bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fine Structure of the Chenghai Fault Zone, Yunnan, China, Constrained From Teleseismic Travel Time and Ambient Noise Tomography
Authors: Yang Hongfeng , Duan Yaohui , Song Junhao , Jiang Xiaohuan , Tian Xiaofeng , Yang Wei , Wang Weitao , Yang Jun 
Published: June 2020

AbstractTo derive high‐resolution fault zone (FZ) structure of the Chenghai fault in Yunnan, southwestern China, we deployed a linear dense array crossing the fault from January to February 2018. The array consisted of 158 short‐period (5 s) three‐component instruments and spanned an aperture of ~8 km with average station spacing of 40–50 m. During the 1‐month deployment, 20 teleseismic earthquakes with moment magnitudes larger than 5.5 and 41 local earthquakes were recorded. We first analyzed the travel times of P and S waves from teleseismic earthquakes to determine the boundaries of the FZ. After correcting the station‐event geometry effects, teleseismic travel time differences between the reference station, and all other stations clearly marked a zone of 3.4 km in width with distinct travel time anomaly, suggesting a low‐velocity zone (LVZ) surrounding the Chenghai fault. We then conducted ambient noise tomography and found that the S wave velocity of the LVZ was reduced by 60% and 40% compared to the northwest and southeast of the LVZ, respectively. Our ambient noise results suggested the LVZ extending to ~1.5 km in depth, consistent with the travel time anomalies of teleseismic earthquakes. Integrating ambient noise tomography with teleseismic travel times in a dense array with such an aperture is an effective approach for resolving FZ structure and depth extent.
Assessment of Observational Evidence for Direct Convective Hydration of the Lower Stratosphere
Authors: Jensen E. J. , Pan Laura L. , Honomichl Shawn , Diskin Glenn S. , Krämer Martina , Spelten Nicole , Günther Gebhard , Hurst Dale F. , Fujiwara Masatomo , Vömel Holger , Selkirk Henry B. , Suzuki Junko , Schwartz Michael J. , Smith Jessica B. 
Published: June 2020

AbstractIn situ and remote sensing observations of water vapor are analyzed to assess the evidence for direct convective hydration of the lower stratosphere. We have examined several hundred balloon‐borne and airborne in situ measurements of lower stratospheric humidity in the tropics and northern midlatitudes. We find that the tropical lower stratospheric H2O enhancements above the background occur quite infrequently, and the height of the enhancements is within about 1 km of the cold‐point tropopause. Following Schwartz et al. (2013, https://doi.org/10.1002/grl.50421), we examine the anomalously high (above 8 ppmv) water vapor mixing ratios retrieved by the Aura Microwave Limb Sounder (MLS) at 100‐ and 82‐hPa pressure levels, and we determine their vertical location relative to the local tropopause based on both Global Forecast System (GFS) operational analysis and the ERA5 reanalysis temperature data. We find that essentially all of the >8‐ppmv MLS water vapor measurements over the extratropical North American monsoon region are above the relatively low lapse‐rate tropopause in the region, and most are above the local cold‐point tropopause. Over the Asian monsoon region, most (80/90%) of the high H2O values occur below the relatively high‐altitude local lapse‐rate/cold‐point tropopause. Anomalously high MLS water vapor retrievals at 100 and 82 hPa almost never occur in the deep tropics. We show that this result is consistent with the in situ observations given the broad vertical averaging kernel of the MLS measurement. The available evidence suggests that direct hydration of the lower stratosphere is important over North America during the monsoon season but likely has limited impact in the tropics.
Gα12/13 signaling in metabolic diseases
Authors: Yang Yoon Mee , Kuen Da-Sol , Chung Yeonseok , Kurose Hitoshi , Kim Sang Geon 
Published: June 2020

AbstractAs the key governors of diverse physiological processes, G protein-coupled receptors (GPCRs) have drawn attention as primary targets for several diseases, including diabetes and cardiovascular disease. Heterotrimeric G proteins converge signals from ~800 members of the GPCR family. Among the members of the G protein α family, the Gα12 family members comprising Gα12 and Gα13 have been referred to as gep oncogenes. Gα12/13 levels are altered in metabolic organs, including the liver and muscles, in metabolic diseases. The roles of Gα12/13 in metabolic diseases have been investigated. In this review, we highlight findings demonstrating Gα12/13 amplifying or dampening regulators of phenotype changes. We discuss the molecular basis of G protein biology in the context of posttranslational modifications to heterotrimeric G proteins and the cell signaling axis. We also highlight findings providing insights into the organ-specific, metabolic and pathological roles of G proteins in changes associated with specific cells, energy homeostasis, glucose metabolism, liver fibrosis and the immune and cardiovascular systems. This review summarizes the currently available knowledge on the importance of Gα12/13 in the physiology and pathogenesis of metabolic diseases, which is presented according to the basic understanding of their metabolic actions and underlying cellular and molecular bases.
Deazaflavin reductive photocatalysis involves excited semiquinone radicals
Authors: Graml Andreas , Neveselý Tomáš , Jan Kutta Roger , Cibulka Radek , König Burkhard 
Published: June 2020

AbstractFlavin-mediated photocatalytic oxidations are established in synthetic chemistry. In contrast, their use in reductive chemistry is rare. Deazaflavins with a much lower reduction potential are even better suited for reductive chemistry rendering also deazaflavin semiquinones as strong reductants. However, no direct evidence exists for the involvement of these radical species in reductive processes. Here, we synthesise deazaflavins with different substituents at C5 and demonstrate their photocatalytic activity in the dehalogenation of p-halogenanisoles with best performance under basic conditions. Mechanistic investigations reveal a consecutive photo-induced electron transfer via the semiquinone form of the deazaflavin as part of a triplet-correlated radical pair after electron transfer from a sacrificial electron donor to the triplet state. A second electron transfer from the excited semiquinone to p-halogenanisoles triggers the final product formation. This study provides first evidence that the reductive power of excited deazaflavin semiquinones can be used in photocatalytic reductive chemistry.
Diaphanous-related formin mDia2 regulates beta2 integrins to control hematopoietic stem and progenitor cell engraftment
Authors: Mei Yang , Han Xu , Liu Yijie , Yang Jing , Sumagin Ronen , Ji Peng 
Published: June 2020

AbstractBone marrow engraftment of the hematopoietic stem and progenitor cells (HSPCs) involves homing to the vasculatures and lodgment to their niches. How HSPCs transmigrate from the vasculature to the niches is unclear. Here, we show that loss of diaphanous-related formin mDia2 leads to impaired engraftment of long-term hematopoietic stem cells and loss of competitive HSPC repopulation. These defects are likely due to the compromised trans-endothelial migration of HSPCs since their homing to the bone marrow vasculatures remained intact. Mechanistically, loss of mDia2 disrupts HSPC polarization and induced cytoplasmic accumulation of MAL, which deregulates the activity of serum response factor (SRF). We further reveal that beta2 integrins are transcriptional targets of SRF. Knockout of beta2 integrins in HSPCs phenocopies mDia2 deficient mice. Overexpression of SRF or beta2 integrins rescues HSPC engraftment defects associated with mDia2 deficiency. Our findings show that mDia2-SRF-beta2 integrin signaling is critical for HSPC lodgment to the niches.
An amphipathic peptide with antibiotic activity against multidrug-resistant Gram-negative bacteria
Authors: Elliott Alysha G. , Huang Johnny X. , Neve Søren , Zuegg Johannes , Edwards Ingrid A. , Cain Amy K. , Boinett Christine J. , Barquist Lars , Lundberg Carina Vingsbo , Steen Jason , Butler Mark S. , Mobli Mehdi , Porter Kaela M. , Blaskovich Mark A. T. , Lociuro Sergio , Strandh Magnus , Cooper Matthew A. 
Published: June 2020

ABSTRACTPeptide antibiotics are an abundant and synthetically tractable source of molecular diversity, but they are often cationic and can be cytotoxic, nephrotoxic and/or ototoxic, which has limited their clinical development. Here we report structure-guided optimization of an amphipathic peptide, arenicin-3, originally isolated from the marine lugworm Arenicola marina. The peptide induces bacterial membrane permeability and ATP release, with serial passaging resulting in a mutation in mlaC, a phospholipid transport gene. Structure-based design led to AA139, an antibiotic with broad-spectrum in vitro activity against multidrug-resistant and extensively drug-resistant bacteria, including ESBL, carbapenem- and colistin-resistant clinical isolates. The antibiotic induces a 3–4 log reduction in bacterial burden in mouse models of peritonitis, pneumonia and urinary tract infection. Cytotoxicity and haemolysis of the progenitor peptide is ameliorated with AA139, and the ‘no observable adverse effect level’ (NOAEL) dose in mice is ~10-fold greater than the dose generally required for efficacy in the infection models.
Contribution of land use to the interannual variability of the land carbon cycle
Authors: Yue Chao , Ciais Philippe , Houghton Richard A. , Nassikas Alexander A. 
Published: June 2020

AbstractUnderstanding the driving mechanisms of the interannual variability (IAV) of the net land carbon balance (Snet) is important to predict future climate–carbon cycle feedbacks. Past studies showed that the IAV of Snet was correlated with tropical climate variation and controlled by semiarid vegetation. But today’s land ecosystems are also under extensive human land use and management. Here, we report a previously hidden role of land use in driving the IAV of Snet by using an improved biosphere model. We found that managed land accounted for 30–45% of the IAV of Snet over 1959–2015, while the contribution of intact land is reduced by more than half compared with previous assessments of the global carbon budget. Given the importance of land use in modulating future land climate–carbon cycle feedbacks, climate mitigation efforts should strive to reduce land-use emissions and enhance the climate resilience of carbon sinks over managed land.
Widespread transcript shortening through alternative polyadenylation in secretory cell differentiation
Authors: Cheng Larry C. , Zheng Dinghai , Baljinnyam Erdene , Sun Fangzheng , Ogami Koichi , Yeung Percy Luk , Hoque Mainul , Lu Chi-Wei , Manley James L. , Tian Bin 
Published: June 2020

AbstractMost eukaryotic genes produce alternative polyadenylation (APA) isoforms. Here we report that, unlike previously characterized cell lineages, differentiation of syncytiotrophoblast (SCT), a cell type critical for hormone production and secretion during pregnancy, elicits widespread transcript shortening through APA in 3’UTRs and in introns. This global APA change is observed in multiple in vitro trophoblast differentiation models, and in single cells from placentas at different stages of pregnancy. Strikingly, the transcript shortening is unrelated to cell proliferation, a feature previously associated with APA control, but instead accompanies increased secretory functions. We show that 3’UTR shortening leads to transcripts with higher mRNA stability, which augments transcriptional activation, especially for genes involved in secretion. Moreover, this mechanism, named secretion-coupled APA (SCAP), is also executed in B cell differentiation to plasma cells. Together, our data indicate that SCAP tailors the transcriptome during formation of secretory cells, boosting their protein production and secretion capacity.
The NIN transcription factor coordinates CEP and CLE signaling peptides that regulate nodulation antagonistically
Authors: Laffont Carole , Ivanovici Ariel , Gautrat Pierre , Brault Mathias , Djordjevic Michael Anthony , Frugier Florian 
Published: June 2020

Abstract
Legumes tightly regulate nodule number to balance the cost of supporting symbiotic rhizobia with the benefits of nitrogen fixation. C-terminally Encoded Peptides (CEPs) and CLAVATA3-like (CLE) peptides positively and negatively regulate nodulation, respectively, through independent systemic pathways, but how these regulations are coordinated remains unknown. Here, we show that rhizobia, Nod Factors, and cytokinins induce a symbiosis-specific CEP gene, MtCEP7, which positively regulates rhizobial infection. Via grafting and split root studies, we reveal that MtCEP7 increases nodule number systemically through the MtCRA2 receptor. MtCEP7 and MtCLE13 expression in rhizobia-inoculated roots rely on the MtCRE1 cytokinin receptor and on the MtNIN transcription factor. MtNIN binds and transactivates Mt
CEP7 and MtCLE13, and a NIN Binding Site (NBS) identified within the proximal MtCEP7 promoter is required for its symbiotic activation. Overall, these results demonstrate that a cytokinin-MtCRE1-MtNIN regulatory module coordinates the expression of two antagonistic, symbiosis-related, peptide hormones from different families to fine-tune nodule number.
Rad9/53BP1 promotes DNA repair via crossover recombination by limiting the Sgs1 and Mph1 helicases
Authors: Ferrari Matteo , Rawal Chetan C. , Lodovichi Samuele , Vietri Maria Y. , Pellicioli Achille 
Published: June 2020

AbstractThe DNA damage checkpoint (DDC) is often robustly activated during the homologous recombination (HR) repair of DNA double strand breaks (DSBs). DDC activation controls several HR repair factors by phosphorylation, preventing premature segregation of entangled chromosomes formed during HR repair. The DDC mediator 53BP1/Rad9 limits the nucleolytic processing (resection) of a DSB, controlling the formation of the 3′ single-stranded DNA (ssDNA) filament needed for recombination, from yeast to human. Here we show that Rad9 promotes stable annealing between the recombinogenic filament and the donor template in yeast, limiting strand rejection by the Sgs1 and Mph1 helicases. This regulation allows repair by long tract gene conversion, crossover recombination and break-induced replication (BIR), only after DDC activation. These findings shed light on how cells couple DDC with the choice and effectiveness of HR sub-pathways, with implications for genome instability and cancer.
Comparative targeting analysis of KLF1, BCL11A, and HBG1/2 in CD34+ HSPCs by CRISPR/Cas9 for the induction of fetal hemoglobin
Authors: Lamsfus-Calle Andrés , Daniel-Moreno Alberto , Antony Justin S. , Epting Thomas , Heumos Lukas , Baskaran Praveen , Admard Jakob , Casadei Nicolas , Latifi Ngadhnjim , Siegmund Darina M. , Kormann Michael S. D. , Handgretinger Rupert , Mezger Markus 
Published: June 2020

Abstractβ-hemoglobinopathies are caused by abnormal or absent production of hemoglobin in the blood due to mutations in the β-globin gene (HBB). Imbalanced expression of adult hemoglobin (HbA) induces strong anemia in patients suffering from the disease. However, individuals with natural-occurring mutations in the HBB cluster or related genes, compensate this disparity through γ-globin expression and subsequent fetal hemoglobin (HbF) production. Several preclinical and clinical studies have been performed in order to induce HbF by knocking-down genes involved in HbF repression (KLF1 and BCL11A) or disrupting the binding sites of several transcription factors in the γ-globin gene (HBG1/2). In this study, we thoroughly compared the different CRISPR/Cas9 gene-disruption strategies by gene editing analysis and assessed their safety profile by RNA-seq and GUIDE-seq. All approaches reached therapeutic levels of HbF after gene editing and showed similar gene expression to the control sample, while no significant off-targets were detected by GUIDE-seq. Likewise, all three gene editing platforms were established in the GMP-grade CliniMACS Prodigy, achieving similar outcome to preclinical devices. Based on this gene editing comparative analysis, we concluded that BCL11A is the most clinically relevant approach while HBG1/2 could represent a promising alternative for the treatment of β-hemoglobinopathies.
Multi-Domain Negative Capacitance Effects in Metal-Ferroelectric-Insulator-Semiconductor/Metal Stacks: A Phase-field Simulation Based Study
Authors: Saha Atanu K. , Gupta Sumeet K. 
Published: June 2020

AbstractWe analyze the ferroelectric domain-wall induced negative capacitance (NC) effect in Metal-FE-Insulator-Metal (MFIM) and Metal-FE-Insulator-Semiconductor (MFIS) stacks through phase-field simulations by self-consistently solving time-dependent Ginzburg Landau equation, Poisson’s equation and semiconductor charge equations. Considering Hf0.5Zr0.5O2 as the ferroelectric material, we study 180° ferroelectric domain formation in MFIM and MFIS stacks and their polarization switching characteristics. Our analysis signifies that the applied voltage-induced polarization switching via soft domain-wall displacement exhibits non-hysteretic characteristics. In addition, the change in domain-wall energy, due to domain-wall displacement, exhibits a long-range interaction and thus, leads to a non-homogeneous effective local negative permittivity in the ferroelectric. Such effects yield an average negative effective permittivity that further provides an enhanced charge response in the MFIM stack, compared to Metal-Insulator-Metal. Furthermore, we show that the domain-wall induced negative effective permittivity is not an intrinsic property of the ferroelectric material and therefore, is dependent on its thickness, the gradient energy coefficient and the in-plane permittivity of the underlying insulator. Similar to the MFIM stack, MFIS stack also exhibits an enhanced charge/capacitance response compared to Metal-Oxide-Semiconductor (MOS) capacitor. Simultaneously, the multi-domain state of the ferroelectric induces non-homogeneous potential in the underlying insulator and semiconductor layer. At low applied voltages, such non-homogeneity leads to the co-existence of electrons and holes in an undoped semiconductor. In addition, we show that with the ferroelectric layer being in the 180° multi-domain state, the minimum potential at the ferroelectric-dielectric interface and hence, the minimum surface potential in the semiconductor, does not exceed the applied voltage (in-spite of the local differential amplification and charge enhancement).
The hydrolytic water molecule of Class A β-lactamase relies on the acyl-enzyme intermediate ES* for proper coordination and catalysis
Authors: He Yunjiao , Lei Jinping , Pan Xuehua , Huang Xuhui , Zhao Yanxiang 
Published: June 2020

AbstractSerine-based β-lactamases of Class A, C and D all rely on a key water molecule to hydrolyze and inactivate β-lactam antibiotics. This process involves two conserved catalytic steps. In the first acylation step, the β-lactam antibiotic forms an acyl-enzyme intermediate (ES*) with the catalytic serine residue. In the second deacylation step, an activated water molecule serves as nucleophile (WAT_Nu) to attack ES* and release the inactivated β-lactam. The coordination and activation of WAT_Nu is not fully understood. Using time-resolved x-ray crystallography and QM/MM simulations, we analyzed three intermediate structures of Class A β-lactamase PenP as it slowly hydrolyzed cephaloridine. WAT_Nu is centrally located in the apo structure but becomes slightly displaced away by ES* in the post-acylation structure. In the deacylation structure, WAT_Nu moves back and is positioned along the Bürgi–Dunitz trajectory with favorable energetic profile to attack ES*. Unexpectedly, WAT_Nu is also found to adopt a catalytically incompetent conformation in the deacylation structure forming a hydrogen bond with ES*. Our results reveal that ES* plays a significant role in coordinating and activating WAT_Nu through subtle yet distinct interactions at different stages of the catalytic process. These interactions may serve as potential targets to circumvent β-lactamase-mediated antibiotic resistance.
Amyloid precursor protein-b facilitates cell adhesion during early development in zebrafish
Authors: Banote Rakesh Kumar , Chebli Jasmine , Şatır Tuğçe Munise , Varshney Gaurav K. , Camacho Rafael , Ledin Johan , Burgess Shawn M. , Abramsson Alexandra , Zetterberg Henrik 
Published: June 2020

AbstractUnderstanding the biological function of amyloid beta (Aβ) precursor protein (APP) beyond its role in Alzheimer’s disease is emerging. Yet, its function during embryonic development is poorly understood. The zebrafish APP orthologue, Appb, is strongly expressed during early development but thus far has only been studied via morpholino-mediated knockdown. Zebrafish enables analysis of cellular processes in an ontogenic context, which is limited in many other vertebrates. We characterized zebrafish carrying a homozygous mutation that introduces a premature stop in exon 2 of the appb gene. We report that appb mutants are significantly smaller until 2 dpf and display perturbed enveloping layer (EVL) integrity and cell protrusions at the blastula stage. Moreover, appb mutants surviving beyond 48 hpf exhibited no behavioral defects at 6 dpf and developed into healthy and fertile adults. The expression of the app family member, appa, was also found to be altered in appb mutants. Taken together, we show that appb is involved in the initial development of zebrafish by supporting the integrity of the EVL, likely by mediating cell adhesion properties. The loss of Appb might then be compensated for by other app family members to maintain normal development.
Evidence of Inverse Hall-Petch Behavior and Low Friction and Wear in High Entropy Alloys
Authors: Jones Morgan R. , Nation Brendan L. , Wellington-Johnson John A. , Curry John F. , Kustas Andrew B. , Lu Ping , Chandross Michael , Argibay Nicolas 
Published: June 2020

AbstractWe present evidence of inverse Hall-Petch behavior for a single-phase high entropy alloy (CoCrFeMnNi) in ultra-high vacuum and show that it is associated with low friction coefficients (~0.3). Grain size measurements by STEM validate a recently proposed dynamic amorphization model that accurately predicts grain size-dependent shear strength in the inverse Hall-Petch regime. Wear rates in the initially soft (coarse grained) material were shown to be remarkably low (~10–6mm3/N-m), the lowest for any HEA tested in an inert environment where oxidation and the formation of mixed metal-oxide films is mitigated. The combined high wear resistance and low friction are linked to the formation of an ultra-nanocrystalline near-surface layer. The dynamic amorphization model was also used to predict an average high angle grain boundary energy (0.87 J/m2). This value was used to explain cavitation-induced nanoporosity found in the highly deformed surface layer, a phenomenon that has been linked to superplasticity.