69 research outputs found

    Analysis of ATP Synthase Super-Complex Assembly and Mitochondrial Morphology in Pcp1 Mutants

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    Mitochondria are double membraned organelles responsible for the majority of ATP production in eukaryotic cells. The mitochondrial inner membrane is folded into cristae structures and is the site of the electron transport chain which terminates in ATP generation. ATP is produced by ATP synthase, a protein complex that has also been shown to have a role in the maintenance of cristae folding. This activity is dependent on Tim11p, a subunit required for the dimerization of ATP synthase super-complexes. Additional proteins located within the inner membrane that are important to mitochondrial morphology include Pcp1p, a serine protease, and its substrate, Mgm1p. Mgm1p is required for mitochondrial fusion and cells deleted for MGM1 do not contain detectable Tim11p. Using biochemical assays and transmission electron microscopy, this study characterized pcp1 mutants in order to analyze the link between Pcp1p functionality, ATP synthase super-complex assembly, and mitochondrial morphology

    Pre-Clinical Assessment of Single-Use Negative Pressure Wound Therapy During In Vivo Porcine Wound Healing

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    Objective: Traditional negative pressure wound therapy systems can be large and cumbersome, limiting patient mobility and adversely affecting quality of life. PICO™, a no canister single-use system offers a lightweight, portable alternative to traditional negative pressure wound therapy, with improved clinical performance. The aim of this study was to determine the potential mechanism(s) of action of single-use negative pressure wound therapy versus traditional negative pressure wound therapy.Approach: Single-use negative pressure wound therapy and traditional negative pressure wound therapy were applied to in in vivo porcine excisional wound model, following product use guidelines. Macroscopic, histological and biochemical analyses were performed at defined healing time-points to assess multiple aspects of the healing response. Results: Wounds treated with single-use negative pressure displayed greater wound closure and increased re-epithelialisation versus those treated with traditional negative pressure. The resulting granulation tissue was more advanced with fewer neutrophils, reduced inflammatory markers, more mature collagen and no wound filler-associated foreign body reactions. Of note, single-use negative pressure therapy failed to induce wound edge epithelial hyperproliferation, while traditional negative pressure therapy compromised peri-wound skin, which remained inflamed with high transepidermal water loss; features not observed following single-use treatment. Innovation: Single-use negative pressure was identified to improve multiple aspects of healing versus traditional negative pressure treatment.Conclusion: This study provides important new insight into the differing mode of action of single-use versus traditional negative pressure and may go some way to explain the improved clinical outcomes observed with single use negative pressure therapy

    Early parenting and children\u27s relational and physical aggression in the preschool and home contexts

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    This study investigated early parent- child relationships and how children\u27s use of relational and physical aggression varies with aspects of those relationships during the preschool years. Specifically, parenting styles, parents\u27 use of psychological control, and parents\u27 report of their children\u27s reunion behaviors were assessed. Analyses revealed significant associations between children\u27s use of both relational and physical aggression and parents\u27 reports of their own and their partner\u27s parenting style, psychological control behaviors, and indicators of the attachment relationship. The results highlight the importance of investigating both mothers\u27 and fathers\u27 parenting and the sex of the child in studies of potential links between parenting behaviors and young children’s relational and physical aggression. Findings were considered in the context of each perspective and suggestions for future research and implications for intervention and prevention are discussed

    Education Journal Magazine: Volume 3, Edition 3

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    Contents: Supporting bereaved students in a Walsall Secondary School: What strategies can be implemented in addition to those that are currently available to teachers? By Aliya Levene Is there an impact on a student’s participation levels in extra-curricular rugby based on their socio-economic status? By Lewis Jones How does the physical layout of a science classroom affect teaching secondary science? By Stephen Caton Does the English National Curriculum, with a focus on writing, offer enough opportunity for children’s agency? By Simone Douglas An exploration into the application of social learning theories in an early years classroom – SEN case study by Robyn Weir Writing for Pleasure: How comic strips can inspire children (and adults) to love writing by Suzanne Swan How prepared are Primary Pre-Service Teachers when teaching Physical Education? The study outline – Part one. By Simon Chapman Teachers’ perceptions of Criteria-Based Assessment Model of the International Baccalaureate Middle Years Program by Pousali Poddar In music and through music: Inclusion and equity for pupils with PMLD in the context of classroom music-making by Ben Seller

    Education Journal Magazine: Volume 3, Edition 2

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    Contents: Perceived Stress in Early Career Mathematics Teachers by Helen Lowther Questioning The Demise of Creativity within the Current Educational System by Charlotte Reid Is introducing a zero-tolerance behaviour policy the best decision for your school? By Georgina Williams The benefits of collaboration to develop health, education and wellbeing outcomes across educational institutions utilising the School Games Programme by Hannah Reed Using a thematic curriculum in Secondary Physical Education by Aliya Levene Since the emergence of statutory assessments, has the broad and balanced curriculum been eliminated? by Deanah Al-Dean Saleem Building the capacity to provide effective personalised feedback to students in the early years setting by Sonali Malhotra Random musings on education instruction applied to a STEM subject by Kash Haq and Martin Goldberg A phenomenological approach to inclusion: prioritising textual analysis and lived experiences by Israel Chukwuka Okunwaye The Space in-between by Kevin Daje

    Dysphagia training for speech-language pathologists: implications for clinical practice

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    There are competency standards available in countries with established speech-language pathology services to guide basic dysphagia training with ongoing workplace mentoring for advanced skills development. Such training processes, however, are not as well established in countries where speech-language pathology training and practice is relatively new, such as Malaysia. The current study examines the extent of dysphagia training and workplace support available to speech-language pathologists (SLPs) in Malaysia and Queensland, Australia, and explores clinicians’ perceptions of the training and support provided, and of their knowledge, skills, and confidence. Using a matched cohort cross-sectional design, a purpose-built survey was administered to 30 SLPs working in Malaysian government hospitals and 30 SLPs working in Queensland Health settings in Australia. Malaysian clinicians were found to have received significantly less university training, less mentoring in the workplace, and were lacking key infrastructure needed to support professional development in dysphagia management. Over 90% of Queensland clinicians were confident and felt they had adequate skills in dysphagia management; in contrast, significantly lower levels of knowledge, skills, and confidence were observed in the Malaysian cohort. The findings identify a need for improved university training and increased opportunities for workplace mentoring, training, and support for Malaysian SLPs

    Mechanism of cellular rejection in transplantation

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    The explosion of new discoveries in the field of immunology has provided new insights into mechanisms that promote an immune response directed against a transplanted organ. Central to the allograft response are T lymphocytes. This review summarizes the current literature on allorecognition, costimulation, memory T cells, T cell migration, and their role in both acute and chronic graft destruction. An in depth understanding of the cellular mechanisms that result in both acute and chronic allograft rejection will provide new strategies and targeted therapeutics capable of inducing long-lasting, allograft-specific tolerance

    The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

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    Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

    The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

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    INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century
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