Knockdown of Bardet-Biedl Syndrome Gene BBS9/PTHB1 Leads to Cilia Defects

Bardet-Biedl Syndrome (BBS, MIM#209900) is a genetically heterogeneous disorder with pleiotropic phenotypes that include retinopathy, mental retardation, obesity and renal abnormalities. Of the 15 genes identified so far, seven encode core proteins that form a stable complex called BBSome, which is implicated in trafficking of proteins to cilia. Though BBS9 (also known as PTHB1) is reportedly a component of BBSome, its direct function has not yet been elucidated. Using zebrafish as a model, we show that knockdown of bbs9 with specific antisense morpholinos leads to developmental abnormalities in retina and brain including hydrocephaly that are consistent with the core phenotypes observed in syndromic ciliopathies. Knockdown of bbs9 also causes reduced number and length of cilia in Kupffer's vesicle. We also demonstrate that an orthologous human BBS9 mRNA, but not one carrying a missense mutation identified in BBS patients, can rescue the bbs9 morphant phenotype. Consistent with these findings, knockdown of Bbs9 in mouse IMCD3 cells results in the absence of cilia. Our studies suggest a key conserved role of BBS9 in biogenesis and/or function of cilia in zebrafish and mammals

A profile of patients receiving palliative care in Queensland for January - June 2019

The Palliative Care Outcomes Collaboration (PCOC) is a national program that aims to improve the quality and outcomes of palliative care in Australia. This is achieved via a standardised clinical language that supports a national data collection. This report provides a high level profile of 4,625 patients who received palliative care in Queensland during January to June 2019 and had their pain, symptom, family / carer and psychological / spiritual issues assessed as part of routine clinical care

A profile of patients receiving palliative care in Western Australia for January - June 2019

The Palliative Care Outcomes Collaboration (PCOC) is a national program that aims to improve the quality and outcomes of palliative care in Australia. This is achieved via a standardised clinical language that supports a national data collection. This report provides a high level profile of 4,181 patients who received palliative care in Western Australia during July to December 2018 and had their pain, symptom, family / carer and psychological / spiritual issues assessed as part of routine clinical care

Patient Outcomes in Palliative Care - NSW and ACT, January - June 2019

The Australian palliative care sector is a world leader in using routine clinical assessment information to guide patient centred care and measure patient and family outcomes. Providers of palliative care are commended for their commitment to excellence in delivering evidence-based, patient-centred care by using the routine Palliative Care Outcomes Collaboration (PCOC) assessment framework and contributing patient data toward national outcome measurement and benchmarking. PCOC acknowledges the dedication and willingness of clinicians to improve the care of patients, their families and caregivers. The information collected is not just data - it represents the real-life outcomes of over 40,000 Australians who die an expected death every year. While the focus of this report is on the most recent information relating to January to June 2019, results over the last three years are also presented to highlight achievements and improvement in outcomes. The most recent information corresponds to 24,562 patients, having 31,826 episodes of care and 73,209 palliative care phases from 138 services who provide palliative care in hospital / hospice or in the person\u27s home

Study of Acute Liver Failure in Children Using Next Generation Sequencing Technology

OBJECTIVE: To use next generation sequencing (NGS) technology to identify undiagnosed, monogenic diseases in a cohort of children who suffered from acute liver failure (ALF) without an identifiable etiology. STUDY DESIGN: We identified 148 under 10 years of age admitted to King's College Hospital, London, with ALF of indeterminate etiology between 2000 and 2018. A custom NGS panel of 64 candidate genes known to cause ALF and/or metabolic liver disease was constructed. Targeted sequencing was carried out on 41 children in whom DNA samples were available. Trio exome sequencing was performed on 4 children admitted during 2019. A comparison of the clinical characteristics of those identified with biallelic variants against those without biallelic variants was then made. RESULTS: Homozygous and compound heterozygous variants were identified in 8 out of 41 children (20%) and 4 out of 4 children (100%) in whom targeted and exome sequencing were carried out, respectively. The genes involved were NBAS (3 children); DLD (2 children); and CPT1A, FAH, LARS1, MPV17, NPC1, POLG, SUCLG1, and TWINK (1 each). The 12 children who were identified with biallelic variants were younger at presentation and more likely to die in comparison with those who did not: median age at presentation of 3 months and 30 months and survival rate 75% and 97%, respectively. CONCLUSIONS: NGS was successful in identifying several specific etiologies of ALF. Variants in NBAS and mitochondrial DNA maintenance genes were the most common findings. In the future, a rapid sequencing NGS workflow could help in reaching a timely diagnosis and facilitate clinical decision making in children with ALF

Assessment innovation and student experience: a new assessment challenge and call for a multi-perspective approach to assessment research

The impact of innovative assessment on student experience in higher education is a neglected research topic. This represents an important gap in the literature given debate around the marketization of higher education, international focus on student satisfaction measurement tools and political calls to put students at the heart of higher education in the UK. This paper reports on qualitative findings from a research project examining the impact of assessment preferences and familiarity on student attainment and experience. It argues that innovation is defined by the student, shaped by diverse assessment experiences and preferences and therefore its impact is difficult to predict. It proposes that future innovations must explore assessment choice mechanisms which allow students to shape their own assessments. Cultural change and staff development will be required to achieve this. To be accepted, assessment for student experience must be viewed as a complementary layer within a complex multi perspective model of assessment which also embraces assessment of learning, assessment for learning and assessment for life long learning. Further research is required to build a meta theory of assessment to enhance the synergies between these alternative approaches and to minimise tensions between them

Essential Regulation of Cell Bioenergetics by Constitutive InsP3 Receptor Ca2+ Transfer to Mitochondria

SummaryMechanisms that regulate cellular metabolism are a fundamental requirement of all cells. Most eukaryotic cells rely on aerobic mitochondrial metabolism to generate ATP. Nevertheless, regulation of mitochondrial activity is incompletely understood. Here we identified an unexpected and essential role for constitutive InsP3R-mediated Ca2+ release in maintaining cellular bioenergetics. Macroautophagy provides eukaryotes with an adaptive response to nutrient deprivation that prolongs survival. Constitutive InsP3R Ca2+ signaling is required for macroautophagy suppression in cells in nutrient-replete media. In its absence, cells become metabolically compromised due to diminished mitochondrial Ca2+ uptake. Mitochondrial uptake of InsP3R-released Ca2+ is fundamentally required to provide optimal bioenergetics by providing sufficient reducing equivalents to support oxidative phosphorylation. Absence of this Ca2+ transfer results in enhanced phosphorylation of pyruvate dehydrogenase and activation of AMPK, which activates prosurvival macroautophagy. Thus, constitutive InsP3R Ca2+ release to mitochondria is an essential cellular process that is required for efficient mitochondrial respiration and maintenance of normal cell bioenergetics

The research-teaching nexus: A case study of students' awareness, experiences and perceptions of research

This paper presents a case study of students' awareness, experiences and perceptions of research in a 'new' university in the UK. The findings are based on a questionnaire of almost 200 students and five small group interviews. Many of the students participating in this research perceived clear benefits to their learning from staff research, including being taught by enthusiastic staff, enhanced staff credibility, and the reflected glory of being taught by well-known researchers. However, they also perceived disadvantages, particularly with regard to staff availability, and did not believe that staff research should take priority over their needs as learners. They recognised that their awareness of the nature of research and the development of research skills increased most when they were actively involved in undertaking research projects. Several students also perceived benefits for future employment from their participation in research activities. The questionnaire has been used by several other universities around the world to benchmark their practices. © 2010 Taylor & Francis