bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brittle Faulting of Ductile Rock Induced by Pore Fluid Pressure Build‐Up
Authors: Noël Corentin , Passelègue François X. , Violay Marie 
Published: February 2021

AbstractUnder upper crustal conditions, deformations are primarily brittle (i.e., localized) and accommodated by frictional mechanisms. At greater depth, deformations are ductile (i.e., distributed) and accommodated by crystal plasticity, diffusion mass transfer or cataclastic flow. The transition from the brittle to the ductile domain is not associated with a critical depth, but rather varies in time and space. One main parameter controlling the variation of this transition is the pore fluid pressure. On the one hand, a pore fluid pressure increase reduces the effective stresses and possibly increases the strain rate, bringing the system closer to brittle conditions. On the other hand, pore fluid can favor ductile mechanisms, mostly via chemical effects, by facilitating intra‐crystalline plasticity, enhancing fluid‐solid diffusion and fracture healing/sealing. We report triaxial laboratory experiments that investigated the effect of pore fluid pressure increase during the ductile deformation of Tavel limestone. Three injection rates were tested: 1, 5, and 10 MPa/min. We demonstrate that: (1) Under initially ductile conditions pore fluid pressure increase immediately turns the system from compaction to dilation. (2) Dilation is due to the development of localized shear fractures. However, the macroscopic localization of the deformation is not instantaneous when the ductile to brittle transition is surpassed; a transient creeping phase is first needed. (3) To reach macroscopic brittle failure of initially ductile samples, a critical dilatancy is required. (4) Injection rate controls the final fracture distribution. We demonstrate that pore pressure build‐up in a rock undergoing ductile deformation can induce shear fracturing of the system.
Connecting Sediment Retention to Distributary‐Channel Hydrodynamics and Sediment Dynamics in a Tide‐dominated Delta: The Ayeyarwady Delta, Myanmar
Authors: Glover H. E. , Ogston A. S. , Fricke A. T. , Nittrouer C. A. , Aung Cherry , Naing Thet , Kyu Kyu Khin , Htike Htike 
Published: February 2021

AbstractThe largest deltas on Earth are tide‐dominated with multiple distributaries, which can experience different forcings. Yet, most observational studies of sediment dynamics in these systems focus on a single distributary. Comparison of the tidal‐to‐estuarine reaches of three representative distributaries of the Ayeyarwady Delta, Myanmar highlights the variability in sediment retention and export within a megadelta. The Ayeyarwady River has no mainstem dams, providing an opportunity to examine a relatively natural, monsoon‐dominated system. Observations were collected during high flow (September 2017) and low flow (March 2018 and 2019). The eastern Yangon distributary empties into the sheltered Gulf of Mottoma while the central Bogale and western Pathein distributaries are exposed to seasonal waves. During high flow, suspended‐sediment concentration (SSC) was consistent across all three distributaries (0.2–0.4 g/L). The upper delta retained 20%–60% of the mainstem sediment load, while the lower distributaries were tidal rivers exporting sediment. During low flow, the lower distributaries were partially mixed estuaries with little net discharge. However, SSC increased to >1 g/L in the Yangon distributary, remained constant in the Bogale distributary, and decreased in the Pathein distributary compared to high flow. This difference was driven by offshore sediment supply; fine sediment is retained near the mouth of the Yangon and advected away from the Pathein distributary. Consequently, nearshore sediment residence time in monsoon‐influenced megadeltas is controlled by coastal orientation, the timing of discharge with respect to ocean conditions, and tidal amplification. Changes to fluvial sediment delivery can cause non‐uniform coastal impacts due to these differing distributary processes.
Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota
Authors: Wang Yan , Tong Qian , Ma Shu-Rong , Zhao Zhen-Xiong , Pan Li-Bin , Cong Lin , Han Pei , Peng Ran , Yu Hang , Lin Yuan , Gao Tian-Le , Shou Jia-Wen , Li Xiao-Yang , Zhang Xian-Feng , Zhang Zheng-Wei , Fu Jie , Wen Bao-Ying , Yu Jin-Bo , Cao Xuetao , Jiang Jian-Dong 
Published: February 2021

AbstractThe phenylalanine–tyrosine–dopa–dopamine pathway provides dopamine to the brain. In this process, tyrosine hydroxylase (TH) is the rate-limiting enzyme that hydroxylates tyrosine and generates levodopa (l-dopa) with tetrahydrobiopterin (BH4) as a coenzyme. Here, we show that oral berberine (BBR) might supply H• through dihydroberberine (reduced BBR produced by bacterial nitroreductase) and promote the production of BH4 from dihydrobiopterin; the increased BH4 enhances TH activity, which accelerates the production of l-dopa by the gut bacteria. Oral BBR acts in a way similar to vitamins. The l-dopa produced by the intestinal bacteria enters the brain through the circulation and is transformed to dopamine. To verify the gut–brain dialog activated by BBR’s effect, Enterococcus faecalis or Enterococcus faecium was transplanted into Parkinson’s disease (PD) mice. The bacteria significantly increased brain dopamine and ameliorated PD manifestation in mice; additionally, combination of BBR with bacteria showed better therapeutic effect than that with bacteria alone. Moreover, 2,4,6-trimethyl-pyranylium tetrafluoroborate (TMP-TFB)-derivatized matrix-assisted laser desorption mass spectrometry (MALDI-MS) imaging of dopamine identified elevated striatal dopamine levels in mouse brains with oral Enterococcus, and BBR strengthened the imaging intensity of brain dopamine. These results demonstrated that BBR was an agonist of TH in Enterococcus and could lead to the production of l-dopa in the gut. Furthermore, a study of 28 patients with hyperlipidemia confirmed that oral BBR increased blood/fecal l-dopa by the intestinal bacteria. Hence, BBR might improve the brain function by upregulating the biosynthesis of l-dopa in the gut microbiota through a vitamin-like effect.
Neuroticism alters the transcriptome of the frontal cortex to contribute to the cognitive decline and onset of Alzheimer’s disease
Authors: De Jager Céline H. , White Charles C. , Bennett David A. , Ma Yiyi 
Published: February 2021

AbstractAccumulating evidence has suggested that the molecular transcriptional mechanism contributes to Alzheimer’s disease (AD) and its endophenotypes of cognitive decline and neuropathological traits, β-amyloid (Aβ) and phosphorylated tangles (TAU). However, it is unknown what is the impact of the AD risk factors, personality characteristics assessed by the NEO Five-Factor Inventory, on the human brain’s transcriptome. Using postmortem human brain samples from 466 subjects, we found that neuroticism has a significant overall impact on the brain transcriptome (omnibusP = 0.005) but not the other four personality characteristics. Focused on those cognitive decline related gene co-expressed modules, neuroticism has nominally significant associations (P < 0.05) with four neuronal modules, which are more related to PHFtau than Aβ across all eight brain regions. Furthermore, the effect of neuroticism on cognitive decline and AD might be mediated through the expression of module 7 and TAU pathology (P = 0.008). To conclude, neuroticism has a broad impact on the transcriptome of human brains, and its effect on cognitive decline and AD may be mediated through gene transcription programs related to TAU pathology.
Neuregulin signaling mediates the acute and sustained antidepressant effects of subanesthetic ketamine
Authors: Grieco Steven F. , Qiao Xin , Johnston Kevin G. , Chen Lujia , Nelson Renetta R. , Lai Cary , Holmes Todd C. , Xu Xiangmin 
Published: February 2021

AbstractSubanesthetic ketamine evokes rapid antidepressant effects in human patients that persist long past ketamine’s chemical half-life of ~2 h. Ketamine’s sustained antidepressant action may be due to modulation of cortical plasticity. We find that ketamine ameliorates depression-like behavior in the forced swim test in adult mice, and this depends on parvalbumin-expressing (PV) neuron-directed neuregulin-1 (NRG1)/ErbB4 signaling. Ketamine rapidly downregulates NRG1 expression in PV inhibitory neurons in mouse medial prefrontal cortex (mPFC) following a single low-dose ketamine treatment. This NRG1 downregulation in PV neurons co-tracks with the decreases in synaptic inhibition to mPFC excitatory neurons for up to a week. This results from reduced synaptic excitation to PV neurons, and is blocked by exogenous NRG1 as well as by PV targeted ErbB4 receptor knockout. Thus, we conceptualize that ketamine’s effects are mediated through rapid and sustained cortical disinhibition via PV-specific NRG1 signaling. Our findings reveal a novel neural plasticity-based mechanism for ketamine’s acute and long-lasting antidepressant effects.
Oxidative stress-induced mitophagy is suppressed by the miR-106b-93-25 cluster in a protective manner
Authors: Zhang Cheng , Nie Pengqing , Zhou Chunliu , Hu Yue , Duan Suling , Gu Meijia , Jiang Dongxu , Wang Yunfu , Deng Zixin , Chen Jincao , Chen Shi , Wang Lianrong 
Published: February 2021

AbstractIncreased reactive oxygen species levels in the mitochondrial matrix can induce Parkin-dependent mitophagy, which selectively degrades dysfunctional mitochondria via the autolysosome pathway. Phosphorylated mitofusin-2 (MFN2), a receptor of parkin RBR E3 ubiquitin-protein ligase (Parkin), interacts with Parkin to promote the ubiquitination of mitochondrial proteins; meanwhile, the mitophagy receptors Optineurin (OPTN) and nuclear dot protein 52 (NDP52) are recruited to damaged mitochondria to promote mitophagy. However, previous studies have not investigated changes in the levels of OPTN, MFN2, and NDP52 during Parkin-mediated mitophagy. Here, we show that mild and sustained hydrogen peroxide (H2O2) stimulation induces Parkin-dependent mitophagy accompanied by downregulation of the mitophagy-associated proteins OPTN, NDP52, and MFN2. We further demonstrate that H2O2promotes the expression of the miR-106b-93-25 cluster and that miR-106b and miR-93 synergistically inhibit the translation of OPTN, NDP52, and MFN2 by targeting their 3’ untranslated regions. We further reveal that compromised phosphorylation of MYC proto-oncogene protein (c-Myc) at threonine 58 (T58) (producing an unstable form of c-Myc) caused by reduced nuclear glycogen synthase kinase-3 beta (GSK3β) levels contributes to the promotion of miR-106b-93-25 cluster expression upon H2O2induction. Furthermore, miR-106b-mediated and miR-93-mediated inhibition of mitophagy-associated proteins (OPTN, MFN2, and NDP52) restrains cell death by controlling excessive mitophagy. Our data suggest that microRNAs (miRNAs) targeting mitophagy-associated proteins maintain cell survival, which is a novel mechanism of mitophagy control. Thus, our findings provide mechanistic insight into how miRNA-mediated regulation alters the biological process of mitophagy.
SIV-induced terminally differentiated adaptive NK cells in lymph nodes associated with enhanced MHC-E restricted activity
Authors: Huot Nicolas , Rascle Philippe , Petitdemange Caroline , Contreras Vanessa , Stürzel Christina M. , Baquero Eduard , Harper Justin L. , Passaes Caroline , Legendre Rachel , Varet Hugo , Madec Yoann , Sauermann Ulrike , Stahl-Hennig Christiane , Nattermann Jacob , Saez-Cirion Asier , Le Grand Roger , Keith Reeves R. , Paiardini Mirko , Kirchhoff Frank , Jacquelin Beatrice , Müller-Trutwin Michaela 
Published: February 2021

AbstractNatural killer (NK) cells play a critical understudied role during HIV infection in tissues. In a natural host of SIV, the African green monkey (AGM), NK cells mediate a strong control of SIVagm infection in secondary lymphoid tissues. We demonstrate that SIVagm infection induces the expansion of terminally differentiated NKG2alowNK cells in secondary lymphoid organs displaying an adaptive transcriptional profile and increased MHC-E-restricted cytotoxicity in response to SIV Env peptides while expressing little IFN-γ. Such NK cell differentiation was lacking in SIVmac-infected macaques. Adaptive NK cells displayed no increasedNKG2Cexpression. This study reveals a previously unknown profile of NK cell adaptation to a viral infection, thus accelerating strategies toward NK-cell directed therapies and viral control in tissues.
Discovery of exolytic heparinases and their catalytic mechanism and potential application
Authors: Zhang Qingdong , Cao Hai-Yan , Wei Lin , Lu Danrong , Du Min , Yuan Min , Shi Deling , Chen Xiangxue , Wang Peng , Chen Xiu-Lan , Chi Lianli , Zhang Yu-Zhong , Li Fuchuan 
Published: February 2021

AbstractHeparinases (Hepases) are critical tools for the studies of highly heterogeneous heparin (HP)/heparan sulfate (HS). However, exolytic heparinases urgently needed for the sequencing of HP/HS chains remain undiscovered. Herein, a type of exolytic heparinases (exoHepases) is identified from the genomes of different bacteria. These exoHepases share almost no homology with known Hepases and prefer to digest HP rather than HS chains by sequentially releasing unsaturated disaccharides from their reducing ends. The structural study of an exoHepase (BIexoHep) shows that an N-terminal conserved DUF4962 superfamily domain is essential to the enzyme activities of these exoHepases, which is involved in the formation of a unique L-shaped catalytic cavity controlling the sequential digestion of substrates through electrostatic interactions. Further, several HP octasaccharides have been preliminarily sequenced by using BIexoHep. Overall, this study fills the research gap of exoHepases and provides urgently needed tools for the structural and functional studies of HP/HS chains.
Fibrogranular materials function as organizers to ensure the fidelity of multiciliary assembly
Authors: Zhao Huijie , Chen Qingxia , Li Fan , Cui Lihong , Xie Lele , Huang Qiongping , Liang Xin , Zhou Jun , Yan Xiumin , Zhu Xueliang 
Published: February 2021

AbstractMulticilia are delicate motile machineries, and how they are accurately assembled is poorly understood. Here, we show that fibrogranular materials (FGMs), large arrays of electron-dense granules specific to multiciliated cells, are essential for their ultrastructural fidelity. Pcm1 forms the granular units that further network into widespread FGMs, which are abundant in spherical FGM cores. FGM cores selectively concentrate multiple important centriole-related proteins as clients, including Cep131 that specifically decorates a foot region of ciliary central pair (CP) microtubules. FGMs also tightly contact deuterosome-procentriole complexes. Disruption of FGMs in mouse cells undergoing multiciliogenesis by Pcm1 RNAi markedly deregulates centriolar targeting of FGM clients, elongates CP-foot, and alters deuterosome size, number, and distribution. Although the multicilia are produced in correct numbers, they display abnormal ultrastructure and motility. Our results suggest that FGMs organize deuterosomes and centriole-related proteins to facilitate the faithful assembly of basal bodies and multiciliary axonemes.
Flexible thermal interface based on self-assembled boron arsenide for high-performance thermal management
Authors: Cui Ying , Qin Zihao , Wu Huan , Li Man , Hu Yongjie 
Published: February 2021

AbstractThermal management is the most critical technology challenge for modern electronics. Recent key materials innovation focuses on developing advanced thermal interface of electronic packaging for achieving efficient heat dissipation. Here, for the first time we report a record-high performance thermal interface beyond the current state of the art, based on self-assembled manufacturing of cubic boron arsenide (s-BAs). The s-BAs exhibits highly desirable characteristics of high thermal conductivity up to 21 W/m·K and excellent elastic compliance similar to that of soft biological tissues down to 100 kPa through the rational design of BAs microcrystals in polymer composite. In addition, the s-BAs demonstrates high flexibility and preserves the high conductivity over at least 500 bending cycles, opening up new application opportunities for flexible thermal cooling. Moreover, we demonstrated device integration with power LEDs and measured a superior cooling performance of s-BAs beyond the current state of the art, by up to 45 °C reduction in the hot spot temperature. Together, this study demonstrates scalable manufacturing of a new generation of energy-efficient and flexible thermal interface that holds great promise for advanced thermal management of future integrated circuits and emerging applications such as wearable electronics and soft robotics.
Revealing the role of the human blood plasma proteome in obesity using genetic drivers
Authors: Zaghlool Shaza B. , Sharma Sapna , Molnar Megan , Matías-García Pamela R. , Elhadad Mohamed A. , Waldenberger Melanie , Peters Annette , Rathmann Wolfgang , Graumann Johannes , Gieger Christian , Grallert Harald , Suhre Karsten 
Published: February 2021

AbstractBlood circulating proteins are confounded readouts of the biological processes that occur in different tissues and organs. Many proteins have been linked to complex disorders and are also under substantial genetic control. Here, we investigate the associations between over 1000 blood circulating proteins and body mass index (BMI) in three studies including over 4600 participants. We show that BMI is associated with widespread changes in the plasma proteome. We observe 152 replicated protein associations with BMI. 24 proteins also associate with a genome-wide polygenic score (GPS) for BMI. These proteins are involved in lipid metabolism and inflammatory pathways impacting clinically relevant pathways of adiposity. Mendelian randomization suggests a bi-directional causal relationship of BMI with LEPR/LEP, IGFBP1, and WFIKKN2, a protein-to-BMI relationship for AGER, DPT, and CTSA, and a BMI-to-protein relationship for another 21 proteins. Combined with animal model and tissue-specific gene expression data, our findings suggest potential therapeutic targets further elucidating the role of these proteins in obesity associated pathologies.
The tumor therapy landscape of synthetic lethality
Authors: Zhang Biyu , Tang Chen , Yao Yanli , Chen Xiaohan , Zhou Chi , Wei Zhiting , Xing Feiyang , Chen Lan , Cai Xiang , Zhang Zhiyuan , Sun Shuyang , Liu Qi 
Published: February 2021

AbstractSynthetic lethality is emerging as an important cancer therapeutic paradigm, while the comprehensive selective treatment opportunities for various tumors have not yet been explored. We develop the Synthetic Lethality Knowledge Graph (SLKG), presenting the tumor therapy landscape of synthetic lethality (SL) and synthetic dosage lethality (SDL). SLKG integrates the large-scale entity of different tumors, drugs and drug targets by exploring a comprehensive set of SL and SDL pairs. The overall therapy landscape is prioritized to identify the best repurposable drug candidates and drug combinations with literature supports, in vitro pharmacologic evidence or clinical trial records. Finally, cladribine, an FDA-approved multiple sclerosis treatment drug, is selected and identified as a repurposable drug for treating melanoma with CDKN2A mutation by in vitro validation, serving as a demonstrating SLKG utility example for novel tumor therapy discovery. Collectively, SLKG forms the computational basis to uncover cancer-specific susceptibilities and therapy strategies based on the principle of synthetic lethality.
Fundamental limits of electron and nuclear spin qubit lifetimes in an isolated self-assembled quantum dot
Authors: Gillard George , Griffiths Ian M. , Ragunathan Gautham , Ulhaq Ata , McEwan Callum , Clarke Edmund , Chekhovich Evgeny A. 
Published: February 2021

AbstractCombining external control with long spin lifetime and coherence is a key challenge for solid state spin qubits. Tunnel coupling with electron Fermi reservoir provides robust charge state control in semiconductor quantum dots, but results in undesired relaxation of electron and nuclear spins through mechanisms that lack complete understanding. Here, we unravel the contributions of tunnelling-assisted and phonon-assisted spin relaxation mechanisms by systematically adjusting the tunnelling coupling in a wide range, including the limit of an isolated quantum dot. These experiments reveal fundamental limits and trade-offs of quantum dot spin dynamics: while reduced tunnelling can be used to achieve electron spin qubit lifetimes exceeding 1 s, the optical spin initialisation fidelity is reduced below 80%, limited by Auger recombination. Comprehensive understanding of electron-nuclear spin relaxation attained here provides a roadmap for design of the optimal operating conditions in quantum dot spin qubits.
Identification of LINC00665-miR-let-7b-CCNA2 competing endogenous RNA network associated with prognosis of lung adenocarcinoma
Authors: Huang Yusheng , Zhong Limei , Nie Kechao , Li Lijuan , Song Shaohua , Liu Fengbin , Li Peiwu , Cao Donglin , Liu Yufeng 
Published: February 2021

AbstractPrognosis of patients with lung cancer remains extremely poor; thus, we sought to unearth novel competing endogenous RNA (ceRNA) networks associated with the prognosis of lung adenocarcinoma (LUAD). Aberrant mRNAs were identified from the intersection of three Gene Expression Omnibus (GEO) datasets. A protein–protein interaction (PPI) network was constructed, and miRNAs and long noncoding RNAs (lncRNAs) upstream of mRNAs were predicted. In the present study, 402 upregulated and 638 downregulated genes in lung cancer tissues were identified. Functional analysis showed significant enrichment of cancer pathways. In these top hub genes, 10 upregulated and 7 downregulated genes had substantial prognostic values in LUAD. Thirty-seven miRNAs were predicted to target 17 key genes, and only five miRNAs exhibited prognostic correlation.
Through stepwise reverse prediction and validation from miRNA to lncRNA, four key lncRNAs were identified using expression and survival analysis. Ultimately, the co-expression analysis identified LINC00665-miR-let-7b-CCNA2 as the key ceRNA network associated with the prognosis of LUAD. We successfully constructed a novel ceRNA network wherein each component was significantly associated with the prognosis of LUAD. Hence, we propose that this network may provide key biomarkers or potential therapeutic targets for LUAD prognosis.
Development of a deep learning-based software for calculating cleansing score in small bowel capsule endoscopy
Authors: Nam Ji Hyung , Hwang Youngbae , Oh Dong Jun , Park Junseok , Kim Ki Bae , Jung Min Kyu , Lim Yun Jeong 
Published: February 2021

AbstractA standardized small bowel (SB) cleansing scale is currently not available. The aim of this study was to develop an automated calculation software for SB cleansing score using deep learning. Consecutively performed capsule endoscopy cases were enrolled from three hospitals. A 5-step scoring system based on mucosal visibility was trained for deep learning in the training set. Performance of the trained software was evaluated in the validation set. Average cleansing score (1.0 to 5.0) by deep learning was compared to clinical grading (A to C) reviewed by clinicians. Cleansing scores decreased as clinical grading worsened (scores of 4.1, 3.5, and 2.9 for grades A, B, and C, respectively, P < 0.001). Adequate preparation was achieved for 91.7% of validation cases. The average cleansing score was significantly different between adequate and inadequate group (4.0 vs. 2.9, P < 0.001). ROC curve analysis revealed that a cut-off value of cleansing score at 3.25 had an AUC of 0.977. Diagnostic yields for small, hard-to-find lesions were associated with high cleansing scores (4.3 vs. 3.8, P < 0.001). We developed a novel scoring software which calculates objective, automated cleansing scores for SB preparation. The cut-off value we suggested provides a standard criterion for adequate bowel preparation as a quality indicator.