bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristic Depths, Fluxes, and Timescales for Greenland's Tidewater Glacier Fjords From Subglacial Discharge‐Driven Upwelling During Summer
Authors: Slater D. A. , Carroll D. , Oliver H. , Hopwood M. J. , Straneo F. , Wood M. , Willis J. K. , Morlighem M. 
Published: May 2022

AbstractGreenland's glacial fjords are a key bottleneck in the earth system, regulating exchange of heat, freshwater and nutrients between the ice sheet and ocean and hosting societally important fisheries. We combine recent bathymetric, atmospheric, and oceanographic data with a buoyant plume model to show that summer subglacial discharge from 136 tidewater glaciers, amounting to 0.02 Sv of freshwater, drives 0.6–1.6 Sv of upwelling. Bathymetric analysis suggests that this is sufficient to renew most major fjords within a single summer, and that these fjords provide a path to the continental shelf that is deeper than 200 m for two‐thirds of the glaciers. Our study provides a first pan‐Greenland inventory of tidewater glacier fjords and quantifies regional and ice sheet‐wide upwelling fluxes. This analysis provides important context for site‐specific studies and is a step toward implementing fjord‐scale heat, freshwater and nutrient fluxes in large‐scale ice sheet and climate models.
The Tides of Enceladus' Porous Core
Authors: Rovira‐Navarro Marc , Katz Richard F. , Liao Yang , van der Wal Wouter , Nimmo Francis 
Published: May 2022

AbstractThe inferred density of Enceladus' core, together with evidence of hydrothermal activity within the moon, suggests that the core is porous. Tidal dissipation in an unconsolidated core has been proposed as the main source of Enceladus' geological activity. However, the tidal response of its core has generally been modeled assuming it behaves viscoelastically rather than poroviscoelastically. In this work, we analyze the poroviscoelastic response to better constrain the distribution of tidal dissipation within Enceladus. A poroviscoelastic body has a different tidal response than a viscoelastic one; pressure within the pores alters the stress field and induces a Darcian porous flow. This flow represents an additional pathway for energy dissipation. Using Biot's theory of poroviscoelasticity, we develop a new framework to obtain the tidal response of a spherically symmetric, self‐gravitating moon with porous layers and apply it to Enceladus. We show that the boundary conditions at the interface of the core and overlying ocean play a key role in the tidal response. The ocean hinders the development of a large‐amplitude Darcian flow, making negligible the Darcian contribution to the dissipation budget. We therefore infer that Enceladus' core can be the source of its geological activity only if it has a low rigidity and a very low viscosity. A future mission to Enceladus could test this hypothesis by measuring the phase lags of tidally induced changes of gravitational potential and surface displacements.
Sensitivity of the Arctic Sea Ice Cover to the Summer Surface Scattering Layer
Authors: Smith Madison M. , Light Bonnie , Macfarlane Amy R. , Perovich Don K. , Holland Marika M. , Shupe Matthew D. 
Published: May 2022

AbstractThe “surface scattering layer” (SSL) is the highly‐scattering, coarse‐grained ice layer that forms on the surface of melting, drained sea ice during spring and summer. Ice of sufficient thickness with an SSL has an observed persistent broadband albedo of ∼0.65, resulting in a strong influence on the regional solar partitioning. Experiments during the Multidisciplinary drifting Observatory for the Study of the Arctic Climate expedition showed that the SSL re‐forms in approximately 1 day following manual removal. Coincident spectral albedo measurements provide insight into the SSL evolution, where albedo increased on sunny days with higher solar insolation. Comparison with experiments in radiative transfer and global climate models show that the sea ice albedo is greatly impacted by the SSL thickness. The presence of SSL is a significant component of the ice‐albedo feedback, with an albedo impact of the same order as melt ponds. Changes in SSL and implications for Arctic sea ice within a warming climate are uncertain.
Record Low Arctic Sea Ice Extent in 2012 Linked to Two‐Year La Niña‐Driven Sea Surface Temperature Pattern
Authors: Jeong Hyein , Park Hyo‐Seok , Stuecker Malte F. , Yeh Sang‐Wook 
Published: May 2022

AbstractArctic summer sea ice decline accelerated from the mid‐2000s to 2012, with the 2012 record low remaining unbroken. While frequent La Niña events during this period have been suggested as a driver of this trend acceleration, no convincing evidence has been presented. Here, using a climate model nudged to observed pan‐tropical sea surface temperatures (SST), we show that the back‐to‐back La Niña events during 2010–2011, followed by a North Pacific cooling and a marginal El Niño, were a key contribution to the 2012 record low. Specifically, the La Niña events in 2010–2011 warmed the Arctic Pacific sector, whereas tropical SST anomalies in 2012 strengthened the Greenland high pressure, leading to an Arctic dipole‐like pressure pattern and strengthening of transpolar ice drift. These Arctic temperature and circulation anomalies led to the record low sea ice extent in 2012, highlighting the strong influence of tropical SSTs on Arctic climate.
Suberoylanilide hydroxamic acid suppresses axonal damage and neurological dysfunction after subarachnoid hemorrhage via the HDAC1/HSP70/TDP-43 axis
Authors: Luo Kui , Wang Zhifei , Zhuang Kai , Yuan Shishan , Liu Fei , Liu Aihua 
Published: May 2022

AbstractIncreased focus has been placed on the role of histone deacetylase inhibitors as crucial players in subarachnoid hemorrhage (SAH) progression. Therefore, this study was designed to expand the understanding of SAH by exploring the downstream mechanism of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in SAH. The expression of TDP-43 in patients with SAH and rat models of SAH was measured. Then, western blot analysis, immunofluorescence staining, and transmission electron microscope were used to investigate the in vitro effect of TDP-43 on a neuronal cell model of SAH established by oxyhemoglobin treatment. Immunofluorescence staining and coimmunoprecipitation assays were conducted to explore the relationship among histone deacetylase 1 (HDAC1), heat shock protein 70 (HSP70), and TDP-43. Furthermore, the in vivo effect of HDAC1 on SAH was investigated in rat models of SAH established by endovascular perforation. High expression of TDP-43 in the cerebrospinal fluid of patients with SAH and brain tissues of rat models of SAH was observed, and TDP-43 accumulation in the cytoplasm and the formation of inclusion bodies were responsible for axonal damage, abnormal nuclear membrane morphology, and apoptosis in neurons. TDP-43 degradation was promoted by the HDAC1 inhibitor SAHA via the acetylation of HSP70, alleviating SAH, and this effect was verified in vivo in rat models. In conclusion, SAHA relieved axonal damage and neurological dysfunction after SAH via the HSP70 acetylation-induced degradation of TDP-43, highlighting a novel therapeutic target for SAH.
Predicted cardiovascular disease risk and prescribing of antihypertensive therapy among patients with hypertension in Australia using MedicineInsight
Authors: Roseleur Jacqueline , Gonzalez-Chica David A. , Karnon Jonathan , Stocks Nigel P. 
Published: May 2022

AbstractHypertension guidelines recommend that absolute cardiovascular disease (CVD) risk guide the management of hypertensive patients. This study aimed to assess the proportion of patients with diagnosed hypertension with sufficient data to calculate absolute CVD risk and determine whether CVD risk is associated with prescribing of antihypertensive therapies. This was a cross-sectional study using a large national database of electronic medical records of patients attending general practice in 2018 (MedicineInsight). Of 571,492 patients aged 45–74 years without a history of CVD, 251,733 [40.6% (95% CI: 39.8–41.2)] had a recorded hypertension diagnosis. The proportion of patients with sufficient recorded data available to calculate CVD risk was higher for patients diagnosed with hypertension [51.0% (95% CI: 48.0–53.9)] than for patients without a diagnosis of hypertension [38.7% (95% CI: 36.5–41.0)]. Of those patients with sufficient data to calculate CVD risk, 29.3% (95% CI: 28.1–30.6) were at high risk clinically, 6.0% (95% CI: 5.8–6.3) were at high risk based on their CVD risk score, 12.8% (95% CI: 12.5–13.2) at moderate risk and 51.8% (95% CI: 50.8–52.9) at low risk. The overall prevalence of antihypertensive therapy was 60.9% (95% CI: 59.3–62.5). Prescribing was slightly lower in patients at high risk based on their CVD risk score [57.4% (95% CI: 55.4–59.4)] compared with those at low [63.3% (95% CI: 61.9–64.8)] or moderate risk [61.8% (95% CI: 60.2–63.4)] or at high risk clinically [64.1% (95% CI: 61.9–66.3)]. Guideline adherence is suboptimal, and many patients miss out on treatments that may prevent future CVD events.
An epigenetic association analysis of childhood trauma in psychosis reveals possible overlap with methylation changes associated with PTSD
Authors: Løkhammer Solveig , Stavrum Anne-Kristin , Polushina Tatiana , Aas Monica , Ottesen Akiah A. , Andreassen Ole A. , Melle Ingrid , Le Hellard Stephanie 
Published: May 2022

AbstractPatients with a severe mental disorder report significantly higher levels of childhood trauma (CT) than healthy individuals. Studies have suggested that CT may affect brain plasticity through epigenetic mechanisms and contribute to developing various psychiatric disorders. We performed a blood-based epigenome-wide association study using the Childhood Trauma Questionnaire-short form in 602 patients with a current severe mental illness, investigating DNA methylation association separately for five trauma subtypes and the total trauma score. The median trauma score was set as the predefined cutoff for determining whether the trauma was present or not. Additionally, we compared our genome-wide results with methylation probes annotated to candidate genes previously associated with CT. Of the patients, 83.2% reported CT above the cutoff in one or more trauma subtypes, and emotional neglect was the trauma subtype most frequently reported. We identified one significant differently methylated position associated with the geneTANGO6for physical neglect. Seventeen differentially methylated regions (DMRs) were associated with different trauma categories. Several of these DMRs were annotated to genes previously associated with neuropsychiatric disorders such as post-traumatic stress disorder and cognitive impairments. Our results support a biomolecular association between CT and severe mental disorders. Genes that were previously identified as differentially methylated in CT-exposed subjects with and without psychosis did not show methylation differences in our analysis. We discuss this inconsistency, the relevance of our findings, and the limitations of our study.
POH1/Rpn11/PSMD14: a journey from basic research in fission yeast to a prognostic marker and a druggable target in cancer cells
Authors: Spataro Vito , Buetti-Dinh Antoine 
Published: May 2022

AbstractPOH1/Rpn11/PSMD14 is a highly conserved protein in eukaryotes from unicellular organisms to human and has a crucial role in cellular homoeostasis. It is a subunit of the regulatory particle of the proteasome, where it acts as an intrinsic deubiquitinase removing polyubiquitin chains from substrate proteins. This function is not only coupled to the translocation of substrates into the core of the proteasome and their subsequent degradation but also, in some instances, to the stabilisation of ubiquitinated proteins through their deubiquitination. POH1 was initially discovered as a functional homologue of the fission yeast gene pad1+, which confers drug resistance when overexpressed. In translational studies, expression of POH1 has been found to be increased in several tumour types relative to normal adjacent tissue and to correlate with tumour progression, higher tumour grade, decreased sensitivity to cytotoxic drugs and poor prognosis. Proteasome inhibitors targeting the core particle of the proteasome are highly active in the treatment of myeloma, and recently developed POH1 inhibitors, such as capzimin and thiolutin, have shown promising anticancer activity in cell lines of solid tumours and leukaemia. Here we give an overview of POH1 function in the cell, of its potential role in oncogenesis and of recent progress in developing POH1-targeting drugs.
Types of necroinflammation, the effect of cell death modalities on sterile inflammation
Authors: Mázló Anett , Jenei Viktória , Burai Sára , Molnár Tamás , Bácsi Attila , Koncz Gábor 
Published: May 2022

AbstractDistinct types of immune responses are activated by infections, which cause the development of type I, II, or III inflammation, regulated by Th1, Th2, Th17 helper T cells and ILC1, ILC2 and ILC3 cells, respectively. While the classification of immune responses to different groups of pathogens is widely accepted, subtypes of the immune response elicited by sterile inflammation have not yet been detailed. Necroinflammation is associated with the release of damage-associated molecular patterns (DAMP) from dying cells. In this review, we present that the distinct molecular mechanisms activated during apoptosis, necroptosis, pyroptosis, and ferroptosis lead to the release of different patterns of DAMPs and their suppressors, SAMPs. We summarize the currently available data on how regulated cell death pathways and released DAMPs and SAMPs direct the differentiation of T helper and ILC cells. Understanding the subtypes of necroinflammation can be crucial in developing strategies for the treatment of sterile inflammatory diseases caused by cell death processes.
Genetic analysis of the PCSK9 locus in psychological, psychiatric, metabolic and cardiovascular traits in UK Biobank
Authors: Hay Rachel , Cullen Breda , Graham Nicholas , Lyall Donald M. , Aman Alisha , Pell Jill P. , Ward Joey , Smith Daniel J. , Strawbridge Rona J. 
Published: May 2022

AbstractThe association between severe mental illness (SMI) and cardiovascular and metabolic disease (CMD) is poorly understood. PCSK9 is expressed in systems critical to both SMI and CMD and influences lipid homeostasis and brain function. We systematically investigated relationships between genetic variation within the PCSK9 locus and risk for both CMD and SMI. UK Biobank recruited ~500,000 volunteers and assessed a wide range of SMI and CMD phenotypes. We used genetic data from white British ancestry individuals of UK Biobank. Genetic association analyses were conducted in PLINK, with statistical significance defined by the number of independent SNPs. Conditional analyses and linkage disequilibrium assessed the independence of SNPs and the presence of multiple signals. Two genetic risk scores of lipid-lowering alleles were calculated and used as proxies for putative lipid-lowering effects of PCSK9. PCSK9 variants were associated with central adiposity, venous thrombosis embolism, systolic blood pressure, mood instability, and neuroticism (all p < 1.16 × 10−4). No secondary signals were identified. Conditional analyses and high linkage disequilibrium (r2 = 0.98) indicated that mood instability and central obesity may share a genetic signal. Genetic risk scores suggested that the lipid-lowering effects of PCSK9 may be causal for greater mood instability and higher neuroticism. This is the first study to implicate the PCSK9 locus in mood-disorder symptoms and related traits, as well as the shared pathology of SMI and CMD. PCSK9 effects on mood may occur via lipid-lowering mechanisms. Further work is needed to understand whether repurposing PCSK9-targeting therapies might improve SMI symptoms and prevent CMD.
Noise reduction by upstream open reading frames
Authors: Wu Ho-Wei , Fajiculay Erickson , Wu Jing-Fen , Yan Ching-Cher Sanders , Hsu Chao-Ping , Wu Shu-Hsing 
Published: May 2022

AbstractGene expression is prone to burst production, making it a highly noisy process that requires additional controls. Upstream open reading frames (uORFs) are widely present in the 5′ leader sequences of 30–50% of eukaryotic messenger RNAs1–3. The translation of uORFs can repress the translation efficiency of the downstream main coding sequences. Whether the low translation efficiency leads to a different variation, or noise, in gene expression has not been investigated, nor has the direct biological impact of uORF-repressed translation. Here we show that uORFs achieve low but precise protein production in plant cells, possibly by reducing the protein production rate. We also demonstrate that, by buffering a stable TIMING OF CAB EXPRESSION 1 (TOC1) protein production level, uORFs contribute to the robust operation of the plant circadian clock. Our results provide both an action model and the biological impact of uORFs in translational control to mitigate transcriptional noise for precise protein production.
Primary endocrine resistance of ER+ breast cancer with ESR1 mutations interrogated by droplet digital PCR
Authors: Ahn Sung Gwe , Bae Soong June , Kim Yoonjung , Ji Jung Hwan , Chu Chihhao , Kim Dooreh , Lee Janghee , Cha Yoon Jin , Lee Kyung-A , Jeong Joon 
Published: May 2022

AbstractWe investigated the patterns of recurrence and primary endocrine resistance according to estrogen receptor (ER) alpha gene (ESR1) mutations, as assessed by digital droplet (dd) PCR, in patients with non-metastatic ER+ breast cancer. We collected 121 formalin-fixed paraffin-embedded (FFPE) surgical specimens from ER+ breast cancer patients who had relapsed after surgery. Genomic DNA was extracted from the FFPE samples and ESR1 mutations were evaluated using ddPCR. ESR1 mutations were detected in 9 (7.4%) of 121 primary breast cancer specimens. The median recurrence-free interval and overall survival were significantly lower in patients with ESR1 mutations than in those without. Of the patients treated with ET (N = 98), eight had ESR1 mutations. Of these, six (75.0%) had primary endocrine resistance and two (25.0%) had secondary endocrine resistance. By contrast, only 22 of 90 (24.4%) patients without ESR1 mutations had primary endocrine resistance. A multivariable model showed that an ESR1 mutation is a significant risk factor for primary endocrine resistance. Our findings provide clinical evidence that the presence of rare ESR1 mutant clones identified by ddPCR in primary tumors is associated with primary endocrine resistance in an adjuvant setting.
Connector theory for reusing model results to determine materials properties
Authors: Vanzini Marco , Aouina Ayoub , Panholzer Martin , Gatti Matteo , Reining Lucia 
Published: May 2022

AbstractThe success of Density Functional Theory (DFT) is partly due to that of simple approximations, such as the Local Density Approximation (LDA), which uses results of a model, the homogeneous electron gas, to simulate exchange-correlation effects in real materials. We turn this intuitive approximation into a general and in principle exact theory by introducing the concept of a connector: a prescription how to use results of a model system in order to simulate a given quantity in a real system. In this framework, the LDA can be understood as one particular approximation for a connector that is designed to link the exchange-correlation potentials in the real material to that of the model. Formulating the in principle exact connector equations allows us to go beyond the LDA in a systematic way. Moreover, connector theory is not bound to DFT, and it suggests approximations also for other functionals and other observables. We explain why this very general approach is indeed a convenient starting point for approximations. We illustrate our purposes with simple but pertinent examples.
Sugars dominate the seagrass rhizosphere
Authors: Sogin E. Maggie , Michellod Dolma , Gruber-Vodicka Harald R. , Bourceau Patric , Geier Benedikt , Meier Dimitri V. , Seidel Michael , Ahmerkamp Soeren , Schorn Sina , D’Angelo Grace , Procaccini Gabriele , Dubilier Nicole , Liebeke Manuel 
Published: May 2022

AbstractSeagrasses are among the most efficient sinks of carbon dioxide on Earth. While carbon sequestration in terrestrial plants is linked to the microorganisms living in their soils, the interactions of seagrasses with their rhizospheres are poorly understood. Here, we show that the seagrass, Posidonia oceanica excretes sugars, mainly sucrose, into its rhizosphere. These sugars accumulate to µM concentrations—nearly 80 times higher than previously observed in marine environments. This finding is unexpected as sugars are readily consumed by microorganisms. Our experiments indicated that under low oxygen conditions, phenolic compounds from P. oceanica inhibited microbial consumption of sucrose. Analyses of the rhizosphere community revealed that many microbes had the genes for degrading sucrose but these were only expressed by a few taxa that also expressed genes for degrading phenolics. Given that we observed high sucrose concentrations underneath three other species of marine plants, we predict that the presence of plant-produced phenolics under low oxygen conditions allows the accumulation of labile molecules across aquatic rhizospheres.
Multi-omics single-cell data integration and regulatory inference with graph-linked embedding
Authors: Cao Zhi-Jie , Gao Ge 
Published: May 2022

AbstractDespite the emergence of experimental methods for simultaneous measurement of multiple omics modalities in single cells, most single-cell datasets include only one modality. A major obstacle in integrating omics data from multiple modalities is that different omics layers typically have distinct feature spaces. Here, we propose a computational framework called GLUE (graph-linked unified embedding), which bridges the gap by modeling regulatory interactions across omics layers explicitly. Systematic benchmarking demonstrated that GLUE is more accurate, robust and scalable than state-of-the-art tools for heterogeneous single-cell multi-omics data. We applied GLUE to various challenging tasks, including triple-omics integration, integrative regulatory inference and multi-omics human cell atlas construction over millions of cells, where GLUE was able to correct previous annotations. GLUE features a modular design that can be flexibly extended and enhanced for new analysis tasks. The full package is available online at https://github.com/gao-lab/GLUE.