Investigating the Controls on Surface Snow δ18O Values in the Coastal Northeast Pacific: Implications for Paleoclimate Interpretations

Stable water isotope ratios (18O and D) in snow pit (Juneau Icefield) and fresh snow (Eclipse Icefield) samples are included in a compilation of all available snow isotope data from coastal Alaska, and used to evaluate observed isotope shifts in regional paleoclimate records. I compiled existing isotope data in coastal Alaska (primarily the Saint Elias Range) in order to better understand the elevation dependence of stable atmospheric water isotope ratios in the region. The values that make up the compilation are reflective of multiple fractionation regimes associated with synoptic scale cyclonic events, described using the Cyclone-Water Isotope Model (Holdsworth and Krouse 2002). Using this Cyclone-Water Isotope Model as a link between high frequency spatial and temporal variability, fresh snow data characterizing five different events within a 17 day time span from the Eclipse Icefield were analyzed for δ18O values. Average isotope values among these five events vary by as much as 8‰. Meteorological conditions over the domain are investigated with NCEP Climate Forecast System Reanalysis (CFSR), and show that events with more depleted δ18O are associated with systems that have higher pressure and a zonal (northern) moisture source, whereas events with less depleted δ18O are related to events with lower pressure and a more significant component of southern moisture. These observations of event-based meteorological controls on δ18O variability shed light on paleoclimate interpretations of shifts in the isotopic record seen in the Mount Logan ice core and Jellybean Lake sediment core at around A.D. 800 and A.D. 1840. The findings in the paper support Fields et al. (2010) in the interpretation that the shift to lower δ18O values seen in the isotopic record is caused by a transition to a more zonal (northern) moisture source paradigm

Limitation of fixed nitrogen and deepening of the carbonate-compensation depth through the Hirnantian at Dob's Linn, Scotland

This study was funded by University of Washington Department of Earth and Space Sciences Harry Wheeler Scholarship and Jody Bourgeois Graduate Student Support Fund granted to MCK. Stephen Hillier acknowledges support of the Scottish Government's Rural and Environment Science and Analytical Services Division (RESAS).The late Ordovician is characterized by dramatic changes in global climate concurrent with a major mass extinction and possible changes in ocean redox. To further refine our understanding of these events, we present nitrogen and carbon isotope and abundance data from the Ordovician-Silurian (O-S) Global Boundary Stratotype Section and Point at Dob's Linn, Scotland. We show that this section experienced post-depositional ammonium migration from the organic-rich to the organic-poor horizons. However, our data suggest that isotopic fractionations from ammonium substitution into illitic clay minerals are small and can be corrected. Reconstructed primary nitrogen isotope ratios indicate that unlike in tropical continental shelf sections that were transiently enriched in nitrate during the Hirnantian glaciation, the sub-tropical continental slope setting at Dob's Linn experienced persistent limitation of fixed nitrogen across the O-S boundary. Shallow subpolar settings appear to be the only environment that shows persistent nitrate availability at that time. This pattern suggests that spatial trends in marine nitrate concentrations – which are observed in the modern ocean as a result of latitudinal temperature gradients – were already established during the Paleozoic. While the average marine O2 chemocline depth may have deepened during the Hirnantian glaciation, it probably did not lead to global ventilation of the deep ocean, which may have been delayed until the Carboniferous. Furthermore, carbonate data from this and other sections suggest a deepening of the carbonate compensation depth (CCD) during the Hirnantian. This observation indicates that Pacific-style responses of the CCD to glacial/interglacial periods were operational across the O-S boundary, and that the expansion of abiotic carbonate deposition and preservation beyond the shelf break could have in-part mediated changes to surface CO2 during these extreme changes in climate.PostprintPeer reviewe

The evolution of Earth’s biogeochemical nitrogen cycle

Financial support during the compilation of this manuscript was provided by the NASA postdoctoral program (EES), the NSF Graduate Research Fellowship Program (MAK), the Agouron Institute (MCK, RB) and the NSF FESD program (grant number 1338810, subcontract to RB).Nitrogen is an essential nutrient for all life on Earth and it acts as a major control on biological productivity in the modern ocean. Accurate reconstructions of the evolution of life over the course of the last four billion years therefore demand a better understanding of nitrogen bioavailability and speciation through time. The biogeochemical nitrogen cycle has evidently been closely tied to the redox state of the ocean and atmosphere. Multiple lines of evidence indicate that the Earth’s surface has passed in a non-linear fashion from an anoxic state in the Hadean to an oxic state in the later Phanerozoic. It is therefore likely that the nitrogen cycle has changed markedly over time, with potentially severe implications for the productivity and evolution of the biosphere. Here we compile nitrogen isotope data from the literature and review our current understanding of the evolution of the nitrogen cycle, with particular emphasis on the Precambrian. Combined with recent work on redox conditions, trace metal availability, sulfur and iron cycling on the early Earth, we then use the nitrogen isotope record as a platform to test existing and new hypotheses about biogeochemical pathways that may have controlled nitrogen availability through time. Among other things, we conclude that (a) abiotic nitrogen sources were likely insufficient to sustain a large biosphere, thus favoring an early origin of biological N2 fixation, (b) evidence of nitrate in the Neoarchean and Paleoproterozoic confirm current views of increasing surface oxygen levels at those times, (c) abundant ferrous iron and sulfide in the mid-Precambrian ocean may have affected the speciation and size of the fixed nitrogen reservoir, and (d) nitrate availability alone was not a major driver of eukaryotic evolution.PostprintPeer reviewe

Spatial and temporal trends in Precambrian nitrogen cycling: a Mesoproterozoic offshore nitrate minimum

We thank NSF EAR FESD grant #1338810 (RB), NASA grant NNX16AI37G (RB), the Agouron Institute (RB), the NASA Astrobiology Institute’s Virtual Planetary Laboratory (RB), the NSF Graduate Research Fellowship Program (MAK), and the Department of Earth and Space Sciences, University of Washington Goodspeed Geology Fellowship (MCK), Misch Fellowship (MCK), and the Kenneth C. Robbins Field Study Fellowship (2014, MCK) for funding.Fixed nitrogen is an essential nutrient for eukaryotes. As N2 fixation and assimilation of nitrate are catalyzed by metalloenzymes, it has been hypothesized that in Mesoproterozoic oceans nitrate was limited in offshore environments by low trace metal concentrations and high rates of denitrification in anoxic and episodically euxinic deep water masses, restricting eukaryotes to near-shore environments and limiting their evolutionary innovation. To date this hypothesis has only been tested in the Belt Supergroup (∼1.4 Ga), with results that support an onshore-offshore nitrate gradient as a potential control on eukaryote ecology. Here we present bulk nitrogen and organic carbon isotopic data from non-isochronous cross-basinal facies across the Bangemall (∼1.5 Ga) and the Roper (∼1.4-1.5 Ga) basins to better understand the extent and variability of onshore-offshore nitrogen isotope gradients in the Mesoproterozoic. Both basins show an average ∼1-2‰ enrichment in δ15Nbulk from deep to shallow facies, with a maximum range from -1‰ offshore to +7.5‰ onshore. Unlike the Belt basin, the Bangemall and Roper basins show some offshore δ15Nbulk values that are enriched beyond the isotopic range induced by biological N2 fixation alone. This suggests a mixture of aerobic and anaerobic metabolisms offshore. In shallow waters, where δ15Nbulk enrichment peaks, an aerobic nitrogen cycle was evidently operating vigorously. Even though isotopic signatures of aerobic nitrogen cycling are seen in all parts of the Bangemall and Roper basins, our data are consistent with a lateral gradient in nitrate availability within the photic zone, with higher concentrations in near-shore environments than offshore. The variability in δ15Nbulk values in each depositional environment and the consistently low δ15N values from Mesoproterozoic units compared to the Paleoproterozoic and Neoproterozoic suggest that nitrate concentrations in the global ocean were likely low. This trend is now seen in all three Mesoproterozoic basins so far examined, and contrasts with the Paleoproterozoic and Neoproterozoic where nearly all δ15Nbulk data plot above the N2 fixation window. Thus, we propose that the Mesoproterozoic ocean was characterized by a nitrate minimum between the Paleo- and Neoproterozoic, with the lowest concentrations in offshore environments. This inference is consistent with a Mesoproterozoic O2 decline following a temporary Paleoproterozoic O2 peak, and it further supports the idea that nitrate limitation offshore may have contributed to the restriction of photosynthetic eukaryotes to near-shore environments, delaying their rise to ecological dominance until the Neoproterozoic Era.PostprintPeer reviewe

Friedrich Heinrich Jacobi: O Spinozinu nauku u pismima Mosesu Mendelssohnu / Spisi o sporu o božanskim stvarima i njihovoj objavi

Understanding how and when Earth's surface became oxygenated is essential for understanding its biogeochemical evolution. Incipient oxygenation of Earth's surface environments before the Great Oxidation Event (GOE; 2.4 Ga) has been well-documented, but the nature of these redox changes, whether protracted or transient, is poorly understood. We present nitrogen isotope ratios, selenium abundances, and selenium isotope ratios from the Jeerinah Formation (2.66 Ga; Fortescue Group, Western Australia) that represent (i) high-resolution evidence of transient surface ocean oxygenation 260 My before the GOE, (ii) a possible muted pulse of oxidative continental weathering, and (iii) the oldest firm evidence for nitrification and denitrification metabolisms. These results, in concert with previous studies, highlight the variability in mechanisms and magnitudes of Neoarchean oxygen fluctuations.Many paleoredox proxies indicate low-level and dynamic incipient oxygenation of Earth's surface environments during the Neoarchean (2.8textendash2.5 Ga) before the Great Oxidation Event (GOE) at 2.4 Ga. The mode, tempo, and scale of these redox changes are poorly understood, because data from various locations and ages suggest both protracted and transient oxygenation. Here, we present bulk rock and kerogen-bound nitrogen isotope ratios as well as bulk rock selenium abundances and isotope ratios from drill cores sampled at high stratigraphic resolution through the Jeerinah Formation (2.66 Ga; Fortescue Group, Western Australia) to test for changes in the redox state of the surface environment. We find that both shallow and deep depositional facies in the Jeerinah Formation display episodes of positive primary δ15N values ranging from +4 to +6textperthousand, recording aerobic nitrogen cycling that requires free O2 in the upper water column. Moderate selenium enrichments up to 5.4 ppm in the near-shore core may indicate coincident oxidative weathering of sulfide minerals on land, although not to the extent seen in the younger Mt. McRae Shale that records a well-documented textquotedblleftwhifftextquotedblright of atmospheric oxygen at 2.5 Ga. Unlike the Mt. McRae Shale, Jeerinah selenium isotopes do not show a significant excursion concurrent with the positive δ15N values. Our data are thus most parsimoniously interpreted as evidence for transient surface ocean oxygenation lasting less than 50 My, extending over hundreds of kilometers, and occurring well before the GOE. The nitrogen isotope data clearly record nitrification and denitrification, providing the oldest firm evidence for these microbial metabolisms.PostprintPeer reviewe

Dynamic Click Hydrogels for Xeno-Free Culture of Induced Pluripotent Stem Cells

Xeno-free, chemically defined poly(ethylene glycol) (PEG)-based hydrogels are being increasingly used for in vitro culture and differentiation of human induced pluripotent stem cells (hiPSCs). These synthetic matrices provide tunable gelation and adaptable material properties crucial for guiding stem cell fate. Here, sequential norbornene-click chemistries are integrated to form synthetic, dynamically tunable PEG-peptide hydrogels for hiPSCs culture and differentiation. Specifically, hiPSCs are photoencapsulated in thiol-norbornene hydrogels crosslinked by multiarm PEG-norbornene (PEG-NB) and proteaselabile crosslinkers. These matrices are used to evaluate hiPSC growth under the influence of extracellular matrix properties. Tetrazine-norbornene (Tz-NB) click reaction is then employed to dynamically stiffen the cell-laden hydrogels. Fast reactive Tz and its stable derivative methyltetrazine (mTz) are tethered to multiarm PEG, yielding mono-functionalized PEG-Tz, PEG-mTz, and dualfunctionalized PEG-Tz/mTz that react with PEG-NB to form additional crosslinks in the cell-laden hydrogels. The versatility of Tz-NB stiffening is demonstrated with different Tz-modified macromers or by intermittent incubation of PEG-Tz for temporal stiffening. Finally, the Tz-NB-mediated dynamic stiffening is explored for 4D culture and definitive endoderm differentiation of hiPSCs. Overall, this dynamic hydrogel platform affords exquisite controls of hydrogel crosslinking for serving as a xeno-free and dynamic stem cell niche

Creation of an NCI comparative brain tumor consortium: informing the translation of new knowledge from canine to human brain tumor patients

On September 14–15, 2015, a meeting of clinicians and investigators in the fields of veterinary and human neuro-oncology, clinical trials, neuropathology, and drug development was convened at the National Institutes of Health campus in Bethesda, Maryland. This meeting served as the inaugural event launching a new consortium focused on improving the knowledge, development of, and access to naturally occurring canine brain cancer, specifically glioma, as a model for human disease. Within the meeting, a SWOT (strengths, weaknesses, opportunities, and threats) assessment was undertaken to critically evaluate the role that naturally occurring canine brain tumors could have in advancing this aspect of comparative oncology aimed at improving outcomes for dogs and human beings. A summary of this meeting and subsequent discussion are provided to inform the scientific and clinical community of the potential for this initiative. Canine and human comparisons represent an unprecedented opportunity to complement conventional brain tumor research paradigms, addressing a devastating disease for which innovative diagnostic and treatment strategies are clearly needed

Simulation Modelling in Ophthalmology : Application to Cost Effectiveness of Ranibizumab and Aflibercept for the Treatment of Wet Age-Related Macular Degeneration in the United Kingdom

Previously developed models in ophthalmology have generally used a Markovian structure. There are a number of limitations with this approach, most notably the ability to base patient outcomes on best-corrected visual acuity (BCVA) in both eyes, which may be overcome using a different modelling structure. Simulation modelling allows for this to be modelled more precisely, and therefore may provide more accurate and relevant estimates of the cost effectiveness of ophthalmology interventions

Hair-bearing human skin generated entirely from pluripotent stem cells

The skin is a multilayered organ, equipped with appendages (that is, follicles and glands), that is critical for regulating body temperature and the retention of bodily fluids, guarding against external stresses and mediating the sensation of touch and pain1,2. Reconstructing appendage-bearing skin in cultures and in bioengineered grafts is a biomedical challenge that has yet to be met3-9. Here we report an organoid culture system that generates complex skin from human pluripotent stem cells. We use stepwise modulation of the transforming growth factor β (TGFβ) and fibroblast growth factor (FGF) signalling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. During an incubation period of 4-5 months, we observe the emergence of a cyst-like skin organoid composed of stratified epidermis, fat-rich dermis and pigmented hair follicles that are equipped with sebaceous glands. A network of sensory neurons and Schwann cells form nerve-like bundles that target Merkel cells in organoid hair follicles, mimicking the neural circuitry associated with human touch. Single-cell RNA sequencing and direct comparison to fetal specimens suggest that the skin organoids are equivalent to the facial skin of human fetuses in the second trimester of development. Moreover, we show that skin organoids form planar hair-bearing skin when grafted onto nude mice. Together, our results demonstrate that nearly complete skin can self-assemble in vitro and be used to reconstitute skin in vivo. We anticipate that our skin organoids will provide a foundation for future studies of human skin development, disease modelling and reconstructive surgery

The histone demethylase LSD1 regulates inner ear progenitor differentiation through interactions with Pax2 and the NuRD repressor complex

The histone demethylase LSD1 plays a pivotal role in cellular differentiation, particularly in silencing lineage-specific genes. However, little is known about how LSD1 regulates neurosensory differentiation in the inner ear. Here we show that LSD1 interacts directly with the transcription factor Pax2 to form the NuRD co-repressor complex at the Pax2 target gene loci in a mouse otic neuronal progenitor cell line (VOT-N33). VOT-N33 cells expressing a Pax2-response element reporter were GFP-negative when untreated, but became GFP positive after forced differentiation or treatment with a potent LSD inhibitor. Pharmacological inhibition of LSD1 activity resulted in the enrichment of mono- and di-methylation of H3K4, upregulation of sensory neuronal genes and an increase in the number of sensory neurons in mouse inner ear organoids. Together, these results identify the LSD1/NuRD complex as a previously unrecognized modulator for Pax2-mediated neuronal differentiation in the inner ear