The Role of FRMD7 in Idiopathic Infantile Nystagmus

Idiopathic infantile nystagmus (IIN) is an inherited disorder in which the nystagmus arises independently of any other symptoms, leading to the speculation that the disorder represents a primary defect in the area of the brain responsible for ocular motor control. The inheritance patterns are heterogeneous, however the most common form is X-linked. FRMD7 resides at Xq26-27 and approximately 50% of X-linked IIN families map to this region. Currently 45 mutations within FRMD7 have been associated with IIN, confirming the importance of FRMD7 in the pathogenesis of the disease. Although mutations in FRMD7 are known to cause IIN, very little is known about the function of the protein. FRMD7 contains a conserved N-terminal FERM domain suggesting that it may provide a link between the plasma membrane and actin cytoskeleton. Limited studies together with the knowledge of the function of other FERM domain containing proteins, suggest that FRMD7 may play a role in membrane extension during neuronal development through remodeling of the actin cytoskeleton

Congenital monocular elevation deficiency associated with a novel TUBB3 gene variant

Background The genetic basis of monocular elevation deficiency (MED) is unclear. It has previously been considered to arise due to a supranuclear abnormality.Methods Two brothers with MED were referred to Leicester Royal Infirmary, UK from the local opticians. Their father had bilateral ptosis and was unable to elevate both eyes, consistent with the diagnosis of congenital fibrosis of extraocular muscles (CFEOM). Candidate sequencing was performed in all family members.Results Both affected siblings (aged 7 and 12 years) were unable to elevate the right eye. Their father had bilateral ptosis, left esotropia and bilateral limitation of elevation. Chin up head posture was present in the older sibling and the father. Bell’s phenomenon and vertical rotational vestibulo-ocular reflex were absent in the right eye for both children. Mild bilateral facial nerve palsy was present in the older sibling and the father. Both siblings had slight difficulty with tandem gait. MRI revealed hypoplastic oculomotor nerve. Left anterior insular focal cortical dysplasia was seen in the older sibling. Sequencing of TUBB3 revealed a novel heterozygous variant (c.1263G>C, p.E421D) segregating with the phenotype. This residue is in the C-terminal H12 α-helix of β-tubulin and is one of three putative kinesin binding sites.Conclusion We show that familial MED can arise from a TUBB3 variant and could be considered a limited form of CFEOM. Neurological features such as mild facial palsy and cortical malformations can be present in patients with MED. Thus, in individuals with congenital MED, consideration may be made for TUBB3 mutation screening

Gender Differences in Russian Colour Naming

In the present study we explored Russian colour naming in a web-based psycholinguistic experiment (http://www.colournaming.com). Colour singletons representing the Munsell Color Solid (N=600 in total) were presented on a computer monitor and named using an unconstrained colour-naming method. Respondents were Russian speakers (N=713). For gender-split equal-size samples (NF=333, NM=333) we estimated and compared (i) location of centroids of 12 Russian basic colour terms (BCTs); (ii) the number of words in colour descriptors; (iii) occurrences of BCTs most frequent non-BCTs. We found a close correspondence between females’ and males’ BCT centroids. Among individual BCTs, the highest inter-gender agreement was for seryj ‘grey’ and goluboj ‘light blue’, while the lowest was for sinij ‘dark blue’ and krasnyj ‘red’. Females revealed a significantly richer repertory of distinct colour descriptors, with great variety of monolexemic non-BCTs and “fancy” colour names; in comparison, males offered relatively more BCTs or their compounds. Along with these measures, we gauged denotata of most frequent CTs, reflected by linguistic segmentation of colour space, by employing a synthetic observer trained by gender-specific responses. This psycholinguistic representation revealed females’ more refined linguistic segmentation, compared to males, with higher linguistic density predominantly along the redgreen axis of colour space

Crop Updates 2001 - Oilseeds

ABSTRACT This session covers twenty five papers from different authors: FORWARD, Mervyn McDougall, CHAIRMAN, PULSES AND OILSEEDS PARTNERSHIP GROUP PLENARY 1. Implications of the ‘green-bridge’ for viral and fungal disease carry-over between seasons, Debbie Thackray, Agriculture Western Australia and Centre for Legumes in Mediterranean Agriculture 2. Insect pest development in WA via the ‘green-bridge’, Kevin Walden, Agriculture Western Australia VARIETIES 3. Performance of new canola varieties in AGWEST variety trials, G. Walton, Crop Improvement Institute, Agriculture Western Australia 4. New herbicide tolerant varieties in WA, Kevin Morthorpe, Stephen Addenbrooke, Pioneer Hi-Bred Australia P/L 5. IT v’s TT – Head to head, Paul Carmody, Centre for Cropping Systems, Agriculture Western Australia ESTABLISHMENT 6. Effect of stubble, seeding technique and seed size on crop establishment and yield of canola, Rafiul Alam, Glen Riethmuller and Greg Hamilton, Agriculture Western Australia 7. Canola establishment survey 2000, Rafiul Alam, Paul Carmody, Greg Hamilton and Adrian Cox, Agriculture Western Australia 8. Tramline farming for more canola, Paul Blackwell, Agriculture Western Australia NUTRITION 9. Comparing the phosphorus requirement of canola and wheat in WA, M.D.A. Bolland and M.J. Baker, Agriculture Western Australia 10. Will a rainy summer affect nitrogen requirement: Tailoring your fertiliser decisions using the new nitrogen calculator, A.J. Diggle, Agriculture Western Australia 11. Canola – More response to lime, Chris Gazeyand Paul Carmody, Centre for Cropping Systems, Agriculture Western Australia AGRONOMY 12. Hormone manipulation of canola development, Paul Carmody and Graham Walton, Agriculture Western Australia 13. Yield penalties with delayed sewing of canola, Imma Farre, CSIRO Plant Industry, Michael J. Robertson, CSIRO Sustainable Ecosystems, Graham H. Walton, Agriculture Western Australia, Senthold Asseng, CSIRO Plant Industry 14. Dry matter and oil accumulation in developing seeds of canola varieties at different sowing dates, Ping Si1, David Turner1 and David Harris2 , 1Plant Sciences, Faculty of Agriculture, The University of Western Australia, 2Chemistry Centre of Western Australia 13. Simulating oil concentrations in canola – virtually just the beginning, David Turner1 and Imma Farré2, 1Plant Sciences, Faculty of Agriculture, The University of Western Australia, 2CSIRO Plant Industry, Centre for Mediterranean Agricultural Research PESTS AND DISEASES 14. Further evidence that canola crops are resilient to damage by aphids, Françoise Berlandier and Christiaan Valentine, Entomology, Agriculture Western Australia 15. Management of Diamondback moth (DBM) in canola, David Cook, Peter Mangano, David Cousins, Françoise Berlandier, and Darryl Hardie, Crop Improvement Institute,Agriculture Western Australia 16. Effect of time of sowing in conjunction with fungicides on blackleg and yield of canola, Ravjit Khangura and Martin Barbetti, Agriculture Western Australia 17. Further developments in forecasting aphid and virus risk in canola, Debbie Thackray, Jenny Hawkes and Roger Jones, Agriculture Western Australia and Centre for Legumes in Mediterranean Agriculture 18. Efficiency of selected insecticides for the use on Diamondback Moth in canola, Kevin Walden, Agriculture Western Australia 19. Impact® applied ‘in furrow’ controls blackleg in canola, Cameron Weeks and Erin Hasson, Mingenew-Irwin Group Inc. 20. Effect of time of sowing and Impact® on canola yield, Esperance, Dave Eksteen, Agriculture Western Australia 21. Australian Plague Locust Campaign 2000, Kevin Walden, Agriculture Western Australia WEED CONTROL 22. New herbicide options for canola, John Moore and Paul Matson, Agriculture Western Australia HARVESTING 23. Effects of time of swathing and desiccant application on the seed yield and oil content of canola, Carla Thomas and Lionel Martin, Muresk Institute of Agriculture, Curtin University of Technology DECISION SUPPORT AND ADOPTION 24. Using canola monitoring groups to understand factors affecting canola production in Esperance, Dave Eksteen, Agriculture Western Australia 25. Nitrogen and canola, Dave Eksteen, Agriculture Western Australi

SLC38A8 mutations result in arrested retinal development with loss of cone photoreceptor specialization

Foveal hypoplasia, optic nerve decussation defects and anterior segment dysgenesis is an autosomal recessive disorder arising from SLC38A8 mutations. SLC38A8 is a putative glutamine transporter with strong expression within the photoreceptor layer in the retina. Previous studies have been limited due to lack of quantitative data on retinal development and nystagmus characteristics. In this multi-centre study, a custom-targeted next generation sequencing (NGS) gene panel was used to identify SLC38A8 mutations from a cohort of 511 nystagmus patients. We report 16 novel SLC38A8 mutations. The sixth transmembrane domain is most frequently disrupted by missense SLC38A8 mutations. Ninety percent of our cases were initially misdiagnosed as PAX6-related phenotype or ocular albinism prior to NGS. We characterized the retinal development in vivo in patients with SLC38A8 mutations using high-resolution optical coherence tomography. All patients had severe grades of arrested retinal development with lack of a foveal pit and no cone photoreceptor outer segment lengthening. Loss of foveal specialization features such as outer segment lengthening implies reduced foveal cone density, which contributes to reduced visual acuity. Unlike other disorders (such as albinism or PAX6 mutations) which exhibit a spectrum of foveal hypoplasia, SLC38A8 mutations have arrest of retinal development at an earlier stage resulting in a more under-developed retina and severe phenotype

Management of nystagmus in children : a review of the literature and current practice in UK specialist services

Nystagmus is an eye movement disorder characterised by abnormal, involuntary rhythmic oscillations of one or both eyes, initiated by a slow phase. It is not uncommon in the UK and regularly seen in paediatric ophthalmology and adult general/strabismus clinics. In some cases, it occurs in isolation, and in others, it occurs as part of a multisystem disorder, severe visual impairment or neurological disorder. Similarly, in some cases, visual acuity can be normal and in others can be severely degraded. Furthermore, the impact on vision goes well beyond static acuity alone, is rarely measured and may vary on a minute-to-minute, day-to-day or month-to-month basis. For these reasons, management of children with nystagmus in the UK is varied, and patients report hugely different experiences and investigations. In this review, we hope to shine a light on the current management of children with nystagmus across five specialist centres in the UK in order to present, for the first time, a consensus on investigation and clinical management

Learning together for and with the Martuwarra Fitzroy River

Co-production across scientific and Indigenous knowledge systems has become a cornerstone of research to enhance knowledge, practice, ethics, and foster sustainability transformations. However, the profound differences in world views and the complex and contested histories of nation-state colonisation on Indigenous territories, highlight both opportunities and risks for Indigenous people when engaging with knowledge co-production. This paper investigates the conditions under which knowledge co-production can lead to improved Indigenous adaptive environmental planning and management among remote land-attached Indigenous peoples through a case study with ten Traditional Owner groups in the Martuwarra (Fitzroy River) Catchment in Western Australia’s Kimberley region. The research team built a 3D map of the river and used it, together with an interactive table-top projector, to bring together both scientific and Indigenous spatial knowledge. Participatory influence mapping, aligned with Traditional Owner priorities to achieve cultural governance and management planning goals set out in the Fitzroy River Declaration, investigated power relations. An analytical framework, examining underlying mechanisms of social learning, knowledge promotion and enhancing influence, based on different theories of change, was applied to unpack the immediate outcomes from these activities. The analysis identified that knowledge co-production activities improved the accessibility of the knowledge, the experiences of the knowledge users, strengthened collective identity and partnerships, and strengthened Indigenous-led institutions. The focus on cultural governance and management planning goals in the Fitzroy River Declaration enabled the activities to directly affect key drivers of Indigenous adaptive environmental planning and management—the Indigenous-led institutions. The nation-state arrangements also gave some support to local learning and decision-making through a key Indigenous institution, Martuwarra Fitzroy River Council. Knowledge co-production with remote land-attached Indigenous peoples can improve adaptive environmental planning and management where it fosters learning together, is grounded in the Indigenous-led institutions and addresses their priorities

Identification and characterisation of a rare MTTP variant underlying hereditary non-alcoholic fatty liver disease

Background and aimsNon-alcoholic fatty liver disease (NAFLD) is a complex trait with an estimated prevalence of 25% globally. We aimed to identify the genetic variant underlying a four-generation family with progressive NAFLD leading to cirrhosis, decompensation and development of hepatocellular carcinoma in the absence of common risk factors such as obesity and type 2 diabetes.MethodsExome sequencing and genome comparisons were used to identify the likely causal variant. We extensively characterised the clinical phenotype and post-prandial metabolic responses of family members with the identified novel variant in comparison to healthy non-carriers and wild-type patients with NAFLD. Variant-expressing hepatocyte-like cells (HLCs) were derived from human induced pluripotent stem cells generated from homozygous donor skin fibroblasts and restored to wild-type using CRISPR-Cas9. The phenotype was assessed using imaging, targeted RNA analysis and molecular expression arrays.ResultsWe identified a rare causal variant c.1691T>C p.I564T (rs745447480) in MTTP, encoding microsomal triglyceride transfer protein (MTP), associated with progressive NAFLD, unrelated to metabolic syndrome and without characteristic features of abetalipoproteinemia. HLCs derived from a homozygote donor had significantly lower MTP activity and lower lipoprotein ApoB secretion compared to wild-type cells, while having similar levels of MTP mRNA and protein. Cytoplasmic triglyceride accumulation in HLCs triggered endoplasmic reticulum stress, secretion of pro-inflammatory mediators and production of reactive oxygen species.ConclusionWe have identified and characterized a rare causal variant in MTTP and homozygosity for MTTP p.I564T is associated with progressive NAFLD without any other manifestations of abetalipoproteinemia. Our findings provide insights into mechanisms driving progressive NAFLD