Planktic Foraminiferal and Pteropod Contributions to Carbon Dynamics in the Arctic Ocean (North Svalbard Margin)

Planktic foraminifera and shelled pteropods are some of the major producers of calcium carbonate (CaCO3) in the ocean. Their calcitic (foraminifera) and aragonitic (pteropods) shells are particularly sensitive to changes in the carbonate chemistry and play an important role for the inorganic and organic carbon pump of the ocean. Here, we have studied the abundance distribution of planktic foraminifera and pteropods (individuals m–3) and their contribution to the inorganic and organic carbon standing stocks (μg m–3) and export production (mg m–2 day–1) along a longitudinal transect north of Svalbard at 81° N, 22–32° E, in the Arctic Ocean. This transect, sampled in September 2018 consists of seven stations covering different oceanographic regimes, from the shelf to the slope and into the deep Nansen Basin. The sea surface temperature ranged between 1 and 5°C in the upper 300 m. Conditions were supersaturated with respect to CaCO3 (Ω > 1 for both calcite and aragonite). The abundance of planktic foraminifera ranged from 2.3 to 52.6 ind m–3 and pteropods from 0.1 to 21.3 ind m–3. The planktic foraminiferal population was composed mainly of the polar species Neogloboquadrina pachyderma (55.9%) and the subpolar species Turborotalita quinqueloba (21.7%), Neogloboquadrina incompta (13.5%) and Globigerina bulloides (5.2%). The pteropod population was dominated by the polar species Limacina helicina (99.6%). The rather high abundance of subpolar foraminiferal species is likely connected to the West Spitsbergen Current bringing warm Atlantic water to the study area. Pteropods dominated at the surface and subsurface. Below 100 m water depth, foraminifera predominated. Pteropods contribute 66–96% to the inorganic carbon standing stocks compared to 4–34% by the planktic foraminifera. The inorganic export production of planktic foraminifera and pteropods together exceeds their organic contribution by a factor of 3. The overall predominance of pteropods over foraminifera in this high Arctic region during the sampling period suggest that inorganic standing stocks and export production of biogenic carbonate would be reduced under the effects of ocean acidification

Conserved chromosome 2q31 conformations are associated with transcriptional regulation of GAD1 GABA synthesis enzyme and altered in prefrontal cortex of subjects with schizophrenia

Little is known about chromosomal loopings involving proximal promoter and distal enhancer elements regulating GABAergic gene expression, including changes in schizophrenia and other psychiatric conditions linked to altered inhibition. Here, we map in human chromosome 2q31 the 3D configuration of 200 kb of linear sequence encompassing the GAD1 GABA synthesis enzyme gene locus, and we describe a loop formation involving the GAD1 transcription start site and intergenic noncoding DNA elements facilitating reporter gene expression. The GAD1-TSS(-50kbLoop) was enriched with nucleosomes epigenetically decorated with the transcriptional mark, histone H3 trimethylated at lysine 4, and was weak or absent in skin fibroblasts and pluripotent stem cells compared with neuronal cultures differentiated from them. In the prefrontal cortex of subjects with schizophrenia, GAD1-TSS(-50kbLoop) was decreased compared with controls, in conjunction with downregulated GAD1 expression. We generated transgenic mice expressing Gad2 promoter-driven green fluorescent protein-conjugated histone H2B and confirmed that Gad1-TSS(-55kbLoop), the murine homolog to GAD1-TSS(-50kbLoop), is a chromosomal conformation specific for GABAergic neurons. In primary neuronal culture, Gad1-TSS(-55kbLoop) and Gad1 expression became upregulated when neuronal activity was increased. We conclude that 3D genome architectures, including chromosomal loopings for promoter-enhancer interactions involved in the regulation of GABAergic gene expression, are conserved between the rodent and primate brain, and subject to developmental and activity-dependent regulation, and disordered in some cases with schizophrenia. More broadly, the findings presented here draw a connection between noncoding DNA, spatial genome architecture, and neuronal plasticity in development and disease

The effects of low doses of pregabalin on morphine analgesia in advanced cancer patients

Abstract OBJECTIVES: The aim of this study was to evaluate the opioid response in patients receiving morphine and pregabalin, independently from the presumed pain mechanisms, in comparison with patients receiving morphine treatment only. METHODS: A multicenter prospective randomized controlled study was carried out in a sample of 70 advanced cancer patients with pain requiring strong opioids. Thirty-five patients (group MO) were randomized to receive sustained-release morphine using initial doses of 60 mg/day. Thirty-five patients (group MO-PR) were randomized to start the same morphine doses and pregabalin in increasing doses, starting with 25 mg/day up to 150 mg/day in one week. The following data were also recorded before starting the treatments (T0) and then at week intervals for four weeks (W1-4): age, gender, primary cancer and known metastases, pain causes and mechanisms, symptoms associated with opioid therapy, pain intensity, Brief Pain Inventory (BPI), morphine doses and escalation indexes (OEIs), and quality of life. RESULTS: Forty-eight patients completed the study, twenty-eight and sixteen patients in group MO and MO-PR, respectively. Twenty patients were females, the mean age was 65.5 (± 10.3), and the mean Karnofsky status was 66.0 (± 18.9). No differences between groups were found in age (P = 0.839), Karnofsky status (P = 0.741), opioid doses as well as escalation indexes (OEI mg, P = 0.260, and OEI%, P = 0.270). No differences between the two groups were found in quality of life and all BPI items. CONCLUSION: The use of low doses of pregabalin added to morphine therapy in advanced cancer patients does not seem to provide advantageous analgesic effects, despite limitations of the present study due to the number of drop-outs

Dickkopf-1 Overexpression in vitro Nominates Candidate Blood Biomarkers Relating to Alzheimer's Disease Pathology

Previous studies suggest that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, plays a role in amyloid-induced toxicity and hence Alzheimer's disease (AD). However, the effect of DKK1 expression on protein expression, and whether such proteins are altered in disease, is unknown. We aim to test whether DKK1 induced protein signature obtained in vitro were associated with markers of AD pathology as used in the amyloid/tau/neurodegeneration (ATN) framework as well as with clinical outcomes. We first overexpressed DKK1 in HEK293A cells and quantified 1,128 proteins in cell lysates using aptamer capture arrays (SomaScan) to obtain a protein signature induced by DKK1. We then used the same assay to measure the DKK1-signature proteins in human plasma in two large cohorts, EMIF (n = 785) and ANM (n = 677). We identified a 100-protein signature induced by DKK1 in vitro. Subsets of proteins, along with age and apolipoprotein E ɛ 4 genotype distinguished amyloid pathology (A + T-N-, A+T+N-, A+T-N+, and A+T+N+) from no AD pathology (A-T-N-) with an area under the curve of 0.72, 0.81, 0.88, and 0.85, respectively. Furthermore, we found that some signature proteins (e.g., Complement C3 and albumin) were associated with cognitive score and AD diagnosis in both cohorts. Our results add further evidence for a role of DKK regulation of Wnt signaling in AD and suggest that DKK1 induced signature proteins obtained in vitro could reflect theATNframework as well as predict disease severity and progression in vivo

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

On the use of surrogate-based modeling for the numerical analysis of Low Impact Development techniques

Mechanistic models have proven to be accurate tools for the numerical analysis of the hydraulic behavior of Low Impact Development (LIDs) techniques. However, their widespread adoption has been limited by their computational cost. In this view, surrogate modeling is focused on developing and using a computationally inexpensive surrogate of the original model. While having been previously applied to various water-related and environmental modeling problems, no studies have used surrogate models for the analysis of LIDs. The aim of this research thus was to investigate the benefit of surrogate-based modeling in the numerical analysis of LIDs. The kriging technique was used to approximate the deterministic response of the widely used mechanistic model HYDRUS-2D, which was employed to simulate the variably-saturated hydraulic behavior of a contained stormwater filter. The Nash-Sutcliffe efficiency (NSE) index was used to compare the simulated and measured outflows and as the variable of interest for the construction of the response surface. The validated kriging model was first used to carry out a Global Sensitivity Analysis of the unknown soil hydraulic parameters of the filter layer, revealing that only the shape parameter α and the saturated hydraulic conductivity Ks significantly affected the model response. Next, the Particle Swarm Optimization algorithm was used to estimate their values. The NSE value of 0.85 indicated a good accuracy of estimated parameters. Finally, the calibrated model was validated against an independent set of measured outflows with a NSE value of 0.8, which again corroborated the reliability of the surrogate-based optimized parameters

Structural Perturbation of alphaB-Crystallin by Zinc and Temperature related to its chaperonelike activity

alphaB-crystallin is a small heat shock protein that shows chaperone-like activity, as it protects the aggregation of denatured proteins. In this work, the possible relationships between structural characteristics and the biological activity of alphaB-crystallin were investigated on the native protein and on the protein undergoing the separate effects of metal ligation and temperature. The chaperone-like activity of alphaB-crystallin increased in the presence of zinc and when temperature was increased. By using fluorescent probes to monitor hydrophobic surfaces on alphaB-crystallin, it was found that exposed hydrophobic patches on the protein surface increased significantly both in the presence of zinc and when the temperature was raised from 25 to 37 degrees C. The zinc-induced increased exposure of lipophilic residues is in agreement with theoretical calculations performed on 3D-models of monomeric alphaB-crystallin, and may be significant to its increased biological activity

Structural perturbation of alphaB-crystallin by zinc and temperature related to its <i>chaperone-like</i> activity

αB-crystallin is a small heat shock protein that shows chaperone-like activity, as it protects the aggregation of denatured proteins. In this work, the possible relationships between structural characteristics and the biological activity of αB-crystallin were investigated on the native protein and on the protein undergoing the separate effects of metal ligation and temperature. The chaperone-like activity of αB-crystallin increased in the presence of zinc and when temperature was increased. By using fluorescent probes to monitor hydrophobic surfaces on αB-crystallin, it was found that exposed hydrophobic patches on the protein surface increased significantly both in the presence of zinc and when the temperature was raised from 25 to 37°C. The zinc-induced increased exposure of lipophilic residues is in agreement with theoretical calculations performed on 3D-models of monomeric αB-crystallin, and may be significant to its increased biological activity

Seasonality of marine calcifiers in the northern Barents Sea: Spatiotemporal distribution of planktonic foraminifers and shelled pteropods and their contribution to carbon dynamics

The Barents Sea is presently undergoing rapid warming and the sea-ice edge and the productive zones are retreating northward at accelerating rates. Planktonic foraminifers and shelled pteropods are ubiquitous marine calcifiers that play an important role in the carbon budget and being particularly sensitive to ocean biogeochemical changes and ocean acidification. Their distribution at high latitudes have rarely been studied, and usually only for the summer season. Here we present results of their distribution patterns in the upper 300 m in the water column (individuals m−3), protein content and size distribution on a seasonal basis to estimate their inorganic and organic carbon standing stocks (µg m−3) and export production (mg m−2 d−1). The study area constitutes a latitudinal transect in the northern Barents Sea from 76˚ N to 82˚ N including seven stations through both Atlantic, Arctic, and Polar surface water regimes and the marginal and seasonal sea-ice zones. The transect was sampled in 2019 (August and December) and 2021 (March, May, and July). The highest carbon standing stocks and export production were found at the Polar seasonally sea-ice covered shelf stations with the contribution from shelled pteropods being significantly higher than planktonic foraminifers during all seasons. We recorded the highest production of foraminifers and pteropods in summer (August 2019 and July 2021) and autumn (December 2019) followed by spring (May 2021), and the lowest in winter (March 2021)