bluuebunny/crossref_metadata_2025 huggingface dataset:
Fault Slip Behaviors Modulated by Locally Increased Fluid Pressure: Earthquake Nucleation and Slow Slip Events
Authors: Dong Peng , Xu Ran , Yang Hongfeng , Guo Zhiyin , Xia Kaiwen
Published: November 2022

Huge earthquakes are frequently preceded by slow slip events (SSEs) that are speculated as the precursor to regular earthquakes (REs). However, the way in which earthquakes initiate, as well as the interactions between SSEs and REs remain poorly understood, adding more mysteries to the initiation of earthquakes. Here, we perform systematic numerical simulations to explore the relationships between SSEs and REs on faults including locally increased fluid pressure. We identify four types of fault slip behaviors distinguished by SSE and earthquake initiation mode. The observed interactions between SSEs and REs share similar features with those reported for natural earthquakes. Our results show that the occurrence of SSEs may temporarily hasten fault decoupling, leading to the clock advance of mainshocks. Furthermore, the interactions between SSEs and REs are more complicated than previously thought. On the one hand, since SSEs with extremely high peak slip rates tend to directly transform into huge earthquakes, the possibility of huge earthquakes may increase when SSEs happen. On the other hand, there is no threshold in peak slip rate for SSEs to trigger the nucleation of REs. Therefore, it is difficult to distinguish the SSEs that could trigger a huge earthquake from regular ones only with the knowledge of the peak slip rate. We also verify that the spatial extent of SSEs is related to the occurrence of earthquakes to some extent. These findings may have major implications for understanding the interactions between SSEs and REs, and the mechanism of earthquake initiation.
SMP30-mediated synthesis of vitamin C activates the liver PPARα/FGF21 axis to regulate thermogenesis in mice
Authors: Lee Bonggi , An Hye Jin , Kim Dae Hyun , Lee Min-Kyeong , Jeong Hyeon Hak , Chung Ki Wung , Go Younghoon , Seo Arnold Y. , Kim Il Yong , Seong Je Kyung , Yu Byung Pal , Lee Jaewon , Im Eunok , Lee In-Kyu , Lee Myung-Shik , Yamada Ken-ichi , Chung Hae Young
Published: November 2022

The vitamin-C-synthesizing enzyme senescent marker protein 30 (SMP30) is a cold resistance gene in Drosophila, and vitamin C concentration increases in brown adipose tissue post-cold exposure. However, the roles of SMP30 in thermogenesis are unknown. Here, we tested the molecular mechanism of thermogenesis using wild-type (WT) and vitamin C-deficient SMP30-knockout (KO) mice. SMP30-KO mice gained more weight than WT mice without a change in food intake in response to short-term high-fat diet feeding. Indirect calorimetry and cold-challenge experiments indicated that energy expenditure is lower in SMP30-KO mice, which is associated with decreased thermogenesis in adipose tissues. Therefore, SMP30-KO mice do not lose weight during cold exposure, whereas WT mice lose weight markedly. Mechanistically, the levels of serum FGF21 were notably lower in SMP30-KO mice, and vitamin C supplementation in SMP30-KO mice recovered FGF21 expression and thermogenesis, with a marked reduction in body weight during cold exposure. Further experiments revealed that vitamin C activates PPARα to upregulate FGF21. Our findings demonstrate that SMP30-mediated synthesis of vitamin C activates the PPARα/FGF21 axis, contributing to the maintenance of thermogenesis in mice.
Intracellular common gardens reveal niche differentiation in transposable element community during bacterial adaptive evolution
Authors: Guo Hui , Shi Wen-Tao , Zhang Biliang , Xu Yan-Hui , Jiao Jian , Tian Chang-Fu
Published: November 2022

The distribution and abundance of transposable elements across the tree of life have significantly shaped the evolution of cellular organisms, but the underlying mechanisms shaping these ecological patterns remain elusive. Here we establish a “common garden” approach to study causal ecological interactions between a xenogeneic conditional lethal sacB gene and the community of transposable insertion sequences (ISs) in a multipartite prokaryote genome. Xenogeneic sacB of low, medium, or high GC content was individually inserted into three replicons of a model bacterium Sinorhizobium fredii, and exhibited replicon- and GC-dependent variation in genetic stability. This variation was largely attributable to multidimensional niche differentiation for IS community members. The transposition efficiency of major active ISs depended on the nucleoid-associated xenogeneic silencer MucR. Experimentally eliminating insertion activity of specific ISs by deleting MucR strongly demonstrated a dominant role of niche differentiation among ISs. This intracellular common garden approach in the experimental evolution context allows not only for evaluating genetic stability of natural and synthetic xenogeneic genes of different sequence signatures in host cells but also for tracking and testing causal relationships in unifying ecological principles in genome ecology.
PDPN contributes to constructing immunosuppressive microenvironment in IDH wildtype glioma
Authors: Wang Xuya , Wang Xisen , Li Jiabo , Liang Jianshen , Ren Xiao , Yun Debo , Liu Jie , Fan Jikang , Zhang Yiming , Zhang Jinhao , Ren Xiude , Zhang Hao , Shang Guanjie , Sun Jinzhang , Chen Lulu , Chen Lei , Li Tao , Tong Luqing , Zhang Chen , Yu Shengping , Yang Xuejun
Published: November 2022

The tumor immunosuppressive microenvironment (IME) significantly affects tumor occurrence, progression, and prognosis, but the underlying molecular mechanisms remain to make known. We investigated the prognostic significance of PDPN and its role in IME in glioma. Weighted gene co-expression network analysis (WGCNA) found PDPN closely related to IDH wildtype status and higher immune score. Correlation analysis suggested PDPN was highly positively relevant to immune checkpoints expression and immune checkpoints block responding status. Correlation analysis together with verification in vitro suggested PDPN highly positively relevant tumor-associated neutrophils (TANs) and tumor-associated macrophages (TAMs). Least absolute shrinkage and selection operator (LASSO) regression employed to develop the prediction model with TANs and TAMs markers showed that high risk scores predicted worse prognosis. We highlight that PDPN overexpression is an independent prognostic indicator, and promotes macrophage M2 polarization and neutrophil degranulation, ultimately devotes to the formation of an immunosuppressive tumor microenvironment. Our findings contribute to re-recognizing the role of PDPN in IDH wildtype gliomas and implicate promising target therapy combined with immunotherapy for this highly malignant tumor.
Tuning of oscillation modes by controlling dimensionality of spin structures
Authors: Han Hee-Sung , Lee Sooseok , Jung Min-Seung , Kim Namkyu , Jung Dae-Han , Kang Myeonghwan , Ok Hye-Jin , Chao Weilun , Yu Young-Sang , Hong Jung-Il , Im Mi-Young , Lee Ki‐Suk
Published: November 2022

Harmonic oscillation of spin structures is a physical phenomenon that offers great potential for applications in nanotechnologies such as nano-oscillators and bio-inspired computing. The effective tuning of oscillations over wide frequency ranges within a single ferromagnetic nanoelement is a prerequisite to realize oscillation-based nanodevices, but it has not been addressed experimentally or theoretically. Here, utilizing a vortex core structure, one of spin structures, we report a drastic change of oscillation modes over the frequency range from MHz to sub-GHz in a 100 nm-thick permalloy circular disk. Oscillation mode was found to considerably depend on the shape and dimension of the vortex core structure and various oscillation modes over a wide range of frequencies appeared with dimensional change in the vortex core structure. This work demonstrates that oscillation modes of the vortex core structure can be effectively tuned and opens a way to apply spin structures to oscillation-based technology.
Rigidity-dependent formation process of DNA supramolecular hydrogels
Authors: Pan Yufan , Yang Bo , Xu Rui , Li Xin , Dong Yuanchen , Liu Dongsheng
Published: November 2022

A DNA building block with tunable rigidity was constructed, and the corresponding hydrogel formation process was investigated accordingly. A high rigidity was demonstrated to facilitate fast gelation. Different gelation pathways of the rigid and flexible building blocks were revealed, and a cyclized dimer intermediate was proposed. The energy barrier of the ring-opening process was also shown to play a fundamental role in determining the gelation kinetics. Furthermore, the hydrogel molecular network rigidity was also tuned in situ through strand displacement, which also supports the kinetic control mechanism of the formation process of DNA hydrogels.
AMPK induces degradation of the transcriptional repressor PROX1 impairing branched amino acid metabolism and tumourigenesis
Authors: Wang Yanan , Luo Mengjun , Wang Fan , Tong Yu , Li Linfeng , Shu Yu , Qiao Ke , Zhang Lei , Yan Guoquan , Liu Jing , Ji Hongbin , Xie Youhua , Zhang Yonglong , Gao Wei-Qiang , Liu Yanfeng
Published: November 2022

Tumour cell metabolic plasticity is essential for tumour progression and therapeutic responses, yet the underlying mechanisms remain poorly understood. Here, we identify Prospero-related homeobox 1 (PROX1) as a crucial factor for tumour metabolic plasticity. Notably, PROX1 is reduced by glucose starvation or AMP-activated protein kinase (AMPK) activation and is elevated in liver kinase B1 (LKB1)-deficient tumours. Furthermore, the Ser79 phosphorylation of PROX1 by AMPK enhances the recruitment of CUL4-DDB1 ubiquitin ligase to promote PROX1 degradation. Downregulation of PROX1 activates branched-chain amino acids (BCAA) degradation through mediating epigenetic modifications and inhibits mammalian target-of-rapamycin (mTOR) signalling. Importantly, PROX1 deficiency or Ser79 phosphorylation in liver tumour shows therapeutic resistance to metformin. Clinically, the AMPK-PROX1 axis in human cancers is important for patient clinical outcomes. Collectively, our results demonstrate that deficiency of the LKB1-AMPK axis in cancers reactivates PROX1 to sustain intracellular BCAA pools, resulting in enhanced mTOR signalling, and facilitating tumourigenesis and aggressiveness.
Giant switchable non thermally-activated conduction in 180° domain walls in tetragonal Pb(Zr,Ti)O3
Authors: Risch Felix , Tikhonov Yuri , Lukyanchuk Igor , Ionescu Adrian M. , Stolichnov Igor
Published: November 2022

Conductive domain walls in ferroelectrics offer a promising concept of nanoelectronic circuits with 2D domain-wall channels playing roles of memristors or synoptic interconnections. However, domain wall conduction remains challenging to control and pA-range currents typically measured on individual walls are too low for single-channel devices. Charged domain walls show higher conductivity, but are generally unstable and difficult to create. Here, we show highly conductive and stable channels on ubiquitous 180° domain walls in the archetypical ferroelectric, tetragonal Pb(Zr,Ti)O3. These electrically erasable/rewritable channels show currents of tens of nanoamperes (200 to 400 nA/μm) at voltages ≤2 V and metallic-like non thermally-activated transport properties down to 4 K, as confirmed by nanoscopic mapping. The domain structure analysis and phase-field simulations reveal complex switching dynamics, in which the extraordinary conductivity in strained Pb(Zr,Ti)O3 films is explained by an interplay between ferroelastic a- and c-domains. This work demonstrates the potential of accessible and stable arrangements of nominally uncharged and electrically switchable domain walls for nanoelectronics.
Sound velocity of hexagonal close-packed iron to the Earth’s inner core pressure
Authors: Ikuta Daijo , Ohtani Eiji , Fukui Hiroshi , Sakai Takeshi , Ishikawa Daisuke , Baron Alfred Q. R.
Published: November 2022

Here we determine the compressional and shear wave velocities (vp and vs) of hexagonal close-packed iron, a candidate for the main constituent of the Earth’s inner core, to pressures above 300 gigapascals using a newly designed diamond anvil cell and inelastic X-ray scattering combined with X-ray diffraction. The present results reveal that the vp and vs of the Preliminary reference Earth model (PREM) inner core are 4(±2)% and 36(±17)% slower than those of the pure iron, respectively at the centre of the core. The density and sound velocity of the PREM inner core can be explained by addition of 3(±1) wt% silicon and 3(±2) wt% sulphur to iron‒5 wt% nickel alloy. Our suggested inner core composition is consistent with the existing outer core model with oxygen, as the growth of the inner core may have created a secular enrichment of the element in the outer core.
Growth of ocean thermal energy conversion resources under greenhouse warming regulated by oceanic eddies
Authors: Du Tianshi , Jing Zhao , Wu Lixin , Wang Hong , Chen Zhaohui , Ma Xiaohui , Gan Bolan , Yang Haiyuan
Published: November 2022

The concept of utilizing a large temperature difference (>20 °C) between the surface and deep seawater to generate electricity, known as the ocean thermal energy conversion (OTEC), provides a renewable solution to fueling our future. However, it remains poorly assessed how the OTEC resources will respond to future climate change. Here, we find that the global OTEC power potential is projected to increase by 46% around the end of this century under a high carbon emission scenario, compared to its present-day level. The augmented OTEC power potential due to the rising sea surface temperature is partially offset by the deep ocean warming. The offsetting effect is more evident in the Atlantic Ocean than Pacific and Indian Oceans. This is mainly attributed to the weakening of mesoscale eddy-induced upward heat transport, suggesting an important role of mesoscale eddies in regulating the response of thermal stratification and OTEC power potential to greenhouse warming.
Reduced secretion of neuronal growth regulator 1 contributes to impaired adipose-neuronal crosstalk in obesity
Authors: Duregotti Elisa , Reumiller Christina M. , Mayr Ursula , Hasman Maria , Schmidt Lukas E. , Burnap Sean A. , Theofilatos Konstantinos , Barallobre-Barreiro Javier , Beran Arne , Grandoch Maria , Viviano Alessandro , Jahangiri Marjan , Mayr Manuel
Published: November 2022

While the endocrine function of white adipose tissue has been extensively explored, comparatively little is known about the secretory activity of less-investigated fat depots. Here, we use proteomics to compare the secretory profiles of male murine perivascular depots with those of canonical white and brown fat. Perivascular secretomes show enrichment for neuronal cell-adhesion molecules, reflecting a higher content of intra-parenchymal sympathetic projections compared to other adipose depots. The sympathetic innervation is reduced in the perivascular fat of obese (ob/ob) male mice, as well as in the epicardial fat of patients with obesity. Degeneration of sympathetic neurites is observed in presence of conditioned media of fat explants from ob/ob mice, that show reduced secretion of neuronal growth regulator 1. Supplementation of neuronal growth regulator 1 reverses this neurodegenerative effect, unveiling a neurotrophic role for this protein previously identified as a locus associated with human obesity. As sympathetic stimulation triggers energy-consuming processes in adipose tissue, an impaired adipose-neuronal crosstalk is likely to contribute to the disrupted metabolic homeostasis characterising obesity.
Multidimensional hyperspin machine
Authors: Calvanese Strinati Marcello , Conti Claudio
Published: November 2022

From condensed matter to quantum chromodynamics, multidimensional spins are a fundamental paradigm, with a pivotal role in combinatorial optimization and machine learning. Machines formed by coupled parametric oscillators can simulate spin models, but only for Ising or low-dimensional spins. Currently, machines implementing arbitrary dimensions remain a challenge. Here, we introduce and validate a hyperspin machine to simulate multidimensional continuous spin models. We realize high-dimensional spins by pumping groups of parametric oscillators, and show that the hyperspin machine finds to a very good approximation the ground state of complex graphs. The hyperspin machine can interpolate between different dimensions by tuning the coupling topology, a strategy that we call “dimensional annealing”. When interpolating between the XY and the Ising model, the dimensional annealing substantially increases the success probability compared to conventional Ising simulators. Hyperspin machines are a new computational model for combinatorial optimization. They can be realized by off-the-shelf hardware for ultrafast, large-scale applications in classical and quantum computing, condensed-matter physics, and fundamental studies.
Postnatal expansion of mesenteric lymph node stromal cells towards reticular and CD34+ stromal cell subsets
Authors: Pezoldt Joern , Wiechers Carolin , Zou Mangge , Litovchenko Maria , Biocanin Marjan , Beckstette Michael , Sitnik Katarzyna , Palatella Martina , van Mierlo Guido , Chen Wanze , Gardeux Vincent , Floess Stefan , Ebel Maria , Russeil Julie , Arampatzi Panagiota , Vafardanejad Ehsan , Saliba Antoine-Emmanuel , Deplancke Bart , Huehn Jochen
Published: November 2022

Gut-draining mesenteric lymph nodes (LN) provide the framework to shape intestinal adaptive immune responses. Based on the transcriptional signatures established by our previous work, the composition and immunomodulatory function of LN stromal cells (SC) vary according to location. Here, we describe the single-cell composition and development of the SC compartment within mesenteric LNs derived from postnatal to aged mice. We identify CD34+SC and fibroblastic reticular stromal cell (FRC) progenitors as putative progenitors, both supplying the typical rapid postnatal mesenteric LN expansion. We further establish the location-specific chromatin accessibility and DNA methylation landscape of non-endothelial SCs and identify a microbiota-independent core epigenomic signature, showing characteristic differences between SCs from mesenteric and skin-draining peripheral LNs. The epigenomic landscape of SCs points to dynamic expression of Irf3 along the differentiation trajectories of FRCs. Accordingly, a mesenchymal stem cell line acquires a Cxcl9+FRC molecular phenotype upon lentiviral overexpression of Irf3, and the relevance of Irf3 for SC biology is further underscored by the diminished proportion of Ccl19+and Cxcl9+FRCs in LNs of Irf3-/-mice. Together, our data constitute a comprehensive transcriptional and epigenomic map of mesenteric LNSC development in early life and dissect location-specific, microbiota-independent properties of non-endothelial SCs.
A single-cell analysis reveals tumor heterogeneity and immune environment of acral melanoma
Authors: Zhang Chao , Shen Hongru , Yang Tielong , Li Ting , Liu Xinyue , Wang Jin , Liao Zhichao , Wei Junqiang , Lu Jia , Liu Haotian , Xiang Lijie , Yang Yichen , Yang Meng , Wang Duan , Li Yang , Xing Ruwei , Teng Sheng , Zhao Jun , Yang Yun , Zhao Gang , Chen Kexin , Li Xiangchun , Yang Jilong
Published: November 2022

Acral melanoma is a dismal subtype of melanoma occurring in glabrous acral skin, and has a higher incidence in East Asians. We perform single-cell RNA sequencing for 63,394 cells obtained from 5 acral and 3 cutaneous melanoma samples to investigate tumor heterogeneity and immune environment. We define 5 orthogonal functional cell clusters that are involved in TGF-beta signaling, Type I interferon, Wnt signaling, Cell cycle, and Cholesterol efflux signaling. Signatures of enriched TGF-beta, Type I interferon, and cholesterol efflux signaling are significantly associated with good prognosis of melanoma. Compared with cutaneous melanoma, acral melanoma samples have significantly severe immunosuppressive state including depletion of cytotoxic CD8+ T cells, enrichment of Treg cells, and exhausted CD8+ T cells. PD1 and TIM-3 have higher expression in the exhaustive CD8+ T cells of acral melanoma. Key findings are verified in two independent validation sets. This study contributes to our better understanding of acral melanoma.
Defective activation and regulation of type I interferon immunity is associated with increasing COVID-19 severity
Authors: Smith Nikaïa , Possémé Céline , Bondet Vincent , Sugrue Jamie , Townsend Liam , Charbit Bruno , Rouilly Vincent , Saint-André Violaine , Dott Tom , Pozo Andre Rodriguez , Yatim Nader , Schwartz Olivier , Cervantes-Gonzalez Minerva , Ghosn Jade , Bastard Paul , Casanova Jean Laurent , Szwebel Tali-Anne , Terrier Benjamin , Conlon Niall , O’Farrelly Cliona , Cheallaigh Clíona Ní , Bourke Nollaig M. , Duffy Darragh
Published: November 2022

Host immunity to infection with SARS-CoV-2 is highly variable, dictating diverse clinical outcomes ranging from asymptomatic to severe disease and death. We previously reported reduced type I interferon in severe COVID-19 patients preceded clinical worsening. Further studies identified genetic mutations in loci of the TLR3- or TLR7-dependent interferon-I pathways, or neutralizing interferon-I autoantibodies as risk factors for development of COVID-19 pneumonia. Here we show in patient cohorts with different severities of COVID-19, that baseline plasma interferon α measures differ according to the immunoassay used, timing of sampling, the interferon α subtype measured, and the presence of autoantibodies. We also show a consistently reduced induction of interferon-I proteins in hospitalized COVID-19 patients upon immune stimulation, that is not associated with detectable neutralizing autoantibodies against interferon α or interferon ω. Intracellular proteomic analysis shows increased monocyte numbers in hospitalized COVID-19 patients but impaired interferon-I response after stimulation. We confirm this by ex vivo whole blood stimulation with interferon-I which induces transcriptomic responses associated with inflammation in hospitalized COVID-19 patients, that is not seen in controls or non-hospitalized moderate cases. These results may explain the dichotomy of the poor clinical response to interferon-I based treatments in late stage COVID-19, despite the importance of interferon-I in early acute infection and may guide alternative therapeutic strategies.
Low-dose AAV-CRISPR-mediated liver-specific knock-in restored hemostasis in neonatal hemophilia B mice with subtle antibody response
Authors: He Xiangjun , Zhang Zhenjie , Xue Junyi , Wang Yaofeng , Zhang Siqi , Wei Junkang , Zhang Chenzi , Wang Jue , Urip Brian Anugerah , Ngan Chun Christopher , Sun Junjiang , Li Yuefeng , Lu Zhiqian , Zhao Hui , Pei Duanqing , Li Chi-Kong , Feng Bo
Published: November 2022

AAV-delivered CRISPR/Cas9 (AAV-CRISPR) has shown promising potentials in preclinical models to efficiently insert therapeutic gene sequences in somatic tissues. However, the AAV input doses required were prohibitively high and posed serious risk of toxicity. Here, we performed AAV-CRISPR mediated homology-independent knock-in at a new target site in mAlb 3’UTR and demonstrated that single dose of AAVs enabled long-term integration and expression of hF9 transgene in both adult and neonatal hemophilia B mice (mF9 −/−), yielding high levels of circulating human Factor IX (hFIX) and stable hemostasis restoration during entire 48-week observation period. Furthermore, we achieved hemostasis correction with a significantly lower AAV dose (2 × 109 vg/neonate and 1 × 1010 vg/adult mouse) through liver-specific gene knock-in using hyperactive hF9R338L variant. The plasma antibodies against Cas9 and AAV in the neonatal mice receiving low-dose AAV-CRISPR were negligible, which lent support to the development of AAV-CRISPR mediated somatic knock-in for treating inherited diseases.
A marine sponge-derived lectin reveals hidden pathway for thrombopoietin receptor activation
Authors: Watari Hiromi , Kageyama Hiromu , Masubuchi Nami , Nakajima Hiroya , Onodera Kako , Focia Pamela J. , Oshiro Takumi , Matsui Takashi , Kodera Yoshio , Ogawa Tomohisa , Yokoyama Takeshi , Hirayama Makoto , Hori Kanji , Freymann Douglas M. , Imai Misa , Komatsu Norio , Araki Marito , Tanaka Yoshikazu , Sakai Ryuichi
Published: November 2022

N-glycan-mediated activation of the thrombopoietin receptor (MPL) under pathological conditions has been implicated in myeloproliferative neoplasms induced by mutant calreticulin, which forms an endogenous receptor-agonist complex that traffics to the cell surface and constitutively activates the receptor. However, the molecular basis for this mechanism is elusive because oncogenic activation occurs only in the cell-intrinsic complex and is thus cannot be replicated with external agonists. Here, we describe the structure and function of a marine sponge-derived MPL agonist, thrombocorticin (ThC), a homodimerized lectin with calcium-dependent fucose-binding properties. In-depth characterization of lectin-induced activation showed that, similar to oncogenic activation, sugar chain-mediated activation persists due to limited receptor internalization. The strong synergy between ThC and thrombopoietin suggests that ThC catalyzes the formation of receptor dimers on the cell surface. Overall, the existence of sugar-mediated MPL activation, in which the mode of activation is different from the original ligand, suggests that receptor activation is unpredictably diverse in living organisms.
Critical Offset Magnetic PArticle SpectroScopy for rapid and highly sensitive medical point-of-care diagnostics
Authors: Vogel Patrick , Rückert Martin Andreas , Friedrich Bernhard , Tietze Rainer , Lyer Stefan , Kampf Thomas , Hennig Thomas , Dölken Lars , Alexiou Christoph , Behr Volker Christian
Published: November 2022

Magnetic nanoparticles (MNPs) have been adapted for many applications, e.g., bioassays for the detection of biomarkers such as antibodies, by controlled engineering of specific surface properties. Specific measurement of such binding states is of high interest but currently limited to highly sensitive techniques such as ELISA or flow cytometry, which are relatively inflexible, difficult to handle, expensive and time-consuming. Here we report a method named COMPASS (Critical-Offset-Magnetic-Particle-SpectroScopy), which is based on a critical offset magnetic field, enabling sensitive detection to minimal changes in mobility of MNP ensembles, e.g., resulting from SARS-CoV-2 antibodies binding to the S antigen on the surface of functionalized MNPs. With a sensitivity of 0.33 fmole/50 µl (≙7 pM) for SARS-CoV-2-S1 antibodies, measured with a low-cost portable COMPASS device, the proposed technique is competitive with respect to sensitivity while providing flexibility, robustness, and a measurement time of seconds per sample. In addition, initial results with blood serum demonstrate high specificity.
GPSM1 impairs metabolic homeostasis by controlling a pro-inflammatory pathway in macrophages
Authors: Yan Jing , Zhang Yuemei , Yu Hairong , Zong Yicen , Wang Daixi , Zheng Jiangfei , Jin Li , Yu Xiangtian , Liu Caizhi , Zhang Yi , Jiang Feng , Zhang Rong , Fang Xiangnan , Xu Ting , Li Mingyu , Di Jianzhong , Lu Yan , Ma Xinran , Zhang Jian , Jia Weiping , Hu Cheng
Published: November 2022

G-protein-signaling modulator 1 (GPSM1) exhibits strong genetic association with Type 2 diabetes (T2D) and Body Mass Index in population studies. However, how GPSM1 carries out such control and in which types of cells are poorly understood. Here, we demonstrate that myeloid GPSM1 promotes metabolic inflammation to accelerate T2D and obesity development. Mice with myeloid-specific GPSM1 ablation are protected against high fat diet-induced insulin resistance, glucose dysregulation, and liver steatosis via repression of adipose tissue pro-inflammatory states. Mechanistically, GPSM1 deficiency mainly promotes TNFAIP3 transcription via the Gαi3/cAMP/PKA/CREB axis, thus inhibiting TLR4-induced NF-κB signaling in macrophages. In addition, we identify a small-molecule compound, AN-465/42243987, which suppresses the pro-inflammatory phenotype by inhibiting GPSM1 function, which could make it a candidate for metabolic therapy. Furthermore, GPSM1 expression is upregulated in visceral fat of individuals with obesity and is correlated with clinical metabolic traits. Overall, our findings identify macrophage GPSM1 as a link between metabolic inflammation and systemic homeostasis.
Gating and ion selectivity of Channelrhodopsins are critical for photo-activated orientation of Chlamydomonas as shown by in vivo point mutation
Authors: Baidukova Olga , Oppermann Johannes , Kelterborn Simon , Fernandez Lahore Rodrigo G. , Schumacher Dimitri , Evers Heide , Kamrani Yousef Yari , Hegemann Peter
Published: November 2022

The green unicellular alga Chlamydomonas reinhardtii with two photoreceptors called channelrhodopsins is a model organism that gave birth to a new scientific field of biomedical studies, optogenetics. Although channelrhodopsins are helping to decipher the activity of the human brain, their functionality has never been extensively studied in the organism of origin, mainly due to the difficulties connected to reverse genetic interventions. In this study, we present a CRISPR-Cas9-based technique that enables a precise in vivo exchange of single amino acids in a selected gene. To shed light on the function of channelrhodopsins ChR1 (C1) and ChR2 (C2) in vivo, we deleted both channelrhodopsins independently in the wild-type strain and introduced point mutations in the remaining channel, causing modified photocycle kinetics and ion selectivity. The mutated strains, ΔC1C2-E123T, ΔC1C2-E90R and ΔC1C2-E90Q, showed about 100-fold decrease in photosensitivity, a reduced photophobic response and faster light adaptation rates due to accelerated photocycle kinetics and reduced Ca2+ conductance. Moreover, the ΔC1C2-E90Q with an additionally reduced H+ permeability produced an electrical response only in the presence of Na+ ions, highlighting a contribution and importance of H+ conductance to photocurrents in the wild-type algae. Finally, in the ΔC1C2-E90R strain with the channelrhodopsin selectivity converted to anions, no photo-responses were detected. We conclude that the precise photocycle kinetics and the particular ion selectivity of channelrhodopsins are the key parameters for efficient phototaxis in low light conditions.
Hybrid chalcogen bonds in prodrug nanoassemblies provides dual redox-responsivity in the tumor microenvironment
Authors: Liu Tian , Li Lingxiao , Wang Shuo , Dong Fudan , Zuo Shiyi , Song Jiaxuan , Wang Xin , Lu Qi , Wang Helin , Zhang Haotian , Cheng Maosheng , Liu Xiaohong , He Zhonggui , Sun Bingjun , Sun Jin
Published: November 2022

Sulfur bonds, especially trisulfide bond, have been found to ameliorate the self-assembly stability of homodimeric prodrug nanoassemblies and could trigger the sensitive reduction-responsive release of active drugs. However, the antitumor efficacy of homodimeric prodrug nanoassemblies with single reduction-responsivity may be restricted due to the heterogeneous tumor redox microenvironment. Herein, we replace the middle sulfur atom of trisulfide bond with an oxidizing tellurium atom or selenium atom to construct redox dual-responsive sulfur-tellurium-sulfur and sulfur-selenium-sulfur hybrid chalcogen bonds. The hybrid chalcogen bonds, especially the sulfur-tellurium-sulfur bond, exhibit ultrahigh dual-responsivity to both oxidation and reduction conditions, which could effectively address the heterogeneous tumor microenvironment. Moreover, the hybrid sulfur-tellurium-sulfur bond promotes the self-assembly of homodimeric prodrugs by providing strong intermolecular forces and sufficient steric hindrance. The above advantages of sulfur-tellurium-sulfur bridged homodimeric prodrug nanoassemblies result in the improved antitumor efficacy of docetaxel with satisfactory safety. The exploration of hybrid chalcogen bonds in drug delivery deepened insight into the development of prodrug-based chemotherapy to address tumor redox heterogeneity, thus enriching the design theory of prodrug-based nanomedicines.
Resource sharing is sufficient for the emergence of division of labour
Authors: Kreider Jan J. , Janzen Thijs , Bernadou Abel , Elsner Daniel , Kramer Boris H. , Weissing Franz J.
Published: November 2022

Division of labour occurs in a broad range of organisms. Yet, how division of labour can emerge in the absence of pre-existing interindividual differences is poorly understood. Using a simple but realistic model, we show that in a group of initially identical individuals, division of labour emerges spontaneously if returning foragers share part of their resources with other group members. In the absence of resource sharing, individuals follow an activity schedule of alternating between foraging and other tasks. If non-foraging individuals are fed by other individuals, their alternating activity schedule becomes interrupted, leading to task specialisation and the emergence of division of labour. Furthermore, nutritional differences between individuals reinforce division of labour. Such differences can be caused by increased metabolic rates during foraging or by dominance interactions during resource sharing. Our model proposes a plausible mechanism for the self-organised emergence of division of labour in animal groups of initially identical individuals. This mechanism could also play a role for the emergence of division of labour during the major evolutionary transitions to eusociality and multicellularity.
PICH acts as a force-dependent nucleosome remodeler
Authors: Spakman Dian , Clement Tinka V. M. , Biebricher Andreas S. , King Graeme A. , Singh Manika I. , Hickson Ian D. , Peterman Erwin J. G. , Wuite Gijs J. L.
Published: November 2022

In anaphase, any unresolved DNA entanglements between the segregating sister chromatids can give rise to chromatin bridges. To prevent genome instability, chromatin bridges must be resolved prior to cytokinesis. The SNF2 protein PICH has been proposed to play a direct role in this process through the remodeling of nucleosomes. However, direct evidence of nucleosome remodeling by PICH has remained elusive. Here, we present an in vitro single-molecule assay that mimics chromatin under tension, as is found in anaphase chromatin bridges. Applying a combination of dual-trap optical tweezers and fluorescence imaging of PICH and histones bound to a nucleosome-array construct, we show that PICH is a tension- and ATP-dependent nucleosome remodeler that facilitates nucleosome unwrapping and then subsequently slides remaining histones along the DNA. This work elucidates the role of PICH in chromatin-bridge dissolution, and might provide molecular insights into the mechanisms of related SNF2 proteins.
Growing polarization around climate change on social media
Authors: Falkenberg Max , Galeazzi Alessandro , Torricelli Maddalena , Di Marco Niccolò , Larosa Francesca , Sas Madalina , Mekacher Amin , Pearce Warren , Zollo Fabiana , Quattrociocchi Walter , Baronchelli Andrea
Published: November 2022

Climate change and political polarization are two of the twenty-first century’s critical socio-political issues. Here we investigate their intersection by studying the discussion around the United Nations Conference of the Parties on Climate Change (COP) using Twitter data from 2014 to 2021. First, we reveal a large increase in ideological polarization during COP26, following low polarization between COP20 and COP25. Second, we show that this increase is driven by growing right-wing activity, a fourfold increase since COP21 relative to pro-climate groups. Finally, we identify a broad range of ‘climate contrarian’ views during COP26, emphasizing the theme of political hypocrisy as a topic of cross-ideological appeal; contrarian views and accusations of hypocrisy have become key themes in the Twitter climate discussion since 2019. With future climate action reliant on negotiations at COP27 and beyond, our results highlight the importance of monitoring polarization and its impacts in the public climate discourse.
Image-seq: spatially resolved single-cell sequencing guided by in situ and in vivo imaging
Authors: Haase Christa , Gustafsson Karin , Mei Shenglin , Yeh Shu-Chi , Richter Dmitry , Milosevic Jelena , Turcotte Raphaël , Kharchenko Peter V. , Sykes David B. , Scadden David T. , Lin Charles P.
Published: November 2022

Tissue function depends on cellular organization. While the properties of individual cells are increasingly being deciphered using powerful single-cell sequencing technologies, understanding their spatial organization and temporal evolution remains a major challenge. Here, we present Image-seq, a technology that provides single-cell transcriptional data on cells that are isolated from specific spatial locations under image guidance, thus preserving the spatial information of the target cells. It is compatible with in situ and in vivo imaging and can document the temporal and dynamic history of the cells being analyzed. Cell samples are isolated from intact tissue and processed with state-of-the-art library preparation protocols. The technique therefore combines spatial information with highly sensitive RNA sequencing readouts from individual, intact cells. We have used both high-throughput, droplet-based sequencing as well as SMARTseq-v4 library preparation to demonstrate its application to bone marrow and leukemia biology. We discovered that DPP4 is a highly upregulated gene during early progression of acute myeloid leukemia and that it marks a more proliferative subpopulation that is confined to specific bone marrow microenvironments. Furthermore, the ability of Image-seq to isolate viable, intact cells should make it compatible with a range of downstream single-cell analysis tools including multi-omics protocols.
Unsharp masking image enhancement the parallel algorithm based on cross-platform
Authors: Song Yupu , Li Cailin , Xiao Shiyang , Xiao Han , Guo Baoyun
Published: November 2022

In view of the low computational efficiency and the limitations of the platform of the unsharp masking image enhancement algorithm, an unsharp masking image enhancement parallel algorithm based on Open Computing Language (OpenCL) is proposed. Based on the analysis of the parallel characteristics of the algorithm, the problem of unsharp masking processing is implemented in parallel. Making use of the characteristics of data reuse in the algorithm, the effective allocation and optimization of global memory and constant memory are realized according to the access attributes of the data and the characteristics of the OpenCL storage model, and the use efficiency of off-chip memory is improved. Through the data storage access mode, the fast computing local memory access mode is discovered, and the logical data space transformation is used to convert the storage access mode, so as to improve the bandwidth utilization of the on-chip memory. The experimental results show that, compared with the CPU serial algorithm, the OpenCL accelerated unsharp masking image enhancement parallel algorithm greatly reduces the execution time of the algorithm while maintaining the same image quality, and achieves a maximum speedup of 16.71 times. The high performance and platform transplantation of the algorithm on different hardware platforms are realized. It provides a reference method for real-time processing of a large amount of data of high-resolution images for image enhancement.
Factors influencing compliance in RRD patients with the face-down position via grounded theory approach
Authors: Li Yahong , Li Jining , Shao Ying , Feng Ronghua , Li Jinkun , Duan Yajian
Published: November 2022

Patients with rhegmatogenous retinal detachment (RRD) require face-down positioning (FDP) for 3–6 months or longer after pars plana vitrectomy (PPV) combined with silicone oil (SO) tamponade. This paper aimed to identify the factors that influenced FDP compliance. This study adopted semi-structured interviews with patients who require FDP after SO tamponade. Constructivist grounded theory was utilized in this study. The qualitative data was analyzed and coded via NVivo 11.0 through open coding, axial coding and selective coding. Twenty-four RRD patients were involved. The interviews yielded five main themes that defined home FDP compliance were identified: posture discomfort, doctor-patient communication, psychological factors, occupational character, and family factors. A theoretical model of the influencing factors of postural compliance of FDP was constructed based on the interview analysis. A variety of factors can affect FDP conformity. We can increase compliance of RRD patients by enhancing comfort, encouraging doctor-patient communication, providing comprehensive care, promoting community-based intervention, and strengthening family education.
Spatiotemporal image quality of virtual reality head mounted displays
Authors: Zhao Chumin , Kim Andrea S. , Beams Ryan , Badano Aldo
Published: November 2022

Virtual reality (VR) head mounted displays (HMDs) require both high spatial resolution and fast temporal response. However, methods to quantify the VR image quality in the spatiotemporal domain when motion exists are not yet standardized. In this study, we characterize the spatiotemporal capabilities of three VR devices: the HTC VIVE, VIVE Pro, and VIVE Pro 2 during smooth pursuit. A spatiotemporal model for VR HMDs is presented using measured spatial and temporal characteristics. Among the three evaluated headsets, the VIVE Pro 2 improves the display temporal performance using a fast 120 Hz refresh rate and pulsed emission with a small duty cycle of 5%. In combination with a high pixel resolution beyond 2 k $$\times$$
×
2 k per eye, the VIVE Pro 2 achieves an improved spatiotemporal performance compared to the VIVE and VIVE Pro in the high spatial frequency range above 8 cycles per degree during smooth pursuit. The result demonstrates that reducing the display emission duty cycle to less than 20% is beneficial to mitigate motion blur in VR HMDs. Frame rate reduction (e.g., to below 60 Hz) of the input signal compared to the display refresh rate of 120 Hz yields replicated shadow images that can affect the image quality under motion. This work supports the regulatory science research efforts in development of testing methods to characterize the spatiotemporal performance of VR devices for medical use.
Rac1 deficiency impairs postnatal development of the renal papilla
Authors: Ayuzawa Nobuhiro , Nishimoto Mitsuhiro , Kawarazaki Wakako , Oba Shigeyoshi , Marumo Takeshi , Aiba Atsu , Fujita Toshiro
Published: November 2022

Development of the renal medulla continues after birth to form mature renal papilla and obtain urine-concentrating ability. Here, we found that a small GTPase, Rac1, plays a critical role in the postnatal development of renal papilla. Mice with distal tubule-specific deletion of Rac1 reached adulthood but showed polydipsia and polyuria with an impaired ability to concentrate urine. The elongation of renal papilla that occurs in the first weeks after birth was impaired in the Rac1-deficient infants, resulting in shortening and damage of the renal papilla. Moreover, the osmoprotective signaling mediated by nuclear factor of activated T cells 5, which is a key molecule of osmotic response to osmotic stress in renal medulla, was significantly impaired in the kidneys of the Rac1-deficient infants. These results demonstrate that Rac1 plays an important role in the development of renal papilla in the postnatal period, and suggested a potential link between Rac1 and osmotic response.
Hormonal contraceptive use and the risk of sexually transmitted infections: a systematic review and meta-analysis
Authors: Akter Tasnima , Festin Mario , Dawson Angela
Published: November 2022

There are 150 million women worldwide using combined or progestogen-only hormonal contraceptive methods who may be at risk of sexually transmitted infections (STIs). Previous systematic reviews that have sought to establish whether there is an aetiological association between hormonal contraceptive methods/use and STIs have been limited in their methods and have mixed findings. We sought to update these reviews using appropriate control groups. We undertook a systematic review following the PRISMA guidelines and meta-analysis to examine the association between the use of all hormonal contraceptive methods and the acquisition of STIs (Neisseria gonorrhoeae, syphilis/Treponema pallidum, Chlamydia trachomatis, herpes simplex virus, and Trichomonas vaginalis) and/or bacterial vaginosis in literature published between 2005 and 2020. We analysed the effect of hormonal contraceptive methods/use separately on the prevalence, incidence and recurrence of STIs. A total of 37 studies were included in this review that reported 61 associations, in which 27 prevalence, eight incidence and two recurrence studies provided 43, 16, and two associations, respectively. We observed a positive association between hormonal contraceptive methods/use and the risk of chlamydia and herpes but a negative association for trichomoniasis and vaginosis. A negative but statistically insignificant association was observed between hormonal contraceptive methods/use and gonorrhoea. Hormonal contraceptive methods/use influences a woman's risk of STIs/ bacterial vaginosis, but the risk may differ depending on the type of STI. These findings should be contextualized carefully, particularly when formulating practice guidelines and policy, as the effects of hormonal contraceptive methods/use on the risk of STIs varied in direction when analysed separately by STI.
Characterisation of visual guidance of steering to intercept targets following curving trajectories using Qualitative Inconsistency Detection
Authors: van Opstal Albertha A. M. , Casanova Remy , Zaal Frank T. J. M. , Bootsma Reinoud J.
Published: November 2022

This study explored the informational variables guiding steering behaviour in a locomotor interception task with targets moving along circular trajectories. Using a new method of analysis focussing on the temporal co-evolution of steering behaviour and the potential information sources driving it, we set out to invalidate reliance on plausible informational candidates. Applied to individual trials rather than ensemble averages, this Qualitative Inconsistency Detection (QuID) method revealed that steering behaviour was not compatible with reliance on information grounded in any type of change in the agent-centred target-heading angle. First-order changes in the environment-centred target’s bearing angle could also not adequately account for the variations in behaviour observed under the different experimental conditions. Capturing the observed timing of unfolding steering behaviour ultimately required a combination of (velocity-based) first-order and (acceleration-based) second-order changes in bearing angle. While this result may point to reliance on fractional-order based changes in bearing angle, the overall importance of the present findings resides in the demonstration of the necessity to break away from the existing practice of trying to fit behaviour into a priori postulated functional strategies based on categorical differences between operative heuristic rules or control laws.