This study evaluates the utility of sedimentary mercury (Hg) contents as a proxy for fingerprinting ancient massive volcanism, which is often associated with biogeochemical perturbations. Herein we ...present new Hg geochemical data from anoxic marine basins across the Toarcian Oceanic Anoxic Event (T-OAE; ∼183 Ma) as a test of the complex Hg cycle. The T-OAE was likely initiated by the main eruptive phase of the Karoo–Ferrar large igneous province, which caused a subsequent cascade of environmental perturbations and resulting mass extinction. At present the leading interpretation of sedimentary Hg anomalies has been volcanogenic outgassing as the primary source. Our study and compilation results suggest, however, that Hg/TOC anomalies were restricted to shallow-water, and/or proximal environments, while deep-water, more distal depositional settings document no significant Hg-related anomalies. Furthermore, asynchronous stratigraphic deviations in Hg enrichments favor terrestrially sourced materials and local redox variability, rather than direct volcanogenic emissions, as a primary control mechanism. Additionally, Hg isotope signatures from our only study site documenting an Hg anomaly are also consistent with a terrestrial Hg origin during the T-OAE. Therefore, our results suggest that Hg anomalies in the geological record need to be re-evaluated as a “smoking gun” proxy that only infers volcanogenic inputs.
•Mercury concentration and isotopes from anoxic basins across the Toarcian OAE.•Compilation shows mercury anomalies are observed near landmasses.•Compilation suggests that Hg is dominantly delivered via terrestrial sources.•Mercury isotopes from one section agree with terrestrial source delivering Hg.•Sedimentary Hg anomalies are not a direct proxy for past volcanism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The Mesozoic Era experienced several instances of abrupt environmental change that are associated with instabilities in the climate, reorganizations of the global carbon cycle, and elevated ...extinction rates. Often during these perturbations, oxygen-deficient conditions developed in the oceans resulting in the widespread deposition of organic-rich sediments — these events are referred to as Oceanic Anoxic Events or OAEs. Such events have been linked to massive injections of greenhouse gases into the ocean–atmosphere system by transient episodes of voluminous volcanism and the destabilization of methane clathrates within marine environments. Nevertheless, uncertainty surrounds the specific environmental drivers and feedbacks that occurred during the OAEs that caused perturbations in the carbon cycle; this is particularly true of the Early Jurassic Toarcian OAE (∼183.1 Ma). Here, we present biostratigraphically constrained carbon isotope data from western North America (Alberta and British Columbia, Canada) to better assess the global extent of the carbon cycle perturbations. We identify the large negative carbon isotope excursion associated with the OAE along with high-frequency oscillations and steps within the onset of this excursion. We propose that these high-frequency carbon isotope excursions reflect changes to the global carbon cycle and also that they are related to the production and release of greenhouse gases from terrestrial environments on astronomical timescales. Furthermore, increased terrestrial methanogenesis should be considered an important climatic feedback during Ocean Anoxic Events and other similar events in Earth history after the proliferation of land plants.
•Analyzed δ13Corg values from two North American sites across the Toarcian Oceanic Anoxic Event.•Highest-resolution study of Toarcian carbon isotope excursions from outside of Europe.•Documented small-scale carbon isotope excursions during onset of Toarcian carbon isotope excursion.•Small-scale carbon isotope excursions during Toarcian were global phenomena.•Increased terrestrial methanogenesis implicated in global warming and carbon isotope excursions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Many metals present in trace concentrations in the oceans are sensitive to reduction and oxidation reactions (termed redox‐sensitive trace metals or RSTMs) and can therefore be affected during ...intervals of expanded oceanic anoxia and euxinia (anoxic and sulfidic waters). These RSTMs are important micronutrients; and their availability plays a significant role in controlling metabolic pathways and therefore ecosystem structure. Understanding the links to ecosystem restructuring and potential collapse is important since past deoxygenation events are associated with biological turnover. The Early Jurassic Toarcian Oceanic Anoxic Event (T‐OAE) was one such event. We focus on the RSTM molybdenum (Mo), important in the nitrogen cycle, from a basin transect where local redox conditions permit the tracking of the marine reservoir of Mo. Mo enrichments start to decline in the Pliensbachian, continue to decline in the early Toarcian, drop precipitously during the T‐OAE interval, and remain low afterward before a protracted increase toward the initial values seen in the Pliensbachian. From a compilation of available data, we estimate that ∼41 Gt of Mo was buried during the T‐OAE using a range of possible flux estimates. Given the known correlations of Mo with total organic carbon, the estimated burial of organic carbon during the T‐OAE interval was ∼244,000 Gt. This requires a minimum of 3.25% of the ocean floor to be covered by euxinic waters. Finally, we suggest that the intervals traditionally classified as OAEs are associated with the greatest extent of euxinia.
Plain Language Summary
Marine metal availability in low amounts is important for organisms that use sunlight to produce energy; thus, a significant reduction in their availability would have profound impacts on the base of marine ecosystems. Using sedimentary molybdenum (Mo) concentrations from a unique region of the Panthalassan (ancient Pacific) superocean, we have reconstructed the marine Mo contents of the global oceans, for the first time, across the Early Jurassic Pliensbachian‐Toarcian mass extinction and the Toarcian Oceanic Anoxic Event (T‐OAE). We document a significant decrease in the availability of this bioessential trace metal during this time interval, which may have contributed to the observed marine mass extinction. Using our new Mo data, we calculated the amount of organic carbon (OC) buried in the oceans and compared it with previous estimations of carbon release that occurred during the T‐OAE. Our new estimates suggest that much more OC was buried than previously estimated. If our modern oceans continue to lose oxygen at high rates, then the future oceans may experience another catastrophic reorganization of the marine ecosystem structure due to not only oxygen loss, but also major decreases in bioessential trace metals.
Key Points
Significant global depletion of redox‐sensitive trace metals during the early Toarcian may have affected marine microbial ecology
Estimated organic carbon burial during Toarcian Oceanic Anoxic Event significantly larger than previous estimations for carbon release
The traditional oceanic anoxic event interval likely associated with greatest extent of euxinia
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Molecular imaging agents are extending the potential of noninvasive medical diagnosis from basic gross anatomical descriptions to complicated phenotypic characterizations based upon the recognition ...of unique cell-surface biochemical signatures. Although originally the purview of nuclear medicine, “molecular imaging” is now studied in conjunction with all clinically relevant imaging modalities. Of the myriad of particles that have emerged as prospective candidates for clinical translation, perfluorocarbon nanoparticles offer great potential for combining targeted imaging with drug delivery, much like the “magic bullet” envisioned by Paul Ehrlich 100 years ago. Perfluorocarbon nanoparticles, once studied in Phase III clinical trials as blood substitutes, have found new life for molecular imaging and drug delivery. The particles have been adapted for use with all clinically relevant modalities and for targeted drug delivery. In particular, their intravascular constraint due to particle size provides a distinct advantage for angiogenesis imaging and antiangiogenesis therapy. As perfluorocarbon nanoparticles have recently entered Phase I clinical study, this review provides a timely focus on the development of this platform technology and its application for angiogenesis-related pathologies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•New Triassic-Jurassic section, paleontological-geochemical data, open Panthalassa.•Complete record, new δ13Corg curve across the Triassic-Jurassic transition.•Norian-Rhaetian and Triassic-Jurassic ...boundaries constrained by paleontological data.•Four U–Pb dates across the Norian-Rhaetian Boundary support a long Rhaetian (∼8 Ma).•New global interpretation: variable carbon cycle dynamics, Panthalassa vs. Tethys.
The end-Triassic mass extinction is one of the big five extinction events in Phanerozoic Earth history. It is linked with the emplacement of the Central Atlantic Magmatic Province and a host of interconnected environmental and climatic responses that caused profound deterioration of terrestrial and marine biospheres. Current understanding, however, is hampered by (i) a geographically limited set of localities and data; (ii) incomplete stratigraphic records caused by low relative sea-level in European sections during the Late Triassic and earliest Jurassic; and (iii) major discrepancies in the estimated duration of the latest Triassic Rhaetian that limit spatiotemporal evaluation of climatic and biotic responses locally and globally. Here, we investigate the Late Triassic–Early Jurassic time interval from a stratigraphically well-preserved sedimentary succession deposited in tropical oceanic Panthalassa. We present diverse new data from the lower McCarthy Formation exposed at Grotto Creek (Wrangell Mountains, southern Alaska), including ammonoid, bivalve, hydrozoan, and conodont biostratigraphy; organic carbon isotope (δ13Corg) stratigraphy; and CA-ID TIMS zircon U–Pb dates. These data are consistent with a Norian-Rhaetian Boundary (NRB) of ∼209 Ma, providing new evidence to support a long duration of the Rhaetian. They also constrain the Triassic-Jurassic boundary (TJB) to a ∼6 m interval in the section. Our TJB δ13Corg record from Grotto Creek, in conjunction with previous data, demonstrates consistent features that not only appear correlative on a global scale but also shows local heterogeneities compared to some Tethyan records. Notably, smaller excursions within a large negative carbon isotope excursion NCIE known from Tethyan localities are absent in Panthalassan records. This new comparative isotopic record becomes useful for (i) distinguishing regional overprinting of the global signal; (ii) raising questions about the ubiquity of smaller-scale NCIEs across the TJB; and (iii) highlighting the largely unresolved regional vs. global scale of some presumed carbon cycle perturbations. These paleontological and geochemical data establish the Grotto Creek section as an important Upper Triassic to Lower Jurassic succession due to its paleogeographic position and complete marine record. Our record represents the best documentation of the NRB and TJB intervals from Wrangellia, and likely the entire North American Cordillera.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
It is a great privilege to contribute to the Reflections essays. In my particular case, this essay has allowed me to weave some of my major scientific contributions into a tapestry held together by ...what I have learned from three colleagues (Robert Letsinger, Gobind Khorana, and George Rathmann) who molded my career at every important junction. To these individuals, I remain eternally grateful, as they always led by example and showed many of us how to break new ground in both science and biotechnology. Relative to my scientific career, I have focused primarily on two related areas. The first is methodologies we developed for chemically synthesizing DNA and RNA. Synthetic DNA and RNA continue to be an essential research tool for biologists, biochemists, and molecular biologists. The second is developing new approaches for solving important biological problems using synthetic DNA, RNA, and their analogs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Phosphorodiamidate morpholinos (PMOs) are known as premier gene knockdown tools in developmental biology. PMOs are usually 25 nucleo-base-long morpholino subunits with a neutral phosphorodiamidate ...linkage. PMOs work via a steric blocking mechanism and are stable towards nucleases' inside cells. PMOs are usually synthesized using phosphoramidate P(V) chemistry. In this review, we will discuss the synthesis of PMOs, phosphoroamidate morpholinos (MO), and thiophosphoramidate morpholinos (TMO).
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Molecular imaging agents are extending the potential of noninvasive medical diagnosis from basic gross anatomic descriptions to complicated phenotypic characterizations based on the recognition of ...unique cell surface biochemical signatures. Although originally the purview of nuclear medicine, molecular imaging is now a prominent feature of most clinically relevant imaging modalities, in particular magnetic resonance (MR) imaging. MR nanoparticulate agents afford the opportunity not only for targeted diagnostic studies but also for image-monitored site-specific therapeutic delivery, much like the “magic bullet” envisioned by Paul Erhlich 100 years ago. Combining high-resolution MR molecular imaging with drug delivery will facilitate verification and quantification of treatment (ie, rational targeted therapy) and will offer new clinical approaches to many diseases.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPUK, VKSCE, ZAGLJ
Chemically modified oligonucleotides are being developed as a new class of medicines for curing conditions that previously remained untreatable. Three primary classes of therapeutic oligonucleotides ...are single-stranded antisense oligonucleotides (ASOs), double stranded small interfering RNAs (siRNAs), and oligonucleotides that induce exon skipping. Recently, ASOs, siRNAs, and exon skipping oligonucleotides have been approved for patients with unmet medical needs, and many other candidates are being tested in late stage clinical trials. In coming years, therapeutic oligonucleotides may match the promise of small molecules and antibodies. Interestingly, in the 1980s when we developed chemical methods for synthesizing oligonucleotides, no one would have imagined that these highly charged macromolecules could become future medicines. Indeed, the anionic nature and poor metabolic stability of the natural phosphodiester backbone provided a major challenge for the use of oligonucleotides as therapeutic drugs. Thus, chemical modifications of oligonucleotides were essential in order to improve their pharmacokinetic properties. Keeping this view in mind, my laboratory has developed a series of novel oligonucleotides where one or both nonbridging oxygens in the phosphodiester backbone are replaced with an atom or molecule that introduces molecular properties that enhance biological activity. We followed two complementary approaches. One was the use of phosphoramidites that could act directly as synthons for the solid phase synthesis of oligonucleotide analogues. This approach sometimes was not feasible due to instability of various synthons toward the reagents used during synthesis of oligonucleotides. Therefore, using a complementary approach, we developed phosphoramidite synthons that can be incorporated into oligonucleotides with minimum changes in the solid phase DNA synthesis protocols but contain a handle for generating appropriate analogues postsynthetically.This Account summarizes our efforts toward preparing these types of analogues over the past three decades and discusses synthesis and properties of backbone modified oligonucleotides that originated from the Caruthers' laboratory. For example, by replacing one of the internucleotide oxygens with an acetate group, we obtained so-called phosphonoacetate oligonucleotides that were stable to nucleases and, when delivered as esters, entered into cells unaided. Alternatively oligonucleotides bearing borane phosphonate linkages were found to be RNase H active and compatible with the endogenous RNA induced silencing complex (RISC). Oligonucleotides containing an alkyne group directly linked to phosphorus in the backbone were prepared as well and used to attach molecules such as amino acids and peptides.
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IJS, KILJ, NUK, PNG, UL, UM
This Article outlines the optimized chemical synthesis and preliminary biochemical characterization of a new oligonucleotide analogue called thiophosphoramidate morpholinos (TMOs). Their rational ...design hinges upon integrating two well-studied pharmacophores, namely, phosphorothioates (pS) and morpholinos, to create morpholino-pS hybrid oligonucleotides. Our simple synthesis strategy enables the easy incorporation of morpholino-pS moieties and therapeutically relevant sugar modifications in tandem to create novel oligonucleotide (ON) analogues that are hitherto unexplored in the oligotherapeutics arena. Exclusively TMO-modified ONs demonstrate high stability toward 3'-exonuclease. Hybridization studies show that TMO chimeras consisting of alternating TMO and DNA-pS subunits exhibit higher binding affinity toward complementary RNA relative to the canonical DNA/RNA duplex (∼10 °C). Oligonucleotides that consist entirely of TMO linkages also show higher RNA binding affinity but do not recruit ribonuclease H1 (RNase H1). Chimeric TMO analogues demonstrate high gene silencing efficacy, comparable to that of a chimeric 2'-OMe-pS/pO control, during
bioassay screens designed to evaluate their potential as microRNA inhibitors of hsa-miR-15b-5p in HeLa cells.
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IJS, KILJ, NUK, PNG, UL, UM
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