bluuebunny/crossref_metadata_2025_split huggingface dataset:
The HDO Cycle on Mars: Comparison of ACS Observations With GCM Simulations
Authors: Rossi Loïc , Vals Margaux , Alday Juan , Montmessin Franck , Fedorova Anna , Trokhimovskiy Alexander , Korablev Oleg , Lefèvre Franck , Gonzalez‐Galindo Francisco , Luginin Mikhail , Bierjon Antoine , Forget François , Millour Ehouarn 
Published: July 2022

AbstractThe D/H ratio and its implications on the atmospheric escape, make it an essential observable to study the current and past inventory of water on Mars. With the arrival of the Trace Gas Orbiter around Mars, new measurements of the D/H ratio are now available and require tools to interpret the observations and understand the HDO cycle. We here present simulations of an updated version of the Laboratoire de Météorologie Dynamique Mars Global Climate Model which includes HDO and in particular the fractionation processes it undergoes. We compare our model simulations with the HDO observations in solar occultation from the Atmospheric Chemistry Suite mid‐infrared channel on board the Trace Gas Orbiter (Alday et al., 2021; https://doi.org/10.5281/ZENODO.5100448). The model successfully reproduces the general trends of the D/H ratio, indicating that the main physical processes are captured by theory. A consistent simulation of condensation processes is found to be key in the representation of the D/H ratio. Improvements in the representation of clouds and on the water cycle will help improving the representation of the HDO cycle and better help extrapolate back in times the conditions of water escape on Mars.
Gene-based polygenic risk scores analysis of alcohol use disorder in African Americans
Authors: Lai Dongbing , Schwantes-An Tae-Hwi , Abreu Marco , Chan Grace , Hesselbrock Victor , Kamarajan Chella , Liu Yunlong , Meyers Jacquelyn L. , Nurnberger John I. , Plawecki Martin H. , Wetherill Leah , Schuckit Marc , Zhang Pengyue , Edenberg Howard J. , Porjesz Bernice , Agrawal Arpana , Foroud Tatiana 
Published: July 2022

AbstractGenome-wide association studies (GWAS) in admixed populations such as African Americans (AA) have limited sample sizes, resulting in poor performance of polygenic risk scores (PRS). Based on the observations that many disease-causing genes are shared between AA and European ancestry (EA) populations, and some disease-causing variants are located within the boundaries of these genes, we proposed a novel gene-based PRS framework (PRSgene) by using variants located within disease-associated genes. Using the AA GWAS of alcohol use disorder (AUD) from the Million Veteran Program and the EA GWAS of problematic alcohol use as the discovery GWAS, we identified 858 variants from 410 genes that were AUD-related in both AA and EA. PRSgene calculated using these variants were significantly associated with AUD in three AA target datasets (P-values ranged from 7.61E−05 to 6.27E−03; Betas ranged from 0.15 to 0.21) and outperformed PRS calculated using all variants (P-values ranged from 7.28E−03 to 0.16; Betas ranged from 0.06 to 0.18). PRSgene were also associated with AUD in an EA target dataset (P-value = 0.02, Beta = 0.11). In AA, individuals in the highest PRSgene decile had an odds ratio of 1.76 (95% CI: 1.32–2.34) to develop AUD compared to those in the lowest decile. The 410 genes were enriched in 54 Gene Ontology biological processes, including ethanol oxidation and processes involving the synaptic system, which are known to be AUD-related. In addition, 26 genes were targets of drugs used to treat AUD or other diseases that might be considered for repurposing to treat AUD. Our study demonstrated that the gene-based PRS had improved performance in evaluating AUD risk in AA and provided new insight into AUD genetics.
The epidemiology of endodontic complexity in general dental practice: a prevalence study
Authors: Essam Obyda , Kasperek Dariusz , Boyle Edward L. , Jarad Fadi 
Published: July 2022

AbstractAim To determine the prevalence and the epidemiology of the factors influencing endodontic complexities in general dental practice.Method Eligible cases where endodontic treatment was indicated as a treatment option were collected by a total of 30 general dental practitioners based in the UK. Online-based Endodontic Complexity Assessment Tool (E-CAT) was used to determine the perceived complexity of each case. In total, 22 categories, including patient- and tooth-related factors, were recorded.Results Collectively, 435 non-surgical root canal treatment cases were assessed. Overall, 72% of the root canal treatments encountered in general dental practice were found to be either uncomplicated (Class I) or moderately complicated (Class II) and can be considered within the remit of general dental practitioners. Despite the relatively equal distribution of the assessed teeth, the proportion of extraction as a proposed treatment for posterior teeth was more than double that of anterior teeth.Conclusion The results obtained in this study provide a good resource and databank for researchers, educators, public health commissioners and academic institutions to access a wide range of information concerning the prevalence and distribution of endodontic complexity.
Stanniocalcin 2 drives malignant transformation of human glioblastoma cells by targeting SNAI2 and Matrix Metalloproteinases
Authors: Yun Eun-Jin , Kim Donghwi , Hsieh Jer-Tsong , Baek Seung Tae 
Published: July 2022

AbstractGlioblastoma multiforme (GBM) is the most malignant brain tumor and is refractory to conventional therapies. Although previous studies have proposed that the interaction between gene mutations and the external environment leads to the occurrence of GBM, the pathogenesis of GBM is still unclear and much remains to be studied. Herein, we show an association between human glycoprotein stanniocalcin-2 (STC2) and aggressive GBM progression, and demonstrate the underlying mechanism. Elevated STC2 expression and secretion greatly increase GBM cell growth and invasive phenotypes. Mechanistically, both, conditioned media (CM) containing STC2 and recombinant STC2, can induce the transformation of GBM cells into more malignant phenotypes by upregulating the expression of the epithelial-mesenchymal transition transcription factor, snail family transcription repressor 2 (SNAI2) as well as matrix metalloproteinases (MMPs). Moreover, we further demonstrate that the oncogenic function of STC2 in GBM is mediated through the MAPK signaling pathway. Collectively, these results identify the mechanism of STC2 targeting SNAI2 and MMPs through the MAPK pathway in GBM, and provide insights into a potential therapeutic strategy for GBM.
Oncogenic TRIB2 interacts with and regulates PKM2 to promote aerobic glycolysis and lung cancer cell procession
Authors: Liu Yuan-Rong , Song Dan-Dan , Liang Dong-Min , Li You-Jie , Yan Yun-Fei , Sun Hong-Fang , Zhang Mei-Ling , Hu Jin-Xia , Zhao Yu-Long , Liang Yan , Li Yan-Mei , Yang Zhen , Wang Ran-Ran , Zheng Hou-Feng , Wang Pingyu , Xie Shu-Yang 
Published: July 2022

AbstractPKM2 is an important regulator of the aerobic glycolysis that plays a vital role in cancer cell metabolic reprogramming. In general, Trib2 is considered as a “pseudokinase”, contributing to different kinds of cancer. However, the detailed roles of TRIB2 in regulating cancer metabolism by PKM2 remain unclear. This study demonstrated that TRIB2, not a “pseudokinase”, has the kinase activity to directly phosphorylate PKM2 at serine 37 in cancer cells. The elevated pSer37-PKM2 would subsequently promote the PKM2 dimers to enter into nucleus and increase the expression of LDHA, GLUT1, and PTBP1. The aerobic glycolysis is then elevated to promote cancer cell proliferation and migration in TRIB2- or PKM2-overexpressed cultures. The glucose uptake and lactate production increased, but the ATP content decreased in TRIB2- or PKM2-treated cultures. Experiments of TRIB2−/− mice further supported that TRIB2 could regulate aerobic glycolysis by PKM2. Thus, these results reveal the new kinase activity of TRIB2 and its mechanism in cancer metabolism may be related to regulating PKM2 to promote lung cancer cell proliferation in vitro and in vivo, suggesting promising therapeutic targets for cancer therapy by controlling cancer metabolism.
Selective activation and expansion of regulatory T cells using lipid encapsulated mRNA encoding a long-acting IL-2 mutein
Authors: de Picciotto Seymour , DeVita Nicholas , Hsiao Chiaowen Joyce , Honan Christopher , Tse Sze-Wah , Nguyen Mychael , Ferrari Joseph D. , Zheng Wei , Wipke Brian T. , Huang Eric 
Published: July 2022

AbstractInterleukin-2 (IL-2) is critical for regulatory T cell (Treg) function and homeostasis. At low doses, IL-2 can suppress immune pathologies by expanding Tregs that constitutively express the high affinity IL-2Rα subunit. However, even low dose IL-2, signaling through the IL2-Rβ/γ complex, may lead to the activation of proinflammatory, non-Treg T cells, so improving specificity toward Tregs may be desirable. Here we use messenger RNAs (mRNA) to encode a half-life-extended human IL-2 mutein (HSA-IL2m) with mutations promoting reliance on IL-2Rα. Our data show that IL-2 mutein subcutaneous delivery as lipid-encapsulated mRNA nanoparticles selectively activates and expands Tregs in mice and non-human primates, and also reduces disease severity in mouse models of acute graft versus host disease and experimental autoimmune encephalomyelitis. Single cell RNA-sequencing of mouse splenic CD4+T cells identifies multiple Treg states with distinct response dynamics following IL-2 mutein treatment. Our results thus demonstrate the potential of mRNA-encoded HSA-IL2m immunotherapy to treat autoimmune diseases.
Healthy cloned offspring derived from freeze-dried somatic cells
Authors: Wakayama Sayaka , Ito Daiyu , Hayashi Erika , Ishiuchi Takashi , Wakayama Teruhiko 
Published: July 2022

AbstractMaintaining biodiversity is an essential task, but storing germ cells as genetic resources using liquid nitrogen is difficult, expensive, and easily disrupted during disasters. Our aim is to generate cloned mice from freeze-dried somatic cell nuclei, preserved at −30 °C for up to 9 months after freeze drying treatment. All somatic cells died after freeze drying, and nucleic DNA damage significantly increased. However, after nuclear transfer, we produced cloned blastocysts from freeze-dried somatic cells, and established nuclear transfer embryonic stem cell lines. Using these cells as nuclear donors for re-cloning, we obtained healthy cloned female and male mice with a success rate of 0.2–5.4%. Here, we show that freeze-dried somatic cells can produce healthy, fertile clones, suggesting that this technique may be important for the establishment of alternative, cheaper, and safer liquid nitrogen-free bio-banking solutions.
A versatile active learning workflow for optimization of genetic and metabolic networks
Authors: Pandi Amir , Diehl Christoph , Yazdizadeh Kharrazi Ali , Scholz Scott A. , Bobkova Elizaveta , Faure Léon , Nattermann Maren , Adam David , Chapin Nils , Foroughijabbari Yeganeh , Moritz Charles , Paczia Nicole , Cortina Niña Socorro , Faulon Jean-Loup , Erb Tobias J. 
Published: July 2022

AbstractOptimization of biological networks is often limited by wet lab labor and cost, and the lack of convenient computational tools. Here, we describe METIS, a versatile active machine learning workflow with a simple online interface for the data-driven optimization of biological targets with minimal experiments. We demonstrate our workflow for various applications, including cell-free transcription and translation, genetic circuits, and a 27-variable synthetic CO2-fixation cycle (CETCH cycle), improving these systems between one and two orders of magnitude. For the CETCH cycle, we explore 1025 conditions with only 1,000 experiments to yield the most efficient CO2-fixation cascade described to date. Beyond optimization, our workflow also quantifies the relative importance of individual factors to the performance of a system identifying unknown interactions and bottlenecks. Overall, our workflow opens the way for convenient optimization and prototyping of genetic and metabolic networks with customizable adjustments according to user experience, experimental setup, and laboratory facilities.
Atypical sideways recognition of CD1a by autoreactive γδ T cell receptors
Authors: Wegrecki Marcin , Ocampo Tonatiuh A. , Gunasinghe Sachith D. , von Borstel Anouk , Tin Shin Yi , Reijneveld Josephine F. , Cao Thinh-Phat , Gully Benjamin S. , Le Nours Jérôme , Moody D. Branch , Van Rhijn Ildiko , Rossjohn Jamie 
Published: July 2022

AbstractCD1a is a monomorphic antigen-presenting molecule on dendritic cells that presents lipids to αβ T cells. Whether CD1a represents a ligand for other immune receptors remains unknown. Here we use CD1a tetramers to show that CD1a is a ligand for Vδ1+γδ T cells. Functional studies suggest that two γδ T cell receptors (TCRs) bound CD1a in a lipid-independent manner. The crystal structures of three Vγ4Vδ1 TCR-CD1a-lipid complexes reveal that the γδ TCR binds at the extreme far side and parallel to the long axis of the β-sheet floor of CD1a’s antigen-binding cleft. Here, the γδ TCR co-recognises the CD1a heavy chain and β2 microglobulin in a manner that is distinct from all other previously observed γδ TCR docking modalities. The ‘sideways’ and lipid antigen independent mode of autoreactive CD1a recognition induces TCR clustering on the cell surface and proximal T cell signalling as measured by CD3ζ phosphorylation. In contrast with the ‘end to end’ binding of αβ TCRs that typically contact carried antigens, autoreactive γδ TCRs support geometrically diverse approaches to CD1a, as well as antigen independent recognition.
Engineering consortia by polymeric microbial swarmbots
Authors: Wang Lin , Zhang Xi , Tang Chenwang , Li Pengcheng , Zhu Runtao , Sun Jing , Zhang Yunfeng , Cui Hua , Ma Jiajia , Song Xinyu , Zhang Weiwen , Gao Xiang , Luo Xiaozhou , You Lingchong , Chen Ye , Dai Zhuojun 
Published: July 2022

AbstractSynthetic microbial consortia represent a new frontier for synthetic biology given that they can solve more complex problems than monocultures. However, most attempts to co-cultivate these artificial communities fail because of the winner-takes-all in nutrients competition. In soil, multiple species can coexist with a spatial organization. Inspired by nature, here we show that an engineered spatial segregation method can assemble stable consortia with both flexibility and precision. We create microbial swarmbot consortia (MSBC) by encapsulating subpopulations with polymeric microcapsules. The crosslinked structure of microcapsules fences microbes, but allows the transport of small molecules and proteins. MSBC method enables the assembly of various synthetic communities and the precise control over the subpopulations. These capabilities can readily modulate the division of labor and communication. Our work integrates the synthetic biology and material science to offer insights into consortia assembly and serve as foundation to diverse applications from biomanufacturing to engineered photosynthesis.
An expanded reference map of the human gut microbiome reveals hundreds of previously unknown species
Authors: Leviatan Sigal , Shoer Saar , Rothschild Daphna , Gorodetski Maria , Segal Eran 
Published: July 2022

AbstractThe gut is the richest ecosystem of microbes in the human body and has great influence on our health. Despite many efforts, the set of microbes inhabiting this environment is not fully known, limiting our ability to identify microbial content and to research it. In this work, we combine new microbial metagenomic assembled genomes from 51,052 samples, with previously published genomes to produce a curated set of 241,118 genomes. Based on this set, we procure a new and improved human gut microbiome reference set of 3594 high quality species genomes, which successfully matches 83.65% validation samples’ reads. This improved reference set contains 310 novel species, including one that exists in 19% of validation samples. Overall, this study provides a gut microbial genome reference set that can serve as a valuable resource for further research.
Wavelength-multiplexed hook nanoantennas for machine learning enabled mid-infrared spectroscopy
Authors: Ren Zhihao , Zhang Zixuan , Wei Jingxuan , Dong Bowei , Lee Chengkuo 
Published: July 2022

AbstractInfrared (IR) plasmonic nanoantennas (PNAs) are powerful tools to identify molecules by the IR fingerprint absorption from plasmon-molecules interaction. However, the sensitivity and bandwidth of PNAs are limited by the small overlap between molecules and sensing hotspots and the sharp plasmonic resonance peaks. In addition to intuitive methods like enhancement of electric field of PNAs and enrichment of molecules on PNAs surfaces, we propose a loss engineering method to optimize damping rate by reducing radiative loss using hook nanoantennas (HNAs). Furthermore, with the spectral multiplexing of the HNAs from gradient dimension, the wavelength-multiplexed HNAs (WMHNAs) serve as ultrasensitive vibrational probes in a continuous ultra-broadband region (wavelengths from 6 μm to 9 μm). Leveraging the multi-dimensional features captured by WMHNA, we develop a machine learning method to extract complementary physical and chemical information from molecules. The proof-of-concept demonstration of molecular recognition from mixed alcohols (methanol, ethanol, and isopropanol) shows 100% identification accuracy from the microfluidic integrated WMHNAs. Our work brings another degree of freedom to optimize PNAs towards small-volume, real-time, label-free molecular recognition from various species in low concentrations for chemical and biological diagnostics.
Bixbyite-type Ln2O3 as promoters of metallic Ni for alkaline electrocatalytic hydrogen evolution
Authors: Sun Hongming , Yan Zhenhua , Tian Caiying , Li Cha , Feng Xin , Huang Rong , Lan Yinghui , Chen Jing , Li Cheng-Peng , Zhang Zhihong , Du Miao 
Published: July 2022

AbstractThe active-site density, intrinsic activity, and durability of Ni-based catalysts are critical to their application in industrial alkaline water electrolysis. This work develops a kind of promoters, the bixbyite-type lanthanide metal sesquioxides (Ln2O3), which can be implanted into metallic Ni by selective high-temperature reduction to achieve highly efficient Ni/Ln2O3hybrid electrocatalysts toward hydrogen evolution reaction. The screened Ni/Yb2O3catalyst shows the low overpotential (20.0 mV at 10 mA cm−2), low Tafel slope (44.6 mV dec−1), and excellent long-term durability (360 h at 500 mA cm−2), significantly outperforming the metallic Ni and benchmark Pt/C catalysts. The remarkable hydrogen evolution activity and stability of Ni/Yb2O3are attributed to that the Yb2O3promoter with high oxophilicity and thermodynamic stability can greatly enlarge the active-site density, reduce the energy barrier of water dissociation, optimize the free energy of hydrogen adsorption, and avoid the oxidation corrosion of Ni.
Structures of LIG1 that engage with mutagenic mismatches inserted by polβ in base excision repair
Authors: Tang Qun , Gulkis Mitchell , McKenna Robert , Çağlayan Melike 
Published: July 2022

AbstractDNA ligase I (LIG1) catalyzes the ligation of the nick repair intermediate after gap filling by DNA polymerase (pol) β during downstream steps of the base excision repair (BER) pathway. However, how LIG1 discriminates against the mutagenic 3′-mismatches incorporated by polβ at atomic resolution remains undefined. Here, we determine the X-ray structures of LIG1/nick DNA complexes with G:T and A:C mismatches and uncover the ligase strategies that favor or deter the ligation of base substitution errors. Our structures reveal that the LIG1 active site can accommodate a G:T mismatch in the wobble conformation, where an adenylate (AMP) is transferred to the 5′-phosphate of a nick (DNA-AMP), while it stays in the LIG1-AMP intermediate during the initial step of the ligation reaction in the presence of an A:C mismatch at the 3′-strand. Moreover, we show mutagenic ligation and aberrant nick sealing of dG:T and dA:C mismatches, respectively. Finally, we demonstrate that AP-endonuclease 1 (APE1), as a compensatory proofreading enzyme, removes the mismatched bases and interacts with LIG1 at the final BER steps. Our overall findings provide the features of accurate versus mutagenic outcomes coordinated by a multiprotein complex including polβ, LIG1, and APE1 to maintain efficient repair.
Monomethyl auristatin antibody and peptide drug conjugates for trimodal cancer chemo-radio-immunotherapy
Authors: Hingorani Dina V. , Allevato Michael M. , Camargo Maria F. , Lesperance Jacqueline , Quraishi Maryam A. , Aguilera Joseph , Franiak-Pietryga Ida , Scanderbeg Daniel J. , Wang Zhiyong , Molinolo Alfredo A. , Alvarado Diego , Sharabi Andrew B. , Bui Jack D. , Cohen Ezra E. W. , Adams Stephen R. , Gutkind J. Silvio , Advani Sunil J. 
Published: July 2022

AbstractLocally advanced cancers remain therapeutically challenging to eradicate. The most successful treatments continue to combine decades old non-targeted chemotherapies with radiotherapy that unfortunately increase normal tissue damage in the irradiated field and have systemic toxicities precluding further treatment intensification. Therefore, alternative molecularly guided systemic therapies are needed to improve patient outcomes when applied with radiotherapy. In this work, we report a trimodal precision cytotoxic chemo-radio-immunotherapy paradigm using spatially targeted auristatin warheads. Tumor-directed antibodies and peptides conjugated to radiosensitizing monomethyl auristatin E (MMAE) specifically produce CD8 T cell dependent durable tumor control of irradiated tumors and immunologic memory. In combination with ionizing radiation, MMAE sculpts the tumor immune infiltrate to potentiate immune checkpoint inhibition. Here, we report therapeutic synergies of targeted cytotoxic auristatin radiosensitization to stimulate anti-tumor immune responses providing a rationale for clinical translational of auristatin antibody drug conjugates with radio-immunotherapy combinations to improve tumor control.
Mechanistic basis for maintenance of CHG DNA methylation in plants
Authors: Fang Jian , Jiang Jianjun , Leichter Sarah M. , Liu Jie , Biswal Mahamaya , Khudaverdyan Nelli , Zhong Xuehua , Song Jikui 
Published: July 2022

AbstractDNA methylation is an evolutionarily conserved epigenetic mechanism essential for transposon silencing and heterochromatin assembly. In plants, DNA methylation widely occurs in the CG, CHG, and CHH (H = A, C, or T) contexts, with the maintenance of CHG methylation mediated by CMT3 chromomethylase. However, how CMT3 interacts with the chromatin environment for faithful maintenance of CHG methylation is unclear. Here we report structure-function characterization of the H3K9me2-directed maintenance of CHG methylation by CMT3 and its Zea mays ortholog ZMET2. Base-specific interactions and DNA deformation coordinately underpin the substrate specificity of CMT3 and ZMET2, while a bivalent readout of H3K9me2 and H3K18 allosterically stimulates substrate binding. Disruption of the interaction with DNA or H3K9me2/H3K18 led to loss of CMT3/ZMET2 activity in vitro and impairment of genome-wide CHG methylation in vivo. Together, our study uncovers how the intricate interplay of CMT3, repressive histone marks, and DNA sequence mediates heterochromatic CHG methylation.