Super-resolution Reconstruction MRI Application in Fetal Neck Masses and Congenital High Airway Obstruction Syndrome

OBJECTIVE: Reliable airway patency diagnosis in fetal tracheolaryngeal obstruction is crucial to select and plan ex utero intrapartum treatment (EXIT) surgery. We compared the clinical utility of magnetic resonance imaging (MRI) super-resolution reconstruction (SRR) of the trachea, which can mitigate unpredictable fetal motion effects, with standard 2-dimensional (2D) MRI for airway patency diagnosis and assessment of fetal neck mass anatomy. STUDY DESIGN: A single-center case series of 7 consecutive singleton pregnancies with complex upper airway obstruction (2013-2019). SETTINGS: A tertiary fetal medicine unit performing EXIT surgery. METHODS: MRI SRR of the trachea was performed involving rigid motion correction of acquired 2D MRI slices combined with robust outlier detection to reconstruct an isotropic high-resolution volume. SRR, 2D MRI, and paired data were blindly assessed by 3 radiologists in 3 experimental rounds. RESULTS: Airway patency was correctly diagnosed in 4 of 7 cases (57%) with 2D MRI as compared with 2 of 7 cases (29%) with SRR alone or paired 2D MRI and SRR. Radiologists were more confident (P = .026) in airway patency diagnosis when using 2D MRI than SRR. Anatomic clarity was higher with SRR (P = .027) or paired data (P = .041) in comparison with 2D MRI alone. Radiologists detected further anatomic details by using paired images versus 2D MRI alone (P < .001). Cognitive load, as assessed by the NASA Task Load Index, was increased with paired or SRR data in comparison with 2D MRI. CONCLUSION: The addition of SRR to 2D MRI does not increase fetal airway patency diagnostic accuracy but does provide improved anatomic information, which may benefit surgical planning of EXIT procedures

Defective Interfering Viral Particles in Acute Dengue Infections

While much of the genetic variation in RNA viruses arises because of the error-prone nature of their RNA-dependent RNA polymerases, much larger changes may occur as a result of recombination. An extreme example of genetic change is found in defective interfering (DI) viral particles, where large sections of the genome of a parental virus have been deleted and the residual sub-genome fragment is replicated by complementation by co-infecting functional viruses. While most reports of DI particles have referred to studies in vitro, there is some evidence for the presence of DI particles in chronic viral infections in vivo. In this study, short fragments of dengue virus (DENV) RNA containing only key regulatory elements at the 3′ and 5′ ends of the genome were recovered from the sera of patients infected with any of the four DENV serotypes. Identical RNA fragments were detected in the supernatant from cultures of Aedes mosquito cells that were infected by the addition of sera from dengue patients, suggesting that the sub-genomic RNA might be transmitted between human and mosquito hosts in defective interfering (DI) viral particles. In vitro transcribed sub-genomic RNA corresponding to that detected in vivo could be packaged in virus like particles in the presence of wild type virus and transmitted for at least three passages in cell culture. DENV preparations enriched for these putative DI particles reduced the yield of wild type dengue virus following co-infections of C6–36 cells. This is the first report of DI particles in an acute arboviral infection in nature. The internal genomic deletions described here are the most extensive defects observed in DENV and may be part of a much broader disease attenuating process that is mediated by defective viruses

RNA Gain-of-Function in Spinocerebellar Ataxia Type 8

Microsatellite expansions cause a number of dominantly-inherited neurological diseases. Expansions in coding-regions cause protein gain-of-function effects, while non-coding expansions produce toxic RNAs that alter RNA splicing activities of MBNL and CELF proteins. Bi-directional expression of the spinocerebellar ataxia type 8 (SCA8) CTG CAG expansion produces CUG expansion RNAs (CUGexp) from the ATXN8OS gene and a nearly pure polyglutamine expansion protein encoded by ATXN8 CAGexp transcripts expressed in the opposite direction. Here, we present three lines of evidence that RNA gain-of-function plays a significant role in SCA8: 1) CUGexp transcripts accumulate as ribonuclear inclusions that co-localize with MBNL1 in selected neurons in the brain; 2) loss of Mbnl1 enhances motor deficits in SCA8 mice; 3) SCA8 CUGexp transcripts trigger splicing changes and increased expression of the CUGBP1-MBNL1 regulated CNS target, GABA-A transporter 4 (GAT4/Gabt4). In vivo optical imaging studies in SCA8 mice confirm that Gabt4 upregulation is associated with the predicted loss of GABAergic inhibition within the granular cell layer. These data demonstrate that CUGexp transcripts dysregulate MBNL/CELF regulated pathways in the brain and provide mechanistic insight into the CNS effects of other CUGexp disorders. Moreover, our demonstration that relatively short CUGexp transcripts cause RNA gain-of-function effects and the growing number of antisense transcripts recently reported in mammalian genomes suggest unrecognized toxic RNAs contribute to the pathophysiology of polyglutamine CAG CTG disorders

A Call to Integrate Economic, Social and Environmental Motives into Guidance for Business Support for the Transition to a Circular Economy

A broad range of organizations, from small and medium-sized enterprises to large multi-nationals, are interested in adopting circular economy practices. A circular economy can help companies make better use of materials by minimizing the input of natural resources, reducing waste, and optimizing the economic, social, technical and environmental costs and benefits of materials and products throughout their lifecycle. Despite the interest of companies in a circular economy, only 9% of material flows in the global economy are circular. There is formal guidance for those offering business support with the aim to expedite the transition to a circular economy. However, support measures narrowly confine the role of companies and the motivations of business managers to the economic realms, assuming that companies are solely driven by monetary factors. Conversely, pluralist economic views emphasize the broader role of companies in society: for example, in respect of the well-being of their staff and the communities in which they reside. Indeed, our practical experiences of business support have brought alternative motivations to explore a circular economy to the fore. We argue that business support should stem from a broader conception of the role of business in society. The diverse motivations and willingness of business managers to engage in a circular economy should be investigated further with results feeding into broader and more inclusive business support guidelines in the future to accelerate the transition towards a circular economy

Spatial ecology and habitat use of two-spined blackfish Gadopsis bispinosus in an upland reservoir

The scale and patterns of movement and habitat use are primary considerations in the conservation and management of threatened species. Movement, activity and habitat use of the threatened two-spined blackfish Gadopsis bispinosus were assessed in a small upland reservoir in south-eastern Australia using manual and remote radio-telemetry. Movements and activity of two-spined blackfish (n = 19) were studied over a 28-day period and exhibited proportionately large directional crepuscular movement and activity with heightened activity continuing throughout the night (although movement was subdued). Two daily movement strategies were observed: movements from diurnal home-shelter habitats (predominantly rock) to macrophytes at night (14 individuals), and occupation of macrophytes during the entire diel period and restricted movement (five individuals). Daily movement strategies were fixed (not plastic) among all individuals, with one exception, for the duration of the study period. Rock, fallen timber and macrophytes were the most commonly used daytime shelter habitat (in order of preference). Although some information exists on movements and habitat use of this species and the congeneric river blackfish G. Marmoratus in lotic environments, we present the first study of movements and habitat use for either species in lentic environments. Given the occupation of lentic environments by this threatened species, the data presented in this study provide insight into the habitat requirements for this species, and offer opportunities for habitat enhancement in existing reservoirs within the species' geographic range