells to CDK11 inhibitor OTS964. [ABSTRACT FROM AUTHOR]

Ecological theory predicts interactions between species to become more positive under abiotic stress, while competition should prevail in more benign environments. However, experimental tests of this stress gradient hypothesis in natural microbial communities are lacking. We test this hypothesis by measuring interactions between 10 different members of a bacterial community inhabiting potting compost in the presence or absence of toxic copper stress. We found that copper stress caused significant net changes in species interaction signs, shifting the net balance towards more positive interactions. This pattern was at least in part driven by copper‐sensitive isolates – that produced relatively small amounts of metal‐detoxifying siderophores – benefitting from the presence of other species that produce extracellular detoxifying agents. As well as providing support for the stress gradient hypothesis, our results highlight the importance of community‐wide public goods in shaping microbial community composition. [ABSTRACT FROM AUTHOR]

Dynamic modifications of chromatin allow rapid access of the gene regulatory machinery to condensed genomic regions facilitating subsequent gene expression. Inflammatory cytokine stimulation of cells can cause rapid gene expression changes through direct signalling pathway-mediated transcription factor activation and regulatory element binding. Here we used the Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) to assess regions of the genome that are differentially accessible following treatment of cells with interleukin-1 (IL-1). We identified 126,483 open chromatin regions, with 241 regions significantly differentially accessible following stimulation, with 64 and 177 more or less accessible, respectively. These differentially accessible regions predominantly correspond to regions of the genome marked as enhancers. Motif searching identified an overrepresentation of a number of transcription factors, most notably RelA, in the regions becoming more accessible, with analysis of ChIP-seq data confirmed RelA binding to these regions. A significant correlation in differential chromatin accessibility and gene expression was also observed. Functionality in regulating gene expression was confirmed using CRISPR/Cas9 genome-editing to delete regions that became more accessible following stimulation in the genes MMP13, IKBKE and C1QTNF1. These same regions were also accessible for activation using a dCas9-transcriptional activator and showed enhancer activity in a cellular model. Together, these data describe and functionally validate a number of dynamically accessible chromatin regions involved in inflammatory signalling. [ABSTRACT FROM AUTHOR]

Heterogeneity in resources is a ubiquitous feature of natural landscapes affecting many aspects of biology. However, the effect of environmental heterogeneity on the evolution of cooperation has been less well studied. Here, using a mixture of theory and experiments measuring siderophore production by the bacterium Pseudomonas aeruginosa as a model for public goods based cooperation, we explore the effect of heterogeneity in resource availability. We show that cooperation in metapopulations that were spatially heterogeneous in terms of resources can be maintained at a higher level than in homogeneous metapopulations of the same average resource value. The results can be explained by a positive covariance between fitness of cooperators, population size, and local resource availability, which allowed cooperators to have a disproportionate advantage within the heterogeneous metapopulations. These results suggest that natural environmental variation may help to maintain cooperation. [ABSTRACT FROM AUTHOR]

Activation of Wnt signaling entails βcatenin protein stabilization and translocation to the nucleus to regulate context-specific transcriptional programs. The majority of colorectal cancers (CRCs) initiate following APC mutations, resulting in Wnt ligand-independent stabilization and nuclear accumulation of βcatenin. The mechanisms underlying βcatenin nucleocytoplasmic shuttling remain incompletely defined. Using a novel, positive selection, functional genomic strategy, DEADPOOL, we performed a genome-wide CRISPR screen and identified IPO11 as a required factor for βcatenin-mediated transcription in APC mutant CRC cells. IPO11 (Importin-11) is a nuclear import protein that shuttles cargo from the cytoplasm to the nucleus. IPO11-/- cells exhibit reduced nuclear βcatenin protein levels and decreased βcatenin target gene activation, suggesting IPO11 facilitates βcatenin nuclear import. IPO11 knockout decreased colony formation of CRC cell lines and decreased proliferation of patient-derived CRC organoids. Our findings uncover a novel nuclear import mechanism for βcatenin in cells with high Wnt activity. [ABSTRACT FROM AUTHOR]

CDK11 is a cyclin-dependent kinase that controls proliferation by regulating transcription, RNA splicing, and the cell cycle. As its activity is increasingly associated with cancer, CDK11 is an attractive target for the development of small-molecule inhibitors. However, the development of CDK11 inhibitors with limited off-target effects against other CDKs poses a challenge based on the high conservation of sequence across family members. OTS964 is notable as it displays a measure of specificity for CDK11 in cells. To understand the basis for OTS964's specificity for CDK11, we solved a 2.6 Å crystal structure of the CDK11 kinase domain bound to OTS964. Despite the absence of cyclin, CDK11 adopts an active-like conformation when bound to OTS964. We identified amino acids likely to contribute to the specificity of OTS964 for CDK11 and assessed their contribution to OTS964 binding by isothermal titration calorimetry (ITC) in vitro and by resistance to OTS964 in cells. [Display omitted] • Determined the crystal structure of CDK11 bound to the kinase inhibitor OTS964 • The CDK11 kinase domain adopts an active-like conformation • The G223S mutation causes OTS964 resistance by interfering with OTS964 binding Kelso et al. report the crystal structure of the CDK11 kinase domain bound to the small-molecule inhibitor OTS964. Mutational analysis explores the contribution of specific contact residues toward OTS964 binding and specificity. [ABSTRACT FROM AUTHOR]

Positive transcription elongation factor b (P-TEFb), the complex of Cyclin T1 and CDK9, activates the transcription of many viral and eukaryotic genes at the point of mRNA elongation. The activity of P-TEFb has been implicated in the differentiation of a number of cell types, including skeletal muscle. In order to promote transcription, P-TEFb hyperphosphorylates RNA Pol II, thereby increasing its processivity. Our previous work identified histone H1 as a P-TEFb substrate during HIV-1 and immediate-early transcription. Here, we examine the role of P-TEFb phosphorylation of histone H1 during differentiation, using the myoblast cell line C2C12 as a model for skeletal muscle differentiation. We found that H1 phosphorylation is elevated in differentiating C2C12, and this phosphorylation is sensitive to P-TEFb inhibition. H1 phosphorylation was also necessary for the induction of three muscle marker genes that require P-TEFb for expression. Additionally, ChIP experiments demonstrate that H1 dissociates from muscle differentiation marker genes in C2C12 cells under active P-TEFb conditions. We determine that both P-TEFb activity and H1 phosphorylation are necessary for the full differentiation of C2C12 myoblasts into myotubes. J. Cell. Physiol. 227: 383-389, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Transcription of HIV-1 genes depends on the RNA polymerase II kinase and elongation factor positive transcription elongation factor b (P-TEFb), the complex of cyclin T1 and CDK9. Recent evidence suggests that regulation of transcription by P-TEFb involves chromatin binding and modifying factors. To determine how P-TEFb may connect chromatin remodeling to transcription, we investigated the relationship between P-TEFb and histone H1. We identify histone H1 as a substrate for P-TEFb involved in cellular and HIV-1 transcription. We show that P-TEFb interacts with H1 and that P-TEFb inhibition by RNAi, flavopiridol, or dominant negative CDK9 expression correlates with loss of phosphorylation and mobility of H1 in vivo. Importantly, P-TEFb directs H1 phosphorylation in response to wild-type HIV-1 infection, but not Tat-mutant HIV-1 infection. Our results show that P-TEFb phosphorylates histone H1 at a specific C-terminal phosphorylation site. Expression of a mutant H1.1 that cannot be phosphorylated by P-TEFb also disrupts Tat transactivation in an HIV reporter cell line as well as transcription of the c-fos and hsp70 genes in HeLa cells. We identify histone H1 as a novel P-TEFb substrate, and our results suggest new roles for P-TEFb in both cellular and HIV-1 transcription. [ABSTRACT FROM AUTHOR]

Background. Malnutrition is common among dialysis patients and is associated with an adverse outcome. One cause of this is a persistent reduction in nutrient intake, suggesting an abnormality of appetite regulation. [ABSTRACT FROM PUBLISHER]

Introduction: Socially excluded individuals have higher morbidity and mortality, use a disproportionate amount of healthcare resources and generate a large volume of potentially preventable healthcare and other costs compared to more privileged individuals. Through a person-centred, whole-system and multi-disciplinary approach to care delivery, integrated care improves care for people with complex needs who are likely to have poor outcomes. Homeless and other socially excluded individuals frequently need the input of multiple health and social care providers. The rehabilitation needs of these individuals have not been explored previously and this projects aim was to establish a baseline of need for this cohort. Design, subjects and setting: A prospective cohort study of cases presenting for discussion at an inclusion health multidisciplinary team meeting in an urban homeless service. Methods: All cases discussed at the inclusion health MDT were studied to identify demographics, inclusion health and rehabilitative needs over a 4 month period. Results: 97 cases were studied over the 4-month period. 66 (68%) were male and 31 (32%) were female. 15 (15%) were over 60 and 82 (85%) were under 60 (age range 18-80). The inclusion health needs of this population are diverse and complex. 50% of cases discussed were considered to have rehabilitation needs. 37% had a physical impairment the most common causes of which were fractures and chronic leg ulcers mainly in intravenous drug users and chronic alcoholics. 42% were considered to have a cognitive impairment. The aetiology of cognitive impairment was uncertain due to significant comorbidity and increased prevalence of mental health conditions. A history of learning disability was proposed in a number of cases. 20% of cases had both physical and cognitive impairments. 76% of individuals were currently addicted to alcohol or drugs. 63% had mental health needs including severe and enduring mental illnesses, and 71% had a chronic medical condition. Discussion: The inclusion health needs of this population are diverse and complex. A traditional rehabilitation programme would not suit the chaotic lifestyles of these individuals and often access requires a fixed address which none of these individuals have. Conclusion: The results of this study show that the rehabilitative needs of this cohort are significant and are not being met through traditional rehabilitation medicine models of care. Limitations: A detailed analysis of the specifics of the rehabilitative needs was not possible at this stage of the project and efforts are underway to identify a biopsychosocial needs assessment tool that can identify all the needs of individuals. We were also not able to assess if individuals had access to community based general rehabilitation services but it was the view of the MDT that a traditional rehabilitation programme would not suit the chaotic lifestyles of these individuals. Suggestions for future research: Development of innovative ways to assess and provide appropriate services to these individuals. [ABSTRACT FROM AUTHOR]