| 1. |
- Palmer, Elizabeth E., et al.
(author)
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Functional and clinical studies reveal pathophysiological complexity of CLCN4-related neurodevelopmental condition
- 2023
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In: Molecular Psychiatry. - : SPRINGERNATURE. - 1359-4184 .- 1476-5578. ; 28:2, s. 668-697
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Journal article (peer-reviewed)abstract
- Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a "shift" of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis.
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| 2. |
- Wijayatunga, Priyantha, 1967-, et al.
(author)
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Discussion on the meeting on 'Data visualization'
- 2019
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In: Journal of the Royal Statistical Society. - UK : Royal Statistical Society. - 0964-1998 .- 1467-985X. ; 182:2, s. 433-441
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Journal article (other academic/artistic)abstract
- Visualizing both conditional and marginal associations in contingency tables by using simple diagrams is discussed
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| 3. |
- Zhang, Chen, et al.
(author)
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Physiological and nutritional constraints on zooplankton productivity due to eutrophication and climate change predicted using a resource-based modeling approach
- 2022
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In: Canadian Journal of Fisheries and Aquatic Sciences. - : Canadian Science Publishing. - 0706-652X .- 1205-7533. ; 79:3, s. 472-486
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Journal article (peer-reviewed)abstract
- Emerging evidence suggests that zooplankton production is affected by physiological and nutritional constraints due to climate change and eutrophication, which in turn could have broad implications for food-web dynamics and fisheries production. In this study, we developed a resource-based zooplankton production dynamics model that causally links freshwater cladoceran and copepod daily production-to-biomass (P/B) ratios with water temperature, phytoplankton biomass and community composition, and zooplankton feeding selectivity. This model was used to evaluate constraints on zooplankton growth under four hypothetical scenarios: involving natural plankton community seasonal succession; lake fertilization to enhance fisheries production; eutrophication; and climatic warming. Our novel modeling approach predicts zooplankton production is strongly dependent on seasonal variation in resource availability and quality, which results in more complex zooplankton dynamics than predicted by simpler temperature-dependent models. For mesotrophic and hypereutrophic lakes, our study suggests that the ultimate control over zooplankton P/B ratios shifts from physiological control during colder periods to strong resource control during warmer periods. Our resource-based model provides important insights into the nature of biophysical control of zooplankton under a changing climate that has crucial implications for food web energy transfer and fisheries production.
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