Agnoprotein Is an Essential Egress Factor during BK Polyomavirus Infection.

BK polyomavirus (BKPyV; hereafter referred to as BK) causes a lifelong chronic infection and is associated with debilitating disease in kidney transplant recipients. Despite its importance, aspects of the virus life cycle remain poorly understood. In addition to the structural proteins, the late region of the BK genome encodes for an auxiliary protein called agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to virion infectivity. Here, we demonstrate an essential role for agnoprotein in BK virus release. Viruses lacking agnoprotein fail to release from host cells and do not propagate to wild-type levels. Despite this, agnoprotein is not essential for virion infectivity or morphogenesis. Instead, agnoprotein expression correlates with nuclear egress of BK virions. We demonstrate that the agnoprotein binding partner α-soluble N-ethylmaleimide sensitive fusion (NSF) attachment protein (α-SNAP) is necessary for BK virion release, and siRNA knockdown of α-SNAP prevents nuclear release of wild-type BK virions. These data highlight a novel role for agnoprotein and begin to reveal the mechanism by which polyomaviruses leave an infected cell

The transformative potential of engaging in science inquiry and design-based challenges: the ATSE Wonder of Science Challenge

Well-documented declines in student participation in Science, Technology, Engineering and Mathematics (STEM) in schools are regularly linked to perceived inadequacies in both the science curriculum and teachers' self-efficacy for teaching science inquiry. In 2012, the Australian Academy of Technological Science and Engineering (ATSE) Wonder of Science Challenge pilot focused on these concerns. Students in 15 schools across northern Queensland, Australia, were provided with a design- or inquiry-based research problem. The Challenge required student teams to conduct research and present their findings at a regional student forum. This paper presents a case study of the experiences of one primary teacher – Mr Matthews – and his students. Analysis of interview and survey data revealed improvements in students' attitudes towards science-related careers, increased motivation and ownership of the inquiry process, and developed depth of science knowledge and understanding. For Mr Matthews, his participation in the Challenge enhanced his confidence in developing his students' science inquiry skills, and he reported plans to transform his teaching and assessment practices. Evidence from the case study suggest that the design and inquiry underpinnings of the Challenge created a transformative space to support and enhance students’ move from participation in teacher led-school science to making a 'shared' contribution to their science learning experiences

The transformative potential of engaging in science inquiry and design-based challenges: the ATSE Wonder of Science Challenge

Well-documented declines in student participation in Science, Technology, Engineering and Mathematics (STEM) in schools are regularly linked to perceived inadequacies in both the science curriculum and teachers' self-efficacy for teaching science inquiry. In 2012, the Australian Academy of Technological Science and Engineering (ATSE) Wonder of Science Challenge pilot focused on these concerns. Students in 15 schools across northern Queensland, Australia, were provided with a design- or inquiry-based research problem. The Challenge required student teams to conduct research and present their findings at a regional student forum. This paper presents a case study of the experiences of one primary teacher – Mr Matthews – and his students. Analysis of interview and survey data revealed improvements in students' attitudes towards science-related careers, increased motivation and ownership of the inquiry process, and developed depth of science knowledge and understanding. For Mr Matthews, his participation in the Challenge enhanced his confidence in developing his students' science inquiry skills, and he reported plans to transform his teaching and assessment practices. Evidence from the case study suggest that the design and inquiry underpinnings of the Challenge created a transformative space to support and enhance students’ move from participation in teacher led-school science to making a 'shared' contribution to their science learning experiences

ATSE Wonder of Science Evaluation Report

[Extract] In Term 3, 2012, students from Year 6 to Year 9 from 15 schools across North, Far North and North West Queensland participated in the Australian Academy of Technological Sciences and Engineering (ATSE) Wonder of Science Challenge. This program aimed to enthuse students about science-based careers, and linked teachers and students with Young Science Ambassadors from universities and industry (ATSE, Queensland Division, 2012a). Student representatives from each class presented findings from a research project to an audience comprised of their peers and scientists at a culminating student\ud challenge day

The transformative potential of engaging in science inquiry-based challenges: the ATSE Wonder of Science Challenge

In 2012, the Australian Academy of Technological Science and Engineering (ATSE) piloted the Wonder of Science Challenge with a view to enhance school students' interest in Science, Technology, Engineering and Mathematics (STEM). Students in 15 schools across northern Queensland were provided with an inquiry-based research problem and presented their findings at a regional competition. This paper explores the experiences of one primary teacher, Mr. Matthews, and his students. Evidence drawn from the analysis of interview and survey data suggests that the key features of the Challenge – namely, open inquiry, engagement with practicing scientists, and the student presentations – had transformative outcomes for both teacher and students

Design and conduct of randomized clinical trials evaluating surgical innovations in ophthalmology: a systematic review

PURPOSE: Surgical innovations are necessary to improve patient care. After an initial exploratory phase novel surgical technique should be compared with alternative options or standard care in randomized clinical trials (RCTs). However surgical RCTs have unique methodological challenges. Our study sought to investigate key aspects of the design, conduct and reporting of RCTs of novel surgeries. DESIGN: Systematic Review METHODS: The protocol was prospectively registered in PROSPERO (CRD42021253297). RCTs evaluating novel surgeries for cataract, vitreoretinal, glaucoma and corneal diseases were included. Medline, EMBASE, Cochrane Library and Clinicaltrials.gov were searched. The search period was January 1, 2016, to June 16, 2021. RESULTS: Fifty-two ophthalmic surgery RCTs were identified in the fields of glaucoma (n=12), vitreoretinal surgery (n=5) cataract (n=19) and cornea (n=16). A description defining the surgeon's experience or level of expertise was reported in 30 RCTs (57%); and was presented in both, control and intervention groups, in eleven (21%). Specification of number of cases performed in the particular surgical innovation being assessed prior to the trial was reported in 10 RCTs (19%); and an evaluation of quality of the surgical intervention in seven (13%). Prospective trial registration was recorded in 12 RCTs (23%), retrospective registration in 13 (25%) and there was no registration record in the remaining 28 (53%) studies. CONCLUSION: Important aspects of the study design such as surgical learning curve, surgeon's previous experience, quality assurance, and trial registration details were often missing in novel ophthalmic surgical procedures. The IDEAL framework aims to improve the quality of study design

Agnoprotein Is an Essential Egress Factor during BK Polyomavirus Infection.

BK polyomavirus (BKPyV; hereafter referred to as BK) causes a lifelong chronic infection and is associated with debilitating disease in kidney transplant recipients. Despite its importance, aspects of the virus life cycle remain poorly understood. In addition to the structural proteins, the late region of the BK genome encodes for an auxiliary protein called agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to virion infectivity. Here, we demonstrate an essential role for agnoprotein in BK virus release. Viruses lacking agnoprotein fail to release from host cells and do not propagate to wild-type levels. Despite this, agnoprotein is not essential for virion infectivity or morphogenesis. Instead, agnoprotein expression correlates with nuclear egress of BK virions. We demonstrate that the agnoprotein binding partner α-soluble N-ethylmaleimide sensitive fusion (NSF) attachment protein (α-SNAP) is necessary for BK virion release, and siRNA knockdown of α-SNAP prevents nuclear release of wild-type BK virions. These data highlight a novel role for agnoprotein and begin to reveal the mechanism by which polyomaviruses leave an infected cell

HCV Genetic Diversity Can Be Used to Infer Infection Recency and Time since Infection.

HIV-1 genetic diversity can be used to infer time since infection (TSI) and infection recency. We adapted this approach for HCV and identified genomic regions with informative diversity. We included 72 HCV/HIV-1 coinfected participants of the Swiss HIV Cohort Study, for whom reliable estimates of infection date and viral sequences were available. Average pairwise diversity (APD) was calculated over each codon position for the entire open reading frame of HCV. Utilizing cross validation, we evaluated the correlation of APD with TSI, and its ability to infer TSI via a linear model. We additionally studied the ability of diversity to classify infections as recent (infected for <1 year) or chronic, using receiver-operator-characteristic area under the curve (ROC-AUC) in 50 patients whose infection could be unambiguously classified as either recent or chronic. Measuring HCV diversity over third or all codon positions gave similar performances, and notable improvement over first or second codon positions. APD calculated over the entire genome enabled classification of infection recency (ROC-AUC = 0.76). Additionally, APD correlated with TSI (R2 = 0.33) and could predict TSI (mean absolute error = 1.67 years). Restricting the region over which APD was calculated to E2-NS2 further improved accuracy (ROC-AUC = 0.85, R2 = 0.54, mean absolute error = 1.38 years). Genetic diversity in HCV correlates with TSI and is a proxy for infection recency and TSI, even several years post-infection

HCV genetic diversity can be used to infer infection recency and time since Iifection

HIV-1 genetic diversity can be used to infer time since infection (TSI) and infection recency. We adapted this approach for HCV and identified genomic regions with informative diversity. We included 72 HCV/HIV-1 coinfected participants of the Swiss HIV Cohort Study, for whom reliable estimates of infection date and viral sequences were available. Average pairwise diversity (APD) was calculated over each codon position for the entire open reading frame of HCV. Utilizing cross validation, we evaluated the correlation of APD with TSI, and its ability to infer TSI via a linear model. We additionally studied the ability of diversity to classify infections as recent (infected for <1 year) or chronic, using receiver-operator-characteristic area under the curve (ROC-AUC) in 50 patients whose infection could be unambiguously classified as either recent or chronic. Measuring HCV diversity over third or all codon positions gave similar performances, and notable improvement over first or second codon positions. APD calculated over the entire genome enabled classification of infection recency (ROC-AUC = 0.76). Additionally, APD correlated with TSI (R$^{2}$ = 0.33) and could predict TSI (mean absolute error = 1.67 years). Restricting the region over which APD was calculated to E2-NS2 further improved accuracy (ROC-AUC = 0.85, R$^{2}$ = 0.54, mean absolute error = 1.38 years). Genetic diversity in HCV correlates with TSI and is a proxy for infection recency and TSI, even several years post-infection