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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]

Plateau icefields are large stores of freshwater, preconditioned to enhanced mass loss due to their gently sloping accumulation areas. Accurately modelling the mass-balance of these icefields is therefore vital for obtaining projections of their future contribution to sea-level rise. Here, we use the COupled Snowpack and Ice surface energy and mass-balance model in PYthon (COSIPY) to simulate the historical and potential future mass balance of the Juneau Icefield, Alaska -- a high elevation (>1200 m) plateau icefield. We force the model with dynamically downscaled climate simulations, pertaining to both the past and potential future (RCP 8.5) conditions. The rich dataset of surface mass balance observations of the Juneau Icefield allows us to tune COSIPY, providing confidence in our future predictions and highlighting changes to the icefield between the years 1980 and 2019. Icefield-wide negative mass balances were simulated from the start of the 21st century, as many glaciers transitioned from positive to negative mass-balances. Under RCP8.5, the model simulates increasing negative mass balance across Juneau Icefield, with the entire icefield potentially displaying a negative mass balance by the mid-21st century. This simulated loss of accumulation is driven by increased temperatures and reduced amounts of snowfall, exposing more of the icefield to thinning. Ice thinning is likely to be exacerbated by the exposure of ice to melting across the plateau surface, and prolonged melt may lead to an increase in disconnections, splitting glaciers between their accumulation and ablation areas at icefalls. The similar hypsometry of other high latitude plateau icefields and ice caps may mean that similar processes will act to determine their potential fate in our changing climate. [ABSTRACT FROM AUTHOR]

The occurrence and impact of fructose in the American food supply has garnered much recent attention in the popular press as well as the scientific community. This paper provides an overview of a workshop cosponsored by the International Life Sciences Institute North America and the USDA, Agricultural Research Service, titled 'State of the Science on Dietary Sweeteners Containing Fructose.' Papers in the workshop addressed the chemical composition and properties of dietary sweeteners that contain fructose, the sources and amount of fructose in the American diet, and the metabolism of fructose in the human body. Further, the authors of each paper assessed the strength of the existing data linking dietary fructose intake and risk for overweight, metabolic syndrome, type 2 diabetes mellitus, cardiovascular disease, and other disorders. The assessment considered factors in study design, including the amount fed, the food form, the length of the study, the characteristics of the subjects, the specific methodology, and other potential confounders including diet. In addition to papers assessing the basic science of fructose, some papers also addressed consumer concern about sugars and fructose in the diet, the way fructose and other sugars are presented in the media, and the resulting confusion of consumers about fructose and other sugars in the diet. The purpose of the papers in the aggregate was to clarify what data exist about fructose and what the gaps are in the data and to help both scientists and consumers understand issues surrounding fructose in the food supply.

The nonsynonymous variants of lipid phosphatase (FIG4) in patients with amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) is described. Heterozygosity for a deleterious allele FIG 4 that regulates PI(3,5)[P.sub.2] is found to be a risk factor for ALS and PLS, extending the list of known ALS genes and increasing the clinical spectrum of FIG4-related diseases.

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 SCN[M1.sup.R187TX], which is defective in splicing the mutated donor site in the Scn[8a.sup.medJ] transcript. To further probe the in vivo function of SCNM1, we constructed a floxed allele and generated a mouse with constitutive deletion of exons 3-5. The SCN[M1.sup.[DELTA]3-5] 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 I-mfa and Brunol4. The phenotypes of the Scn[ml.sup.[DELTA]3-5] mutant confirm the role of this splice factor in processing the Scn[8a.sup.medJ] transcript and provide a new allele of greater severity for future studies.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jada.2006.09.033 Byline: Marci J. Levine, Julie M. Jones, David R. Lineback

Author(s): Julie M. Jones [1]; Pinaki Datta [4]; Srinivasa M. Srinivasula [4]; Weizhen Ji [1]; Sanjeev Gupta [4]; ZhiJia Zhang [4]; Erika Davies [5]; György Hajnóczky [5]; Thomas L. Saunders [...]

Surface meltwater is widespread around the Antarctic Ice Sheet margin and has the potential to influence ice shelf stability, ice flow and ice–albedo feedbacks. Our understanding of the seasonal and multi-year evolution of Antarctic surface meltwater is limited. Attempts to generate robust meltwater cover time series have largely been constrained by computational expense or limited ice surface visibility associated with mapping from optical satellite imagery. Here, we add a novel method for calculating visibility metrics to an existing meltwater detection method within Google Earth Engine. This enables us to quantify uncertainty induced by cloud cover and variable image data coverage, allowing time series of surface meltwater area to be automatically generated over large spatial and temporal scales. We demonstrate our method on the Amery Ice Shelf region of East Antarctica, analysing 4164 Landsat 7 and 8 optical images between 2005 and 2020. Results show high interannual variability in surface meltwater cover, with mapped cumulative lake area totals ranging from 384 to 3898 km 2 per melt season. By incorporating image visibility assessments, however, we estimate that cumulative total lake areas are on average 42 % higher than minimum mapped values. We show that modelled melt predictions from a regional climate model provide a good indication of lake cover in the Amery region and that annual lake coverage is typically highest in years with a negative austral summer SAM index. Our results demonstrate that our method could be scaled up to generate a multi-year time series record of surface water extent from optical imagery at a continent-wide scale. [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 years, 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]

The Kidney and retinal defects (Krd) mouse carries a 7-cM transgene-induced deletion on chromosome 19 that includes the Pax2 locus. Adult mice heterozygous for the Krd deletion (Krd/+) are haploid for Pax2 and have a variable, semidominant phenotype characterized by structural defects of the kidney, retina, and optic disc. Renal and ocular anomalies present in heterozygous Pax2 mutants in both mice and humans support the hypothesis that haploinsufficiency of Pax2 underlies the Krd phenotype. To understand the embryonic basis of ocular defects observed in adult Krd/+ mice, we used immunohistochemistry, digital three-dimensional reconstructions, and quantitative morphometry to examine Pax2 protein distribution and ocular development in normal and Krd/+ mice from E10.5 to P2. In +/+ embryos, Pax2 immunopositive (Pax2+) cells demarcate the embryonic fissure as it forms in the ventral optic cup and optic stalk. After closure of the embryonic fissure, Pax2 immunostaining disappears from the ventral retina, but persists in a cuff of cells encircling the developing optic disc, the site where ganglion cell axons exit the retina. In Krd/+ embryos, Pax2+ cells in the posterior optic cup and the optic stalk undergo abnormal morphogenetic movements and the embryonic fissure fails to form normally. This results in an abnormal organization of the Pax2+ cells and ganglion cell axons at the nascent optic disc. The abnormal morphogenetic movements of the Pax2+ cells in the embryonic retina and optic stalk and the initial misrouting of the ganglion cell axons give rise to retinal and optic disc defects observed in the adult Krd/+ mice. Key Words: development; embryo; retina; optic cup; optic disc; optic stalk; embryonic fissure; gene expression; immunohistochemistry; reconstruction.

A positional candidate approach was employed to determine that the ataxia and seizures in the lethargic (lh) mouse arise from mutation of the beta-subunit gene Cchb4 on mouse chromosome 2. A four-nucleotide insertion within a 5' splice site in lh/lh mice was identified after reduced abundance of the Cchb4 transcript in lh/lh brain was observed. Exon skipping, translational frameshifts and protein truncation were also noted. It is concluded that the lethargic locus is likely to represent a functionally null allele of the Cchb4 gene.

While gridded seasonal pressure reconstructions poleward of 60°S extending back to 1905 have been recently completed, their skill has not been assessed prior to 1958. To provide a more thorough evaluation of the skill and performance in the early 20th century, these reconstructions are compared to other gridded datasets, historical data from early Antarctic expeditions, ship records, and temporary bases. Overall, the comparison confirms that the reconstruction uncertainty of 2–4 hPa (evaluated after 1979) over the Southern Ocean is a valid estimate of the reconstruction error in the early 20th century. Over the interior and near the coast of Antarctica, direct comparisons with historical data are challenged by elevation‐based reductions to sea level pressure. In a few cases, a simple linear adjustment of the reconstruction to sea level matches the historical data well, but in other cases, the differences remain greater than 10 hPa. Despite these large errors, comparisons with continuous multi‐season observations demonstrate that aspects of the interannual variability are often still captured, suggesting that the reconstructions have skill representing variations on this timescale, even if it is difficult to determine how well they capture the mean pressure at these higher elevations. Additional comparisons with various 20th‐century reanalysis products demonstrate the value of assimilating the historical observations in these datasets, which acts to substantially reduce the reanalysis ensemble spread, and bring the reanalysis ensemble mean within the reconstruction and observational uncertainty. [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]

Abstract: Knowing the long‐term frequency of high magnitude storm events that cause coastal inundation is critical for present coastal management, especially in the context of rising sea levels and potentially increasing frequency and severity of storm events. Coastal sand dunes may provide a sedimentary archive of past storm events from which long‐term frequencies of large storms can be reconstructed. This study uses novel portable optically stimulated luminescence (POSL) profiles from coastal dunes to reconstruct the sedimentary archive of storm and surge activity for Norfolk, UK. Application of POSL profiling with supporting luminescence ages and particle size analysis to coastal dunes provides not only information of dunefield evolution but also on past coastal storms. In this study, seven storm events, two major, were identified from the dune archive spanning the last 140 years. These appear to correspond to historical reports of major storm surges. Dunes appear to be only recording (at least at the sampling resolution used here) the highest storm levels that were associated with significant flooding. As such the approach seems to hold promise to obtain a better understanding of the frequency of large storms by extending the dune archive records further back to times when documentation of storm surges was sparse. © 2017 The Authors. Earth Surface Processes and Landforms published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

The meteorological information found within ships’ logbooks is a unique and fascinating source of data for historical climatology. This study uses wind observations from logbooks covering the period 1815 to 1854 to reconstruct an index of El Niño Southern Oscillation (ENSO) for boreal winter (DJF). Statistically-based reconstructions of the Southern Oscillation Index (SOI) are obtained using two methods: principal component regression (PCR) and composite-plus-scale (CPS). Calibration and validation are carried out over the modern period 1979–2014, assessing the relationship between re-gridded seasonal ERA-Interim reanalysis wind data and the instrumental SOI. The reconstruction skill of both the PCR and CPS methods is found to be high with reduction of error skill scores of 0.80 and 0.75, respectively. The relationships derived during the fitting period are then applied to the logbook wind data to reconstruct the historical SOI. We develop a new method to assess the sensitivity of the reconstructions to using a limited number of observations per season and find that the CPS method performs better than PCR with a limited number of observations. A difference in the distribution of wind force terms used by British and Dutch ships is found, and its impact on the reconstruction assessed. The logbook reconstructions agree well with a previous SOI reconstructed from Jakarta rain day counts, 1830–1850, adding robustness to our reconstructions. Comparisons to additional documentary and proxy data sources are provided in a companion paper. [ABSTRACT FROM AUTHOR]

During the late twentieth century, the Antarctic atmospheric circulation has changed and significantly influenced the overall Antarctic climate, through processes including a poleward shift of the circumpolar westerlies. However, little is known about the full spatial pattern of atmospheric pressure over the Antarctic continent prior to 1979. Here we investigate surface pressure changes across the entire Antarctic continent back to 1905 by developing a new summer pressure reconstruction poleward of 60°S. We find that only across East Antarctica are the recent pressures significantly lower than pressures in the early twentieth century; we also discern periods of significant positive pressure trends in the early twentieth century across the coastal South Atlantic sector of Antarctica. Climate model simulations reveal that both tropical sea surface temperature variability and other radiative forcing mechanisms, in addition to ozone depletion, have played an important role in forcing the recent observed negative trends. [ABSTRACT FROM AUTHOR]