Earliest Holocene south Greenland ice sheet retreat within its late Holocene extent

Early Holocene summer warmth drove dramatic Greenland ice sheet (GIS) retreat. Subsequent insolation-driven cooling caused GIS margin readvance to late Holocene maxima, from which ice margins are now retreating. We use 10Be surface exposure ages from four locations between 69.4°N and 61.2°N to date when in the early Holocene south to west GIS margins retreated to within these late Holocene maximum extents. We find that this occurred at 11.1 ± 0.2 ka to 10.6 ± 0.5 ka in south Greenland, significantly earlier than previous estimates, and 6.8 ± 0.1 ka to 7.9 ± 0.1 ka in southwest to west Greenland, consistent with existing 10Be ages. At least in south Greenland, these 10Be ages likely provide a minimum constraint for when on a multicentury timescale summer temperatures after the last deglaciation warmed above late Holocene temperatures in the early Holocene. Current south Greenland ice margin retreat suggests that south Greenland may have now warmed to or above earliest Holocene summer temperatures

Sea-level constraints on the amplitude and source distribution of Meltwater Pulse 1A.

During the last deglaciation, sea levels rose as ice sheets retreated. This climate transition was punctuated by periods of more intense melting; the largest and most rapid of these—Meltwater Pulse 1A—occurred about 14,500 years ago, with rates of sea-level rise reaching approximately 4 m per century1, 2, 3. Such rates of rise suggest ice-sheet instability, but the meltwater sources are poorly constrained, thus limiting our understanding of the causes and impacts of the event4, 5, 6, 7. In particular, geophysical modelling studies constrained by tropical sea-level records1, 8, 9 suggest an Antarctic contribution of more than seven metres, whereas most reconstructions10 from Antarctica indicate no substantial change in ice-sheet volume around the time of Meltwater Pulse 1A. Here we use a glacial isostatic adjustment model to reinterpret tropical sea-level reconstructions from Barbados2, the Sunda Shelf3 and Tahiti1. According to our results, global mean sea-level rise during Meltwater Pulse 1A was between 8.6 and 14.6 m (95% probability). As for the melt partitioning, we find an allowable contribution from Antarctica of either 4.1 to 10.0 m or 0 to 6.9 m (95% probability), using two recent estimates11, 12 of the contribution from the North American ice sheets. We conclude that with current geologic constraints, the method applied here is unable to support or refute the possibility of a significant Antarctic contribution to Meltwater Pulse 1A

Pharmacological Targeting of Native CatSper Channels Reveals a Required Role in Maintenance of Sperm Hyperactivation

The four sperm-specific CatSper ion channel proteins are required for hyperactivated motility and male fertility, and for Ca2+ entry evoked by alkaline depolarization. In the absence of external Ca2+, Na+ carries current through CatSper channels in voltage-clamped sperm. Here we show that CatSper channel activity can be monitored optically with the [Na+]i-reporting probe SBFI in populations of intact sperm. Removal of external Ca2+ increases SBFI signals in wild-type but not CatSper2-null sperm. The rate of the indicated rise of [Na+]i is greater for sperm alkalinized with NH4Cl than for sperm acidified with propionic acid, reflecting the alkaline-promoted signature property of CatSper currents. In contrast, the [Na+]i rise is slowed by candidate CatSper blocker HC-056456 (IC50 ∼3 µM). HC-056456 similarly slows the rise of [Ca2+]i that is evoked by alkaline depolarization and reported by fura-2. HC-056456 also selectively and reversibly decreased CatSper currents recorded from patch-clamped sperm. HC-056456 does not prevent activation of motility by HCO3− but does prevent the development of hyperactivated motility by capacitating incubations, thus producing a phenocopy of the CatSper-null sperm. When applied to hyperactivated sperm, HC-056456 causes a rapid, reversible loss of flagellar waveform asymmetry, similar to the loss that occurs when Ca2+ entry through the CatSper channel is terminated by removal of external Ca2+. Thus, open CatSper channels and entry of external Ca2+ through them sustains hyperactivated motility. These results indicate that pharmacological targeting of the CatSper channel may impose a selective late-stage block to fertility, and that high-throughput screening with an optical reporter of CatSper channel activity may identify additional selective blockers with potential for male-directed contraception

The age of the opening of the Ice-Free Corridor and implications for the peopling of the Americas

The Clovis-first model for the peopling of the Americas by ∼13.4 ka has long invoked the Ice-Free Corridor (IFC) between the retreating margins of the Cordilleran and Laurentide ice sheets as the migration route from Alaska and the Yukon down to the Great Plains. Evidence from archaeology and ancient genomics, however, now suggests that pre-Clovis migrations occurred by at least ∼15.5 to 16.0 ka or earlier than most recent assessments of the age of IFC opening at ∼14 to 15 ka, lending support to the use of a Pacific coast migration route instead. Uncertainties in ages from the IFC used in these assessments, however, allow for an earlier IFC opening which would be consistent with the availability of the IFC as a migration route by ∼15.5 to 16.0 ka. Here, we use 64 cosmogenic (10Be) exposure ages to closely date the age of the full opening of the IFC at 13.8 ± 0.5 ka. Our results thus clearly establish that the IFC was not available for the first peopling of the Americas after the Last Glacial Maximum, whereas extensive geochronological data from the Pacific coast support its earlier availability as a coastal migration route

Automated data analysis to rapidly derive and communicate ecological insights from satellite-tag data: A case study of reintroduced red kites

Analysis of satellite-telemetry data mostly occurs long after it has been collected, due to the time and effort needed to collate and interpret such material. Such delayed reporting does reduce the usefulness of such data for nature conservation when timely information about animal movements is required. To counter this problem we present a novel approach which combines automated analysis of satellite-telemetry data with rapid communication of insights derived from such data. A relatively simple algorithm (comprising speed of movement and turning angle calculated from fixes), allowed instantaneous detection of excursions away from settlement areas and automated calculation of home ranges on the remaining data Automating the detection of both excursions and home range calculations enabled us to disseminate ecological insights from satellite-tag data instantaneously through a dedicated web portal to inform conservationists and wider audiences. We recommend automated analysis, interpretation and communication of satellite tag and other ecological data to advance nature conservation research and practice

Challenges and research priorities to understand interactions between climate, ice sheets and global mean sea level during past interglacials

Quaternary interglacials provide key observations of the Earth system's responses to orbital and greenhouse gas forcing. They also inform on the capabilities of Earth system models, used for projecting the polar ice-sheet and sea-level responses to a regional warmth comparable to that expected by 2100 C.E. However, a number of uncertainties remain regarding the processes and feedbacks linking climate, ice-sheet and sea-level changes during past warm intervals. Here, we delineate the major research questions that need to be resolved and future research directions that should be taken by the paleoclimate, sea-level and ice-sheet research communities in order to increase confidence in the use of past interglacial climate, ice-sheet and sea-level reconstructions to constrain future predictions. These questions were formulated during a joint workshop held by the PAGES-INQUA PALSEA (PALeo constraints on SEA level rise) and the PAGES-PMIP QUIGS (QUaternary InterGlacialS) Working Groups in September 2018.PAGE

Fulvestrant: an oestrogen receptor antagonist with a novel mechanism of action

Due to their favourable tolerability profiles, endocrine therapies have long been considered the treatment of choice for hormone-sensitive metastatic breast cancer. However, the oestrogen agonist effects of the available selective oestrogen receptor modulators, such as tamoxifen, and the development of cross-resistance between endocrine therapies with similar modes of action have led to the need for new treatments that act through different mechanisms. Fulvestrant (‘Faslodex’) is the first of a new type of endocrine treatment – an oestrogen receptor (ER) antagonist that downregulates the ER and has no agonist effects. This article provides an overview of the current understanding of ER signalling and illustrates the unique mode of action of fulvestrant. Preclinical and clinical study data are presented in support of the novel mechanism of action of this new type of ER antagonist

A Prospective Study of the Association of Metacognitive Beliefs and Processes with Persistent Emotional Distress After Diagnosis of Cancer

Two hundred and six patients, diagnosed with primary breast or prostate cancer completed self-report questionnaires on two occasions: before treatment (T1) and 12 months later (T2). The questionnaires included: the Hospital Anxiety and Depression Scale; Impact of Events Scale; the Metacognitions Questionnaire-30 (MCQ-30) and the Illness Perceptions Questionnaire-revised. A series of regression analyses indicated that metacognitive beliefs at T1 predicted between 14 and 19 % of the variance in symptoms of anxiety, depression and trauma at T2 after controlling for age and gender. For all three outcomes, the MCQ-30 subscale ‘negative beliefs about worry’ made the largest individual contribution with ‘cognitive confidence’ also contributing in each case. For anxiety, a third metacognitive variable, ‘positive beliefs about worry’ also predicted variance in T2 symptoms. In addition, hierarchical analyses indicated that metacognitive beliefs explained a small but significant amount of variance in T2 anxiety (2 %) and T2 depression (4 %) over and above that explained by demographic variables, T1 symptoms and T1 illness perceptions. The findings suggest that modifying metacognitive beliefs and processes has the potential to alleviate distress associated with cancer

Evidence for solar cycles in a late Holocene speleothem record from Dongge Cave, China

The association between solar activity and Asian monsoon (AM) remains unclear. Here we evaluate the possible connection between them based on a precisely-dated, high-resolution speleothem oxygen isotope record from Dongge Cave, southwest China during the past 4.2 thousand years (ka). Without being adjusted chronologically to the solar signal, our record shows a distinct peak-to-peak correlation with cosmogenic nuclide 14C, total solar irradiance (TSI) and sunspot number (SN) at multi-decadal to centennial timescales. Further cross-wavelet analyses between our calcite δ18O and atmospheric 14C show statistically strong coherence at three typical periodicities of ~80, 200 and 340 years, suggesting important roles of solar activities in modulating AM changes at those timescales. Our result has further indicated a better correlation between our calcite δ18O record and atmospheric 14C than between our record and TSI. This better correlation may imply that the Sun–monsoon connection is dominated most likely by cosmic rays and oceanic circulation (both associated to atmospheric 14C), instead of the direct solar heating (TSI)