bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of two culture media on morphokinetics and ploidy status of sibling embryos
Authors: Urich Michael , Ugur Muhammet Rasit , Li Fang , Shamma F. Nicholas , Hammoud Ahmad , Cottrell Hanh N. , Dogan Sule
Published: December 2021

To investigate the effects of culture media with different lactate concentrations on early embryonic development, data collected from our patients undergoing preimplantation genetic testing (PGT) were assessed using the EmbryoScope™ time-lapse culturing system. After intracytoplasmic sperm injection (ICSI), sibling oocytes were cultured in the same EmbryoScope (Vitrolife) slides including two different commercially available media. The patients with fewer than five mature oocytes were not included in the analyses. All embryos were hatched on day 3, and trophectoderm biopsies (n= 212) were performed accordingly. PGT for aneuploidy (PGT-A) on biopsied materials was carried out using next generation sequencing. Morphokinetic parameters, fertilization, irregular division, degeneration, blastulation, euploidy, and pregnancy rates of embryos cultured in LifeGlobal Global Total medium (LGGT) and Continuous Single Culture-NX Complete medium (CSCM-NXC) were compared. There were no differences observed in time to pronuclear fade, or in time spent as 2-cell (cc2) and 3-cell (s2), to 4-cell, 5-cell, morula and blastocyst stages (P> 0.05). Embryos reached the 2-cell (t2) and 3-cell (t3) stages significantly faster in LGGT (P< 0.05), whereas embryos grown in CSCM-NXC with lower lactate reached starting blastulation significantly sooner (P= 0.026). However, there were no statistical differences observed in fertilization, blastulation, degeneration, irregular division euploidy, and pregnancy rates between the two groups (P> 0.05). Even though pregnancy and fertilization rates did not indicate statistical differences, results are significant to provide better insight on potential roles of lactate in embryo development. These finding will advance the fundamental knowledge of human embryo development and assisted reproductive technologies.
The Carbon Cycle of Southeast Australia During 2019–2020: Drought, Fires, and Subsequent Recovery
Authors: Byrne B. , Liu J. , Lee M. , Yin Y. , Bowman K. W. , Miyazaki K. , Norton A. J. , Joiner J. , Pollard D. F. , Griffith D. W. T. , Velazco V. A. , Deutscher N. M. , Jones N. B. , Paton‐Walsh C.
Published: December 2021

2019 was the hottest and driest year on record for southeast Australia leading to bushfires of unprecedented extent. Ecosystem carbon losses due to drought and fire are believed to have been substantial, but have not been well quantified. Here, we utilize space‐based measurements of trace gases (TROPOspheric Monitoring Instrument XCO, Orbiting Carbon Observatory 2 ) and up‐scaled GPP (FluxSat GPP) to quantify the carbon cycle anomalies resulting from drought and fire in southeast Australia during the 2019–2020 growing season. We find that biomass burning released 113–236 TgC of CO2 while drought and fire‐induced anomalies in net ecosystem exchange reduced growing season carbon uptake by an additional 19–52 TgC of CO2. These carbon losses were concentrated during the spring and early summer, when hot‐dry conditions were most severe. A shift to cooler conditions with above average rainfall during February is found to result in a partial recovery and greening in unburned ecosystems, but not in fire‐impacted areas. The net 2019–2020 carbon loss substantially exceeded interannual variations in net uptake over 2010–2019 estimated from top‐down constraints (∼5σ anomaly), and exceeded Australia's annual fossil fuel emissions (∼104 TgC year−1). Top‐down constraints show that the regional carbon budget is strongly regulated by climate variability, and suggest that cool‐wet conditions are required for a rapid recovery of carbon stocks. This has implications for the regional carbon budget as more frequent climate‐change‐driven heat and drought events may increase the frequency of fire events and the recovery time of ecosystems, threatening the carbon stocks of the region.
The Regular Features Recorded by the Langmuir Probe Onboard the Low Earth Polar Orbit Satellite CSES
Authors: Yan Rui , Guan Yibin , Miao Yuanqing , Zhima Zeren , Xiong Chao , Zhu Xinghong , Liu Chao , Shen Xuhui , Yuan Shigeng , Liu Dapeng , Zhang Aibing , Guo Feng , Zhou Na , Zhu Keying , Zheng Lin , Lv Fangxian
Published: December 2021

This paper presents two kinds of regular features revealed from the observations of the Langmuir probe (LAP) onboard the low‐earth polar orbit satellite ‐ China Seismo‐Electromagnetic Satellite (CSES). The first feature behaves as a sudden drop (SD) in the plasma potential (Vp) and floating potential (Vf) data, while the second one appears as a spike (SP) in the dayside Vp and Vf data. The SD structure occurs at geo‐latitudes from 40°N to 65°N, roughly from mid‐March to mid‐September months but with an apparent yearly growth of its amplitude. The SD is caused by the satellite‐current system adjustment at the terminator transition zone. The SP feature predominately appears at geo‐latitudes from 10°S to 40°N, showing annual recurrence and growing amplitude. Simulation suggests that the SP is caused by instantaneous illumination changes of probe surface when the boom of the electric field detector in the windward panel shades the LAP. According to the analysis of I‐V curves both inside and outside the SD and SP structures, we exclude the possibility of probe contamination and confirm that the scientific data of CSES LAP are reliable. These two regular features depend on the solar illumination conditions and the corresponding adjustment of the satellite‐current system equilibrium. This study provides a valuable reference for validating and pre‐calibrating data from LAP in‐situ measurements onboard similar low‐earth polar orbit satellites.
MLT‐Dependence of Sustained Spectral Gaps of Proton and Oxygen in the Inner Magnetosphere
Authors: Yue Chao , Liu Ying , Zhou Xuzhi , Zong Qiu‐Gang , Reeves Geoffrey D. , Spence Harlan E.
Published: December 2021

To examine the species dependence of the sustained energy spectrum gaps, in this letter, we analyzed the magnetic local time distribution of sustained proton and oxygen gaps and find that there is a clear difference between proton and oxygen ions: proton sustained gaps are predominantly distributed near the prenoon sector, while oxygen sustained gaps are mostly in the afternoon sector with lower occurrence rate than that for protons. This is primarily due to the different charge exchange loss rates of protons and oxygen ions. This scenario is supported by particle‐tracing simulations, which reproduce most of the observed characteristics. Through model‐data comparison, we found that the spectral gaps at different local times are formed by two different types of mechanisms: (a) the gap is formed due to the extended drift time which is responsible for the gap appearing on the dayside for both proton and oxygen ions; (b) the gap is formed inside the Alfven layer, which accounts for the observed sustained gaps in proton energy spectrums but not in oxygen ions due to the different charge exchange losses at various energies on the preexisting ion populations that lie on closed drift paths. These findings may provide insight into our understanding of ion composition and possible wave generation in the inner magnetosphere.
Surface Water Dynamics and Rapid Lake Drainage in the Western Canadian Subarctic (1985–2020)
Authors: Travers‐Smith H. Z. , Lantz T. C. , Fraser R. H.
Published: December 2021

The area and distribution of surface water are shifting rapidly in many regions across the circumpolar Arctic. In this study, we explore the effects of climate and terrain factors on the area of lakes in the Northwest Territories, Canada. We used the Landsat satellite archive to map interannual changes in 5,328 lakes and ponds in the Lower Mackenzie Plain between 1985 and 2020. The high temporal resolution of our dataset allowed us to classify gradual and abrupt changes in lake area and identify rapid drainage events. We used Generalized Additive Models and Random Forests to test the effects of climate and terrain factors on changes in lake area. Despite increases in the area of smaller lakes driven by increasing precipitation, we found that the total lake area has decreased by approximately 1%. Overall, 29% of lakes exhibited an increasing trend in the area, while 11% exhibited a decreasing trend, and the majority of these changes (65%) were non‐linear in nature. Lakes located in fire scars were also 3.8 times more likely to show a decreasing trend in area. Analysis of a large fire indicates that lakes within the burned region exhibited declines in an area that persisted until the end of the study period 20 years after the fire. These declines are likely related to the impact of fire on thaw depth, groundwater connectivity, and the development of new drainage pathways. Our results highlight the importance of rapid drainage and wildfire as drivers of declines in the lake area.
Halftone spatial frequency domain imaging enables kilohertz high-speed label-free non-contact quantitative mapping of optical properties for strongly turbid media
Authors: Zhao Yanyu , Song Bowen , Wang Ming , Zhao Yang , Fan Yubo
Published: December 2021

The ability to quantify optical properties (i.e., absorption and scattering) of strongly turbid media has major implications on the characterization of biological tissues, fluid fields, and many others. However, there are few methods that can provide wide-field quantification of optical properties, and none is able to perform quantitative optical property imaging with high-speed (e.g., kilohertz) capabilities. Here we develop a new imaging modality termed halftone spatial frequency domain imaging (halftone-SFDI), which is approximately two orders of magnitude faster than the state-of-the-art, and provides kilohertz high-speed, label-free, non-contact, wide-field quantification for the optical properties of strongly turbid media. This method utilizes halftone binary patterned illumination to target the spatial frequency response of turbid media, which is then mapped to optical properties using model-based analysis. We validate the halftone-SFDI on an array of phantoms with a wide range of optical properties as well as in vivo human tissue. We demonstrate with an in vivo rat brain cortex imaging study, and show that halftone-SFDI can longitudinally monitor the absolute concentration as well as spatial distribution of functional chromophores in tissue. We also show that halftone-SFDI can spatially map dual-wavelength optical properties of a highly dynamic flow field at kilohertz speed. Together, these results highlight the potential of halftone-SFDI to enable new capabilities in fundamental research and translational studies including brain science and fluid dynamics.
DNA methylation in the inflammatory genes after neurosurgery and diagnostic ability of post-operative delirium
Authors: Yamanashi Takehiko , Nagao Takaaki , Wahba Nadia E. , Marra Pedro S. , Crutchley Kaitlyn J. , Meyer Alissa A. , Andreasen Ally J. , Hellman Mandy M. , Jellison Sydney S. , Hughes Christopher G. , Pandharipande Pratik P. , Howard, III Matthew A. , Kawasaki Hiroto , Iwata Masaaki , Hefti Marco M. , Shinozaki Gen
Published: December 2021

The pathophysiological mechanisms of postoperative delirium (POD) are still not clear, and no reliable biomarker is available to differentiate those with and without POD. Pre- and post-surgery blood from epilepsy subjects undergoing neurosurgery were collected. DNA methylation (DNAm) levels of the TNF gene, IL1B gene, and IL6 gene by the Illumina EPIC array method, and DNAm levels of the TNF gene by pyrosequencing, were analyzed. Blood from 37 subjects were analyzed by the EPIC array method, and blood from 27 subjects were analyzed by pyrosequencing. Several CpGs in the TNF gene in preoperative blood showed a negative correlation between their DNAm and age both in the POD group and in the non-POD group. However, these negative correlations were observed only in the POD group after neurosurgery. Neurosurgery significantly altered DNAm levels at 17 out of 24 CpG sites on the TNF gene, 8 out of 14 CpG sites on the IL1B gene, and 4 out of 14 CpG sites on the IL6 gene. Furthermore, it was found that the Inflammatory Methylation Index (IMI), which was based on the post-surgery DNAm levels at the selected five CpG sites, can be a potential detection tool for delirium with moderate accuracy; area under the curve (AUC) value was 0.84. The moderate accuracy of this IMI was replicated using another cohort from our previous study, in which the AUC was 0.79. Our findings provide further evidence of the potential role of epigenetics and inflammation in the pathophysiology of delirium.
SPTBN2 regulated by miR-424-5p promotes endometrial cancer progression via CLDN4/PI3K/AKT axis
Authors: Wang Pengling , Liu Ting , Zhao Zhendan , Wang Zhiling , Liu Shujie , Yang Xingsheng
Published: December 2021

Endometrioid Endometrial Cancer (EEC) is the main subtype of endometrial cancer. In our study, we demonstrated that SPTBN2 was significantly overexpressed in EEC tissues. Upregulated SPTBN2 expression was positively associated with poor prognosis. In addition, we testified that SPTBN2 knockdown significantly inhibited the proliferation, migration, and invasion of EEC cells. Moreover, we found SPTBN2 could interact with CLDN4 to promote endometrial cancer metastasis via PI3K/AKT pathway. Then we further demonstrated that CLDN4 is upregulated in EEC and promotes EEC metastasis. CLDN4 overexpression could partially reversed the decrease in cell migration and invasion caused by SPTBN2 downregulation. In addition, we confirmed that SPTBN2 was a target of miR-424-5p, which plays a tumor suppressor in endometrial cancer. Rescue experiments showed that inhibition of SPTBN2 could partially reverse the effect of miR-424-5p in EEC. In conclusion, we demonstrated that by acting as a significant target of miR-424-5p, SPTBN2 could interact with CLDN4 to promote endometrial cancer metastasis via PI3K/AKT pathway in EEC. Our study revealed the prognostic and metastatic effects of SPTBN2 in EEC, suggesting that SPTBN2 could serve as a prognostic biomarker and a target for metastasis therapy.
Visualizing band selective enhancement of quasiparticle lifetime in a metallic ferromagnet
Authors: Jo Na Hyun , Wu Yun , Trevisan Thaís V. , Wang Lin-Lin , Lee Kyungchan , Kuthanazhi Brinda , Schrunk Benjamin , Bud’ko S. L. , Canfield P. C. , Orth P. P. , Kaminski Adam
Published: December 2021

Electrons navigate more easily in a background of ordered magnetic moments than around randomly oriented ones. This fundamental quantum mechanical principle is due to their Bloch wave nature and also underlies ballistic electronic motion in a perfect crystal. As a result, a paramagnetic metal that develops ferromagnetic order often experiences a sharp drop in the resistivity. Despite the universality of this phenomenon, a direct observation of the impact of ferromagnetic order on the electronic quasiparticles in a magnetic metal is still lacking. Here we demonstrate that quasiparticles experience a significant enhancement of their lifetime in the ferromagnetic state of the low-density magnetic semimetal EuCd2As2, but this occurs only in selected bands and specific energy ranges. This is a direct consequence of the magnetically induced band splitting and the multi-orbital nature of the material. Our detailed study allows to disentangle different electronic scattering mechanisms due to non-magnetic disorder and magnon exchange. Such high momentum and energy dependence quasiparticle lifetime enhancement can lead to spin selective transport and potential spintronic applications.
Exponentially selective molecular sieving through angstrom pores
Authors: Sun P. Z. , Yagmurcukardes M. , Zhang R. , Kuang W. J. , Lozada-Hidalgo M. , Liu B. L. , Cheng H.-M. , Wang F. C. , Peeters F. M. , Grigorieva I. V. , Geim A. K.
Published: December 2021

Two-dimensional crystals with angstrom-scale pores are widely considered as candidates for a next generation of molecular separation technologies aiming to provide extreme, exponentially large selectivity combined with high flow rates. No such pores have been demonstrated experimentally. Here we study gas transport through individual graphene pores created by low intensity exposure to low kV electrons. Helium and hydrogen permeate easily through these pores whereas larger species such as xenon and methane are practically blocked. Permeating gases experience activation barriers that increase quadratically with molecules’ kinetic diameter, and the effective diameter of the created pores is estimated as ∼2 angstroms, about one missing carbon ring. Our work reveals stringent conditions for achieving the long sought-after exponential selectivity using porous two-dimensional membranes and suggests limits on their possible performance.
The concerted change in the distribution of cell cycle phases and zone composition in germinal centers is regulated by IL-21
Authors: Zotos Dimitra , Quast Isaak , Li-Wai-Suen Connie S. N. , McKenzie Craig I. , Robinson Marcus J. , Kan Andrey , Smyth Gordon K. , Hodgkin Philip D. , Tarlinton David M.
Published: December 2021

Humoral immune responses require germinal centres (GC) for antibody affinity maturation. Within GC, B cell proliferation and mutation are segregated from affinity-based positive selection in the dark zone (DZ) and light zone (LZ) substructures, respectively. While IL-21 is known to be important in affinity maturation and GC maintenance, here we show it is required for both establishing normal zone representation and preventing the accumulation of cells in the G1 cell cycle stage in the GC LZ. Cell cycle progression of DZ B cells is unaffected by IL-21 availability, as is the zone phenotype of the most highly proliferative GC B cells. Collectively, this study characterises the development of GC zones as a function of time and B cell proliferation and identifies IL-21 as an important regulator of these processes. These data help explain the requirement for IL-21 in normal antibody affinity maturation.
Cell-type-specific chromatin occupancy by the pioneer factor Zelda drives key developmental transitions in Drosophila
Authors: Larson Elizabeth D. , Komori Hideyuki , Gibson Tyler J. , Ostgaard Cyrina M. , Hamm Danielle C. , Schnell Jack M. , Lee Cheng-Yu , Harrison Melissa M.
Published: December 2021

During Drosophila embryogenesis, the essential pioneer factor Zelda defines hundreds of cis-regulatory regions and in doing so reprograms the zygotic transcriptome. While Zelda is essential later in development, it is unclear how the ability of Zelda to define cis-regulatory regions is shaped by cell-type-specific chromatin architecture. Asymmetric division of neural stem cells (neuroblasts) in the fly brain provide an excellent paradigm for investigating the cell-type-specific functions of this pioneer factor. We show that Zelda synergistically functions with Notch to maintain neuroblasts in an undifferentiated state. Zelda misexpression reprograms progenitor cells to neuroblasts, but this capacity is limited by transcriptional repressors critical for progenitor commitment. Zelda genomic occupancy in neuroblasts is reorganized as compared to the embryo, and this reorganization is correlated with differences in chromatin accessibility and cofactor availability. We propose that Zelda regulates essential transitions in the neuroblasts and embryo through a shared gene-regulatory network driven by cell-type-specific enhancers.
Safety and effectiveness of ulotaront (SEP-363856) in schizophrenia: results of a 6-month, open-label extension study
Authors: Correll Christoph U. , Koblan Kenneth S. , Hopkins Seth C. , Li Yan , Heather Dworak  , Goldman Robert , Loebel Antony
Published: December 2021

Ulotaront, a trace amine-associated receptor 1 (TAAR1) and serotonin 5-HT1A receptors agonist, has demonstrated efficacy in the treatment of patients with an acute exacerbation of schizophrenia in a 4-week, double-blind, placebo-controlled study. The aim of this 26-week open-label extension study was to evaluate the safety and effectiveness of ulotaront (25/50/75 mg/d) in patients who completed the initial 4-week study. Of the 193 4-week completers, 157 patients (81.3%) continued into the open-label extension study; 66.9% were completers. Among all extension phase patients, treatment with ulotaront was associated with minimal changes in body weight (mean [SD] change from double-blind baseline: −0.3 [3.7] kg), cholesterol (median change, −2.0 mg/dL), triglycerides (median, −5.0 mg/dL), and prolactin (female, median, −3.4 ng/mL; male, median, −2.7 ng/mL). Movement disorder scales showed no extrapyramidal effects. Twenty-six weeks of extension phase treatment was associated with a mean (95% CI) observed change from open-label baseline in the PANSS total score of −22.6 (−25.6, −19.6; effect size, 1.46), and a mean (95% CI) change in the CGI-Severity score of −1.0 (−1.2, −0.8; effect size, 1.07). Long-term treatment with the TAAR1 agonist ulotaront, in the daily dose range of 25–75 mg, was characterized by a relatively high completion rate, an adverse event profile notable for the absence of extrapyramidal-related adverse effects, a low liability for adverse weight and metabolic effects, and no effect on prolactin levels. Additional studies are needed to further confirm the long-term efficacy and safety of ulotaront.
Constructing gene regulatory networks using epigenetic data
Authors: Sonawane Abhijeet Rajendra , DeMeo Dawn L. , Quackenbush John , Glass Kimberly
Published: December 2021

The biological processes that drive cellular function can be represented by a complex network of interactions between regulators (transcription factors) and their targets (genes). A cell’s epigenetic state plays an important role in mediating these interactions, primarily by influencing chromatin accessibility. However, how to effectively use epigenetic data when constructing a gene regulatory network remains an open question. Almost all existing network reconstruction approaches focus on estimating transcription factor to gene connections using transcriptomic data. In contrast, computational approaches for analyzing epigenetic data generally focus on improving transcription factor binding site predictions rather than deducing regulatory network relationships. We bridged this gap by developing SPIDER, a network reconstruction approach that incorporates epigenetic data into a message-passing framework to estimate gene regulatory networks. We validated SPIDER’s predictions using ChIP-seq data from ENCODE and found that SPIDER networks are both highly accurate and include cell-line-specific regulatory interactions. Notably, SPIDER can recover ChIP-seq verified transcription factor binding events in the regulatory regions of genes that do not have a corresponding sequence motif. The networks estimated by SPIDER have the potential to identify novel hypotheses that will allow us to better characterize cell-type and phenotype specific regulatory mechanisms.
A phase 1 trial of lipid-encapsulated mRNA encoding a monoclonal antibody with neutralizing activity against Chikungunya virus
Authors: August Allison , Attarwala Husain Z. , Himansu Sunny , Kalidindi Shiva , Lu Sophia , Pajon Rolando , Han Shu , Lecerf Jean-Michel , Tomassini Joanne E. , Hard Marjie , Ptaszek Leon M. , Crowe James E. , Zaks Tal
Published: December 2021

Chikungunya virus (CHIKV) infection causes acute disease characterized by fever, rash and arthralgia, which progresses to severe and chronic arthritis in up to 50% of patients. Moreover, CHIKV infection can be fatal in infants or immunocompromised individuals and has no approved therapy or prevention. This phase 1, first-in-human, randomized, placebo-controlled, proof-of-concept trial conducted from January 2019 to June 2020 evaluated the safety and pharmacology of mRNA-1944, a lipid nanoparticle-encapsulated messenger RNA encoding the heavy and light chains of a CHIKV-specific monoclonal neutralizing antibody, CHKV-24 (NCT03829384). The primary outcome was to evaluate the safety and tolerability of escalating doses of mRNA-1944 administered via intravenous infusion in healthy participants aged 18–50 years. The secondary objectives included determination of the pharmacokinetics of mRNA encoding for CHKV-24 immunoglobulin heavy and light chains and ionizable amino lipid component and the pharmacodynamics of mRNA-1944 as assessed by serum concentrations of mRNA encoding for CHKV-24 immunoglobulin G (IgG), plasma concentrations of ionizable amino lipid and serum concentrations of CHKV-24 IgG. Here we report the results of a prespecified interim analysis of 38 healthy participants who received intravenous single doses of mRNA-1944 or placebo at 0.1, 0.3 and 0.6 mg kg−1, or two weekly doses at 0.3 mg kg−1. At 12, 24 and 48 h after single infusions, dose-dependent levels of CHKV-24 IgG with neutralizing activity were observed at titers predicted to be therapeutically relevant concentrations (≥1 µg ml−1) across doses that persisted for ≥16 weeks at 0.3 and 0.6 mg kg−1 (mean t1/2 approximately 69 d). A second 0.3 mg kg−1 dose 1 week after the first increased CHKV-24 IgG levels 1.8-fold. Adverse effects were mild to moderate in severity, did not worsen with a second mRNA-1944 dose and none were serious. To our knowledge, mRNA-1944 is the first mRNA-encoded monoclonal antibody showing in vivo expression and detectable ex vivo neutralizing activity in a clinical trial and may offer a treatment option for CHIKV infection. Further evaluation of the potential therapeutic use of mRNA-1944 in clinical trials for the treatment of CHIKV infection is warranted.
Cryo-EM structures of human RNA polymerase I
Authors: Misiaszek Agata D. , Girbig Mathias , Grötsch Helga , Baudin Florence , Murciano Brice , Lafita Aleix , Müller Christoph W.
Published: December 2021

RNA polymerase I (Pol I) specifically synthesizes ribosomal RNA. Pol I upregulation is linked to cancer, while mutations in the Pol I machinery lead to developmental disorders. Here we report the cryo-EM structure of elongating human Pol I at 2.7 Å resolution. In the exit tunnel, we observe a double-stranded RNA helix that may support Pol I processivity. Our structure confirms that human Pol I consists of 13 subunits with only one subunit forming the Pol I stalk. Additionally, the structure of human Pol I in complex with the initiation factor RRN3 at 3.1 Å resolution reveals stalk flipping upon RRN3 binding. We also observe an inactivated state of human Pol I bound to an open DNA scaffold at 3.3 Å resolution. Lastly, the high-resolution structure of human Pol I allows mapping of disease-related mutations that can aid understanding of disease etiology.
Fast-running theropods tracks from the Early Cretaceous of La Rioja, Spain
Authors: Navarro-Lorbés Pablo , Ruiz Javier , Díaz-Martínez Ignacio , Isasmendi Erik , Sáez-Benito Patxi , Viera Luis , Pereda-Suberbiola Xabier , Torices Angélica
Published: December 2021

Theropod behaviour and biodynamics are intriguing questions that paleontology has been trying to resolve for a long time. The lack of extant groups with similar bipedalism has made it hard to answer some of the questions on the matter, yet theoretical biomechanical models have shed some light on the question of how fast theropods could run and what kind of movement they showed. The study of dinosaur tracks can help answer some of these questions due to the very nature of tracks as a product of the interaction of these animals with the environment. Two trackways belonging to fast-running theropods from the Lower Cretaceous Enciso Group of Igea (La Rioja) are presented here and compared with other fast-running theropod trackways published to date. The Lower Cretaceous Iberian fossil record and some features present in these footprints and trackways suggest a basal tetanuran, probably a carcharodontosaurid or spinosaurid, as a plausible trackmaker. Speed analysis shows that these trackways, with speed ranges of 6.5–10.3 and 8.8–12.4 ms−1, testify to some of the top speeds ever calculated for theropod tracks, shedding light on the question of dinosaur biodynamics and how these animals moved.
Role of acquired von Willebrand syndrome in the development of bleeding complications in patients treated with Impella RP devices
Authors: Oezkur Mehmet , Reda Sara , Rühl Heiko , Theuerkauf Nils , Kreyer Stefan , Duerr Georg Daniel , Charitos Efstratios , Silaschi Miriam , Medina Marta , Zimmer Sebastian , Putensen Christian , Treede Hendrik
Published: December 2021

Axial flow pumps are standard treatment in cases of cardiogenic shock and high-risk interventions in cardiology and cardiac surgery, although the optimal anticoagulation strategy remains unclear. We evaluated whether laboratory findings could predict bleeding complications and acquired von Willebrand syndrome (avWS) among patients who were treated using axial flow pumps. We retrospectively evaluated 60 consecutive patients who received Impella devices (Impella RP: n = 20, Impella CP/5.0: n = 40; Abiomed Inc., Danvers, USA) between January 2019 and December 2020. Thirty-two patients (53.3%) experienced major or fatal bleeding complications (Bleeding Academic Research Consortium score of > 3) despite intravenous heparin being used to maintain normal activated partial thromboplastin times (40–50 s). Extensive testing was performed for 28 patients with bleeding complications (87.5%). Relative to patients with left ventricular support, patients with right ventricular support were less likely to develop avWS (87.5% vs. 58.8%, p = 0.035). Bleeding was significantly associated with avWS (odds ratio [OR]: 20.8, 95% confidence interval [CI]: 3.3–128.5; p = 0.001) and treatment duration (OR: 1.3, 95% CI 1.09–1.55; p = 0.003). Patients with avWS had longer Impella treatment than patients without avWS (2 days [1–4.7 days] vs. 7.3 days [3.2–13.0 days]). Bleeding complications during Impella support were associated with avWS in our cohort, while aPTT monitoring was not sufficient to prevent bleeding complications. A more targeted anticoagulation monitoring might be needed for patients who receive Impella devices.
Enzyme systems involved in glucosinolate metabolism in Companilactobacillus farciminis KB1089
Authors: Watanabe Hiroko , Usami Riku , Kishino Shigenobu , Osada Kengo , Aoki Yudai , Morisaka Hironobu , Takahashi Masatomo , Izumi Yoshihiro , Bamba Takeshi , Aoki Wataru , Suganuma Hiroyuki , Ogawa Jun
Published: December 2021

Cruciferous vegetables are rich sources of glucosinolates (GSLs). GSLs are degraded into isothiocyanates, which are potent anticarcinogens, by human gut bacteria. However, the mechanisms and enzymes involved in gut bacteria-mediated GSL metabolism are currently unclear. This study aimed to elucidate the enzymes involved in GSL metabolism in lactic acid bacteria, a type of gut bacteria. Companilactobacillus farciminis KB1089 was selected as a lactic acid bacteria strain model that metabolizes sinigrin, which is a GSL, into allylisothiocyanate. The sinigrin-metabolizing activity of this strain is induced under glucose-absent and sinigrin-present conditions. A quantitative comparative proteomic analysis was conducted and a total of 20 proteins that were specifically expressed in the induced cells were identified. Three candidate proteins, β-glucoside-specific IIB, IIC, IIA phosphotransferase system (PTS) components (CfPttS), 6-phospho-β-glucosidase (CfPbgS) and a hypothetical protein (CfNukS), were suspected to be involved in sinigrin-metabolism and were thus investigated further. We hypothesize a pathway for sinigrin degradation, wherein sinigrin is taken up and phosphorylated by CfPttS, and subsequently, the phosphorylated entity is degraded by CfPbgS. As expression of both pttS and pbgS genes clearly gave Escherichia coli host strain sinigrin converting activity, these genes were suggested to be responsible for sinigrin degradation. Furthermore, heterologous expression analysis using Lactococcus lactis suggested that CfPttS was important for sinigrin degradation and CfPbgS degraded phosphorylated sinigrin.
Chewing increases postprandial diet-induced thermogenesis
Authors: Hamada Yuka , Hayashi Naoyuki
Published: December 2021

Slow eating, which involves chewing food slowly and thoroughly, is an effective strategy for controlling appetite in order to avoid being overweight or obese. Slow eating also has the effect of increasing postprandial energy expenditure (diet-induced thermogenesis). It is still unclear whether this is due to oral stimuli; that is, the duration of tasting food in the mouth and the duration of chewing. To investigate the effects of oral stimuli on diet-induced thermogenesis in 11 healthy normal weight males, we conducted a randomized crossover study comprising three trials: (1) drinking liquid food normally, (2) drinking liquid food after tasting, and (3) adding chewing while tasting. Oral stimuli (i.e., the duration of tasting liquid food in the mouth and the duration of chewing) significantly increased diet-induced thermogenesis after drinking liquid food. This result demonstrates that the increase in diet-induced thermogenesis is due to oral stimuli rather than the influence of the food bolus. Increased diet-induced thermogenesis induced by chewing and taste stimuli may help to prevent overweight and obesity.
Detection of increased serum miR-122-5p and miR-455-3p levels before the clinical diagnosis of liver cancer in people with type 2 diabetes
Authors: Lee Heung Man , Wong Willy Kwun Kiu , Fan Baoqi , Lau Eric Siu , Hou Yong , O Chun Kwan , Luk Andrea On Yan , Chow Elaine Yee Kwan , Ma Ronald Ching Wan , Chan Juliana Chung Ngor , Kong Alice Pik Shan
Published: December 2021

People with type 2 diabetes (T2D) have increased cancer risk. Liver cancer (LC) has a high prevalence in East Asia and is one of the leading causes of cancer death globally. Diagnosis of LC at early stage carries good prognosis. We used stored serum from patients of Hong Kong Diabetes Register before cancer diagnosis to extract RNA to screen for microRNA markers for early detection of LC in T2D. After screening with Affymetrix GeneChip microarray with serum RNA from 19 incident T2D LC (T2D-LC), 20 T2D cancer free (T2D-CF) and 20 non-T2D non-cancer patients, top signals were validated in a 3-group comparison including 1888 T2D-CF, 127 T2D-LC, and 487 T2D patients with non-liver cancer patients using qPCR. We detected 2.55-fold increase in miR-122-5p and 9.21-fold increase in miR-455-3p in the T2D-LC group. Using ROC analysis, miR-122-5p and miR-455-3p jointly predicted LC with an area under the curve of 0.770. After adjustment for confounders, each unit increase of miR-455-3p increased the odds ratio for liver cancer by 1.022. Increased serum levels of miR-122-5p and miR-455-3p were independently associated with increased risk of incident LC in T2D and may serve as potential biomarkers for early detection of LC in T2D.
AMPK modulation ameliorates dominant disease phenotypes of CTRP5 variant in retinal degeneration
Authors: Miyagishima Kiyoharu J. , Sharma Ruchi , Nimmagadda Malika , Clore-Gronenborn Katharina , Qureshy Zoya , Ortolan Davide , Bose Devika , Farnoodian Mitra , Zhang Congxiao , Fausey Andrew , Sergeev Yuri V. , Abu-Asab Mones , Jun Bokkyoo , Do Khanh V. , Kautzman Guerin Marie-Audrey , Calandria Jorgelina , George Aman , Guan Bin , Wan Qin , Sharp Rachel C. , Cukras Catherine , Sieving Paul A. , Hufnagel Robert B. , Bazan Nicolas G. , Boesze-Battaglia Kathleen , Miller Sheldon , Bharti Kapil
Published: December 2021

Late-onset retinal degeneration (L-ORD) is an autosomal dominant disorder caused by a missense substitution in CTRP5. Distinctive clinical features include sub-retinal pigment epithelium (RPE) deposits, choroidal neovascularization, and RPE atrophy. In induced pluripotent stem cells-derived RPE from L-ORD patients (L-ORD-iRPE), we show that the dominant pathogenic CTRP5 variant leads to reduced CTRP5 secretion. In silico modeling suggests lower binding of mutant CTRP5 to adiponectin receptor 1 (ADIPOR1). Downstream of ADIPOR1 sustained activation of AMPK renders it insensitive to changes in AMP/ATP ratio resulting in defective lipid metabolism, reduced Neuroprotectin D1(NPD1) secretion, lower mitochondrial respiration, and reduced ATP production. These metabolic defects result in accumulation of sub-RPE deposits and leave L-ORD-iRPE susceptible to dedifferentiation. Gene augmentation of L-ORD-iRPE with WT CTRP5 or modulation of AMPK, by metformin, re-sensitize L-ORD-iRPE to changes in cellular energy status alleviating the disease cellular phenotypes. Our data suggests a mechanism for the dominant behavior of CTRP5 mutation and provides potential treatment strategies for L-ORD patients.
Grazing weakens competitive interactions between active methanotrophs and nitrifiers modulating greenhouse-gas emissions in grassland soils
Authors: Pan Hong , Feng Haojie , Liu Yaowei , Lai Chun-Yu , Zhuge Yuping , Zhang Qichun , Tang Caixian , Di Hongjie , Jia Zhongjun , Gubry-Rangin Cécile , Li Yong , Xu Jianming
Published: December 2021

Grassland soils serve as a biological sink and source of the potent greenhouse gases (GHG) methane (CH4) and nitrous oxide (N2O). The underlying mechanisms responsible for those GHG emissions, specifically, the relationships between methane- and ammonia-oxidizing microorganisms in grazed grassland soils are still poorly understood. Here, we characterized the effects of grazing on in situ GHG emissions and elucidated the putative relations between the active microbes involving in methane oxidation and nitrification activity in grassland soils. Grazing significantly decreases CH4 uptake while it increases N2O emissions basing on 14-month in situ measurement. DNA-based stable isotope probing (SIP) incubation experiment shows that grazing decreases both methane oxidation and nitrification processes and decreases the diversity of active methanotrophs and nitrifiers, and subsequently weakens the putative competition between active methanotrophs and nitrifiers in grassland soils. These results constitute a major advance in our understanding of putative relationships between methane- and ammonia-oxidizing microorganisms and subsequent effects on nitrification and methane oxidation, which contribute to a better prediction and modeling of future balance of GHG emissions and active microbial communities in grazed grassland ecosystems.
Extensive Mendelian randomization study identifies potential causal risk factors for severe COVID-19
Authors: Sun Yitang , Zhou Jingqi , Ye Kaixiong
Published: December 2021

Background

Identifying causal risk factors for severe coronavirus disease 2019 (COVID-19) is critical for its prevention and treatment. Many associated pre-existing conditions and biomarkers have been reported, but these observational associations suffer from confounding and reverse causation.

Methods

Here, we perform a large-scale two-sample Mendelian randomization (MR) analysis to evaluate the causal roles of many traits in severe COVID-19.

Results

Our results highlight multiple body mass index (BMI)-related traits as risk-increasing: BMI (OR: 1.89, 95% CI: 1.51–2.37), hip circumference (OR: 1.46, 1.15–1.85), and waist circumference (OR: 1.82, 1.36–2.43). Our multivariable MR analysis further suggests that the BMI-related effect might be driven by fat mass (OR: 1.63, 1.03–2.58), but not fat-free mass (OR: 1.00, 0.61–1.66). Several white blood cell counts are negatively associated with severe COVID-19, including those of neutrophils (OR: 0.76, 0.61–0.94), granulocytes (OR: 0.75, 0.601–0.93), and myeloid white blood cells (OR: 0.77, 0.62–0.96). Furthermore, some circulating proteins are associated with an increased risk of (e.g., zinc-alpha-2-glycoprotein) or protection from severe COVID-19 (e.g., prostate-associated microseminoprotein).

Conclusions

Our study suggests that fat mass and white blood cells might be involved in the development of severe COVID-19. It also prioritizes potential risk and protective factors that might serve as drug targets and guide the effective protection of high-risk individuals.
A dissolved inorganic carbon measurement method featuring self-calibration function via an electrodialytic generator
Authors: Peng Yonghan , Wang Jiaying , Zhang Feifang , Yang Bingcheng
Published: December 2021

A simple dissolved inorganic carbon (DIC) measurement method featuring self-calibration function via an electrodialytic bicarbonate eluent generator (cEDG) is described.
Rapid determination of 210Pb and 210Po by sequential cloud point extraction for environmental monitoring
Authors: Blanchet-Chouinard Guillaume , Larivière Dominic
Published: December 2021

A sequential cloud point extraction procedure was developed and validated for the quantification of 210Pb and 210Po in environmental matrices.
Enantioselective formal [2 + 2 + 2] cycloaddition of 1,3,5-triazinanes to construct tetrahydropyrimidin-4-one derivatives
Authors: Ruan Peiran , Tang Qiong , Yang Zun , Liu Xiaohua , Feng Xiaoming
Published: December 2021

An enantioselective [2 + 2 + 2] cycloaddition of 1,3,5-triazinanes was achieved and a broad range of chiral tertiary/quaternary tetrahydropyrimidin-4-one derivatives were obtained.
Dual nature of high-temperature electronic transport in layered perovskite-like cobaltites: exhaustive consideration of experimental features observed
Authors: Politov B. V. , Suntsov A. Yu.
Published: December 2021

Complex oxides with the general formula Pr1−xYxBaCo2−yNiyO6−δ (x = 0, 0.1, y = 0, 0.2) were successfully synthesized via combustion of organo-metallic precursors.
A recyclable metal-free catalytic system for the cationic ring-opening polymerization of glycidol under ambient conditions
Authors: Kim Si Eun , Yang Hyun Ji , Choi Soonyoung , Hwang Eunbyul , Kim Minseong , Paik Hyun-Jong , Jeong Ji-Eun , Park Young Il , Kim Jin Chul , Kim Byeong-Su , Lee Sang-Ho
Published: December 2021

We developed a recyclable catalytic system for the metal-free cationic polymerization under ambient conditions, which provides mild and environmentally friendly polymerization condition as well as unique polymer topology.
Elucidation of reaction network and kinetics between cellulose-derived 1,2-propanediol and methanol for one-pot biofuel production
Authors: Dastidar Raka G. , Galebach Peter H. , Lanci Michael P. , Wang Chengrong , Du Yi , Huber George W.
Published: December 2021

Cellulose-derived 1,2-propanediol undergoes C–C coupling with methanol to produce higher diols, which then undergo C–O and C–C scission to produce fuel-range aliphatic alcohols.
A fast, single column extraction chromatography method for the isolation of neodymium from iron-rich materials prior to radiogenic isotope ratio measurements
Authors: Gannoun Abdelmouhcine , Suchorski Krzysztof , Pin Christian
Published: December 2021

A novel separation method is described for the separation of Nd from Fe-rich, silicate samples in view of isotopic analyses.
Electroreduction of carbon dioxide to formate using highly efficient bimetallic Sn–Pd aerogels
Authors: Abdinejad Maryam , Motlagh Mozhgan Khorasani , Noroozifar Meissam , Kraatz Heinz Bernhard
Published: December 2021

Electrochemical reduction of carbon dioxide (CO2) to valuable materials is a promising approach to suppress atmospheric CO2 levels.
Post-synthetic modification and chemical modulation of the ZIF-8 MOF using 3-mercaptopropionic acid (MPA): a multi-technique study on thermodynamic and kinetic aspects
Authors: Segovia Gustavo M. , Allegretto Juan A. , Tuninetti Jimena S. , Pizarro Lucía B. , Picco Agustín S. , Ceolín Marcelo , Lüdtke Tanja Ursula , Bindini Elisa , Di Silvio Desiré , Moya Sergio E. , Azzaroni Omar , Rafti Matías
Published: December 2021

We hereby report on the thermodynamic and kinetic aspects of ZIF-8 MOF synthesis when performed using methanolic solutions of precursors and 3-mercaptopropionic acid (MPA) acting as a chemical modifying agent.
Sequential design of adsorption simulations in metal–organic frameworks
Authors: Mukherjee Krishnendu , Dowling Alexander W. , Colón Yamil J.
Published: December 2021

An active learning protocol is introduced to sequentially build surrogate models for predicting gas adsorption. The method is shown to work for methane and carbon dioxide adsorption in Cu–BTC MOF for isotherms and pressure–temperature phase space.
Enantio- and regioselective asymmetric allylic substitution using a chiral aminophosphinite ruthenium complex: an experimental and theoretical investigation
Authors: Jena Rajesh K. , Das Dhiraj
Published: December 2021

A new chiral –P,N-ligand, and its ruthenium(ii) complex has been synthesized, which catalyzed the highly regioselective O-allylation of phenols and carboxylic acids to afford the branched product as the major product with high to low enantioselectivities.
Exploring the therapeutic mechanisms of Cassia glauca in diabetes mellitus through network pharmacology, molecular docking and molecular dynamics
Authors: Dwivedi Prarambh S. R. , Patil Rajesh , Khanal Pukar , Gurav Nilambari S. , Murade Vaishali D. , Hase Dinesh P. , Kalaskar Mohan G. , Ayyanar Muniappan , Chikhale Rupesh V. , Gurav Shailendra S.
Published: December 2021

Cassia glauca is reported for anti-diabetic action and is also used as an ethnomedicine.
LASP-1 interacts with ErbB2 in ovarian cancer cells
Authors: Sidhanth Chirukandath , Bindhya Sadhanandhan , Shabna Aboo , Krishnapriya Shyama , Manasa Pacharla , Nagare Rohit Pravin , Joshua Thanda , Sneha Smarkan , Murhekar Kanchan , Ganesan Trivadi Sundaram
Published: December 2021

LASP-1 was identified as a protein following mass spectrometric analysis of phosphoproteins consequent to signaling by ErbB2 in SKOV-3 cells. It has been previously identified as an oncogene and is located on chromosomal arm 17q 0.76 Mb centromeric to ErbB2. It is expressed in serous ovarian cancer cell lines as a 40 kDa protein. In SKOV-3 cells, it was phosphorylated and was inhibited by Lapatinib and CP7274714. LASP-1 co-immunoprecipitated with ErbB2 in SKOV-3 cells, suggesting a direct interaction. This interaction and phosphorylation were independent of the kinase activity of ErbB2. Moreover, the binding of LASP-1 to ErbB2 was independent of the tyrosine phosphorylation of LASP-1. LASP-1 was neither expressed on the surface epithelium of the normal ovary nor in the fallopian tube. It was expressed in 28% of ovarian tumours (n = 101) that did not significantly correlate with other clinical factors. In tumours from patients with invasive ductal carcinoma of the breast who had ErbB2 amplification (3+), LASP-1 was expressed in 3/20 (P < 0.001). Analysis of the expression of an independent dataset of ovarian and breast tumours from TCGA showed the significant co-occurrence of ErbB2 and LASP-1 (P < 0.01). These results suggest that LASP-1 and ErbB2 interaction could be important in the pathogenesis of ovarian cancer.
Predicting aircraft taxiing estimated time of arrival by cluster analysis
Authors: Tang Xinmin , Ji Xiaoqi , Liu Jinan
Published: December 2021

In order to predict the aircraft taxiing estimated time of arrival (ETA) to reduce scene conflicts and improve the operating efficiency of airports, the Kalman filter algorithm is employed to preprocess historical trajectory data for an airport scene. For the first time, in order to measure the distance between trajectory samples, the aircraft taxiing period and the number of aircraft in a scene are used as sample features for aircraft taxiing ETA prediction. The dynamic time warping algorithm is employed to extract the different features of the trajectory. The Euclidean distance between two sample features is taken as their similarity. The initial clustering centre is determined based on the divided difference maximum principle by using the K‐means algorithm to cluster samples and selecting the cluster with the highest matching degree according to the time period of the aircraft under planning and the number of aircraft operating in the scene. The trajectory sequence for the sample at the cluster centre and the static path planned by the tower are combined to predict the aircraft taxiing ETA. The accuracy of this method at predicting the aircraft taxiing ETA was demonstrated in simulations by comparing and analysing actual trajectory data with predicted taxiing ETA.