bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential germination response of Navua sedge (Cyperus aromaticus) populations to environmental factors
Authors: Chauhan Bhagirath S.
Published: July 2021

Navua sedge [Cyperus aromaticus (Ridl.) Mattf. & Kuek.], is a hard to control C4 perennial weed species in tropical regions of Australia. Knowledge of its seed biology could help to develop integrated weed management programs for this species. This study was conducted under laboratory and screenhouse conditions to evaluate the effect of alternating day/night temperatures, light, pretreatment high temperatures, burial depth, and flooding depth on the germination and emergence of two populations (Ingham and Tablelands) of C. aromaticus. Both populations germinated at temperatures ranging from 20/10 to 35/25 C; however, the Ingham population germination (76%) was greater than the Tablelands population (42%) at the highest temperature regime (35/25 C). None of the populations germinated at 15/5 C. Darkness completely inhibited germination in both populations, suggesting that the seeds are positively photoblastic. Seeds (dry and wet) of both populations germinated after exposure to pretreatment temperatures of up to 100 C for 5 min. After pretreatment at 150 C, only the Ingham population germinated, and germination was greater for dry seeds (62%) than for wet seeds (1%). Neither population germinated after exposure to 200 C. For both populations, maximum germination was observed for seeds at 0 cm; a burial depth of 0.5 cm completely inhibited emergence of the Tablelands population, and a burial depth of 2.0 cm completely inhibited germination of the Ingham population. A flooding depth of 10 cm greatly reduced emergence in both populations compared with 0 cm (62% and 78%) but 12% to 14% of seedlings still emerged, suggesting the need to integrate flooding with other management tools. The results also suggest that the Ingham population may have a greater potential to spread into new areas or become more invasive than the Tablelands population. Knowledge gained from this study can be used to manage C. aromaticus by fire/burning, tillage, and flooding.
Aftershock Triggering and Spatial Aftershock Zones in Fluid‐Driven Settings: Discriminating Induced Seismicity From Natural Swarms
Authors: Karimi Kamran , Davidsen Jörn
Published: July 2021

Aftershock cascades play an important role in forecasting seismicity in natural and human‐made situations. While their behavior including the spatial aftershock zone has been the focus of many studies in tectonic settings, this is not the case when fluid flows are involved. Using high‐quality seismic catalogs, we probe aftershocks dynamics in five settings influenced by fluids: (a) induced seismicity in Oklahoma and Kansas, (b) natural swarms in California and Nevada, and (c) suspected swarms in the Yuha Desert (California). All settings exhibit significant aftershock behavior highlighting the importance of event‐event triggering processes. The spatial aftershock zones scale with mainshock magnitude as expected based on the rupture length. While (a) and (b) show a rapid decay beyond their rupture length, (c) exhibits long‐range behavior suggesting that fluid migration might not be the dominant mechanism. We also find that the scaling of aftershock productivity with mainshock magnitude together with the Gutenberg‐Richter ‐value might allow to distinguish between natural swarms and induced seismicity.
The Universal Time Variations of the Intensity of Afternoon Aurora in Equinoctial Seasons
Authors: Wang Lingmin , Luan Xiaoli , Lei Jiuhou , Lynch Kristina A. , Zhang Binzheng
Published: July 2021

The afternoon auroral emissions are investigated in the equinoxes for geomagnetically quiet conditions (Kp = 1) using auroral images from ultraviolet imager (UVI) aboard the Polar satellite. They are compared with solar illumination effects (the solar zenith angle [SZA] and the consequent ionospheric conductivity) and the dipole tilt angle, as well as the observational region 1 upward field‐aligned currents (FACs) from AMPERE data. The averaged afternoon auroral emissions have pronounced universal time (UT) variations with valley (2.8 photons/cm2/s) at around 01:00–03:00 UT and peak (4.7 photons/cm2/s) at around 17:00–19:00 UT. They generally vary with the solar illumination, the dipole tilt angle and the observed region 1 upward FACs as a function of UT. The afternoon auroral intensity is anticorrelated with the SZA and positively proportional to the solar EUV‐produced Pedersen conductivity, region 1 upward FACs and dipole tilt angle. Additionally, they depend weakly on solar flux under geomagnetically quiet conditions. These results suggest that in the afternoon auroral region, the peak auroral emissions are closely associated with the peak conductivity and the maximum upward FACs. Other mechanisms, such as the dipole tilt angle, may also contribute. Further comparison between the northern afternoon aurora and the FACs in the two conjugate hemispheres suggests little contributions on the auroral UT variations from the interhemispheric FACs in the equinoxes.
Slip Rate and Paleoseismology of the Bolokenu‐Aqikekuduk (Dzhungarian) Right‐Lateral Strike‐Slip Fault in the Northern Tian Shan, NW China
Authors: Hu Zongkai , Yang Xiaoping , Yang Haibo , Huang Weiliang , Wu Guodong , Miao Shuqing , Zhang Ling
Published: July 2021

The ∼1,000 km‐long Bolokenu‐Aqikekuduk fault (Dzhungarian fault, BAF) is one of the major right‐lateral strike‐slip faults that cut across the Tian Shan Range. Although the BAF plays an important role in accommodating crustal shorting of the Tian Shan and cuts through densely populated cities, little is known about its late Quaternary tectonic activity or earthquake history. Here we quantify the late Quaternary dextral strike‐slip rate of the BAF along the Jinghe segment based on interpretation of high‐resolution remote sensing images and structure‐from‐motion (SfM)‐derived DEMs, field observations and the abandonment ages of displaced alluvial fans, which were constrained by optically stimulated luminescence (OSL) and cosmogenic 10Be depth profile dating methods. Using the offset of fan risers and gullies incised into the fan surfaces, we yielded a right‐lateral strike‐slip rate of 3.2 + 1.4/−1.1 mm/a. Compared with the entire crustal shortening rates across the Tian Shan, the BAF accommodates ∼23% of the N‐S crustal shortening rate. Additionally, a paleoseismic trench reveals four events since the late Pleistocene with an average recurrence time of ∼4–6 ka. The last event occurred after ∼6.6 ka, which is slightly larger than the average recurrence time, suggesting that the BAF represents a potential high seismic risk for the densely populated area nearby.
Upper Mantle Hydration Indicated by Decreased Shear Velocity Near the Southern Mariana Trench From Rayleigh Wave Tomography
Authors: Zhu Gaohua , Wiens Douglas A. , Yang Hongfeng , Lin Jian , Xu Min , You Qingyu
Published: July 2021

Reduction of seismic velocities has been employed to study the hydration of incoming plates and forearc mantle in recent years. However, few constraints have been obtained in the Southern Mariana Trench. We use an ocean bottom seismograph (OBS) deployment to conduct Rayleigh wave tomographic studies to derive the SV‐wave velocity structure near the Southern Mariana Trench. Measured group and phase velocities as a function of period are inverted to determine the SV‐wave velocity using a Bayesian Monte Carlo algorithm. The incoming Pacific Plate is characterized by low velocities (3.6–4.1 km/s) within the upper ∼25 km of the mantle near the trench, indicating extensive mantle hydration of the incoming plate in southern Mariana. The velocity reduction in the forearc mantle is not as large as in central Mariana, most likely indicating a lower forearc serpentinization in this region, which is consistent with the absence of serpentinite mud volcanoes.
Near Surface Properties of Martian Regolith Derived From InSight HP3‐RAD Temperature Observations During Phobos Transits
Authors: Mueller N. , Piqueux S. , Lemmon M. , Maki J. , Lorenz R. D. , Grott M. , Spohn T. , Smrekar S. E. , Knollenberg J. , Hudson T. L. , Krause C. , Millour E. , Forget F. , Golombek M. , Hagermann A. , Attree N. , Siegler M. , Banerdt W. B.
Published: July 2021

We use the Martian surface temperature response to Phobos transits observed next to the InSight lander in Elysium Planitia to constrain the thermal properties of the uppermost layer of regolith. Modeled transit lightcurves validated by solar panel current measurements are used to modify the boundary conditions of a 1D heat conduction model. We test several model parameter sets, varying the thickness and thermal conductivity of the top layer to explore the range of parameters that match the observed temperature response within its uncertainty both during the eclipse as well as the full diurnal cycle. The measurements indicate a thermal inertia (TI) of in the uppermost layer of 0.2–4 mm, significantly smaller than the TI of derived from the diurnal temperature curve. This could be explained by larger particles, higher density, or some or slightly higher amount of cementation in the lower layers.
Impact of High Temporal Resolution FY‐4A Geostationary Interferometric Infrared Sounder (GIIRS) Radiance Measurements on Typhoon Forecasts: Maria (2018) Case With GRAPES Global 4D‐Var Assimilation System
Authors: Yin Ruoying , Han Wei , Gao Zhiqiu , Li Jun
Published: July 2021

Targeted observations for Typhoon Maria (2018) using the Geostationary Interferometric Infrared Sounder (GIIRS) at a temporal resolution of 15 min provide unprecedented information for impact studies of high‐temporal‐resolution from geostationary hyperspectral IR sounders. This study investigates the impacts of different temporal resolutions for GIIRS assimilation on Maria analyses and forecasts. Results reveal that assimilating higher resolution data captures more detailed temporal and spatial structures and stronger warm anomalies. Additionally, the track forecast for Maria from assimilating higher temporal resolution GIIRS radiances is better than those from assimilating radiances with lower temporal resolution, and both are better than the control experiment. The accuracy of the different temporal resolutions GIIRS experiments (from 3 h to 15 min) is improved (from 18% to 43%), and the intensity forecast errors are also reduced (from 12% to 18%). Meanwhile, high‐temporal GIIRS assimilation also improves the coastal precipitation forecasts during typhoon landfall.
Resolving the Paleogeographic Puzzle of the Lhasa Terrane in Southern Tibet
Authors: Wang Qing , Zhu Di‐Cheng , Cawood Peter A. , Chung Sun‐Lin , Zhao Zhi‐Dan
Published: July 2021

The widespread Tibetan Permo‐Carboniferous glaciogenic diamictites (PCGDs) are conventionally thought to be sourced from Indian Gondwana during glacier transport and deglaciation. However, the Lhasa PCGDs differ in detrital zircon U‐Pb age spectra and εHf(t) values from those in Southern Qiangtang and Tethyan Himalaya. The similarities in εHf(t) values for similar‐age detrital zircons, the development of glacier transport pathways, and the large volumes of the Tibetan PCGDs indicate an Australian source for the Lhasa PCDGs, and an Indian source for the Southern Qiangtang and Tethyan Himalayan PCDGs. We conclude that the Southern Qiangtang and Tethyan Himalayan are paleographically linked to northern India, whereas Lhasa is positioned adjacent to NW Australia during the Paleozoic. Magmatic and metamorphic records further indicate that eastern Lhasa (E90°–E95°) represents the outboard extension of events recorded in northern Central Australia, whereas western Lhasa (E80°–E90°) was located outboard of the West Australian Craton.
Relationship Between Active Faulting/Fracturing and Magmatism Around Santorini: Seismic Anisotropy From an Active Source Tomography Experiment
Authors: Heath B. A. , Hooft E. E. E. , Toomey D. R. , Paulatto M. , Papazachos C. B. , Nomikou P. , Morgan J. V.
Published: July 2021

In extending volcanic arcs such as the Aegean, tectonic processes exert a significant control on magmatism. Spanning scales from 1 to 10s of km, volcanic vents, edifices, and eruptive centers follow the orientation of, and are located near, fault zones. Whether this tectonic control on magmatism results from individual faults/fractures weakening the crust or because regional stresses control magma input into the crust is debated. Here we investigate the scales of tectonic and magmatic interactions, specifically focusing on the role of local‐scale (<10 km) faults/fractures in controlling magmatism. We infer local‐scale fault/fracture orientations from anisotropic active‐source P‐wave travel‐time tomography to investigate tectonic and magmatic interactions in the upper crust of Santorini Volcano, Greece, and the actively deforming region to the east. We use the anisotropy magnitude and seismic velocity reduction to model the relative distribution of both consistently oriented and randomly oriented faults/fractures. Our results show that oriented faulting/fracturing resulting from regional‐scale (>10 km) tectonic stresses is distributed broadly across the region at 2–3 km depth, approximately paralleling volcanic/magmatic features. On a local‐scale, magmatism is neither localized in areas of higher oriented fault/fracture density, nor is it accommodating enough extensional strain to inhibit oriented faulting/fracturing of host rock. The alignment of magmatic features shows strong tectonic control despite the lack of correlation with local oriented fault/fracture density. These results suggest that magmatic processes are strongly influenced by regional‐scale, not local‐scale, tectonic processes. We infer regional processes have a greater impact on magmatism than local features due to their greater effect at depth.
Hydrological Modeling of the Effect of the Transition From Flood to Drip Irrigation on Groundwater Recharge Using Multi‐Objective Calibration
Authors: Pool Sandra , Francés Félix , Garcia‐Prats Alberto , Puertes Cristina , Pulido‐Velazquez Manuel , Sanchis‐Ibor Carles , Schirmer Mario , Yang Hong , Jiménez‐Martínez Joaquín
Published: July 2021

The replacement of flood‐irrigation systems by drip‐irrigation technology has been widely promoted with the aim of a more sustainable use of freshwater resources in irrigated agriculture. However, evidence for an irrigation efficiency paradox emphasizes the need to improve our understanding of the impacts of irrigation transformations on water resources. Here, we developed a distributed hydrological modeling approach to investigate the spatiotemporal effect of flood and drip irrigation on groundwater recharge. The approach recognizes differences in the water balance resulting from the localized application of water in surface drip‐irrigated fields and the more extensive application of water in flood irrigation. The approach was applied to the semi‐arid Mediterranean region of Valencia (Spain) and calibrated using a multi‐objective framework. Multiple process scales were addressed within the framework by considering the annual evaporative index, monthly groundwater level dynamics, and daily soil moisture dynamics. Daily simulations from 1994 to 2015 suggested that, in our hydroclimatic conditions, (a) annual recharge is strongly related to annual rainfall, which had a four times higher impact on recharge than the type of irrigation practice, (b) flood‐irrigated recharge tends to exceed drip‐irrigated recharge by 10% at annual time scales, (c) however, recharge response to a particular precipitation event is smaller in flood irrigation than in drip irrigation, and (d) 8–18 rainfall events could generate more than half of the annual recharge in drip and flood irrigation, respectively. Our results highlight the importance of understanding the hydrological dynamics under different irrigation practices for supporting irrigation infrastructure policies.
ETV7 regulates breast cancer stem-like cell features by repressing IFN-response genes
Authors: Pezzè Laura , Meškytė Erna Marija , Forcato Mattia , Pontalti Stefano , Badowska Kalina Aleksandra , Rizzotto Dario , Skvortsova Ira-Ida , Bicciato Silvio , Ciribilli Yari
Published: July 2021

Cancer stem cells (CSCs) represent a population of cells within the tumor able to drive tumorigenesis and known to be highly resistant to conventional chemotherapy and radiotherapy. In this work, we show a new role for ETV7, a transcriptional repressor member of the ETS family, in promoting breast cancer stem-like cells plasticity and resistance to chemo- and radiotherapy in breast cancer (BC) cells. We observed that MCF7 and T47D BC-derived cells stably over-expressing ETV7 showed reduced sensitivity to the chemotherapeutic drug 5-fluorouracil and to radiotherapy, accompanied by an adaptive proliferative behavior observed in different culture conditions. We further noticed that alteration of ETV7 expression could significantly affect the population of breast CSCs, measured by CD44+/CD24low cell population and mammosphere formation efficiency. By transcriptome profiling, we identified a signature of Interferon-responsive genes significantly repressed in cells over-expressing ETV7, which could be responsible for the increase in the breast CSCs population, as this could be partially reverted by the treatment with IFN-β. Lastly, we show that the expression of the IFN-responsive genes repressed by ETV7 could have prognostic value in breast cancer, as low expression of these genes was associated with a worse prognosis. Therefore, we propose a novel role for ETV7 in breast cancer stem cells’ plasticity and associated resistance to conventional chemotherapy and radiotherapy, which involves the repression of a group of IFN-responsive genes, potentially reversible upon IFN-β treatment. We, therefore, suggest that an in-depth investigation of this mechanism could lead to novel breast CSCs targeted therapies and to the improvement of combinatorial regimens, possibly involving the therapeutic use of IFN-β, with the aim of avoiding resistance development and relapse in breast cancer.
Tissue-specific expression of p73 and p63 isoforms in human tissues
Authors: Marshall Clayton B. , Beeler J. Scott , Lehmann Brian D. , Gonzalez-Ericsson Paula , Sanchez Violeta , Sanders Melinda E. , Boyd Kelli L. , Pietenpol Jennifer A.
Published: July 2021

p73 and p63 are members of the p53 family that exhibit overlapping and distinct functions in development and homeostasis. The evaluation of p73 and p63 isoform expression across human tissue can provide greater insight to the functional interactions between family members. We determined the mRNA isoform expression patterns of TP73 and TP63 across a panel of 36 human tissues and protein expression within the highest-expressing tissues. TP73 and TP63 expression significantly correlated across tissues. In tissues with concurrent mRNA expression, nuclear co-expression of both proteins was observed in a majority of cells. Using GTEx data, we quantified p73 and p63 isoform expression in human tissue and identified that the α-isoforms of TP73 and TP63 were the predominant isoform expressed in nearly all tissues. Further, we identified a previously unreported p73 mRNA product encoded by exons 4 to 14. In sum, these data provide the most comprehensive tissue-specific atlas of p73 and p63 protein and mRNA expression patterns in human and murine samples, indicating coordinate expression of these transcription factors in the majority of tissues in which they are expressed.
Super-resolution microscopy reveals that Na+/K+-ATPase signaling protects against glucose-induced apoptosis by deactivating Bad
Authors: Bernhem Kristoffer , Fontana Jacopo M. , Svensson Daniel , Zhang Liang , Nilsson Linnéa M. , Scott Lena , Blom Hans , Brismar Hjalmar , Aperia Anita
Published: July 2021

Activation of the apoptotic pathway is a major cause of progressive loss of function in chronic diseases such as neurodegenerative and diabetic kidney diseases. There is an unmet need for an anti-apoptotic drug that acts in the early stage of the apoptotic process. The multifunctional protein Na+,K+-ATPase has, in addition to its role as a transporter, a signaling function that is activated by its ligand, the cardiotonic steroid ouabain. Several lines of evidence suggest that sub-saturating concentrations of ouabain protect against apoptosis of renal epithelial cells, a common complication and major cause of death in diabetic patients. Here, we induced apoptosis in primary rat renal epithelial cells by exposing them to an elevated glucose concentration (20 mM) and visualized the early steps in the apoptotic process using super-resolution microscopy. Treatment with 10 nM ouabain interfered with the onset of the apoptotic process by inhibiting the activation of the BH3-only protein Bad and its translocation to mitochondria. This occurred before the pro-apoptotic protein Bax had been recruited to mitochondria. Two ouabain regulated and Akt activating Ca2+/calmodulin-dependent kinases were found to play an essential role in the ouabain anti-apoptotic effect. Our results set the stage for further exploration of ouabain as an anti-apoptotic drug in diabetic kidney disease as well as in other chronic diseases associated with excessive apoptosis.
Chromatin remodeler ARID1A binds IRF3 to selectively induce antiviral interferon production in macrophages
Authors: Hu Ye , Wang Xin , Song Jiaying , Wu Jiacheng , Xu Jia , Chai Yangyang , Ding Yuanyuan , Wang Bingjing , Wang Chunmei , Zhao Yong , Shen Zhongyang , Xu Xiaoqing , Cao Xuetao
Published: July 2021

Transcription factor IRF3 is critical for the induction of antiviral type I interferon (IFN-I). The epigenetic regulation of IFN-I production in antiviral innate immunity needs to be further identified. Here, we reported that epigenetic remodeler ARID1A, a critical component of the mSWI/SNF complex, could bind IRF3 and then was recruited to the Ifn-I promoter by IRF3, thus selectively promoting IFN-I but not TNF-α, IL-6 production in macrophages upon viral infection. Myeloid cell-specific deficiency of Arid1a rendered mice more susceptible to viral infection, accompanied with less IFN-I production. Mechanistically, ARID1A facilitates chromatin accessibility of IRF3 at the Ifn-I promoters by interacting with histone methyltransferase NSD2, which methylates H3K4 and H3K36 of the promoter regions. Our findings demonstrated the new roles of ARID1A and NSD2 in innate immunity, providing insight into the crosstalks of chromatin remodeling, histone modification, and transcription factors in the epigenetic regulation of antiviral innate immunity.
GWAS of serum ALT and AST reveals an association of SLC30A10 Thr95Ile with hypermanganesemia symptoms
Authors: Ward Lucas D. , Tu Ho-Chou , Quenneville Chelsea B. , Tsour Shira , Flynn-Carroll Alexander O. , Parker Margaret M. , Deaton Aimee M. , Haslett Patrick A. J. , Lotta Luca A. , Verweij Niek , Ferreira Manuel A. R. ,   Regeneron Genetics Center,   RGC Management and Leadership Team, Abecasis Goncalo , Cantor Michael , Coppola Giovanni , Reid Jeffrey G. , Shuldiner Alan , Karalis Katia , Siminovitch Katherine ,   Sequencing and Lab Operations, Beechert Christina , Forsythe Caitlin , Fuller Erin D. , Gu Zhenhua , Lattari Michael , Lopez Alexander , Schleicher Thomas D. , Padilla Maria Sotiropoulos , Widom Louis , Wolf Sarah E. , Pradhan Manasi , Manoochehri Kia , Ulloa Ricardo H. ,   Genome Informatics, Bai Xiaodong , Balasubramanian Suganthi , Blumenfeld Andrew , Boutkov Boris , Eom Gisu , Habegger Lukas , Hawes Alicia , Khalid Shareef , Krasheninina Olga , Lanche Rouel , Mansfield Adam J. , Maxwell Evan K. , Nafde Mrunali , O’Keeffe Sean , Orelus Max , Panea Razvan , Polanco Tommy , Rasool Ayesha , Salerno William , Staples Jeffrey C. ,   Clinical Informatics, Li Dadong , Sharma Deepika , Kury Fabricio ,   Translational Genetics, Nielsen Jonas , De Tanima ,   Research Program Management, Jones Marcus B. , Mighty Jason , LeBlanc Michelle G. , Mitnaul Lyndon J. ,   Geisinger-Regeneron DiscovEHR Collaboration, Baras Aris , Cantor Michael , Economides Aris , Reid Jeffrey G. , Deubler Andrew , Siminovitch Katherine , Adams Lance J. , Blank Jackie , Bodian Dale , Boris Derek , Buchanan Adam , Carey David J. , Colonie Ryan D. , Davis F. Daniel , Hartzel Dustin N. , Kelly Melissa , Kirchner H. Lester , Leader Joseph B. , Ledbetter David H. , Manus J. Neil , Martin Christa L. , Metpally Raghu P. , Meyer Michelle , Mirshahi Tooraj , Oetjens Matthew , Person Thomas Nate , Still Christopher , Strande Natasha , Sturm Amy , Wagner Jen , Williams Marc , Baras Aris , Hinkle Gregory , Nioi Paul
Published: July 2021

Understanding mechanisms of hepatocellular damage may lead to new treatments for liver disease, and genome-wide association studies (GWAS) of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum activities have proven useful for investigating liver biology. Here we report 100 loci associating with both enzymes, using GWAS across 411,048 subjects in the UK Biobank. The rare missense variantSLC30A10Thr95Ile (rs188273166) associates with the largest elevation of both enzymes, and this association replicates in the DiscovEHR study. SLC30A10 excretes manganese from the liver to the bile duct, and rare homozygous loss of function causes the syndrome hypermanganesemia with dystonia-1 (HMNDYT1) which involves cirrhosis. Consistent with hematological symptoms of hypermanganesemia,SLC30A10Thr95Ile carriers have increased hematocrit and risk of iron deficiency anemia. Carriers also have increased risk of extrahepatic bile duct cancer. These results suggest that genetic variation inSLC30A10adversely affects more individuals than patients with diagnosed HMNDYT1.
Transporter characterisation reveals aminoethylphosphonate mineralisation as a key step in the marine phosphorus redox cycle
Authors: Murphy Andrew R. J. , Scanlan David J. , Chen Yin , Adams Nathan B. P. , Cadman William A. , Bottrill Andrew , Bending Gary , Hammond John P. , Hitchcock Andrew , Wellington Elizabeth M. H. , Lidbury Ian D. E. A.
Published: July 2021

The planktonic synthesis of reduced organophosphorus molecules, such as alkylphosphonates and aminophosphonates, represents one half of a vast global oceanic phosphorus redox cycle. Whilst alkylphosphonates tend to accumulate in recalcitrant dissolved organic matter, aminophosphonates do not. Here, we identify three bacterial 2-aminoethylphosphonate (2AEP) transporters, named AepXVW, AepP and AepSTU, whose synthesis is independent of phosphate concentrations (phosphate-insensitive). AepXVW is found in diverse marine heterotrophs and is ubiquitously distributed in mesopelagic and epipelagic waters. Unlike the archetypal phosphonate binding protein, PhnD, AepX has high affinity and high specificity for 2AEP (Stappia stellulata AepX Kd 23 ± 4 nM; methylphosphonate Kd 3.4 ± 0.3 mM). In the global ocean, aepX is heavily transcribed (~100-fold>phnD) independently of phosphate and nitrogen concentrations. Collectively, our data identifies a mechanism responsible for a major oxidation process in the marine phosphorus redox cycle and suggests 2AEP may be an important source of regenerated phosphate and ammonium, which are required for oceanic primary production.
NEK2 inhibition triggers anti-pancreatic cancer immunity by targeting PD-L1
Authors: Zhang Xiaozhen , Huang Xing , Xu Jian , Li Enliang , Lao Mengyi , Tang Tianyu , Zhang Gang , Guo Chengxiang , Zhang Xiaoyu , Chen Wen , Yadav Dipesh Kumar , Bai Xueli , Liang Tingbo
Published: July 2021

Despite the substantial impact of post-translational modifications on programmed cell death 1 ligand 1 (PD-L1), its importance in therapeutic resistance in pancreatic cancer remains poorly defined. Here, we demonstrate that never in mitosis gene A-related kinase 2 (NEK2) phosphorylates PD-L1 to maintain its stability, causing PD-L1-targeted pancreatic cancer immunotherapy to have poor efficacy. We identify NEK2 as a prognostic factor in immunologically “hot” pancreatic cancer, involved in the onset and development of pancreatic tumors in an immune-dependent manner. NEK2 deficiency results in the suppression of PD-L1 expression and enhancement of lymphocyte infiltration. A NEK binding motif (F/LXXS/T) is identified in the glycosylation-rich region of PD-L1. NEK2 interacts with PD-L1, phosphorylating the T194/T210 residues and preventing ubiquitin-proteasome pathway-mediated degradation of PD-L1 in ER lumen. NEK2 inhibition thereby sensitizes PD-L1 blockade, synergically enhancing the anti-pancreatic cancer immune response. Together, the present study proposes a promising strategy for improving the effectiveness of pancreatic cancer immunotherapy.
The upstream 5′ splice site remains associated to the transcription machinery during intron synthesis
Authors: Leader Yodfat , Lev Maor Galit , Sorek Matan , Shayevitch Ronna , Hussein Maram , Hameiri Ofir , Tammer Luna , Zonszain Jonathan , Keydar Ifat , Hollander Dror , Meshorer Eran , Ast Gil
Published: July 2021

In the earliest step of spliceosome assembly, the two splice sites flanking an intron are brought into proximity by U1 snRNP and U2AF along with other proteins. The mechanism that facilitates this intron looping is poorly understood. Using a CRISPR interference-based approach to halt RNA polymerase II transcription in the middle of introns in human cells, we discovered that the nascent 5′ splice site base pairs with a U1 snRNA that is tethered to RNA polymerase II during intron synthesis. This association functionally corresponds with splicing outcome, involves bona fide 5′ splice sites and cryptic intronic sites, and occurs transcriptome-wide. Overall, our findings reveal that the upstream 5′ splice sites remain attached to the transcriptional machinery during intron synthesis and are thus brought into proximity of the 3′ splice sites; potentially mediating the rapid splicing of long introns.
Functional and epigenetic phenotypes of humans and mice with DNMT3A Overgrowth Syndrome
Authors: Smith Amanda M. , LaValle Taylor A. , Shinawi Marwan , Ramakrishnan Sai M. , Abel Haley J. , Hill Cheryl A. , Kirkland Nicole M. , Rettig Michael P. , Helton Nichole M. , Heath Sharon E. , Ferraro Francesca , Chen David Y. , Adak Sangeeta , Semenkovich Clay F. , Christian Diana L. , Martin Jenna R. , Gabel Harrison W. , Miller Christopher A. , Ley Timothy J.
Published: July 2021

Germline pathogenic variants inDNMT3Awere recently described in patients with overgrowth, obesity, behavioral, and learning difficulties (DNMT3AOvergrowthSyndrome/DOS). Somatic mutations in theDNMT3Agene are also the most common cause of clonal hematopoiesis, and can initiate acute myeloid leukemia (AML). Using whole genome bisulfite sequencing, we studied DNA methylation in peripheral blood cells of 11 DOS patients and found a focal, canonical hypomethylation phenotype, which is most severe with the dominant negativeDNMT3AR882Hmutation. A germline mouse model expressing the homologousDnmt3aR878Hmutation phenocopies most aspects of the human DOS syndrome, including the methylation phenotype and an increased incidence of spontaneous hematopoietic malignancies, suggesting that all aspects of this syndrome are caused by this mutation.
Gαq activation modulates autophagy by promoting mTORC1 signaling
Authors: Cabezudo Sofía , Sanz-Flores Maria , Caballero Alvaro , Tasset Inmaculada , Rebollo Elena , Diaz Antonio , Aragay Anna M. , Cuervo Ana María , Mayor Federico , Ribas Catalina
Published: July 2021

The mTORC1 node plays a major role in autophagy modulation. We report a role of the ubiquitous Gαq subunit, a known transducer of plasma membrane G protein-coupled receptors signaling, as a core modulator of mTORC1 and autophagy. Cells lacking Gαq/11 display higher basal autophagy, enhanced autophagy induction upon different types of nutrient stress along with a decreased mTORC1 activation status. They are also unable to reactivate mTORC1 and thus inactivate ongoing autophagy upon nutrient recovery. Conversely, stimulation of Gαq/11 promotes sustained mTORC1 pathway activation and reversion of autophagy promoted by serum or amino acids removal. Gαq is present in autophagic compartments and lysosomes and is part of the mTORC1 multi-molecular complex, contributing to its assembly and activation via its nutrient status-sensitive interaction with p62, which displays features of a Gαq effector. Gαq emerges as a central regulator of the autophagy machinery required to maintain cellular homeostasis upon nutrient fluctuations.
Individual environmental niches in mobile organisms
Authors: Carlson Ben S. , Rotics Shay , Nathan Ran , Wikelski Martin , Jetz Walter
Published: July 2021

Individual variation is increasingly recognized as a central component of ecological processes, but its role in structuring environmental niche associations remains largely unknown. Species’ responses to environmental conditions are ultimately determined by the niches of single individuals, yet environmental associations are typically captured only at the level of species. Here, we develop scenarios for how individual variation may combine to define the compound environmental niche of populations, use extensive movement data to document individual environmental niche variation, test associated hypotheses of niche configuration, and examine the consistency of individual niches over time. For 45 individual white storks (Ciconia ciconia;116 individual-year combinations), we uncover high variability in individual environmental associations, consistency of individual niches over time, and moderate to strong niche specialization. Within populations, environmental niches follow a nested pattern, with individuals arranged along a specialist-to-generalist gradient. These results reject common assumptions of individual niche equivalency among conspecifics, as well as the separation of individual niches into disparate parts of environmental space. These findings underscore the need for a more thorough consideration of individualistic environmental responses in global change research.
Stiff and tough PDMS-MMT layered nanocomposites visualized by AIE luminogens
Authors: Peng Jingsong , Tomsia Antoni P. , Jiang Lei , Tang Ben Zhong , Cheng Qunfeng
Published: July 2021

Polydimethylsiloxane (PDMS) is a widely used soft material that exhibits excellent stability and transparency. But the difficulty of fine-tuning its Young’s modulus and its low toughness significantly hinder its application in fields such as tissue engineering and flexible devices. Inspired by nacre, here we report on the development of PDMS-montmorillonite layered (PDMS-MMT-L) nanocomposites via the ice-templating technique, resulting in 23 and 12 times improvement in Young’s modulus and toughness as compared with pure PDMS. Confocal fluorescence microscopy assisted by aggregation-induced emission (AIE) luminogens reveals three-dimensional reconstruction and in situ crack tracing of the nacre-inspired PDMS-MMT-L nanocomposite. The PDMS-MMT-L nanocomposite is toughened with mechanisms such as crack deflection and bridging. The AIE-assisted visualization of the crack propagation for nacre-inspired layered nanocomposites provides an advanced and universal characterization technique for organic-inorganic nanocomposites.
STING suppresses bone cancer pain via immune and neuronal modulation
Authors: Wang Kaiyuan , Donnelly Christopher R. , Jiang Changyu , Liao Yihan , Luo Xin , Tao Xueshu , Bang Sangsu , McGinnis Aidan , Lee Michael , Hilton Matthew J. , Ji Ru-Rong
Published: July 2021

Patients with advanced stage cancers frequently suffer from severe pain as a result of bone metastasis and bone destruction, for which there is no efficacious treatment. Here, using multiple mouse models of bone cancer, we report that agonists of the immune regulator STING (stimulator of interferon genes) confer remarkable protection against cancer pain, bone destruction, and local tumor burden. Repeated systemic administration of STING agonists robustly attenuates bone cancer-induced pain and improves locomotor function. Interestingly, STING agonists produce acute pain relief through direct neuronal modulation. Additionally, STING agonists protect against local bone destruction and reduce local tumor burden through modulation of osteoclast and immune cell function in the tumor microenvironment, providing long-term cancer pain relief. Finally, these in vivo effects are dependent on host-intrinsic STING and IFN-I signaling. Overall, STING activation provides unique advantages in controlling bone cancer pain through distinct and synergistic actions on nociceptors, immune cells, and osteoclasts.
Correlative 3D microscopy of single cells using super-resolution and scanning ion-conductance microscopy
Authors: Navikas Vytautas , Leitao Samuel M. , Grussmayer Kristin S. , Descloux Adrien , Drake Barney , Yserentant Klaus , Werther Philipp , Herten Dirk-Peter , Wombacher Richard , Radenovic Aleksandra , Fantner Georg E.
Published: July 2021

High-resolution live-cell imaging is necessary to study complex biological phenomena. Modern fluorescence microscopy methods are increasingly combined with complementary, label-free techniques to put the fluorescence information into the cellular context. The most common high-resolution imaging approaches used in combination with fluorescence imaging are electron microscopy and atomic-force microscopy (AFM), originally developed for solid-state material characterization. AFM routinely resolves atomic steps, however on soft biological samples, the forces between the tip and the sample deform the fragile membrane, thereby distorting the otherwise high axial resolution of the technique. Here we present scanning ion-conductance microscopy (SICM) as an alternative approach for topographical imaging of soft biological samples, preserving high axial resolution on cells. SICM is complemented with live-cell compatible super-resolution optical fluctuation imaging (SOFI). To demonstrate the capabilities of our method we show correlative 3D cellular maps with SOFI implementation in both 2D and 3D with self-blinking dyes for two-color high-order SOFI imaging. Finally, we employ correlative SICM/SOFI microscopy for visualizing actin dynamics in live COS-7 cells with subdiffraction-resolution.
Comparison of COVID-19 outcomes among shielded and non-shielded populations
Authors: Jani Bhautesh D. , Ho Frederick K. , Lowe David J. , Traynor Jamie P. , MacBride-Stewart Sean P. , Mark Patrick B. , Mair Frances S. , Pell Jill P.
Published: July 2021

Many western countries used shielding (extended self-isolation) of people presumed to be at high-risk from COVID-19 to protect them and reduce healthcare demand. To investigate the effectiveness of this strategy, we linked family practitioner, prescribing, laboratory, hospital and death records and compared COVID-19 outcomes among shielded and non-shielded individuals in the West of Scotland. Of the 1.3 million population, 27,747 (2.03%) were advised to shield, and 353,085 (26.85%) were classified a priori as moderate risk. COVID-19 testing was more common in the shielded (7.01%) and moderate risk (2.03%) groups, than low risk (0.73%). Referent to low-risk, the shielded group had higher confirmed infections (RR 8.45, 95% 7.44–9.59), case-fatality (RR 5.62, 95% CI 4.47–7.07) and population mortality (RR 57.56, 95% 44.06–75.19). The moderate-risk had intermediate confirmed infections (RR 4.11, 95% CI 3.82–4.42) and population mortality (RR 25.41, 95% CI 20.36–31.71) but, due to their higher prevalence, made the largest contribution to deaths (PAF 75.30%). Age ≥ 70 years accounted for 49.55% of deaths. In conclusion, in spite of the shielding strategy, high risk individuals were at increased risk of death. Furthermore, to be effective as a population strategy, shielding criteria would have needed to be widely expanded to include other criteria, such as the elderly.
Sarcopenia, severe anxiety and increased C-reactive protein are associated with severe fatigue in patients with inflammatory bowel diseases
Authors: Tasson Laura , Zingone Fabiana , Barberio Brigida , Valentini Romina , Ballotta Pamela , Ford Alexander C. , Scarpa Marco , Angriman Imerio , Fassan Matteo , Savarino Edoardo
Published: July 2021

Patients with inflammatory bowel disease (IBD) report fatigue more frequently than healthy population, but the precise mechanisms underlying its presence are unknown. This study aimed to evaluate the prevalence of fatigue in IBD and its relation with potential causative factors. A survey on fatigue, depression, anxiety, sleep disorders, and the presence of sarcopenia and malnutrition, was sent by email to 244 IBD outpatients of the Gastroenterology Unit of Academic Hospital of Padua.Demographics and clinical data, including the levels of fecal calprotectin (FC) and C-reactive protein (CRP), and current pharmacological treatments were obtained from patients’ medical records. Ninety-nine (40.5%) subjects answered the survey. Ninety-two (92.9%) patients reported fatigue, with sixty-six having mild to moderate fatigue and twenty-six severe fatigue. Multivariate analysis showed that abnormal values of CRP (OR 5.1), severe anxiety (OR 3.7) and sarcopenia (OR 4.4) were the factors independently associated with severe fatigue. Fatigue has a high prevalence in subject affected by IBD. Subjects with altered CRP, sarcopenia and severe anxiety appear more at risk of severe fatigue.
Association of CNR1 and INSIG2 polymorphisms with antipsychotics-induced weight gain: a prospective nested case–control study
Authors: Jimeno Natalia , Velasco-Gonzalez Veronica , Fierro Inmaculada , Duran Mercedes , Carvajal Alfonso
Published: July 2021

Weight gain is a frequent and severe adverse reaction in patients taking antipsychotics. The objective was to further investigate in a natural setting influential risk factors associated with clinically significant weight gain. An observational follow-up study was conducted. Patients when initiating treatment with whatever antipsychotic were included; a structured questionnaire was applied at baseline, 3 and 6 months later; a blood sample was obtained. In a nested case–control approach, patients with an increase ≥ 7% of their initial weight were considered as cases, the remaining, as controls. The results showed that, out of 185 patients, 137 completed the 6-month follow-up (cases, 38; controls, 99). Weight gain gradually and significantly increased in cases (baseline, 65.0 kg; 6 months, 74.0 kg) but not in controls (65.6 kg and 65.8 kg, respectively). Age (adjusted OR = 0.97, 95% CI = 0.96–0.99, p = 0.004), olanzapine (adjusted OR = 2.98, 95% CI = 1.13–7.80, p = 0.027) and quetiapine (adjusted OR = 0.25, 95% = 0.07–0.92, p = 0.037) significantly associated with weight gain. An association was also found for the CNR1 (rs1049353) and INSIG2 (rs7566605) polymorphisms. In conclusion, an increased risk of antipsychotics-induced weight gain was observed for younger age and olanzapine, and a relative lower risk for quetiapine. A potential role of CNR1 rs1049353 and INSIG2 rs7566605 polymorphisms is suggested.
Knockdown screening of chromatin binding and regulatory proteins in zebrafish identified Suz12b as a regulator of tfpia and an antithrombotic drug target
Authors: Raman Revathi , Fallatah Weam , Al Qaryoute Ayah , Dhinoja Sanchi , Jagadeeswaran Pudur
Published: July 2021

Tissue factor pathway inhibitor (TFPI) is an anticoagulant protein that inhibits factor VIIa and Xa in the coagulation cascade. It has been shown that forkhead box P3 protein is a TFPI transcriptional repressor. However, there are no studies on chromatin remodeling that control TFPI expression. We hypothesized that the genome-wide knockdowns of the chromatin binding and regulatory proteins (CBRPs) in zebrafish could identify novel tfpia gene regulators. As an initial step, we selected 69 CBRP genes from the list of zebrafish thrombocyte-expressed genes. We then performed a 3-gene piggyback knockdown screen of these 69 genes, followed by quantification of tfpia mRNA levels. The results revealed that knockdown of brd7, ing2, ing3, ing4, and suz12b increased tfpia mRNA levels. The simultaneous knockdown of these 5 genes also increased tfpia mRNA levels. We also performed individual gene and simultaneous 5-gene knockdowns on the 5 genes in zebrafish larvae. We found that after laser injury, it took a longer time for the formation of the thrombus to occlude the caudal vessel compared to the control larvae. We then treated the larvae and adults with a chemical UNC6852 known to proteolytically degrade polycomb repressor complex 2, where SUZ12 is a member, and observed prolongation of time to occlude (TTO) the caudal vein after laser injury and increased tfpia mRNA levels in larvae and adults, respectively. In summary, our results have identified novel epigenetic regulators for tfpia and exploited this information to discover a drug that enhances tfpia mRNA levels and prolongation of TTO. This discovery provides the basis for testing whether UNC6852 could be used as an antithrombotic drug. This approach could be used to study the regulation of other plasma proteins, including coagulant and anticoagulant factors.
The effectiveness of the use of augmented reality in anatomy education: a systematic review and meta-analysis
Authors: Bölek Kerem A. , De Jong Guido , Henssen Dylan
Published: July 2021

The use of Augmented Reality (AR) in anatomical education has been promoted by numerous authors. Next to financial and ethical advantages, AR has been described to decrease cognitive load while increasing student motivation and engagement. Despite these advantages, the effects of AR on learning outcome varies in different studies and an overview and aggregated outcome on learning anatomy is lacking. Therefore, a meta-analysis on the effect of AR vs. traditional anatomical teaching methods on learning outcome was performed. Systematic database searches were conducted by two independent investigators using predefined inclusion and exclusion criteria. This yielded five papers for meta-analysis totaling 508 participants; 240 participants in the AR-groups and 268 participants in the control groups. (306 females/202 males). Meta-analysis showed no significant difference in anatomic test scores between the AR group and the control group (− 0.765 percentage-points (%-points); P = 0.732). Sub analysis on the use of AR vs. the use of traditional 2D teaching methods showed a significant disadvantage when using AR (− 5.685%-points; P = 0.024). Meta-regression analysis showed no significant co-relation between mean difference in test results and spatial abilities (as assessed by the mental rotations test scores). Student motivation and/or engagement could not be included since studies used different assessment tools. This meta-analysis showed that insufficient evidence is present to conclude AR significantly impacts learning outcome and that outcomes are significantly impacted by students’ spatial abilities. However, only few papers were suitable for meta-analysis, indicating that there is a need for more well-designed, randomized-controlled trials on AR in anatomy education research.