An ancient river landscape preserved beneath the East Antarctic Ice Sheet.

The East Antarctic Ice Sheet (EAIS) has its origins ca. 34 million years ago. Since then, the impact of climate change and past fluctuations in the EAIS margin has been reflected in periods of extensive vs. restricted ice cover and the modification of much of the Antarctic landscape. Resolving processes of landscape evolution is therefore critical for establishing ice sheet history, but it is rare to find unmodified landscapes that record past ice conditions. Here, we discover an extensive relic pre-glacial landscape preserved beneath the central EAIS despite millions of years of ice cover. The landscape was formed by rivers prior to ice sheet build-up but later modified by local glaciation before being dissected by outlet glaciers at the margin of a restricted ice sheet. Preservation of the relic surfaces indicates an absence of significant warm-based ice throughout their history, suggesting any transitions between restricted and expanded ice were rapid.

Response of the East Antarctic Ice Sheet to past and future climate change.

The East Antarctic Ice Sheet contains the vast majority of Earth's glacier ice (about 52 metres sea-level equivalent), but is often viewed as less vulnerable to global warming than the West Antarctic or Greenland ice sheets. However, some regions of the East Antarctic Ice Sheet have lost mass over recent decades, prompting the need to re-evaluate its sensitivity to climate change. Here we review the response of the East Antarctic Ice Sheet to past warm periods, synthesize current observations of change and evaluate future projections. Some marine-based catchments that underwent notable mass loss during past warm periods are losing mass at present but most projections indicate increased accumulation across the East Antarctic Ice Sheet over the twenty-first century, keeping the ice sheet broadly in balance. Beyond 2100, high-emissions scenarios generate increased ice discharge and potentially several metres of sea-level rise within just a few centuries, but substantial mass loss could be averted if the Paris Agreement to limit warming below 2 degrees Celsius is satisfied.

High spatial and temporal variability in Antarctic ice discharge linked to ice shelf buttressing and bed geometry.

Antarctica's contribution to global mean sea level rise has been driven by an increase in ice discharge into the oceans. The rate of change and the mechanisms that drive variability in ice discharge are therefore important to consider in the context of projected future warming. Here, we report observations of both decadal trends and inter-annual variability in ice discharge across the Antarctic Ice Sheet at a variety of spatial scales that range from large drainage basins to individual outlet glacier catchments. Overall, we find a 37 ± 11 Gt year-1 increase in discharge between 1999 and 2010, but a much smaller increase of 4 ± 8 Gt year-1 between 2010 and 2018. Furthermore, comparisons reveal that neighbouring outlet glaciers can behave synchronously, but others show opposing trends, despite their close proximity. We link this spatial and temporal variability to changes in ice shelf buttressing and the modulating effect of local glacier geometry.

Large interannual variability in supraglacial lakes around East Antarctica.

Antarctic supraglacial lakes (SGLs) have been linked to ice shelf collapse and the subsequent acceleration of inland ice flow, but observations of SGLs remain relatively scarce and their interannual variability is largely unknown. This makes it difficult to assess whether some ice shelves are close to thresholds of stability under climate warming. Here, we present the first observations of SGLs across the entire East Antarctic Ice Sheet over multiple melt seasons (2014-2020). Interannual variability in SGL volume is >200% on some ice shelves, but patterns are highly asynchronous. More extensive, deeper SGLs correlate with higher summer (December-January-February) air temperatures, but comparisons with modelled melt and runoff are complex. However, we find that modelled January melt and the ratio of November firn air content to summer melt are important predictors of SGL volume on some potentially vulnerable ice shelves, suggesting large increases in SGLs should be expected under future atmospheric warming.

Author Correction: Widespread distribution of supraglacial lakes around the margin of the East Antarctic Ice Sheet.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Widespread distribution of supraglacial lakes around the margin of the East Antarctic Ice Sheet.

Supraglacial lakes are important to ice sheet mass balance because their development and drainage has been linked to changes in ice flow velocity and ice shelf disintegration. However, little is known about their distribution on the world's largest ice sheet in East Antarctica. Here, we use ~5 million km2 of high-resolution satellite imagery to identify >65,000 lakes (>1,300 km2) that formed around the peak of the melt season in January 2017. Lakes occur in most marginal areas where they typically develop at low elevations (<100 m) and on low surface slopes (<1°), but they can exist 500 km inland and at elevations >1500 m. We find that lakes often cluster a few kilometres down-ice from grounding lines and ~60% (>80% by area) develop on ice shelves, including some potentially vulnerable to collapse driven by lake-induced hydro-fracturing. This suggests that parts of the ice sheet may be highly sensitive to climate warming.

Leveraging Industry-Academia Collaborations in Adaptive Biomedical Innovation.

Despite the rapid pace of biomedical innovation, research and development (R&D) productivity in the pharmaceutical industry has not improved broadly. Increasingly, firms need to leverage new approaches to product development and commercial execution, while maintaining adaptability to rapid changes in the marketplace and in biomedical science. Firms are also seeking ways to capture some of the talent, infrastructure, and innovation that depends on federal R&D investment. As a result, a major transition to external innovation is taking place across the industry. One example of these external innovation initiatives is the Sanofi-MIT Partnership, which provided seed funding to MIT investigators to develop novel solutions and approaches in areas of interest to Sanofi. These projects were highly collaborative, with information and materials flowing both ways. The relatively small amount of funding and short time frame of the awards built an adaptable and flexible process to advance translational science.

Pan-ice-sheet glacier terminus change in East Antarctica reveals sensitivity of Wilkes Land to sea-ice changes.

The dynamics of ocean-terminating outlet glaciers are an important component of ice-sheet mass balance. Using satellite imagery for the past 40 years, we compile an approximately decadal record of outlet-glacier terminus position change around the entire East Antarctic Ice Sheet (EAIS) marine margin. We find that most outlet glaciers retreated during the period 1974-1990, before switching to advance in every drainage basin during the two most recent periods, 1990-2000 and 2000-2012. The only exception to this trend was in Wilkes Land, where the majority of glaciers (74%) retreated between 2000 and 2012. We hypothesize that this anomalous retreat is linked to a reduction in sea ice and associated impacts on ocean stratification, which increases the incursion of warm deep water toward glacier termini. Because Wilkes Land overlies a large marine basin, it raises the possibility of a future sea level contribution from this sector of East Antarctica.

Rapid advance of two mountain glaciers in response to mine-related debris loading.

Rapid glacier advance is known to occur by a range of mechanisms. However, although large-scale debris loading has been proposed as a process for causing rapid terminus advance, it has rarely been observed. We use satellite remote sensing data to observe accelerated glacier terminus advance in response to massive supraglacial loading on two glaciers in Kyrgyzstan. Over a 15 year period, mining activity has led to the dumping of spoil of up to 180 m thick on large parts of these valley glaciers. We find that the termini of these glaciers advance by 1.2 and 3.2 km, respectively, at a rate of up to 350 m yr-1. Our analysis suggests that although enhanced basal sliding could be an important process, massive supraglacial loads have also caused enhanced internal ice deformation that would account for most, or all, of the glacier terminus advance. In addition, narrowing of the glacier valley and mining and dumping of ice alter the mass balance and flow regime of the glaciers. Although the scale of supraglacial loading is massive, this full-scale experiment provides insight into glacier flow acceleration response where small valley glaciers are impacted by very large volumes of landslide debris.

Persistent near-tropical warmth on the Antarctic continent during the early Eocene epoch.

The warmest global climates of the past 65 million years occurred during the early Eocene epoch (about 55 to 48 million years ago), when the Equator-to-pole temperature gradients were much smaller than today and atmospheric carbon dioxide levels were in excess of one thousand parts per million by volume. Recently the early Eocene has received considerable interest because it may provide insight into the response of Earth's climate and biosphere to the high atmospheric carbon dioxide levels that are expected in the near future as a consequence of unabated anthropogenic carbon emissions. Climatic conditions of the early Eocene 'greenhouse world', however, are poorly constrained in critical regions, particularly Antarctica. Here we present a well-dated record of early Eocene climate on Antarctica from an ocean sediment core recovered off the Wilkes Land coast of East Antarctica. The information from biotic climate proxies (pollen and spores) and independent organic geochemical climate proxies (indices based on branched tetraether lipids) yields quantitative, seasonal temperature reconstructions for the early Eocene greenhouse world on Antarctica. We show that the climate in lowland settings along the Wilkes Land coast (at a palaeolatitude of about 70° south) supported the growth of highly diverse, near-tropical forests characterized by mesothermal to megathermal floral elements including palms and Bombacoideae. Notably, winters were extremely mild (warmer than 10 °C) and essentially frost-free despite polar darkness, which provides a critical new constraint for the validation of climate models and for understanding the response of high-latitude terrestrial ecosystems to increased carbon dioxide forcing.

Pyrimidine-rich region mutations compensate for a stem-loop V lesion in the 5' noncoding region of poliovirus genomic RNA.

Five revertants of a linker-scanning mutation adjacent to the stem-loop V attenuation determinant (X472) in the 5' noncoding region of poliovirus RNA were independently isolated from neuroblastoma cells and contained RNAs with seven nucleotide changes in the pyrimidine-rich region. Generation of the identical rare second-site mutations suggests the existence of a replicase-dependent mutagenesis mechanism during poliovirus replication. Enzymatic structure probing of the mutated pyrimidine-rich domain identified secondary structure changes between stem-loops V and VI. A consensus secondary structure model is presented for wild-type stem-loops V and VI and the pyrimidine-rich region located in the 5' noncoding region of poliovirus RNA. A pyrimidine-rich region mutant (X472-R4N) produced large plaques in neuroblastoma cells and small plaques in HeLa cells, but the plaque size differences were not due to cell-type differences in viral translation or RNA replication. Release of X472-R4N from HeLa cells was 10-fold lower than release from neuroblastoma cells, which may explain the small plaque phenotype of X472-R4N in HeLa cells. Wild-type poliovirus was also released more efficiently from neuroblastoma cells (approximately 4-fold increase compared with release from HeLa cells), indicating that poliovirus neurotropism may be influenced by the cell-type efficiency of virus release. Thermal treatment increased the levels of infectious X472-R4N virions but not wild-type virus particles; thus RNA sequence and structural changes in the mutated 5' noncoding region of X472-R4N may have altered RNA-protein interactions necessary for virus infectivity.

RNA structure adjacent to the attenuation determinant in the 5'-non-coding region influences poliovirus viability.

In attenuated Sabin strains, point mutations within stem-loop V of the 5'-non-coding region (NCR) reduce neurovirulence and cell-specific cap-independent translation. The stem-loop V attenuation determinants lie within the highly structured internal ribosome entry site. Although stem-loop V Sabin mutations have been proposed to alter RNA secondary structure, efforts to identify such conformational changes have been unsuccessful. A previously described linker-scanning mutation (X472) modified five nucleotides adjacent to the attenuation determinant at nt 480 [for poliovirus (PV) type 1]. Transfection of X472 RNA generated only pseudo-revertants in HeLa (cervical carcinoma) or SK-N-SH (neuroblastoma) cells. Pseudo-revertants from both cell types contained nucleotide changes within the X472 linker. In addition, some neuroblastoma-isolated revertants revealed second site mutations within the pyrimidine-rich region located approximately 100 nt distal to the original lesion. Enzymatic RNA structure probing determined that the X472 linker substitution did not disrupt the overall conformation of stem-loop V but abolished base pairing adjacent to the attenuation determinant. Our analyses correlated increased base pairing proximal to the stem-loop V attenuation determinant with growth of X472 revertant RNAs (measured by northern blot analysis). Potential roles of second site mutations in the pyrimidine-rich region are discussed. In addition, our enzymatic structure probing results are shown on a consensus secondary structure model for stem-loop V of the PV 5'-NCR.

Attenuation stem-loop lesions in the 5' noncoding region of poliovirus RNA: neuronal cell-specific translation defects.

The nucleotide at position 480 in the 5' noncoding region of the viral RNA genome plays an important role in directing the attenuation phenotype of the Sabin vaccine strain of poliovirus type 1. In vitro translation studies have shown that the attenuated viral genomes of the Sabin strains direct levels of viral protein synthesis lower than those of their neurovirulent counterparts. We previously described the isolation of pseudorevertant polioviruses derived from transfections of HeLa cells with genome-length RNA harboring an eight-nucleotide lesion in a stem-loop structure (stem-loop V) that contains the attenuation determinant at position 480 (A. A. Haller and B. L. Semler, J. Virol. 66:5075-5086, 1992). This stem-loop structure is a major component of the poliovirus internal ribosome entry site required for initiation of viral protein synthesis. The eight-nucleotide lesion (X472) was lethal for virus growth and gave rise only to viruses which had partially reverted nucleotides within the original substituted sequences. In this study, we analyzed two of the poliovirus revertants (X472RI and X472R2) for cell-type-specific growth properties. The X472RI and X472R2 RNA templates directed protein synthesis to wild-type levels in in vitro translation reaction mixtures supplemented with crude cytoplasmic HeLa cell extracts. In contrast, the same X472 revertant RNAs displayed a decreased translation initiation efficiency when translated in a cell-free system supplemented with extracts from neuronal cells. This translation initiation defect of the X472R templates correlated with reduced yields of infectious virus particles in neuronal cells compared with those obtained from HeLa cells infected with the X472 poliovirus revertants. Our results underscore the important of RNA secondary structures within the poliovirus internal ribosome entry site in directing translation initiation and suggest that such structures interact with neuronal cell factors in a specific manner.

Silicon-zinc interactions and potential roles for dietary zinc and copper in minimizing silica urolithiasis in rats.

Two 8-wk experiments were conducted with Sprague-Dawley weanling rats to determine whether interactions occurring between Zn and Si, or a nutritional deficiency of either Cu or Zn, affect silica urolith formation. In Exp. 1, concentrations of 0, 540, and 2,700 mg of Si/kg of diet from tetraethylorthosilicate were used with dietary Zn concentrations of 4, 12, and 500 mg/kg of diet in a 3 x 3 factorial arrangement. In Exp. 2, copper at 1 or 5 mg/kg of diet and Zn at 4, 12, and 500 mg/kg of diet were used in a 2 x 3 factorial arrangement. All diets in Exp. 2 contained 2,700 mg of Si/kg. Silica uroliths occurred in all treatments providing, 2,700 mg of Si/kg of diet. There was a trend (P = .17) toward a reduction of silica urolith incidence with increasing concentrations of dietary Zn in Exp. 1. In Exp. 2, a deficiency of Zn, and a Cu deficiency exacerbated by 500 mg of Zn/kg of diet, increased (P < .05) silica urolith formation. An antagonism between Si and Zn, as demonstrated previously in the rat, may not be of a sufficient magnitude to be applicable to the prevention of silica urolithiasis. The data further demonstrate that Zn deficiency and, to a lesser extent, Cu deficiency contributed to silica urolith formation in rats fed diets having a high content of absorbable Si. However, 540 mg of Si/kg of diet may potentiate the metabolic activity of Zn, as indicated by a 23% Si-mediated weight gain response in Zn-deficient rats.

Zinc-silicon interactions influencing sperm chromatin integrity and testicular cell development in the rat as measured by flow cytometry.

Flow-cytometric procedures were used to determine effects of dietary Zn and Si variations on rat testicular cell development, including integrity of caudal epididymal sperm chromatin structure defined as the susceptibility of DNA to denaturation in situ. Concentrations of 4 (deficient), 12 (adequate), and 500 (excessive) mg of Zn/kg of diet were used with Si concentrations of 0 (low), 540 (medium), and 2,700 (high) mg/kg of diet in a 3 x 3 factorial arrangement. Three-week-old Sprague-Dawley male rats were fed the experimental diets for 8 wk. Rats fed the Zn-deficient/Si-low diet demonstrated significant deviations in the ratio of testicular cell types present, including a reduction of S phase and total haploid cells. Furthermore, approximately 50% of epididymal sperm had a significant decrease in resistance to DNA denaturation in situ. In the Zn-deficient/Si-medium treatment, the effects of Si on animal and testicular growth, distribution of testicular cell types, and sperm chromatin structure integrity were quite similar to the effects of the Zn-adequate diets. A toxic effect of Zn on sperm chromatin structure integrity observed in the Zn-excess/Si-medium treatment seemed to be counteracted by Si in the Zn-excess/Si-high treatment. Silicon at medium and high levels seems to affect Zn metabolism through potentiation and antagonistic reactions, respectively. Zinc deficiency likely disrupts the normal sperm chromatin quaternary structure in which Zn plays a role by providing stability and resistance to DNA denaturation in situ.

Effects of dietary ammonium chloride and variations in calcium to phosphorus ratio on silica urolithiasis in sheep.

Ammonium chloride was added to diets varying in Ca content to evaluate its potential in preventing silica urolith formation in sheep. A 2 x 2 factorial experiment involved wether lambs with ad libitum access to a diet of 50% grass hay and 50% ground oats plus supplement. The basal diet contained on a DM basis 3.3% SiO2, .31% Ca, .22% P, 11.6% CP, and 26% ADF. Treatments (38 to 39 lambs/treatment) consisted of a control (C), limestone to increase dietary calcium to .6% (L), 1% ammonium chloride (A), and L + A (LA). After a 118-d experimental period, siliceous kidney deposits were found only in C and L, with silica making up 93% to 95% of the urolithic ash. Urolith incidences were 13% (C) and 18% (L), respectively. The lack of urolith development in lambs fed A and LA (ammonium chloride effect, P less than .01) and a trend toward a lower urolith incidence in C vs L (P less than .02) support the hypothesis that acid-forming effects of the diet and a reduction in the dietary Ca to P ratio reduce silica urolith formation.

High dietary calcium to phosphorus ratio and alkali-forming potential as factors promoting silica urolithiasis in sheep.

Sheep were used to study factors previously found to promote silica urolithiasis in a rat model. In addition to high silica, these dietary factors included elevated calcium, a high calcium to phosphorus ratio and alkali-forming effects. Wether lambs had ad libitum access to a diet of 50% of grass hay and 50% ground oats plus supplement. Diet analysis was 3.4% total SiO2, .29% calcium, .25% phosphorus, 11.3% CP and 28% ADF. Treatments (40 lambs/treatment) consisted of a control (C), limestone to increase dietary calcium to .6% (L), L + 1% sodium bicarbonate (LS) and L + 1% ammonium chloride (LA). After a 91-d experimental period followed by a 56-d postexperimental finishing period, silica kidney deposits were found in all treatments, and SiO2 made up 74% to 97% of the urolithic ash. Kidney urolith incidences in the four treatments were C, 7/40; L, 12/40; LS, 20/40; and LA, 9/40. A higher urolith incidence in LS (LS vs C, P less than .05) and a trend toward a higher incidence in L (L vs C, P less than .2), accompanied by elevated urine pH (L = LS greater than C greater than LA, P less than .01), lend support to the concept that high-silica diets having high calcium to phosphorus ratios and alkali-forming potentials contribute to silica urolithiasis.

Sensitivity and specificity of transcranial Doppler ultrasonography in the diagnosis of vasospasm following subarachnoid hemorrhage.

Vasospasm is the leading cause of death and disability in patients with aneurysmal subarachnoid hemorrhage (SAH). Transcranial Doppler ultrasonography (TCD) can detect the arterial narrowing noninvasively, but the sensitivity and specificity of this technique have not been reported in a population of patients with a high frequency of angiographic vasospasm. In this study, 34 consecutive patients with SAH undergoing angiography during the period of risk for vasospasm had technically adequate TCD examinations within 24 hours of the angiogram. Using a mean flow velocity of 120 cm/sec and above as indicative of vasospasm, TCD correctly detected angiographic vasospasm in 17 patients; there were no false positives. It correctly determined that 5 patients did not have vasospasm, whereas there were 12 false negatives. False negatives were frequently due to angiographic vasospasm involving vessels not assessable by TCD. The correlation between mean flow velocity and the angiographic residual lumen diameter of the middle cerebral artery was statistically significant. These data suggest that TCD is a highly specific (100%), but less sensitive (58.6%) test for the detection of angiographic vasospasm following SAH. Confirmatory angiography may be avoided if the TCD study is positive, but additional studies may be necessary if the clinical picture is suspicious and the TCD study is negative.

Articulation norms used by practicing speech-language pathologists in Oregon: results of a survey.

Recent investigations of children's developing articulation abilities indicate substantially earlier ages for speech-sound acquistion as compared to traditional norms. Speech-language pathologists in Oregon were asked which developmental norms they used when assessing articulation development. The majority refer to Templin's 1957 investigation instead of more recent norms. Those respondents who did not use developmental norms reported other factors and sources as useful references when determining articulation status. Clinical implications of these findings are discussed.