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The Antarctic ice sheet (AIS) is the Earth's largest store of frozen water; understanding how it changed in the past allows us to improve projections of how it, and sea levels, may change. Here, we use previous AIS reconstructions, water isotope ratios from ice cores, and simulator predictions of the relationship between the ice-sheet shape and isotope ratios to create a model of the AIS at the Last Glacial Maximum. We develop a prior distribution that captures expert opinion about the AIS, generate a designed ensemble of potential shapes, run these through the climate model HadCM3, and train a Gaussian process emulator of the link between ice-sheet shape and isotope ratios. To make the analysis computationally tractable, we develop a preferential principal component method that allows us to reduce the dimension of the problem in a way that accounts for the differing importance we place in reconstructions, allowing us to create a basis that reflects prior uncertainty. We use Markov chain Monte Carlo to sample from the posterior distribution, finding shapes for which HadCM3 predicts isotope ratios closely matching observations from ice cores. The posterior distribution allows us to quantify the uncertainty in the reconstructed shape, a feature missing in other analyses. [ABSTRACT FROM AUTHOR]

The Dietary Guidelines for Americans (DGA) provide science-based recommendations for healthy dietary patterns to promote health and reduce risk of chronic diseases. Yet, since their inception in 1980 and updates every 5 y, Americans fall short of meeting dietary recommendations and diet-related chronic diseases continue to be a public health concern. In May of 2021, the Institute of Food Technologists and the Department of Food Science at the University of Massachusetts, Amherst, convened a diverse group of thought leaders in health, nutrition, and food science to identify opportunities and approaches to improve consumer adoption of the DGA recommendations. The invited leaders collaborated in roundtable discussions to develop recommendations and strategies to promote adoption of the DGA recommendations after hearing sessions on the latest consumer trends, advances in food science and technology, and effective communications approaches. Participants agreed that changes in consumer behaviors and heightened interest in health due to the novel coronavirus pandemic have created an opportune time to engage consumers about healthy eating. Communications must be simple, tailored to the consumer, and delivered by influencer(s)/spokesperson(s) who are credible sources and share personal values. Innovations in food science and technology have enabled improvements in the safety, health, acceptability, affordability, and availability of foods, but opportunities to provide more options to enhance consumption of desired food groups, such as fruits, vegetables, and whole grains, remain. Moving Americans toward healthier dietary patterns aligned with DGA recommendations will require collaborations within the food sector and beyond to achieve broad-scale amplification and investment. [ABSTRACT FROM AUTHOR]

De novo mutations of the sodium channel gene SCN8A result in an epileptic encephalopathy with refractory seizures, developmental delay, and elevated risk of sudden death. p.Arg1872Trp is a recurrent de novo SCN8A mutation reported in 14 unrelated individuals with epileptic encephalopathy that included seizure onset in the prenatal or infantile period and severe verbal and ambulatory comorbidities. The major biophysical effect of the mutation was previously shown to be impaired channel inactivation accompanied by increased current density. We have generated a conditional mouse mutation in which expression of this severe gain-of-function mutation is dependent upon Cre recombinase. Global activation of p.Arg1872Trp by EIIa-Cre resulted in convulsive seizures and lethality at 2 weeks of age. Neural activation of the p.Arg1872Trp mutation by Nestin-Cre also resulted in early onset seizures and death. Restriction of p.Arg1872Trp expression to excitatory neurons using Emx1-Cre recapitulated seizures and juvenile lethality between 1 and 2 months of age. In contrast, activation of p.Arg1872Trp in inhibitory neurons by Gad2-Cre or Dlx5/6-Cre did not induce seizures or overt neurological dysfunction. The sodium channel modulator GS967/Prax330 prolonged survival of mice with global expression of R1872W and also modulated the activity of the mutant channel in transfected cells. Activation of the p.Arg1872Trp mutation in adult mice was sufficient to generate seizures and death, indicating that successful therapy will require lifelong treatment. These findings provide insight into the pathogenic mechanism of this gain-of-function mutation of SCN8A and identify excitatory neurons as critical targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Examines the expression of a novel hybrid gene in neurological mutant flailer derived by exon shuffling. Localization of smooth endoplasmic reticulum vesicles in dendritic spines of cerebellar Purkinje cells; Mode of inheritance; Recombination between globin genes and hybrid red-green opsin genes.

The auxiliary spliceosomal protein SCNM1 contributes to recognition of nonconsensus splice donor sites. SCNM1 was first identified as a modifier of the severity of a sodium channelopathy in the mouse. The most severely affected strain, C57BL/6J, carries the variant allele SCNM1R187X, which is defective in splicing the mutated donor site in the Scn8amedJ transcript. To further probe the in vivo function of SCNM1, we constructed a foxed allele and generated a mouse with constitutive deletion of exons 3-5. The SCNM1Δ3-5 protein is produced and correctly localized to the nucleus, but is more functionally impaired than the C57BL/6J allele. Deficiency of SCNM1 did not significantly alter other brain transcripts. We characterized an ENU-induced allele of Scnm1 and evaluated the ability of wild-type SCNM1 to rescue lethal mutations of J-1-mfa and Brunol4. The phenotypes of the Scnm1Δ3-5 mutant confirm the role of this splice factor in processing the Scn8amedJ transcript and provide a new allele of greater severity for future studies. [ABSTRACT FROM AUTHOR]