bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling Magma System Evolution During 2006–2007 Volcanic Unrest of Atka Volcanic Center, Alaska
Authors: Zhan Yan , Gregg Patricia M. , Lu Zhong
Published: February 2021

Surface deformation and seismicity provide critical information to understand the dynamics of volcanic unrest. During 2006–2007, >80 mm/yr uplift was observed by interferometric synthetic aperture radar (InSAR) at the central Atka volcanic center, Alaska, coinciding with an increasing seismicity rate. On November 25, 2006, a phreatic eruption occurred at the Korovin volcanic vent, 5‐km north of the central Atka, following the drainage of its crater lake a month prior to the eruption. The InSAR data are assimilated into three‐dimensional finite element models using the Ensemble Kalman Filter to investigate: (1) the pressure source creating the surface deformation; (2) the triggering of the volcano‐tectonic (VT) earthquakes in the Atka volcanic center; and (3) the triggering of the phreatic eruption at Korovin. The models show that the pressure source required to create the surface deformation is a NE‐tilted, oblate ellipsoid, which rotated from steep to gentle dipping from June to November 2006 before the eruption. The modeled dilatancy in a pre‐existing weak zone, coinciding with the Amlia‐Amukta fault, driven by the pressure source has a spatial and temporal correlation with the evolution of the VT earthquakes during the unrest. The fault dilatancy may have increased the connected porosity and permeability of the fault zone allowing fluid injection which triggered the observed seismicity. In addition, the dilatated fault may have increased the fluid capacity of the fault zone by ∼105 m3, causing the discharge of the crater lake at Korovin. Consequently, the phreatic eruption of the Korovin volcano may have been triggered.
Effects of Porosity and Water Saturation on the Yield Surface of Upper Cretaceous Reservoir Chalks From the Danish North Sea
Authors: Amour F. , Christensen H. F. , Hajiabadi M. R. , Nick H. M.
Published: February 2021

The locus and shape of the yield surface of chalk in the stress space represent key input parameters in geomechanical models, as it dictates the onset and amount of plastic deformation. The study aims at reconstructing for the first time the initial end cap and shear failure line of intact reservoir chalk in plots of mean‐deviatoric stress versus porosity. One hundred and thirty‐seven stress‐strain measurements describe the effects of initial porosity between 30% and 45% and initial water saturation on the yield surface in order to cover a wide spectrum of reservoir rocks. The physico‐chemical processes taking place at pore collapse under oil‐ and water‐saturated conditions are discussed. The experimental data collected from previous works quantify the hardening and softening effects observed with decreasing porosity and increasing water saturation. The results also indicate that the stress interval characterizing the elastic to elasto‐plastic transition zone and the curvature of the end cap are dependent on porosity and quartz content. These observed trends suggest changes in the sequence of local failures acting in the rock matrix at the onset of compaction. Comparisons with previous studies suggest that the water weakening effect differs between outcrop and reservoir chalk likely due to a change in mineralogy. A yield function is proposed to build the yield surface and to capture the porosity‐dependent change in the shape of end cap and the water weakening effect. The outcomes provide key input data describing the mechanical behavior and properties of chalk under laboratory conditions required for compaction simulation studies.
New Evidence for the Fluctuation Characteristics of Intradecadal Periodic Signals in Length‐Of‐Day Variation
Authors: Ding Hao , An Yachong , Shen Wenbin
Published: February 2021

The intradecadal fluctuations in the length‐of‐day variation (∆LOD) are considered likely to play an important role in core motions. Two intradecadal oscillations, with ∼5.9  and ∼8.5 years periods (referred to as SYO and EYO, respectively), have been detected in previous studies. However, whether the SYO and the EYO have exhibited stable damping trends since 1962 and whether geomagnetic jerks are possible excitation sources for the SYO/EYO are still debated. In this study, based on different methods and different ∆LOD records with different time spans, we showed robust evidence to prove that the SYO and the EYO have had no stable damping trends since 1962. We also found that there may be a ∼7.6 years signal, but given that its average amplitude is too small, further confirmations are needed in the future. After confirming that the jerks have no special consistency with the peaks/valleys of the EYO/SYO, we further used a deconvolution process and confirmed that the geomagnetic jerks seem to be related to sudden changes in the SYO/EYO time series and their excitation series. Thus we finally suggest that jerks are possible excitation sources of the SYO/EYO. After using a deconvolution process, we estimate that the periodPand quality factorQof the SYO and the EYO are [P = 5.85 ± 0.06 years,Q ≥ 180] and [P = 8.45 ± 0.17 years,Q ≥ 350], respectively.
High‐Pressure Deformation of Iron–Nickel–Silicon Alloys and Implications for Earth’s Inner Core
Authors: Brennan Matthew C. , Fischer Rebecca A. , Couper Samantha , Miyagi Lowell , Antonangeli Daniele , Morard Guillaume
Published: February 2021

Earth’s inner core exhibits strong seismic anisotropy, often attributed to the alignment of hexagonal close‐packed iron (hcp‐Fe) alloy crystallites with the Earth’s poles. How this alignment developed depends on material properties of the alloy and is important to our understanding of the core’s crystallization history and active geodynamical forcing. Previous studies suggested that hcp‐Fe is weak under deep Earth conditions but did not investigate the effects of the lighter elements known to be part of the inner core alloy. Here, we present results from radial X‐ray diffraction experiments in a diamond anvil cell that constrain the strength and deformation properties of iron‐nickel‐silicon (Fe–Ni–Si) alloys up to 60 GPa. We also show the results of laser heating to 1650 K to evaluate the effect of temperature. Observed alloy textures suggest different relative activities of the various hcp deformation mechanisms compared to pure Fe, but these textures could still account for the theorized polar alignment. Fe–Ni–Si alloys are mechanically stronger than Fe and Fe–Ni; extrapolated to inner core conditions, Si‐bearing alloys may be more than an order of magnitude stronger. This enhanced strength proportionally reduces the effectivity of dislocation creep as a deformation mechanism, which may suggest that texture developed during crystallization rather than as the result of postsolidification plastic flow.
Regional‐Scale, Sector‐Specific Evaluation of Global CO2 Inversion Models Using Aircraft Data From the ACT‐America Project
Authors: Gaudet B. J. , Davis K. J. , Pal S. , Jacobson A. R. , Schuh A. , Lauvaux T. , Feng S. , Browell E. V.
Published: February 2021

We use 148 airborne vertical profiles of CO2 for frontal cases from the summer 2016 Atmospheric Carbon and Transport—America (ACT‐America) campaign to evaluate the skill of 10 global CO2 in situ inversion models from the version 7 Orbiting Carbon Observatory–2 (OCO‐2) Model Intercomparison Project (MIP). Model errors (model posterior—observed CO2 dry air mole fractions) were categorized by region (Mid‐Atlantic, Midwest, and South), frontal sector (warm or cold), and transport model (predominantly Tracer Model 5 (TM5) and Goddard Earth Observing System—Chemistry [GEOS‐Chem]). All inversions assimilated the same CO2 observations. Overall, the median inversion profiles reproduce the general structures of the observations (enhanced/depleted low‐level CO2 in warm/cold sectors), but 1) they underestimate the magnitude of the warm/cold sector mole fraction difference, and 2) the spread among individual inversions can be quite large (>5 ppm). Uniquely in the Mid‐Atlantic, inversion biases segregated according to atmospheric transport model, where TM5 inversions biases were −3 to −4 ppm in warm sectors, while those of GEOS‐Chem were +2 to +3 ppm in cold sectors. The large spread among the mean posterior CO2 profiles is not explained by the different atmospheric transport models. These results show that the inversion systems themselves are the dominant cause of this spread, and that the aircraft campaign data are clearly able to identify these large biases. Future controlled experiments should identify which inversions best reproduce mid‐latitude CO2 mole fractions, and how inversion system components are linked to system performance.
Constraining Martian Regolith and Vortex Parameters From Combined Seismic and Meteorological Measurements
Authors: Murdoch N. , Spiga A. , Lorenz R. , Garcia R. F. , Perrin C. , Widmer‐Schnidrig R. , Rodriguez S. , Compaire N. , Warner N. H. , Mimoun D. , Banfield D. , Lognonné P. , Banerdt W. B.
Published: February 2021

The InSight mission landed on Mars in November 2018 and has since observed multiple convective vortices with both the high performance barometer and the low‐noise seismometer SEIS that has unprecedented sensitivity. Here, we present a new method that uses the simultaneous pressure and seismic measurements of convective vortices to place constraints on the elastic properties of the Martian subsurface and the Martian vortex properties, while also allowing a reconstruction of the convective vortex trajectories. From data filtered in the (0.02–0.3 Hz) frequency band, we estimate that the mean value ofη(η = E/[1 − ν2], whereEis the Young's modulus andνis the Poisson's ratio) of the Martian ground in the region around SEIS is 239 ± 140 MPa. In addition, we suggest that the previously reported paucity of vortex seismic observations to the west of InSight may be due to the fact that the ground is harder to the west than to the east, consistent with geomorphological surface interpretations.
Relationship Between Leaf Maximum Carboxylation Rate and Chlorophyll Content Preserved Across 13 Species
Authors: Qian X. , Liu L. , Croft H. , Chen J.
Published: February 2021

The leaf maximum carboxylation rate (Vcmax) is a crucial parameter in determining the photosynthetic capacity of plants. Providing accurate estimates of leaf Vcmax, that cover large geographic areas and incorporate plant seasonality is central to correctly predicting carbon fluxes within the terrestrial global carbon cycle. Chlorophyll, as the main photon‐harvesting molecule in leaves, is closely linked to plant photosynthesis. However, how the nature of the relationship between the leaf maximum carboxylation rate (scaled to 25°C; Vcmax,25) and leaf chlorophyll content varies according to plant type is uncertain. In this study, we investigate whether a universal and stable relationship exists between leaf Vcmax,25 and leaf chlorophyll content across different plant types and verify it using field experiments. Measurements of leaf chlorophyll content (Chl) and CO2 response curves were made on 283 crop, shrub, tree, and vegetable leaves, across 13 species, in China and southern Ontario, Canada. A strong relationship was found between the leaf Vcmax,25 and chlorophyll content across different plant types (R2 = 0.65, p < 0.001). Cross‐validation showed that the model performs well, producing an RMSE value of 15.4 μmol m−2 s−1. The results confirm that leaf chlorophyll content can be a reliable proxy for estimating Vcmax,25, opening the door to accurate, spatially continuous estimates of Vcmax,25 at the global scale.
Loess‐Like Dust Appearance at 40 Ma in Central China
Authors: Meijer Niels , Dupont‐Nivet Guillaume , Barbolini Natasha , Woutersen Amber , Rohrmann Alexander , Zhang Yang , Liu Xiang‐Jun , Licht Alexis , Abels Hemmo A. , Hoorn Carina , Tjallingii Rik , Andermann Christoff , Dietze Michael , Nowaczyk Norbert
Published: February 2021

Asian mineral dust has been studied extensively for its role in affecting regional‐to global‐scale climate and for its deposits, which enable reconstructing Asian atmospheric circulation in the past. However, the timing and origin of the dust deposits remain debated. Numerous loess records have been reported across the Asian continent with ages varying from the Miocene to the Eocene and linked to various mechanisms including global cooling, Tibetan Plateau uplift and retreat of the inland proto‐Paratethys Sea. Here, we study the Eocene terrestrial mudrocks of the Xining Basin in central China and use nonparametric end‐member analysis of grain‐size distributions to identify a loess‐like dust component appearing in the record at 40 Ma. This is coeval with the onset of high‐latitude orbital cycles and a shift to predominant steppe‐desert vegetation as recognized by previous studies in the same record. Furthermore, we derive wind directions from eolian dune deposits which suggest northwesterly winds, similar to the modern‐day winter monsoon which is driven by a high pressure system developing over Siberia. We propose that the observed shifts at 40 Ma reflect the onset of the Siberian High interacting with westerly derived moisture at obliquity timescales and promoting dust storms and aridification in central China. The timing suggests that the onset may have been triggered by increased continentality due to the retreating proto‐Paratethys Sea.
A Review on Different Techniques of Mutual Coupling Reduction Between Elements of Any MIMO Antenna. Part 1: DGSs and Parasitic Structures
Authors: Kumar Amit , Ansari Abdul Quaiyum , Kanaujia Binod Kumar , Kishor Jugul , Matekovits Ladislau
Published: February 2021

This two‐part article presents a review of different techniques of mutual coupling (MC) reduction. MC is a major issue when an array of antennas is densely packed. When the separation between the antennas is <λ0/2, i.e., half of the free‐space wavelength, the antenna parameters suffer from the surface wave, and the space wave coupling effect between the antenna elements. To reduce the MC influence, several techniques have been discussed in the scientific literature. This part of the review paper will discuss strategies: antenna placement and orientation approach, Defected Ground Structures (DGSs), slots/slits‐etching approach, protruding ground stub structures, and parasitic elements/structures. This article concludes with feasibility, applications, and comparison of the techniques mentioned above. Simultaneously, the applications and possibilities of the remaining methods are discussed in part two of the article.
Geological Surveys Unite to Improve Critical Mineral Security
Authors: Emsbo Poul , Lawley Christopher , Czarnota Karol
Published: February 2021

A three-nation consortium is pooling geological expertise and resources to address vulnerabilities in supplies of these crucial natural resources.
Loss-induced nonreciprocity
Authors: Huang Xinyao , Lu Cuicui , Liang Chao , Tao Honggeng , Liu Yong-Chun
Published: February 2021

Nonreciprocity is important in both optical information processing and topological photonics studies. Conventional principles for realizing nonreciprocity rely on magnetic fields, spatiotemporal modulation, or nonlinearity. Here we propose a generic principle for generating nonreciprocity by taking advantage of energy loss, which is usually regarded as harmful. The loss in a resonance mode induces a phase lag, which is independent of the energy transmission direction. When multichannel lossy resonance modes are combined, the resulting interference gives rise to nonreciprocity, with different coupling strengths for the forward and backward directions, and unidirectional energy transmission. This study opens a new avenue for the design of nonreciprocal devices without stringent requirements.
How machine-learning recommendations influence clinician treatment selections: the example of antidepressant selection
Authors: Jacobs Maia , Pradier Melanie F. , McCoy Thomas H. , Perlis Roy H. , Doshi-Velez Finale , Gajos Krzysztof Z.
Published: February 2021

Decision support systems embodying machine learning models offer the promise of an improved standard of care for major depressive disorder, but little is known about how clinicians’ treatment decisions will be influenced by machine learning recommendations and explanations. We used a within-subject factorial experiment to present 220 clinicians with patient vignettes, each with or without a machine-learning (ML) recommendation and one of the multiple forms of explanation. We found that interacting with ML recommendations did not significantly improve clinicians’ treatment selection accuracy, assessed as concordance with expert psychopharmacologist consensus, compared to baseline scenarios in which clinicians made treatment decisions independently. Interacting with incorrect recommendations paired with explanations that included limited but easily interpretable information did lead to a significant reduction in treatment selection accuracy compared to baseline questions. These results suggest that incorrect ML recommendations may adversely impact clinician treatment selections and that explanations are insufficient for addressing overreliance on imperfect ML algorithms. More generally, our findings challenge the common assumption that clinicians interacting with ML tools will perform better than either clinicians or ML algorithms individually.
Metabolomics reveals biomarkers of opioid use disorder
Authors: Ghanbari Reza , Li Yuanyuan , Pathmasiri Wimal , McRitchie Susan , Etemadi Arash , Pollock Jonathan D. , Poustchi Hossein , Rahimi-Movaghar Afarin , Amin-Esmaeili Masoumeh , Roshandel Gholamreza , Shayanrad Amaneh , Abaei Behrouz , Malekzadeh Reza , Sumner Susan C. J.
Published: February 2021

Opioid use disorder (OUD) is diagnosed using the qualitative criteria defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Diagnostic biomarkers for OUD do not currently exist. Our study focused on developing objective biological markers to differentiate chronic opiate users with OUD from chronic opiate users without OUD. Using biospecimens from the Golestan Cohort Study, we compared the metabolomics profiles of high opium users who were diagnosed as OUD positive with high opium users who were diagnosed as OUD negative. High opium use was defined as maximum weekly opium usage greater than or equal to the median usage (2.4 g per week), and OUD was defined as having 2 or more DSM-5 criteria in any 12-month period. Among the 218 high opium users in this study, 80 were diagnosed as OUD negative, while 138 were diagnosed as OUD positive. Seven hundred and twelve peaks differentiated high opium users diagnosed as OUD positive from high opium users diagnosed as OUD negative. Stepwise logistic regression modeling of subject characteristics data together with the 712 differentiating peaks revealed a signature that is 95% predictive of an OUD positive diagnosis, a significant (p < 0.0001) improvement over a 63% accurate prediction based on subject characteristic data for these samples. These results suggest that a metabolic profile can be used to predict an OUD positive diagnosis.
Functional network alterations differently associated with suicidal ideas and acts in depressed patients: an indirect support to the transition model
Authors: Wagner Gerd , Li Meng , Sacchet Matthew D. , Richard-Devantoy Stéphane , Turecki Gustavo , Bär Karl-Jürgen , Gotlib Ian H. , Walter Martin , Jollant Fabrice
Published: February 2021

The transition from suicidal ideas to a suicide act is an important topic of research for the identification of those patients at risk of acting out. We investigated here whether specific brain activity and connectivity measures at rest may be differently associated with suicidal thoughts and behaviors. A large sample of acutely depressed patients with major depressive disorder was recruited in three different centers (Montreal/Canada, Stanford/USA, and Jena/Germany), covering four different phenotypes: patients with a past history of suicide attempt (n = 53), patients with current suicidal ideas but no past history of suicide attempt (n = 40), patients without current suicidal ideation nor past suicide attempts (n = 42), and healthy comparison subjects (n = 107). 3-T resting-state functional magnetic resonance imaging (fMRI) measures of the amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) were obtained and examined in a whole-brain data-driven analysis. Past suicide attempt was associated with a double cortico-subcortical dissociation in ALFF values. Decreased ALFF and DC values mainly in a frontoparietal network and increased ALFF values in some subcortical regions (hippocampus and thalamus) distinguished suicide attempters from suicide ideators, patient controls, and healthy controls. No clear neural differences were identified in relation to suicidal ideas. Suicide attempters appear to be a distinct subgroup of patients with widespread brain alterations in functional activity and connectivity that could represent factors of vulnerability. Our results also indirectly support at the neurobiological level the relevance of the transition model described at the psychological and clinical levels. The brain bases of suicidal ideas occurrence in depressed individuals needs further investigations.
Cortical thinning and associated connectivity changes in patients with anorexia nervosa
Authors: de la Cruz Feliberto , Schumann Andy , Suttkus Stefanie , Helbing Nadin , Zopf Regine , Bär Karl-Jürgen
Published: February 2021

Structural brain abnormalities are a consistent finding in anorexia nervosa (AN) and proposed as a state biomarker of the disorder. Yet little is known about how regional structural changes affect intrinsic resting-state functional brain connectivity (rsFC). Using a cross-sectional, multimodal imaging approach, we investigated the association between regional cortical thickness abnormalities and rsFC in AN. Twenty-two acute AN patients and twenty-six age- and gender-matched healthy controls underwent a resting-state functional magnetic resonance imaging scan and cognitive tests. We performed group comparisons of whole-brain cortical thickness, seed-based rsFC, and network-based statistical (NBS) analyses. AN patients showed cortical thinning in the precuneus and inferior parietal lobules, regions involved in visuospatial memory and imagery. Cortical thickness in the precuneus correlated with nutritional state and cognitive functions in AN, strengthening the evidence for a critical role of this region in the disorder. Cortical thinning was accompanied by functional connectivity reductions in major brain networks, namely default mode, sensorimotor and visual networks. Similar to the seed-based approach, the NBS analysis revealed a single network of reduced functional connectivity in patients, comprising mainly sensorimotor- occipital regions. Our findings provide evidence that structural and functional brain abnormalities in AN are confined to specific regions and networks involved in visuospatial and somatosensory processing. We show that structural changes of the precuneus are linked to nutritional and functional states in AN, and future longitudinal research should assess how precuneus changes might be related to the evolution of the disorder.
Inhibition of mPGES-1 attenuates efficient resolution of acute inflammation by enhancing CX3CL1 expression
Authors: Rappl Peter , Rösser Silvia , Maul Patrick , Bauer Rebekka , Huard Arnaud , Schreiber Yannick , Thomas Dominique , Geisslinger Gerd , Jakobsson Per-Johan , Weigert Andreas , Brüne Bernhard , Schmid Tobias
Published: February 2021

Despite the progress to understand inflammatory reactions, mechanisms causing their resolution remain poorly understood. Prostanoids, especially prostaglandin E2(PGE2), are well-characterized mediators of inflammation. PGE2is produced in an inducible manner in macrophages (Mϕ) by microsomal PGE2-synthase-1 (mPGES-1), with the notion that it also conveys pro-resolving properties. We aimed to characterize the role of mPGES-1 during resolution of acute, zymosan-induced peritonitis. Experimentally, we applied the mPGES-1 inhibitor compound III (CIII) once the inflammatory response was established and confirmed its potent PGE2-blocking efficacy. mPGES-1 inhibition resulted in an incomplete removal of neutrophils and a concomitant increase in monocytes and Mϕ during the resolution process. The mRNA-seq analysis identified enhanced C-X3-C motif receptor 1 (CX3CR1) expression in resident and infiltrating Mϕ upon mPGES-1 inhibition. Besides elevatedCx3cr1expression, its ligand CX3CL1 was enriched in the peritoneal lavage of the mice, produced by epithelial cells upon mPGES-1 inhibition. CX3CL1 not only increased adhesion and survival of Mϕ but its neutralization also completely reversed elevated inflammatory cell numbers, thereby normalizing the cellular, peritoneal composition during resolution. Our data suggest that mPGES-1-derived PGE2contributes to the resolution of inflammation by preventing CX3CL1-mediated retention of activated myeloid cells at sites of injury.
Overexpressed P75CUX1 promotes EMT in glioma infiltration by activating β-catenin
Authors: Xu Anqi , Wang Xizhao , Luo Jie , Zhou Mingfeng , Yi Renhui , Huang Tengyue , Lin Jie , Wu Zhiyong , Xie Cheng , Ding Shengfeng , Zeng Yu , Song Ye
Published: February 2021

The homeobox protein cut-like 1 (CUX1) comprises three isoforms and has been shown to be involved in the development of various types of malignancies. However, the expression and role of the CUX1 isoforms in glioma remain unclear. Herein, we first identified that P75CUX1 isoform exhibited consistent expression among three isoforms in glioma with specifically designed antibodies to identify all CUX1 isoforms. Moreover, a significantly higher expression of P75CUX1 was found in glioma compared with non-tumor brain (NB) tissues, analyzed with western blot and immunohistochemistry, and the expression level of P75CUX1 was positively associated with tumor grade. In addition, Kaplan–Meier survival analysis indicated that P75CUX1 could serve as an independent prognostic indicator to identify glioma patients with poor overall survival. Furthermore, CUX1 knockdown suppressed migration and invasion of glioma cells both in vitro and in vivo. Mechanistically, this study found that P75CUX1 regulated epithelial–mesenchymal transition (EMT) process mediated via β-catenin, and CUX1/β-catenin/EMT is a novel signaling cascade mediating the infiltration of glioma. Besides, CUX1 was verified to promote the progression of glioma via multiple other signaling pathways, such as Hippo and PI3K/AKT. In conclusion, we suggested that P75CUX1 could serve as a potential prognostic indicator as well as a novel treatment target in malignant glioma.
ABIN-1 is a key regulator in RIPK1-dependent apoptosis (RDA) and necroptosis, and ABIN-1 deficiency potentiates necroptosis-based cancer therapy in colorectal cancer
Authors: Cai Jiali , Hu Die , Sakya Judy , Sun Tao , Wang Daoyong , Wang Lin , Mao Xiaohua , Su Zhenyi
Published: February 2021

ABIN-1, also called TNIP1, is an ubiquitin-binding protein that serves an important role in suppressing RIPK1-independent apoptosis, necroptosis, and NF-κB activation. However, the involvement of ABIN-1 in the regulation of RIPK1-dependent apoptosis (RDA) is unknown. In this study, we found that poly(I:C) + TAK1 inhibitor 5Z-7-oxozeaenol (P5) concurrently induces RDA and necroptosis in Abin-1−/−, but not in Abin-1+/+ mouse embryonic fibroblasts (MEFs). Upon P5 stimulation, cells initially die by necroptosis and subsequently by RDA. Furthermore, we explored the therapeutic effect of ABIN-1 deficiency in necroptosis-based cancer therapy in colorectal cancer (CRC). We found that poly(I:C) + 5Z-7-oxozeaenol + IDN-6556 (P5I) yields a robust pro-necroptosis response, and ABIN-1 deficiency additionally enhances this P5I-induced necroptosis. Moreover, phase I/II cIAP inhibitor birinapant with clinical caspase inhibitor IDN-6556 (BI) alone and 5-fluorouracil with IDN-6556 (FI) alone are sufficient to induce necroptotic cell death in CRC cells by promoting auto-secretion of tumor necrosis factor (TNF); ABIN-1 deficiency amplifies the BI- or FI-induced necroptosis. Two independent xenograft experiments using HT-29 or COLO205 cells show that both BI and P5I remarkably inhibit tumor growth via necroptosis activation. For poly(I:C)-induced cell death, the sensitizing effect of ABIN-1 deficiency on cell death may be attributed to increased expression of TLR3. In TNF-induced necroptosis, ABIN-1 deficiency increases TNF-induced RIPK1 polyubiquitination by reducing the recruitment of ubiquitin-editing enzyme A20 to the TNFR1 signaling complex and induces more TNF secretion in CRC cells upon pro-necroptosis stimulation. With this combined data, ABIN-1 deficiency promotes greater sensitization of CRC cells to necroptosis.
The novel ZEB1-upregulated protein PRTG induced by Helicobacter pylori infection promotes gastric carcinogenesis through the cGMP/PKG signaling pathway
Authors: Xiang Tian , Yuan Chunhui , Guo Xia , Wang Honghao , Cai Qinzhen , Xiang Yun , Luo Wei , Liu Gao
Published: February 2021

Helicobacter pylori (H. pylori) is listed as a class I carcinogen in human gastric cancer; however, the underlying mechanisms are poorly understood. In this study, we identified Protogenin (PRTG) was upregulated in both gastric cancer tissues and H. pylori-infected tissues by analyzing dysregulated genes in TCGA and GEO databases. Importantly, upregulated PRTG predicted poor prognosis of gastric cancer patients and integrative analysis revealed that PRTG served as an oncogenic protein in gastric cancer and was required for H. pylori-mediated tumorigenic activities in in vitro cellular and in vivo tumor-bearing mouse models. Mechanistically, H. pylori infection enhanced PRTG expression by promoting transcriptional factor ZEB1 stabilization and recruitment to the PRTG promoter, and which then activated the sub-following cGMP/PKG signaling pathway in bioinformatic and cellular studies. Cellular studies further confirmed that PRTG depended on activating cGMP/PKG axis to promote proliferation, metastasis, and chemoresistance of gastric cancer cells. The PKG inhibitor KT5823 played synergistic anti-tumor effects with cisplatin and paclitaxel to gastric cancer cells in in vitro cellular and in vivo tumor-bearing mouse models. Taken together, our findings suggested that H. pylori infection depends on ZEB1 to induce PRTG upregulation, and which leading to the development and progression of gastric cancer through activating cGMP/PKG signaling pathway. Blocking PRTG/cGMP/PKG axis, therefore, presents a promising novel therapeutic strategy for gastric cancer.
Transcriptional coregualtor NUPR1 maintains tamoxifen resistance in breast cancer cells
Authors: Wang Lingling , Sun Jiashen , Yin Yueyuan , Sun Yanan , Ma Jinyi , Zhou Ruimin , Chang Xinzhong , Li Ding , Yao Zhi , Tian Shanshan , Zhang Kai , Liu Zhe , Ma Zhenyi
Published: February 2021

To support cellular homeostasis and mitigate chemotherapeutic stress, cancer cells must gain a series of adaptive intracellular processes. Here we identify that NUPR1, a tamoxifen (Tam)-induced transcriptional coregulator, is necessary for the maintenance of Tam resistance through physical interaction with ESR1 in breast cancers. Mechanistically, NUPR1 binds to the promoter regions of several genes involved in autophagy process and drug resistance such as BECN1, GREB1, RAB31, PGR, CYP1B1, and regulates their transcription. In Tam-resistant ESR1 breast cancer cells, NUPR1 depletion results in premature senescence in vitro and tumor suppression in vivo. Moreover, enforced-autophagic flux augments cytoplasmic vacuolization in NUPR1-depleted Tam resistant cells, which facilitates the transition from autophagic survival to premature senescence. Collectively, these findings suggest a critical role for NUPR1 as a transcriptional coregulator in enabling endocrine persistence of breast cancers, thus providing a vulnerable diagnostic and/or therapeutic target for endocrine resistance.
Bi-allelic loss of function variants in SLC30A5 as cause of perinatal lethal cardiomyopathy
Authors: Lieberwirth Johann Kaspar , Joset Pascal , Heinze Anja , Hentschel Julia , Stein Anja , Iannaccone Antonella , Steindl Katharina , Kuechler Alma , Abou Jamra Rami
Published: February 2021

Perinatal mortality is a heavy burden for both affected parents and physicians. However, the underlying genetic causes have not been sufficiently investigated and most cases remain without diagnosis. This impedes appropriate counseling or therapy. We describe four affected children of two unrelated families with cardiomyopathy, hydrops fetalis, or cystic hygroma that all deceased perinatally. In the four patients, we found the following homozygous loss of function (LoF) variants in SLC30A5 NM_022902.4:c.832_836del p.(Ile278Phefs*33) and NM_022902.4:c.1981_1982del p.(His661Tyrfs*10). Knockout of SLC30A5 has previously been shown a cardiac phenotype in mouse models and no homozygous LoF variants in SLC30A5 are currently described in gnomAD. Taken together, we present SLC30A5 as a new gene for a severe and perinatally lethal form of cardiomyopathy.
LlWRKY39 is involved in thermotolerance by activating LlMBF1c and interacting with LlCaM3 in lily (Lilium longiflorum)
Authors: Ding Liping , Wu Ze , Teng Renda , Xu Sujuan , Cao Xing , Yuan Guozhen , Zhang Dehua , Teng Nianjun
Published: February 2021

WRKY transcription factors (TFs) are of great importance in plant responses to different abiotic stresses. However, research on their roles in the regulation of thermotolerance remains limited. Here, we investigated the function of LlWRKY39 in the thermotolerance of lily (Lilium longiflorum ‘white heaven’). According to multiple alignment analyses, LlWRKY39 is in the WRKY IId subclass and contains a potential calmodulin (CaM)-binding domain. Further analysis has shown that LlCaM3 interacts with LlWRKY39 by binding to its CaM-binding domain, and this interaction depends on Ca2+. LlWRKY39 was induced by heat stress (HS), and the LlWRKY39-GFP fusion protein was detected in the nucleus. The thermotolerance of lily and Arabidopsis was increased with the ectopic overexpression of LlWRKY39. The expression of heat-related genes AtHSFA1, AtHSFA2, AtMBF1c, AtGolS1, AtDREB2A, AtWRKY39, and AtHSP101 was significantly elevated in transgenic Arabidopsis lines, which might have promoted an increase in thermotolerance. Then, the promoter of LlMBF1c was isolated from lily, and LlWRKY39 was found to bind to the conserved W-box element in its promoter to activate its activity, suggesting that LlWRKY39 is an upstream regulator of LlMBF1c. In addition, a dual-luciferase reporter assay showed that via protein interaction, LlCaM3 negatively affected LlWRKY39 in the transcriptional activation of LlMBF1c, which might be an important feedback regulation pathway to balance the LlWRKY39-mediated heat stress response (HSR). Collectively, these results imply that LlWRKY39 might participate in the HSR as an important regulator through Ca2+-CaM and multiprotein bridging factor pathways.
Novel ARG1 variants identified in a patient with arginase 1 deficiency
Authors: Yokoi Katsuyuki , Nakajima Yoko , Yasui Toshihiro , Yoshino Makoto , Yoshikawa Tetsushi , Kurahashi Hiroki , Ito Tetsuya
Published: February 2021

We report a case of a 13-year-old boy with arginase 1 deficiency carrying a new variant in ARG1. Sanger sequencing identified the compound heterozygous variants: NM_000045.4: c.365G>A (p.Trp122*)/c.820G>A (p.Asp274Asn). Although not previously reported, the p.Asp274Asn variant is predicted to have strong pathogenicity because it is located in a highly conserved domain in the protein core and arginase activity in the patient was below measurement sensitivity.
Gating the pore of the calcium-activated chloride channel TMEM16A
Authors: Lam Andy K. M. , Rheinberger Jan , Paulino Cristina , Dutzler Raimund
Published: February 2021

The binding of cytoplasmic Ca2+ to the anion-selective channel TMEM16A triggers a conformational change around its binding site that is coupled to the release of a gate at the constricted neck of an hourglass-shaped pore. By combining mutagenesis, electrophysiology, and cryo-electron microscopy, we identified three hydrophobic residues at the intracellular entrance of the neck as constituents of this gate. Mutation of each of these residues increases the potency of Ca2+ and results in pronounced basal activity. The structure of an activating mutant shows a conformational change of an α-helix that contributes to Ca2+ binding as a likely cause for the basal activity. Although not in physical contact, the three residues are functionally coupled to collectively contribute to the stabilization of the gate in the closed conformation of the pore, thus explaining the low open probability of the channel in the absence of Ca2+.
Responses of intended and unintended receivers to a novel sexual signal suggest clandestine communication
Authors: Tinghitella Robin M. , Broder E. Dale , Gallagher James H. , Wikle Aaron W. , Zonana David M.
Published: February 2021

Inadvertent cues can be refined into signals through coevolution between signalers and receivers, yet the earliest steps in this process remain elusive. In Hawaiian populations of the Pacific field cricket, a new morph producing a novel and incredibly variable song (purring) has spread across islands. Here we characterize the current sexual and natural selection landscape acting on the novel signal by (1) determining fitness advantages of purring through attraction to mates and protection from a prominent deadly natural enemy, and (2) testing alternative hypotheses about the strength and form of selection acting on the novel signal. In field studies, female crickets respond positively to purrs, but eavesdropping parasitoid flies do not, suggesting purring may allow private communication among crickets. Contrary to the sensory bias and preference for novelty hypotheses, preference functions (selective pressure) are nearly flat, driven by extreme inter-individual variation in function shape. Our study offers a rare empirical test of the roles of natural and sexual selection in the earliest stages of signal evolution.
Ribosome-bound Get4/5 facilitates the capture of tail-anchored proteins by Sgt2 in yeast
Authors: Zhang Ying , De Laurentiis Evelina , Bohnsack Katherine E. , Wahlig Mascha , Ranjan Namit , Gruseck Simon , Hackert Philipp , Wölfle Tina , Rodnina Marina V. , Schwappach Blanche , Rospert Sabine
Published: February 2021

The guided entry of tail-anchored proteins (GET) pathway assists in the posttranslational delivery of tail-anchored proteins, containing a single C-terminal transmembrane domain, to the ER. Here we uncover how the yeast GET pathway component Get4/5 facilitates capture of tail-anchored proteins by Sgt2, which interacts with tail-anchors and hands them over to the targeting component Get3. Get4/5 binds directly and with high affinity to ribosomes, positions Sgt2 close to the ribosomal tunnel exit, and facilitates the capture of tail-anchored proteins by Sgt2. The contact sites of Get4/5 on the ribosome overlap with those of SRP, the factor mediating cotranslational ER-targeting. Exposure of internal transmembrane domains at the tunnel exit induces high-affinity ribosome binding of SRP, which in turn prevents ribosome binding of Get4/5. In this way, the position of a transmembrane domain within nascent ER-targeted proteins mediates partitioning into either the GET or SRP pathway directly at the ribosomal tunnel exit.
Internal constraints and arrested relaxation in main-chain nematic elastomers
Authors: Ohzono Takuya , Katoh Kaoru , Minamikawa Hiroyuki , Saed Mohand O. , Terentjev Eugene M.
Published: February 2021

Nematic liquid crystal elastomers (N-LCE) exhibit intriguing mechanical properties, such as reversible actuation and soft elasticity, which manifests as a wide plateau of low nearly-constant stress upon stretching. N-LCE also have a characteristically slow stress relaxation, which sometimes prevents their shape recovery. To understand how the inherent nematic order retards and arrests the equilibration, here we examine hysteretic stress-strain characteristics in a series of specifically designed main-chain N-LCE, investigating both macroscopic mechanical properties and the microscopic nematic director distribution under applied strains. The hysteretic features are attributed to the dynamics of thermodynamically unfavoured hairpins, the sharp folds on anisotropic polymer strands, the creation and transition of which are restricted by the nematic order. These findings provide a new avenue for tuning the hysteretic nature of N-LCE at both macro- and microscopic levels via different designs of polymer networks, toward materials with highly nonlinear mechanical properties and shape-memory applications.
SPT6 promotes epidermal differentiation and blockade of an intestinal-like phenotype through control of transcriptional elongation
Authors: Li Jingting , Xu Xiaojun , Tiwari Manisha , Chen Yifang , Fuller Mackenzie , Bansal Varun , Tamayo Pablo , Das Soumita , Ghosh Pradipta , Sen George L.
Published: February 2021

In adult tissue, stem and progenitor cells must tightly regulate the balance between proliferation and differentiation to sustain homeostasis. How this exquisite balance is achieved is an area of active investigation. Here, we show that epidermal genes, including ~30% of induced differentiation genes already contain stalled Pol II at the promoters in epidermal stem and progenitor cells which is then released into productive transcription elongation upon differentiation. Central to this process are SPT6 and PAF1 which are necessary for the elongation of these differentiation genes. Upon SPT6 or PAF1 depletion there is a loss of human skin differentiation and stratification. Unexpectedly, loss of SPT6 also causes the spontaneous transdifferentiation of epidermal cells into an intestinal-like phenotype due to the stalled transcription of the master regulator of epidermal fate P63. Our findings suggest that control of transcription elongation through SPT6 plays a prominent role in adult somatic tissue differentiation and the inhibition of alternative cell fate choices.
Machine learning aided carrier recovery in continuous-variable quantum key distribution
Authors: Chin Hou-Man , Jain Nitin , Zibar Darko , Andersen Ulrik L. , Gehring Tobias
Published: February 2021

The secret key rate of a continuous-variable quantum key distribution (CV-QKD) system is limited by excess noise. A key issue typical to all modern CV-QKD systems implemented with a reference or pilot signal and an independent local oscillator is controlling the excess noise generated from the frequency and phase noise accrued by the transmitter and receiver. Therefore accurate phase estimation and compensation, so-called carrier recovery, is a critical subsystem of CV-QKD. Here, we explore the implementation of a machine learning framework based on Bayesian inference, namely an unscented Kalman filter (UKF), for estimation of phase noise and compare it to a standard reference method and a previously demonstrated machine learning method. Experimental results obtained over a 20-km fibre-optic link indicate that the UKF can ensure very low excess noise even at low pilot powers. The measurements exhibited low variance and high stability in excess noise over a wide range of pilot signal to noise ratios. This may enable CV-QKD systems with low hardware implementation complexity which can seamlessly work on diverse transmission lines.
Directional excitation of surface plasmon using multi-mode interference in an aperture
Authors: Alam M. Z. , Yang Z. , Sheik-Bahae M. , Aitchison J. S. , Mojahedi M.
Published: February 2021

Plasmonics is a promising technology that can find many applications in nanophotonics and biosensing. Local excitation of surface plasmons with high directionality is required for many of these applications. We demonstrate that by controlling the interference of light in a metal slot with the adjustment of the angle of incidence, it is possible to achieve highly directional surface plasmon excitation. Our numerical analysis of the structure showing a strong directionality of excited surface plasmon is confirmed by near field scanning measurements. The proposed structure can be useful for many applications including excitation of plasmonic waveguides, nanolithography, and optical sensing. To illustrate its usefulness, we experimentally demonstrate that it can be used for highly directional excitation of a dielectric loaded plasmonic waveguide. We also propose a simple structure for surface plasmon interference lithography capable of providing high image contrast using this scheme.
Thiourea and hydrogen peroxide priming improved K+ retention and source-sink relationship for mitigating salt stress in rice
Authors: Pandey Manish , Paladi Radha Krishna , Srivastava Ashish Kumar , Suprasanna Penna
Published: February 2021

Plant bioregulators (PBRs) represent low-cost chemicals for boosting plant defense, especially under stress conditions. In the present study, redox based PBRs such as thiourea (TU; a non-physiological thiol-based ROS scavenger) and hydrogen peroxide (H2O2; a prevalent biological ROS) were assessed for their ability to mitigate NaCl stress in rice variety IR 64. Despite their contrasting redox chemistry, TU or H2O2 supplementation under NaCl [NaCl + TU (NT) or NaCl + H2O2 (NH)] generated a reducing redox environment in planta, which improved the plant growth compared with those of NaCl alone treatment. This was concomitant with better K+ retention and upregulated expression of NaCl defense related genes including HAK21, LEA1, TSPO and EN20 in both NT and NH treated seedlings. Under field conditions, foliar applications of TU and H2O2, at vegetative growth, pre-flowering and grain filling stages, increased growth and yield attributes under both control and NaCl stress conditions. Principal component analysis revealed glutathione reductase dependent reduced ROS accumulation in source (flag leaves) and sucrose synthase mediated sucrose catabolism in sink (developing inflorescence), as the key variables associated with NT and NH mediated effects, respectively. In addition, photosystem-II efficiency, K+ retention and source-sink relationship were also improved in TU and H2O2 treated plants. Taken together, our study highlights that reducing redox environment acts as a central regulator of plant’s tolerance responses to salt stress. In addition, TU and H2O2 are proposed as potential redox-based PBRs for boosting rice productivity under the realistic field conditions.
Assessment of corneal biomechanics, tonometry and pachymetry with the Corvis ST in myopia
Authors: Wang Xiaorui , McAlinden Colm , Zhang Hongbing , Yan Jie , Wang Dan , Wei Wei , Mi Shengjian
Published: February 2021

To evaluate the repeatability of Corvis ST corneal biomechanical, tonometry and pachymetry measurements, and agreement of pachymetry measures with the Pentacam HR and RTVue OCT. Three consecutive measurements of the right eye of 238 myopic subjects were acquired with the Corvis ST, Pentacam HR, and RTVue OCT. Repeatability of Corvis ST was evaluated by within-subject standard deviation [Sw] and repeatability limit [r]. The agreement of central corneal thickness (CCT) measurements were compared among the three instruments using the Bland–Altman limits of agreement. Comparisons were further stratified by CCT (Corneathin ≤ 500 µm; Corneanormal = 500–550 µm; Corneathick > 550 µm). Sw was below 1 mmHg in Corneathin, Corneanormal, and Corneathick groups for IOP and bIOP. Sw for SP-A1 were 4.880, 6.128, 7.719 mmHg/mm respectively. Sw for CBI were 0.228, 0.157, 0.076, and correspondingly Sw for TBI and SSI were 0.094 and 0.056, 0.079 and 0.053, 0.070 and 0.053. The Bland–Altman plots for CCT implied poor agreement with mean differences of 29.49 µm between Corvis and OCT, 9.33 µm between Pentacam and OCT, and 20.16 µm between Corvis and Pentacam. The Corvis ST showed good repeatability with the exception of CBI in the various CCT groups. The CCT measured by Corvis ST was not interchangeable with Pentacam HR and RTVue OCT.