bluuebunny/crossref_metadata_2025_split huggingface dataset:
ExoMars TGO/NOMAD‐UVIS Vertical Profiles of Ozone: 2. The High‐Altitude Layers of Atmospheric Ozone
Authors: Khayat Alain S. J. , Smith Michael D. , Wolff Michael , Daerden Frank , Neary Lori , Patel Manish R. , Piccialli Arianna , Vandaele Ann C. , Thomas Ian , Ristic Bojan , Mason Jon , Willame Yannick , Depiesse Cedric , Bellucci Giancarlo , López‐Moreno José Juan 
Published: October 2021

AbstractSolar occultations performed by the Nadir and Occultation for MArs Discovery (NOMAD) ultraviolet and visible spectrometer (UVIS) onboard the ExoMars Trace Gas Orbiter (TGO) have provided a comprehensive mapping of atmospheric ozone density. The observations here extend over a full Mars year (MY) between April 21, 2018 at the beginning of the TGO science operations during late northern summer on Mars (MY 34, Ls = 163°) and March 9, 2020 (MY 35). UVIS provided transmittance spectra of the Martian atmosphere allowing measurements of the vertical distribution of ozone density using its Hartley absorption band (200–300 nm). The overall comparison to water vapor is found in the companion paper to this work (Patel et al., 2021, https://doi.org/10.1029/2021JE006837). Our findings indicate the presence of (a) a high‐altitude peak of ozone between 40 and 60 km in altitude over the north polar latitudes for at least 45% of the Martian year during midnorthern spring, late northern summer‐early southern spring, and late southern summer, and (b) a second, but more prominent, high‐altitude ozone peak in the south polar latitudes, lasting for at least 60% of the year including the southern autumn and winter seasons. When present, both high‐altitude peaks are observed in the sunrise and sunset occultations, suggesting that the layers could persist during the day. Results from the Mars general circulation models predict the general behavior of these peaks of ozone and are used in an attempt to further our understanding of the chemical processes controlling high‐altitude ozone on Mars.
Structural gray matter differences in Problematic Usage of the Internet: a systematic review and meta-analysis
Authors: Solly Jeremy E. , Hook Roxanne W. , Grant Jon E. , Cortese Samuele , Chamberlain Samuel R. 
Published: October 2021

AbstractProblematic Usage of the Internet (PUI) has been linked to diverse structural gray matter changes in individual data studies. However, no quantitative synthesis across studies has been conducted. We aimed to identify gray matter regions showing significant spatial convergence across neuroimaging studies in PUI. We searched PubMed and PsycINFO up to 10/03/2021 and included original, cross-sectional comparative studies that examined structural gray matter imaging in PUI versus control groups; reported a whole-brain analysis; and provided peak coordinates for gray matter differences. From a total of 624 potentially relevant studies, 15 (including 355 individuals with PUI and 363 controls) were included in a meta-analysis of voxel-based morphometry studies. Anatomical likelihood estimation (ALE) meta-analysis was performed using extracted coordinates and identified significant spatial convergence in the medial/superior frontal gyri, the left anterior cingulate cortex/cingulate gyrus, and the left middle frontal/precentral gyri. Datasets contributing to these findings all indicated reduced gray matter in cases compared to controls. In conclusion, voxel-based morphometric studies indicate replicable gray matter reductions in the dorsolateral prefrontal cortex and anterior cingulate cortex in PUI, regions implicated in reward processing and top-down inhibitory control. Further studies are required to understand the nature of gray matter differences across PUI behaviors, as well as the contribution of particular mental health disorders, and the influence of variation in study and sample characteristics.
CRHCeA→VTA inputs inhibit the positive ensembles to induce negative effect of opiate withdrawal
Authors: Jiang Changyou , Yang Xiao , He Guanhong , Wang Fan , Wang Zhilin , Xu Wendong , Mao Ying , Ma Lan , Wang Feifei 
Published: October 2021

AbstractPlasticity of neurons in the ventral tegmental area (VTA) is critical for establishment of drug dependence. However, the remodeling of the circuits mediating the transition between positive and negative effect remains unclear. Here, we used neuronal activity-dependent labeling technique to characterize and temporarily control the VTA neuronal ensembles recruited by the initial morphine exposure (morphine-positive ensembles, Mor-Ens). Mor-Ens preferentially projected to NAc, and induced dopamine-dependent positive reinforcement. Electrophysiology and rabies viral tracing revealed the preferential connections between the VTA-projective corticotrophin-releasing hormone (CRH) neurons of central amygdala (CRHCeA→VTA) and Mor-Ens, which was enhanced after escalating morphine exposure and mediated the negative effect during opiate withdrawal. Pharmacologic intervention or CRISPR-mediated repression of CRHR1 in Mor-Ens weakened the inhibitory CRHCeA→VTA inputs, and alleviated the negative effect during opiate withdrawal. These data suggest that neurons encoding opioid reward experience are inhibited by enhanced CRHCeA→VTA inputs induced by chronic morphine exposure, leading to negative effect during opiate withdrawal, and provide new insight into the pathological changes in VTA plasticity after drug abuse and mechanism of opiate dependence.
TTPAL promotes gastric tumorigenesis by directly targeting NNMT to activate PI3K/AKT signaling
Authors: Liu Wenxiu , Gou Hongyan , Wang Xiaohong , Li Xiaoming , Hu Xiaoxu , Su Hao , Li Shengmian , Yu Jun 
Published: October 2021

AbstractCopy number alterations are crucial for gastric cancer (GC) development. In this study, Tocopherol alpha transfer protein-like (TTPAL) was identified to be highly amplified in our primary GC cohort (30/86). Multivariate analysis showed that high TTPAL expression was correlated with the poor prognosis of GC patients. Ectopic expression of TTPAL promoted GC cell proliferation, migration, and invasion in vitro and promoted murine xenograft tumor growth and lung metastasis in vivo. Conversely, silencing of TTPAL exerted significantly opposite effects in vitro. Moreover, RNA-sequencing and co-immunoprecipitation (Co-IP) followed by liquid chromatograph-mass spectrometry (LC-MS) identified that TTPAL exerted oncogenic functions via the interaction of Nicotinamide-N-methyl transferase (NNMT) and activated PI3K/AKT signaling pathway. Collectively, TTPAL plays a pivotal oncogenic role in gastric carcinogenesis through promoting PI3K/AKT pathway via cooperating with NNMT. TTPAL may serve as a prognostic biomarker of patients with GC.
TRPC1 promotes the genesis and progression of colorectal cancer via activating CaM-mediated PI3K/AKT signaling axis
Authors: Sun Yang , Ye Chen , Tian Wen , Ye Wen , Gao Yuan-Yuan , Feng Ying-Da , Zhang Hui-Nan , Ma Guang-Yuan , Wang Shou-Jia , Cao Wei , Li Xiao-Qiang 
Published: October 2021

AbstractTransient receptor potential canonical (TRPC) channels are the most prominent nonselective cation channels involved in various diseases. However, the function, clinical significance, and molecular mechanism of TRPCs in colorectal cancer (CRC) progression remain unclear. In this study, we identified that TRPC1 was the major variant gene of the TRPC family in CRC patients. TRPC1 was upregulated in CRC tissues compared with adjacent normal tissues and high expression of TRPC1 was associated with more aggressive tumor progression and poor overall survival. TRPC1 knockdown inhibited cell proliferation, cell-cycle progression, invasion, and migration in vitro, as well as tumor growth in vivo; whereas TRPC1 overexpression promoted colorectal tumor growth and metastasis in vitro and in vivo. In addition, colorectal tumorigenesis was significantly attenuated in Trpc1-/- mice. Mechanistically, TRPC1 could enhance the interaction between calmodulin (CaM) and the PI3K p85 subunit by directly binding to CaM, which further activated the PI3K/AKT and its downstream signaling molecules implicated in cell cycle progression and epithelial-mesenchymal transition. Silencing of CaM attenuated the oncogenic effects of TRPC1. Taken together, these results provide evidence that TRPC1 plays a pivotal oncogenic role in colorectal tumorigenesis and tumor progression by activating CaM-mediated PI3K/AKT signaling axis. Targeting TRPC1 represents a novel and specific approach for CRC treatment.
New insight into the catalytic -dependent and -independent roles of METTL3 in sustaining aberrant translation in chronic myeloid leukemia
Authors: Ianniello Zaira , Sorci Melissa , Ceci Ginistrelli Lavinia , Iaiza Alessia , Marchioni Marcella , Tito Claudia , Capuano Ernestina , Masciarelli Silvia , Ottone Tiziana , Attrotto Cristina , Rizzo Manuela , Franceschini Luca , de Pretis Stefano , Voso Maria Teresa , Pelizzola Mattia , Fazi Francesco , Fatica Alessandro 
Published: October 2021

AbstractChronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by the presence of tyrosine kinase BCR-ABL1 fusion protein, which deregulate transcription and mRNA translation. Tyrosine kinase inhibitors (TKIs) are the first-choice treatment. However, resistance to TKIs remains a challenge to cure CML patients. Here, we reveal that the m6A methyltransferase complex METTL3/METTL14 is upregulated in CML patients and that is required for proliferation of primary CML cells and CML cell lines sensitive and resistant to the TKI imatinib. We demonstrate that depletion of METTL3 strongly impairs global translation efficiency. In particular, our data show that METTL3 is crucial for the expression of genes involved in ribosome biogenesis and translation. Specifically, we found that METTL3 directly regulates the level of PES1 protein identified as an oncogene in several tumors. We propose a model in which nuclear METTL3/METTL14 methyltransferase complex modified nascent transcripts whose translation is enhanced by cytoplasmic localization of METTL3, independently from its catalytic activity. In conclusion, our results point to METTL3 as a novel relevant oncogene in CML and as a promising therapeutic target for TKI resistant CML.
The polarity protein Par3 coordinates positively self-renewal and negatively invasiveness in glioblastoma
Authors: Dadras Mahsa Shahidi , Caja Laia , Mezheyeuski Artur , Liu Sijia , Gélabert Caroline , Gomez-Puerto Maria Catalina , Gallini Radiosa , Rubin Carl-Johan , ten Dijke Peter , Heldin Carl-Henrik , Moustakas Aristidis 
Published: October 2021

AbstractGlioblastoma (GBM) is a brain malignancy characterized by invasiveness to the surrounding brain tissue and by stem-like cells, which propagate the tumor and may also regulate invasiveness. During brain development, polarity proteins, such as Par3, regulate asymmetric cell division of neuro-glial progenitors and neurite motility. We, therefore, studied the role of the Par3 protein (encoded by PARD3) in GBM. GBM patient transcriptomic data and patient-derived culture analysis indicated diverse levels of expression of PARD3 across and independent from subtypes. Multiplex immunolocalization in GBM tumors identified Par3 protein enrichment in SOX2-, CD133-, and NESTIN-positive (stem-like) cells. Analysis of GBM cultures of the three subtypes (proneural, classical, mesenchymal), revealed decreased gliomasphere forming capacity and enhanced invasiveness upon silencing Par3. GBM cultures with suppressed Par3 showed low expression of stemness (SOX2 and NESTIN) but higher expression of differentiation (GFAP) genes. Moreover, Par3 silencing reduced the expression of a set of genes encoding mitochondrial enzymes that generate ATP. Accordingly, silencing Par3 reduced ATP production and concomitantly increased reactive oxygen species. The latter was required for the enhanced migration observed upon silencing of Par3 as anti-oxidants blocked the enhanced migration. These findings support the notion that Par3 exerts homeostatic redox control, which could limit the tumor cell-derived pool of oxygen radicals, and thereby the tumorigenicity of GBM.
Src acts as the target of matrine to inhibit the proliferation of cancer cells by regulating phosphorylation signaling pathways
Authors: Zhang Xi , Xu Hui , Bi Xiaoyang , Hou Guoqing , Liu Andong , Zhao Youyun , Wang Guoping , Cao Xuan 
Published: October 2021

AbstractStudies have shown that matrine has antitumor activity against many types of cancers. However, the direct target in cancer cells of its anticancer effect has not been identified. The purpose of this study was to find the molecular target of matrine to inhibit the proliferation of cancer cells and explore its mechanism of action. Herein we showed that matrine inhibited the proliferation of cancer in vitro and in vivo. Pull-down assay with matrine-amino coupling resins and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) identified Src as the target of matrine. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) provided solid evidences that matrine directly bound to Src. Bioinformatics prediction and pull-down experiment demonstrated that Src kinase domain was required for its interaction with matrine and Ala392 in the kinase domain participated in matrine–Src interaction. Intriguingly, matrine was proven to inhibit Src kinase activity in a non-ATP-competitive manner by blocking the autophosphorylation of Tyr419 in Src kinase domain. Matrine down-regulated the phosphorylation levels of MAPK/ERK, JAK2/STAT3, and PI3K/Akt signaling pathways via targeting Src. Collectively, matrine targeted Src, inhibited its kinase activity, and down-regulated its downstream MAPK/ERK, JAK2/STAT3, and PI3K/Akt phosphorylation signaling pathways to inhibit the proliferation of cancer cells.
Stat1 confers sensitivity to radiation in cervical cancer cells by controlling Parp1 levels: a new perspective for Parp1 inhibition
Authors: Raspaglio Giuseppina , Buttarelli Marianna , Filippetti Flavia , Battaglia Alessandra , Buzzonetti Alexia , Scambia Giovanni , Gallo Daniela 
Published: October 2021

AbstractCervical cancer (CC) is the fourth most common cause of cancer-related death in women. According to international guidelines, a standard treatment for locally advanced cervical cancer (LACC) consists of exclusive concurrent chemoradiation treatment (CRT). However, chemoradioresistance and subsequent relapse and metastasis of cancer occur in many patients, and survival for these women has generally remained poor. Therefore, strategies to overcome resistance are urgently needed. We have recently reported a radiosensitizing effect of the signal transducer and activator of transcription 1 (STAT1) in CC, associated with the control of [Poly(ADP-ribose) polymerase −1] PARP1 levels, a key factor in cell response to DNA damage induced by radiation. Here, we sought to decipher the underlying mechanism of STAT1-mediated control of PARP1, elucidating its role as a radiosensitizer in CC. Functional and molecular biology studies demonstrated that STAT1 may act at both transcriptional and posttranscriptional levels to modulate PARP1 expression in CC cells. In light of these results, we tested the effect of Olaparib in sensitizing CC cells to radiation and investigated signaling pathways involved in the activity observed. Results showed that PARP1 inhibition, at clinically achievable doses, may indeed selectively improve the sensitivity of resistant CC cells to DNA-damaging treatment. The translational relevance of our findings was supported by preliminary results in a limited patient cohort, confirming that higher PARP1 levels are significantly associated with a radioresistant phenotype. Finally, bioinformatics analysis of GEPIA and TCGA databases, demonstrated that PARP1 mRNA is higher in CC than in normal tissues and that increased PARP1 mRNA expression levels are associated with poor prognosis of LACC patients. Overall, our data open new opportunities for the development of personalized treatments in women diagnosed with CC.
Vezatin regulates seizures by controlling AMPAR-mediated synaptic activity
Authors: Wang You , Yuan Jinxian , Yu Xinyuan , Liu Xi , Tan Changhong , Chen Yangmei , Xu Tao 
Published: October 2021

AbstractAlthough many studies have explored the mechanism of epilepsy, it remains unclear and deserves further investigation. Vezatin has been reported to be a synaptic regulatory protein involved in regulating neuronal synaptic transmission (NST). However, the role of vezatin in epilepsy remains unknown. Therefore, the aims of this study are to investigate the underlying roles of vezatin in epilepsy. In this study, vezatin expression was increased in hippocampal tissues from pilocarpine (PILO)-induced epileptic mice and a Mg2+-free medium-induced in vitro seizure-like model. Vezatin knockdown suppressed seizure activity in PILO-induced epileptic mice. Mechanistically, vezatin knockdown suppressed AMPAR-mediated synaptic events in epileptic mice and downregulated the surface expression of the AMPAR GluA1 subunit (GluA1). Interestingly, vezatin knockdown decreased the phosphorylation of GluA1 at serine 845 and reduced protein kinase A (PKA) phosphorylation; when PKA phosphorylation was suppressed by H-89 (a selective inhibitor of PKA phosphorylation) in vitro, the effects of vezatin knockdown on reducing the phosphorylation of GluA1 at serine 845 and the surface expression of GluA1 were blocked. Finally, we investigated the pattern of vezatin in brain tissues from patients with temporal lobe epilepsy (TLE), and we found that vezatin expression was also increased in patients with TLE. In summary, the vezatin expression pattern is abnormal in individuals with epilepsy, and vezatin regulates seizure activity by affecting AMPAR-mediated NST and the surface expression of GluA1, which is involved in PKA-mediated phosphorylation of GluA1 at serine 845, indicating that vezatin-mediated regulation of epileptic seizures represents a novel target for epilepsy.
Distinct immune signatures discriminate between asymptomatic and presymptomatic SARS-CoV-2pos subjects
Authors: Yu Shanhe , Di Caixia , Chen Shijun , Guo Mingquan , Yan Jiayang , Zhu Zhaoqin , Liu Li , Feng Ruixue , Xie Yinyin , Zhang Ruihong , Chen Juan , Wang Mengxi , Wei Dong , Fang Hai , Yin Tong , Huang Jinyan , Chen Saijuan , Lu Hongzhou , Zhu Jiang , Qu Jieming 
Published: October 2021

AbstractIncreasing numbers of SARS-CoV-2-positive (SARS-CoV-2pos) subjects are detected at silent SARS-CoV-2 infection stage (SSIS). Yet, SSIS represents a poorly examined time-window wherein unknown immunity patterns may contribute to the fate determination towards persistently asymptomatic or overt disease. Here, we retrieved blood samples from 19 asymptomatic and 12 presymptomatic SARS-CoV-2pos subjects, 47 age/gender-matched patients with mild or moderate COVID-19 and 27 normal subjects, and interrogated them with combined assays of 44-plex CyTOF, RNA-seq and Olink. Notably, both asymptomatic and presymptomatic subjects exhibited numerous readily detectable immunological alterations, while certain parameters including more severely decreased frequencies of CD107alow classical monocytes, intermediate monocytes, non-classical monocytes and CD62Lhi CD8+ Tnaïve cells, reduced plasma STC1 level but an increased frequency of CD4+ NKT cells combined to distinguish the latter. Intercorrelation analyses revealed a particular presymptomatic immunotype mainly manifesting as monocytic overactivation and differentiation blockage, a likely lymphocyte exhaustion and immunosuppression, yielding mechanistic insights into SSIS fate determination, which could potentially improve SARS-CoV-2 management.
Proliferating coacervate droplets as the missing link between chemistry and biology in the origins of life
Authors: Matsuo Muneyuki , Kurihara Kensuke 
Published: October 2021

AbstractThe hypothesis that prebiotic molecules were transformed into polymers that evolved into proliferating molecular assemblages and eventually a primitive cell was first proposed about 100 years ago. To the best of our knowledge, however, no model of a proliferating prebiotic system has yet been realised because different conditions are required for polymer generation and self-assembly. In this study, we identify conditions suitable for concurrent peptide generation and self-assembly, and we show how a proliferating peptide-based droplet could be created by using synthesised amino acid thioesters as prebiotic monomers. Oligopeptides generated from the monomers spontaneously formed droplets through liquid–liquid phase separation in water. The droplets underwent a steady growth–division cycle by periodic addition of monomers through autocatalytic self-reproduction. Heterogeneous enrichment of RNA and lipids within droplets enabled RNA to protect the droplet from dissolution by lipids. These results provide experimental constructs for origins-of-life research and open up directions in the development of peptide-based materials.
Giant room temperature electrocaloric effect in a layered hybrid perovskite ferroelectric: [(CH3)2CHCH2NH3]2PbCl4
Authors: Liu Xitao , Wu Zhenyue , Guan Tong , Jiang Haidong , Long Peiqing , Li Xiaoqi , Ji Chengmin , Chen Shuang , Sun Zhihua , Luo Junhua 
Published: October 2021

AbstractElectrocaloric effect driven by electric fields displays great potential in realizing highly efficient solid-state refrigeration. Nevertheless, most known electrocaloric materials exhibit relatively poor cooling performance near room temperature, which hinders their further applications. The emerging family of hybrid perovskite ferroelectrics, which exhibits superior structural diversity, large heat exchange and broad property tenability, offers an ideal platform. Herein, we report an exceptionally large electrocaloric effect near room temperature in a designed hybrid perovskite ferroelectric [(CH3)2CHCH2NH3]2PbCl4, which exhibits a sharp first-order phase transition at 302 K, superior spontaneous polarization (>4.8 μC/cm2) and relatively small coercive field (<15 kV/cm). Strikingly, a large isothermal entropy change ΔS of 25.64 J/kg/K and adiabatic temperature change ΔT of 11.06 K under a small electric field ΔE of 29.7 kV/cm at room temperature are achieved, with giant electrocaloric strengths of isothermal ΔS/ΔE of 0.86 J·cm/kg/K/kV and adiabatic ΔT/ΔE of 370 mK·cm/kV, which is larger than those of traditional ferroelectrics. This work presents a general approach to the design of hybrid perovskite ferroelectrics, as well as provides a family of candidate materials with potentially prominent electrocaloric performance for room temperature solid-state refrigeration.
Captivity and the co-diversification of great ape microbiomes
Authors: Nishida Alex H. , Ochman Howard 
Published: October 2021

AbstractWild great apes harbor clades of gut bacteria that are restricted to each host species. Previous research shows the evolutionary relationships among several host-restricted clades mirror those of great-ape species. However, processes such as geographic separation, host-shift speciation, and host-filtering based on diet or gut physiology can generate host-restricted bacterial clades and mimic patterns of co-diversification across host species. To gain insight into the distribution of host-restricted taxa, we examine captive great apes living under conditions where sharing of bacterial strains is readily possible. Here, we show that increased sampling of wild and captive apes identifies additional host-restricted lineages whose relationships are not concordant with the host phylogeny. Moreover, the gut microbiomes of captive apes converge through the displacement of strains that are restricted to their wild conspecifics by human-restricted strains. We demonstrate that host-restricted and co-diversifying bacterial strains in wild apes lack persistence and fidelity in captive environments.