bluuebunny/crossref_metadata_2025 huggingface dataset:
Likely P‐to‐S Conversion at the Core‐Mantle Boundary Extracted From Array Processing of Noise Records
Authors: Liu Tianze , Shearer Peter M.
Published: March 2022

Seismic noise has been widely used to image Earth's structure in the past decades as a powerful supplement to earthquake signals. Although the seismic noise field contains both surface‐wave and body‐wave components, most previous studies have focused on surface waves due to their large amplitudes. Here, we use array analyses to identify body‐wave noise traveling as PKP waves. We find that by cross‐correlating the array‐stacked horizontal‐ and vertical‐component data in the time windows containing the PKP noise signals, we extract a phase likely representing PKS‐PKP, the differential phase between PKS and PKP. This phase can potentially be used for shear‐wave‐splitting analysis. Our results also suggest that the sources of body‐wave noise are extremely heterogeneous in both space and time, which should be accounted for in future studies using body‐wave noise to image Earth structure.
Thermal Tides in the Martian Atmosphere Near Northern Summer Solstice Observed by ACS/TIRVIM Onboard TGO
Authors: Fan Siteng , Guerlet Sandrine , Forget François , Bierjon Antoine , Millour Ehouarn , Ignatiev Nikolay , Shakun Alexey , Grigoriev Alexey , Trokhimovskiy Alexander , Montmessin Franck , Korablev Oleg
Published: March 2022

Thermal tides in the Martian atmosphere are analyzed using temperature profiles retrieved from nadir observations obtained by the TIRVIM Fourier‐spectrometer, part of the Atmospheric Chemistry Suite onboard the ExoMars Trace Gas Orbiter. The data is selected near the northern summer solstice at solar longitude (LS) 75°–105° of Martian Year 35. The observations have a full local time coverage, which enables analyses of daily temperature anomalies. The observed zonal mean temperature is lower by 4–6 K at ∼100 Pa, but higher toward the summer pole, compared to the Laboratoire de Météorologie Dynamique (LMD) Mars General Circulation Model (GCM). Wave mode decomposition shows dominant diurnal tide and important semi‐diurnal tide and diurnal Kelvin wave, with maximal amplitudes of 5, 3, and 2.5 K, respectively, from tens to hundreds of Pa. The results generally agree well with the LMD Mars GCM, but with noticeable earlier phases of diurnal (∼1 hr) and semi‐diurnal (∼3 hr) tides.
Widespread Aseismic Slip Along the Makran Megathrust Triggered by the 2013 Mw 7.7 Balochistan Earthquake
Authors: Lv Xiaoran , Amelung Falk , Shao Yun
Published: March 2022

InSAR time series data for the 2014–2021 period reveal up to 20 cm of radar line‐of‐sight displacements in the area of the 2013 Mw 7.7 Balochistan earthquake northwest of the Hoshab Fault in the eastern Makran subduction zone in southwest Pakistan. We show that surface displacements were caused by ∼80 cm of aseismic slip along a 5,500‐km2‐wide subhorizontal patch of the megathrust fault. The corresponding moment is Mw 7.3. The percentage of slip in plate‐perpendicular direction ranges from ∼65% in the northwest to 96% in the southeast. Slip is consistent with shear stress imparted by the 2013 earthquake. The triggered aseismic slip suggests that this section of the megathrust is decoupled. The implication for the seismic potential of the subduction zone is that the megathrust is fully locked to at most 220 km distance from the trench, consistent with the lack of M ≥ 9 earthquakes in the historic record.
The Influencing Mechanism of a Mid‐Latitude Westerly Trough on Stratospheric Gravity Waves Generated by Typhoon Lekima (2019)
Authors: Wang Xu , Zhang Lifeng , Wang Yuan , Zhang Yun
Published: March 2022

The mechanism by which a mid‐latitude trough influenced the gravity waves (GWs) generated by Typhoon Lekima (2019) was studied by changing the initial fields in a series of model experiments. A peak in GW intensity (GWI) develops as typhoons weaken. The vertical speed shows the patterns of GWs generated by the typhoon and trough are the same during this peak GWI period. The typhoon generates the main part of the GWs and the trough enhances their intensity. The phase speed spectra show intense GWs occur when the GWs generated by the typhoon and trough propagate at the same phase speed. The GWI generated by the trough and typhoon were calculated separately in the control experiment, and their sum shows the peak GWI was caused mainly by in‐phase superposition. Finally, the model of the GWs superposition was proposed to quantitatively verify the existence of waves liner positive superposition.
High‐Resolution and Accurate Low‐Latitude Gridded Electron Density Generation and Evaluation
Authors: He Jianhui , Yue Xinan , Le Huijun , Ren Zhipeng , Ding Feng
Published: March 2022

The accurate specification of three‐dimensional (3‐D) ionosphere states is crucial to positioning, navigation, and communication systems, especially in low‐latitude and equatorial regions. In this work, the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC‐2) radio occultation total electron content was assimilated around a whole year from October 2020 to September 2021 via the Kalman filter (KF) data assimilation system. This system includes an empirical ionosphere background model and the KF data assimilation algorithm. Accurate 3‐D ionosphere data assimilation results were produced hourly with spatial resolutions of 2° latitude, 5° longitude, and 20 km height in low‐latitude and equatorial regions. First, the results were validated by Massachusetts Institute of Technology vertical total electron content and global ionosonde data. The ionosphere vertical total electron content and the critical frequency at the F2 layer agree well with the independent observations. Then, a general ionosphere climatological pattern is found in the reconstructed 3D ionosphere results, including seasonal variation, annual asymmetry, and December anomaly. In addition, the results can well capture the daily spatial and temporal ionospheric variations in the day‐to‐day variability, the longitudinal wave 4 structures, and the interhemispheric asymmetry transition of the equatorial ionization anomaly crests. The current results demonstrate that assimilating COSMIC‐2 TEC observations can further improve the 3D ionosphere specification in low‐latitude and equatorial regions and can also contribute to physical research on ionosphere variability characteristics.
Landing Site Selection and Characterization of Tianwen‐1 (Zhurong Rover) on Mars
Authors: Wu Bo , Dong Jie , Wang Yiran , Rao Wei , Sun Zezhou , Li Zhaojin , Tan Zhiyun , Chen Zeyu , Wang Chuang , Liu Wai Chung , Chen Long , Zhu Jiaming , Li Hongliang
Published: March 2022

The Chinese Mars rover Zhurong onboard the Tianwen‐1 probe successfully landed on Mars in May 2021. Here, we report our efforts in selecting a landing site for Zhurong within a pre‐identified landing region in southern Utopia Planitia. Using the high‐resolution images collected by a camera onboard the Tianwen‐1 orbiter, the landing region was analyzed in detail in terms of surface slopes, crater densities and rock abundances, which enabled the optimized determination of a landing ellipse (56 × 22 km for the major and minor axes) with minimum hazards and assisted the successful landing of the Zhurong rover. We also characterized the landing site and region after landing. Surface images captured by a camera onboard the Zhurong rover revealed a low rock abundance of approximately 4% at the landing site, similar to the rock measurements from orbital data before landing. Images of the surface features and a hole excavated by the pulsed retrorockets beneath the lander suggested a shallow regolith structure with a surficial layer of dust and sand over a layer of duricrust, and brecciated/fragmented rocks and bedrocks beneath. Crater size‐frequency distribution analysis indicated that the landing region might have experienced multiple episodes of resurfacing.
The Influence of In‐Channel Obstacles on River Sound
Authors: Osborne William A. , Hodge Rebecca A. , Love Gordon D. , Hawkin Peter , Hawkin Ruth E.
Published: March 2022

The sound of a river can change from a babbling brook to a thunderous torrent, and we have previously shown that there is the potential to predict river stage from the river's sub‐aerial sound. Here, we examined how alterations in channel configuration can change the relationship between stage and sound pressure level using a white water course to simulate a real‐world scale channel. By using blocks as roughness elements (REs), we were able to customize the course's obstacles, creating towers of different heights and placements. We then ran a varied flow discharge of up to 10 m3 s−1. We used data collected from microphones, a hydrophone and cameras to monitor the flow and to understand the processes occurring. In addition to sound processing, we used image analysis to calculate the area of white water on the surface of the water to determine the mechanism for sound production. Our analysis showed the likeliest source of sub‐aerial sound is from white water being produced from the flow's interaction with the REs, with the relationship between white water value and sound relationship having an R2 between 0.35 and 0.82. In terms of influence on sound, we found that the height of the REs is more important than their spatial distribution, with the taller the RE, the better the logarithmic relationship between sound and stage. We suggest that monitoring in a natural setting will work best in the places with the tallest obstacles and that the quality of the sound‐stage relationship is dependent on RE height.
Maintenance of Cyclonic Vortex During Monsoon Intraseasonal Oscillation: A View From Kinetic Energy Budget
Authors: Li Baosheng , Zhou Lei , Qin Jianhuang , Meng Ze
Published: March 2022

The Monsoon intraseasonal oscillation (MISO) is the predominant variability over the tropical Indian Ocean during the Indian summer monsoon. A cyclonic vortex plays a critical role in the northward propagation of MISO. Here, we find that the pronounced intraseasonal kinetic energy accompanying the vortex is attributable to the barotropic energy gain from the background circulation. In particular, due to the phase shift between vortex and low‐level horizontal wind convergence, the covariance of the intraseasonal easterly and downdraft reinforces the intraseasonal kinetic energy before vortex. In contrast, the interaction between westerly and updraft nourishes the kinetic energy after vortex. Overall, the nonlinear processes across different scales are vital for the energy exchange during MISO, and this is dynamically different from that of Madden‐Julian oscillations. It implies that although these two major intraseasonal oscillations share the same spatiotemporal scales over the Indian Ocean, they are controlled by fundamentally different dynamical processes.
Characteristic Features of V0 Layer in the Venus Ionosphere as Observed by the Akatsuki Orbiter: Evidence for Its Presence During the Local Noon and Post‐Sunset Conditions
Authors: Tripathi Keshav R. , Choudhary R. K. , Ambili K. M. , Imamura T. , Ando H.
Published: March 2022

Characteristic features of the Venus ionosphere below the V1 base, named as V0 layer, have been studied using the Radio Science payload onboard Akatsuki orbiter. An ionospheric layer below the V1 base is known to be present in the Venus ionosphere but found to be geographically localized, seen mostly during the daytime between 55 and 90° solar zenith angle (SZA). We, for the first time, show its presence at different latitudes and SZA, including near the equator during the local noon and post‐sunset hours. The maximum density of this layer was ∼4 × 1010 m−3 at the altitude range of 110 ± 4 km. In the absence of in‐situ measurements, it's difficult to comment on the origin but the presence of such layers during post‐sunset hours suggests their meteoric origin as the observed altitudes are consistent with the height range predicted by the meteor models. Other possible sources of such layers are also discussed.
A Statistical Study of the Moon's Magnetotail Plasma Environment
Authors: Liuzzo Lucas , Poppe Andrew R. , Halekas Jasper S.
Published: March 2022

This study investigates the lunar plasma environment when embedded within Earth's magnetotail. We use data from 10 years of tail crossings by the Acceleration, Reconnection, Turbulence, and Electrodynamics of the Moon's Interaction with the Sun (ARTEMIS) spacecraft in orbit around the Moon. We separate the plasma environments by magnetosheath‐like, magnetotail lobe‐like, and plasma sheet‐like conditions. Our findings highlight that the lobe‐like plasma is associated with low densities and a strong magnetic field, while the plasma sheet is characterized by higher densities and a weaker magnetic field. These regions are flanked by the fast, predominantly tailward flows of the terrestrial magnetosheath. During a single lunar crossing, however, the magnetotail displays a wide range of variability, with transient features—including reconnection events—intermixed between periods of lobe‐like or sheet‐like conditions. We compare and contrast the Moon's local magnetotail plasma to the environments near various outer‐planet moons. In doing so, we find that properties of the ambient lunar plasma are, at times, unique to the terrestrial magnetotail, while at others, may resemble those near the Jovian, Saturnian, and Neptunian moons. These findings highlight the complementary role of the ARTEMIS mission in providing a deeper understanding of the plasma interactions of the outer‐planet moons.
HSP70 attenuates compression-induced apoptosis of nucleus pulposus cells by suppressing mitochondrial fission via upregulating the expression of SIRT3
Authors: Hu Binwu , Wang Peng , Zhang Shuo , Liu Weijian , Lv Xiao , Shi Deyao , Zhao Lei , Liu Hongjian , Wang Baichuan , Chen Songfeng , Shao Zengwu
Published: March 2022

Compression-induced apoptosis of nucleus pulposus (NP) cells plays a pivotal role in the pathogenesis of intervertebral disc degeneration (IVDD). Recent studies have shown that the dysregulation of mitochondrial fission and fusion is implicated in the pathogenesis of a variety of diseases. However, its role in and regulatory effects on compression-induced apoptosis of NP cells have not yet been fully elucidated. Heat shock protein 70 (HSP70) is a major cytoprotective heat shock protein, but its physiological role in IVDD, especially its effect on mitochondrial fission and fusion, is still unknown. Herein, we found that compression could induce mitochondrial fission, which ultimately trigger apoptosis of NP cells via the mitochondrial apoptotic pathway. In addition, we identified the cytoprotective effects of HSP70 on NP cells, and we found that promoting the expression of HSP70 could protect NP cells from abnormal mechanical loading in vitro and in vivo. Finally, we showed that HSP70 inhibited compression-induced mitochondrial fission by promoting SIRT3 expression, thereby attenuating mitochondrial dysfunction and the production of reactive oxygen species and ultimately inhibiting the mitochondrial apoptotic pathway in NP cells. In conclusion, our results demonstrated that HSP70 could attenuate compression-induced apoptosis of NP cells by suppressing mitochondrial fission via upregulating SIRT3 expression. Promoting the expression of HSP70 might be a novel strategy for the treatment of IVDD.
Questions concerning tyrosine kinase-inhibitor therapy and transplants in chronic phase chronic myeloid leukaemia
Authors: Baccarani Michele , Bonifazi Francesca , Soverini Simona , Castagnetti Fausto , Gugliotta Gabriele , Saber Wael , Estrada-Merly Noel , Rosti Gianantonio , Gale Robert Peter
Published: March 2022

In this provocative commentary, we consider several questions posed by the late chronic myeloid leukaemia (CML) expert Prof. Michele Baccarani, which he challenged us to address after his death. He noted only a small proportion of people with chronic phase CML receiving tyrosine kinase-inhibitor (TKI)-therapy are likely to achieve sustained therapy-free remission (TFR) and even fewer are likely to be cured. Persons most likely to fail TKItherapy can be identified at diagnosis or soon after starting TKI-therapy. These persons are likely to need lifetime TKI-therapy with attendant risks of adverse events, cost and psychological consequences. Allogeneic transplants achieve much higher rates of leukaemia-free survival compared with TKI-therapy but are associated with transplant-related adverse events including an almost 20 percent risk of transplant-related deaths within 1 year post-transplant and a compromised quality-of-life because of complications such as chronic graft-versus-host disease. Subject-, disease- and transplant-related co-variates associated with transplant outcomes are known with reasonable accuracy. Not everyone likely to fail TKI-therapy is a transplant candidate. However, in those who candidates are physicians and patients need to weigh benefits and risks of TKI-therapy versus a transplant. We suggest transplants should be more often considered in the metric when counseling people with chronic phase CML unlikely to achieve TFR with TKI-therapy. We question whether we are discounting a possible important therapy intervention; we think so.
LocoMMotion: a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed and/or refractory multiple myeloma
Authors: Mateos Maria-Victoria , Weisel Katja , De Stefano Valerio , Goldschmidt Hartmut , Delforge Michel , Mohty Mohamad , Cavo Michele , Vij Ravi , Lindsey-Hill Joanne , Dytfeld Dominik , Angelucci Emanuele , Perrot Aurore , Benjamin Reuben , van de Donk Niels W. C. J. , Ocio Enrique M. , Scheid Christof , Gay Francesca , Roeloffzen Wilfried , Rodriguez-Otero Paula , Broijl Annemiek , Potamianou Anna , Sakabedoyan Caline , Semerjian Maria , Keim Sofia , Strulev Vadim , Schecter Jordan M. , Vogel Martin , Wapenaar Robert , Nesheiwat Tonia , San-Miguel Jesus , Sonneveld Pieter , Einsele Hermann , Moreau Philippe
Published: March 2022

Despite treatment advances, patients with multiple myeloma (MM) often progress through standard drug classes including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies (mAbs). LocoMMotion (ClinicalTrials.gov identifier: NCT04035226) is the first prospective study of real-life standard of care (SOC) in triple-class exposed (received at least a PI, IMiD, and anti-CD38 mAb) patients with relapsed/refractory MM (RRMM). Patients (N = 248; ECOG performance status of 0–1, ≥3 prior lines of therapy or double refractory to a PI and IMiD) were treated with median 4.0 (range, 1–20) cycles of SOC therapy. Overall response rate was 29.8% (95% CI: 24.2–36.0). Median progression-free survival (PFS) and median overall survival (OS) were 4.6 (95% CI: 3.9–5.6) and 12.4 months (95% CI: 10.3–NE). Treatment-emergent adverse events (TEAEs) were reported in 83.5% of patients (52.8% grade 3/4). Altogether, 107 deaths occurred, due to progressive disease (n = 74), TEAEs (n = 19), and other reasons (n = 14). The 92 varied regimens utilized demonstrate a lack of clear SOC for heavily pretreated, triple-class exposed patients with RRMM in real-world practice and result in poor outcomes. This supports a need for new treatments with novel mechanisms of action.
4th generation synchrotron source boosts crystalline imaging at the nanoscale
Authors: Li Peng , Allain Marc , Grünewald Tilman A. , Rommel Marcus , Campos Andrea , Carbone Dina , Chamard Virginie
Published: March 2022

New 4th-generation synchrotron sources, with their increased brilliance, promise to greatly improve the performances of coherent X-ray microscopy. This perspective is of major interest for crystal microscopy, which aims at revealing the 3D crystalline structure of matter at the nanoscale, an approach strongly limited by the available coherent flux. Our results, based on Bragg ptychography experiments performed at the first 4th-generation synchrotron source, demonstrate the possibility of retrieving a high-quality image of the crystalline sample, with unprecedented quality. Importantly, the larger available coherent flux produces datasets with enough information to overcome experimental limitations, such as strongly deteriorated scanning conditions. We show this achievement would not be possible with 3rd-generation sources, a limit that has inhibited the development of this otherwise powerful microscopy method, so far. Hence, the advent of next-generation synchrotron sources not only makes Bragg ptychography suitable for high throughput studies but also strongly relaxes the associated experimental constraints, making it compatible with a wider range of experimental set-ups at the new synchrotrons.
Phosphodiesterase 2A inhibition corrects the aberrant behavioral traits observed in genetic and environmental preclinical models of Autism Spectrum Disorder
Authors: Schiavi Sara , Carbone Emilia , Melancia Francesca , di Masi Alessandra , Jarjat Marielle , Brau Fréderic , Cardarelli Silvia , Giorgi Mauro , Bardoni Barbara , Trezza Viviana
Published: March 2022

Pharmacological inhibition of phosphodiesterase 2A (PDE2A), which catalyzes the hydrolysis of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), has recently been proposed as a novel therapeutic tool for Fragile X Syndrome (FXS), the leading monogenic cause of Autism Spectrum Disorder (ASD). Here, we investigated the role of PDE2A in ASD pathogenesis using two rat models that reflect one of either the genetic or environmental factors involved in the human disease: the genetic Fmr1-Δexon 8 rat model and the environmental rat model based on prenatal exposure to valproic acid (VPA, 500 mg/kg). Prior to behavioral testing, the offspring was treated with the PDE2A inhibitor BAY607550 (0.05 mg/kg at infancy, 0.1 mg/kg at adolescence and adulthood). Socio-communicative symptoms were assessed in both models through the ultrasonic vocalization test at infancy and three-chamber test at adolescence and adulthood, while cognitive impairments were assessed by the novel object recognition test in Fmr1-Δexon 8 rats (adolescence and adulthood) and by the inhibitory avoidance test in VPA-exposed rats (adulthood). PDE2A enzymatic activity in VPA-exposed infant rats was also assessed. In line with the increased PDE2A enzymatic activity previously observed in the brain of Fmr1-KO animals, we found an altered upstream regulation of PDE2A activity in the brain of VPA-exposed rats at an early developmental age (p < 0.05). Pharmacological inhibition of PDE2A normalized the communicative (p < 0.01, p < 0.05), social (p < 0.001, p < 0.05), and cognitive impairment (p < 0.001) displayed by both Fmr1-Δexon 8 and VPA-exposed rats. Altogether, these data highlight a key role of PDE2A in brain development and point to PDE2A inhibition as a promising pharmacological approach for the deficits common to both FXS and ASD.
A prognostic hypoxia gene signature with low heterogeneity within the dominant tumour lesion in prostate cancer patients
Authors: Salberg Unn Beate , Skingen Vilde Eide , Fjeldbo Christina Sæten , Hompland Tord , Ragnum Harald Bull , Vlatkovic Ljiljana , Hole Knut Håkon , Seierstad Therese , Lyng Heidi
Published: March 2022

Background

Gene signatures measured in a biopsy have been proposed as hypoxia biomarkers in prostate cancer. We assessed a previously developed signature, and aimed to determine its relationship to hypoxia and its heterogeneity within the dominant (index) lesion of prostate cancer.

Methods

The 32-gene signature was assessed from gene expression data of 141 biopsies from the index lesion of 94 patients treated with prostatectomy. A gene score calculated from the expression levels was applied in the analyses. Hypoxic fraction from pimonidazole immunostained whole-mount and biopsy sections was used as reference standard for hypoxia.

Results

The gene score was correlated with pimonidazole-defined hypoxic fraction in whole-mount sections, and the two parameters showed almost equal association with clinical markers of tumour aggressiveness. Based on the gene score, incorrect classification according to hypoxic fraction in whole-mount sections was seen in one third of the patients. The incorrect classifications were apparently not due to intra-tumour heterogeneity, since the score had low heterogeneity compared to pimonidazole-defined hypoxic fraction in biopsies. The score showed prognostic significance in uni-and multivariate analysis in independent cohorts.

Conclusions

Our signature from the index lesion reflects tumour hypoxia and predicts prognosis in prostate cancer, independent of intra-tumour heterogeneity in pimonidazole-defined hypoxia.
LncRNA SNHG5 promotes the proliferation and cancer stem cell-like properties of HCC by regulating UPF1 and Wnt-signaling pathway
Authors: Li Yarui , Hu Junbi , Guo Dan , Ma Wenhui , Zhang Xu , Zhang Zhiyong , Lu Guifang , He Shuixiang
Published: March 2022

The role of long noncoding RNA (lncRNAs) had been demonstrated in different types of cancer, including hepatocellular carcinoma. This study was intended to investigate the role of lncRNA small nucleolar RNA host gene 5 (SNHG5) in HCC proliferation and the liver CSC-like properties. Through functional experiments, we determined that knockdown of SNHG5 repressed HCC cell proliferation and CSC-like properties, while over-expression of SNHG5 promoted cell growth. At the same time, CSC markers (CD44, CD133, and ALDH1) and related transcription factors (OCT4, SOX2, and NANOG) were downregulated when SNHG5 was knocked down. Mechanically, RNA immunoprecipitation (RIP) and RNA pulldown assay showed that SNHG5 regulated the proliferation and CSC-like properties of HCC by binding UPF1. Further investigations showed that expression of critical components of Wnt/β-catenin pathway (β-catenin, TCF4, c-myc, cyclinD1, and c-Jun) were upregulated with depletion of UPF1 in liver CSCs, which were downregulated with depletion of SNHG5. After use of the inhibitor of Wnt/β-catenin pathway, the formation of liver CSCs sphere decreased. Taken together, SNHG5 plays a critical role to promote HCC cell proliferation and cancer stem cell-like properties via UPF1 and Wnt/β-catenin pathway.
Long noncoding RNA NEAT1 promotes ferroptosis by modulating the miR-362-3p/MIOX axis as a ceRNA
Authors: Zhang Ying , Luo Meiying , Cui Xiaohong , O’Connell Douglas , Yang Yongfei
Published: March 2022

Ferroptosis, a novel form of regulated cell death induced by iron-dependent lipid peroxidation, plays an essential role in the development and drug resistance of tumors. Long noncoding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to be involved in the regulation of cell cycle, proliferation, apoptosis, and migration of tumor cells. However, the function and molecular mechanism of NEAT1 in regulating ferroptosis in tumors remain unclear. Here, we found that ferroptosis inducers erastin and RSL3 increased NEAT1 expression by promoting the binding of p53 to the NEAT1 promoter. Induced NEAT1 promoted the expression of MIOX by competitively binding to miR-362-3p. MIOX increased ROS production and decreased the intracellular levels of NADPH and GSH, resulting in enhanced erastin- and RSL3-induced ferroptosis. Importantly, overexpression of NEAT1 increased the anti-tumor activity of erastin and RSL3 by enhancing ferroptosis both in vitro and in vivo. Collectively, these data suggest that NEAT1 plays a novel and indispensable role in ferroptosis by regulating miR-362-3p and MIOX. Considering the clinical findings that HCC patients are insensitive to chemotherapy and immunotherapy, ferroptosis induction may be a promising therapeutic strategy for HCC patients with high NEAT1 expression.
MicroRNA-495 suppresses pre-eclampsia via activation of p53/PUMA axis
Authors: Zhao Yi , Zhao Ge , Li Weiwei
Published: March 2022

Linkage between microRNAs (miRNAs) and pre-eclampsia (PE) has been documented. Here, we focused on miR-495 in PE and its underlying mechanism in regulation of trophoblast cells. Expression of miR-495, HDAC2, p53 and PUMA was determined in collected placental tissue samples. Loss- and gain-function was performed to determine the roles of miR-495, HDAC2, p53, and PUMA in biological processes of HTR8/SVneo cells and primary trophoblast cells. The relationships among miR-495, HDAC2, and p53 were pinpointed. PE patients presented with higher expression of miR-495, p53, and PUMA in placental tissues, but lower HDAC2. miR-495 negatively targeted HDAC2 expression. HDAC2 suppressed p53 expression via deacetylation. Overexpression of miR-495, p53, or PUMA inhibited biological properties of HTR8/SVneo cells and primary trophoblast cells, while opposite trends were observed in response to oe-HDAC2. In conclusion, miR-495 knockdown can suppress p53/PUMA axis by targeting HDAC2 to enhance biological behaviors of trophoblast cells, which may prevent occurrence of PE.
Sulforaphane suppresses metastasis of triple-negative breast cancer cells by targeting the RAF/MEK/ERK pathway
Authors: Zhang Ying , Lu Qian , Li Nan , Xu Ming , Miyamoto Tatsuo , Liu Jing
Published: March 2022

Breast cancer metastasis is the main cause of cancer death in women, so far, no effective treatment has inhibited breast cancer metastasis. Sulforaphane (SFN), a natural compound derived from broccoli, has shown potential health benefits in many cancers. However, research on breast cancer metastasis is still insufficient. Here, we showed that SFN, including its two isomers of R-SFN and S-SFN, significantly inhibited TGF-β1-induced migration and invasion in breast cancer cells. Proteomic and phosphoproteomic analysis showed that SFN affected the formation of the cytoskeleton. Subsequent experiments confirmed that SFN significantly inhibited TGF-β1-induced actin stress fiber formation and the expression of actin stress fiber formation-associated proteins, including paxillin, IQGAP1, FAK, PAK2, and ROCK. Additionally, SFN is directly bound to RAF family proteins (including ARAF, BRAF, and CRAF) and inhibited MEK and ERK phosphorylation. These in vitro results indicate that SFN targets the RAF/MEK/ERK signaling pathway to inhibit the formation of actin stress fibers, thereby inhibiting breast cancer cell metastasis.
Gate- versus defect-induced voltage drop and negative differential resistance in vertical graphene heterostructures
Authors: Kim Tae Hyung , Lee Juho , Lee Ryong-Gyu , Kim Yong-Hoon
Published: March 2022

To enable the computer-aided design of vertically stacked two-dimensional (2D) van der Waals (vdW) heterostructure devices, we here introduce a non-equilibrium first-principles simulation method based on the multi-space constrained-search density functional formalism. Applying it to graphene/few-layer hBN/graphene field-effect transistors, we show that the negative differential resistance (NDR) characteristics can be produced not only from the gating-induced mismatch between two graphene Dirac cones in energy-momentum space but from the bias-dependent energetic shift of defect levels. Specifically, for a carbon atom substituted for a nitrogen atom (CN) within inner hBN layers, the increase of bias voltage is found to induce a self-consistent electron filling of in-gap CN states, which in turn changes voltage drop profiles and produces symmetric NDR characteristics. With the CN placed on outer hBN layers, however, the pinning of CN states to nearby graphene significantly modifies device characteristics, demonstrating the critical impact of atomic details for 2D vdW devices.
Spin-triplet superconductivity in Weyl nodal-line semimetals
Authors: Shang Tian , Ghosh Sudeep K. , Smidman Michael , Gawryluk Dariusz Jakub , Baines Christopher , Wang An , Xie Wu , Chen Ye , Ajeesh Mukkattu O. , Nicklas Michael , Pomjakushina Ekaterina , Medarde Marisa , Shi Ming , Annett James F. , Yuan Huiqiu , Quintanilla Jorge , Shiroka Toni
Published: March 2022

Topological semimetals are three dimensional materials with symmetry-protected massless bulk excitations. As a special case, Weyl nodal-line semimetals are realized in materials having either no inversion or broken time-reversal symmetry and feature bulk nodal lines. The 111-family, including LaNiSi, LaPtSi and LaPtGe materials (all lacking inversion symmetry), belongs to this class. Here, by combining muon-spin rotation and relaxation with thermodynamic measurements, we find that these materials exhibit a fully-gapped superconducting ground state, while spontaneously breaking time-reversal symmetry at the superconducting transition. Since time-reversal symmetry is essential for protecting the normal-state topology, its breaking upon entering the superconducting state should remarkably result in a topological phase transition. By developing a minimal model for the normal-state band structure and assuming a purely spin-triplet pairing, we show that the superconducting properties across this family can be described accurately. Our results demonstrate that the 111 materials reported here provide an ideal test-bed for investigating the rich interplay between the exotic properties of Weyl nodal-line fermions and unconventional superconductivity.
A single-cell atlas of non-haematopoietic cells in human lymph nodes and lymphoma reveals a landscape of stromal remodelling
Authors: Abe Yoshiaki , Sakata-Yanagimoto Mamiko , Fujisawa Manabu , Miyoshi Hiroaki , Suehara Yasuhito , Hattori Keiichiro , Kusakabe Manabu , Sakamoto Tatsuhiro , Nishikii Hidekazu , Nguyen Tran B. , Owada Yohei , Enomoto Tsuyoshi , Sawa Aya , Bando Hiroko , Yoshida Chikashi , Tabata Rikako , Terao Toshiki , Nakayama Masahiro , Ohshima Koichi , Usuki Kensuke , Oda Tatsuya , Matsue Kosei , Chiba Shigeru
Published: March 2022

The activities of non-haematopoietic cells (NHCs), including mesenchymal stromal cells and endothelial cells, in lymphomas are reported to underlie lymphomagenesis. However, our understanding of lymphoma NHCs has been hampered by unexplained NHC heterogeneity, even in normal human lymph nodes (LNs). Here we constructed a single-cell transcriptome atlas of more than 100,000 NHCs collected from 27 human samples, including LNs and various nodal lymphomas, and it revealed 30 distinct subclusters, including some that were previously unrecognized. Notably, this atlas was useful for comparative analyses with lymphoma NHCs, which revealed an unanticipated landscape of subcluster-specific changes in gene expression and interaction with malignant cells in follicular lymphoma NHCs. This facilitates our understanding of stromal remodelling in lymphoma and highlights potential clinical biomarkers. Our study largely updates NHC taxonomy in human LNs and analysis of disease status, and provides a rich resource and deeper insights into LN and lymphoma biology to advance lymphoma management and therapy.
Daily motionless activities: A dataset with accelerometer, magnetometer, gyroscope, environment, and GPS data
Authors: Pires Ivan Miguel , Garcia Nuno M. , Zdravevski Eftim , Lameski Petre
Published: March 2022

The dataset presented in this paper presents a dataset related to three motionless activities, including driving, watching TV, and sleeping. During these activities, the mobile device may be positioned in different locations, including the pants pockets, in a wristband, over the bedside table, on a table, inside the car, or on other furniture, for the acquisition of accelerometer, magnetometer, gyroscope, GPS, and microphone data. The data was collected by 25 individuals (15 men and 10 women) in different environments in Covilhã and Fundão municipalities (Portugal). The dataset includes the sensors’ captures related to a minimum of 2000 captures for each motionless activity, which corresponds to 2.8 h (approximately) for each one. This dataset includes 8.4 h (approximately) of captures for further analysis with data processing techniques, and machine learning methods. It will be useful for the complementary creation of a robust method for the identification of these type of activities.
Aggressiveness, ADHD-like behaviour, and environment influence repetitive behaviour in dogs
Authors: Sulkama Sini , Salonen Milla , Mikkola Salla , Hakanen Emma , Puurunen Jenni , Araujo César , Lohi Hannes
Published: March 2022

Repetitive behaviour ranges from variants of normal repetitive behaviours to abnormal repetitive behaviours. The domestic dog spontaneously performs different repetitive behaviours, which can be severe and impair the quality of life and the dog-owner relationship. We collected comprehensive behavioural questionnaire data from almost 4500 Finnish pet dogs and studied the effect of several demographic, environmental, and behavioural factors on canine repetitive behaviour with logistic regression. We replicated findings from previous studies by revealing comorbidity between repetitive behaviour and behavioural factors aggressiveness, hyperactivity/impulsivity, and inattention. We also found a novel association between repetitive behaviour and the owner’s dog experience. In addition, we showed that repetitive behaviour is more common in dogs that live without conspecifics, dogs that were given a low amount of exercise, dogs that lived in larger families, young dogs and elderly dogs, and neutered dogs. Finally, we identified breed differences in repetitive behaviour, suggesting that some breeds are more vulnerable to repetitive behaviour and indicate a genetic susceptibility. As abnormal repetitive behaviour can considerably worsen the well-being of dogs and impair the dog-owner relationship, a better understanding of the environmental, lifestyle, and molecular factors affecting canine repetitive behaviour can benefit both dogs and humans.
Prognostic determinants of hearing outcomes in children with congenital cytomegalovirus infection
Authors: Lo Ta-Hsuan , Lin Pei-Hsuan , Hsu Wei-Chung , Tsao Po-Nien , Liu Tien-Chen , Yang Tzong-Hann , Hsu Chuan-Jen , Huang Li-Min , Lu Chun-Yi , Wu Chen-Chi
Published: March 2022

Congenital cytomegalovirus (cCMV) infection is the most prevalent cause of non-genetic sensorineural hearing loss (SNHL) in children. However, the prognostic determinants of SNHL remain unclear. Children with cCMV infection in a tertiary hospital were enrolled. The presence of cCMV-related symptoms at birth, the newborn hearing screening (NHS) results, and the blood viral loads were ascertained. Audiologic outcomes and initial blood viral loads were compared between different groups. Of the 39 children enrolled, 16 developed SNHL. SNHL developed in 60% of children who were initially symptomatic, and in 34.5% of those who were initially asymptomatic with normal hearing or isolated hearing loss, respectively. Failuire in NHS was a reliable tool for early detection of SNHL. The initial viral loads were higher in children who were symptomatic at birth, those who failed NHS, and those who developed SNHL. We observed SNHL deterioration in a patient after CMV DNAemia clearance was achieved, and in another patient with the flare-up of viral load. The presence of cCMV-related symptoms at birth, failure in NHS, and blood viral load might be the prognostic factors for hearing outcomes. Regular audiologic examinations are necessary in all children with cCMV infection even after CMV DNAemia clearance.
Determining an effective short term COVID-19 prediction model in ASEAN countries
Authors: Sharif Omar , Hasan Md Zobaer , Rahman Azizur
Published: March 2022

The challenge of accurately short-term forecasting demand is due to model selection and the nature of data trends. In this study, the prediction model was determined based on data patterns (trend data without seasonality) and the accuracy of prediction measurement. The cumulative number of COVID-19 affected people in some ASEAN countries had been collected from the Worldometers database. Three models [Holt’s method, Wright’s modified Holt’s method, and unreplicated linear functional relationship model (ULFR)] had been utilized to identify an efficient model for short-time prediction. Moreover, different smoothing parameters had been tested to find the best combination of the smoothing parameter. Nevertheless, using the day-to-day reported cumulative case data and 3-days and 7-days in advance forecasts of cumulative data. As there was no missing data, Holt’s method and Wright’s modified Holt’s method showed the same result. The text-only result corresponds to the consequences of the models discussed here, where the smoothing parameters (SP) were roughly estimated as a function of forecasting the number of affected people due to COVID-19. Additionally, the different combinations of SP showed diverse, accurate prediction results depending on data volume. Only 1-day forecasting illustrated the most efficient prediction days (1 day, 3 days, 7 days), which was validated by the Nash–Sutcliffe efficiency (NSE) model. The study also validated that ULFR was an efficient forecasting model for the efficient model identifying. Moreover, as a substitute for the traditional R-squared, the study applied NSE and R-squared (ULFR) for model selection. Finally, the result depicted that the prediction ability of ULFR was superior to Holt’s when it is compared to the actual data.
Revealing microhabitat requirements of an endangered specialist lizard with LiDAR
Authors: Bradley Holly S. , Craig Michael D. , Cross Adam T. , Tomlinson Sean , Bamford Michael J. , Bateman Philip W.
Published: March 2022

A central principle of threatened species management is the requirement for detailed understanding of species habitat requirements. Difficult terrain or cryptic behaviour can, however, make the study of habitat or microhabitat requirements difficult, calling for innovative data collection techniques. We used high-resolution terrestrial LiDAR imaging to develop three-dimensional models of log piles, quantifying the structural characteristics linked with occupancy of an endangered cryptic reptile, the western spiny-tailed skink (Egernia stokesii badia). Inhabited log piles were generally taller with smaller entrance hollows and a wider main log, had more high-hanging branches, fewer low-hanging branches, more mid- and understorey cover, and lower maximum canopy height. Significant characteristics linked with occupancy were longer log piles, an average of three logs, less canopy cover, and the presence of overhanging vegetation, likely relating to colony segregation, thermoregulatory requirements, and foraging opportunities. In addition to optimising translocation site selection, understanding microhabitat specificity of E. s. badia will help inform a range of management objectives, such as targeted monitoring and invasive predator control. There are also diverse opportunities for the application of this technology to a wide variety of future ecological studies and wildlife management initiatives pertaining to a range of cryptic, understudied taxa.
The gut microbiome as mediator between diet and its impact on immune function
Authors: Shi Huiqing , ter Horst Rob , Nielen Suzanne , Bloemendaal Mirjam , Jaeger Martin , Joosten Irma , Koenen Hans , Joosten Leo A. B. , Schweren Lizanne J. S. , Vasquez Alejandro Arias , Netea Mihai G. , Buitelaar Jan
Published: March 2022

Dietary habits may affect inflammatory status in humans. Here we explore this interaction as well as the potential mediating role of the gut microbiome (GM), given that the GM is both involved in processing of dietary components and influences the immune system. A cross-sectional analysis of a sample of 482 healthy participants (207 males and 275 females) was performed. Dietary intake was assessed by a semiquantitative food questionnaire. Adipokines and soluble inflammatory mediators were assayed with multiple immunoassays and ELISA. Microbial DNA was extracted from frozen stool samples of 471 participants. Polychoric correlation analysis was used to establish dietary patterns, and joint multivariate associations between these dietary patterns and immune biomarkers were studied using regression analyses with adjustment for sex, age, BMI, smoking, education levels and physical exercise and other dietary patterns. Non-parametric entropy mediation was applied to investigate whether diet-immune relationships are mediated by abundance of microbial species. In this cohort, we identified three dietary patterns, characterized as “high-meat” (meat and sweetened drink), “prudent diet” (fish, fruit, legumes and vegetables) and “high alcohol” (higher alcohol consumption). Higher adherence to prudent diet was associated with a higher adiponectin level. The high alcohol pattern was associated with high concentrations of circulating concentrations of pro-inflammatory markers (CRP, IL-6, VEGF).Dialister invisuswas found to mediate the relationship between a prudent dietary pattern and adiponectin, AAT, CRP, IL-6, and VEGF. In conclusion, a meat-based diet and a diet with high alcohol consumption were associated with high concentrations of biomarkers of chronic low-grade inflammation, and conversely, a prudent diet was associated with anti-inflammatory biomarkers. Diet-inflammation regulation may differ between sexes. Mediation analyses revealed that the association between prudent diet and immune function was partially mediated by the GM. The study adds to our understanding of the associations between diet, the immune system and the GM in a healthy population.
Altered intercellular communication and extracellular matrix signaling as a potential disease mechanism in human hypertrophic cardiomyopathy
Authors: Larson Amy , Codden Christina J. , Huggins Gordon S. , Rastegar Hassan , Chen Frederick Y. , Maron Barry J. , Rowin Ethan J. , Maron Martin S. , Chin Michael T.
Published: March 2022

Hypertrophic cardiomyopathy (HCM) is considered a primary disorder of the sarcomere resulting in unexplained left ventricular hypertrophy but the paradoxical association of nonmyocyte phenotypes such as fibrosis, mitral valve anomalies and microvascular occlusion is unexplained. To understand the interplay between cardiomyocyte and nonmyocyte cell types in human HCM, single nuclei RNA-sequencing was performed on myectomy specimens from HCM patients with left ventricular outflow tract obstruction and control samples from donor hearts free of cardiovascular disease. Clustering analysis based on gene expression patterns identified a total of 34 distinct cell populations, which were classified into 10 different cell types based on marker gene expression. Differential gene expression analysis comparing HCM to Normal datasets revealed differences in sarcomere and extracellular matrix gene expression. Analysis of expressed ligand-receptor pairs across multiple cell types indicated profound alteration in HCM intercellular communication, particularly between cardiomyocytes and fibroblasts, fibroblasts and lymphocytes and involving integrin β1 and its multiple extracellular matrix (ECM) cognate ligands. These findings provide a paradigm for how sarcomere dysfunction is associated with reduced cardiomyocyte secretion of ECM ligands, altered fibroblast ligand-receptor interactions with other cell types and increased fibroblast to lymphocyte signaling, which can further alter the ECM composition and promote nonmyocyte phenotypes.