bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revisiting the Timpson Induced Earthquake Sequence: A System of Two Parallel Faults
Authors: Wang Kaiwen , Ellsworth William , Beroza Gregory C. 
Published: July 2020

AbstractThe 17 May 2012 M4.8 Timpson earthquake is the largest known earthquake in eastern Texas. It is thought to have been induced by wastewater injection from two nearby, high‐volume wells. Its cataloged aftershocks form a NW‐SE trend, which unlike other induced earthquakes sequences is unfavorably oriented for failure in the local stress field. To understand this, we enriched the catalog using PhaseNet, a deep‐learning‐based picker followed by double‐difference relocation with cross‐correlation‐based differential traveltimes. We clustered the aftershocks based on waveform similarity. Most of the seismicity falls into two clusters, which define a detailed fault structure of two parallel subfaults that are more favorably oriented than the overall trend. We inferred from waveform similarity that the sequence initiated on the northern subfault with a M3.9 foreshock and M4.8 mainshock, then extended to the southern subfault with a M4.1 aftershock, and was finally reactivated on the northern subfault with two more M4 events.
Therapeutic inhibition of FcγRIIb signaling targets leukemic stem cells in chronic myeloid leukemia
Authors: Parting Oliver , Langer Samantha , Kuepper Maja Kim , Wessling Caroline , Li Shaoguang , Braunschweig Till , Chatain Nicolas , Maié Tiago , Costa Ivan G. , Crysandt Martina , Huber Michael , Brümmendorf Tim H. , Koschmieder Steffen , Schemionek Mirle 
Published: July 2020

AbstractDespite the successes achieved with molecular targeted inhibition of the oncogenic driver Bcr-Abl in chronic myeloid leukemia (CML), the majority of patients still require lifelong tyrosine kinase inhibitor (TKI) therapy. This is primarily caused by resisting leukemic stem cells (LSCs), which prevent achievement of treatment-free remission in all patients. Here we describe the ITIM (immunoreceptor tyrosine-based inhibition motif)-containing Fc gamma receptor IIb (FcγRIIb, CD32b) for being critical in LSC resistance and show that targeting FcγRIIb downstream signaling, by using a Food and Drug Administration-approved BTK inhibitor, provides a successful therapeutic approach. First, we identified FcγRIIb upregulation in primary CML stem cells. FcγRIIb depletion caused reduced serial re-plaiting efficiency and cell proliferation in malignant cells. FcγRIIb targeting in both a transgenic and retroviral CML mouse model provided in vivo evidence for successful LSC reduction. Subsequently, we identified BTK as a main downstream mediator and targeting the Bcr-Abl-FcγRIIb-BTK axis in primary CML CD34+cells using ibrutinib, in combination with standard TKI therapy, significantly increased apoptosis in quiescent CML stem cells thereby contributing to the eradication of LSCs.. As a potential curative therapeutic approach, we therefore suggest combining Bcr-Abl TKI therapy along with BTK inhibition.
Infrared chemical imaging through non-degenerate two-photon absorption in silicon-based cameras
Authors: Knez David , Hanninen Adam M. , Prince Richard C. , Potma Eric O. , Fishman Dmitry A. 
Published: July 2020

AbstractChemical imaging based on mid-infrared (MIR) spectroscopic contrast is an important technique with a myriad of applications, including biomedical imaging and environmental monitoring. Current MIR cameras, however, lack performance and are much less affordable than mature Si-based devices, which operate in the visible and near-infrared regions. Here, we demonstrate fast MIR chemical imaging through non-degenerate two-photon absorption (NTA) in a standard Si-based charge-coupled device (CCD). We show that wide-field MIR images can be obtained at 100 ms exposure times using picosecond pulse energies of only a few femtojoules per pixel through NTA directly on the CCD chip. Because this on-chip approach does not rely on phase matching, it is alignment-free and does not necessitate complex postprocessing of the images. We emphasize the utility of this technique through chemically selective MIR imaging of polymers and biological samples, including MIR videos of moving targets, physical processes and live nematodes.
A reciprocal inhibition model of alternations between under-/overemotional modulatory states in patients with PTSD
Authors: Chiba Toshinori , Ide Kentaro , Taylor Jessica E. , Boku Shuken , Toda Hiroyuki , Kanazawa Tetsufumi , Kato Sumie , Horiuchi Yuka , Hishimoto Akitoyo , Maruyama Toru , Yamamoto Taisuke , Shirakawa Miyako , Sora Ichiro , Kawato Mitsuo , Koizumi Ai 
Published: July 2020

AbstractPatients with posttraumatic stress disorder (PTSD) appear to manifest two opposing tendencies in their attentional biases and symptoms. However, whether common neural mechanisms account for their opposing attentional biases and symptoms remains unknown. We here propose a model in which reciprocal inhibition between the amygdala and ventromedial prefrontal cortex (vmPFC) predicts synchronized alternations between emotional under- and overmodulatory states at the neural, behavioral, and symptom levels within the same patients. This reciprocal inhibition model predicts that when the amygdala is dominant, patients enter an emotional undermodulatory state where they show attentional bias toward threat and manifest re-experiencing symptoms. In contrast, when the vmPFC is dominant, patients are predicted to enter an emotional overmodulatory state where they show attentional bias away from threat and avoidance symptoms. To test the model, we performed a behavioral meta-analysis (total N = 491), analyses of own behavioral study (N = 20), and a neuroimaging meta-analysis (total N = 316). Supporting the model, we found the distributions of behavioral attentional measurements to be bimodal, suggesting alternations between the states within patients. Moreover, attentional bias toward threat was related to re-experiencing symptoms, whereas attentional bias away from threat was related with avoidance symptoms. We also found that the increase and decrease of activity in the left amygdala activity was related with re-experiencing and avoidance symptoms, respectively. Our model may help elucidate the neural mechanisms differentiating nondissociative and dissociative subtypes of PTSD, which usually show differential emotional modulatory levels. It may thus provide a new venue for therapies targeting each subtype.
Glutamine-to-glutamate ratio in the nucleus accumbens predicts effort-based motivated performance in humans
Authors: Strasser Alina , Luksys Gediminas , Xin Lijing , Pessiglione Mathias , Gruetter Rolf , Sandi Carmen 
Published: July 2020

AbstractSubstantial evidence implicates the nucleus accumbens in motivated performance, but very little is known about the neurochemical underpinnings of individual differences in motivation. Here, we applied 1H magnetic resonance spectroscopy (1H-MRS) at ultra-high-field in the nucleus accumbens and inquired whether levels of glutamate (Glu), glutamine (Gln), GABA or their ratios predict interindividual differences in effort-based motivated task performance. Given the incentive value of social competition, we also examined differences in performance under self-motivated or competition settings. Our results indicate that higher accumbal Gln-to-Glu ratio predicts better overall performance and reduced effort perception. As performance is the outcome of multiple cognitive, motor and physiological processes, we applied computational modeling to estimate best-fitting individual parameters related to specific processes modeled with utility, effort and performance functions. This model-based analysis revealed that accumbal Gln-to-Glu ratio specifically relates to stamina; i.e., the capacity to maintain performance over long periods. It also indicated that competition boosts performance from task onset, particularly for low Gln-to-Glu individuals. In conclusion, our findings provide novel insights implicating accumbal Gln and Glu balance on the prediction of specific computational components of motivated performance. This approach and findings can help developing therapeutic strategies based on targeting metabolism to ameliorate deficits in effort engagement.
Inflammatory modulation of the associations between prenatal maternal depression and neonatal brain
Authors: Wu Yonghui , Zhang Han , Wang Changqing , Broekman Birit F. P. , Chong Yap-Seng , Shek Lynette P. , Gluckman Peter D. , Meaney Michael J. , Fortier Marielle V. , Qiu Anqi 
Published: July 2020

AbstractInflammatory signaling has a role in sensing intrauterine environment, which may be moderators in altering fetal brain development upon maternal environment. This study integrated cytokine transcriptome of post-mortem fetal brains, neonatal brain imaging and genetic variants (n = 161) to examine whether cytokines are candidates for modulating the relationship between prenatal maternal depression and fetal brain development. This study obtained the transcriptome data of 208 cytokine genes in 12 fetal brain regions from the BrainSpan database. We also included 161 mother–child dyads with prenatal maternal depressive symptoms assessed at 26 weeks of gestation, cytokine genotype data extracted from umbilical cord specimens, and neonatal brain images from a longitudinal prospective birth cohort. We revealed that 22 cytokine genes are expressed in specific brain regions in utero, whose variants have roles in modulating the effects of the prenatal environment on the accelerated fetal development of the hippocampus, auditory, parietal, orbitofrontal, and dorsal prefrontal cortex. Neonates high in the genetic expression score (GES) of TNFRSF19 and IL17RB showed a larger right hippocampal volume, high in the GES of BMPR1B showed the thicker thickness of the sensorimotor cortex, and high in the GES of IL1RAP and CXCR4 demonstrated the thicker thickness of the dorsal and orbital prefrontal cortex in relation with greater prenatal maternal depressive symptoms. Our findings suggest that in humans, the cytokine genes are expressed in a brain region-specific manner in utero and may have potential roles in modulating the fetal development of the corresponding brain regions in response to the maternal environment.
Intracellular symbionts drive sex ratio in the whitefly by facilitating fertilization and provisioning of B vitamins
Authors: Wang Yan-Bin , Ren Fei-Rong , Yao Ya-Lin , Sun Xiang , Walling Linda L , Li Na-Na , Bai Bing , Bao Xi-Yu , Xu Xiao-Rui , Luan Jun-Bo 
Published: July 2020

Abstract
Symbionts can regulate animal reproduction in multiple ways, but the underlying physiological and biochemical mechanisms remain largely unknown. The presence of multiple lineages of maternally inherited, intracellular symbionts (the primary and secondary symbionts) in terrestrial arthropods is widespread in nature. However, the biological, metabolic, and evolutionary role of co-resident secondary symbionts for hosts is poorly understood. The bacterial symbionts Hamiltonella and Arsenophonus have very high prevalence in two globally important pests, the whiteflies Bemisia tabaci and Trialeurodes vaporariorum, respectively. Both symbionts coexist with the primary symbiont Portiera in the same host cell (bacteriocyte) and are maternally transmitted. We found that elimination of both Hamiltonella and Arsenophonous by antibiotic treatment reduced the percentage of female offspring in whiteflies. Microsatellite genotyping and cytogenetic analysis revealed that symbiont deficiency inhibited fertilization in whiteflies, leading to more haploid males with one maternal allele, which is consistent with distorted sex ratio in whiteflies. Quantification of essential amino acids and B vitamins in whiteflies indicated that symbiont deficiency reduced B vitamin levels, and dietary B vitamin supplementation rescued fitness of whiteflies. This study, for the first time, conclusively demonstrates that these two intracellular symbionts affect sex ratios in their whitefly hosts by regulating fertilization and supplying B vitamins. Our results reveal that both symbionts have the convergent function of regulating reproduction in phylogenetically-distant whitefly species. The 100% frequency, the inability of whiteflies to develop normally without their symbiont, and rescue with B vitamins suggests that both symbionts may be better considered co-primary symbionts.
Discovery of new fluorescent thiazole–pyrazoline derivatives as autophagy inducers by inhibiting mTOR activity in A549 human lung cancer cells
Authors: Lin ZhaoMin , Wang ZhaoYang , Zhou XueWen , Zhang Ming , Gao DongFang , Zhang Lu , Wang Peng , Chen Yuan , Lin YuXing , Zhao BaoXiang , Miao JunYing , Kong Feng 
Published: July 2020

AbstractA series of fluorescent thiazole–pyrazoline derivatives was synthesized and their structures were characterized by 1H NMR, 13C NMR, and HRMS. Biological evaluation demonstrated that these compounds could effectively inhibit the growth of human non-small cell lung cancer (NSCLC) A549 cells in a dose- and time-dependent manner in vitro and inhibit tumor growth in vivo. The structure–activity relationship (SAR) of the compounds was analyzed. Further mechanism research revealed they could induce autophagy and cell cycle arrest while had no influence on cell necrosis. Compound 5e inhibited the activity of mTOR via FKBP12, which could be reversed by 3BDO, an mTOR activator and autophagy inhibitor. Compound 5e inhibited growth, promoted autophagy of A549 cells in vivo. Moreover, compound 5e showed good selectivity with no influence on normal vascular endothelial cell growth and the normal chick embryo chorioallantoic membrane (CAM) capillary formation. Therefore, our research provides potential lead compounds for the development of new anticancer drugs against human lung cancer.
Inactivating p53 is essential for nerve growth factor receptor to promote melanoma-initiating cell-stemmed tumorigenesis
Authors: Jiang Leiwei , Huang Shibo , Wang Jieqiong , Zhang Yiwei , Xiong Yuqing , Zeng Shelya X. , Lu Hua 
Published: July 2020

AbstractNerve growth factor receptor (NGFR, CD271, or p75NTR) is highly expressed in melanoma-initiating cells (MICs) and is critical for their proliferation and tumorigenesis, and yet the underlying mechanism(s) remain incompletely understood. We previously showed that NGFR inhibits p53 activity in a negative feedback manner in various cancer cells. Here we report that this feedback inhibition of p53 by NGFR plays an essential role in maintaining the sphere formation (stem-like phenotype) and proliferation of MICs, and in promoting MIC-derived melanoma growth in vivo. Knockdown of NGFR markedly reduced the size and number of spheroid formation of melanoma cells, which can be rescued by ectopically expressed NGFR. This reduction was also reversed by depleting p53. Consistently, knockdown of NGFR led to the suppression of MIC-derived xenograft tumor growth by inducing the p53 pathway. These results demonstrate that the NGFR-p53 feedback loop is essential for maintaining MIC stem-like phenotype and MIC-derived tumorigenesis, and further validates NGFR as a potential target for developing a molecule-based therapy against melanoma.
Preserving nanoscale features in polymers during laser induced graphene formation using sequential infiltration synthesis
Authors: Bergsman David S. , Getachew Bezawit A. , Cooper Christopher B. , Grossman Jeffrey C. 
Published: July 2020

AbstractDirect lasing of polymeric membranes to form laser induced graphene (LIG) offers a scalable and potentially cheaper alternative for the fabrication of electrically conductive membranes. However, the high temperatures induced during lasing can deform the substrate polymer, altering existing micro- and nanosized features that are crucial for a membrane’s performance. Here, we demonstrate how sequential infiltration synthesis (SIS) of alumina, a simple solvent-free process, stabilizes polyethersulfone (PES) membranes against deformation above the polymers’ glass transition temperature, enabling the formation of LIG without any changes to the membrane’s underlying pore structure. These membranes are shown to have comparable sheet resistance to carbon-nanotube-composite membranes. They are electrochemically stable and maintain their permeability after lasing, demonstrating their competitive performance as electrically conductive membranes. These results demonstrate the immense versatility of SIS for modifying materials when combined with laser induced graphitization for a variety of applications.
Imaging spatiotemporal evolution of molecules and active sites in zeolite catalyst during methanol-to-olefins reaction
Authors: Gao Mingbin , Li Hua , Liu Wenjuan , Xu Zhaochao , Peng Shichao , Yang Miao , Ye Mao , Liu Zhongmin 
Published: July 2020

AbstractDirect visualization of spatiotemporal evolution of molecules and active sites during chemical transformation in individual catalyst crystal will accelerate the intuitive understanding of heterogeneous catalysis. So far, widespread imaging techniques can only provide limited information either with large probe molecules or in model catalyst of large size, which are beyond the interests of industrial catalysis. Herein, we demonstrate a feasible deep data approach via synergy of multiscale reaction-diffusion simulation and super-resolution structured illumination microscopy to illustrate the dynamical evolution of spatiotemporal distributions of gas molecules, carbonaceous species and acid sites in SAPO-34 zeolite crystals of several micrometers that are typically used in industrial methanol-to-olefins process. The profound insights into the inadequate utilization of activated acid sites and rapid deactivation are unveiled. The notable elucidation of molecular reaction-diffusion process at the scale of single catalyst crystal via this approach opens an interesting method for mechanism study in materials synthesis and catalysis.
Light-triggered switching of liposome surface charge directs delivery of membrane impermeable payloads in vivo
Authors: Arias-Alpizar Gabriela , Kong Li , Vlieg Redmar C. , Rabe Alexander , Papadopoulou Panagiota , Meijer Michael S. , Bonnet Sylvestre , Vogel Stefan , van Noort John , Kros Alexander , Campbell Frederick 
Published: July 2020

AbstractSurface charge plays a fundamental role in determining the fate of a nanoparticle, and any encapsulated contents, in vivo. Herein, we describe, and visualise in real time, light-triggered switching of liposome surface charge, from neutral to cationic, in situ and in vivo (embryonic zebrafish). Prior to light activation, intravenously administered liposomes, composed of just two lipid reagents, freely circulate and successfully evade innate immune cells present in the fish. Upon in situ irradiation and surface charge switching, however, liposomes rapidly adsorb to, and are taken up by, endothelial cells and/or are phagocytosed by blood resident macrophages. Coupling complete external control of nanoparticle targeting together with the intracellular delivery of encapsulated (and membrane impermeable) cargos, these compositionally simple liposomes are proof that advanced nanoparticle function in vivo does not require increased design complexity but rather a thorough understanding of the fundamental nano-bio interactions involved.
Inhibition of transition metals dissolution in cobalt-free cathode with ultrathin robust interphase in concentrated electrolyte
Authors: Liu Wei , Li Jinxing , Li Wenting , Xu Hanying , Zhang Chao , Qiu Xinping 
Published: July 2020

AbstractThe low Coulombic efficiency during cycling hinders the application of Cobalt-free lithium-rich materials in lithium-ion batteries. Here we demonstrated that the dissolution of iron, rather than traditionally acknowledged manganese, is mainly responsible for the low Coulombic efficiency of the iron-substituted cobalt-free lithium-rich material. Besides, we presented an approach to inhibit the dissolution of transition metal ions by using concentrated electrolytes. We found that the cathode electrolyte interphase (CEI) layer formed in the concentrated electrolyte is a uniform and robust LiF-rich CEI, which is a sharp contrast with the uneven and fragile organic-rich CEI formed in the dilute electrolyte. The LiF-rich CEI not only effectively inhibits the dissolution of TMs but also stabilizes the cathode structure. The Coulombic efficiency, cycling stability, rate performance, and safety of the Fe-substituted cobalt-free lithium-rich cathode material in the concentrated electrolyte have been improved tremendously.
Basement membrane damage by ROS- and JNK-mediated Mmp2 activation drives macrophage recruitment to overgrown tissue
Authors: Diwanji Neha , Bergmann Andreas 
Published: July 2020

AbstractMacrophages are a major immune cell type infiltrating tumors and promoting tumor growth and metastasis. To elucidate the mechanism of macrophage recruitment, we utilize an overgrowth tumor model (“undead” model) in larval Drosophila imaginal discs that are attached by numerous macrophages. Here we report that changes to the microenvironment of the overgrown tissue are important for recruiting macrophages. First, we describe a correlation between generation of reactive oxygen species (ROS) and damage of the basement membrane (BM) in all neoplastic, but not hyperplastic, models examined. ROS and the stress kinase JNK mediate the accumulation of matrix metalloproteinase 2 (Mmp2), damaging the BM, which recruits macrophages to the tissue. We propose a model where macrophage recruitment to and activation at overgrowing tissue is a multi-step process requiring ROS- and JNK-mediated Mmp2 upregulation and BM damage. These findings have implications for understanding the role of the tumor microenvironment for macrophage activation.
PDZD8 interacts with Protrudin and Rab7 at ER-late endosome membrane contact sites associated with mitochondria
Authors: Elbaz-Alon Yael , Guo Yuting , Segev Nadav , Harel Michal , Quinnell Daniel E. , Geiger Tamar , Avinoam Ori , Li Dong , Nunnari Jodi 
Published: July 2020

AbstractEndosomes are compositionally dynamic organelles that regulate signaling, nutrient status and organelle quality by specifying whether material entering the cells will be shuttled back to the cell surface or degraded by the lysosome. Recently, membrane contact sites (MCSs) between the endoplasmic reticulum (ER) and endosomes have emerged as important players in endosomal protein sorting, dynamics and motility. Here, we show that PDZD8, a Synaptotagmin-like Mitochondrial lipid-binding Proteins (SMP) domain-containing ER transmembrane protein, utilizes distinct domains to interact with Rab7-GTP and the ER transmembrane protein Protrudin and together these components localize to an ER-late endosome MCS. At these ER-late endosome MCSs, mitochondria are also recruited to form a three-way contact. Thus, our data indicate that PDZD8 is a shared component of two distinct MCSs and suggest a role for SMP-mediated lipid transport in the regulation of endosome function.