Ion Regulation by miR-51 in C. elegans Muscle Tissue

MicroRNAs serve a regulatory function in an array of cellular pathways. Using existing immunoprecipitation data that identified distinct differences in miRNA and gene enrichment in muscle cells in C. elegans, a preliminary RNAi screen was run to identify potential significant miRNA targets in muscle cells. The screen identified two potential genes, twk-12 and calm-1, predicted to be regulated by miRNA-51. In order to determine the importance of miR-51 regulation of different muscle targets, RT-PCR was performed in a number of miRNA mutant strains and 3’-UTR reporters were constructed for twk-12 and calm-1. Based on these experiments, twk-12 may be regulated by mir-51, and calm-1, twk-28, and other important genes in muscle cells are likely subject to miRNA regulation. To determine any physiological consequences of miRNA regulation, ion assays were performed by subjecting worms to different concentrations of pharmacological agents that alter cellular ion concentrations. Mir-51(-) mutant worms proved to be more susceptible to altered calcium concentrations, suggesting a role of miR-51 in calcium regulation

A cluster randomised trial of a Needs Assessment Tool for adult Cancer patients and their carers (NAT-C) in primary care: A feasibility study.

BackgroundPeople with cancer often have unidentified symptoms and social care needs. The Needs Assessment Tool-Cancer (NAT-C) is a validated, structured method of assessing patient/carer concerns and prompting action, to address unmet need.AimsAssess feasibility and acceptability of a definitive two-armed cluster randomised trial of NAT-C in primary care by evaluating: recruitment of GP practices, patients and carers; most effective approach of ensuring NAT-C appointments, acceptability of study measures and follow-up.MethodsNon-blinded, feasibility study in four General Practices, with cluster randomisation to method of NAT-C appointment delivery, and process evaluation. Adults with active cancer were invited to participate with or without carer. Practices cluster randomised (1:1) to Arm I: promotion and use of NAT-C with a NAT-C trained clinician or Arm II: clinician of choice irrespective of training status. Participants completed study questionnaires at: baseline, 1, 3 and 6 months. Patients booked a 20 minute needs-assessment appointment post-baseline. Patients, carers and GP practice staff views regarding the study sought through interviews/focus groups. Quantitative data were analysed descriptively. Qualitative data were analysed thematically, informed by Normalisation Process Theory. Progression to a definitive trial was assessed against feasibility outcomes, relating to: recruitment rate, uptake and delivery of the NAT-C, data collection and quality.ResultsFive GP practices approached, four recruited and trained to use the NAT-C. Forty-seven participants and 17 carers recruited. At baseline, 34/47 (72%) participants reported at least one moderate-severe unmet need, confirming study rationale. 32/47 (68%) participants received a NAT-C-guided consultation, 19 of which on Arm I. Study attrition at one month (n = 44 (94%), n = 16 (94%)), three months (n = 38 (81%), n = 14 (82%)) and six months (n = 32 (68%), n = 10 (59%)). Fifteen patient interviews conducted across the whole study and one focus group at each GP practice. Participants supported a definitive study and found measures acceptable.ConclusionThe feasibility trial indicated that recruitment rate, intervention uptake and data collection were appropriate, with refinements, for a definitive multi-centre cluster randomised controlled trial. Feasibility outcomes informed the design of a 2-armed cluster randomised controlled trial to test the effectiveness and cost-effectiveness of the NAT-C compared with usual care

The Contributions of Community-Based Monitoring and Traditional Knowledge to Arctic Observing Networks: Reflections on the State of the Field

Community-based monitoring (CBM) in the Arctic is gaining increasing support from a wide range of interested parties, including community members, scientists, government agencies, and funders. Through CBM initiatives, Arctic residents conduct or are involved in ongoing observing and monitoring activities. Arctic Indigenous peoples have been observing the environment for millennia, and CBM often incorporates traditional knowledge, which may be used independently from or in partnership with conventional scientific monitoring methods. Drawing on insights from the first Arctic Observing Summit, we provide an overview of the state of CBM in the Arctic. The CBM approach to monitoring is centered on community needs and interests. It offers fine-grained, local-scale data that are readily accessible to community and municipal decision makers. In spite of these advantages, CBM initiatives remain little documented and are often unconnected to wider networks, with the result that many practitioners lack a clear sense of the field and how best to support its growth and development. CBM initiatives are implemented within legal and governance frameworks that vary significantly both within and among different national contexts. Further documentation of differences and similarities among Arctic communities in relation to observing needs, interests, and legal and institutional capacities will help assess how CBM can contribute to Arctic observing networks. While CBM holds significant potential to meet observing needs of communities, more investment and experimentation are needed to determine how observations and data generated through CBM approaches might effectively inform decision making beyond the community level.Dans l’Arctique, la surveillance communautaire (SC) reçoit un appui de plus en plus grand de la part de nombreuses parties intéressées, dont les membres de la communauté, les scientifiques, les organismes gouvernementaux et les bailleurs de fonds. Dans le cadre des initiatives de SC, des habitants de l’Arctique effectuent des tâches permanentes d’observation et de surveillance ou participent à de telles tâches. Les peuples indigènes de l’Arctique observent l’environnement depuis des millénaires. Souvent, la SC fait appel aux connaissances traditionnelles, connaissances qui peuvent être employées seules ou conjointement avec les méthodes classiques de surveillance scientifique. Nous nous sommes appuyés sur les connaissances dérivées du premier sommet d’observation de l’Arctique pour donner un aperçu de l’état de la SC dans l’Arctique. La méthode de SC est centrée sur les besoins et les intérêts de la communauté. Elle permet d’obtenir des données à grain fin à l’échelle locale, données qui sont facilement accessibles par la communauté et les preneurs de décisions municipaux. Malgré ces avantages, il existe peu de documentation au sujet des initiatives de SC et souvent, ces initiatives ne sont pas rattachées aux grands réseaux, ce qui fait que bien des intervenants ne comprennent pas clairement ce qui se passe sur le terrain et ne savent pas vraiment comment appuyer la croissance et le développement de la surveillance communautaire. Les initiatives de SC respectent les cadres de référence nécessaires en matière de droit et de gouvernance, et ceux-ci varient considérablement au sein des contextes nationaux. L’enrichissement de la documentation en ce qui a trait aux différences et aux similitudes qui existent entre les communautés de l’Arctique en matière de besoins d’observation, d’intérêts et de capacités juridiques et institutionnelles aidera à déterminer en quoi la SC pourra jouer un rôle au sein des réseaux d’observation de l’Arctique. Bien que la SC ait la possibilité de jouer un rôle important dans les besoins d’observation des communautés, il y a lieu de faire plus d’investissements et d’expériences pour déterminer comment les observations et les données découlant des méthodes de SC pourront favoriser la prise de décisions au-delà des communautés

Lipidomic Evaluation of Feline Neurologic Disease after AAV Gene Therapy

GM1 gangliosidosis is a fatal lysosomal disorder, for which there is no effective treatment. Adeno-associated virus (AAV) gene therapy in GM1 cats has resulted in a greater than 6-fold increase in lifespan, with many cats remaining alive at \u3e 5.7 years of age, with minimal clinical signs. Glycolipids are the principal storage product in GM1 gangliosidosis whose pathogenic mechanism is not completely understood. Targeted lipidomics analysis was performed to better define disease mechanisms and identify markers of disease progression for upcoming clinical trials in humans. 36 sphingolipids and subspecies associated with ganglioside biosynthesis were tested in the cerebrospinal fluid of untreated GM1 cats at a humane endpoint ( approximately 8 months), AAV-treated GM1 cats ( approximately 5 years old), and normal adult controls. In untreated GM1 cats, significant alterations were noted in 16 sphingolipid species, including gangliosides (GM1 and GM3), lactosylceramides, ceramides, sphingomyelins, monohexosylceramides, and sulfatides. Variable degrees of correction in many lipid metabolites reflected the efficacy of AAV gene therapy. Sphingolipid levels were highly predictive of neurologic disease progression, with 11 metabolites having a coefficient of determination (R(2)) \u3e 0.75. Also, a specific detergent additive significantly increased the recovery of certain lipid species in cerebrospinal fluid samples. This report demonstrates the methodology and utility of targeted lipidomics to examine the pathophysiology of lipid storage disorders

Sex and size influence the spatiotemporal distribution of white sharks, with implications for interactions with fisheries and spatial management in the southwest Indian Ocean

The study was made possible through generous funding by Fischer Productions for fieldwork and equipment costs. TP was supported by a postdoctoral fellowship funded by the Nelson Mandela University Research Career Development Office (2016-2018) and funding from the South African Research Chairs Initiative awarded to Prof AT Lombard by the National Research Foundation, and by a Royal Society Newton International Fellowship (2018-2020, NF170682).Human activities in the oceans increase the extinction risk of marine megafauna. Interventions require an understanding of movement patterns and the spatiotemporal overlap with threats. We analysed the movement patterns of 33 white sharks (Carcharodon carcharias) satellite-tagged in South Africa between 2012 and 2014 to investigate the influence of size, sex and season on movement patterns and the spatial and temporal overlap with longline and gillnet fisheries and marine protected areas (MPAs). We used a hidden Markov model to identify ‘resident’ and ‘transient’ movement states and investigate the effect of covariates on the transition probabilities between states. A model with sex, total length and season had the most support. Tagged sharks were more likely to be in a resident state near the coast and a transient state away from the coast, while the probability of finding a shark in the transient state increased with size. White sharks moved across vast areas of the southwest Indian Ocean, emphasising the need for a regional management plan. White sharks overlapped with longline and gillnet fisheries within 25% of South Africa’s Exclusive Economic Zone and spent 15% of their time exposed to these fisheries during the study period. The demersal shark longline fishery had the highest relative spatial and temporal overlap, followed by the pelagic longline fishery and the KwaZulu-Natal (KZN) shark nets and drumlines. However, the KZN shark nets and drumlines reported the highest white shark catches, emphasising the need to combine shark movement and fishing effort with reliable catch records to assess risks to shark populations accurately. White shark exposure to shark nets and drumlines, by movement state, sex and maturity status, corresponded with the catch composition of the fishery, providing support for a meaningful exposure risk estimate. White sharks spent significantly more time in MPAs than expected by chance, likely due to increased prey abundance or less disturbance, suggesting that MPAs can benefit large, mobile marine megafauna. Conservation of white sharks in Southern Africa can be improved by implementing non-lethal solutions to beach safety, increasing the observer coverage in fisheries, and continued monitoring of movement patterns and existing and emerging threats.Publisher PDFPeer reviewe

The cellular and synaptic architecture of the mechanosensory dorsal horn

The deep dorsal horn is a poorly characterized spinal cord region implicated in processing low-threshold mechanoreceptor (LTMR) information. We report an array of mouse genetic tools for defining neuronal components and functions of the dorsal horn LTMR-recipient zone (LTMR-RZ), a role for LTMR-RZ processing in tactile perception, and the basic logic of LTMR-RZ organization. We found an unexpectedly high degree of neuronal diversity in the LTMR-RZ: seven excitatory and four inhibitory subtypes of interneurons exhibiting unique morphological, physiological, and synaptic properties. Remarkably, LTMRs form synapses on between four and 11 LTMR-RZ interneuron subtypes, while each LTMR-RZ interneuron subtype samples inputs from at least one to three LTMR classes, as well as spinal cord interneurons and corticospinal neurons. Thus, the LTMR-RZ is a somatosensory processing region endowed with a neuronal complexity that rivals the retina and functions to pattern the activity of ascending touch pathways that underlie tactile perception

Early Home Learning Study: Overview and outcomes. Final Report to the Victorian Government Department of Education and Early Child Development

This report presents findings from the Early Home Learning Study (EHLS), a cluster randomised controlled trial (RCT) conducted by the Parenting Research Centre (PRC) between 2009 and 2012. The study was commissioned by the Department of Education and Early Childhood Development (DEECD) in recognition that children from families experiencing high levels of disadvantage are vulnerable to poorer developmental outcomes in the early years of life, particularly in relation to language and communication skills. To improve support for these children, the PRC was engaged to design, implement and evaluate a program to enhance children’s early learning at home, with an emphasis on parenting and children’s language and communication skills. The EHLS had three broad goals: 1. To improve the early learning and development foundations of babies (6 to 12 months) and toddlers (12 to 36 months) in vulnerable circumstances in up to 2,000 families. 2. To build the capacity of the existing Victorian service system to support parents in creating positive home learning experiences for their children. 3. In the Victorian context, to develop scientific knowledge of how best to support parents to create enriched home learning environments in the early years. The ‘smalltalk’ programs were community-based programs designed for parents experiencing vulnerable circumstances with children aged 6 months to 3 years. To ensure acceptability and accessibility, and for ease of implementation, smalltalk was developed for two existing service platforms: - a six-week parenting group program delivered in the Maternal and Child Health (MCH) platform for parents of children aged 6 to 12 months, and - a ten-week playgroup and parenting program delivered through the supported playgroup (SPG) platform for parents of children aged 12 to 36 months. Two models of intervention intensity were trialled in each platform: the parent group or supported playgroup alone (‘smalltalk’) or the parent group/supported playgroup supplemented by an additional six home-based, individual coaching sessions (‘smalltalk plus’)

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

UNBOUND

Featured here, are the extraordinary works of our graduating Fashion Design class. This accomplishment is truly a celebration of the tree years of passion, hard work, and dedication of our students. It\u27s our hope that the fashion industry will partake in the creative endeavors of the emerging designers from the Fashion Design program at Fanshawe College in London, Ontario.https://first.fanshawec.ca/famd_design_fashiondesign_unbound/1002/thumbnail.jp