Publications by authors named "Spencer W"

Supporting older people to age well is a global policy priority, however the development and implementation of strategies to support ageing well for older Aboriginal people must be determined by the communities affected. This is necessary in colonial contexts, where socio-political structures impinge on Aboriginal rights and mainstream policy and practice creates and maintains health and social inequities. This article reports on research conducted in partnership with the Dharriwaa Elders Group, an Aboriginal Community Controlled Organisation.

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In humans, inositol polyphosphate-5-phosphatase E (INPP5E) mutations cause retinal degeneration as part of Joubert and MORM syndromes and can also cause non-syndromic blindness. In mice, mutations cause a spectrum of brain, kidney and other anomalies and prevent the formation of photoreceptor outer segments. To further explore the function of Inpp5e in photoreceptors, we generated conditional and inducible knockouts of mouse Inpp5e where the gene was deleted either during outer segment formation or after outer segments were fully formed.

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Objective: To measure current levels and experiences of food and water security in Walgett to guide a community-led program and to provide a baseline measure.

Design: A community-led cross-sectional survey conducted in April 2022 by trained local researchers.

Setting: Walgett, a regional town in NSW, Australia.

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Pathogenic coding mutations are prevalent in human neuronal transcription factors (TFs) but how they disrupt development is poorly understood. Lmx1b is a master transcriptional regulator of postmitotic neurons that give rise to mature serotonin (5-HT) neurons; over two hundred pathogenic heterozygous mutations have been discovered in human yet their impact on brain development has not been investigated. Here, we developed mouse models with different DNA-binding missense mutations.

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Article Synopsis
  • Age-related macular degeneration (AMD) and related macular dystrophies (MDs) primarily impact the retinal pigment epithelium (RPE) with drusen deposits being a key feature in the progression of these diseases.
  • The research indicates that reduced activity of matrix metalloproteinase 2 (MMP2) in RPE contributes to drusen formation by causing sterile inflammation and disrupting lipid balance, interacting with specific receptors and molecules.
  • Therapeutic approaches including MMP2 supplementation and inhibiting RAGE and sPLA2-IIA have shown promise in reducing drusen accumulation in patient-derived RPE cells, highlighting a potential treatment pathway for AMD/MDs.
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Aims: Researchers were invited by Aboriginal leaders to collaborate on this study which aimed to assess food intake in the Walgett Aboriginal community to inform long-term community-led efforts to improve food and water security and nutrition.

Methods: Aboriginal adults living in or near Walgett, a remote community in north-west NSW, Australia, completed an adapted Menzies Remote Short-item Dietary Assessment Tool, which was administered verbally and face-to-face in early 2022. Aboriginal people were involved in the survey design, training and collection, and analysis of data.

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In humans, inositol polyphosphate-5-phosphatase e (INPP5E) mutations cause retinal degeneration as part of Joubert and MORM syndromes and can also cause non-syndromic blindness. In mice, mutations cause a spectrum of brain, kidney, and other anomalies and prevent the formation of photoreceptor outer segments. To further explore the function of Inpp5e in photoreceptors, we generated conditional and inducible knockouts of mouse Inpp5e where the gene was deleted either during outer segment formation or after outer segments were fully formed.

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Objectives: First, to understand Papua New Guinea (PNG) oncology nursing issues perceived through the nurses' lens of unmet supportive care needs of people affected by cancer and to identify nurses' self-perceived educational priorities in cancer care. Second, to evaluate the tailored bidirectional learning and knowledge transfer among the participants of the Australia Capital Territory Health and PNG Oncology Nursing Development Program hosted in Australia in June 2023.

Methods: A qualitative descriptive study was conducted.

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The retina is light-sensitive neuronal tissue in the back of the eye. The phospholipid composition of the retina is unique and highly enriched in polyunsaturated fatty acids, including docosahexaenoic fatty acid (DHA). While it is generally accepted that a high DHA content is important for vision, surprisingly little is known about the mechanisms of DHA enrichment in the retina.

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The first steps of vision take place in the ciliary outer segment compartment of photoreceptor cells. The protein composition of outer segments is uniquely suited to perform this function. The most abundant among these proteins is the visual pigment, rhodopsin, whose outer segment trafficking involves intraflagellar transport (IFT).

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Article Synopsis
  • Gene therapy has struggled to gain traction in treating various diseases over the past 30 years due to challenges in effectively delivering therapeutic nucleic acids to their targets.
  • * The limitations of current plasmid DNA delivery methods, including naked pDNA and nanoparticles, have prompted the search for more efficient systems that minimize side effects and maximize efficacy.
  • * This review focuses on using exosomes derived from bovine milk and colostrum as a promising delivery platform for plasmid DNA in gene therapy, highlighting their scalability, cost-effectiveness, and ability to target multiple tissues.
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Photoreceptor cells generate neuronal signals in response to capturing light. This process, called phototransduction, takes place in a highly specialized outer segment organelle. There are significant discrepancies in the reported amounts of many proteins supporting this process, particularly those of low abundance, which limits our understanding of their molecular organization and function.

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The light-detecting organelle of the photoreceptor cell is a modified primary cilium, called the outer segment. The outer segment houses hundreds of light-sensitive membrane, "discs," that are continuously renewed by the constant formation of new discs at the outer segment base and the phagocytosis of old ones from outer segment tips by the retinal pigment epithelium. In this chapter, we describe how an actin cytoskeleton network, residing precisely at the site of disc formation, provides the driving force that pushes out the ciliary plasma membrane to form each disc evagination that subsequently can mature into a bona fide disc.

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The release of extracellular vesicles is observed across numerous cell types and serves a range of biological functions including intercellular communication and waste disposal. One cell type which stands out for its robust capacity to release extracellular vesicles is the vertebrate photoreceptor cell. For decades, the release of extracellular vesicles by photoreceptors has been documented in many different animal models of photoreceptor degeneration and, more recently, in wild type photoreceptors.

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Article Synopsis
  • - Chemotherapy remains a key treatment for various cancers but often causes severe side effects and compromises patients' quality of life; new methods for drug delivery, such as nanoparticles and liposomes, have seen limited success due to various challenges.
  • - Exosomes, particularly those derived from bovine milk, offer a promising alternative for delivering cancer treatments, as they can be engineered for targeted delivery and help reduce toxicity while enhancing drug efficacy.
  • - The article reviews studies on exosomal delivery systems, particularly for small molecules and biologics like siRNA, highlighting the benefits of milk exosomes but also emphasizing the need for further research on their safety and effectiveness compared to existing nanoformulations.
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The photoreceptor outer segment is a modified cilium filled with hundreds of flattened "disc" membranes responsible for efficient light capture. To maintain photoreceptor health and functionality, outer segments are continuously renewed through the addition of new discs at their base. This process is driven by branched actin polymerization nucleated by the Arp2/3 complex.

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Purpose: To describe the establishment of an oncology unit at the National Referral Hospital (NRH) in the Solomon Islands, a low-income nation in the South Pacific.

Methods: A scoping visit was carried out in 2016 to assist in the development of coordinated cancer services and to establish a medical oncology unit at the NRH at the request of the Medical Superintendent. This was followed by an observership visit to Canberra by an NRH doctor training in oncology in 2017.

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Photoreceptor cells generate neuronal signals in response to capturing light. This process, called phototransduction, takes place in a highly specialized outer segment organelle. There are significant discrepancies in the reported amounts of many proteins supporting this process, particularly those of low abundance, which limits our understanding of their molecular organization and function.

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Article Synopsis
  • The text indicates a correction made to the original article identified by the DOI 10.1016/j.omtn.2022.08.011.
  • This correction may address errors or inaccuracies that were present in the initial publication.
  • Understanding the specifics of the correction could be important for readers relying on the findings or data presented in the original article.
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Article Synopsis
  • Emerging viral diseases like Ebola, SARS, MERS, and COVID-19 pose challenges for therapy development due to strict safety protocols and rapid viral mutations.
  • A novel colostrum exosome-based nanoparticle delivery system, EPM, was created to simulate viral protein expression and facilitate antiviral therapeutic screening in a safer environment.
  • The EPM system successfully expressed key SARS-CoV-2 proteins and identified siRNAs that effectively reduced protein expression by 80%-95%, producing antibodies that persisted for up to 45 days, demonstrating its potential for therapeutic research.
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Assembly of transcriptomes encoding unique neuronal identities requires selective accessibility of transcription factors to cis-regulatory sequences in nucleosome-embedded postmitotic chromatin. Yet, the mechanisms controlling postmitotic neuronal chromatin accessibility are poorly understood. Here, we show that unique distal enhancers define the neuron lineage that generates serotonin (5-HT) neurons in mice.

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Neurons must function for decades of life, but how these non-dividing cells are preserved is poorly understood. Using mouse serotonin (5-HT) neurons as a model, we report an adult-stage transcriptional program specialized to ensure the preservation of neuronal connectivity. We uncover a switch in Lmx1b and Pet1 transcription factor function from controlling embryonic axonal growth to sustaining a transcriptomic signature of 5-HT connectivity comprising functionally diverse synaptic and axonal genes.

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Illegal cannabis cultivation on public lands has emerged as a major threat to wildlife in California and southern Oregon due to the rampant use of pesticides, habitat destruction, and water diversions associated with trespass grow sites. The spatial distribution of cultivation sites, and the factors influencing where they are placed, remain largely unknown due to covert siting practices and limited surveillance funding. We obtained cannabis grow-site locality data from law enforcement agencies and used them to model the potential distribution of cultivation sites in forested regions of California and southern Oregon using maximum entropy (MaxEnt) methods.

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