bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatic metastasis of gastric cancer is associated with enhanced expression of ethanolamine kinase 2 via the p53–Bcl-2 intrinsic apoptosis pathway
Authors: Miwa Takashi , Kanda Mitsuro , Shimizu Dai , Umeda Shinichi , Sawaki Koichi , Tanaka Haruyoshi , Tanaka Chie , Hattori Norifumi , Hayashi Masamichi , Yamada Suguru , Nakayama Goro , Koike Masahiko , Kodera Yasuhiro 
Published: February 2021

Abstract
Background
Gastric cancer (GC) with hepatic metastasis has a poor prognosis. Understanding the molecular mechanisms involved in hepatic metastasis may contribute to the development of sensitive diagnostic biomarkers and novel therapeutic strategies.

Methods
We performed transcriptome analysis of surgically resected specimens from patients with advanced GC. One of the genes identified as specifically associated with hepatic metastasis was selected for detailed analysis. GC cell lines with knockout of the candidate gene were evaluated in vitro and in vivo. Expression of the candidate gene was analysed in GC tissues from 300 patients.

Results
Ethanolamine kinase 2 (ETNK2) was differentially upregulated in GC patients with hepatic metastasis. ETNK2 expression was elevated in GC cell lines derived from haematogenous metastases. ETNK2 knockout significantly suppressed proliferation, invasion, and migration; increased apoptosis; reduced Bcl-2 protein expression; and increased phosphorylated p53 expression. In mouse xenograft models, ETNK2 knockout virtually abolished hepatic metastasis. Stratification of GC patients based on ETNK2 mRNA level revealed significant associations between high ETNK2 tumour expression and both hepatic recurrence and worse prognosis.

Conclusions
Upregulation of ETNK2 in GC enhances hepatic metastasis, possibly via dysregulation of p53–Bcl-2-associated apoptosis. ETNK2 expression may serve as a biomarker for predicting hepatic recurrence and a therapeutic target.
Novel STAR gene variant in a patient with classic lipoid congenital adrenal hyperplasia and combined pituitary hormone deficiency
Authors: Higa Moritake , Zaha Akiko , Takushi Akiko , Morishima Nami , Majikina Toyofumi , Touma Takeshi , Shimabukuro Michio , Masuzaki Hiroaki , Honda Misa , Hasegawa Tomonobu 
Published: February 2021

AbstractWe report the first case of classic lipoid congenital adrenal hyperplasia and combined pituitary hormone deficiency. We identified pathogenic variants in the STAR gene: a novel variant of c.126_127delCCinsG, namely, p.Thr44Profs*2 and an already reported variant of c.634C>T, namely, p.Gln212*. The association with combined pituitary hormone deficiency might be just a coincidence.
A fast and efficient colocalization algorithm for identifying shared genetic risk factors across multiple traits
Authors: Foley Christopher N. , Staley James R. , Breen Philip G. , Sun Benjamin B. , Kirk Paul D. W. , Burgess Stephen , Howson Joanna M. M. 
Published: February 2021

AbstractGenome-wide association studies (GWAS) have identified thousands of genomic regions affecting complex diseases. The next challenge is to elucidate the causal genes and mechanisms involved. One approach is to use statistical colocalization to assess shared genetic aetiology across multiple related traits (e.g. molecular traits, metabolic pathways and complex diseases) to identify causal pathways, prioritize causal variants and evaluate pleiotropy. We propose HyPrColoc (Hypothesis Prioritisation for multi-trait Colocalization), an efficient deterministic Bayesian algorithm using GWAS summary statistics that can detect colocalization across vast numbers of traits simultaneously (e.g. 100 traits can be jointly analysed in around 1 s). We perform a genome-wide multi-trait colocalization analysis of coronary heart disease (CHD) and fourteen related traits, identifying 43 regions in which CHD colocalized with ≥1 trait, including 5 previously unknown CHD loci. Across the 43 loci, we further integrate gene and protein expression quantitative trait loci to identify candidate causal genes.
Simulating the ghost: quantum dynamics of the solvated electron
Authors: Lan Jinggang , Kapil Venkat , Gasparotto Piero , Ceriotti Michele , Iannuzzi Marcella , Rybkin Vladimir V. 
Published: February 2021

AbstractThe nature of the bulk hydrated electron has been a challenge for both experiment and theory due to its short lifetime and high reactivity, and the need for a high-level of electronic structure theory to achieve predictive accuracy. The lack of a classical atomistic structural formula makes it exceedingly difficult to model the solvated electron using conventional empirical force fields, which describe the system in terms of interactions between point particles associated with atomic nuclei. Here we overcome this problem using a machine-learning model, that is sufficiently flexible to describe the effect of the excess electron on the structure of the surrounding water, without including the electron in the model explicitly. The resulting potential is not only able to reproduce the stable cavity structure but also recovers the correct localization dynamics that follow the injection of an electron in neat water. The machine learning model achieves the accuracy of the state-of-the-art correlated wave function method it is trained on. It is sufficiently inexpensive to afford a full quantum statistical and dynamical description and allows us to achieve accurate determination of the structure, diffusion mechanisms, and vibrational spectroscopy of the solvated electron.
Laboratory disruption of scaled astrophysical outflows by a misaligned magnetic field
Authors: Revet G. , Khiar B. , Filippov E. , Argiroffi C. , Béard J. , Bonito R. , Cerchez M. , Chen S. N. , Gangolf T. , Higginson D. P. , Mignone A. , Olmi B. , Ouillé M. , Ryazantsev S. N. , Skobelev I. Yu. , Safronova M. I. , Starodubtsev M. , Vinci T. , Willi O. , Pikuz S. , Orlando S. , Ciardi A. , Fuchs J. 
Published: February 2021

AbstractThe shaping of astrophysical outflows into bright, dense, and collimated jets due to magnetic pressure is here investigated using laboratory experiments. Here we look at the impact on jet collimation of a misalignment between the outflow, as it stems from the source, and the magnetic field. For small misalignments, a magnetic nozzle forms and redirects the outflow in a collimated jet. For growing misalignments, this nozzle becomes increasingly asymmetric, disrupting jet formation. Our results thus suggest outflow/magnetic field misalignment to be a plausible key process regulating jet collimation in a variety of objects from our Sun’s outflows to extragalatic jets. Furthermore, they provide a possible interpretation for the observed structuring of astrophysical jets. Jet modulation could be interpreted as the signature of changes over time in the outflow/ambient field angle, and the change in the direction of the jet could be the signature of changes in the direction of the ambient field.
Improving hindlimb locomotor function by Non-invasive AAV-mediated manipulations of propriospinal neurons in mice with complete spinal cord injury
Authors: Brommer Benedikt , He Miao , Zhang Zicong , Yang Zhiyun , Page Jessica C. , Su Junfeng , Zhang Yu , Zhu Junjie , Gouy Emilia , Tang Jing , Williams Philip , Dai Wei , Wang Qi , Solinsky Ryan , Chen Bo , He Zhigang 
Published: February 2021

AbstractAfter complete spinal cord injuries (SCI), spinal segments below the lesion maintain inter-segmental communication via the intraspinal propriospinal network. However, it is unknown whether selective manipulation of these circuits can restore locomotor function in the absence of brain-derived inputs. By taking advantage of the compromised blood-spinal cord barrier following SCI, we optimized a set of procedures in which AAV9 vectors administered via the tail vein efficiently transduce neurons in lesion-adjacent spinal segments after a thoracic crush injury in adult mice. With this method, we used chemogenetic actuators to alter the excitability of propriospinal neurons in the thoracic cord of the adult mice with a complete thoracic crush injury. We showed that activating these thoracic neurons enables consistent and significant hindlimb stepping improvement, whereas direct manipulations of the neurons in the lumbar spinal cord led to muscle spasms without meaningful locomotion. Strikingly, manipulating either excitatory or inhibitory propriospinal neurons in the thoracic levels leads to distinct behavioural outcomes, with preferential effects on standing or stepping, two key elements of the locomotor function. These results demonstrate a strategy of engaging thoracic propriospinal neurons to improve hindlimb function and provide insights into optimizing neuromodulation-based strategies for treating SCI.
Imaging non-collinear antiferromagnetic textures via single spin relaxometry
Authors: Finco Aurore , Haykal Angela , Tanos Rana , Fabre Florentin , Chouaieb Saddem , Akhtar Waseem , Robert-Philip Isabelle , Legrand William , Ajejas Fernando , Bouzehouane Karim , Reyren Nicolas , Devolder Thibaut , Adam Jean-Paul , Kim Joo-Von , Cros Vincent , Jacques Vincent 
Published: February 2021

AbstractAntiferromagnetic materials are promising platforms for next-generation spintronics owing to their fast dynamics and high robustness against parasitic magnetic fields. However, nanoscale imaging of the magnetic order in such materials with zero net magnetization remains a major experimental challenge. Here we show that non-collinear antiferromagnetic spin textures can be imaged by probing the magnetic noise they locally produce via thermal populations of magnons. To this end, we perform nanoscale, all-optical relaxometry with a scanning quantum sensor based on a single nitrogen-vacancy (NV) defect in diamond. Magnetic noise is detected through an increase of the spin relaxation rate of the NV defect, which results in an overall reduction of its photoluminescence signal under continuous laser illumination. As a proof-of-concept, the efficiency of the method is demonstrated by imaging various spin textures in synthetic antiferromagnets, including domain walls, spin spirals and antiferromagnetic skyrmions. This imaging procedure could be extended to a large class of intrinsic antiferromagnets and opens up new opportunities for studying the physics of localized spin wave modes for magnonics.
Cryptochrome 1 mediates light-dependent inclination magnetosensing in monarch butterflies
Authors: Wan Guijun , Hayden Ashley N. , Iiams Samantha E. , Merlin Christine 
Published: February 2021

AbstractMany animals use the Earth’s geomagnetic field for orientation and navigation. Yet, the molecular and cellular underpinnings of the magnetic sense remain largely unknown. A biophysical model proposed that magnetoreception can be achieved through quantum effects of magnetically-sensitive radical pairs formed by the photoexcitation of cryptochrome (CRY) proteins. Studies in Drosophila are the only ones to date to have provided compelling evidence for the ultraviolet (UV)-A/blue light-sensitive type 1 CRY (CRY1) involvement in animal magnetoreception, and surprisingly extended this discovery to the light-insensitive mammalian-like type 2 CRYs (CRY2s) of both monarchs and humans. Here, we show that monarchs respond to a reversal of the inclination of the Earth’s magnetic field in an UV-A/blue light and CRY1, but not CRY2, dependent manner. We further demonstrate that both antennae and eyes, which express CRY1, are magnetosensory organs. Our work argues that only light-sensitive CRYs function in animal light-dependent inclination-based magnetic sensing.
Ferroelectric columnar assemblies from the bowl-to-bowl inversion of aromatic cores
Authors: Furukawa Shunsuke , Wu Jianyun , Koyama Masaya , Hayashi Keisuke , Hoshino Norihisa , Takeda Takashi , Suzuki Yasutaka , Kawamata Jun , Saito Masaichi , Akutagawa Tomoyuki 
Published: February 2021

AbstractOrganic ferroelectrics, in which the constituent molecules retain remanent polarization, represent an important topic in condensed-matter science, and their attractive properties, which include lightness, flexibility, and non-toxicity, are of potential use in state-of-the-art ferroelectric devices. However, the mechanisms for the generation of ferroelectricity in such organic compounds remain limited to a few representative concepts, which has hitherto severely hampered progress in this area. Here, we demonstrate that a bowl-to-bowl inversion of a relatively small organic molecule with a bowl-shaped π-aromatic core generates ferroelectric dipole relaxation. The present results thus reveal an unprecedented concept to produce ferroelectricity in small organic molecules, which can be expected to strongly impact materials science.
Conserved strategies of RNA polymerase I hibernation and activation
Authors: Heiss Florian B. , Daiß Julia L. , Becker Philipp , Engel Christoph 
Published: February 2021

AbstractRNA polymerase (Pol) I transcribes the ribosomal RNA precursor in all eukaryotes. The mechanisms ‘activation by cleft contraction’ and ‘hibernation by dimerization’ are unique to the regulation of this enzyme, but structure-function analysis is limited to baker’s yeast. To understand whether regulation by such strategies is specific to this model organism or conserved among species, we solve three cryo-EM structures of Pol I fromSchizosaccharomyces pombein different functional states. Comparative analysis of structural models derived from high-resolution reconstructions shows that activation is accomplished by a conserved contraction of the active center cleft. In contrast to current beliefs, we find that dimerization of theS. pombepolymerase is also possible. This dimerization is achieved independent of the ‘connector’ domain but relies on two previously undescribed interfaces. Our analyses highlight the divergent nature of Pol I transcription systems from their counterparts and suggest conservation of regulatory mechanisms among organisms.
A scaffold lncRNA shapes the mitosis to meiosis switch
Authors: Andric Vedrana , Nevers Alicia , Hazra Ditipriya , Auxilien Sylvie , Menant Alexandra , Graille Marc , Palancade Benoit , Rougemaille Mathieu 
Published: February 2021

AbstractLong non-coding RNAs (lncRNAs) contribute to the regulation of gene expression in response to intra- or extracellular signals but the underlying molecular mechanisms remain largely unexplored. Here, we identify an uncharacterized lncRNA as a central player in shaping the meiotic gene expression program in fission yeast. We report that this regulatory RNA, termed mamRNA, scaffolds the antagonistic RNA-binding proteins Mmi1 and Mei2 to ensure their reciprocal inhibition and fine tune meiotic mRNA degradation during mitotic growth. Mechanistically, mamRNA allows Mmi1 to target Mei2 for ubiquitin-mediated downregulation, and conversely enables accumulating Mei2 to impede Mmi1 activity, thereby reinforcing the mitosis to meiosis switch. These regulations also occur within a unique Mmi1-containing nuclear body, positioning mamRNA as a spatially-confined sensor of Mei2 levels. Our results thus provide a mechanistic basis for the mutual control of gametogenesis effectors and further expand our vision of the regulatory potential of lncRNAs.
CD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer
Authors: Tallón de Lara Paulino , Castañón Héctor , Vermeer Marijne , Núñez Nicolás , Silina Karina , Sobottka Bettina , Urdinez Joaquín , Cecconi Virginia , Yagita Hideo , Movahedian Attar Farkhondeh , Hiltbrunner Stefanie , Glarner Isabelle , Moch Holger , Tugues Sònia , Becher Burkhard , van den Broek Maries 
Published: February 2021

AbstractSome breast tumors metastasize aggressively whereas others remain dormant for years. The mechanism governing metastatic dormancy remains largely unknown. Through high-parametric single-cell mapping in mice, we identify a discrete population of CD39+PD-1+CD8+T cells in primary tumors and in dormant metastasis, which is hardly found in aggressively metastasizing tumors. Using blocking antibodies, we find that dormancy depends on TNFα and IFNγ. Immunotherapy reduces the number of dormant cancer cells in the lungs. Adoptive transfer of purified CD39+PD-1+CD8+T cells prevents metastatic outgrowth. In human breast cancer, the frequency of CD39+PD-1+CD8+but not total CD8+T cells correlates with delayed metastatic relapse after resection (disease-free survival), thus underlining the biological relevance of CD39+PD-1+CD8+T cells for controlling experimental and human breast cancer. Thus, we suggest that a primary breast tumor could prime a systemic, CD39+PD-1+CD8+T cell response that favors metastatic dormancy in the lungs.
High-throughput phenotypic screen and transcriptional analysis identify new compounds and targets for macrophage reprogramming
Authors: Hu Guangan , Su Yang , Kang Byong Ha , Fan Zhongqi , Dong Ting , Brown Douglas R. , Cheah Jaime , Wittrup Karl Dane , Chen Jianzhu 
Published: February 2021

AbstractMacrophages are plastic and, in response to different local stimuli, can polarize toward multi-dimensional spectrum of phenotypes, including the pro-inflammatory M1-like and the anti-inflammatory M2-like states. Using a high-throughput phenotypic screen in a library of ~4000 FDA-approved drugs, bioactive compounds and natural products, we find ~300 compounds that potently activate primary human macrophages toward either M1-like or M2-like state, of which ~30 are capable of reprogramming M1-like macrophages toward M2-like state and another ~20 for the reverse repolarization. Transcriptional analyses of macrophages treated with 34 non-redundant compounds identify both shared and unique targets and pathways through which the tested compounds modulate macrophage activation. One M1-activating compound, thiostrepton, is able to reprogram tumor-associated macrophages toward M1-like state in mice, and exhibit potent anti-tumor activity. Our compound-screening results thus help to provide a valuable resource not only for studying the macrophage biology but also for developing therapeutics through modulating macrophage activation.
Interdependence between nanoclusters AuAg24 and Au2Ag41
Authors: Liu Danyu , Du Wenjun , Chen Shuang , Kang Xi , Chen Along , Zhen Yaru , Jin Shan , Hu Daqiao , Wang Shuxin , Zhu Manzhou 
Published: February 2021

AbstractWhole series of nanoparticles have now been reported, but probing the competing or coexisting effects in their synthesis and growth remains challenging. Here, we report a bi-nanocluster system comprising two ultra-small, atomically precise nanoclusters, AuAg24(SR)18− and Au2Ag41(SR)26(Dppm)2+ (SR = cyclohexyl mercaptan, Dppm = bis(diphenylphosphino)-methane). The mechanism by which these two nanoclusters coexist is elucidated, and found to entail formation of the unstable AuAg24(SR)18−, followed by its partial conversion to Au2Ag41(SR)26(Dppm)2+ in the presence of di-phosphorus ligands, and an interdependent bi-nanocluster system is established, wherein the two oppositely charged nanoclusters protect each other from decomposition. AuAg24(SR)18 and Au2Ag41(SR)26(Dppm)2 are fully characterized by single crystal X-ray diffraction (SC-XRD) analysis – it is found that their co-crystallization results in single crystals comprising equimolar amounts of each. The findings highlight the interdependent relationship between two individual nanoclusters, which paves the way for new perspectives on nanocluster formation and stability.
Increased random exploration in schizophrenia is associated with inflammation
Authors: Cathomas Flurin , Klaus Federica , Guetter Karoline , Chung Hui-Kuan , Raja Beharelle Anjali , Spiller Tobias R. , Schlegel Rebecca , Seifritz Erich , Hartmann-Riemer Matthias N. , Tobler Philippe N. , Kaiser Stefan 
Published: February 2021

AbstractOne aspect of goal-directed behavior, which is known to be impaired in patients with schizophrenia (SZ), is balancing between exploiting a familiar choice with known reward value and exploring a lesser known, but potentially more rewarding option. Despite its relevance to several symptom domains of SZ, this has received little attention in SZ research. In addition, while there is increasing evidence that SZ is associated with chronic low-grade inflammation, few studies have investigated how this relates to specific behaviors, such as balancing exploration and exploitation. We therefore assessed behaviors underlying the exploration–exploitation trade-off using a three-armed bandit task in 45 patients with SZ and 19 healthy controls (HC). This task allowed us to dissociate goal-unrelated (random) from goal-related (directed) exploration and correlate them with psychopathological symptoms. Moreover, we assessed a broad range of inflammatory proteins in the blood and related them to bandit task behavior. We found that, compared to HC, patients with SZ showed reduced task performance. This impairment was due to a shift from exploitation to random exploration, which was associated with symptoms of disorganization. Relative to HC, patients with SZ showed a pro-inflammatory blood profile. Furthermore, high-sensitivity C-reactive protein (hsCRP) positively correlated with random exploration, but not with directed exploration or exploitation. In conclusion, we show that low-grade inflammation in patients with SZ is associated with random exploration, which can be considered a behavioral marker for disorganization. hsCRP may constitute a marker for severity of, and a potential treatment target for maladaptive exploratory behaviors.
Low muscle strength and increased arterial stiffness go hand in hand
Authors: König Maximilian , Buchmann Nikolaus , Seeland Ute , Spira Dominik , Steinhagen-Thiessen Elisabeth , Demuth Ilja 
Published: February 2021

AbstractLow handgrip strength and increased arterial stiffness are both associated with poor health outcomes, but evidence on the relationship between handgrip strength and arterial stiffness is limited. In this cross-sectional analysis of combined baseline datasets from the LipidCardio and Berlin Aging Study II cohorts we aimed to examine whether handgrip strength (HGS) is associated with arterial stiffness. 1511 participants with a median age of 68.56 (IQR 63.13–73.08) years were included. Arterial stiffness was assessed by aortal pulse wave velocity (PWV) with the Mobil-O-Graph device. Handgrip strength was assessed with a handheld dynamometer.The mean HGS was 39.05 ± 9.07 kg in men and 26.20 ± 7.47 kg in women. According to multivariable linear regression analysis per 5 kg decrease in handgrip strength there was a mean increase in PWV of 0.08 m/s after adjustment for the confounders age, sex, coronary artery disease, systolic blood pressure, body mass index, cohort, and smoking. Thus, there was evidence that low handgrip strength and increased arterial stiffness go hand in hand. Arterial stiffness can possibly create the missing link between low handgrip strength and increased cardiovascular morbidity and mortality. Causality and direction of causality remain to be determined.