bluuebunny/crossref_metadata_2025 huggingface dataset:
Chinese politics and comparative authoritarianism: institutionalization and adaptation for regime resilience
Authors: Takeuchi Hiroki , Desai Saavni
Published: October 2021

China's authoritarian regime under the Chinese Communist Party (CCP) remains resilient and responsive to domestic and international threats to its survival, especially considering the inherent instability of other authoritarian regimes. What strategies allow the CCP to stay in power? How do institutions help the CCP to sustain one-party rule, if at all? How does the regime maintain centralized rule over its vast population and territory? Finally, how does the regime respond to the people's demands and dissatisfactions? This review essay discusses how the growing literature of comparative authoritarianism helps (or does not help) us to answer these questions. It discusses three books – one on comparative authoritarianism and two on Chinese politics. InHow Dictatorships Work: Power, Personalization, and Collapse, the authors (i.e., Barbara Geddes, Joseph Wright, and Erica Frantz) test various hypotheses exploring the issues regarding the central political processes that shape the policy choices of authoritarian regimes, such as seizing power, consolidation of elites, information gathering, and how dictatorships break down. Are their findings consistent or contradictory with observation of Chinese authoritarian politics? To answer this question, we draw empirical evidence from Bruce Dickson'sThe Dictator's Dilemma: The Chinese Communist Party's Strategy for Survivaland Min Ye'sThe Belt Road and Beyond: State Mobilized Globalization in China, 1998–2018. These books suggest why China's authoritarian regime remains resilient.
Dual-band-notched UWB MIMO antennas with miniaturization using half-cutting technology
Authors: Du Zhonghong , Zhang Xiaohui , Qin Peiyu , Yuan Yanning , Liu Jiangfan , Xi Xiaoli
Published: October 2021

A compact four-element ultra-wideband (UWB) multiple-input–multiple-output (MIMO) antenna with dual polarization and dual-notched capabilities was developed and fabricated. The MIMO antenna is composed of four orthogonally placed half-cutting UWB antenna elements. This orthogonal placement improves the isolation. Furthermore, an L-shaped slot and a continuous bending slot are etched to realize the band-rejection function in the WiMAX and WLAN bands. The result shows that the antenna achieved operating bands of 2.9–16.5 GHz (140.2%, S11 < −10 dB), fully covering the UWB (3.1–10.6 GHz). The port isolation is greater than 23 dB in the frequency band of interest, excluding two rejected bands. Moreover, the MIMO antenna has excellent diversity performance, such as a low envelope correlation coefficient (<0.004), high diversity gain (approximately 10 dB), and good omnidirectional radiation characteristics.
Detention in the context of counterterrorism and armed conflict: Continuities and new challenges
Authors: Hill-Cawthorne Lawrence
Published: October 2021

This article explores recent practices of States in relation to counterterrorism and armed conflict detention. Recent cases in the courts of the UK and US are drawn on to demonstrate the continued defence by those States of their administrative detention practices. Furthermore, the practice of other States in adopting new administrative detention laws as part of their counterterrorism strategies is explored. Finally, two examples of contemporary controversies are then considered to show where much of the debate is likely to be focused in the coming years, namely the use of other administrative measures short of detention, particularly assigned residence, and detentions carried out by armed groups that are supported by foreign States.
Mediterranean meal favorably effects postprandial oxidative stress response compared with a Western meal in healthy women
Authors: Tüccar Tuğçe Bulmuş , Akbulut Gamze
Published: October 2021

Abstract: Oxidative stress and inflammation are underlying factors in the pathogenesis of chronic diseases. The postprandial state is characterized by low-grade oxidative and inflammatory responses, but the impact of different dietary patterns on these responses is unclear. The objective of this study was to investigate postprandial oxidative and inflammatory responses to Mediterranean diet (MED) and Western diet (WD) meals. In a randomised crossover design, eleven healthy women, aged between 19–45 years with a body mass index of 20.0–24.9 kg/m2, consumed two different isocaloric meals: MED and WD. Blood samples were collected at fasting and 2, 3, 4 h postprandially and analyzed for oxidative [total antioxidant status (TAS), total oxidant status (TOS), total thiol, native thiol, malondialdehyde (MDA)] and inflammatory [high sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-17, IL-23, tumor necrosis factor alpha (TNF-α) and nuclear factor kappa B (NF-κB)] markers. MED meal intake resulted in increases in TAS (0.05±0.02 mmol/L; p=0.017), total thiol (23.00±7.69 μmol/L; p=0.013) and native thiol (12.82±4.94 μmol/L; p=0.027), while a decrease in MDA (−0.17±0.06 nmol/L; p=0.022) at 2 h. On the other hand, TAS reduced significantly overall (p=0.005) after WD meal intake. There was a significant increase after WD meal intake for IL-6 (1.39±0.49 pg/mL; p=0.017), IL-17 (4.30±1.50 pg/mL; p=0.017), IL-23 (8.38±3.51 pg/mL; p=0.038) at 4 h. However, serum hs-CRP, TNF-α and NF-κB levels were not changed significantly by meal intake. The results indicate that MED meal induces favorable effects on oxidative stress, while WD meal partially increases inflammation in daily life.
Sweeping Effects Modify Taylor’s Frozen Turbulence Hypothesis for Scalars in the Roughness Sublayer
Authors: Everard K. A. , Katul G. G. , Lawrence G. A. , Christen A. , Parlange M. B.
Published: October 2021

Taylor’s frozen turbulence hypothesis (FTH) is investigated in the roughness sublayer of a sloped vineyard canopy using a spatial array of fine‐wire thermocouples and ultrasonic anemometers. The Ellipse Approximation (EA) method is applied to the measured space‐time temperature correlation function to delineate sweeping effects from advection velocity. Sweeping effects are explained primarily by the turbulence kinetic energy. Upon the removal of sweeping effects, the advection velocity is found to be commensurate with the mean velocity.
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

Solar 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

Problematic 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

Plasticity 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

Copy 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

Transient 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

Chronic 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

Glioblastoma (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

Studies 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

Cervical 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

Although 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

Increasing 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

The 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

Electrocaloric 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

Wild 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.
Rapid prototyping and design of cybergenetic single-cell controllers
Authors: Kumar Sant , Rullan Marc , Khammash Mustafa
Published: October 2021

The design and implementation of synthetic circuits that operate robustly in the cellular context is fundamental for the advancement of synthetic biology. However, their practical implementation presents challenges due to low predictability of synthetic circuit design and time-intensive troubleshooting. Here, we present the Cyberloop, a testing framework to accelerate the design process and implementation of biomolecular controllers. Cellular fluorescence measurements are sent in real-time to a computer simulating candidate stochastic controllers, which in turn compute the control inputs and feed them back to the controlled cells via light stimulation. Applying this framework to yeast cells engineered with optogenetic tools, we examine and characterize different biomolecular controllers, test the impact of non-ideal circuit behaviors such as dilution on their operation, and qualitatively demonstrate improvements in controller function with certain network modifications. From this analysis, we derive conditions for desirable biomolecular controller performance, thereby avoiding pitfalls during its biological implementation.
Investigating the shared genetic architecture between multiple sclerosis and inflammatory bowel diseases
Authors: Yang Yuanhao , Musco Hannah , Simpson-Yap Steve , Zhu Zhihong , Wang Ying , Lin Xin , Zhang Jiawei , Taylor Bruce , Gratten Jacob , Zhou Yuan
Published: October 2021

An epidemiological association between multiple sclerosis (MS) and inflammatory bowel disease (IBD) is well established, but whether this reflects a shared genetic aetiology, and whether consistent genetic relationships exist between MS and the two predominant IBD subtypes, ulcerative colitis (UC) and Crohn’s disease (CD), remains unclear. Here, we use large-scale genome-wide association study summary data to investigate the shared genetic architecture between MS and IBD overall and UC and CD independently. We find a significantly greater genetic correlation between MS and UC than between MS and CD, and identify three SNPs shared between MS and IBD (rs13428812), UC (rs116555563) and CD (rs13428812, rs9977672) in cross-trait meta-analyses. We find suggestive evidence for a causal effect of MS on UC and IBD using Mendelian randomization, but no or weak and inconsistent evidence for a causal effect of IBD or UC on MS. We observe largely consistent patterns of tissue-specific heritability enrichment for MS and IBDs in lung, spleen, whole blood and small intestine, and identify cell-type-specific enrichment for MS and IBDs in CD4+T cells in lung and CD8+cytotoxic T cells in lung and spleen. Our study sheds light on the biological basis of comorbidity between MS and IBD.
A longitudinal sampling study of transcriptomic and epigenetic profiles in patients with thrombocytopenia syndrome
Authors: Wang Yafen , Han Shaoqing , Ran Ruoxi , Li Anling , Liu Huanyu , Liu Mingjun , Duan Yongwei , Zhang Xiong , Zhao Zhigang , Song Shihui , Weng Xiaocheng , Liu Song-Mei , Zhou Xiang
Published: October 2021

Severe fever with thrombocytopenia syndrome (SFTS) is a novel tick-borne infectious disease caused by a new type of SFTS virus (SFTSV). Here, a longitudinal sampling study is conducted to explore the differences in transcript levels after SFTSV infection, and to characterize the transcriptomic and epigenetic profiles of hospitalized patients. The results reveal significant changes in the mRNA expression of certain genes from onset to recovery. Moreover, m6A-seq reveals that certain genes related with immune regulation may be regulated by m6A. Besides the routine tests such as platelet counts, serum ALT and AST levels testing, distinct changes in myocardial enzymes, coagulation function, and inflammation are well correlated with the clinical data and sequencing data, suggesting that clinical practitioners should monitor the above indicators to track disease progression and guide personalized treatment. In this study, the transcript changes and RNA modification may lend a fresh perspective to our understanding of the SFTSV and play a significant role in the discovery of drugs for effective treatment of this disease.
Differentially expressed genes reflect disease-induced rather than disease-causing changes in the transcriptome
Authors: Porcu Eleonora , Sadler Marie C. , Lepik Kaido , Auwerx Chiara , Wood Andrew R. , Weihs Antoine , Sleiman Maroun S. Bou , Ribeiro Diogo M. , Bandinelli Stefania , Tanaka Toshiko , Nauck Matthias , Völker Uwe , Delaneau Olivier , Metspalu Andres , Teumer Alexander , Frayling Timothy , Santoni Federico A. , Reymond Alexandre , Kutalik Zoltán
Published: October 2021

Comparing transcript levels between healthy and diseased individuals allows the identification of differentially expressed genes, which may be causes, consequences or mere correlates of the disease under scrutiny. We propose a method to decompose the observational correlation between gene expression and phenotypes driven by confounders, forward- and reverse causal effects. The bi-directional causal effects between gene expression and complex traits are obtained by Mendelian Randomization integrating summary-level data from GWAS and whole-blood eQTLs. Applying this approach to complex traits reveals that forward effects have negligible contribution. For example, BMI- and triglycerides-gene expression correlation coefficients robustly correlate with trait-to-expression causal effects (rBMI = 0.11, PBMI = 2.0 × 10−51 and rTG = 0.13, PTG = 1.1 × 10−68), but not detectably with expression-to-trait effects. Our results demonstrate that studies comparing the transcriptome of diseased and healthy subjects are more prone to reveal disease-induced gene expression changes rather than disease causing ones.
Optomechanical synchronization across multi-octave frequency spans
Authors: Rodrigues Caique C. , Kersul Cauê M. , Primo André G. , Lipson Michal , Alegre Thiago P. Mayer , Wiederhecker Gustavo S.
Published: October 2021

Experimental exploration of synchronization in scalable oscillator microsystems has unfolded a deeper understanding of networks, collective phenomena, and signal processing. Cavity optomechanical devices have played an important role in this scenario, with the perspective of bridging optical and radio frequencies through nonlinear classical and quantum synchronization concepts. In its simplest form, synchronization occurs when an oscillator is entrained by a signal with frequency nearby the oscillator’s tone, and becomes increasingly challenging as their frequency detuning increases. Here, we experimentally demonstrate entrainment of a silicon-nitride optomechanical oscillator driven up to the fourth harmonic of its 32 MHz fundamental frequency. Exploring this effect, we also experimentally demonstrate a purely optomechanical RF frequency divider, where we performed frequency division up to a 4:1 ratio, i.e., from 128 MHz to 32 MHz. Further developments could harness these effects towards frequency synthesizers, phase-sensitive amplification and nonlinear sensing.
Evolutionarily informed machine learning enhances the power of predictive gene-to-phenotype relationships
Authors: Cheng Chia-Yi , Li Ying , Varala Kranthi , Bubert Jessica , Huang Ji , Kim Grace J. , Halim Justin , Arp Jennifer , Shih Hung-Jui S. , Levinson Grace , Park Seo Hyun , Cho Ha Young , Moose Stephen P. , Coruzzi Gloria M.
Published: October 2021

Inferring phenotypic outcomes from genomic features is both a promise and challenge for systems biology. Using gene expression data to predict phenotypic outcomes, and functionally validating the genes with predictive powers are two challenges we address in this study. We applied an evolutionarily informed machine learning approach to predict phenotypes based on transcriptome responses shared both within and across species. Specifically, we exploited the phenotypic diversity in nitrogen use efficiency and evolutionarily conserved transcriptome responses to nitrogen treatments across Arabidopsis accessions and maize varieties. We demonstrate that using evolutionarily conserved nitrogen responsive genes is a biologically principled approach to reduce the feature dimensionality in machine learning that ultimately improved the predictive power of our gene-to-trait models. Further, we functionally validated seven candidate transcription factors with predictive power for NUE outcomes in Arabidopsis and one in maize. Moreover, application of our evolutionarily informed pipeline to other species including rice and mice models underscores its potential to uncover genes affecting any physiological or clinical traits of interest across biology, agriculture, or medicine.
Out-of-equilibrium processes in crystallization of organic-inorganic perovskites during spin coating
Authors: Pratap Shambhavi , Babbe Finn , Barchi Nicola S. , Yuan Zhenghao , Luong Tina , Haber Zach , Song Tze-Bin , Slack Jonathan L. , Stan Camelia V. , Tamura Nobumichi , Sutter-Fella Carolin M. , Müller-Buschbaum Peter
Published: October 2021

Complex phenomena are prevalent during the formation of materials, which affect their processing-structure-function relationships. Thin films of methylammonium lead iodide (CH3NH3PbI3, MAPI) are processed by spin coating, antisolvent drop, and annealing of colloidal precursors. The structure and properties of transient and stable phases formed during the process are reported, and the mechanistic insights of the underlying transitions are revealed by combining in situ data from grazing-incidence wide-angle X-ray scattering and photoluminescence spectroscopy. Here, we report the detailed insights on the embryonic stages of organic-inorganic perovskite formation. The physicochemical evolution during the conversion proceeds in four steps: i) An instant nucleation of polydisperse MAPI nanocrystals on antisolvent drop, ii) the instantaneous partial conversion of metastable nanocrystals into orthorhombic solvent-complex by cluster coalescence, iii) the thermal decomposition (dissolution) of the stable solvent-complex into plumboiodide fragments upon evaporation of solvent from the complex and iv) the formation (recrystallization) of cubic MAPI crystals in thin film.
Extensive regulation of enzyme activity by phosphorylation in Escherichia coli
Authors: Schastnaya Evgeniya , Raguz Nakic Zrinka , Gruber Christoph H. , Doubleday Peter Francis , Krishnan Aarti , Johns Nathan I. , Park Jimin , Wang Harris H. , Sauer Uwe
Published: October 2021

Protein serine/threonine/tyrosine (S/T/Y) phosphorylation is an essential and frequent post-translational modification in eukaryotes, but historically has been considered less prevalent in bacteria because fewer proteins were found to be phosphorylated and most proteins were modified to a lower degree. Recent proteomics studies greatly expanded the phosphoproteome of Escherichia coli to more than 2000 phosphorylation sites (phosphosites), yet mechanisms of action were proposed for only six phosphosites and fitness effects were described for 38 phosphosites upon perturbation. By systematically characterizing functional relevance of S/T/Y phosphorylation in E. coli metabolism, we found 44 of the 52 mutated phosphosites to be functional based on growth phenotypes and intracellular metabolome profiles. By effectively doubling the number of known functional phosphosites, we provide evidence that protein phosphorylation is a major regulation process in bacterial metabolism. Combining in vitro and in vivo experiments, we demonstrate how single phosphosites modulate enzymatic activity and regulate metabolic fluxes in glycolysis, methylglyoxal bypass, acetate metabolism and the split between pentose phosphate and Entner-Doudoroff pathways through mechanisms that include shielding the substrate binding site, limiting structural dynamics, and disrupting interactions relevant for activity in vivo.
Endurance exercise training-responsive miR-19b-3p improves skeletal muscle glucose metabolism
Authors: Massart Julie , Sjögren Rasmus J. O. , Egan Brendan , Garde Christian , Lindgren Magnus , Gu Weifeng , Ferreira Duarte M. S. , Katayama Mutsumi , Ruas Jorge L. , Barrès Romain , O’Gorman Donal J. , Zierath Juleen R. , Krook Anna
Published: October 2021

Skeletal muscle is a highly adaptable tissue and remodels in response to exercise training. Using short RNA sequencing, we determine the miRNA profile of skeletal muscle from healthy male volunteers before and after a 14-day aerobic exercise training regime. Among the exercise training-responsive miRNAs identified, miR-19b-3p was selected for further validation. Overexpression of miR-19b-3p in human skeletal muscle cells increases insulin signaling, glucose uptake, and maximal oxygen consumption, recapitulating the adaptive response to aerobic exercise training. Overexpression of miR-19b-3p in mouse flexor digitorum brevis muscle enhances contraction-induced glucose uptake, indicating that miR-19b-3p exerts control on exercise training-induced adaptations in skeletal muscle. Potential targets of miR-19b-3p that are reduced after aerobic exercise training include KIF13A, MAPK6, RNF11, and VPS37A. Amongst these, RNF11 silencing potentiates glucose uptake in human skeletal muscle cells. Collectively, we identify miR-19b-3p as an aerobic exercise training-induced miRNA that regulates skeletal muscle glucose metabolism.
Interleukin-31 promotes fibrosis and T helper 2 polarization in systemic sclerosis
Authors: Kuzumi Ai , Yoshizaki Ayumi , Matsuda Kazuki M. , Kotani Hirohito , Norimatsu Yuta , Fukayama Maiko , Ebata Satoshi , Fukasawa Takemichi , Yoshizaki-Ogawa Asako , Asano Yoshihide , Morikawa Kyojiro , Kazoe Yutaka , Mawatari Kazuma , Kitamori Takehiko , Sato Shinichi
Published: October 2021

Systemic sclerosis (SSc) is a chronic multisystem disorder characterized by fibrosis and autoimmunity. Interleukin (IL)-31 has been implicated in fibrosis and T helper (Th) 2 immune responses, both of which are characteristics of SSc. The exact role of IL-31 in SSc pathogenesis is unclear. Here we show the overexpression of IL-31 and IL-31 receptor A (IL-31RA) in dermal fibroblasts (DFs) from SSc patients. We elucidate the dual role of IL-31 in SSc, where IL-31 directly promotes collagen production in DFs and indirectly enhances Th2 immune responses by increasing pro-Th2 cytokine expression in DFs. Furthermore, blockade of IL-31 with anti-IL-31RA antibody significantly ameliorates fibrosis and Th2 polarization in a mouse model of SSc. Therefore, in addition to defining IL-31 as a mediator of fibrosis and Th2 immune responses in SSc, our study provides a rationale for targeting the IL-31/IL-31RA axis in the treatment of SSc.
Relationship of insect biomass and richness with land use along a climate gradient
Authors: Uhler Johannes , Redlich Sarah , Zhang Jie , Hothorn Torsten , Tobisch Cynthia , Ewald Jörg , Thorn Simon , Seibold Sebastian , Mitesser Oliver , Morinière Jérôme , Bozicevic Vedran , Benjamin Caryl S. , Englmeier Jana , Fricke Ute , Ganuza Cristina , Haensel Maria , Riebl Rebekka , Rojas-Botero Sandra , Rummler Thomas , Uphus Lars , Schmidt Stefan , Steffan-Dewenter Ingolf , Müller Jörg
Published: October 2021

Recently reported insect declines have raised both political and social concern. Although the declines have been attributed to land use and climate change, supporting evidence suffers from low taxonomic resolution, short time series, a focus on local scales, and the collinearity of the identified drivers. In this study, we conducted a systematic assessment of insect populations in southern Germany, which showed that differences in insect biomass and richness are highly context dependent. We found the largest difference in biomass between semi-natural and urban environments (−42%), whereas differences in total richness (−29%) and the richness of threatened species (−56%) were largest from semi-natural to agricultural environments. These results point to urbanization and agriculture as major drivers of decline. We also found that richness and biomass increase monotonously with increasing temperature, independent of habitat. The contrasting patterns of insect biomass and richness question the use of these indicators as mutual surrogates. Our study provides support for the implementation of more comprehensive measures aimed at habitat restoration in order to halt insect declines.
Metal-catalyst-free gas-phase synthesis of long-chain hydrocarbons
Authors: Martínez Lidia , Merino Pablo , Santoro Gonzalo , Martínez José I. , Katsanoulis Stergios , Ault Jesse , Mayoral Álvaro , Vázquez Luis , Accolla Mario , Dazzi Alexandre , Mathurin Jeremie , Borondics Ferenc , Blázquez-Blázquez Enrique , Shauloff Nitzan , Lebrón-Aguilar Rosa , Quintanilla-López Jesús E. , Jelinek Raz , Cernicharo José , Stone Howard A. , de la Peña O’Shea Victor A. , de Andres Pedro L. , Haller George , Ellis Gary J. , Martín-Gago José A.
Published: October 2021

Development of sustainable processes for hydrocarbons synthesis is a fundamental challenge in chemistry since these are of unquestionable importance for the production of many essential synthetic chemicals, materials and carbon-based fuels. Current industrial processes rely on non-abundant metal catalysts, temperatures of hundreds of Celsius and pressures of tens of bars. We propose an alternative gas phase process under mild reaction conditions using only atomic carbon, molecular hydrogen and an inert carrier gas. We demonstrate that the presence of CH2 and H radicals leads to efficient C-C chain growth, producing micron-length fibres of unbranched alkanes with an average length distribution between C23-C33. Ab-initio calculations uncover a thermodynamically favourable methylene coupling process on the surface of carbonaceous nanoparticles, which is kinematically facilitated by a trap-and-release mechanism of the reactants and nanoparticles that is confirmed by a steady incompressible flow simulation. This work could lead to future alternative sustainable synthetic routes to critical alkane-based chemicals or fuels.