Geodynamically corrected Pliocene shoreline elevations in Australia consistent with midrange projections of Antarctic ice loss.

The Mid-Pliocene represents the most recent interval in Earth history with climatic conditions similar to those expected in the coming decades. Mid-Pliocene sea level estimates therefore provide important constraints on projections of future ice sheet behavior and sea level change but differ by tens of meters due to local distortion of paleoshorelines caused by mantle dynamics. We combine an Australian sea level marker compilation with geodynamic simulations and probabilistic inversions to quantify and remove these post-Pliocene vertical motions at continental scale. Dynamic topography accounts for most of the observed sea level marker deflection, and correcting for this effect and glacial isostatic adjustment yields a Mid-Pliocene global mean sea level of +16.0 (+10.4 to +21.5) m (50th/16th to 84th percentiles). Recalibration of recent high-end sea level projections using this revised estimate implies a more stable Antarctic Ice Sheet under future warming scenarios, consistent with midrange forecasts of sea level rise that do not incorporate a marine ice cliff instability.

Constraining the contribution of the Antarctic Ice Sheet to Last Interglacial sea level.

Polar temperatures during the Last Interglacial [LIG; ~129 to 116 thousand years (ka)] were warmer than today, making this time period an important testing ground to better understand how ice sheets respond to warming. However, it remains debated how much and when the Antarctic and Greenland ice sheets changed during this period. Here, we present a combination of new and existing absolutely dated LIG sea-level observations from Britain, France, and Denmark. Because of glacial isostatic adjustment (GIA), the LIG Greenland ice melt contribution to sea-level change in this region is small, which allows us to constrain Antarctic ice change. We find that the Antarctic contribution to LIG global mean sea level peaked early in the interglacial (before 126 ka), with a maximum contribution of 5.7 m (50th percentile, 3.6 to 8.7 m central 68% probability) before declining. Our results support an asynchronous melt history over the LIG, with an early Antarctic contribution followed by later Greenland Ice Sheet mass loss.

The origin of carbonate mud and implications for global climate.

Carbonate mud represents one of the most important geochemical archives for reconstructing ancient climatic, environmental, and evolutionary change from the rock record. Mud also represents a major sink in the global carbon cycle. Yet, there remains no consensus about how and where carbonate mud is formed. Here, we present stable isotope and trace-element data from carbonate constituents in the Bahamas, including ooids, corals, foraminifera, and algae. We use geochemical fingerprinting to demonstrate that carbonate mud cannot be sourced from the abrasion and mixture of any combination of these macroscopic grains. Instead, an inverse Bayesian mixing model requires the presence of an additional aragonite source. We posit that this source represents a direct seawater precipitate. We use geological and geochemical data to show that "whitings" are unlikely to be the dominant source of this precipitate and, instead, present a model for mud precipitation on the bank margins that can explain the geographical distribution, clumped-isotope thermometry, and stable isotope signature of carbonate mud. Next, we address the enigma of why mud and ooids are so abundant in the Bahamas, yet so rare in the rest of the world: Mediterranean outflow feeds the Bahamas with the most alkaline waters in the modern ocean (>99.7th-percentile). Such high alkalinity appears to be a prerequisite for the nonskeletal carbonate factory because, when Mediterranean outflow was reduced in the Miocene, Bahamian carbonate export ceased for 3-million-years. Finally, we show how shutting off and turning on the shallow carbonate factory can send ripples through the global climate system.

Sea-level trends across The Bahamas constrain peak last interglacial ice melt.

During the last interglacial (LIG) period, global mean sea level (GMSL) was higher than at present, likely driven by greater high-latitude insolation. Past sea-level estimates require elevation measurements and age determination of marine sediments that formed at or near sea level, and those elevations must be corrected for glacial isostatic adjustment (GIA). However, this GIA correction is subject to uncertainties in the GIA model inputs, namely, Earth's rheology and past ice history, which reduces precision and accuracy in estimates of past GMSL. To better constrain the GIA process, we compare our data and existing LIG sea-level data across the Bahamian archipelago with a suite of 576 GIA model predictions. We calculated weights for each GIA model based on how well the model fits spatial trends in the regional sea-level data and then used the weighted GIA corrections to revise estimates of GMSL during the LIG. During the LIG, we find a 95% probability that global sea level peaked at least 1.2 m higher than today, and it is very unlikely (5% probability) to have exceeded 5.3 m. Estimates increase by up to 30% (decrease by up to 20%) for portions of melt that originate from the Greenland ice sheet (West Antarctic ice sheet). Altogether, this work suggests that LIG GMSL may be lower than previously assumed.

Giant boulders and Last Interglacial storm intensity in the North Atlantic.

As global climate warms and sea level rises, coastal areas will be subject to more frequent extreme flooding and hurricanes. Geologic evidence for extreme coastal storms during past warm periods has the potential to provide fundamental insights into their future intensity. Recent studies argue that during the Last Interglacial (MIS 5e, ∼128-116 ka) tropical and extratropical North Atlantic cyclones may have been more intense than at present, and may have produced waves larger than those observed historically. Such strong swells are inferred to have created a number of geologic features that can be observed today along the coastlines of Bermuda and the Bahamas. In this paper, we investigate the most iconic among these features: massive boulders atop a cliff in North Eleuthera, Bahamas. We combine geologic field surveys, wave models, and boulder transport equations to test the hypothesis that such boulders must have been emplaced by storms of greater-than-historical intensity. By contrast, our results suggest that with the higher relative sea level (RSL) estimated for the Bahamas during MIS 5e, boulders of this size could have been transported by waves generated by storms of historical intensity. Thus, while the megaboulders of Eleuthera cannot be used as geologic proof for past "superstorms," they do show that with rising sea levels, cliffs and coastal barriers will be subject to significantly greater erosional energy, even without changes in storm intensity.

Anxiogenic and Stressor Effects of the Hypothalamic Neuropeptide RFRP-3 Are Overcome by the NPFFR Antagonist GJ14.

RFamide-related peptide-3 (RFRP-3) is a recently discovered neuropeptide that has been proposed to play a role in the stress response. We aimed to elucidate the role of RFRP-3 and its receptor, neuropeptide FF (NPFF1R), in modulation of stress and anxiety responses. To achieve this, we characterized a new NPFF1R antagonist because our results showed that the only commercially available putative antagonist, RF9, is in fact an agonist at both NPFF1R and the kisspeptin receptor (KISS1R). We report here the identification and pharmacological characterization of GJ14, a true NPFFR antagonist. In in vivo tests of hypothalamic-pituitary-adrenal (HPA) axis function, GJ14 completely blocked RFRP-3-induced corticosterone release and neuronal activation in CRH neurons. Furthermore, chronic infusion of GJ14 led to anxiolytic-like behavior, whereas RFRP-3 infusion had anxiogenic effects. Mice receiving chronic RFRP-3 infusion also had higher basal circulating corticosterone levels. These results indicate a stimulatory action of RFRP-3 on the HPA axis, consistent with the dense expression of NPFF1R in the vicinity of CRH neurons. Importantly, coinfusion of RFRP-3 and GJ14 completely reversed the anxiogenic and HPA axis-stimulatory effects of RFRP-3. Here we have established the role of RFRP-3 as a regulator of stress and anxiety. We also show that GJ14 can reverse the effects of RFRP-3 both in vitro and in vivo. Infusion of GJ14 causes anxiolysis, revealing a novel potential target for treating anxiety disorders.

Phosphatidylinositol mannoside ether analogues: syntheses and interleukin-12-inducing properties.

Phosphatidylinositol mannosides (PIMs) isolated from mycobacteria have been identified as an important class of glycolipids with significant immune modulating properties. We present here the syntheses of phosphatidylinositol dimannoside ether analogues 2 and 3 and evaluate their interleukin-12 (IL-12)-inducing properties along with dipalmitoyl PIM2 (1) in an in vitro bovine dendritic cell assay. Both synthetic PIM analogues and synthetic dipalmitoyl PIM2 (1) were effective at enhancing IL-12 production by immature bovine dendritic cells. Unexpectedly, ether analogue 2 was significantly more active than dipalmitoyl PIM2 (1) which indicates that modified PIM compounds can be strongly immunoactive and may have significant adjuvant activities.

Synthesis and structure of phosphatidylinositol dimannoside.

(R)-tuberculostearic acid (2) was synthesized in seven steps from (S)-citronellol (5). The carbon chain of 2 was assembled by copper-catalyzed cross coupling of (S)-citronellol tosylate (6) and hexylmagnesium bromide; subsequent ozonolysis and reaction with 6-benzyloxyhexylmagnesium bromide furnished alcohol 10. Functional group manipulation afforded (R)-2 in 49% overall yield from 5. DCC coupling of (R)-2 with 3-O-benzyl-1-O-palmitoyl-sn-glycerol (16), followed by hydrogenolytic removal of the benzyl group and treatment with benzyl bis(diisopropyl)phosphoramidite, afforded phosphoramidite 20. Tetrazole-mediated coupling of 20 with PIM1 head group 21 gave 22, and subsequent debenzylation afforded phosphatidylinositol mono-mannoside, PIM1 (23). Similarly, coupling of 20 and 24 and removal of the benzyl protecting groups gave PIM2 (1c). Both 23 and 1c have a clearly defined acylation pattern, which was confirmed by mass spectrometry, with sn-1 palmitoyl and sn-2 tuberculostearoyl groups on the glycerol moiety. Both 23 and 1c were shown to modulate the release of the pro-inflammatory cytokine, IL-12, in a dendritic cell assay.