bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global Trends in Air‐Water CO2 Exchange Over Seagrass Meadows Revealed by Atmospheric Eddy Covariance
Authors: Van Dam Bryce , Polsenaere Pierre , Barreras‐Apodaca Aylin , Lopes Christian , Sanchez‐Mejia Zulia , Tokoro Tatsuki , Kuwae Tomohiro , Loza Lucia Gutiérrez , Rutgersson Anna , Fourqurean James , Thomas Helmuth 
Published: March 2021

AbstractCoastal vegetated habitats like seagrass meadows can mitigate anthropogenic carbon emissions by sequestering CO2 as “blue carbon” (BC). Already, some coastal ecosystems are actively managed to enhance BC storage, with associated BC stocks included in national greenhouse gas inventories. However, the extent to which BC burial fluxes are enhanced or counteracted by other carbon fluxes, especially air‐water CO2 flux (FCO2) remains poorly understood. In this study, we synthesized all available direct FCO2 measurements over seagrass meadows made using atmospheric Eddy Covariance, across a globally representative range of ecotypes. Of the four sites with seasonal data coverage, two were net CO2 sources, with average FCO2 equivalent to 44%–115% of the global average BC burial rate. At the remaining sites, net CO2 uptake was 101%–888% of average BC burial. A wavelet coherence analysis demonstrated that FCO2 was most strongly related to physical factors like temperature, wind, and tides. In particular, tidal forcing was a key driver of global‐scale patterns in FCO2, likely due to a combination of lateral carbon exchange, bottom‐driven turbulence, and pore‐water pumping. Lastly, sea‐surface drag coefficients were always greater than the prediction for the open ocean, supporting a universal enhancement of gas‐transfer in shallow coastal waters. Our study points to the need for a more comprehensive approach to BC assessments, considering not only organic carbon storage, but also air‐water CO2 exchange, and its complex biogeochemical and physical drivers.
Kinematics of Footwall Exhumation at Oceanic Detachment faults: Solid‐Block Rotation and Apparent Unbending
Authors: Sandiford Dan , Brune Sascha , Glerum Anne , Naliboff John , Whittaker Joanne M. 
Published: March 2021

AbstractSeafloor spreading at slow rates can be accommodated on large‐offset oceanic detachment faults (ODFs), that exhume lower crustal and mantle rocks in footwall domes termed oceanic core complexes (OCCs). Footwall rocks experience large rotation during exhumation, yet important aspects of the kinematics—particularly the relative roles of solid‐block rotation and flexure—are not clearly understood. Using a high‐resolution numerical model, we explore the exhumation kinematics in the footwall beneath an emergent ODF/OCC. A key feature of the models is that footwall motion is dominated by solid‐block rotation, accommodated by the nonplanar, concave‐down fault interface. A consequence is that curvature measured along the ODF is representative of a neutral stress configuration, rather than a “bent” one. Instead, it is in the subsequent process of “apparent unbending” that significant flexural stresses are developed in the model footwall. The brittle strain associated with apparent unbending is produced dominantly in extension, beneath the OCC, consistent with earthquake clustering observed in the Trans‐Atlantic Geotraverse at the Mid‐Atlantic Ridge.
Ahi1 regulates the nuclear translocation of glucocorticoid receptor to modulate stress response
Authors: Wang Bin , Xin Ning , Qian Xuanchen , Zhai Lijing , Miao Zhigang , Yang Yong , Li Shihua , Sun Miao , Xu Xingshun , Li Xiao-Jiang 
Published: March 2021

AbstractStress activates the nuclear translocation of glucocorticoid receptors (GR) to trigger gene expression. Abnormal GR levels can alter the stress responses in animals and therapeutic effects of antidepressants. Here, we reported that stress-mediated nuclear translocation of GR reduced Ahi1 in the stressed cells and mouse brains. Ahi1 interacts with GR to stabilize each other in the cytoplasm. Importantly, Ahi1 deficiency promotes the degradation of GR in the cytoplasm and reduced the nuclear translocation of GR in response to stress. Genetic depletion of Ahi1 in mice caused hyposensitivity to antidepressants under the stress condition. These findings suggest that AHI1 is an important regulator of GR level and may serve as a therapeutic target for stress-related disorders.
Genetic factors influencing a neurobiological substrate for psychiatric disorders
Authors: Andlauer Till F. M. , Mühleisen Thomas W. , Hoffstaedter Felix , Teumer Alexander , Wittfeld Katharina , Teuber Anja , Reinbold Céline S. , Grotegerd Dominik , Bülow Robin , Caspers Svenja , Dannlowski Udo , Herms Stefan , Hoffmann Per , Kircher Tilo , Minnerup Heike , Moebus Susanne , Nenadić Igor , Teismann Henning , Völker Uwe , Etkin Amit , Berger Klaus , Grabe Hans J. , Nöthen Markus M. , Amunts Katrin , Eickhoff Simon B. , Sämann Philipp G. , Müller-Myhsok Bertram , Cichon Sven 
Published: March 2021

AbstractA retrospective meta-analysis of magnetic resonance imaging voxel-based morphometry studies proposed that reduced gray matter volumes in the dorsal anterior cingulate and the left and right anterior insular cortex—areas that constitute hub nodes of the salience network—represent a common substrate for major psychiatric disorders. Here, we investigated the hypothesis that the common substrate serves as an intermediate phenotype to detect genetic risk variants relevant for psychiatric disease. To this end, after a data reduction step, we conducted genome-wide association studies of a combined common substrate measure in four population-based cohorts (n = 2271), followed by meta-analysis and replication in a fifth cohort (n = 865). After correction for covariates, the heritability of the common substrate was estimated at 0.50 (standard error 0.18). The top single-nucleotide polymorphism (SNP) rs17076061 was associated with the common substrate at genome-wide significance and replicated, explaining 1.2% of the common substrate variance. This SNP mapped to a locus on chromosome 5q35.2 harboring genes involved in neuronal development and regeneration. In follow-up analyses, rs17076061 was not robustly associated with psychiatric disease, and no overlap was found between the broader genetic architecture of the common substrate and genetic risk for major depressive disorder, bipolar disorder, or schizophrenia. In conclusion, our study identified that common genetic variation indeed influences the common substrate, but that these variants do not directly translate to increased disease risk. Future studies should investigate gene-by-environment interactions and employ functional imaging to understand how salience network structure translates to psychiatric disorder risk.
Cryo-EM structures of HIV-1 trimer bound to CD4-mimetics BNM-III-170 and M48U1 adopt a CD4-bound open conformation
Authors: Jette Claudia A. , Barnes Christopher O. , Kirk Sharon M. , Melillo Bruno , Smith Amos B. , Bjorkman Pamela J. 
Published: March 2021

AbstractHuman immunodeficiency virus-1 (HIV-1), the causative agent of AIDS, impacts millions of people. Entry into target cells is mediated by the HIV-1 envelope (Env) glycoprotein interacting with host receptor CD4, which triggers conformational changes allowing binding to a coreceptor and subsequent membrane fusion. Small molecule or peptide CD4-mimetic drugs mimic CD4’s Phe43 interaction with Env by inserting into the conserved Phe43 pocket on Env subunit gp120. Here, we present single-particle cryo-EM structures of CD4-mimetics BNM-III-170 and M48U1 bound to a BG505 native-like Env trimer plus the CD4-induced antibody 17b at 3.7 Å and 3.9 Å resolution, respectively. CD4-mimetic-bound BG505 exhibits canonical CD4-induced conformational changes including trimer opening, formation of the 4-stranded gp120 bridging sheet, displacement of the V1V2 loop, and formation of a compact and elongated gp41 HR1C helical bundle. We conclude that CD4-induced structural changes on both gp120 and gp41 Env subunits are induced by binding to the gp120 Phe43 pocket.
Profiling PRMT methylome reveals roles of hnRNPA1 arginine methylation in RNA splicing and cell growth
Authors: Li Wen-juan , He Yao-hui , Yang Jing-jing , Hu Guo-sheng , Lin Yi-an , Ran Ting , Peng Bing-ling , Xie Bing-lan , Huang Ming-feng , Gao Xiang , Huang Hai-hua , Zhu Helen He , Ye Feng , Liu Wen 
Published: March 2021

AbstractNumerous substrates have been identified for Type I and II arginine methyltransferases (PRMTs). However, the full substrate spectrum of the only type III PRMT, PRMT7, and its connection to type I and II PRMT substrates remains unknown. Here, we use mass spectrometry to reveal features of PRMT7-regulated methylation. We find that PRMT7 predominantly methylates a glycine and arginine motif; multiple PRMT7-regulated arginine methylation sites are close to phosphorylations sites; methylation sites and proximal sequences are vulnerable to cancer mutations; and methylation is enriched in proteins associated with spliceosome and RNA-related pathways. We show that PRMT4/5/7-mediated arginine methylation regulates hnRNPA1 binding to RNA and several alternative splicing events. In breast, colorectal and prostate cancer cells, PRMT4/5/7 are upregulated and associated with high levels of hnRNPA1 arginine methylation and aberrant alternative splicing. Pharmacological inhibition of PRMT4/5/7 suppresses cancer cell growth and their co-inhibition shows synergistic effects, suggesting them as targets for cancer therapy.
Electrochemical reduction of acetonitrile to ethylamine
Authors: Xia Rong , Tian Dong , Kattel Shyam , Hasa Bjorn , Shin Haeun , Ma Xinbin , Chen Jingguang G. , Jiao Feng 
Published: March 2021

AbstractElectrifying chemical manufacturing using renewable energy is an attractive approach to reduce the dependence on fossil energy sources in chemical industries. Primary amines are important organic building blocks; however, the synthesis is often hindered by the poor selectivity because of the formation of secondary and tertiary amine byproducts. Herein, we report an electrocatalytic route to produce ethylamine selectively through an electroreduction of acetonitrile at ambient temperature and pressure. Among all the electrocatalysts, Cu nanoparticles exhibit the highest ethylamine Faradaic efficiency (~96%) at −0.29 V versus reversible hydrogen electrode. Under optimal conditions, we achieve an ethylamine partial current density of 846 mA cm−2. A 20-hour stable performance is demonstrated on Cu at 100 mA cm−2 with an 86% ethylamine Faradaic efficiency. Moreover, the reaction mechanism is investigated by computational study, which suggests the high ethylamine selectivity on Cu is due to the moderate binding affinity for the reaction intermediates.
Gallstone disease, diabetes, calcium, triglycerides, smoking and alcohol consumption and pancreatitis risk: Mendelian randomization study
Authors: Yuan Shuai , Giovannucci Edward L. , Larsson Susanna C. 
Published: March 2021

AbstractWe conducted a Mendelian randomization study to determine the potential causal associations of gallstone disease, diabetes, serum calcium, triglyceride levels, smoking and alcohol consumption with acute and chronic pancreatitis. Genetic variants associated with the exposures at p < 5 × 10−8 were selected from corresponding genome-wide association studies. Summary-level data for pancreatitis were obtained from the FinnGen consortium and UK Biobank. Univariable and multivariable Mendelian randomization analyses were performed and results from FinnGen and UK Biobank were combined using the fixed-effects meta-analysis method. Genetic predisposition to gallstone disease, type 2 diabetes and smoking initiation was associated with an increased risk of acute pancreatitis. The combined odds ratios (ORs) were 1.74 (95% confidence interval (CI), 1.57, 1.93) for gallstone disease, 1.14 (95% CI, 1.06, 1.21) for type 2 diabetes and 1.56 (95% CI, 1.32, 1.83) for smoking initiation. The association for type 2 diabetes attenuated after adjustment for gallstone disease. Genetic predisposition to gallstone disease and smoking initiation as well as higher genetically predicted serum calcium and triglyceride levels were associated with an increased risk of chronic pancreatitis. The combined ORs of chronic pancreatitis were 1.27 (95% CI, 1.08, 1.50) for gallstone disease, 1.86 (95% CI, 1.43, 2.43) for smoking initiation, 2.20 (95% CI, 1.30, 3.72) for calcium and 1.47 (95% CI, 1.23, 1.76) for triglycerides. This study provides evidence in support that gallstone disease, type 2 diabetes, smoking and elevated calcium and triglyceride levels are causally associated with the risk of acute or chronic pancreatitis.
Scaffold-free cell-based tissue engineering therapies: advances, shortfalls and forecast
Authors: De Pieri Andrea , Rochev Yury , Zeugolis Dimitrios I. 
Published: March 2021

AbstractCell-based scaffold-free therapies seek to develop in vitro organotypic three-dimensional (3D) tissue-like surrogates, capitalising upon the inherent capacity of cells to create tissues with efficiency and sophistication that is still unparalleled by human-made devices. Although automation systems have been realised and (some) success stories have been witnessed over the years in clinical and commercial arenas, in vitro organogenesis is far from becoming a standard way of care. This limited technology transfer is largely attributed to scalability-associated costs, considering that the development of a borderline 3D implantable device requires very high number of functional cells and prolonged ex vivo culture periods. Herein, we critically discuss advancements and shortfalls of scaffold-free cell-based tissue engineering strategies, along with pioneering concepts that have the potential to transform regenerative and reparative medicine.
Characterization of antimicrobial-resistant Gram-negative bacteria that cause neonatal sepsis in seven low- and middle-income countries
Authors: Sands Kirsty , Carvalho Maria J. , Portal Edward , Thomson Kathryn , Dyer Calie , Akpulu Chinenye , Andrews Robert , Ferreira Ana , Gillespie David , Hender Thomas , Hood Kerenza , Mathias Jordan , Milton Rebecca , Nieto Maria , Taiyari Khadijeh , Chan Grace J. , Bekele Delayehu , Solomon Semaria , Basu Sulagna , Chattopadhyay Pinaki , Mukherjee Suchandra , Iregbu Kenneth , Modibbo Fatima , Uwaezuoke Stella , Zahra Rabaab , Shirazi Haider , Muhammad Adil , Mazarati Jean-Baptiste , Rucogoza Aniceth , Gaju Lucie , Mehtar Shaheen , Bulabula Andre N. H. , Whitelaw Andrew ,   BARNARDS Group, Walsh Timothy R. 
Published: March 2021

AbstractAntimicrobial resistance in neonatal sepsis is rising, yet mechanisms of resistance that often spread between species via mobile genetic elements, ultimately limiting treatments in low- and middle-income countries (LMICs), are poorly characterized. The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) network was initiated to characterize the cause and burden of antimicrobial resistance in neonatal sepsis for seven LMICs in Africa and South Asia. A total of 36,285 neonates were enrolled in the BARNARDS study between November 2015 and December 2017, of whom 2,483 were diagnosed with culture-confirmed sepsis. Klebsiella pneumoniae (n = 258) was the main cause of neonatal sepsis, with Serratia marcescens (n = 151), Klebsiella michiganensis (n = 117), Escherichia coli (n = 75) and Enterobacter cloacae complex (n = 57) also detected. We present whole-genome sequencing, antimicrobial susceptibility and clinical data for 916 out of 1,038 neonatal sepsis isolates (97 isolates were not recovered from initial isolation at local sites). Enterobacterales (K. pneumoniae, E. coli and E. cloacae) harboured multiple cephalosporin and carbapenem resistance genes. All isolated pathogens were resistant to multiple antibiotic classes, including those used to treat neonatal sepsis. Intraspecies diversity of K. pneumoniae and E. coli indicated that multiple antibiotic-resistant lineages cause neonatal sepsis. Our results will underpin research towards better treatments for neonatal sepsis in LMICs.
Standardization of microbiome studies for urolithiasis: an international consensus agreement
Authors: Kachroo Naveen , Lange Dirk , Penniston Kristina L. , Stern Joshua , Tasian Gregory , Bajic Petar , Wolfe Alan J. , Suryavanshi Mangesh , Ticinesi Andrea , Meschi Tiziana , Monga Manoj , Miller Aaron W. 
Published: March 2021

AbstractNumerous metagenome-wide association studies (MWAS) for urolithiasis have been published, leading to the discovery of potential interactions between the microbiome and urolithiasis. However, questions remain about the reproducibility, applicability and physiological relevance of these data owing to discrepancies in experimental technique and a lack of standardization in the field. One barrier to interpreting MWAS is that experimental biases can be introduced at every step of the experimental pipeline, including sample collection, preservation, storage, processing, sequencing, data analysis and validation. Thus, the introduction of standardized protocols that maintain the flexibility to achieve study-specific objectives is urgently required. To address this need, the first international consortium for microbiome in urinary stone disease — MICROCOSM — was created and consensus panel members were asked to participate in a consensus meeting to develop standardized protocols for microbiome studies if they had published an MWAS on urolithiasis. Study-specific protocols were revised until a consensus was reached. This consensus group generated standardized protocols, which are publicly available via a secure online server, for each step in the typical clinical microbiome–urolithiasis study pipeline. This standardization creates the benchmark for future studies to facilitate consistent interpretation of results and, collectively, to lead to effective interventions to prevent the onset of urolithiasis, and will also be useful for investigators interested in microbiome research in other urological diseases.
STAT3 governs the HIF-1α response in IL-15 primed human NK cells
Authors: Coulibaly Anna , Velásquez Sonia Y. , Kassner Nina , Schulte Jutta , Barbarossa Maria Vittoria , Lindner Holger A. 
Published: March 2021

AbstractNatural killer (NK) cells mediate innate host defense against microbial infection and cancer. Hypoxia and low glucose are characteristic for these tissue lesions but do not affect early interferon (IFN) γ and CC chemokine release by interleukin 15 (IL-15) primed human NK cells in vitro. Hypoxia inducible factor 1α (HIF-1α) mediates cellular adaption to hypoxia. Its production is supported by mechanistic target of rapamycin complex 1 (mTORC1) and signal transducer and activator of transcription 3 (STAT3). We used chemical inhibition to probe the importance of mTORC1 and STAT3 for the hypoxia response and of STAT3 for the cytokine response in isolated and IL-15 primed human NK cells. Cellular responses were assayed by magnetic bead array, RT-PCR, western blotting, flow cytometry, and metabolic flux analysis. STAT3 but not mTORC1 activation was essential for HIF-1α accumulation, glycolysis, and oxygen consumption. In both primed normoxic and hypoxic NK cells, STAT3 inhibition reduced the secretion of CCL3, CCL4 and CCL5, and it interfered with IL-12/IL-18 stimulated IFNγ production, but it did not affect cytotoxic granule degranulation up on target cell contact. We conclude that IL-15 priming promotes the HIF-1α dependent hypoxia response and the early cytokine response in NK cells predominantly through STAT3 signaling.
Early escitalopram administration as a preemptive treatment strategy against spasticity after contusive spinal cord injury in rats
Authors: Ryu Youngjae , Ogata Toru , Nagao Motoshi , Sawada Yasuhiro , Nishimura Ryohei , Fujita Naoki 
Published: March 2021

AbstractIn the majority of spinal cord injury (SCI) patients, spasticity develops in the subacute phase and chronically persists with muscle hypertonia. Among various pathological conditions underlying spasticity, upregulated expression of 5-HT receptors (5-HTR) on the spinal motor neurons due to 5-HT denervation is considered one of crucial factors for hyperexcitability of the spinal circuit. As a 5-HT signal modulator, selective serotonin re-uptake inhibitors (SSRIs) are ordinarily prescribed for diseases associated with 5-HT in the CNS, and are known for their ability to increase 5-HT levels as well as to desensitize 5-HTR. Here, we hypothesized that early SSRI administration as a preemptive treatment strategy would effectively prevent the onset of spasticity. We used a rat model of contusive SCI and administered escitalopram during the first 4 weeks after injury, which is the period required for spasticity development in rodent models. We performed a swimming test to quantify spastic behaviors and conducted the Hoffman reflex test as well as histological analyses for 5-HT2AR and KCC2 expressions. Four weeks of escitalopram administration suppressed spastic behaviors during the swimming test and reduced the population of spasticity-strong rats. Moreover, the treatment resulted in decreased immunoreactivity of 5-HT2AR in the spinal motor neurons. Result of the H-reflex test and membrane expression of KCC2 were not significantly altered. In summary, early escitalopram administration could prevent the onset of spastic behaviors via regulation of 5-HT system after SCI, but could not modulate exaggerated spinal reflex. Our results suggest a novel application of SSRIs for preventative treatment of spasticity.
Impact of transjugular intrahepatic portosystemic shunt creation on the central lymphatic system in liver cirrhosis
Authors: Pieper Claus Christian , Feißt Andreas , Meyer Carsten , Luetkens Julian , Praktiknjo Michael , Trebicka Jonel , Attenberger Ulrike , Jansen Christian 
Published: March 2021

AbstractThe puropse of this study was to evaluate associations of cisterna chyli (CCh) diameter with portal hemodynamics and the influence of TIPS-creation in cirrhotic patients. 93 cirrhotic patients (57 male, mean age 59 years) received CT prior to TIPS-creation. 38/93 additionally underwent post-interventional CT. CCh-diameter was measured. After categorization into patients with and without large venous collaterals (i.e. > 6 mm), data were analyzed regarding associations between CCh-diameter, clinical and portal-hemodynamic parameters and diameter-changes after TIPS-creation. Patient survival post-TIPS was analyzed. Median portosystemic pressure-gradient decreased from 20 to 9 mmHg after TIPS-creation. Large venous collaterals were observed in 59 patients. In 69/93 patients (74.2%) the CCh was detectable. Mean pre-interventional diameter was 9.4 ± 2.7 mm (large collaterals: 8.7 ± 2.0 mm, no large collaterals: 10.7 ± 3.2 mm, p = 0.003). CCh-diameter correlated strongly with pre-TIPS portal-pressure (Rs = 0.685, p = 0.0001), moderately with portosystemic-gradient (Rs = 0.524, p = 0.006), liver shear-wave-elastography (Rs = 0.597, p = 0.004) and spleen size (Rs = 0.501, p = 0.01) in patients without large collaterals, but not in patients with large collaterals. Post-TIPS CCh-diameter decreased significantly from 10.2 ± 2.8 mm to 8.3 ± 3.0 mm (p < 0.001). Patients without a detectable CCh on CT survived significantly shorter. The diameter of the CCh is associated with portal-pressure and decreases after TIPS-creation in cirrhotic patients, reflecting a portal decompression mechanism via the lymphatic system. Lack of larger central lymphatics detectable on CT may be associated with shorter survival.