19683 research outputs found
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BECLIN1 is essential for intestinal homeostasis involving autophagy-independent mechanisms through its function in endocytic trafficking
No full textAutophagy-related genes have been closely associated with intestinal homeostasis. BECLIN1 is a component of Class III phosphatidylinositol 3-kinase complexes that orchestrate autophagy initiation and endocytic trafficking. Here we show intestinal epithelium-specific BECLIN1 deletion in adult mice leads to rapid fatal enteritis with compromised gut barrier integrity, highlighting its intrinsic critical role in gut maintenance. BECLIN1-deficient intestinal epithelial cells exhibit extensive apoptosis, impaired autophagy, and stressed endoplasmic reticulum and mitochondria. Remaining absorptive enterocytes and secretory cells display morphological abnormalities. Deletion of the autophagy regulator, ATG7, fails to elicit similar effects, suggesting additional novel autophagy-independent functions of BECLIN1 distinct from ATG7. Indeed, organoids derived from BECLIN1 KO mice show E-CADHERIN mislocalisation associated with abnormalities in the endocytic trafficking pathway. This provides a mechanism linking endocytic trafficking mediated by BECLIN1 and loss of intestinal barrier integrity. Our findings establish an indispensable role of BECLIN1 in maintaining mammalian intestinal homeostasis and uncover its involvement in endocytic trafficking in this process. Hence, this study has important implications for our understanding of intestinal pathophysiology.</p
Structural and functional characterization of siadenovirus core protein VII nuclear localization demonstrates the existence of multiple nuclear transport pathways
No full textAdenovirus protein VII (pVII) plays a crucial role in the nuclear localization of genomic DNA following viral infection and contains nuclear localization signal (NLS) sequences for the importin (IMP)-mediated nuclear import pathway. However, functional analysis of pVII in adenoviruses to date has failed to fully determine the underlying mechanisms responsible for nuclear import of pVII. Therefore, in the present study, we extended our analysis by examining the nuclear trafficking of adenovirus pVII from a non-human species, psittacine siadenovirus F (PsSiAdV). We identified a putative classical (c)NLS at pVII residues 120–128 (120PGGFKRRRL128). Fluorescence polarization and electrophoretic mobility shift assays demonstrated direct, high-affinity interaction with both IMPα2 and IMPα3 but not IMPβ. Structural analysis of the pVII-NLS/IMPα2 complex confirmed a classical interaction, with the major binding site of IMPα occupied by K124 of pVII-NLS. Quantitative confocal laser scanning microscopy showed that PsSiAdV pVII-NLS can confer IMPα/β-dependent nuclear localization to GFP. PsSiAdV pVII also localized in the nucleus when expressed in the absence of other viral proteins. Importantly, in contrast to what has been reported for HAdV pVII, PsSiAdV pVII does not localize to the nucleolus. In addition, our study demonstrated that inhibition of the IMPα/β nuclear import pathway did not prevent PsSiAdV pVII nuclear targeting, indicating the existence of alternative pathways for nuclear localization, similar to what has been previously shown for human adenovirus pVII. Further examination of other potential NLS signals, characterization of alternative nuclear import pathways, and investigation of pVII nuclear targeting across different adenovirus species is recommended to fully elucidate the role of varying nuclear import pathways in the nuclear localization of pVII.</p
Promoting Healthy Aging for Older People Living with Chronic Disease by Implementing Community Health Programs: A Randomized Controlled Feasibility Study
No full textThe rising prevalence of chronic diseases could be mitigated by expanding community programs. This study aimed to evaluate the feasibility of delivering a community wellness program for older adults living with chronic disease. A two-group randomized controlled study, with blinded assessments, enrolling adults (≥50 years) with chronic disease, was conducted at a Western Australian community hub. Participants randomly allocated to the intervention participated in exercise groups and a wellness activity twice a week. Both the intervention and control groups received a Fitbit™ and workbook. The primary outcomes were recruitment, retention, acceptability, and suitability. The secondary outcomes measured at baseline and 12 weeks included physical function and physical activity (step count). There were 126 older adults approached, of whom 22 (17.5%) were recruited. Eighteen participants (mean age = 70.8 ± 8.1, n = 8 intervention, n = 10 control) completed 12 weeks. Two intervention participants (25% adherence) completed over 70% of sessions and eight participants (44.4% retention) accepted an ongoing 3-month program. Health problems (30.2%) were barriers to both recruitment and adherence. There were no significant between-group differences in physical function. Physical activity was significantly higher in the intervention group compared to the control group (p = 0.01). Tailored programs with ongoing support may be required to improve the health of older adults living with chronic disease.</p
”No White Man’s ground, Black Mans”: Kulin “Trespassers” on Collins Street in early Melbourne’
No full textNo description supplied</p
An optimised protocol for the expression and purification of adenovirus core protein VII
No full textAdenovirus protein VII (pVII) is a highly basic core protein, bearing resemblance to mammalian histones. Despite its diverse functions, a comprehensive understanding of its structural intricacies and the mechanisms underlying its functions remain elusive, primarily due to the complexity of producing a good amount of soluble pVII. This study aimed to optimise the expression and purification of recombinant pVII from four different adenoviruses with a simple vector construct. This study successfully determined the optimal conditions for efficiently purifying pVII across four adenovirus species, revealing the differential preference for bacterial expression systems. The One Shot BL21 Star (DE3) proved favourable over Rosetta 2 (DE3) pLysS with consistent levels of expression between IPTG-induced and auto-induction. We demonstrated that combining chemical and mechanical cell lysis is possible and highly effective. Other noteworthy benefits were observed in using RNase during sample processing. The addition of RNase has significantly improved the quality and quantity of the purified protein as confirmed by chromatographic and western blot analyses. These findings established a solid groundwork for pVII purification methodologies and carry the significant potential to assist in unveiling the core structure of pVII, its arrangement within the core, DNA condensation intricacies, and potential pathways for nuclear transport.</p
Transriver Borders in the Asian Highlands
No full textAsian Highlands rivers flow down to the world’s most heavily populated river plains in South, Southeast, and East Asia. These well-watered, sediment-rich plains have attracted human settlers for millennia. For most of this history, the powerful states that ruled the river plains left highland states and communities alone, and within the highlands, shifting mosaics of states and independent communities governed river valleys. These highlanders’ border practices only restricted the movement of armies and untaxed trade but allowed flows of nomads, animals, and rivers. This system began to change during the mid-19th century, as the British, Russian, and Manchu-Qing empires began drawing competitive maps that claimed overlapping areas of the highlands. Over the next century, the British and Chinese increased their control of the highlands, and from the 1950s onward, the postcolonial Chinese, Indian, and Pakistani states attempted to enforce the ill-defined imperial-era borders on the ground. This territorialization transformed cartographic disputes into actual and threatened conflict as all three nations built up armies and infrastructure in the highlands. By the early 21st century, all three states were maintaining strict, militarized, and monitored bordering practices. The states’ bordering practices transected the Indus, Ganges-Brahmaputra, Salween, Mekong, and Yangzi River Systems. As the rivers preceded the borders, they should be known as transriver boundaries, but as much history and commentary are focused on nation-states, the waterways ahistorically tend to be called transboundary rivers.</p
Research directions for improved responses to young people’s e-cigarette use: A report from a consultation with e-cigarette policy and practice professionals
No full textIn 2024 the Australian Government responded to a rapid increase in vaping among young people with legislation designed to reduce access to e-cigarettes.Debate continues on how to balance the harm reduction potential of e-cigarettes against concerns about their potential risks. Key concerns include the potential acute harms of vaping and its potential to ‘normalise’ nicotine consumption, including smoking. This report presents research findings from a national consultation conducted in 2024 on efforts to address young people’s use of e-cigarettes or vaping. It aims to inform research that can improve policy and practice responses to young people’s vaping.We report on interviews conducted with 11 professionals working in roles related to e-cigarettes—researchers, policy professionals, public health professionals and those providing treatment—to explore their views on key issues for policy and practice responses to young people’s vaping.The consultation generated new insights into how Australian e-cigarette professionals understand young people’s vaping, the most appropriate responses and key knowledge gaps and research opportunities.</p
Yalka Loitjba: Yorta Yorta Langwidj Gunyawoka Wamadaman Woka Maya (Cuppa and Conversation: Yorta Yorta Language Repatriation on Country Therapy)
No full textSubmitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy to the School of Allied Health, Human Services and Sport, La Trobe University, Victoria, Australia.Presentation - titled Yalka Loitjba wamadaman Woka (Cuppa and conversation on country).This thesis was a recipient of the Nancy Millis Award for theses of exceptional merit.</p
Upper Limb Therapy for Infants and Young Children with Unilateral Cerebral Palsy: A Clinical Framework
No full textEarly detection and rehabilitation interventions are essential to optimise motor function in infants and young children with unilateral cerebral palsy. In this paper we report a clinical framework aimed at enhancing upper limb therapy for infants and young children with unilateral cerebral palsy during a sensitive period of brain development. We describe two major therapeutic approaches based on motor learning principles and evidence: constraint-induced movement therapy and bimanual therapy. These two therapies have demonstrated efficacy in older children and emerging evidence is available for their application to infants younger than 2 years of age. To provide clinicians with guidance as to when to implement these therapies, we discuss the key consideration when undertaking upper limb therapy programs. In addition, we describe the factors to consider when choosing which approach may be suitable for an individual child and family. Detailed strategies for implementing these therapies in infants and young children of different ability levels are given.</p
Trigueño International Law: On (Most of) the World Being (Always, Somehow) Out of Place
No full textThe chapter builds an “out of place” theory for international law. The author, Luis Eslava, a scholar of international law and development, draws on postcolonial legal theory, history, and ethnographic research in Colombia and elsewhere to show how the field of international law produces and is produced by “out-of-placeness.” The result is an international legal order that has, for five hundred years, “continually wrecked and disciplined” people and places, especially in the Global South. Eslava points scholars towards seeing that being out of place is fundamentally about dislocation, which is both a global reality and a sensible ethical position for contemporary interdisciplinary scholarship.</p