Flow dynamics of an accumulation basin: a case study of upper Kahiltna Glacier, Mount McKinley, Alaska

We interpreted flow dynamics of the Kahiltna Pass Basin accumulation zone on Mount McKinley, Alaska, USA, using 40, 100 and 900 MHz ground-penetrating radar profiles and GPS surface velocity measurements. We found dipping, englacial surface-conformable strata that experienced vertical thickening as the glacier flowed westward from a steep, higher-velocity (60 m a–1) region into flat terrain associated with a 908 bend in the glacier and lower velocities (15 m a–1) to the south. Stratigraphy near the western side of the basin was surface-conformable to 170 m depth and thinned as flow diverged southward, down-glacier. We found complex strata beneath the conformable stratigraphy and interpret these features as buried crevasses, avalanche debris and deformed ice caused by up-glacier events. We also suggest that basin dimensions, bed topography and the sharp bend each cause flow extension and compression, significantly contributing to conformable and complex strata thickness variations. Our findings show that surface-conformable stratigraphy continuous with depth and consistent strata thicknesses cannot be assumed in accumulation basins, because local and upglacier terrain and flow dynamics can cause structural complexities to occur under and within surfaceconformable layers

Melt regimes, internal stratigraphy, and flow dynamics of three glaciers in the Alaska Range

We used ground-penetrating radar (GPR), GPS and glaciochemistry to evaluate melt regimes and ice depths, important variables for mass-balance and ice-volume studies, of Upper Yentna Glacier, Upper Kahiltna Glacier and the Mount Hunter ice divide, Alaska. We show the wet, percolation and dry snow zones located below 2700 m a.s.l., at 2700 to 3900 m a.s.l. and above 3900 m a.s.l., respectively. We successfully imaged glacier ice depths upwards of 480 m using 40–100 MHz GPR frequencies. This depth is nearly double previous depth measurements reached using mid-frequency GPR systems on temperate glaciers. Few Holocene-length climate records are available in Alaska, hence we also assess stratigraphy and flow dynamics at each study site as a potential ice-core location. Ice layers in shallow firn cores and attenuated glaciochemical signals or lacking strata in GPR profiles collected on Upper Yentna Glacier suggest that regions below 2800 m a.s.l. are inappropriate for paleoclimate studies because of chemical diffusion, through melt. Flow complexities on Kahiltna Glacier preclude ice-core climate studies. Minimal signs of melt or deformation, and depth–age model estimates suggesting 4815 years of ice on the Mount Hunter ice divide (3912 m a.s.l.) make it a suitable Holocene-age ice-core location

Dietary Behaviors Predict Glycemic Control in Youth With Type 1 Diabetes

OBJECTIVE—To investigate the association between dietary adherence and glycemic control among youth with type 1 diabetes

Emphasis on Carbohydrates May Negatively Influence Dietary Patterns in Youth With Type 1 Diabetes

This is an uncopyedited electronic version of an article accepted for publication in Diabetes Care. The American Diabetes Association, publisher of Diabetes Care, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes Care in print and online a

Compensatory Motor Neuron Response to Chromatolysis in the Murine hSOD1(G93A) Model of Amyotrophic Lateral Sclerosis

We investigated neuronal self-defense mechanisms in a murine model of amyotrophic lateral sclerosis (ALS), the transgenic hSOD1(G93A), during both the asymptomatic and symptomatic stages. This is an experimental model of endoplasmic reticulum (ER) stress with severe chromatolysis. As a compensatory response to translation inhibition, chromatolytic neurons tended to reorganize the protein synthesis machinery at the perinuclear region, preferentially at nuclear infolding domains enriched in nuclear pores. This organization could facilitate nucleo-cytoplasmic traffic of RNAs and proteins at translation sites. By electron microscopy analysis, we observed that the active euchromatin pattern and the reticulated nucleolar configuration of control motor neurons were preserved in ALS chromatolytic neurons. Moreover the 5'-fluorouridine (5'-FU) transcription assay, at the ultrastructural level, revealed high incorporation of the RNA precursor 5'-FU into nascent RNA. Immunogold particles of 5'-FU incorporation were distributed throughout the euchromatin and on the dense fibrillar component of the nucleolus in both control and ALS motor neurons. The high rate of rRNA transcription in ALS motor neurons could maintain ribosome biogenesis under conditions of severe dysfunction of proteostasis. Collectively, the perinuclear reorganization of protein synthesis machinery, the predominant euchromatin architecture, and the active nucleolar transcription could represent compensatory mechanisms in ALS motor neurons in response to the disturbance of ER proteostasis. In this scenario, epigenetic activation of chromatin and nucleolar transcription could have important therapeutic implications for neuroprotection in ALS and other neurodegenerative diseases. Although histone deacetylase inhibitors are currently used as therapeutic agents, we raise the untapped potential of the nucleolar transcription of ribosomal genes as an exciting new target for the therapy of some neurodegenerative diseases

Tar DNA Binding Protein-43 (TDP-43) Associates with Stress Granules: Analysis of Cultured Cells and Pathological Brain Tissue

Tar DNA Binding Protein-43 (TDP-43) is a principle component of inclusions in many cases of frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS). TDP-43 resides predominantly in the nucleus, but in affected areas of ALS and FTLD-U central nervous system, TDP-43 is aberrantly processed and forms cytoplasmic inclusions. The mechanisms governing TDP-43 inclusion formation are poorly understood. Increasing evidence indicates that TDP-43 regulates mRNA metabolism by interacting with mRNA binding proteins that are known to associate with RNA granules. Here we show that TDP-43 can be induced to form inclusions in cell culture and that most TDP-43 inclusions co-localize with SGs. SGs are cytoplasmic RNA granules that consist of mixed protein - RNA complexes. Under stressful conditions SGs are generated by the reversible aggregation of prion-like proteins, such as TIA-1, to regulate mRNA metabolism and protein translation. We also show that disease-linked mutations in TDP-43 increased TDP-43 inclusion formation in response to stressful stimuli. Biochemical studies demonstrated that the increased TDP-43 inclusion formation is associated with accumulation of TDP-43 detergent insoluble complexes. TDP-43 associates with SG by interacting with SG proteins, such as TIA-1, via direct protein-protein interactions, as well as RNA-dependent interactions. The signaling pathway that regulates SGs formation also modulates TDP-43 inclusion formation. We observed that inclusion formation mediated by WT or mutant TDP-43 can be suppressed by treatment with translational inhibitors that suppress or reverse SG formation. Finally, using Sudan black to quench endogenous autofluorescence, we also demonstrate that TDP-43 positive-inclusions in pathological CNS tissue co-localize with multiple protein markers of stress granules, including TIA-1 and eIF3. These data provide support for accumulating evidence that TDP-43 participates in the SG pathway

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe