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Language Teacher Emotional Experiences: A Systematic Review
No full textThis handbook synthesizes accumulated research evidence about the main areas of language teacher education. It systematically applies research synthesis to the field, providing coherent, systematic insights into various aspects of language teaching.
Each chapter compares research conducted between 2010–2020 within a specialized area of teacher education. The chapters discuss the theoretical and research underpinnings of each area, describing the purposes, methods and findings of the research, including impacts of teacher education on teacher gains and teaching effectiveness.
Areas addressed in this handbook include: teacher identity, motivation, demotivation and burnout, reflective practice, action research, Content and Language Integrated Learning (CLIL) teacher education, English Medium Instruction (EMI) teacher education, self-efficacy, assessment literacy, language awareness, Technological Pedagogical Content Knowledge (TPACK), supervision and mentoring, and nativeness/non-nativeness.
This handbook is an invaluable resource for teacher educators, student/Preservice teachers, inservice teachers, graduate students of Teaching English to speakers of other languages (TESOL) and Applied Linguistics, and teacher education researchers.</p
Oncogenic PIK3CA corrupts growth factor signaling specificity.
No full textTechnical limitations have prevented understanding of how growth factor signals are encoded in distinct activity patterns of the phosphoinositide 3-kinase (PI3K)/AKT pathway, and how this is altered by oncogenic pathway mutations. We introduce a kinetic, single-cell framework for precise calculations of PI3K-specific information transfer for different growth factors. This features live-cell imaging of PI3K/AKT activity reporters and multiplexed CyTOF measurements of PI3K/AKT and RAS/ERK signaling markers over time. Using this framework, we found that the PIK3CAH1047R oncogene was not a simple, constitutive activator of the pathway as often presented. Dose-dependent expression of PIK3CAH1047R in human cervical cancer and induced pluripotent stem cells corrupted the fidelity of growth factor-induced information transfer, with preferential amplification of epidermal growth factor receptor (EGFR) signaling responses compared to insulin-like growth factor 1 (IGF1) and insulin receptor signaling. PIK3CAH1047R did not only shift these responses to a higher mean but also enhanced signaling heterogeneity. We conclude that oncogenic PIK3CAH1047R corrupts information transfer in a growth factor-dependent manner and suggest new opportunities for tuning of receptor-specific PI3K pathway outputs for therapeutic benefit
A novel de novo missense variant in netrin-1 (NTN1) associated with chorioretinal coloboma, sensorineural hearing loss and polydactyly.
No full textMicrophthalmia, anophthalmia and coloboma (MAC) comprise a highly heterogeneous spectrum of congenital ocular malformations with an estimated incidence of 1 in 5000 to 1 in 30 000 live births. Although there is likely to be a genetic component in the majority of cases, many remain without a molecular diagnosis. Netrin-1 was previously identified as a mediator of optic fissure closure from transcriptome analyses of chick and zebrafish and was shown to cause ocular coloboma when knocked out in both mouse and zebrafish. Here, we report the first patient with chorioretinal coloboma and microphthalmia harbouring a novel heterozygous likely pathogenic NTN1 missense variant, c.1483T>A p.(Tyr495Asn), validating a conserved gene function in ocular development. In addition, the patient displayed bilateral sensorineural hearing loss which was investigated by examining the sensory hair cells of ntn1a morphant zebrafish, suggesting a role for netrin-1 in hair cell development
Antibodies against endogenous retroviruses.
No full textThe human genome harbors hundreds of thousands of integrations of ancient retroviruses, amassed over millions of years of evolution. To reduce further amplification in the genome, the host prevents transcription of these now endogenous retroviruses (ERVs) through epigenetic repression and, with evolutionary time, ERVs are incapacitated by accumulating mutations and deletions. However, several members of recently endogenized ERV groups still retain the capacity to produce viral RNA, retroviral proteins, and higher order structures, including virions. The retention of viral characteristics, combined with the reversible nature of epigenetic repression, particularly as seen in cancer, allow for immunologically unanticipated ERV expression, perceived by the adaptive immune system as a genuine retroviral infection, to which it has to respond. Accordingly, antibodies reactive with ERV antigens have been detected in diverse disorders and, occasionally, in healthy individuals. Although they are part of self, the retroviral legacy of ERV antigens, and association with and, possibly, causation of disease states may set them apart from typical self-antigens. Consequently, the pathogenic or, indeed, host-protective capacity of antibodies targeting ERV antigens is likely to be context-dependent. Here, we review the immunogenicity of typical ERV proteins, with emphasis on the antibody response and its potential disease implications.</p
Using proximity labelling to investigate astrocytic protein profile changes in response to amyloid pathology in a mammalian model of Alzheimer’s disease
No full textBACKGROUND: Astrocytes are a numerous and diverse glial subtype specialised to carry out distinct roles involving maintaining homeostasis and effective functioning of the nervous system. To do so effectively, they respond to and secrete various proteins. In addition, astrocytes have been linked to Alzheimer's disease (AD), where they are believed to become reactive and contribute to neuroinflammation. A key feature of this reactive gliosis is the secretion of inflammatory mediators. Although in some instances this can be protective, in others, secretion of inflammatory mediators can be harmful, thus possibly contributing to AD pathology. At present, there remains a limited understanding of global astrocytic membrane and extracellular protein profiles and potential AD-associated changes. METHOD: Here, we aimed to address this using a proximity labelling-based approach. Specifically, we used a viral construct containing TurboID targetted to the ER under a GFAP promoter in order to study astrocyte-specific proteins trafficked through the classical secretory pathway in an AD mouse model. RESULT: After characterising the construct, we investigated changes in proteins between AD and controls over time in response to amyloid pathology. We have identified protein changes which are now being validated using mammalian biofluids such as CSF and plasma. CONCLUSION: This work enables a better understanding of astrocyte-specific membrane and extracellular protein changes as the disease progresses in a mammalian model of AD. An enhanced understanding of this will not only provide insight into astrocyte biology more generally, but may ultimately be vital for identification of novel biomarkers and therapeutic targets for detecting and treating AD
Optimizing approaches for targeted integration of transgenic cassettes by integrase mediated cassette exchange in mouse and human stem cells.
No full textTo enable robust expression of transgenes in stem cells, recombinase mediated cassette exchange at safe harbour loci is frequently adopted. The choice of recombinase enzyme is a critical parameter to ensure maximum efficiency and accuracy of the integration event. We have explored the serine recombinase family of site-specific integrases and have directly compared the efficiency of PhiC31, W-beta and Bxb1 integrase for targeted transgene integration at the Gt(ROSA)26Sor locus in mouse embryonic stem cells. All three integrases were found to be suitable for efficient engineering and long-term expression of each integrase was compatible with pluripotency, as evidenced by germline transmission. Bxb1 integrase was found to be 2-3 times more efficient than PhiC31 and W-beta. The Bxb1 system was adapted for cassette exchange at the AAVS1 locus in human induced pluripotent stem (iPS) cells, and the two commonly used ubiquitous promoters, CAG and Ef1α (EIF1A), were tested for their suitability in driving expression of the integrated transgenic cargo. AAVS1-integrated Ef1α promoter led to a very mosaic pattern of expression in targeted hiPS cells, whereas the AAVS1-integrated CAG promoter drove consistent and stable expression. To validate the system for the integration of functional machinery, the Bxb1 integrase system was used to integrate CAG-driven CRISPR-activation and CRISPR-inhibition machinery in human iPS cells and robust sgRNA-induced up- and down-regulation of target genes was demonstrated
Initiation and maintenance of the pluripotent epiblast in pre-implantation human development is independent of NODAL signaling.
No full textThe human blastocyst contains the pluripotent epiblast from which human embryonic stem cells (hESCs) can be derived. ACTIVIN/NODAL signaling maintains expression of the transcription factor NANOG and in vitro propagation of hESCs. It is unknown whether this reflects a functional requirement for epiblast development in human embryos. Here, we characterized NODAL signaling activity during pre-implantation human development. We showed that NANOG is an early molecular marker restricted to the nascent human pluripotent epiblast and was initiated prior to the onset of NODAL signaling. We further demonstrated that expression of pluripotency-associated transcription factors NANOG, SOX2, OCT4, and KLF17 were maintained in the epiblast in the absence of NODAL signaling activity. Genome-wide transcriptional analysis showed that NODAL signaling inhibition did not decrease NANOG transcription or impact the wider pluripotency-associated gene regulatory network. These data suggest differences in the signaling requirements regulating pluripotency in the pre-implantation human epiblast compared with existing hESC culture.</p
Implementation of a genotyped African population cohort, with virtual follow-up: A feasibility study in the Western Cape Province, South Africa
No full textBackground There is limited knowledge regarding African genetic drivers of disease due to prohibitive costs of large-scale genomic research in Africa. Methods We piloted a scalable virtual genotyped cohort in South Africa that was affordable in this resource-limited context, cost-effective, scalable virtual genotyped cohort in South Africa, with participant recruitment using a tiered informed consent model and DNA collection by buccal swab. Genotype data was generated using the H3Africa Illumina micro-array, and phenotype data was derived from routine health data of participants. We demonstrated feasibility of nested case control genome wide association studies using these data for phenotypes type 2 diabetes mellitus (T2DM) and severe COVID-19. Results 2267346 variants were analysed in 459 participant samples, of which 229 (66.8%) are female. 78.6% of SNPs and 74% of samples passed quality control (QC). Principal component analysis showed extensive ancestry admixture in study participants. Of the 343 samples that passed QC, 93 participants had T2DM and 63 had severe COVID-19. For 1780 previously published COVID-19-associated variants, 3 SNPs in the pre-imputation data and 23 SNPS in the imputed data were significantly associated with severe COVID-19 cases compared to controls (p<0.05). For 2755 published T2DM associated variants, 69 SNPs in the pre-imputation data and 419 SNPs in the imputed data were significantly associated with T2DM cases when compared to controls (p<0.05). Conclusions The results shown here are illustrative of what will be possible as the cohort expands in the future. Here we demonstrate the feasibility of this approach, recognising that the findings presented here are preliminary and require further validation once we have a sufficient sample size to improve statistical significance of findings. We implemented a genotyped population cohort with virtual follow up data in a resource-constrained African environment, demonstrating feasibility for scale up and novel health discoveries through nested case-control studies
The Global Influenza Hospital Surveillance Network: A multicountry public health collaboration.
No full textRespiratory viruses represent a significant public health threat. There is the need for robust and coordinated surveillance to guide global health responses. Established in 2012, the Global Influenza Hospital Surveillance Network (GIHSN) addresses this need by collecting clinical and virological data on persons with acute respiratory illnesses across a network of hospitals worldwide. GIHSN utilizes a standardized patient enrolment and data collection protocol across its study sites. It leverages pre-existing national infrastructures and expert collaborations to facilitate comprehensive data collection. This includes demographic, clinical, epidemiological, and virologic data, and whole genome sequencing (WGS) for a subset of viruses. Sequencing data are shared in the Global Initiative on Sharing All Influenza Data (GISAID). GIHSN uses financing and governance approaches centered around public-private partnerships. Over time, GIHSN has included more than 100 hospitals across 27 countries and enrolled more than 168,000 hospitalized patients, identifying 27,562 cases of influenza and 44,629 of other respiratory viruses. GIHSN has expanded beyond influenza to include other respiratory viruses, particularly since the COVID-19 pandemic. In November 2023, GIHSN strengthened its global impact through a memorandum of understanding with the World Health Organization, aimed at enhancing collaborative efforts and data sharing for improved health responses. GIHSN exemplifies the value of integrating scientific research with public health initiatives through global collaboration and public-private partnerships governance. Future efforts should enhance the scalability of such models and ensure their sustainability through continued public and private support