bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Assimilating Model Using Broad Learning System for Incorporating Multi‐Source Precipitation Data With Environmental Factors Over Southeast China
Authors: Zhou Yuanyuan , Li Xu , Tang Qiuhong , Kuok Sin Chi , Fei Kai , Gao Liang 
Published: March 2022

AbstractRemote sensing technique is beneficial for rainfall data retrievals, however, enhancing the accuracy remains a challenge. In this study, a novel framework based on a broad learning system (BLS) was proposed to assimilate multi‐source data. The dataset includes six satellite‐based rainfall products (3B42V7, 3B42RT, IMERG, CBLD, GSMaP, and PCDR), gauge‐based rainfall, and environmental data (temperature, specific humidity, wind speed, and locations) from 1 March 2014 to 31 December 2017 over southeast China (SEC). Leave‐one‐year‐out cross‐validation (LOYOCV) and independent validation were used to evaluate the BLS assimilating model. The proposed BLS model outperformed six original satellite‐based products on Pearson's correlation coefficient (CC), root‐mean‐square error (RMSE), and Nash‐Sutcliffe coefficient of efficiency (NSE) in each test year of LOYOCV. BLS model considering the environmental factors performed better on CC, RMSE, and NSE compared to that without environmental factors. Seasonal variations of daily gauge‐based precipitation were accurately captured by BLS‐based estimates. BLS method outperformed satellites on CC, RMSE, and NSE at most validation sites at low altitudes (0–1000 m). According to the independent validation, more accurate daily precipitation estimates could be obtained at more than half of the validation sites using the proposed model compared to the source datasets. The BLS‐based framework considering environmental factors has the potential to improve estimates over SEC and is expected to be applied to other regions.
Pre‐ and Co‐Eruptive Analysis of the September 2021 Eruption at Cumbre Vieja Volcano (La Palma, Canary Islands) Through DInSAR Measurements and Analytical Modeling
Authors: De Luca C. , Valerio E. , Giudicepietro F. , Macedonio G. , Casu F. , Lanari R. 
Published: March 2022

AbstractWe investigate the 19 September 2021 eruption of the Cumbre Vieja volcano (La Palma, Canary Islands, Spain). In particular, we analyze the Differential Interferometric Synthetic Aperture Radar (DInSAR) measurements obtained by processing Sentinel‐1 images acquired from both ascending and descending orbits. First, we show the importance, for oceanic islands like La Palma, of investigating DInSAR products retrieved from time series, instead of single interferograms, to effectively remove possible atmospheric artifacts within the displacement measurements. Subsequently, we invert the retrieved data through analytical modeling. Our results highlight that a sill–like source was active in the pre–eruptive phase (8–16 September), whereas the action of two dikes prevailed during the co‐eruptive phase (17–22 September). This evolution suggests a process of magma rising through a network of interconnected sills and dikes. The seismicity, that preceded and accompanied the onset of the eruption, is consistent with our findings.
Juxtamembrane 2 mimic peptide competitively inhibits mitochondrial trafficking and activates ROS-mediated apoptosis pathway to exert anti-tumor effects
Authors: He Dan , Ma Zhijie , Xue Ke , Li Haiyan 
Published: March 2022

AbstractOur previous study demonstrates that a juxtamembrane 2 (JM2) mimic peptide can inhibit proliferation and induce apoptosis of tumor cells. However, the mechanism remains unclear. In this study, JM2 is found to suppress the growth of 4T1 breast tumors by inducing apoptosis and inhibiting the proliferation of 4T1 tumor cells. Further study indicates that JM2 can stimulate the mitochondria to gather near the microtubule-organizing center of tumor cells and subsequently induce ROS-induced ROS release responses, which results in mitochondrial dysfunction and mitochondria-mediated apoptosis. In addition, JM2 can arrest cell cycle in S phase by regulating the expression of cell cycle-related proteins and consequently inhibit proliferation of tumor cells. Then, a previously designed JM2 grafted hyaluronic acid (HA) injectable hydrogel system (HA-JM2) is injected in a breast tumor-resected model and the HA-JM2 hydrogel can inhibit the malignant proliferation of residual tumor cells and suppress the breast tumor recurrence. These findings not only confirm the application potentials of JM2 in anti-tumor therapy and tumor post-surgery treatments but also provide greater understanding on the mechanisms by which JM2 inhibits tumor growth.
STING agonist diABZI induces PANoptosis and DNA mediated acute respiratory distress syndrome (ARDS)
Authors: Messaoud-Nacer Yasmine , Culerier Elodie , Rose Stéphanie , Maillet Isabelle , Rouxel Nathalie , Briault Sylvain , Ryffel Bernhard , Quesniaux Valerie F. J. , Togbe Dieudonnée 
Published: March 2022

AbstractStimulator of interferon genes (STING) contributes to immune responses against tumors and may control viral infection including SARS-CoV-2 infection. However, activation of the STING pathway by airway silica or smoke exposure leads to cell death, self-dsDNA release, and STING/type I IFN dependent acute lung inflammation/ARDS. The inflammatory response induced by a synthetic non-nucleotide-based diABZI STING agonist, in comparison to the natural cyclic dinucleotide cGAMP, is unknown. A low dose of diABZI (1 µg by endotracheal route for 3 consecutive days) triggered an acute neutrophilic inflammation, disruption of the respiratory barrier, DNA release with NET formation, PANoptosis cell death, and inflammatory cytokines with type I IFN dependent acute lung inflammation. Downstream upregulation of DNA sensors including cGAS, DDX41, IFI204, as well as NLRP3 and AIM2 inflammasomes, suggested a secondary inflammatory response to dsDNA as a danger signal. DNase I treatment, inhibition of NET formation together with an investigation in gene-deficient mice highlighted extracellular DNA and TLR9, but not cGAS, as central to diABZI-induced neutrophilic response. Therefore, activation of acute cell death with DNA release may lead to ARDS which may be modeled by diABZI. These results show that airway targeting by STING activator as a therapeutic strategy for infection may enhance lung inflammation with severe ARDS.
Engineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics
Authors: Hadland Brandon , Varnum-Finney Barbara , Dozono Stacey , Dignum Tessa , Nourigat-McKay Cynthia , Heck Adam M. , Ishida Takashi , Jackson Dana L. , Itkin Tomer , Butler Jason M. , Rafii Shahin , Trapnell Cole , Bernstein Irwin D. 
Published: March 2022

AbstractHematopoietic stem cells (HSCs) develop from hemogenic endothelium within embryonic arterial vessels such as the aorta of the aorta-gonad-mesonephros region (AGM). To identify the signals responsible for HSC formation, here we use single cell RNA-sequencing to simultaneously analyze the transcriptional profiles of AGM-derived cells transitioning from hemogenic endothelium to HSCs, and AGM-derived endothelial cells which provide signals sufficient to support HSC maturation and self-renewal. Pseudotemporal ordering reveals dynamics of gene expression during the hemogenic endothelium to HSC transition, identifying surface receptors specifically expressed on developing HSCs. Transcriptional profiling of niche endothelial cells identifies corresponding ligands, including those signaling to Notch receptors, VLA-4 integrin, and CXCR4, which, when integrated in an engineered platform, are sufficient to support the generation of engrafting HSCs. These studies provide a transcriptional map of the signaling interactions necessary for the development of HSCs and advance the goal of engineering HSCs for therapeutic applications.
MERS-CoV ORF4b employs an unusual binding mechanism to target IMPα and block innate immunity
Authors: Munasinghe Thilini S. , Edwards Megan R. , Tsimbalyuk Sofiya , Vogel Olivia A. , Smith Kate M. , Stewart Murray , Foster Justin K. , Bosence Loretta A. , Aragão David , Roby Justin A. , Basler Christopher F. , Forwood Jade K. 
Published: March 2022

AbstractThe MERS coronavirus (MERS-CoV) is a highly pathogenic, emerging virus that produces accessory proteins to antagonize the host innate immune response. The MERS-CoV ORF4b protein has been shown to bind preferentially to the nuclear import adapter IMPα3 in infected cells, thereby inhibiting NF-κB-dependent innate immune responses. Here, we report high-resolution structures of ORF4b bound to two distinct IMPα family members. Each exhibit highly similar binding mechanisms that, in both cases, lack a prototypical Lys bound at their P2 site. Mutations within the NLS region dramatically alter the mechanism of binding, which reverts to the canonical P2 Lys binding mechanism. Mutational studies confirm that the novel binding mechanism is important for its nuclear import, IMPα interaction, and inhibition of innate immune signaling pathways. In parallel, we determined structures of the nuclear binding domain of NF-κB component p50 bound to both IMPα2 and α3, demonstrating that p50 overlaps with the ORF4b binding sites, suggesting a basis for inhibition. Our results provide a detailed structural basis that explains how a virus can target the IMPα nuclear import adapter to impair immunity, and illustrate how small mutations in ORF4b, like those found in closely related coronaviruses such as HKU5, change the IMPα binding mechanism.
The landscape of receptor-mediated precision cancer combination therapy via a single-cell perspective
Authors: Ahmadi Saba , Sukprasert Pattara , Vegesna Rahulsimham , Sinha Sanju , Schischlik Fiorella , Artzi Natalie , Khuller Samir , Schäffer Alejandro A. , Ruppin Eytan 
Published: March 2022

AbstractMining a large cohort of single-cell transcriptomics data, here we employ combinatorial optimization techniques to chart the landscape of optimal combination therapies in cancer. We assume that each individual therapy can target any one of 1269 genes encoding cell surface receptors, which may be targets of CAR-T, conjugated antibodies or coated nanoparticle therapies. We find that in most cancer types, personalized combinations composed of at most four targets are then sufficient for killing at least 80% of tumor cells while sparing at least 90% of nontumor cells in the tumor microenvironment. However, as more stringent and selective killing is required, the number of targets needed rises rapidly. Emerging individual targets include PTPRZ1 for brain and head and neck cancers and EGFR in multiple tumor types. In sum, this study provides a computational estimate of the identity and number of targets needed in combination to target cancers selectively and precisely.
Randomized clinical trial to assess the protective efficacy of a Plasmodium vivax CS synthetic vaccine
Authors: Arévalo-Herrera Myriam , Gaitán Xiomara , Larmat-Delgado Michelle , Caicedo María Alejandra , Herrera Sonia M. , Henao-Giraldo Juliana , Castellanos Angélica , Devaud Jean-Christophe , Pannatier André , Oñate José , Corradin Giampietro , Herrera Sócrates 
Published: March 2022

AbstractA randomized, double-blind, controlled vaccine clinical trial was conducted to assess, as the primary outcome, the safety and protective efficacy of thePlasmodium vivaxcircumsporozoite (CS) protein in healthy malaria-naïve (phase IIa) and semi-immune (phase IIb) volunteers. Participants (n = 35) were randomly selected from a larger group (n = 121) and further divided into naïve (n = 17) and semi-immune (n = 18) groups and were immunized at months 0, 2, and 6 withPvCS formulated in Montanide ISA-51 adjuvant or placebo (adjuvant alone). Specific antibodies and IFN-γ responses toPvCS were determined as secondary outcome; all experimental volunteers developed specific IgG and IFN-γ. Three months after the last immunization, all participants were subjected to controlled human malaria infection. All naive controls became infected and drastic parasitemia reduction, including sterile protection, developed in several experimental volunteers in phase IIa (6/11) (54%, 95% CI 0.25–0.84) and phase IIb (7/11) (64%, 95% CI 0.35–0.92). However, no difference in parasitemia was observed between the phase IIb experimental and control subgroups. In conclusion, this study demonstrates significant protection in both naïve and semi-immune volunteers, encouraging furtherPvCS vaccine clinical development. Trial registration number NCT 02083068. This trial was funded by Colciencias (grant 529-2009), NHLBI (grant RHL086488 A), and MVDC/CIV Foundation (grant 2014-1206).
The architecture of assisted colonisation in sea turtles: building new populations in a biodiversity crisis
Authors: Barbanti Anna , Blumenthal Janice M. , Broderick Annette C. , Godley Brendan J. , Prat-Varela Alejandro , Turmo Maria , Pascual Marta , Carreras Carlos 
Published: March 2022

AbstractDue to changing environmental conditions, many species will have to migrate or occupy new suitable areas to avoid potential extinction in the current biodiversity crisis. Long-lived animals are especially vulnerable and ex-situ conservation actions can provide solutions through assisted colonisations. However, there is little empirical evidence on the process of founding new populations for such species or the feasibility of assisted colonisations as a viable conservation measure. Here, we combined genetics with reproductive data to study the rise of two wild populations of green turtles (Chelonia mydas) in the Cayman Islands as a possible outcome of a reintroduction program started 50 years ago. We show that both populations are highly related to the captive population but rapidly diverged due to genetic drift. Individuals from the reintroduced populations showed high levels of nest fidelity, within and across nesting seasons, indicating that philopatry may help reinforce the success of new populations. Additionally, we show that reintroduction from captive populations has not undermined the reproductive fitness of first generation individuals. Sea turtle reintroduction programs can, therefore, establish new populations but require scientific evaluation of costs and benefits and should be monitored over time to ensure viability in the long-term.
Topoarchitected polymer networks expand the space of material properties
Authors: Liu Xiao , Wu Jingping , Qiao Keke , Liu Guohan , Wang Zhengjin , Lu Tongqing , Suo Zhigang , Hu Jian 
Published: March 2022

AbstractMany living tissues achieve functions through architected constituents with strong adhesion. An Achilles tendon, for example, transmits force, elastically and repeatedly, from a muscle to a bone through staggered alignment of stiff collagen fibrils in a soft proteoglycan matrix. The collagen fibrils align orderly and adhere to the proteoglycan strongly. However, synthesizing architected materials with strong adhesion has been challenging. Here we fabricate architected polymer networks by sequential polymerization and photolithography, and attain adherent interface by topological entanglement. We fabricate tendon-inspired hydrogels by embedding hard blocks in topological entanglement with a soft matrix. The staggered architecture and strong adhesion enable high elastic limit strain and high toughness simultaneously. This combination of attributes is commonly desired in applications, but rarely achieved in synthetic materials. We further demonstrate architected polymer networks of various geometric patterns and material combinations to show the potential for expanding the space of material properties.
Earlier emergence of a temperature response to mitigation by filtering annual variability
Authors: Samset B. H. , Zhou C. , Fuglestvedt J. S. , Lund M. T. , Marotzke J. , Zelinka M. D. 
Published: March 2022

AbstractThe rate of global surface warming is crucial for tracking progress towards global climate targets, but is strongly influenced by interannual-to-decadal variability, which precludes rapid detection of the temperature response to emission mitigation. Here we use a physics based Green’s function approach to filter out modulations to global mean surface temperature from sea-surface temperature (SST) patterns, and show that it results in an earlier emergence of a response to strong emissions mitigation. For observed temperatures, we find a filtered 2011–2020 surface warming rate of 0.24 °C per decade, consistent with long-term trends. Unfiltered observations show 0.35 °C per decade, partly due to the El Nino of 2015–2016. Pattern filtered warming rates can become a strong tool for the climate community to inform policy makers and stakeholder communities about the ongoing and expected climate responses to emission reductions, provided an effort is made to improve and validate standardized Green’s functions.
Superheating of grain boundaries within bulk colloidal crystals
Authors: Xiao Xiuming , Wang Lilin , Wang Zhijun , Wang Ziren 
Published: March 2022

AbstractWhether grain boundaries (GBs) premelt is a longstanding question, because of the difficulty of direct experimental tests. Here, we focused an optical beam to locally heat single GBs within bulk hard-sphere colloidal crystals, observing the melting dynamics at single-particle resolution by video microscopy. The melting point is determined by analysing both the Lindemann parameter and the critical nucleus size for homogeneous nucleation. We found that all the GBs, including the high-energy GBs, can be superheated and melt via a heterogeneous nucleation mechanism. Based on the classical nucleation theory of GBs, we measured the incubation time and contact angle of the critical nucleus to compute all relevant kinetic factors, as well as the energy barrier, nucleation rate and the diffusion coefficient at the solid–liquid interface under weak superheating. The superheat limits of GBs with various misorientations have also been measured to further explore the instability mechanism. Under traditional uniform heating, premelting occurs only at triple junctions, whereas GBs retain their original structures up to the melting point. The premelted regions at triple junctions further interrupt high-energy GBs from superheating, through intrusion by uniform liquid layers. Overall, our experiments confirm the existence of superheating of GBs.
Membrane thickness, lipid phase and sterol type are determining factors in the permeability of membranes to small solutes
Authors: Frallicciardi Jacopo , Melcr Josef , Siginou Pareskevi , Marrink Siewert J. , Poolman Bert 
Published: March 2022

AbstractCell membranes provide a selective semi-permeable barrier to the passive transport of molecules. This property differs greatly between organisms. While the cytoplasmic membrane of bacterial cells is highly permeable for weak acids and glycerol, yeasts can maintain large concentration gradients. Here we show that such differences can arise from the physical state of the plasma membrane. By combining stopped-flow kinetic measurements with molecular dynamics simulations, we performed a systematic analysis of the permeability of a variety of small molecules through synthetic membranes of different lipid composition to obtain detailed molecular insight into the permeation mechanisms. While membrane thickness is an important parameter for the permeability through fluid membranes, the largest differences occur when the membranes transit from the liquid-disordered to liquid-ordered and/or to gel state, which is in agreement with previous work on passive diffusion of water. By comparing our results with in vivo measurements from yeast, we conclude that the yeast membrane exists in a highly ordered and rigid state, which is comparable to synthetic saturated DPPC-sterol membranes.
Crystal Structures of Wolbachia CidA and CidB Reveal Determinants of Bacteria-induced Cytoplasmic Incompatibility and Rescue
Authors: Wang Haofeng , Xiao Yunjie , Chen Xia , Zhang Mengwen , Sun Guangxin , Wang Feng , Wang Lin , Zhang Hanxiao , Zhang Xiaoyu , Yang Xin , Li Wenling , Wei Yi , Yao Deqiang , Zhang Bing , Li Jun , Cui Wen , Wang Fenghua , Chen Cheng , Shen Wei , Su Dan , Bai Fang , Huang Jinhai , Ye Sheng , Zhang Lei , Ji Xiaoyun , Wang Wei , Wang Zefang , Hochstrasser Mark , Yang Haitao 
Published: March 2022

AbstractCytoplasmic incompatibility (CI) results when Wolbachia bacteria-infected male insects mate with uninfected females, leading to embryonic lethality. “Rescue” of viability occurs if the female harbors the same Wolbachia strain. CI is caused by linked pairs of Wolbachia genes called CI factors (CifA and CifB). The co-evolution of CifA-CifB pairs may account in part for the incompatibility patterns documented in insects infected with different Wolbachia strains, but the molecular mechanisms remain elusive. Here, we use X-ray crystallography and AlphaFold to analyze the CI factors from Wolbachia strain wMel called CidAwMel and CidBwMel. Substituting CidAwMel interface residues with those from CidAwPip (from strain wPip) enables the mutant protein to bind CidBwPip and rescue CidBwPip-induced yeast growth defects, supporting the importance of CifA-CifB interaction in CI rescue. Sequence divergence in CidAwPip and CidBwPip proteins affects their pairwise interactions, which may help explain the complex incompatibility patterns of mosquitoes infected with different wPip strains.
Comparison of clonal architecture between primary and immunodeficient mouse-engrafted acute myeloid leukemia cells
Authors: Kawashima Naomi , Ishikawa Yuichi , Kim Jeong Hui , Ushijima Yoko , Akashi Akimi , Yamaguchi Yohei , Hattori Hikaru , Nakashima Marie , Ikeno Seara , Kihara Rika , Nishiyama Takahiro , Morishita Takanobu , Watamoto Koichi , Ozawa Yukiyasu , Kitamura Kunio , Kiyoi Hitoshi 
Published: March 2022

AbstractPatient-derived xenografts (PDX) are widely used as human cancer models. Previous studies demonstrated clonal discordance between PDX and primary cells. However, in acute myeloid leukemia (AML)-PDX models, the significance of the clonal dynamics occurring in PDX remains unclear. By evaluating changes in the variant allele frequencies (VAF) of somatic mutations in serial samples of paired primary AML and their PDX bone marrow cells, we identify the skewing engraftment of relapsed or refractory (R/R) AML clones in 57% of PDX models generated from multiclonal AML cells at diagnosis, even if R/R clones are minor at <5% of VAF in patients. The event-free survival rate of patients whose AML cells successfully engraft in PDX models is consistently lower than that of patients with engraftment failure. We herein demonstrate that primary AML cells including potentially chemotherapy-resistant clones dominantly engraft in AML-PDX models and they enrich pre-existing treatment-resistant subclones.
Bound nucleotide can control the dynamic architecture of monomeric actin
Authors: Ali Rustam , Zahm Jacob A. , Rosen Michael K. 
Published: March 2022

AbstractPolymerization of actin into cytoskeletal filaments is coupled to its bound adenine nucleotides. The mechanism by which nucleotide modulates actin functions has not been evident from analyses of ATP- and ADP-bound crystal structures of the actin monomer. We report that NMR chemical shift differences between the two forms are globally distributed. Furthermore, microsecond–millisecond motions are spread throughout the molecule in the ATP form, but largely confined to subdomains 1 and 2, and the nucleotide binding site in the ADP form. Through these motions, the ATP- and ADP-bound forms sample different high-energy conformations. A deafness-causing, fast-nucleating actin mutant populates the high-energy conformer of ATP-actin more than the wild-type protein, suggesting that this conformer may be on the pathway to nucleation. Together, the data suggest a model in which differential sampling of a nucleation-compatible form of the actin monomer may contribute to control of actin filament dynamics by nucleotide.