Climate reconstruction from paired oxygen-isotope analyses of chironomid larval head capsules and endogenic carbonate (Hawes Water, UK) - Potential and problems

Temperature and the oxygen isotopic composition (δ18O) of meteoric water are both important palaeoclimatic variables, but separating their influences on proxies such as the δ18O of lake carbonates is often problematic. The large temperature variations that are known to have occurred in the northern mid-latitudes during the Late Glacial make this interval an excellent test for a novel approach that combines oxygen-isotope analyses of chironomid larval head capsules with co-occurring endogenic carbonate. We apply this approach to a Late Glacial lake sediment sequence from Hawes Water (NW England). Oxygen-isotope values in chironomid head capsules show marked variations during the Late Glacial that are similar to the oxygen isotope record from endogenic carbonate. However, summer temperature reconstructions based on the paired isotope values and fractionation between chironomids and calcite yield values between −20 and −4 °C, which are unrealistic and far lower than reconstructions based on chironomid assemblages at the same site. The composition of a limited number of samples of fossil chironomid larval head capsules determined using Pyrolysis gas-chromatography mass spectrometry indicates the presence of aliphatic geopolymers, suggesting that diagenetic alteration of the head capsules has systematically biased the isotope-derived temperature estimates. However, a similar trend in the isotope records of the two sources suggests that a palaeoclimate signal is still preserved

A community effort in SARS-CoV-2 drug discovery.

peer reviewedThe COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against Covid-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find 'consensus compounds'. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding-, cleavage-, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS-CoV-2 treatments.R-AGR-3826 - COVID19-14715687-CovScreen (01/06/2020 - 31/01/2021) - GLAAB Enric

Experimental determination of the temperature dependence of oxygen-isotope fractionation between water and chitinous head capsules of chironomid larvae

Oxygen-isotope values of invertebrate cuticle preserved in lake sediments have been used in palaeoenvironmental reconstructions, generally with the assumption that fractionation of oxygen isotopes between cuticle and water (αcuticle−H2O) is independent of temperature. We cultured chironomid larvae in the laboratory with labelled oxygen-isotope water and across a range of closely controlled temperatures from 5 to 25 °C in order to test the hypothesis that fractionation of oxygen isotopes between chironomid head capsules and water (αchironomid−H2O) is independent of temperature. Results indicate that the hypothesis can be rejected, and that αchironomid−H2O decreases with increasing temperature. The scatter in the data suggests that further experiments are needed to verify the relationship. However, these results indicate that temperature-dependence of αchironomid−H2O should be considered when chironomid δ18O is used as a paleoenvironmental proxy, especially in cases where data from chironomids are combined with oxygen-isotope values from other materials for which fractionation is temperature dependent, such as calcite, in order to derive reconstructions of past water temperature

Growth arrest specific 6 concentration is increased in the cerebrospinal fluid of patients with Alzheimer's disease

Growth arrest specific 6 (Gas6) has neurotrophic and neuroinflammatory functions, and may play a role in Alzheimer's disease (AD). In keeping with this hypothesis, we observed that cerebrospinal fluid (CSF) Gas6 is increased in AD patients compared to controls (63 versus 67 subjects; median value 13.3 versus 9.1ng/ml; p<0.0001). Thereafter, we assessed whether CSF Gas6 concentration was correlated to the following parameters: disease duration, MMSE score two years after clinical diagnosis, AD CSF biomarkers, and years of formal schooling. We detected an inverse correlation between CSF Gas6 levels at diagnosis and both disease duration (p<0.0001) and decrease in the MMSE score two years later (p<0.0001). Conversely, we found no correlation between CSF Gas6 and both AD biomarkers and years of formal schooling. In conclusion, our results suggest that upregulation of CSF Gas6 may be part of a defensive response aimed at counteracting AD progression

Climate reconstruction from paired oxygen-isotope analyses of chironomid larval head capsules and endogenic carbonate (Hawes Water, UK) - Potential and problems

Temperature and the oxygen isotopic composition (δ18O) of meteoric water are both important palaeoclimatic variables, but separating their influences on proxies such as the δ18O of lake carbonates is often problematic. The large temperature variations that are known to have occurred in the northern mid-latitudes during the Late Glacial make this interval an excellent test for a novel approach that combines oxygen-isotope analyses of chironomid larval head capsules with co-occurring endogenic carbonate. We apply this approach to a Late Glacial lake sediment sequence from Hawes Water (NW England). Oxygen-isotope values in chironomid head capsules show marked variations during the Late Glacial that are similar to the oxygen isotope record from endogenic carbonate. However, summer temperature reconstructions based on the paired isotope values and fractionation between chironomids and calcite yield values between −20 and −4 °C, which are unrealistic and far lower than reconstructions based on chironomid assemblages at the same site. The composition of a limited number of samples of fossil chironomid larval head capsules determined using Pyrolysis gas-chromatography mass spectrometry indicates the presence of aliphatic geopolymers, suggesting that diagenetic alteration of the head capsules has systematically biased the isotope-derived temperature estimates. However, a similar trend in the isotope records of the two sources suggests that a palaeoclimate signal is still preserved

Climate reconstruction from paired oxygen-isotope analyses of chironomid larval head capsules and endogenic carbonate (Hawes Water, UK) - Potential and problems

Temperature and the oxygen isotopic composition (δ18O) of meteoric water are both important palaeoclimatic variables, but separating their influences on proxies such as the δ18O of lake carbonates is often problematic. The large temperature variations that are known to have occurred in the northern mid-latitudes during the Late Glacial make this interval an excellent test for a novel approach that combines oxygen-isotope analyses of chironomid larval head capsules with co-occurring endogenic carbonate. We apply this approach to a Late Glacial lake sediment sequence from Hawes Water (NW England). Oxygen-isotope values in chironomid head capsules show marked variations during the Late Glacial that are similar to the oxygen isotope record from endogenic carbonate. However, summer temperature reconstructions based on the paired isotope values and fractionation between chironomids and calcite yield values between −20 and −4 °C, which are unrealistic and far lower than reconstructions based on chironomid assemblages at the same site. The composition of a limited number of samples of fossil chironomid larval head capsules determined using Pyrolysis gas-chromatography mass spectrometry indicates the presence of aliphatic geopolymers, suggesting that diagenetic alteration of the head capsules has systematically biased the isotope-derived temperature estimates. However, a similar trend in the isotope records of the two sources suggests that a palaeoclimate signal is still preserved

Climate reconstruction from paired oxygen-isotope analyses of chironomid larval head capsules and endogenic carbonate (Hawes Water, UK) - Potential and problems

Temperature and the oxygen isotopic composition (δ18O) of meteoric water are both important palaeoclimatic variables, but separating their influences on proxies such as the δ18O of lake carbonates is often problematic. The large temperature variations that are known to have occurred in the northern mid-latitudes during the Late Glacial make this interval an excellent test for a novel approach that combines oxygen-isotope analyses of chironomid larval head capsules with co-occurring endogenic carbonate. We apply this approach to a Late Glacial lake sediment sequence from Hawes Water (NW England). Oxygen-isotope values in chironomid head capsules show marked variations during the Late Glacial that are similar to the oxygen isotope record from endogenic carbonate. However, summer temperature reconstructions based on the paired isotope values and fractionation between chironomids and calcite yield values between −20 and −4 °C, which are unrealistic and far lower than reconstructions based on chironomid assemblages at the same site. The composition of a limited number of samples of fossil chironomid larval head capsules determined using Pyrolysis gas-chromatography mass spectrometry indicates the presence of aliphatic geopolymers, suggesting that diagenetic alteration of the head capsules has systematically biased the isotope-derived temperature estimates. However, a similar trend in the isotope records of the two sources suggests that a palaeoclimate signal is still preserved