bluuebunny/crossref_metadata_2025 huggingface dataset:
Challenges to implementation of humanitarian access norms in the Sahel
Authors: Ferraro Romaric
Published: April 2022

While the rules of international humanitarian law (IHL) on humanitarian access are clear, implementing them at the national level can become challenging. To ensure full respect for those rules, States must strike a balance between preserving the security of the civilian population and humanitarian organizations and ensuring that people have access to goods and services that enable the full enjoyment of their rights. This article seeks to show how the IHL rules governing humanitarian access apply in the context of the Sahel region of Africa. First, it describes the multiplicity of armed actors that are present in the Sahel and the humanitarian situation in this region. Next, it addresses the legal framework applicable to humanitarian access under IHL applicable in non-international armed conflicts. The article then examines the measures that have been taken by the States of the Sahel to protect the civilian population and humanitarian organizations, such as the resort to declaration of states of emergency and to armed escorts. It is shown that these measures can hinder the delivery of impartial humanitarian assistance. Finally, the article describes some creative solutions that have been put forward by Sahelian States to facilitate humanitarian access. Examples of these include the creation of coordination mechanisms to foster dialogue on humanitarian access where all concerned actors are invited to participate; the adoption of domestic legal frameworks related to humanitarian access through which this access is proclaimed and its violation sanctioned; and the recognition of humanitarian exemptions in counterterrorism laws.
Multiple resistance of silky windgrass to acetolactate synthase- and acetyl-CoA synthase–inhibiting herbicides
Authors: Papapanagiotou Aristeides P. , Damalas Christos A. , Bosmali Irene , Madesis Panagiotis , Menexes Georgios , Eleftherohorinos Ilias
Published: April 2022

Field and pot experiments were conducted in Greece to study the occurrence of resistance in silky windgrass to acetolactate synthase (ALS)- and acetyl-CoA synthase (ACCase)-inhibiting herbicides. Twenty-four populations of silky windgrass were examined in whole-plant response experiments. High levels of field-evolved resistance to chlorsulfuron (0% to 28% control in terms of fresh weight reduction) with the recommended field rates were confirmed in most silky windgrass populations. However, other ALS inhibitors, such as pyroxsulam and a premix of mesosulfuron-methyl and iodosulfuron, provided adequate control (76% to 100% in terms of fresh weight reduction) of most populations, except eight silky windgrass populations that were found to be cross-resistant to all ALS-inhibiting herbicides tested (i.e., chlorsulfuron, commercial mixture of mesosulfuron-methyl plus iodosulfuron, and pyroxsulam). Conversely, most silky windgrass populations were controlled effectively (90% to 100% in terms of fresh weight reduction) with the recommended field rates of ACCase inhibitors cycloxydim, clethodim, and pinoxaden, but five populations were also found to be resistant to clodinafop-propargyl (10% to 68% control in terms of fresh weight reduction). The ALS gene sequencing of the eight silky windgrass populations, with cross-resistance to ALS inhibitors, revealed a point mutation at the Pro-197 position, causing amino acid substitution by Ser or Thr in the ALS enzyme. Overall, chlorsulfuron and clodinafop-propargyl were selecting agents of field-evolved multiple resistance to ALS- and ACCase-inhibiting herbicides in five silky windgrass populations. As the available postemergence-applied chemistries/modes of action registered for grass weed control in cereals are rather limited, adopting integrated management practices and implementing proactive and reactive measures to delay the evolution of resistant populations is essential.
Role of the Synergistic Interactions of Environmental Pollutants in the Development of Cancer
Authors: Lagunas‐Rangel Francisco Alejandro , Linnea‐Niemi Jenni Viivi , Kudłak Błażej , Williams Michael J. , Jönsson Jörgen , Schiöth Helgi B.
Published: April 2022

There is a growing awareness that the large number of environmental pollutants we are exposed to on a daily basis are causing major health problems. Compared to traditional studies that focus on individual pollutants, there are relatively few studies on how pollutants mixtures interact. Several studies have reported a relationship between environmental pollutants and the development of cancer, even when pollutant levels are below toxicity reference values. The possibility of synergistic interactions between different pollutants could explain how even low concentrations can cause major health problems. These intricate that molecular interactions can occur through a wide variety of mechanisms, and our understanding of the physiological effects of mixtures is still limited. The purpose of this paper is to discuss recent reports that address possible synergistic interactions between different types of environmental pollutants that could promote cancer development. Our literature studies suggest that key biological pathways are frequently implicated in such processes. These include increased production of reactive oxygen species, activation by cytochrome P450, and aryl hydrocarbon receptor signaling, among others. We discuss the need to understand individual pathological vulnerability not only in relation to basic genetics and gene expression, but also in terms of measurable exposure to contaminants. We also mention the need for significant improvements in future studies using a multitude of disciplines, such as the development of high‐throughput study models, better tools for quantifying pollutants in cancer patients, innovative pharmacological and toxicological studies, and high‐efficiency computer analysis, which allow us to analyze the molecular mechanisms of mixtures.
Coherence Scale and Directivity of Nighttime Equatorial Plasma Irregularities: Results From Swarm Formation Flight
Authors: Park Jaeheung
Published: April 2022

Since the launch in 2013, the three satellites of the Swarm constellation have been conducting multipoint observations of ionospheric plasma density. The variety of their flight formations is advantageous for investigating (a) coherence scale and (b) directivity of nighttime Equatorial Plasma Irregularities (EPIs). In this study, we address the two topics statistically using in situ plasma density measured at 2 Hz rates by the Swarm constellation from 2013 to 2021. Maximum cross‐correlation coefficients between two Swarm density profiles decrease as longitude differences between the observation pair increase. The coefficient is larger than 0.6 only when two satellites are within about 0.1° in geographic longitude (GLON), which approximately corresponds to 10 km. When two density profiles are considerably correlated, we can determine preferred bearings of the EPI structure. A majority of EPIs conform to the backward‐C shapes astride the dip equator. The preference for backward‐C is more conspicuous later at night than in the early evening. Different GLON sectors exhibit slightly different directions of EPI structures, but the behavior is not well organized with the geomagnetic declinations of the respective sectors. EPI directions do not display monotonic dependence on Ap or F10.7, but further studies during the coming solar maximum are necessary to better represent high solar/geomagnetic activity.
Coupled Hydromechanical Modeling of Induced Seismicity From CO2 Injection in the Illinois Basin
Authors: Luu Keurfon , Schoenball Martin , Oldenburg Curtis M. , Rutqvist Jonny
Published: April 2022

Injection of CO2 for geologic carbon sequestration into deep sedimentary formations involves fluid pressure increases that engage hydromechanical processes that can cause seismicity by activation of existing faults. In this work, we use a coupled multiphase fluid flow and geomechanical simulator to model spatiotemporal fluid pressure and stress changes in order to study the poroelastic effect of CO2 injection on faults in crystalline basement rock below the injection zone. The seismicity rate along features interpreted to be basement faults is modeled using Dieterich's rate‐and‐state earthquake nucleation model. The methodology is applied to microseismicity detected during CO2 injection into the Mount Simon formation during the Illinois Basin—Decatur Project. The modeling accurately captures an observed reduction in seismicity rate when the injection in the second well was into a slightly shallower zone above the base of the Mount Simon formation. Moreover, the modeling shows that it is important to consider poroelastic stress changes, in addition to fluid pressure changes for accurately modeling of the observed seismicity rate.
Impact of SST on Present and Future Extreme Precipitation in Hokkaido Investigated Considering Weather Patterns
Authors: Hatsuzuka Daisuke , Sato Tomonori
Published: April 2022

This study investigated the impact of sea surface temperature (SST) on extreme precipitation events in North Japan and its relation to synoptic weather patterns using large‐ensemble climate simulations. Eight weather patterns were identified by applying cluster analysis to sea level pressure anomalies for selected days with extreme precipitation derived from a 3000‐year historical climate experiment. Interannual variability of extreme precipitation days associated with two specific weather patterns, characterized by a weak low‐pressure system and an atmospheric river (AR), significantly correlated with that of SST over the Sea of Japan, with a correlation coefficient of 0.37 and 0.53, respectively. In higher SST years, the increased atmospheric moisture can increase the extreme precipitation in the inland area of Hokkaido for the weather pattern associated with a weak low‐pressure system, whereas it appears to enhance orographic precipitation along the western slopes of mountains for the pattern resembling AR. These results indicate that the effect of local SST on extreme precipitation strongly depends on the weather patterns. In the future projection, the two weather patterns that are sensitive to SST over the Sea of Japan show a sharp increase of more than 4 times under the 4 K warming climate. Moreover, the magnitude of extreme precipitation was also found to increase with SST, broadly following the Clausius–Clapeyron relation in both historical and warmed climates. These results suggest increased risk of heavy precipitation associated with such weather patterns over North Japan in the future.
The Effects of Terrain Properties Upon the Small Crater Population Distribution at Giordano Bruno: Implications for Lunar Chronology
Authors: Williams J.‐P. , Pathare A. V. , Costello E. S. , Gallinger C. L. , Hayne P. O. , Ghent R. R. , Paige D. A. , Siegler M. A. , Russell P. S. , Elder C. M.
Published: April 2022

The distribution of impact craters on the ejecta of Giordano Bruno, a recent (<10 Ma) 22‐km diameter crater within the lunar highlands, exhibits substantial variations. We surveyed craters D ≥ 10 m across a 1,323 km2 area of Giordano Bruno's ejecta and compared the distribution of craters with variations in thermophysical properties derived from the Lunar Reconnaissance Orbiter Diviner instrument. We used Diviner‐derived rock abundance and nighttime regolith temperatures along with thermal model‐predicted surface temperatures for a diversity of terrains to identify and isolate areas of the ejecta based on thermophysical properties such as bulk density and thermal conductivity. We found that thermophysical properties of the ejecta vary considerably both laterally and vertically, and consistently differ from typical regolith, indicating the presence of higher thermal inertia materials. Crater‐size frequencies are significantly lower in areas with terrain properties exhibiting higher: rock abundance, nighttime temperatures, and/or modeled thermal inertia. This discrepancy in crater distribution increases for craters smaller than ∼25 m. These thermophysical variations indicate changes in the mechanical properties of the target materials. We suggest that these variations—specifically, terrain‐dependent crater scaling variations and impactor‐scale heterogeneities in material properties such as the presence or absence of large boulders—may influence crater diameters or inhibit crater production altogether in Giordano Bruno's ejecta; furthermore, these factors are size‐dependent.
Reply to Comment by A.P. Nutman et al. on “Tectonics of the Isua Supracrustal Belt 1: P‐T‐X‐d Constraints of a Poly‐Metamorphic Terrane” by A. Ramírez‐Salazar et al. and “Tectonics of the Isua Supracrustal Belt 2: Microstructures Reveal Distributed Strain in the Absence of Major Fault Structures” by J. Zuo et al.
Authors: Ramírez‐Salazar Anthony , Zuo Jiawei , Müller Thomas , Webb A. Alexander G. , Sorger Dominik , Piazolo Sandra , Haproff Peter , Harvey Jason , Wang Qin , Hauzenberger Christoph , Wong Tsz Kin
Published: April 2022

Structural and metamorphic analyses from the works under discussion (Ramírez‐Salazar et al., 2021, https://doi.org/10.1029/2020tc006516; Zuo et al., 2021, https://doi.org/10.1029/2020tc006514) show that the Isua supracrustal rocks can be interpreted to record one single deformation and metamorphic event featuring quasi‐homogeneous deformation and amphibolite facies metamorphism, followed by late static retrogression or thermal event(s). Observed deformation and metamorphic records are consistent with three hypotheses: (a) they represent Neoarchean plate tectonic overprints following Eoarchean plate tectonic evolution (e.g., Nutman et al., 2022, https://doi.org/10.1029/2021TC007036); (b) they represent Eoarchean heat‐pipe and/or plate tectonic deformation that survived later tectonic event(s) (e.g., Ramírez‐Salazar et al., 2021, https://doi.org/10.1029/2020tc006516; Zuo et al., 2021, https://doi.org/10.1029/2020tc006514), and; (c) they represent one major Neoarchean tectonic event, such that the Isua supracrustal belt (ISB) records Eoarchean protolith‐related processes but does not record Eoarchean metamorphism nor deformation. While a heat‐pipe model for crustal formation is central to hypothesis 2, it is also a viable crustal formation mechanism for hypothesis 3 where the ISB would still form in a heat‐pipe setting in Eoarchean time, but the major deformation of the heat‐pipe lithosphere happened during Neoarchean time, probably by (proto‐)plate tectonic processes. If the data presented in Zuo et al. (2021), https://doi.org/10.1029/2020tc006514 and Ramírez‐Salazar et al. (2021), https://doi.org/10.1029/2020tc006516 only reflect Neoarchean histories, then these cannot be used to refute or support any Eoarchean geodynamic background for the formation of the ISB.
The Role of Prior Probabilities on Parameter Estimation in Hydrological Models
Authors: Gupta A. , Govindaraju R. S. , Morbidelli R. , Corradini C.
Published: April 2022

Bayes theorem provides a formal framework for combining prior and sample information for parameter estimation in the presence of measurement and structural errors. Prior knowledge, however, may not always be available or may be too vague to incorporate into a prior distribution. In such cases, a reference prior must be chosen for an objective analysis. Typically, a uniform density over the possible ranges of parameters is chosen as the reference prior. However, the validity of a uniform prior as a reference prior is seldom questioned. In this study, an information‐theoretic approach is pursued to derive reference priors, and the results are compared to those obtained by using a uniform prior. Examples of estimating saturated hydraulic conductivity are presented. Priors over hydraulic conductivity obtained by using the information‐theoretic approach are transformation‐invariant and typically nonuniform. The choice between information‐theoretic and uniform prior influences the posterior distribution of hydraulic conductivity, when sample information is small. The use of reference prior is also demonstrated through the PDG‐GIUH hydrologic model, and issues of computational tractability are addressed.
A Catchment‐Based Hierarchical Spatial Tessellation Approach to a Better Representation of Land Heterogeneity for Hyper‐Resolution Land Surface Modeling
Authors: Huang Lina , Zhang Shupeng , Niu Guo‐Yue , Wei Nan , Yuan Hua , Wei Zhongwang , Lu Xingjie , Peng Jingman , Li Wenyao , Dai Yongjiu
Published: April 2022

To represent the physical processes at hillslope scales for hyper‐resolution land surface modeling, we propose a hierarchical, catchment‐based spatial tessellation method. The land surface is divided into a hierarchical structure: catchments, height bands along hillslopes within a catchment, and land cover patches within a height band. This catchment‐based structure explicitly represents hillslope drainage networks and can be applied at various resolutions determined by a pre‐defined maximum height band size. The proposed tessellation method is superior to the conventional grid‐based structure in representing land surface heterogeneity, resulting in a higher aggregation skill through the height band representation. The spatial variations in air temperature, leaf area index, saturated soil hydraulic conductivity, and soil porosity are generally lower within a height band than those in a conventional rectangular grid, reflecting the nature of topographic control on climate, vegetation, and soil distribution. The improvement in aggregation skill depends on resolutions and terrain slope angle, more pronounced at 1/6° model resolution and over steeper terrains. Finally, we demonstrate that our proposed catchment‐based structure performs better than the grid‐based structure through modeling tests over the Columbia River basin at resolutions of 1/2°, 1/6°, and 1/20° and a global test at 1/2° using the ILAMB model evaluation metrics.
Spatio‐Temporal Model Variance‐Covariance Approach to Assimilating Streamflow Observations Into a Distributed Landscape Water Balance Model
Authors: Tian Siyuan , Renzullo Luigi J. , Lerat Julien , Pipunic Robert C.
Published: April 2022

Accurate initial conditions play a critical role in improving predictive accuracy of hydrological models for quantities such as streamflow generation. Streamflow observations from in situ gauging sites have been assimilated in a wide range of past research to improve lumped catchment streamflow. However, spatio‐temporal state updating in distributed hydrological models through streamflow data assimilation (DA) remains a challenge due to the large dimensional disparity between model state space and observation space. This study explores the use of model spatio‐temporal variance‐covariance from simulated climatology as a surrogate for model error, as a way of distributing constraint from gauge measurements spatially. In the approach developed here, grid cells within and surrounding gauged catchments were updated simultaneously. The proposed DA method leads to a substantial improvement in performance and reliability compared to open‐loop (OL) estimates of streamflow. In particular, for “ungauged” catchments updated using streamflow observations from neighboring catchments, the mean absolute error (MAE) was reduced by 20% on average after the assimilation. In addition, improvements from using the analyzed states as initial conditions were found to persist for more than 1 week, and even longer for catchments with high annual runoff. The improvement in streamflow forecasts using initial conditions from DA can be more than 40% in terms of MAE compared to OL results for 1 day lead time, and more than 10% for 5 days lead time.
Microbial Sulfate Reduction (MSR) as a Nature‐Based Solution (NBS) to Mine Drainage: Contrasting Spatiotemporal Conditions in Northern Europe
Authors: Fischer Sandra , Mörth Carl‐Magnus , Rosqvist Gunhild , Chalov Sergey R. , Efimov Vasiliy , Jarsjö Jerker
Published: April 2022

An emerging solution in mine waste remediation is the use of biological processes, such as microbial sulfate reduction (MSR), to immobilize metals, reducing their bioavailability and buffering the pH of acid mine drainage. Apart from laboratory tests and local observations of natural MSR in, for example, single wetlands, little is known about spatiotemporal characteristics of freshwater MSR from multiple locations within entire hydrological catchments. We here applied an isotopic fractionation (δ34S values in SO42−) and a Monte Carlo‐based mixing analysis scheme to detect MSR and its variation across two major mining regions (Imetjoki, Sweden and Khibiny, Russia) in the Arctic part of Europe under different seasonal conditions. Results indicate a range of catchment‐scale MSR values in the Arctic of ∼5%–20% where the low end of the range was associated with the non‐vegetated, mountainous terrain of the Khibiny catchment, having low levels of dissolved organic carbon (DOC). The high end of the range was related to vegetated conditions provided by the Imetjoki catchment that also contains wetlands, lakes, and local aquifers. These prolong hydrological residence times and support MSR hot spots reaching values of ∼40%. The present results additionally show evidence of MSR persistence over different seasons, indicating large potential, even under relatively cold conditions, of using MSR as part of nature‐based solutions to mitigate adverse impacts of (acid) mine drainage. The results call for more detailed investigations regarding potential field‐scale correlations between MSR and individual landscape and hydroclimatic characteristics, which, for example, can be supported by the isotopic fractionation and mixing scheme utilized here.
Global Increases in Compound Flood‐Hot Extreme Hazards Under Climate Warming
Authors: Gu Lei , Chen Jie , Yin Jiabo , Slater Louise J. , Wang Hui‐Min , Guo Qiang , Feng Maoyuan , Qin Hui , Zhao Tongtiegang
Published: April 2022

Under global warming, a novel category of extreme events has become increasingly apparent, where flood and hot extremes occur in rapid succession, causing significant damages to infrastructure and ecosystems. However, these bivariate compound flood‐hot extreme (CFH) hazards have not been comprehensively examined at the global scale, and their evolution under climate warming remains unstudied. Here, we present the first global picture of projected changes in CFH hazards by using a cascade modeling chain of CMIP6 models, satellite and reanalysis data sets, bias correction, and hydrological models. We find an increasing percentage of floods will be accompanied by hot extremes under climate change; the joint return periods of CFHs are projected to decrease globally, particularly in the tropics. These decreasing joint return periods are largely driven by changes in hot extremes and indicate a likely increase of CFH hazards, and ultimately highlight the urgent need to conduct adaptation planning for future risks.
c-Myc-driven glycolysis polarizes functional regulatory B cells that trigger pathogenic inflammatory responses
Authors: Wang Xu-Yan , Wei Yuan , Hu Bo , Liao Yuan , Wang Xiaodong , Wan Wen-Hua , Huang Chun-Xiang , Mahabati Mahepali , Liu Zheng-Yu , Qu Jing-Rui , Chen Xiao-Dan , Chen Dong-Ping , Kuang Dong-Ming , Wang Xue-Hao , Chen Yun
Published: April 2022

B cells secreting IL-10 functionally are recognized as functional regulatory B (Breg) cells; however, direct evidence concerning the phenotype, regulation, and functional and clinical relevance of IL-10-secreting Breg cells in humans is still lacking. Here, we demonstrate that, although IL-10 itself is anti-inflammatory, IL-10+ functional Breg cells in patients with systemic lupus erythematosus (SLE) display aggressive inflammatory features; these features shift their functions away from inducing CD8+ T cell tolerance and cause them to induce a pathogenic CD4+ T cell response. Functional Breg cells polarized by environmental factors (e.g., CPG-DNA) or directly isolated from patients with SLE mainly exhibit a CD24intCD27−CD38−CD69+/hi phenotype that is different from that of their precursors. Mechanistically, MAPK/ERK/P38-elicited sequential oncogenic c-Myc upregulation and enhanced glycolysis are necessary for the generation and functional maintenance of functional Breg cells. Consistently, strategies that abrogate the activity of ERK, P38, c-Myc, and/or cell glycolysis can efficiently eliminate the pathogenic effects triggered by functional Breg cells.
Sequential immunizations confer cross-protection against variants of SARS-CoV-2, including Omicron in Rhesus macaques
Authors: Deng Wei , Lv Qi , Li Fengdi , Liu Jiangning , Song Zhiqi , Qi Feifei , Wei Qiang , Yu Pin , Liu Mingya , Zhou Shasha , Zhang Yaqing , Gao Hong , Wang Nan , Jia Zijing , Gao Kai , Liu Jiayi , Xiao Chong , Shang Haiquan , Wang Xiangxi , Bao Linlin , Qin Chuan
Published: April 2022

Variants of concern (VOCs) like Delta and Omicron, harbor a high number of mutations, which aid these viruses in escaping a majority of known SARS-CoV-2 neutralizing antibodies (NAbs). In this study, Rhesus macaques immunized with 2-dose inactivated vaccines (Coronavac) were boosted with an additional dose of homologous vaccine or an RBD-subunit vaccine, or a bivalent inactivated vaccine (Beta and Delta) to determine the effectiveness of sequential immunization. The booster vaccination significantly enhanced the duration and levels of neutralizing antibody titers against wild-type, Beta, Delta, and Omicron. Animals administered with an indicated booster dose and subsequently challenged with Delta or Omicron variants showed markedly reduced viral loads and improved histopathological profiles compared to control animals, indicating that sequential immunization could protect primates against Omicron. These results suggest that sequential immunization of inactivated vaccines or polyvalent vaccines could be a potentially effective countermeasure against newly emerging variants.
Allele-specific analysis reveals exon- and cell-type-specific regulatory effects of Alzheimer’s disease-associated genetic variants
Authors: He Liang , Loika Yury , Kulminski Alexander M.
Published: April 2022

Elucidating regulatory effects of Alzheimer’s disease (AD)-associated genetic variants is critical for unraveling their causal pathways and understanding the pathology. However, their cell-type-specific regulatory mechanisms in the brain remain largely unclear. Here, we conducted an analysis of allele-specific expression quantitative trait loci (aseQTLs) for 33 AD-associated variants in four brain regions and seven cell types using ~3000 bulk RNA-seq samples and >0.25 million single nuclei. We first develop a flexible hierarchical Poisson mixed model (HPMM) and demonstrate its superior statistical power to a beta-binomial model achieved by unifying samples in both allelic and genotype-level expression data. Using the HPMM, we identified 24 (~73%) aseQTLs in at least one brain region, including three new eQTLs associated with CA12, CHRNE, and CASS4. Notably, the APOE ε4 variant reduces APOE expression across all regions, even in AD-unaffected controls. Our results reveal region-dependent and exon-specific effects of multiple aseQTLs, such as rs2093760 with CR1, rs7982 with CLU, and rs3865444 with CD33. In an attempt to pinpoint the cell types responsible for the observed tissue-level aseQTLs using the snRNA-seq data, we detected many aseQTLs in microglia or monocytes associated with immune-related genes, including HLA-DQB1, HLA-DQA2, CD33, FCER1G, MS4A6A, SPI1, and BIN1, highlighting the regulatory role of AD-associated variants in the immune response. These findings provide further insights into potential causal pathways and cell types mediating the effects of the AD-associated variants.
Cooperative effects of RIG-I-like receptor signaling and IRF1 on DNA damage-induced cell death
Authors: Zander David Y. , Burkart Sandy S. , Wüst Sandra , Magalhães Vladimir G. , Binder Marco
Published: April 2022

Properly responding to DNA damage is vital for eukaryotic cells, including the induction of DNA repair, growth arrest and, as a last resort to prevent neoplastic transformation, cell death. Besides being crucial for ensuring homeostasis, the same pathways and mechanisms are at the basis of chemoradiotherapy in cancer treatment, which involves therapeutic induction of DNA damage by chemical or physical (radiological) measures. Apart from typical DNA damage response mediators, the relevance of cell-intrinsic antiviral signaling pathways in response to DNA breaks has recently emerged. Originally known for combatting viruses via expression of antiviral factors including interferons (IFNs) and establishing of an antiviral state, RIG-I-like receptors (RLRs) were found to be critical for adequate induction of cell death upon the introduction of DNA double-strand breaks. We here show that presence of IRF3 is crucial in this process, most likely through direct activation of pro-apoptotic factors rather than transcriptional induction of canonical downstream components, such as IFNs. Investigating genes reported to be involved in both DNA damage response and antiviral signaling, we demonstrate that IRF1 is an obligatory factor for DNA damage-induced cell death. Interestingly, its regulation does not require activation of RLR signaling, but rather sensing of DNA double-strand breaks by ATM and ATR. Hence, even though independently regulated, both RLR signaling and IRF1 are essential for full-fledged induction/execution of DNA damage-mediated cell death programs. Our results not only support more broadly developing IRF1 as a biomarker predictive for the effectiveness of chemoradiotherapy, but also suggest investigating a combined pharmacological stimulation of RLR and IRF1 signaling as a potential adjuvant regimen in tumor therapy.
Cancer cells adapt FAM134B/BiP mediated ER-phagy to survive hypoxic stress
Authors: Chipurupalli Sandhya , Ganesan Raja , Martini Giulia , Mele Luigi , Reggio Alessio , Esposito Marianna , Kannan Elango , Namasivayam Vigneshwaran , Grumati Paolo , Desiderio Vincenzo , Robinson Nirmal
Published: April 2022

In the tumor microenvironment, cancer cells experience hypoxia resulting in the accumulation of misfolded/unfolded proteins largely in the endoplasmic reticulum (ER). Consequently, ER proteotoxicity elicits unfolded protein response (UPR) as an adaptive mechanism to resolve ER stress. In addition to canonical UPR, proteotoxicity also stimulates the selective, autophagy-dependent, removal of discrete ER domains loaded with misfolded proteins to further alleviate ER stress. These mechanisms can favor cancer cell growth, metastasis, and long-term survival. Our investigations reveal that during hypoxia-induced ER stress, the ER-phagy receptor FAM134B targets damaged portions of ER into autophagosomes to restore ER homeostasis in cancer cells. Loss of FAM134B in breast cancer cells results in increased ER stress and reduced cell proliferation. Mechanistically, upon sensing hypoxia-induced proteotoxic stress, the ER chaperone BiP forms a complex with FAM134B and promotes ER-phagy. To prove the translational implication of our mechanistic findings, we identified vitexin as a pharmacological agent that disrupts FAM134B-BiP complex, inhibits ER-phagy, and potently suppresses breast cancer progression in vivo.
Mesenchymal stem cells empower T cells in the lymph nodes via MCP-1/PD-L1 axis
Authors: He Yifan , Qu Yan , Meng Bowen , Huang Weiying , Tang Jianxia , Wang Runci , Chen Zetao , Kou Xiaoxing , Shi Songtao
Published: April 2022

Mesenchymal stem cells (MSCs) are a type of immunosuppressive stromal cell found in multiple tissues and organs. However, whether MSCs possess immunosupportive characteristics remains unclear. In this study, we showed that the lymph nodes contain immunosupportive MSCs. They produce and secrete a high level of MCP-1 to promote T-cell proliferation and differentiation, in contrast to bone marrow MSCs (BMMSCs), which repress T-cell activation. Unlike BMMSCs, lymph node MSCs (LNMSCs) fail to respond to activated T-cell-induced production of PD-L1 to induce T-cell apoptosis. Mechanistically, MCP-1 activates phospho-Erk to sustain T-cell proliferation and activation while it represses NF-κB/PD-L1 pathway to avoid induction of T-cell apoptosis. Interestingly, inflammatory lymph node-derived LNMSCs abolish their immunosupportive function due to reduction of MCP-1 expression. Finally, we show that systemic infusion of LNMSCs rescues immunosuppression in cytoxan (CTX)-treated mice. This study reveals a previously unrecognized mechanism underlying MSC-based immunoregulation using the MCP-1/PD-L1 axis to energize T cells and suggests a potential to use MSCs to treat immunosuppressive disorders.
The Cycas genome and the early evolution of seed plants
Authors: Liu Yang , Wang Sibo , Li Linzhou , Yang Ting , Dong Shanshan , Wei Tong , Wu Shengdan , Liu Yongbo , Gong Yiqing , Feng Xiuyan , Ma Jianchao , Chang Guanxiao , Huang Jinling , Yang Yong , Wang Hongli , Liu Min , Xu Yan , Liang Hongping , Yu Jin , Cai Yuqing , Zhang Zhaowu , Fan Yannan , Mu Weixue , Sahu Sunil Kumar , Liu Shuchun , Lang Xiaoan , Yang Leilei , Li Na , Habib Sadaf , Yang Yongqiong , Lindstrom Anders J. , Liang Pei , Goffinet Bernard , Zaman Sumaira , Wegrzyn Jill L. , Li Dexiang , Liu Jian , Cui Jie , Sonnenschein Eva C. , Wang Xiaobo , Ruan Jue , Xue Jia-Yu , Shao Zhu-Qing , Song Chi , Fan Guangyi , Li Zhen , Zhang Liangsheng , Liu Jianquan , Liu Zhong-Jian , Jiao Yuannian , Wang Xiao-Quan , Wu Hong , Wang Ertao , Lisby Michael , Yang Huanming , Wang Jian , Liu Xin , Xu Xun , Li Nan , Soltis Pamela S. , Van de Peer Yves , Soltis Douglas E. , Gong Xun , Liu Huan , Zhang Shouzhou
Published: April 2022

Cycads represent one of the most ancient lineages of living seed plants. Identifying genomic features uniquely shared by cycads and other extant seed plants, but not non-seed-producing plants, may shed light on the origin of key innovations, as well as the early diversification of seed plants. Here, we report the 10.5-Gb reference genome of Cycas panzhihuaensis, complemented by the transcriptomes of 339 cycad species. Nuclear and plastid phylogenomic analyses strongly suggest that cycads and Ginkgo form a clade sister to all other living gymnosperms, in contrast to mitochondrial data, which place cycads alone in this position. We found evidence for an ancient whole-genome duplication in the common ancestor of extant gymnosperms. The Cycas genome contains four homologues of the fitD gene family that were likely acquired via horizontal gene transfer from fungi, and these genes confer herbivore resistance in cycads. The male-specific region of the Y chromosome of C. panzhihuaensis contains a MADS-box transcription factor expressed exclusively in male cones that is similar to a system reported in Ginkgo, suggesting that a sex determination mechanism controlled by MADS-box genes may have originated in the common ancestor of cycads and Ginkgo. The C. panzhihuaensis genome provides an important new resource of broad utility for biologists.
Development of a clinical polygenic risk score assay and reporting workflow
Authors: Hao Limin , Kraft Peter , Berriz Gabriel F. , Hynes Elizabeth D. , Koch Christopher , Korategere V Kumar Prathik , Parpattedar Shruti S. , Steeves Marcie , Yu Wanfeng , Antwi Ashley A. , Brunette Charles A. , Danowski Morgan , Gala Manish K. , Green Robert C. , Jones Natalie E. , Lewis Anna C. F. , Lubitz Steven A. , Natarajan Pradeep , Vassy Jason L. , Lebo Matthew S.
Published: April 2022

Implementation of polygenic risk scores (PRS) may improve disease prevention and management but poses several challenges: the construction of clinically valid assays, interpretation for individual patients, and the development of clinical workflows and resources to support their use in patient care. For the ongoing Veterans Affairs Genomic Medicine at Veterans Affairs (GenoVA) Study we developed a clinical genotype array-based assay for six published PRS. We used data from 36,423 Mass General Brigham Biobank participants and adjustment for population structure to replicate known PRS–disease associations and published PRS thresholds for a disease odds ratio (OR) of 2 (ranging from 1.75 (95% CI: 1.57–1.95) for type 2 diabetes to 2.38 (95% CI: 2.07–2.73) for breast cancer). After confirming the high performance and robustness of the pipeline for use as a clinical assay for individual patients, we analyzed the first 227 prospective samples from the GenoVA Study and found that the frequency of PRS corresponding to published OR > 2 ranged from 13/227 (5.7%) for colorectal cancer to 23/150 (15.3%) for prostate cancer. In addition to the PRS laboratory report, we developed physician- and patient-oriented informational materials to support decision-making about PRS results. Our work illustrates the generalizable development of a clinical PRS assay for multiple conditions and the technical, reporting and clinical workflow challenges for implementing PRS information in the clinic.
Computational characterization of the behavior of a saliva droplet in a social environment
Authors: Ugarte-Anero Ainara , Fernandez-Gamiz Unai , Portal-Porras Koldo , Zulueta Ekaitz , Urbina-Garcia Oskar
Published: April 2022

The conduct of respiratory droplets is the basis of the study to reduce the spread of a virus in society. The pandemic suffered in early 2020 due to COVID-19 shows the lack of research on the evaporation and fate of droplets exhaled in the environment. The current study, attempts to provide solution through computational fluid dynamics techniques based on a multiphase state with the help of Eulerian–Lagrangian techniques to the activity of respiratory droplets. A numerical study has shown how the behavior of droplets of pure water exhaled in the environment after a sneeze or cough have a dynamic equal to the experimental curve of Wells. The droplets of saliva have been introduced as a saline solution. Considering the mass transferred and the turbulence created, the results has showed that the ambient temperature and relative humidity are parameters that significantly affect the evaporation process, and therefore to the fate. Evaporation time tends to be of a higher value when the temperature affecting the environment is lower. With constant parameters of particle diameter and ambient temperature, an increase in relative humidity increases the evaporation time. A larger particle diameter is consequently transported at a greater distance, since the opposite force it affects is the weight. Finally, a neural network-based model is presented to predict particle evaporation time.
Heavy rainfall following a summer drought stimulates soil redox dynamics and facilitates rapid and deep translocation of glyphosate in floodplain soils
Authors: Schlögl Johanna , Wimmer Benedikt , Cramaro Lena , Wirsching Johannes , Poll Christian , Pagel Holger , Kandeler Ellen , Huhn Carolin , Griebler Christian , Stumpp Christine , Haderlein Stefan B.
Published: April 2022

We present field data on the effects of heavy rainfall after drought on the mobility of glyphosate and redox conditions in a clayey floodplain soil.
Effects of dissolved organic matter characteristics on the photosensitized degradation of pharmaceuticals in wastewater treatment wetlands
Authors: Sardana Arpit , Weaver Leah , Aziz Tarek N.
Published: April 2022

The sunlight-mediated photodegradation of organic contaminants in wastewater treatment wetlands is intricately related to the physicochemical characteristics and processing of dissolved organic matter.
Polydiacetylene-based sensors for food applications
Authors: Weston Max , Pham Andy-Hoai , Tubman Jennessa , Gao Yuan , Tjandra Angie Davina , Chandrawati Rona
Published: April 2022

In this review, we discuss methods of polydiacetylene sensor fabrication, and their use as food quality and food contaminant sensors. Our perspective on the challenges and opportunities for polydiacetylene-based food sensors is included.
Devising ultra-robust mixed-matrix membrane separators using functionalized MOF–poly(phenylene oxide) for high-performance vanadium redox flow batteries
Authors: Sharma Prerana , Goswami Ranadip , Neogi Subhadip , Shahi Vinod K.
Published: April 2022

Tailoring membrane surface via incorporation of ionic MOF mixed-matrix membrane separator for high VRFB performance.
A fluorescence detection method for the determination of β-lactoglobulin in foods
Authors: Yang Jingyi , Zhang Yong , Lu Yang
Published: April 2022

A quantum dot–aptamer–graphene oxide probe-based fluorescence method was developed and utilized to detect β-lactoglobulin in real food products.
A SERS pH sensor for highly alkaline conditions and its application for pH sensing in aerosol droplets
Authors: Liu Boyu , Huang Yuting , Zheng Wenxu , Wang Dongmei , Fan Meikun
Published: April 2022

A SERS pH sensor employing Alizarin Yellow R as the molecular probe was developed for use in strong alkaline solutions.
Construction of rolling circle amplification-based DNA nanostructures for biomedical applications
Authors: Xu Yuwei , Lv Zhaoyue , Yao Chi , Yang Dayong
Published: April 2022

RCA-based DNA nanostructures show accurate molecular recognition capacity, structural controllability, and good biocompatibility, and thus have been studied for biomedical applications including therapeutics and bioimaging.
A reactive molecular dynamics study of bi-modal particle size distribution in binder-jetting additive manufacturing using stainless-steel powders
Authors: Gao Yawei , Clares Ana Paula , Manogharan Guha , van Duin Adri. C. T.
Published: April 2022

The binder-jetting additive manufacturing using a bimodal particle size distribution is modelled using the ReaxFF reactive molecular dynamics method, which provides an atomistic-level insight into the mechanical and chemical property evolution.
Liquid ethylene glycol: prediction of physical properties, conformer population and interfacial enrichment with a refined non-polarizable force field
Authors: Gaur Anjali , Balasubramanian Sundaram
Published: April 2022

A newly developed force field for liquid ethylene glycol predicts its conformer populations accurately as well as agrees with experiments on the increase of OCCO gauche fraction at a liquid–vapour interface.
QM/MM and MM MD simulations on decontamination of the V-type nerve agent VX by phosphotriesterase: toward a comprehensive understanding of steroselectivity and activity
Authors: Fan Fangfang , Zheng Yongchao , Fu Yuzhuang , Zhang Yuwei , Zheng He , Lyu Changjiang , Chen Linyu , Huang Jun , Cao Zexing
Published: April 2022

QM/MM and MM MD simulations reveal that the degraded product release and the P–S cleavage are rate-limiting steps in the enzymatic degradation of RP-VX and SP-VX by PTE, respectively, showing notable stereospecificity of the substrate.
Catalyst sites and active species in the early stages of MTO conversion over cobalt AlPO-18 followed by IR spectroscopy
Authors: Airi Alessia , Damin Alessandro , Xie Jingxiu , Olsbye Unni , Bordiga Silvia
Published: April 2022

Reaction-time resolved IR spectroscopy highlights the role of CO and surface –OCH3 in the MTO conversion catalysed by CoAPO-18 with maximised concentration of acidic sites.
Revealing the role of surface elementary doping in photocatalysis
Authors: Yang Danlu , Wang Zhijian , Chen Jiazang
Published: April 2022

Doping CdS with manganese can catalyze hole extraction and facilitate interfacial electron transfer to metallic cocatalyst. This reduces the activation energy for spatial separation of photogenerated charge carriers and enhances photon utilization.
Dopant-driven tuning of toluene oxidation and sulfur resistance at the B-site of LaCo1−xMxO3 (M = Fe, Cr, Cu) perovskites
Authors: Lv Chunwang , Hu Mingjiang , Yuan Tianhao , Yan Liqiang , Chen Hongwei
Published: April 2022

The optimization effect of Fe dopant on toluene oxidation and sulfur resistance is better than that of Cr and Cu dopants.
2,2′-Ethylenebis(1,3-dithiane) as a polydentate μ2-, μ4- and μ5-assembling ligand for the construction of sulphur-rich Cu(i), Hg(ii) and heterometallic Cu(i)/Hg(ii) coordination polymers featuring uncommon network architectures
Authors: Viau Lydie , Knorr Michael , Knauer Lena , Brieger Lukas , Strohmann Carsten
Published: April 2022

The coordination chemistry of the polydentate thiaheterocycle 2,2′-ethylenebis(1,3-dithiane) L1 towards CuX and HgX2 salts was investigated using different metal-to-ligand ratios.
Syntheses, rearrangements, and structural analyses of unsaturated nitrogen donor ligands derived from diphenyldiazomethane and the chiral rhenium Lewis acid [(η5-C5H5)Re(NO)(PPh3)]+
Authors: Estrada Alexander L. , Wititsuwannakul Taveechai , Kromm Klemenz , Hampel Frank , Hall Michael B. , Gladysz John A.
Published: April 2022

Archivists or museums often use “curiosity cabinets” to present certain collections – an apt unifying concept for this work, which combines a heretofore unknown metal/diazoalkane reactivity mode and a rare type of base-promoted ligand rearrangement.
Identifying single-strain growth patterns of human gut microbes in response to preterm human milk and formula
Authors: Engevik Melinda A. , Stripe Leah K. , Baatz John E. , Wagner Carol L. , Chetta Katherine E.
Published: April 2022

The intestinal microbiota of the preterm neonate has become a major research focus, with evidence emerging that the microbiota influences both short and long-term health outcomes, in the neonatal intensive care unit and beyond.
Ratiometric electrochemical detection of tryptophan based on ferrocene and carboxylated-pillar[6]arene hybrid metal–organic layers
Authors: Wu Zejia , Wen Jia , Li Jiangshan , Zhang Wuyi , Li Yutong , Li Wei , Yang Kui
Published: April 2022

Metal–organic layers (MOLs), which have an ultrathin structure, are a novel class of two dimensional coordination polymers.
In silico design of graphene plasmonic hot-spots
Authors: Bonatti Luca , Nicoli Luca , Giovannini Tommaso , Cappelli Chiara
Published: April 2022

A route for the rational design of engineered graphene-based nanostructures is proposed. The designed structures feature enormously enhanced electric fields in their proximity.
Effects of inorganic metal ions on the mixture of single polyoxyethylene chain carboxylate surfactant and Gemini quaternary ammonium surfactant
Authors: Li Chunhui , Tai Xiumei , Wang Tianzhuang , Guo Lingxiao , Bai Yanyun , Ma Yanjun
Published: April 2022

Complexation mechanisms of polyoxyethylene group and amide group with metal ions were confirmed by a simple method.
Thermally induced spin-crossover in the Fe(3-ethynylpyridine)2[M(CN)4] series with M = Ni, Pd, and Pt. The role of the electron density found at the CN 5σ orbital
Authors: Terrero R. , Avila Y. , Mojica R. , Cano A. , Gonzalez M. , Avila M. , Reguera E.
Published: April 2022

The charge density accumulated at the CN 5σ orbital, via π-back bonding interaction, determines the crystal field splitting for the Fe(ii) atom and the temperature where the spin transition is observed.
Pressure-stimulus-responsive behaviors of core–shell InP/ZnSe nanocrystals: remarkable piezochromic luminescence and structural assembly
Authors: Liu Hao , Wang Yixuan , Yang Xinyi , Zhao Xiaohui , Wang Kai , Wu Min , Zuo Xiaobing , Yang Wenge , Sui Yongming , Zou Bo
Published: April 2022

All-inorganic core–shell InP/ZnSe nanocrystals exhibited remarkable optical and morphological changes in response to the external stimulus of high pressure.
Optimizing the synergy between alloy and alloy–oxide interface for CO oxidation in bimetallic catalysts
Authors: Pan Ya , Xu Liuxin , He Wenxue , Li Hongmei , Chen Wei , Sun Zhihu
Published: April 2022

An optimized synergy between alloy and alloy-oxide in Pt–Co/Al2O3 bimetallic catalysts for CO oxidation.
Cu catalyzed [4 + 2] cycloaddition for the synthesis of highly substituted 3-fluoropyridines
Authors: Fu Yiwei , Shi Haoyu , Lei Shengshu , Shi Lei , Li Hao
Published: April 2022

A copper catalyzed [4 + 2]annulation–aromatization of benzyl trifluoromethyl ketimines with 3-acryloyloxazolidin-2-ones has been developed for the synthesis of 3-fluoropyridines in moderate yields through double C–F bond cleavages.