bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing Decadal Predictability in an Earth‐System Model Using Explainable Neural Networks
Authors: Toms Benjamin A. , Barnes Elizabeth A. , Hurrell James W. 
Published: June 2021

AbstractWe show that explainable neural networks can identify regions of oceanic variability that contribute predictability on decadal timescales in a fully coupled Earth‐system model. The neural networks learn to use sea‐surface temperature anomalies to predict future continental surface temperature anomalies. We then use a neural‐network explainability method called layerwise relevance propagation to infer which oceanic patterns lead to accurate predictions made by the neural networks. In particular, regions within the North Atlantic Ocean and North Pacific Ocean lend the most predictability for surface temperature across continental North America. We apply the proposed methodology to decadal variability, although the concept is generalizable to other timescales of predictability. Furthermore, while our approach focuses on predictable patterns of internal variability within climate models, it should be generalizable to observational data as well. Our study contributes to the growing evidence that explainable neural networks are important tools for advancing geoscientific knowledge.
A Limited Area Modeling Capability for the Finite‐Volume Cubed‐Sphere (FV3) Dynamical Core and Comparison With a Global Two‐Way Nest
Authors: Black T. L. , Abeles J. A. , Blake B. T. , Jovic D. , Rogers E. , Zhang X. , Aligo E. A. , Dawson L. C. , Lin Y. , Strobach E. , Shafran P. C. , Carley J. R. 
Published: June 2021

AbstractThe development of a limited area model (LAM) capability for the nonhydrostatic Finite‐Volume Cubed‐Sphere (FV3) dynamical core is described and compared with a globally nested approach featuring two‐way feedback. Comparisons of the computational performance of the LAM relative to the two‐way nest reveal that the LAM configuration exhibits considerable improvement in efficiency. High‐resolution (i.e., 3‐km) LAM and nest configuration forecasts covering a 1‐month period show statistically comparable results for most parameters. Forecast differences between the two configurations primarily arise in the upper air temperature and height fields, which show a statistically significant increase in the magnitude of negative biases in geopotential height and upper‐air temperature using the LAM configuration relative to the nest at forecast lead times >24‐h. Precipitation forecasts over the full 60‐h forecast period are also evaluated and depict no statistically significant differences between the two configurations, with the nest configuration exhibiting slightly improved scores. Overall results suggest that while the FV3 LAM approach can introduce degradations into the forecast relative to the two‐way interactive nest at lead times >24‐h, these errors are generally small in magnitude and are accompanied by considerable improvement in computational efficiency.
LncRNA Bmp1 promotes the healing of intestinal mucosal lesions via the miR-128-3p/PHF6/PI3K/AKT pathway
Authors: Zhuang Mengmeng , Deng Yuequ , Zhang Wenwen , Zhu Bo , Yan Hao , Lou Jiaqi , Zhang Pan , Cui Qingwei , Tang Hao , Sun Han , Sun Yong 
Published: June 2021

AbstractIntestinal mucosal injuries are directly or indirectly related to many common acute and chronic diseases. Long non-coding RNAs (lncRNAs) are expressed in many diseases, including intestinal mucosal injury. However, the relationship between lncRNAs and intestinal mucosal injury has not been determined. Here, we investigated the functions and mechanisms of action of lncRNA Bmp1 on damaged intestinal mucosa. We found that Bmp1 was increased in damaged intestinal mucosal tissue and Bmp1 overexpression was able to alleviate intestinal mucosal injury. Bmp1 overexpression was found to influence cell proliferation, colony formation, and migration in IEC-6 or HIEC-6 cells. Moreover, miR-128-3p was downregulated after Bmp1 overexpression, and upregulation of miR-128-3p reversed the effects of Bmp1 overexpression in IEC-6 cells. Phf6 was observed to be a target of miR-128-3p. Furthermore, PHF6 overexpression affected IEC-6 cells by activating PI3K/AKT signaling which was mediated by the miR-128-3p/PHF6 axis. In conclusion, Bmp1 was found to promote the expression of PHF6 through the sponge miR-128-3p, activating the PI3K/AKT signaling pathway to promote cell migration and proliferation.
Time trajectories in the transcriptomic response to exercise - a meta-analysis
Authors: Amar David , Lindholm Malene E. , Norrbom Jessica , Wheeler Matthew T. , Rivas Manuel A. , Ashley Euan A. 
Published: June 2021

AbstractExercise training prevents multiple diseases, yet the molecular mechanisms that drive exercise adaptation are incompletely understood. To address this, we create a computational framework comprising data from skeletal muscle or blood from 43 studies, including 739 individuals before and after exercise or training. Using linear mixed effects meta-regression, we detect specific time patterns and regulatory modulators of the exercise response. Acute and long-term responses are transcriptionally distinct and we identify SMAD3 as a central regulator of the exercise response. Exercise induces a more pronounced inflammatory response in skeletal muscle of older individuals and our models reveal multiple sex-associated responses. We validate seven of our top genes in a separate human cohort. In this work, we provide a powerful resource (www.extrameta.org) that expands the transcriptional landscape of exercise adaptation by extending previously known responses and their regulatory networks, and identifying novel modality-, time-, age-, and sex-associated changes.
Thioesterase superfamily member 1 undergoes stimulus-coupled conformational reorganization to regulate metabolism in mice
Authors: Li Yue , Imai Norihiro , Nicholls Hayley T. , Roberts Blaine R. , Goyal Samaksh , Krisko Tibor I. , Ang Lay-Hong , Tillman Matthew C. , Roberts Anne M. , Baqai Mahnoor , Ortlund Eric A. , Cohen David E. , Hagen Susan J. 
Published: June 2021

AbstractIn brown adipose tissue, thermogenesis is suppressed by thioesterase superfamily member 1 (Them1), a long chain fatty acyl-CoA thioesterase. Them1 is highly upregulated by cold ambient temperature, where it reduces fatty acid availability and limits thermogenesis. Here, we show that Them1 regulates metabolism by undergoing conformational changes in response to β-adrenergic stimulation that alter Them1 intracellular distribution. Them1 forms metabolically active puncta near lipid droplets and mitochondria. Upon stimulation, Them1 is phosphorylated at the N-terminus, inhibiting puncta formation and activity and resulting in a diffuse intracellular localization. We show by correlative light and electron microscopy that Them1 puncta are biomolecular condensates that are inhibited by phosphorylation. Thus, Them1 forms intracellular biomolecular condensates that limit fatty acid oxidation and suppress thermogenesis. During a period of energy demand, the condensates are disrupted by phosphorylation to allow for maximal thermogenesis. The stimulus-coupled reorganization of Them1 provides fine-tuning of thermogenesis and energy expenditure.
Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation
Authors: Bauer Moritz , Vidal Enrique , Zorita Eduard , Üresin Nil , Pinter Stefan F. , Filion Guillaume J. , Payer Bernhard 
Published: June 2021

AbstractA hallmark of chromosome organization is the partition into transcriptionally active A and repressed B compartments, and into topologically associating domains (TADs). Both structures were regarded to be absent from the inactive mouse X chromosome, but to be re-established with transcriptional reactivation and chromatin opening during X-reactivation. Here, we combine a tailor-made mouse iPSC reprogramming system and high-resolution Hi-C to produce a time course combining gene reactivation, chromatin opening and chromosome topology during X-reactivation. Contrary to previous observations, we observe A/B-like compartments on the inactive X harbouring multiple subcompartments. While partial X-reactivation initiates within a compartment rich in X-inactivation escapees, it then occurs rapidly along the chromosome, concomitant with downregulation of Xist. Importantly, we find that TAD formation precedes transcription and initiates from Xist-poor compartments. Here, we show that TAD formation and transcriptional reactivation are causally independent during X-reactivation while establishing Xist as a common denominator.
Translation and codon usage regulate Argonaute slicer activity to trigger small RNA biogenesis
Authors: Singh Meetali , Cornes Eric , Li Blaise , Quarato Piergiuseppe , Bourdon Loan , Dingli Florent , Loew Damarys , Proccacia Simone , Cecere Germano 
Published: June 2021

AbstractIn the Caenorhabditis elegans germline, thousands of mRNAs are concomitantly expressed with antisense 22G-RNAs, which are loaded into the Argonaute CSR-1. Despite their essential functions for animal fertility and embryonic development, how CSR-1 22G-RNAs are produced remains unknown. Here, we show that CSR-1 slicer activity is primarily involved in triggering the synthesis of small RNAs on the coding sequences of germline mRNAs and post-transcriptionally regulates a fraction of targets. CSR-1-cleaved mRNAs prime the RNA-dependent RNA polymerase, EGO-1, to synthesize 22G-RNAs in phase with translating ribosomes, in contrast to other 22G-RNAs mostly synthesized in germ granules. Moreover, codon optimality and efficient translation antagonize CSR-1 slicing and 22G-RNAs biogenesis. We propose that codon usage differences encoded into mRNA sequences might be a conserved strategy in eukaryotes to regulate small RNA biogenesis and Argonaute targeting.
A fundamental viewpoint on the hydrogen spillover phenomenon of electrocatalytic hydrogen evolution
Authors: Li Jiayuan , Hu Jun , Zhang Mingkai , Gou Wangyan , Zhang Sai , Chen Zhong , Qu Yongquan , Ma Yuanyuan 
Published: June 2021

AbstractHydrogen spillover phenomenon of metal-supported electrocatalysts can significantly impact their activity in hydrogen evolution reaction (HER). However, design of active electrocatalysts faces grand challenges due to the insufficient understandings on how to overcome this thermodynamically and kinetically adverse process. Here we theoretically profile that the interfacial charge accumulation induces by the large work function difference between metal and support (∆Φ) and sequentially strong interfacial proton adsorption construct a high energy barrier for hydrogen transfer. Theoretical simulations and control experiments rationalize that small ∆Φ induces interfacial charge dilution and relocation, thereby weakening interfacial proton adsorption and enabling efficient hydrogen spillover for HER. Experimentally, a series of Pt alloys-CoP catalysts with tailorable ∆Φ show a strong ∆Φ-dependent HER activity, in which PtIr/CoP with the smallest ∆Φ = 0.02 eV delivers the best HER performance. These findings have conclusively identified ∆Φ as the criterion in guiding the design of hydrogen spillover-based binary HER electrocatalysts.
Regulation of the one carbon folate cycle as a shared metabolic signature of longevity
Authors: Annibal Andrea , Tharyan Rebecca George , Schonewolff Maribel Fides , Tam Hannah , Latza Christian , Auler Markus Max Karl , Grönke Sebastian , Partridge Linda , Antebi Adam 
Published: June 2021

AbstractThe metabolome represents a complex network of biological events that reflects the physiologic state of the organism in health and disease. Additionally, specific metabolites and metabolic signaling pathways have been shown to modulate animal ageing, but whether there are convergent mechanisms uniting these processes remains elusive. Here, we used high resolution mass spectrometry to obtain the metabolomic profiles of canonical longevity pathways in C. elegans to identify metabolites regulating life span. By leveraging the metabolomic profiles across pathways, we found that one carbon metabolism and the folate cycle are pervasively regulated in common. We observed similar changes in long-lived mouse models of reduced insulin/IGF signaling. Genetic manipulation of pathway enzymes and supplementation with one carbon metabolites in C. elegans reveal that regulation of the folate cycle represents a shared causal mechanism of longevity and proteoprotection. Such interventions impact the methionine cycle, and reveal methionine restriction as an underlying mechanism. This comparative approach reveals key metabolic nodes to enhance healthy ageing.
WSX1 act as a tumor suppressor in hepatocellular carcinoma by downregulating neoplastic PD-L1 expression
Authors: Wu Man , Xia Xueqing , Hu Jiemiao , Fowlkes Natalie Wall , Li Shulin 
Published: June 2021

AbstractWSX1, a receptor subunit for IL-27, is widely expressed in immune cells and closely involved in immune response, but its function in nonimmune cells remains unknown. Here we report that WSX1 is highly expressed in human hepatocytes but downregulated in hepatocellular carcinoma (HCC) cells. Using NRAS/AKT-derived spontaneous HCC mouse models, we reveal an IL-27–independent tumor-suppressive effect of WSX1 that largely relies on CD8+ T-cell immune surveillance via reducing neoplastic PD-L1 expression and the associated CD8+ T-cell exhaustion. Mechanistically, WSX1 transcriptionally downregulates an isoform of PI3K—PI3Kδ and thereby inactivates AKT, reducing AKT-induced GSK3β inhibition. Activated GSK3β then boosts PD-L1 degradation, resulting in PD-L1 reduction. Overall, we demonstrate that WSX1 is a tumor suppressor that reinforces hepatic immune surveillance by blocking the PI3Kδ/AKT/GSK3β/PD-L1 pathway. Our results may yield insights into the host homeostatic control of immune response and benefit the development of cancer immunotherapies.
Diagnosis and management of acute appendicitis in 21 pediatric hematology and oncology patients at a tertiary care cancer center
Authors: von Mersi Hannah , Benkö Thomas , Boztug Heidrun , Dworzak Michael , Engstler Gernot , Friesenbichler Waltraud , Hutter Caroline , Lakatos Karoly , Mann Georg , Metzelder Martin , Lüftinger Roswitha , Pichler Herbert , Poyer Fiona , Ronceray Leila , Attarbaschi Andishe 
Published: June 2021

AbstractAcute appendicitis is a rare gastrointestinal complication of anti-cancer chemotherapy and hematopoietic stem cell transplantation. Among a cohort of 2341 hemato-oncologic patients at a pediatric tertiary care cancer center, we identified 21 patients (0.9%) with 23 episodes of acute appendicitis, based on pathological imaging of the appendix and clinical findings. Median age at diagnosis was 10.21 years. Types of underlying disease included acute leukemias (n = 15), solid tumors (n = 4), and aplastic anemia (n = 2). Clinical symptoms seen in > 1 case were recorded for all 23 episodes as follows: abdominal pain, n = 22; abdominal tenderness, n = 4; fever, n = 7; nausea, n = 2; emesis; n = 2; diarrhea, n = 5; and constipation, n = 2. Median leukocyte count at diagnosis was 0.5 × 109/L, with a median of 0.1 × 109/L for the absolute neutrophil count (ANC). All patients received broad-spectrum antibiotics and 18/23 (78%) patients underwent uneventful appendectomy after a median of 5 days and with a median ANC of 0.7 × 109/L. Median duration until continuation of chemotherapy was 17 days for the 20 cases of appendicitis occurring during the patients’ disease course. Overall, 5/21 (19%) patients died including one related to the appendicitis itself which progressed to a typhlitis and was due to a fungal infection. The other fatalities were transplant- (n = 2) and leukemia-related (n = 2). Acute appendicitis is a rare and usually not life-threatening event in pediatric hemato-oncologic patients, which, if managed by prompt administration of broad-spectrum antibiotics (and antimycotics), can be safely followed by an elective (delayed) appendectomy, even before complete recovery of the neutrophils is achieved.
Effect of ammonia and water molecule on OH + CH3OH reaction under tropospheric condition
Authors: Ali Mohamad Akbar , Balaganesh M. , Al-Odail Faisal A. , Lin K. C. 
Published: June 2021

AbstractThe rate coefficients for OH + CH3OH and OH + CH3OH (+ X) (X = NH3, H2O) reactions were calculated using microcanonical, and canonical variational transition state theory (CVT) between 200 and 400 K based on potential energy surface constructed using CCSD(T)//M06-2X/6-311++G(3df,3pd). The results show that OH + CH3OH is dominated by the hydrogen atoms abstraction from CH3 position in both free and ammonia/water catalyzed ones. This result is in consistent with previous experimental and theoretical studies. The calculated rate coefficient for the OH + CH3OH (8.8 × 10−13 cm3 molecule−1 s−1), for OH + CH3OH (+ NH3) [1.9 × 10−21 cm3 molecule−1 s−1] and for OH + CH3OH (+ H2O) [8.1 × 10−16 cm3 molecule−1 s−1] at 300 K. The rate coefficient is at least 8 order magnitude [for OH + CH3OH(+ NH3) reaction] and 3 orders magnitude [OH + CH3OH (+ H2O)] are smaller than free OH + CH3OH reaction. Our calculations predict that the catalytic effect of single ammonia and water molecule on OH + CH3OH reaction has no effect under tropospheric conditions because the dominated ammonia and water-assisted reaction depends on ammonia and water concentration, respectively. As a result, the total effective reaction rate coefficients are smaller. The current study provides a comprehensive example of how basic and neutral catalysts effect the most important atmospheric prototype alcohol reactions.
Appraising Mahallat Geothermal Region using thermal surveying data accompanied by the geological, geochemical and gravity analyses
Authors: Nouraliee Javad , Ebrahimi Davar , Dashti Ali , Gholami Korzani Maziar , Sangin Sepehr 
Published: June 2021

AbstractMahallat Geothermal Region, located in the central part of Iran, is known as one of the largest low-temperature geothermal fields. In this study, Mahallat geothermal resource has been evaluated based on integrated geological, geochemical and geophysical analyses. Gravity data revealed three major negative anomaly zones. Based on the geochemical analyses, quartz geothermometers are more reliable than others and confirmed that the reservoir is about 90 °C. Lithological properties of Jurassic layers and high sulphate content observed in geochemical data showed traces of the coal-rich layers on the hot fluids. Measured temperatures in 7 boreholes with the depths ranging from 50 to 100 m, have proposed that expected geothermal gradient will be about 81.5 °C/km. Among all drilled boreholes, the data coming from only one resulted in this almost reliable gradient. Other boreholes are clearly too shallow or affected by upflow or downflow of water along existing faults. Geological, geochemical, gravity and measurements of drilled boreholes suggested the existence of a shallow reservoir with an approximate temperature of 90 °C. Regarding gravity and observed faults, geothermal reservoir is elongated parallel to one of the main faults of the region with NE-SW strike.
Increasing glycaemia is associated with a significant decline in HDL cholesterol in women with prediabetes in two national populations
Authors: Washirasaksiri Chaiwat , Srivanichakorn Weerachai , Godsland Ian F. , Kositamongkol Chayanis , Chariyalertsak Suwat , Kessomboon Pattapong , Assanangkornchai Sawitri , Taneepanichskul Surasak , Neelapaichit Nareemarn , Phisalprapa Pochamana , Johnston Desmond G. , Oliver Nick S. , Aekplakorn Wichai 
Published: June 2021

AbstractInternationally, studies have shown associations between lipids and glycemia; however, whether the link varies by gender and population has been rarely examined. We investigated relationships between glycemia and HDL- and Non-HDL-cholesterol and their modification by gender. We undertook a cross-sectional analysis from the National Health Examination Survey for Thailand (NHES-Thailand) and the Health Survey for England (HS-England) in adults aged 18–75 year. Glycaemia was assessed by FPG in Thailand and by HbA1c in the UK. In population- and gender-stratified analyses, the relationships between glycemia and lipids were explored. A total of 15,145 Thai and 3484 UK adults with blood measurement were included. The prevalences of prediabetes were: in NHES-Thailand, 16% (SE = 0.004), based on FPG (5.6 to < 7.0 mmol/L) and in HS-England, 19% (0.007) based on HbA1c (39 to < 48 mmol/mol). Increasingly abnormal glucose homeostasis was associated with increasing age, adiposity, SBP, proportion of antihypertensive and lipid-lowering agent use and with decreasing HDL-cholesterol. Independent of age, adiposity, smoking, alcohol, physical activity, and lipid and BP lowering drug use, increasing glycemia was associated with decreasing HDL-cholesterol specifically in women with prediabetes (NHES-Thailand, beta-coefficient − 0.07 (95% CI − 0.15, − 0.001) p = 0.04 and HS-England, − 0.03 (− 0.04, − 0.006) p = 0.01). In both populations, among those with prediabetes, increasing glycaemia is associated with an adverse, significant decline in HDL cholesterol, specifically in women. These adverse effects are apparent in widely-differing international populations.
Rapid manufacturing of micro-drilling devices using FFF-type 3D printing technology
Authors: Park Sangyeun , Ko Byeongjo , Lee Heewon , So Hongyun 
Published: June 2021

AbstractMicro-drilling devices with different blade shapes were fabricated with a rapid and facile manufacturing process using three-dimensional (3D) printing technology. The 3D-printed casting mold was utilized to customize the continuous shape of the blades without the need for expensive manufacturing tools. A computational fluid dynamics simulation was performed to estimate the pressure differences (fluidic resistance) around each rotating device in a flowing stream. Three types of blades (i.e., 45°, 0°, and helical type) were manufactured and compared to a device without blades (i.e., plain type). As a result, the device with the 45° blades exhibited the best drilling performance. At a rotational speed of 1000 rpm, the average drilling depth of the device with the 45° blades to penetrate artificial thrombus for 90 s was 3.64 mm, which was ~ 2.4 times longer than that of helical blades (1.51 mm). This study demonstrates the feasibility of using 3D printing to fabricate microscale drilling devices with sharp blades for various applications, such as in vivo microsurgery and clogged water supply tube maintenance.
vB_BcM_Sam46 and vB_BcM_Sam112, members of a new bacteriophage genus with unusual small terminase structure
Authors: Kazantseva Olesya A. , Piligrimova Emma G. , Shadrin Andrey M. 
Published: June 2021

AbstractOne of the serious public health concerns is food contaminated with pathogens and their vital activity products such as toxins. Bacillus cereus group of bacteria includes well-known pathogenic species such as B. anthracis, B. cereus sensu stricto (ss), B. cytotoxicus and B. thuringiensis. In this report, we describe the Bacillus phages vB_BcM_Sam46 and vB_BcM_Sam112 infecting species of this group. Electron microscopic analyses indicated that phages Sam46 and Sam112 have the myovirus morphotype. The genomes of Sam46 and Sam112 comprise double-stranded DNA of 45,419 bp and 45,037 bp in length, respectively, and have the same GC-content. The genome identity of Sam46 and Sam112 is 96.0%, indicating that they belong to the same phage species. According to the phylogenetic analysis, these phages form a distinct clade and may be members of a new phage genus, for which we propose the name ‘Samaravirus’. In addition, an interesting feature of the Sam46 and Sam112 phages is the unusual structure of their small terminase subunit containing N-terminal FtsK_gamma domain.