bluuebunny/crossref_metadata_2025 huggingface dataset:
Future Drought in the Dry Lands of Asia Under the 1.5 and 2.0 °C Warming Scenarios
Authors: Miao Lijuan , Li Suyuan , Zhang Feng , Chen Tiexi , Shan Yunpeng , Zhang Yushan
Published: April 2020

Drought has become a major threat to local sustainable development in dryland Asia, one of the largest grassland ecosystems in the world. However, empirical‐ and science‐based evidence regarding the extent of drought changes and the future trends of these changes in dryland Asia is variable and incomplete. Here, we first investigate the historical variations in drought conditions in dryland Asia, as measured by the drought intensity and arid area, using three widely used drought indices (the Palmer Drought Severity Index, the Standardized Precipitation Index, and the Standardized Precipitation Evapotranspiration Index). Then, we use Bayesian model averaging to reproduce the future drought conditions under two representative concentration pathways (RCP2.6 and RCP4.5) from the Coupled Model Intercomparison Project Phase 5 Earth system models. The Palmer Drought Severity Index, Standardized Precipitation Index, and Standardized Precipitation Evapotranspiration Index illustrate that dryland Asia has experienced an overall drying trend and an expansion of arid areas over the past 100 years (1901–2016). Both temperature and precipitation are projected to increase under both the 1.5 and 2.0 °C warming scenarios compared with the values from the reference period (1986–2005). The projected drought conditions in the 1.5 and 2.0 °C warming scenarios will worsen, especially across Kazakhstan and Northwest China. We found that the drought conditions under the 2.0 °C warming conditions will not be as severe as those under the 1.5 °C warming conditions due to the mitigating effect of the projected precipitation increase under RCP4.5. These results call for short‐term and long‐term mitigation and adaptation measurements for drought events in dryland Asia.
Fossil Fuel Combustion Is Driving Indoor CO2 Toward Levels Harmful to Human Cognition
Authors: Karnauskas Kristopher B. , Miller Shelly L. , Schapiro Anna C.
Published: April 2020

Human activities are elevating atmospheric carbon dioxide concentrations to levels unprecedented in human history. The majority of anticipated impacts of anthropogenic CO2 emissions are mediated by climate warming. Recent experimental studies in the fields of indoor air quality and cognitive psychology and neuroscience, however, have revealed significant direct effects of indoor CO2 levels on cognitive function. Here, we shed light on this connection and estimate the impact of continued fossil fuel emissions on human cognition. We conclude that indoor CO2 levels may indeed reach levels harmful to cognition by the end of this century, and the best way to prevent this hidden consequence of climate change is to reduce fossil fuel emissions. Finally, we offer recommendations for a broad, interdisciplinary approach to improving such understanding and prediction.
Climatology of the Equatorial Plasma Bubbles Captured by FORMOSAT‐3/COSMIC
Authors: Chou Min‐Yang , Wu Qian , Pedatella N. M. , Cherniak Iurii , Schreiner William S. , Braun John
Published: April 2020

The FORMOSAT‐3/COSMIC (F3/C) satellites are used to study the climatology of equatorial plasma bubbles (EPBs) during the low to moderate solar flux years (2008–2013). We use the F3/C total electron content to identify the presence of EPBs and investigate the background conditions for the initiation of EPBs. The results reveal that the EPB activities have strong solar dependence. The longitudinal and seasonal trends of EPBs are highly correlated to the angle between the dusk solar terminator and magnetic field lines near the magnetic equator. Asymmetries of EPBs between solstices and equinoxes exist and could be due partly to the asymmetry of equatorial ionization anomaly structures, which result in longitudinal differences as well. EPBs extend to higher altitudes and latitudes during the ascending phase of Solar Cycle 24 (2011–2013) due mainly to the increase of background electron density. However, an altitudinal asymmetry of EPBs occurs in moderate solar flux years, which is likely due to the suppression or lower growth and occurrence rates of EPBs. In addition to vertical drift, tidal forcing also contributes to the longitudinal and seasonal distributions of EPBs. Upwellings and precursor waves preceding the EPBs are observed climatologically, which likely play a vital role in initiating the EPBs. This study also reveals a vertical connection between the equatorial ionospheric irregularities and atmospheric forcing on a climatological basis.
Seismic Azimuthal Anisotropy for the Southeastern Tibetan Plateau Extracted by Wave Gradiometry Analysis
Authors: Cao Feihuang , Liang Chuntao , Zhou Lu , Zhu Jieshou
Published: April 2020

Wave Gradiometry (WG) is a dense array data processing method used to extract seismic velocity and other properties of the earth. In this study, we propose using WG for a plane wave field to measure azimuthal anisotropy by fitting the phase velocities from different back azimuths. We applied this new method to the Temporary Western Sichuan Array and obtained the isotropic and azimuthal anisotropy for period bands centered atT = 20, 40, and 60 s in the southeast Tibetan Plateau. Our results show that the fast orientations of anisotropy are well consistent with the strikes of the fault system and orogenic belt. The weak anisotropic magnitude in the northern part of the south Chuandian subblock and a consistence of fast orientation in boundary fault zone (BFZ) at different periods may be attributed to anisotropic relics associated with the Emeishan Large Igneous Province. Comparing our results with those of previous studies, we found that our anisotropic results are consistent with anisotropic structures measured by the Pms phase in the plateau area, while a systematical angular difference exists in the BFZ, Sichuan Basin, and south Chuandian subblock where high Rayleigh wave phase velocity was observed. The Lijiang‐Xiaojin fault and Longmenshan fault appear to form a deep‐rooted strong boundary at the lithospheric scale, as they serve as a boundary for anisotropic structures, isotropic velocity, and the other three WG parameters.
Temporal Characteristics and Potential Sources of Black Carbon in Megacity Shanghai, China
Authors: Wei C. , Wang M. H. , Fu Q. Y. , Dai C. , Huang R. , Bao Q.
Published: April 2020

Black carbon (BC) is a major light absorption material that acts as a climate change driver with high radiative forcing and as an air pollutant that reduces visibility and air quality. Thus, reducing the emission and ambient concentration of BC could help address climate change and improve air quality simultaneously. In this study, the mass concentration of atmospheric BC was continuously measured by an aethalometer in Shanghai in 2017. The annual BC concentration was 2.19 ± 1.28 μg/m3, with the highest loading in winter and the lowest loading in autumn. The BC concentrations varied with year and location when compared with previous studies in different locations in Shanghai. The hourly BC concentration had a bimodal distribution, with two peaks during the morning and evening traffic rush hours. Liquid fuels, biomass, and coal combustion contributed 65.7%, 21.5%, and 12.8%, respectively, of the total BC based on the advanced aethalometer model. The three sources varied in different seasons with a high contribution of liquid source in summer and more coal and biomass emissions in winter. High BC concentrations accumulated in the stable weather conditions in the four seasons and appeared when there were high wind speeds from the northwestern direction in winter. The Yangtze River Delta region was the most likely potential source region of high BC loading in the four seasons, and long‐range transport from North China in winter was another likely source region based on the results of cluster analysis and potential source contribution function analysis of backward trajectories.
Lower Cretaceous Provenance and Sedimentary Deposition in the Eastern Carpathians: Inferences for the Evolution of the Subducted Oceanic Domain and its European Passive Continental Margin
Authors: Roban R. D. , Ducea M. N. , Mațenco L. , Panaiotu G. C. , Profeta L. , Krézsek C. , Melinte‐Dobrinescu M. C. , Anastasiu N. , Dimofte D. , Apotrosoaei V. , Francovschi I.
Published: April 2020

Reconstructing orogenic systems made up dominantly by sediments accreted in trenches is challenging because of the incomplete lithological record of the subducted oceanic domain and its attached passive continental margin thrusted by collisional processes. In this respect, the remarkable ~600 km long continuity of sediments exposed in the Eastern Carpathian thin‐skinned thrust and fold belt and the availability of quantitative reconstructions for adjacent continental units provide excellent conditions for a paleogeographical study by provenance and sedimentological techniques constraining sediment routing and depositional systems. These sediments were deposited in the Ceahlău‐Severin branch of the Alpine Tethys Ocean and over its European passive continental margin. We report sedimentological, paleomagnetic, petrographic, and detrital zircon U‐Pb data of Lower Cretaceous sediments from several thin‐skinned tectonic units presumably deposited in the Moldavides domain of the Eastern Carpathians. Sedimentological observations in the innermost studied unit demonstrate that deposition took place in a deepwater basin floor sheets to sandy turbidite system. Detrital zircon age data demonstrate sourcing from internal Carpathian basement units. The sediment routing changes in more external units, where black shales basin floor sheets to sandy mud turbidites were sourced from an external, European continental area. Although some degree of mixing between sources located on both margins of the ocean occurred, constraining a relatively narrow width of the deep oceanic basin, these results demonstrate that the internal‐most studied unit was deposited near an Early Cretaceous accretionary wedge, located on the opposite internal side relative to the passive continental margin domain of other Moldavides units.
Tectonic Evolution of the Eastern Moroccan Meseta: From Late Devonian Forearc Sedimentation to Early Carboniferous Collision of an Avalonian Promontory
Authors: Accotto Cristina , Martínez Poyatos David , Azor Antonio , Jabaloy‐Sánchez Antonio , Talavera Cristina , Evans Noreen J. , Azdimousa Ali
Published: April 2020

The deformed Paleozoic succession of the Eastern Moroccan Meseta crops out in relatively small and isolated inliers surrounded by Mesozoic and Cenozoic rocks. Two of the largest inliers (Mekkam and Debdou) are characterized by a monotonous succession of slates and greywackes affected by polyphasic folding that occurred at low‐ to very low grade metamorphic conditions. New U‐Pb ages on detrital zircon grains from the Debdou‐Mekkam metasediments constrain the maximal depositional age as Late Devonian, interpreted to be close to the true sedimentation age. Furthermore, the εHf values of the Devonian detrital zircons, together with the presence of a series of scattered zircon grains with ages between c. 0.9 and c. 1.9 Ga, suggest provenance from a subduction‐related magmatic arc located on the Avalonian margin. The Debdou‐Mekkam massif is characterized by an Early Carboniferous first deformational event (D1), which gave way to a pervasive cleavage (S1) associated with plurikilometric‐scale, tight to isoclinal, overturned to recumbent folds. Later events (Dc) occurred at Late Carboniferous time and generated variably developed crenulation cleavages (Sc) associated with variously oriented metric‐ to kilometric‐scale folds, which complicate the pattern of both D1 intersection lineations (L1) and axial traces. The restoration of this pronounced curved pattern yields originally SW‐NE‐oriented D1 fold axes with regional SE‐vergence. This important Early Carboniferous shortening and SE‐directed tectonic transport can be explained by closure of the Rheic Ocean and the first phases of the collision between the northern passive margin of Gondwana and an Avalonian promontory.
Thank You to Our 2019 Reviewers
Authors: Trumbore Susan , Barros Ana P. , Becker Thorsten W. , Davidson Eric A. , Ehlmann Bethany L. , Gruber Nicolas , Hofmann Eileen E. , Hudson Mary K. , Illangasekare Tissa H. , Kang Sarah M. , Malanotte‐Rizzoli Paola , Nimmo Francis , Parsons Tom , Salters Vincent J.M. , Stevens Bjorn , Wuebbles Donald J. , Zeitler Peter , Zhu Tong
Published: April 2020

Members of the editorial board of AGU Advances express their appreciation to those who served as peer reviewers for the journal in its inaugural year.
Seismotectonics and Fault Geometries of the 2019 Ridgecrest Sequence: Insight From Aftershock Moment Tensor Catalog Using 3‐D Green's Functions
Authors: Wang Xin , Zhan Zhongwen
Published: April 2020

The 2019 Mw 7.1 Ridgecrest earthquake occurred on 6 July, preceded by the Mw 6.4 foreshock on 4 July 2019. These two earthquakes occurred close in space and time with partially overlapping surface ruptures and aftershock patterns, raising the question of the relationship between the two events. Geological surveys and satellite observations provide important constraints on the surface traces of faulting. However, the subsurface fault geometries, which are important for understanding the regional stress field, earthquake initiation, propagation, and termination, are not well resolved. In this study, moment tensor solutions for 256 earthquakes in the 2019 Ridgecrest sequence were determined by waveform inversion using 3‐D velocity model. The obtained moment tensor solutions show rotations of the stresses after mainshock, indicating the ratio of mainshock stress drop to the background stress to be 0.5–0.9. The obtained moment tensor catalog also facilitates a better understanding of the subsurface fault geometries, including (1) splay faults and antithetic faults in the northwest aftershock zone; (2) shallow flower structures near the Mw 7.1 epicenter; and (3) subparallel faults in the southeast aftershock zone. The aftershocks' studies suggest the very complex surface ruptures near the 2019 Ridgecrest Mw 7.1 epicenter are near‐surface features that linked to a simple large throughgoing fault at >5 km depth. We also found that the southeastern‐most aftershocks, which are located less than a kilometer from the Garlock fault trace, have significant different strike directions from that of the Garlock fault, indicating the central Garlock fault remains seismically quiet.
Meal Provision Needed for Caregivers Who Stay With a Child in Hospital
Authors: Masters-Awatere Bridgette , Graham Rebekah , Scott Nina , Atatoa Carr Polly
Published: April 2020

The provision of meals for primary caregivers when caring for a child in hospital varies across regions in Aotearoa [New Zealand]. Where meals are not provided, caregivers are expected to bring their own food from home and/or purchase food from on-site (or nearby) vendors. Twenty-four qualitative interviews with 15 Maaori (Maaori are the indigenous people of Aotearoa comprising 16.5% of the national population) whaanau [family/families] from one public hospital revealed that caregivers are reluctant to leave their child alone and that financial constraints meant that caregivers were often alone, isolated, and hungry. We recommend implementing a national meal policy to support caregivers who provide much-needed physical and emotional care for their child during a hospital stay.
Sequence variant analysis reveals poor correlations in microbial taxonomic abundance between humans and mice after gnotobiotic transfer
Authors: Fouladi Farnaz , Glenny Elaine M , Bulik-Sullivan Emily C , Tsilimigras Matthew C B , Sioda Michael , Thomas Stephanie A , Wang Yunfei , Djukic Zorka , Tang Quyen , Tarantino Lisa M , Bulik Cynthia M , Fodor Anthony A , Carroll Ian M
Published: April 2020

Transplanting human gut microbiotas into germ-free (GF) mice is a popular approach to disentangle cause-and-effect relationships between enteric microbes and disease. Algorithm development has enabled sequence variant (SV) identification from 16S rRNA gene sequence data. SV analyses can identify which donor taxa colonize recipient GF mice, and how SV abundance in humans is replicated in these mice. Fecal microbiotas from 8 human subjects were used to generate 77 slurries, which were transplanted into 153 GF mice. Strong correlations between fecal and slurry microbial communities were observed; however, only 42.15 ± 9.95% of SVs successfully transferred from the donor to the corresponding recipient mouse. Firmicutes had a particularly low transfer rate and SV abundance was poorly correlated between donor and recipient pairs. Our study confirms human fecal microbiotas colonize formerly GF mice, but the engrafted community only partially resembles the input human communities. Our findings emphasize the importance of reporting a standardized transfer rate and merit the exploration of other animal models or in silico tools to understand the relationships between human gut microbiotas and disease.
NOXA-dependent contextual synthetic lethality of BCL-XL inhibition and “osmotic reprogramming” in colorectal cancer
Authors: Knoll Gertrud , Riffelsberger Petra , Raats Danielle , Kranenburg Onno , Ehrenschwender Martin
Published: April 2020

A sophisticated network of BCL-2 family proteins regulates the mitochondria-associated (intrinsic) apoptosis pathway. Antiapoptotic members such as BCL-XL or MCL-1 safeguard the outer mitochondrial membrane and prevent accidental cell death in a functionally redundant and/or compensatory manner. However, BCL-XL/MCL-1-mediated “dual apoptosis protection” also impairs response of cancer cells to chemotherapy. Here, we show that hyperosmotic stress in the tumor environment abrogates dual BCL-XL/MCL-1 protection. Hypertonicity triggers upregulation of NOXA and loss of MCL-1 and thereby enforces exclusive BCL-XL addiction. Concomitant targeting of BCL-XL is sufficient to unlock the intrinsic apoptosis pathway in colorectal cancer cells. Functionally, “osmotic reprogramming” of the tumor environment grants contextual synthetic lethality to BCL-XL inhibitors in dually BCL-XL/MCL-1-protected cells. Generation of contextual synthetic lethality through modulation of the tumor environment could perspectively boost efficacy of anticancer drugs.
Transient receptor potential ion channel TRPM2 promotes AML proliferation and survival through modulation of mitochondrial function, ROS, and autophagy
Authors: Chen Shu-jen , Bao Lei , Keefer Kerry , Shanmughapriya Santhanam , Chen Longgui , Lee John , Wang JuFang , Zhang Xue-Qian , Hirschler-Laszkiewicz Iwona , Merali Salim , Merali Carmen , Imamura Yuka , Dovat Sinisa , Madesh Muniswamy , Cheung Joseph Y. , Wang Hong-Gang , Miller Barbara A.
Published: April 2020

Transient receptor potential melastatin 2 (TRPM2) ion channel has an essential function in maintaining cell survival following oxidant injury. Here, we show that TRPM2 is highly expressed in acute myeloid leukemia (AML). The role of TRPM2 in AML was studied following depletion with CRISPR/Cas9 technology in U937 cells. In in vitro experiments and in xenografts, depletion of TRPM2 in AML inhibited leukemia proliferation, and doxorubicin sensitivity was increased. Mitochondrial function including oxygen consumption rate and ATP production was reduced, impairing cellular bioenergetics. Mitochondrial membrane potential and mitochondrial calcium uptake were significantly decreased in depleted cells. Mitochondrial reactive oxygen species (ROS) were significantly increased, and Nrf2 was decreased, reducing the antioxidant response. In TRPM2-depleted cells, ULK1, Atg7, and Atg5 protein levels were decreased, leading to autophagy inhibition. Consistently, ATF4 and CREB, two master transcription factors for autophagosome biogenesis, were reduced in TRPM2-depleted cells. In addition, Atg13 and FIP200, which are known to stabilize ULK1 protein, were decreased. Reconstitution with TRPM2 fully restored proliferation, viability, and autophagy; ATF4 and CREB fully restored proliferation and viability but only partially restored autophagy. TRPM2 expression reduced the elevated ROS found in depleted cells. These data show that TRPM2 has an important role in AML proliferation and survival through regulation of key transcription factors and target genes involved in mitochondrial function, bioenergetics, the antioxidant response, and autophagy. Targeting TRPM2 may represent a novel therapeutic approach to inhibit myeloid leukemia growth and enhance susceptibility to chemotherapeutic agents through multiple pathways.
Carnosol inhibits inflammasome activation by directly targeting HSP90 to treat inflammasome-mediated diseases
Authors: Shi Wei , Xu Guang , Zhan Xiaoyan , Gao Yuan , Wang Zhilei , Fu Shubin , Qin Nan , Hou Xiaorong , Ai Yongqiang , Wang Chunyu , He Tingting , Liu Hongbin , Chen Yuanyuan , Liu Yan , Wang Jiabo , Niu Ming , Guo Yuming , Xiao Xiaohe , Bai Zhaofang
Published: April 2020

Aberrant activation of inflammasomes, a group of protein complexes, is pathogenic in a variety of metabolic and inflammation-related diseases. Here, we report that carnosol inhibits NLRP3 inflammasome activation by directly targeting heat-shock protein 90 (HSP90), which is essential for NLRP3 inflammasome activity, thereby treating inflammasome-mediated diseases. Our data demonstrate that carnosol inhibits NLRP3 inflammasome activation in primary mouse bone marrow-derived macrophages (BMDMs), THP-1 cells and human peripheral blood mononuclear cells (hPBMCs). Mechanistically, carnosol inhibits inflammasome activation by binding to HSP90 and then inhibiting its ATPase activity. In vivo, our results show that carnosol has remarkable therapeutic effects in mouse models of NLRP3 inflammasome-mediated diseases, including endotoxemia and nonalcoholic steatohepatitis (NASH). Our data also suggest that intraperitoneal administration of carnosol (120 mg/kg) once daily for two weeks is well tolerated in mice. Thus, our study reveals the inhibitory effect of carnosol on inflammasome activation and demonstrates that carnosol is a safe and effective candidate for the treatment of inflammasome-mediated diseases.
Switched-capacitor-convertors based on fractal design for output power management of triboelectric nanogenerator
Authors: Liu Wenlin , Wang Zhao , Wang Gao , Zeng Qixuan , He Wencong , Liu Liyu , Wang Xue , Xi Yi , Guo Hengyu , Hu Chenguo , Wang Zhong Lin
Published: April 2020

Owing to the advantages of integration and being magnet-free and light-weight, the switched-capacitor-convertor plays an increasing role compared to traditional transformer in some specific power supply systems. However, the high output impedance and switching loss largely reduces its power efficiency, due to imperfect topology and transistors. Herein, we propose a fractal-design based switched-capacitor-convertors with characteristics including high conversion efficiency, minimum output impedance, and electrostatic voltage applicability. As a double-function output power management system for triboelectric nanogenerators, it delivers over 67 times charge boosting and 954 W m−2 power density in pulse mode, and achieves over 94% total energy transfer efficiency in constant mode. The establishment of the fractal-design switched-capacitor-convertors provides significant guidance for the development of power management toward multi-functional output for numerous applications. The successful demonstration in triboelectric nanogenerators also declares its great potential in electric vehicles, DC micro-grids etc.
Redrawing the Iceland−Scotland Overflow Water pathways in the North Atlantic
Authors: Zou Sijia , Bower Amy , Furey Heather , Susan Lozier M. , Xu Xiaobiao
Published: April 2020

Iceland-Scotland Overflow Water (ISOW) is a primary deep water mass exported from the Norwegian Sea into the North Atlantic as part of the global Meridional Overturning Circulation. ISOW has historically been depicted as flowing counter-clockwise in a deep boundary current around the subpolar North Atlantic, but this single-boundary-following pathway is being challenged by new Lagrangian observations and model simulations. We show here that ISOW leaves the boundary and spreads into the interior towards the central Labrador and Irminger basins after flowing through the Charlie-Gibbs Fracture Zone. We also describe a newly observed southward pathway of ISOW along the western flank of the Mid-Atlantic Ridge. The partitioning of these pathways is shown to be influenced by deep-reaching eddies and meanders of the North Atlantic Current. Our results, in tandem with previous studies, call for a revision in the historical depiction of ISOW pathways throughout the North Atlantic.
Molecular profiling of driver events in metastatic uveal melanoma
Authors: Karlsson Joakim , Nilsson Lisa M. , Mitra Suman , Alsén Samuel , Shelke Ganesh Vilas , Sah Vasu R. , Forsberg Elin M. V. , Stierner Ulrika , All-Eriksson Charlotta , Einarsdottir Berglind , Jespersen Henrik , Ny Lars , Lindnér Per , Larsson Erik , Olofsson Bagge Roger , Nilsson Jonas A.
Published: April 2020

Metastatic uveal melanoma is less well understood than its primary counterpart, has a distinct biology compared to skin melanoma, and lacks effective treatments. Here we genomically profile metastatic tumors and infiltrating lymphocytes. BAP1 alterations are overrepresented and found in 29/32 of cases. Reintroducing a functional BAP1 allele into a deficient patient-derived cell line, reveals a broad shift towards a transcriptomic subtype previously associated with better prognosis of the primary disease. One outlier tumor has a high mutational burden associated with UV-damage. CDKN2A deletions also occur, which are rarely present in primaries. A focused knockdown screen is used to investigate overexpressed genes associated withcopy number gains. Tumor-infiltrating lymphocytes are in several cases found tumor-reactive, but expression of the immune checkpoint receptors TIM-3, TIGIT and LAG3 is also abundant. This study represents the largest whole-genome analysis of uveal melanoma to date, and presents an updated view of the metastatic disease.
Observation of edge solitons in photonic graphene
Authors: Zhang Zhaoyang , Wang Rong , Zhang Yiqi , Kartashov Yaroslav V. , Li Feng , Zhong Hua , Guan Hua , Gao Kelin , Li Fuli , Zhang Yanpeng , Xiao Min
Published: April 2020

Edge states emerge in diverse areas of science, offering promising opportunities for the development of future electronic or optoelectronic devices, sound and light propagation control in acoustics and photonics. Previous experiments on edge states in photonics were carried out mostly in linear regimes, but the current belief is that nonlinearity introduces more striking features into physics of edge states, leading to the formation of edge solitons, optical isolation, making possible stable lasing in such states, to name a few. Here we report the observation of edge solitons at the zigzag edge of a reconfigurable photonic graphene lattice created via the effect of electromagnetically induced transparency in an atomic vapor cell with controllable nonlinearity. To obtain edge solitons, Raman gain is introduced to compensate strong absorption experienced by the edge state during propagation. Our observations may open the way for future experimental exploration of topological photonics on this nonlinear, reconfigurable platform.
Stochasticity constrained by deterministic effects of diet and age drive rumen microbiome assembly dynamics
Authors: Furman Ori , Shenhav Liat , Sasson Goor , Kokou Fotini , Honig Hen , Jacoby Shamay , Hertz Tomer , Cordero Otto X. , Halperin Eran , Mizrahi Itzhak
Published: April 2020

How complex communities assemble through the animal’s life, and how predictable the process is remains unexplored. Here, we investigate the forces that drive the assembly of rumen microbiomes throughout a cow’s life, with emphasis on the balance between stochastic and deterministic processes. We analyse the development of the rumen microbiome from birth to adulthood using 16S-rRNA amplicon sequencing data and find that the animals shared a group of core successional species that invaded early on and persisted until adulthood. Along with deterministic factors, such as age and diet, early arriving species exerted strong priority effects, whereby dynamics of late successional taxa were strongly dependent on microbiome composition at early life stages. Priority effects also manifest as dramatic changes in microbiome development dynamics between animals delivered by C-section vs. natural birth, with the former undergoing much more rapid species invasion and accelerated microbiome development. Overall, our findings show that together with strong deterministic constrains imposed by diet and age, stochastic colonization in early life has long-lasting impacts on the development of animal microbiomes.
A double-hit of stress and low-grade inflammation on functional brain network mediates posttraumatic stress symptoms
Authors: Kim Jungyoon , Yoon Sujung , Lee Suji , Hong Haejin , Ha Eunji , Joo Yoonji , Lee Eun Hee , Lyoo In Kyoon
Published: April 2020

Growing evidence indicates a reciprocal relationship between low-grade systemic inflammation and stress exposure towards increased vulnerability to neuropsychiatric disorders, including posttraumatic stress disorder (PTSD). However, the neural correlates of this reciprocity and their influence on the subsequent development of PTSD are largely unknown. Here we investigated alterations in functional connectivity among brain networks related to low-grade inflammation and stress exposure using two large independent data sets. Functional couplings among the higher-order cognitive network system including the salience, default mode, and central executive networks were reduced in association with low-grade inflammation and stress exposure. This reduced functional coupling may also be related to subsequent posttraumatic stress symptom severity. The current findings propose functional couplings among the higher-order cognitive network system as neural correlates of low-grade inflammation and stress exposure, and suggest that low-grade inflammation, alongside with stress, may render individuals more vulnerable to PTSD.
Mouse tracking reveals structure knowledge in the absence of model-based choice
Authors: Konovalov Arkady , Krajbich Ian
Published: April 2020

Converging evidence has demonstrated that humans exhibit two distinct strategies when learning in complex environments. One is model-free learning, i.e., simple reinforcement of rewarded actions, and the other is model-based learning, which considers the structure of the environment. Recent work has argued that people exhibit little model-based behavior unless it leads to higher rewards. Here we use mouse tracking to study model-based learning in stochastic and deterministic (pattern-based) environments of varying difficulty. In both tasks participants’ mouse movements reveal that they learned the structures of their environments, despite the fact that standard behavior-based estimates suggested no such learning in the stochastic task. Thus, we argue that mouse tracking can reveal whether subjects have structure knowledge, which is necessary but not sufficient for model-based choice.
Scavenger receptor-A is a biomarker and effector of rheumatoid arthritis: A large-scale multicenter study
Authors: Hu Fanlei , Jiang Xiang , Guo Chunqing , Li Yingni , Chen Shixian , Zhang Wei , Du Yan , Wang Ping , Zheng Xi , Fang Xiangyu , Li Xin , Song Jing , Xie Yang , Huang Fei , Xue Jimeng , Bai Mingxin , Jia Yuan , Liu Xu , Ren Limin , Zhang Xiaoying , Guo Jianping , Pan Hudan , Su Yin , Yi Huanfa , Ye Hua , Zuo Daming , Li Juan , Wu Huaxiang , Wang Yongfu , Li Ru , Liu Liang , Wang Xiang-Yang , Li Zhanguo
Published: April 2020

Early diagnosis is critical to improve outcomes in rheumatoid arthritis (RA), but current diagnostic tools have limited sensitivity. Here we report a large-scale multicenter study involving training and validation cohorts of 3,262 participants. We show that serum levels of soluble scavenger receptor-A (sSR-A) are increased in patients with RA and correlate positively with clinical and immunological features of the disease. This discriminatory capacity of sSR-A is clinically valuable and complements the diagnosis for early stage and seronegative RA. sSR-A also has 15.97% prevalence in undifferentiated arthritis patients. Furthermore, administration of SR-A accelerates the onset of experimental arthritis in mice, whereas inhibition of SR-A ameliorates the disease pathogenesis. Together, these data identify sSR-A as a potential biomarker in diagnosis of RA, and targeting SR-A might be a therapeutic strategy.
Transcriptional downregulation of MHC class I and melanoma de- differentiation in resistance to PD-1 inhibition
Authors: Lee Jenny H. , Shklovskaya Elena , Lim Su Yin , Carlino Matteo S. , Menzies Alexander M. , Stewart Ashleigh , Pedersen Bernadette , Irvine Malama , Alavi Sara , Yang Jean Y. H. , Strbenac Dario , Saw Robyn P. M. , Thompson John F. , Wilmott James S. , Scolyer Richard A. , Long Georgina V. , Kefford Richard F. , Rizos Helen
Published: April 2020

Transcriptomic signatures designed to predict melanoma patient responses to PD-1 blockade have been reported but rarely validated. We now show that intra-patient heterogeneity of tumor responses to PD-1 inhibition limit the predictive performance of these signatures. We reasoned that resistance mechanisms will reflect the tumor microenvironment, and thus we examined PD-1 inhibitor resistance relative to T-cell activity in 94 melanoma tumors collected at baseline and at time of PD-1 inhibitor progression. Tumors were analyzed using RNA sequencing and flow cytometry, and validated functionally. These analyses confirm that major histocompatibility complex (MHC) class I downregulation is a hallmark of resistance to PD-1 inhibitors and is associated with the MITFlow/AXLhigh de-differentiated phenotype and cancer-associated fibroblast signatures. We demonstrate that TGFß drives the treatment resistant phenotype (MITFlow/AXLhigh) and contributes to MHC class I downregulation in melanoma. Combinations of anti-PD-1 with drugs that target the TGFß signaling pathway and/or which reverse melanoma de-differentiation may be effective future therapeutic strategies.
Transformable hybrid semiconducting polymer nanozyme for second near-infrared photothermal ferrotherapy
Authors: Jiang Yuyan , Zhao Xuhui , Huang Jiaguo , Li Jingchao , Upputuri Paul Kumar , Sun He , Han Xiao , Pramanik Manojit , Miao Yansong , Duan Hongwei , Pu Kanyi , Zhang Ruiping
Published: April 2020

Despite its growing promise in cancer treatment, ferrotherapy has low therapeutic efficacy due to compromised Fenton catalytic efficiency in tumor milieu. We herein report a hybrid semiconducting nanozyme (HSN) with high photothermal conversion efficiency for photoacoustic (PA) imaging-guided second near-infrared photothermal ferrotherapy. HSN comprises an amphiphilic semiconducting polymer as photothermal converter, PA emitter and iron-chelating Fenton catalyst. Upon photoirradiation, HSN generates heat not only to induce cytotoxicity but also to enhance Fenton reaction. The increased ·OH generation promotes both ferroptosis and apoptosis, oxidizes HSN (42 nm) and transforms it into tiny segments (1.7 nm) with elevated intratumoral permeability. The non-invasive seamless synergism leads to amplified therapeutic effects including a deep ablation depth (9 mm), reduced expression of metastasis-related proteins and inhibition of metastasis from primary tumor to distant organs. Thereby, our study provides a generalized nanozyme strategy to compensate both ferrotherapy and phototherapeutics for complete tumor regression.
Resonant nanostructures for highly confined and ultra-sensitive surface phonon-polaritons
Authors: Dubrovkin Alexander M. , Qiang Bo , Salim Teddy , Nam Donguk , Zheludev Nikolay I. , Wang Qi Jie
Published: April 2020

Plasmonics on metal-dielectric interfaces was widely seen as the main route for miniaturization of components and interconnect of photonic circuits. However recently, ultra-confined surface phonon-polaritonics in high-index chalcogenide films of nanometric thickness has emerged as an important alternative to plasmonics. Here, using mid-IR near-field imaging we demonstrate tunable surface phonon-polaritons in CMOS-compatible interfaces of few-nm thick germanium on silicon carbide. We show that Ge-SiC resonators with nanoscale footprint can support sheet and edge surface modes excited at the free space wavelength hundred times larger than their physical dimensions. Owing to the surface nature of the modes, the sensitivity of real-space polaritonic patterns provides pathway for local detection of the interface composition change at sub-nanometer level. Such deeply subwavelength resonators are of interest for high-density optoelectronic applications, filters, dispersion control and optical delay devices.
Intramolecular chaperone-mediated secretion of an Rhs effector toxin by a type VI secretion system
Authors: Pei Tong-Tong , Li Hao , Liang Xiaoye , Wang Zeng-Hang , Liu Guangfeng , Wu Li-Li , Kim Haeun , Xie Zhiping , Yu Ming , Lin Shuangjun , Xu Ping , Dong Tao G.
Published: April 2020

Bacterial Rhs proteins containing toxic domains are often secreted by type VI secretion systems (T6SSs) through unclear mechanisms. Here, we show that the T6SS Rhs-family effector TseI of Aeromonas dhakensis is subject to self-cleavage at both the N- and the C-terminus, releasing the middle Rhs core and two VgrG-interacting domains (which we name VIRN and VIRC). VIRC is an endonuclease, and the immunity protein TsiI protects against VIRC toxicity through direct interaction. Proteolytic release of VIRC and VIRN is mediated, respectively, by an internal aspartic protease activity and by two conserved glutamic residues in the Rhs core. Mutations abolishing self-cleavage do not block secretion, but reduce TseI toxicity. Deletion of VIRN or the Rhs core abolishes secretion. TseI homologs from Pseudomonas syringae, P. aeruginosa, and Vibrio parahaemolyticus are also self-cleaved. VIRN and VIRC interact with protein VgrG1, while the Rhs core interacts with protein TecI. We propose that VIRN and the Rhs core act as T6SS intramolecular chaperones to facilitate toxin secretion and function.
Author Correction: Temporal dynamic reorganization of 3D chromatin architecture in hormone-induced breast cancer and endocrine resistance
Authors: Zhou Yufan , Gerrard Diana L. , Wang Junbai , Li Tian , Yang Yini , Fritz Andrew J. , Rajendran Mahitha , Fu Xiaoyong , Stein Gary , Schiff Rachel , Lin Shili , Frietze Seth , Jin Victor X.
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Large scale active-learning-guided exploration for in vitro protein production optimization
Authors: Borkowski Olivier , Koch Mathilde , Zettor Agnès , Pandi Amir , Batista Angelo Cardoso , Soudier Paul , Faulon Jean-Loup
Published: April 2020

Lysate-based cell-free systems have become a major platform to study gene expression but batch-to-batch variation makes protein production difficult to predict. Here we describe an active learning approach to explore a combinatorial space of ~4,000,000 cell-free buffer compositions, maximizing protein production and identifying critical parameters involved in cell-free productivity. We also provide a one-step-method to achieve high quality predictions for protein production using minimal experimental effort regardless of the lysate quality.
Author Correction: The effects of mutational processes and selection on driver mutations across cancer types
Authors: Temko Daniel , Tomlinson Ian P. M. , Severini Simone , Schuster-Böckler Benjamin , Graham Trevor A.
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Synthesis of bridged tricyclo[5.2.1.01,5]decanes via nickel-catalyzed asymmetric domino cyclization of enynones
Authors: Chen Jiachang , Wang Yiming , Ding Zhengtian , Kong Wangqing
Published: April 2020

The restricted availability, expense and toxicity of precious metal catalysts such as rhodium and palladium challenge the sustainability of synthetic chemistry. As such, nickel catalysts have garnered increasing attention as replacements for enyne cyclization reactions. On the other hand, bridged tricyclo[5.2.1.01,5]decanes are found as core structures in many biologically active natural products; however, the synthesis of such frameworks with high functionalities from readily available precursors remains a significant challenge. Herein, we report a nickel-catalyzed asymmetric domino cyclization reaction of enynones, providing rapid and modular synthesis of bridged tricyclo[5.2.1.01,5]decane skeletons with three quaternary stereocenters in good yields and remarkable high levels of regio- and enantioselectivities (92–99% ee).
Author Correction: Insight on Tafel slopes from a microkinetic analysis of aqueous electrocatalysis for energy conversion
Authors: Shinagawa Tatsuya , Garcia-Esparza Angel T. , Takanabe Kazuhiro
Published: April 2020

A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Cool White Polymer Coatings based on Glass Bubbles for Buildings
Authors: Nie Xiao , Yoo Youngjae , Hewakuruppu Hasitha , Sullivan Jonathan , Krishna Anirudh , Lee Jaeho
Published: April 2020

While most selective emitter materials are inadequate or inappropriate for building applications, here we present a techno-economically viable optical coating by integrating glass bubbles within a polymer film. A controlled glass bubble volume concentration from 0 to 70% leads to a selective solar reflectivity increase from 0.06 to 0.92 while the mid-infrared emissivity remains above 0.85. Outdoor measurements show the polymer coating on a concrete surface can provide a temperature reduction up to 25 °C during the day when conduction and convection are limited and a net cooling power greater than 78 W/m2 at a cost less than $0.005/W. The impact of polymer coating on common buildings is estimated as potential annual energy savings of 2–12 MJ/m2 and CO2 emission savings of 0.3–1.5 kg/m2. More savings are expected for higher surface-area-to-volume-ratio buildings, and the polymer coating is also expected to resolve cooling issues for old buildings with no air conditioning.
The non-receptor tyrosine kinase Pyk2 modulates acute locomotor effects of cocaine in D1 receptor-expressing neurons of the nucleus accumbens
Authors: de Pins Benoit , Montalban Enrica , Vanhoutte Peter , Giralt Albert , Girault Jean-Antoine
Published: April 2020

The striatum is critical for cocaine-induced locomotor responses. Although the role of D1 receptor-expressing neurons is established, underlying molecular pathways are not fully understood. We studied the role of Pyk2, a non-receptor, calcium-dependent protein-tyrosine kinase. The locomotor coordination and basal activity of Pyk2 knock-out mice were not altered and major striatal protein markers were normal. Cocaine injection increased Pyk2 tyrosine phosphorylation in mouse striatum. Pyk2-deficient mice displayed decreased locomotor response to acute cocaine injection. In contrast, locomotor sensitization and conditioned place preference were normal. Cocaine-activated ERK phosphorylation, a signaling pathway essential for these late responses, was unaltered. Conditional deletion of Pyk2 in the nucleus accumbens or in D1 neurons reproduced decreased locomotor response to cocaine, whereas deletion of Pyk2 in the dorsal striatum or in A2A receptor-expressing neurons did not. In mice lacking Pyk2 in D1-neurons locomotor response to D1 agonist SKF-81297, but not to an anticholinergic drug, was blunted. Our results identify Pyk2 as a regulator of acute locomotor responses to psychostimulants. They highlight the role of tyrosine phosphorylation pathways in striatal neurons and suggest that changes in Pyk2 expression or activation may alter specific responses to drugs of abuse, or possibly other behavioral responses linked to dopamine action.
Effectiveness of decontamination by litter removal in Japanese forest ecosystems affected by the Fukushima nuclear accident
Authors: Koarashi Jun , Atarashi-Andoh Mariko , Nishimura Syusaku , Muto Kotomi
Published: April 2020

The Fukushima Daiichi nuclear power plant accident caused serious radiocesium (137Cs) contamination of forest ecosystems over a wide area. The removal of the forest floor litter layer has been considered a potential method for forest decontamination; however, its effectiveness remains largely unknown. We conducted a pilot-scale decontamination study in a deciduous broadleaved forest in Fukushima. The entire forest was decontaminated by removing the litter layer in July 2014, approximately 3.3 years after the accident, with the exception of two untreated plots. For three years after decontamination, we quantified 137Cs contamination levels in the litter and topsoil layers and in the tree leaves, in the untreated and decontaminated areas. The decreased inventories of litter materials and the litter-associated 137Cs in the decontaminated areas were observed only in the first year after decontamination. Generally, no decontamination effects were observed on the 137Cs transfer in tree leaves. The primary reason for this was the rapid shift in the main reservoir of 137Cs from litter layers to the underlying mineral soil, which differs from the observations in post-Chernobyl studies of European forest ecosystems. The results suggest that litter-removal decontamination can only be successful if it is implemented more quickly (within 1–2 years after the accident) for Japanese forest ecosystems.
Epigenetics and Mitochondrial Stability in the Metabolic Memory Phenomenon Associated with Continued Progression of Diabetic Retinopathy
Authors: Kowluru Renu A. , Mohammad Ghulam
Published: April 2020

Retinopathy continues to progress even when diabetic patients try to control their blood sugar, but the molecular mechanism of this ‘metabolic memory’ phenomenon remains elusive. Retinal mitochondria remain damaged and vicious cycle of free radicals continues to self-propagate. DNA methylation suppresses gene expression, and diabetes activates DNA methylation machinery. Our aim was to investigate the role of DNA methylation in continued compromised mitochondrial dynamics and genomic stability in diabetic retinopathy. Using retinal endothelial cells, incubated in 20 mM glucose for four days, followed by 5 mM glucose for four days, and retinal microvessels from streptozotocin-induced diabetic rats in poor glycemia for four months, followed by normal glycemia for four additional months, DNA methylation of mitochondrial fusion and mismatch repair proteins, Mfn2 and Mlh1 respectively, was determined. Retinopathy was detected in trypsin-digested microvasculature. Re-institution of good glycemia had no beneficial effect on hypermethylation of Mfn2 and Mlh1 and retinal function (electroretinogram), and the  retinopathy continued to progress. However, intervention of good glycemia directly with DNA methylation inhibitors (Azacytidine or Dnmt1-siRNA), prevented Mfn2 and Mlh1 hypermethylation, and ameliorated retinal dysfunction and diabetic retinopathy. Thus, direct regulation of DNA methylation can prevent/reverse diabetic retinopathy by maintaining mitochondrial dynamics and DNA stability, and prevent retinal functional damage.