bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coupled Lithospheric Deformation in the Qinling Orogen, Central China: Insights From Seismic Reflection and Surface‐Wave Tomography
Authors: Zhang Yueqiao , Dong Shuwen , Wang Haiyan , Feng Mei , Thybo H. , Li Jianhua , Gao Rui , Shi Wei 
Published: July 2022

AbstractWe combine a ∼485 km‐long seismic reflection profile and a S‐wave speed transect from surface‐wave tomography, to reveal the lithospheric deformation mode of the intracontinental Qinling orogeny, central China. We observe a thick lithosphere keel in the convergence zone between the Yangtze Block and the North China Craton (NCC) and a shallow‐crustal (8–15 km depth) décollement that extends into the lower crust of the Qinling Orogen. Combining with surface structural geology and magmatism, we interpret these seismic findings as kinematically linked features formed by renewed intracontinental convergence between the NCC and the Yangtze Block in the late Mesozoic. We highlight that the ∼40 km lithospheric thickening in the convergence zone was likely balanced by > 130 km thin‐skinned crustal shortening along a crustal‐scale strain‐transfer décollement, and was responsible for the occurrence of late Mesozoic magmatism (∼160–100 Ma) at the southern edge of the NCC.
Dominant Processes for Dependence of Boreal Summer Intraseasonal Oscillation on El Niño Phases
Authors: Lee Doo Young , Lee June‐Yi , Yang Young‐Min , Hsu Pang‐Chi , Kim Ji‐Eun 
Published: July 2022

AbstractBoreal summer intraseasonal oscillation (BSISO) strongly interacts with background mean fields and tends to be stronger and longer in its northward propagation during La Niña than El Niño summers. However, BSISO dependence on El Niño‐Southern Oscillation phase has not been well understood. Here, we show that BSISO‐related convections are stronger and more organized with northward propagation on 30–60‐day timescales during El Niño developing (E‐DV) than decaying (E‐DC) summers over the western Pacific. The easterly vertical shear, responsible for the next vorticity generation north of the BSISO convection, in the E‐DV (E‐DC) remarkably increases (decreases) due to the enhanced (weakened) upper‐level easterly anomaly. The air‐sea interaction in E‐DV gets stronger due to the larger meridional gradient of sea surface temperature, amplifying northward propagation than in E‐DC.
Synaptic plasticity and mental health: methods, challenges and opportunities
Authors: Appelbaum Lawrence G. , Shenasa Mohammad Ali , Stolz Louise , Daskalakis Zafiris 
Published: July 2022

AbstractActivity-dependent synaptic plasticity is a ubiquitous property of the nervous system that allows neurons to communicate and change their connections as a function of past experiences. Through reweighting of synaptic strengths, the nervous system can remodel itself, giving rise to durable memories that create the biological basis for mental function. In healthy individuals, synaptic plasticity undergoes characteristic developmental and aging trajectories. Dysfunctional plasticity, in turn, underlies a wide spectrum of neuropsychiatric disorders including depression, schizophrenia, addiction, and posttraumatic stress disorder. From a mechanistic standpoint, synaptic plasticity spans the gamut of spatial and temporal scales, from microseconds to the lifespan, from microns to the entire nervous system. With the numbers and strengths of synapses changing on such wide scales, there is an important need to develop measurement techniques with complimentary sensitivities and a growing number of approaches are now being harnessed for this purpose. Through hemodynamic measures, structural and tracer imaging, and noninvasive neuromodulation, it is possible to image structural and functional changes that underlie synaptic plasticity and associated behavioral learning. Here we review the mechanisms of neural plasticity and the historical and future trends in techniques that allow imaging of synaptic changes that accompany psychiatric disorders, highlighting emerging therapeutics and the challenges and opportunities accompanying this burgeoning area of study.
Association between cord blood metabolites in tryptophan pathway and childhood risk of autism spectrum disorder and attention-deficit hyperactivity disorder
Authors: Raghavan Ramkripa , Anand Neha S. , Wang Guoying , Hong Xiumei , Pearson Colleen , Zuckerman Barry , Xie Hehuang , Wang Xiaobin 
Published: July 2022

AbstractAlterations in tryptophan and serotonin have been implicated in various mental disorders; but studies are limited on child neurodevelopmental disabilities such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). This prospective cohort study examined the associations between levels of tryptophan and select metabolites (5-methoxytryptophol (5-MTX), 5-hydroxytryptophan (5-HTP), serotonin, N-acetyltrytophan) in cord plasma (collected at birth) and physician-diagnosed ASD, ADHD and other developmental disabilities (DD) in childhood. The study sample (n = 996) derived from the Boston Birth Cohort, which included 326 neurotypical children, 87 ASD, 269 ADHD, and 314 other DD children (mutually exclusive). These participants were enrolled at birth and followed-up prospectively (from October 1, 1998 to June 30, 2018) at the Boston Medical Center. Higher levels of cord 5-MTX was associated with a lower risk of ASD (aOR: 0.56, 95% CI: 0.41, 0.77) and ADHD (aOR: 0.79, 95% CI: 0.65, 0.96) per Z-score increase, after adjusting for potential confounders. Similarly, children with cord 5-MTX ≥ 25th percentile (vs. <25th percentile) had a reduction in ASD (aOR: 0.27, 95% CI: 0.14, 0.49) and ADHD risks (aOR: 0.45, 95% CI: 0.29, 0.70). In contrast, higher levels of cord tryptophan, 5-HTP and N-acetyltryptophan were associated with higher risk of ADHD, with aOR: 1.25, 95% CI: 1.03, 1.51; aOR: 1.32, 95% CI: 1.08, 1.61; and aOR: 1.27, 95% CI: 1.05, 1.53, respectively, but not with ASD and other DD. Cord serotonin was not associated with ASD, ADHD, and other DD. Most findings remained statistically significant in the sensitivity and subgroup analyses.
A potassium channel agonist protects hearing function and promotes outer hair cell survival in a mouse model for age-related hearing loss
Authors: Peixoto Pinheiro Barbara , Müller Marcus , Bös Michael , Guezguez Jamil , Burnet Michael , Tornincasa Mara , Rizzetto Riccardo , Rolland Jean-Francois , Liberati Chiara , Lohmer Stefan , Adel Youssef , Löwenheim Hubert 
Published: July 2022

AbstractAge-related hearing loss (ARHL) is the most common sensory impairment mainly caused by degeneration of sensory hair cells in the cochlea with no causal medical treatment available. Auditory function and sensory hair cell survival critically depend on the Kv7.4 (KCNQ4) channel, a voltage-gated potassium channel expressed in outer hair cells (OHCs), with its impaired function or reduced activity previously associated with ARHL. Here, we investigated the effect of a potent small-molecule Kv7.4 agonist on ARHL in the senescence-accelerated mouse prone 8 (SAMP8) model. For the first time in vivo, we show that Kv7.4 activation can significantly reduce age-related threshold shifts of auditory brainstem responses as well as OHC loss in the SAMP8 model. Pharmacological activation of Kv7.4 thus holds great potential as a therapeutic approach for ARHL as well as other hearing impairments related to Kv7.4 function.
Gankyrin modulated non-small cell lung cancer progression via glycolysis metabolism in a YAP1-dependent manner
Authors: Yu Tong , Liu Yanyan , Xue Junwen , Sun Xiang , Zhu Di , Ma Lu , Guo Yingying , Jin Tongzhu , Cao Huiying , Chen Yingzhun , Zhu Tong , Li Xuelian , Liang Haihai , Du Zhimin , Shan Hongli 
Published: July 2022

AbstractNon-small cell lung cancer (NSCLC) is highly malignant and heterogeneous form of lung cancer and involves various oncogene alterations. Glycolysis, an important step in tumor metabolism, is closely related to cancer progression. In this study, we investigated the biological function and mechanism of action of Gankyrin in glycolysis and its association with NSCLC. Analyzed of data from The Cancer Genome Atlas as well as NSCLC specimens and adjacent tissues demonstrated that Gankyrin expression was upregulated in NSCLC tissues compared to adjacent normal tissues. Gankyrin was found to significantly aggravate cancer-related phenotypes, including cell viability, migration, invasion, and epithelial mesenchymal transition (EMT), whereas Gankyrin silencing alleviated the malignant phenotype of NSCLC cells. Our results reveal that Gankyrin exerted its function by regulating YAP1 expression and increasing its nuclear translocation. Importantly, YAP1 actuates glycolysis, which involves glucose uptake, lactic acid production, and ATP generation and thus might contribute to the tumorigenic effect of Gankyrin. Furthermore, the Gankyrin-accelerated glycolysis in NSCLC cells was reversed by YAP1 deficiency. Gankyrin knockdown reduced A549 cell tumorigenesis and EMT and decreased YAP1 expression in a subcutaneous xenograft nude mouse model. In conclusion, both Gankyrin and YAP1 play important roles in tumor metabolism, and Gankyrin-targeted inhibition may be a potential anti-cancer therapeutic strategy for NSCLC.
The role of NLRP3 inflammasome in psychotropic drug-induced hepatotoxicity
Authors: Mu Wenqing , Xu Guang , Wei Ziying , Wang Zhilei , Qin Qin , Lin Li , Ren Lutong , Liu Tingting , Fang Zhie , Yang Yan , Zhao Jing , Wang Junnan , Zhan Xiaoyan , Xiao Xiaohe , Bai Zhaofang 
Published: July 2022

AbstractIncreased medical application of psychotropic drugs raised attention concerning their toxicological effects. In fact, more than 160 psychotropic drugs including antidepressants and antipsychotics, have been shown to cause liver side effects, but the underlying mechanisms are still poorly understood. Here, we discovered that fluoxetine, a common antidepressant, was specifically sensed by NLRP3 inflammasome, whose subsequent activation resulted in the maturation of caspase-1 and IL-1β, as well as gasdermin D (GSDMD) cleavage, which could be completely abrogated by a selective NLRP3 inhibitor MCC950 or Nlrp3 knockout (Nlrp3−/−). Mechanistically, mitochondrial damage and the subsequent mitochondrial reactive oxygen species (mtROS) accumulation were crucial upstream signaling events in fluoxetine-triggered NLRP3 inflammasome activation. In fluoxetine hepatotoxicity models, mice showed the alterations of aminotransferase levels, hepatic inflammation and hepatocyte death in an NLRP3-dependent manner, and MCC950 pretreatment could reverse these side effects of fluoxetine. Notably, we also found that multiple antidepressants, such as amitriptyline, paroxetine, and imipramine, and antipsychotics, such as asenapine, could specifically trigger the NLRP3 inflammasome activation. Collectively, our findings implicate multiple psychotropic drugs may act as danger signals sensed by the NLRP3 inflammasome and result in hepatic injury.
Organic phosphorescent scintillation from copolymers by X-ray irradiation
Authors: Gan Nan , Zou Xin , Dong Mengyang , Wang Yanze , Wang Xiao , Lv Anqi , Song Zhicheng , Zhang Yuanyuan , Gong Wenqi , Zhao Zhu , Wang Ziyang , Zhou Zixing , Ma Huili , Liu Xiaowang , Chen Qiushui , Shi Huifang , Yang Huanghao , Gu Long , An Zhongfu , Huang Wei 
Published: July 2022

AbstractScintillators that exhibit X-ray-excited luminescence have great potential in radiation detection, X-ray imaging, radiotherapy, and non-destructive testing. However, most reported scintillators are limited to inorganic or organic crystal materials, which have some obstacles in repeatability and processability. Here we present a facile strategy to achieve the X-ray-excited organic phosphorescent scintillation from amorphous copolymers through the copolymerization of the bromine-substituted chromophores and acrylic acid. These polymeric scintillators exhibit efficient X-ray responsibility and decent phosphorescent quantum yield up to 51.4% under ambient conditions. The universality of the design principle was further confirmed by a series of copolymers with multi-color radioluminescence ranging from green to orange-red. Moreover, we demonstrated their potential application in X-ray radiography. This finding not only outlines a feasible principle to develop X-ray responsive phosphorescent polymers, but also expands the potential applications of polymer materials with phosphorescence features.
Trade off-free entanglement stabilization in a superconducting qutrit-qubit system
Authors: Brown T. , Doucet E. , Ristè D. , Ribeill G. , Cicak K. , Aumentado J. , Simmonds R. , Govia L. , Kamal A. , Ranzani L. 
Published: July 2022

AbstractQuantum reservoir engineering is a powerful framework for autonomous quantum state preparation and error correction. However, traditional approaches to reservoir engineering are hindered by unavoidable coherent leakage out of the target state, which imposes an inherent trade off between achievable steady-state state fidelity and stabilization rate. In this work we demonstrate a protocol that achieves trade off-free Bell state stabilization in a qutrit-qubit system realized on a circuit-QED platform. We accomplish this by creating a purely dissipative channel for population transfer into the target state, mediated by strong parametric interactions coupling the second-excited state of a superconducting transmon and the engineered bath resonator. Our scheme achieves a state preparation fidelity of 84% with a stabilization time constant of 339 ns, leading to a 54 ns error-time product in a solid-state quantum information platform.
Mechanism of fertilization-induced auxin synthesis in the endosperm for seed and fruit development
Authors: Guo Lei , Luo Xi , Li Muzi , Joldersma Dirk , Plunkert Madison , Liu Zhongchi 
Published: July 2022

AbstractThe dominance of flowering plants on earth is owed largely to the evolution of maternal tissues such as fruit and seedcoat that protect and disseminate the seeds. The mechanism of how fertilization triggers the development of these specialized maternal tissues is not well understood. A key event is the induction of auxin synthesis in the endosperm, and the mobile auxin subsequently stimulates seedcoat and fruit development. However, the regulatory mechanism of auxin synthesis in the endosperm remains unknown. Here, we show that a type I MADS box gene AGL62 is required for the activation of auxin synthesis in the endosperm in both Fragaria vesca, a diploid strawberry, and in Arabidopsis. Several strawberry FveATHB genes were identified as downstream targets of FveAGL62 and act to repress auxin biosynthesis. In this work, we identify a key mechanism for auxin induction to mediate fertilization success, a finding broadly relevant to flowering plants.
Probing strigolactone perception mechanisms with rationally designed small-molecule agonists stimulating germination of root parasitic weeds
Authors: Wang Dawei , Pang Zhili , Yu Haiyang , Thiombiano Benjamin , Walmsley Aimee , Yu Shuyi , Zhang Yingying , Wei Tao , Liang Lu , Wang Jing , Wen Xin , Bouwmeester Harro J. , Yao Ruifeng , Xi Zhen 
Published: July 2022

AbstractThe development of potent strigolactone (SL) agonists as suicidal germination inducers could be a useful strategy for controlling root parasitic weeds, but uncertainty about the SL perception mechanism impedes real progress. Here we describe small-molecule agonists that efficiently stimulate Phelipanchce aegyptiaca, and Striga hermonthica, germination in concentrations as low as 10−8 to 10−17 M. We show that full efficiency of synthetic SL agonists in triggering signaling through the Striga SL receptor, ShHTL7, depends on the receptor-catalyzed hydrolytic reaction of the agonists. Additionally, we reveal that the stereochemistry of synthetic SL analogs affects the hydrolytic ability of ShHTL7 by influencing the probability of the privileged conformations of ShHTL7. Importantly, an alternative ShHTL7-mediated hydrolysis mechanism, proceeding via nucleophilic attack of the NE2 atom of H246 to the 2′C of the D-ring, is reported. Together, our findings provide insight into SL hydrolysis and structure-perception mechanisms, and potent suicide germination stimulants, which would contribute to the elimination of the noxious parasitic weeds.
Decoupling PER phosphorylation, stability and rhythmic expression from circadian clock function by abolishing PER-CK1 interaction
Authors: An Yang , Yuan Baoshi , Xie Pancheng , Gu Yue , Liu Zhiwei , Wang Tao , Li Zhihao , Xu Ying , Liu Yi 
Published: July 2022

AbstractRobust rhythms of abundances and phosphorylation profiles of PERIOD proteins were thought be the master rhythms that drive mammalian circadian clock functions. PER stability was proposed to be a major determinant of period length. In mammals, CK1 forms stable complexes with PER. Here we identify the PER residues essential for PER-CK1 interaction. In cells and in mice, their mutation abolishes PER phosphorylation and CLOCK hyperphosphorylation, resulting in PER stabilization, arrhythmic PER abundance and impaired negative feedback process, indicating that PER acts as the CK1 scaffold in circadian feedback mechanism. Surprisingly, the mutant mice exhibit robust short period locomotor activity and other physiological rhythms but low amplitude molecular rhythms. PER-CK1 interaction has two opposing roles in regulating CLOCK-BMAL1 activity. These results indicate that the circadian clock can function independently of PER phosphorylation and abundance rhythms due to another PER-CRY-dependent feedback mechanism and that period length can be uncoupled from PER stability.
Acetyl-CoA-Carboxylase 1-mediated de novo fatty acid synthesis sustains Lgr5+ intestinal stem cell function
Authors: Li Shuting , Lu Chia-Wen , Diem Elia C. , Li Wang , Guderian Melanie , Lindenberg Marc , Kruse Friederike , Buettner Manuela , Floess Stefan , Winny Markus R. , Geffers Robert , Richnow Hans-Hermann , Abraham Wolf-Rainer , Grassl Guntram A. , Lochner Matthias 
Published: July 2022

AbstractBasic processes of the fatty acid metabolism have an important impact on the function of intestinal epithelial cells (IEC). However, while the role of cellular fatty acid oxidation is well appreciated, it is not clear how de novo fatty acid synthesis (FAS) influences the biology of IECs. We report here that interfering with de novo FAS by deletion of the enzyme Acetyl-CoA-Carboxylase (ACC)1 in IECs results in the loss of epithelial crypt structures and a specific decline in Lgr5+ intestinal epithelial stem cells (ISC). Mechanistically, ACC1-mediated de novo FAS supports the formation of intestinal organoids and the differentiation of complex crypt structures by sustaining the nuclear accumulation of PPARδ/β-catenin in ISCs. The dependency of ISCs on cellular de novo FAS is tuned by the availability of environmental lipids, as an excess delivery of external fatty acids is sufficient to rescue the defect in crypt formation. Finally, inhibition of ACC1 reduces the formation of tumors in colitis-associated colon cancer, together highlighting the importance of cellular lipogenesis for sustaining ISC function and providing a potential perspective to colon cancer therapy.
A Nodal enhanced micropeptide NEMEP regulates glucose uptake during mesendoderm differentiation of embryonic stem cells
Authors: Fu Haipeng , Wang Tingyu , Kong Xiaohui , Yan Kun , Yang Yang , Cao Jingyi , Yuan Yafei , Wang Nan , Kee Kehkooi , Lu Zhi John , Xi Qiaoran 
Published: July 2022

AbstractTGF-β family proteins including Nodal are known as central regulators of early development in metazoans, yet our understanding of the scope of Nodal signaling’s downstream targets and associated physiological mechanisms in specifying developmentally appropriate cell fates is far from complete. Here, we identified a highly conserved, transmembrane micropeptide—NEMEP—as a direct target of Nodal signaling in mesendoderm differentiation of mouse embryonic stem cells (mESCs), and this micropeptide is essential for mesendoderm differentiation. We showed that NEMEP interacts with the glucose transporters GLUT1/GLUT3 and promotes glucose uptake likely through these interactions. Thus, beyond expanding the scope of known Nodal signaling targets in early development and showing that this target micropeptide augments the glucose uptake during mesendoderm differentiation, our study provides a clear example for the direct functional impact of altered glucose metabolism on cell fate determination.
In vivo dissection of a clustered-CTCF domain boundary reveals developmental principles of regulatory insulation
Authors: Anania Chiara , Acemel Rafael D. , Jedamzick Johanna , Bolondi Adriano , Cova Giulia , Brieske Norbert , Kühn Ralf , Wittler Lars , Real Francisca M. , Lupiáñez Darío G. 
Published: July 2022

AbstractVertebrate genomes organize into topologically associating domains, delimited by boundaries that insulate regulatory elements from nontarget genes. However, how boundary function is established is not well understood. Here, we combine genome-wide analyses and transgenic mouse assays to dissect the regulatory logic of clustered-CCCTC-binding factor (CTCF) boundaries in vivo, interrogating their function at multiple levels: chromatin interactions, transcription and phenotypes. Individual CTCF binding site (CBS) deletions revealed that the characteristics of specific sites can outweigh other factors such as CBS number and orientation. Combined deletions demonstrated that CBSs cooperate redundantly and provide boundary robustness. We show that divergent CBS signatures are not strictly required for effective insulation and that chromatin loops formed by nonconvergently oriented sites could be mediated by a loop interference mechanism. Further, we observe that insulation strength constitutes a quantitative modulator of gene expression and phenotypes. Our results highlight the modular nature of boundaries and their control over developmental processes.
Multitier mechanics control stromal adaptations in the swelling lymph node
Authors: Assen Frank P. , Abe Jun , Hons Miroslav , Hauschild Robert , Shamipour Shayan , Kaufmann Walter A. , Costanzo Tommaso , Krens Gabriel , Brown Markus , Ludewig Burkhard , Hippenmeyer Simon , Heisenberg Carl-Philipp , Weninger Wolfgang , Hannezo Edouard , Luther Sanjiv A. , Stein Jens V. , Sixt Michael 
Published: July 2022

AbstractLymph nodes (LNs) comprise two main structural elements: fibroblastic reticular cells that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. Immunological challenge causes LNs to increase more than tenfold in size within a few days. Here, we characterized the biomechanics of LN swelling on the cellular and organ scale. We identified lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing fibroblastic reticular cells of the T-zone (TRCs) and their associated conduits to stretch. After an initial phase of relaxation, TRCs sensed the resulting strain through cell matrix adhesions, which coordinated local growth and remodeling of the stromal network. While the expanded TRC network readopted its typical configuration, a massive fibrotic reaction of the organ capsule set in and countered further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multitier fashion.