Guidelines for Genome-Scale Analysis of Biological Rhythms

Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs of the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout the day. These methods hold significant promise for future discovery, particularly when combined with computational modeling. However, genome-scale experiments are costly and laborious, yielding “big data” that are conceptually and statistically difficult to analyze. There is no obvious consensus regarding design or analysis. Here we discuss the relevant technical considerations to generate reproducible, statistically sound, and broadly useful genome-scale data. Rather than suggest a set of rigid rules, we aim to codify principles by which investigators, reviewers, and readers of the primary literature can evaluate the suitability of different experimental designs for measuring different aspects of biological rhythms. We introduce CircaInSilico, a web-based application for generating synthetic genome biology data to benchmark statistical methods for studying biological rhythms. Finally, we discuss several unmet analytical needs, including applications to clinical medicine, and suggest productive avenues to address them

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Guidelines for Genome-Scale Analysis of Biological Rhythms

Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs of the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout the day. These methods hold significant promise for future discovery, particularly when combined with computational modeling. However, genome-scale experiments are costly and laborious, yielding ‘big data’ that is conceptually and statistically difficult to analyze. There is no obvious consensus regarding design or analysis. Here we discuss the relevant technical considerations to generate reproducible, statistically sound, and broadly useful genome scale data. Rather than suggest a set of rigid rules, we aim to codify principles by which investigators, reviewers, and readers of the primary literature can evaluate the suitability of different experimental designs for measuring different aspects of biological rhythms. We introduce CircaInSilico, a web-based application for generating synthetic genome biology data to benchmark statistical methods for studying biological rhythms. Finally, we discuss several unmet analytical needs, including applications to clinical medicine, and suggest productive avenues to address them

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

“Friday is my research day”: chance, time and desire in the search for the teaching-research nexus in the life of a university teacher

This paper builds on some ideas recently presented by Boyd et al. (2010). In that paper, the focus was on the ways in which experienced academic staff articulate the teaching-research nexus. By presenting six short case accounts, this paper describes how a reflective narrative activity enabled some ‘new to academe’ teachers to identify the teaching research nexus in their own work. For each of them, there was some particular reason or stimulus that led to them articulating the teaching-learning nexus in their work. Given the effectiveness of this method for enabling staff to consider the teaching-research nexus, this paper speculates on ways of drawing all academic staff to encounter the ‘concept’ of the teaching-research nexus

A Wolbachia symbiont in Aedes aegypti limits infection with dengue, Chikungunya, and Plasmodium

Submitted by Nuzia Santos ([email protected]) on 2016-04-11T14:06:00Z No. of bitstreams: 1 A Wolbachia Symbiont in Aedes aegypti.pdf: 593492 bytes, checksum: 0238552be9d05f0a9b2df2d52b2392f9 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2016-04-11T14:11:58Z (GMT) No. of bitstreams: 1 A Wolbachia Symbiont in Aedes aegypti.pdf: 593492 bytes, checksum: 0238552be9d05f0a9b2df2d52b2392f9 (MD5)Made available in DSpace on 2016-04-11T14:11:58Z (GMT). No. of bitstreams: 1 A Wolbachia Symbiont in Aedes aegypti.pdf: 593492 bytes, checksum: 0238552be9d05f0a9b2df2d52b2392f9 (MD5) Previous issue date: 2009University of Queensland. School of Biological Sciences. Brisbane, Australia/ Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, BrasilUniversity of Queensland. School of Biological Sciences. Brisbane, AustraliaQueensland Institute of Medical Research. Post Office Royal Brisbane Hospital. Brisbane, AustraliaQueensland Institute of Medical Research. Post Office Royal Brisbane Hospital. Brisbane, AustraliaVirology, Queensland Health Forensic and Scientific Services. Coopers Plains, AustraliaUniversity of Queensland. School of Biological Sciences. Brisbane, AustraliaFundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, BrasilUniversity of Queensland. School of Chemical and Molecular Biosciences. Brisbane, AustraliaUniversity of Queensland. School of Chemical and Molecular Biosciences. Brisbane, AustraliaUniversity of Queensland. School of Biological Sciences. Brisbane, Australia/University of Western Sydney. Centre for Plants and the Environment, School of Natural Sciences. Penrith South DC, NSW, AustraliaQueensland Institute of Medical Research. Post Office Royal Brisbane Hospital. Brisbane, AustraliaUniversity of Queensland. School of Biological Sciences. Brisbane, AustraliaQueensland Institute of Medical Research. Post Office Royal Brisbane Hospital. Brisbane, AustraliaUniversity of Queensland. School of Biological Sciences. Brisbane, AustraliaVirology, Queensland Health Forensic and Scientific Services. Coopers Plains, Australia/niversity of Queensland. School of Chemical and Molecular Biosciences. Brisbane, AustraliaQueensland Institute of Medical Research. Post Office Royal Brisbane Hospital. Brisbane, AustraliaUniversity of Queensland. School of Biological Sciences. Brisbane, AustraliaWolbachia are maternally inherited intracellular bacterial symbionts that are estimated to infect more than 60% of all insect species. While Wolbachia is commonly found in many mosquitoes it is absent from the species that are considered to be of major importance for the transmission of human pathogens. The successful introduction of a life-shortening strain of Wolbachia into the dengue vector Aedes aegypti that halves adult lifespan has recently been reported. Here we show that this same Wolbachia infection also directly inhibits the ability of a range of pathogens to infect this mosquito species. The effect is Wolbachia strain specific and relates to Wolbachia priming of the mosquito innate immune system and potentially competition for limiting cellular resources required for pathogen replication. We suggest that this Wolbachia-mediated pathogen interference may work synergistically with the life-shortening strategy proposed previously to provide a powerful approach for the control of insect transmitted diseases