bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADAR1-dependent miR-3144-3p editing simultaneously induces MSI2 expression and suppresses SLC38A4 expression in liver cancer
Authors: Kim Hyung Seok , Na Min Jeong , Son Keun Hong , Yang Hee Doo , Kim Sang Yean , Shin Eunbi , Ha Jin Woong , Jeon Soyoung , Kang Keunsoo , Moon Kiho , Park Won Sang , Nam Suk Woo 
Published: January 2023

AbstractAberrant adenosine-to-inosine (A-to-I) RNA editing, catalyzed by adenosine deaminase acting on double-stranded RNA (ADAR), has been implicated in various cancers, but the mechanisms by which microRNA (miRNA) editing contributes to cancer development are largely unknown. Our multistage hepatocellular carcinogenesis transcriptome data analyses, together with publicly available data, indicated that ADAR1 was the most profoundly dysregulated gene among RNA-editing enzyme family members in liver cancer. Targeted inactivation of ADAR1 inhibited the in vitro tumorigenesis of liver cancer cells. An integrative computational analyses of RNA-edited hotspots and the known editing frequency of miRNAs suggested that the miRNA miR-3144-3p was edited by ADAR1 during liver cancer progression. Specifically, ADAR1 promoted A-to-I editing of canonical miR-3144-3p to replace the adenosine at Position 3 in the seed region with a guanine (ED_miR-3144-3p(3_A < G)) in liver cancer cells. We then demonstrated that Musashi RNA-binding protein 2 (MSI2) was a specific target of miR-3144-3p and that MSI2 overexpression was due to excessive ADAR1-dependent over-editing of canonical miR-3144-3p in liver cancer. In addition, target prediction analyses and validation experiments identified solute carrier family 38 member 4 (SLC38A4) as a specific gene target of ED_miR-3144-3p(3_A < G). The ectopic expression of both ADAR1 and the ED_miR-3144-3p(3_A < G) mimic enhanced mitotic activities, and ADAR1 suppressed SLC38A4 expression in liver cancer cells. Treatments with mouse-specific ADAR1-, MSI2-siRNA-, or SLC38A4-expressing plasmids suppressed tumorigenesis and tumor growth in a mouse model of spontaneous liver cancer. Our findings suggest that the aberrant regulation of ADAR1 augments oncogenic MSI2 effects by excessively editing canonical miR-3144-3p and that the resultant ED_miR-3144-3p(3_A < G) simultaneously suppresses tumor suppressor SLC38A4 expression, contributing to hepatocellular carcinogenesis.
Biomolecular condensate assembly of nArgBP2 tunes its functionality to manifest the structural plasticity of dendritic spines
Authors: Cho Eunji , Lee Sang-Eun , Lee Unghwi , Goh Yuna , Jeong Seonyoung , Choi Junyoung , Jeong Won-Ki , Chang Sunghoe 
Published: January 2023

AbstractnArgBP2, a candidate gene for intellectual disability, is a postsynaptic protein critical for dendritic spine development and morphogenesis, and its knockdown (KD) in developing neurons severely impairs spine-bearing excitatory synapse formation. Surprisingly, nArgBP2 KD in mature neurons did not cause morphological defects in the existing spines at rest, raising questions of how it functions in mature neurons. We found that unlike its inaction at rest, nArgBP2 KD completely inhibited the enlargement of dendritic spines during chemically induced long-term potentiation (cLTP) in mature neurons. We further found that nArgBP2 forms condensates in dendritic spines and that these condensates are dispersed by cLTP, which spatiotemporally coincides with spine head enlargement. Condensates with CaMKII phosphorylation-deficient mutant or CaMKII inhibition are neither dispersed nor accompanied by spine enlargement during cLTP. We found that nArgBP2 condensates in spines exhibited liquid-like properties, and in heterologous and in vitro expression systems, nArgBP2 undergoes liquid-liquid phase separation via multivalent intermolecular interactions between SH3 domains and proline-rich domains. It also forms coacervates with CaMKIIα, which is rapidly dissembled by calcium/CaMKIIα-dependent phosphorylation. We further showed that the interaction between nArgBP2 and WAVE1 competes with nArgBP2 phase separation and that blocking the nArgBP2-WAVE1 interaction prevents spine enlargement during cLTP. Together, our results suggest that nArgBP2 at rest is confined to the condensates but is released by CaMKIIα-mediated phosphorylation during synaptic plasticity, which regulates its timely interaction with WAVE1 to induce spine head enlargement in mature neurons.
Recent developments in multifunctional neural probes for simultaneous neural recording and modulation
Authors: Li Hongbian , Wang Jinfen , Fang Ying 
Published: January 2023

AbstractNeural probes are among the most widely applied tools for studying neural circuit functions and treating neurological disorders. Given the complexity of the nervous system, it is highly desirable to monitor and modulate neural activities simultaneously at the cellular scale. In this review, we provide an overview of recent developments in multifunctional neural probes that allow simultaneous neural activity recording and modulation through different modalities, including chemical, electrical, and optical stimulation. We will focus on the material and structural design of multifunctional neural probes and their interfaces with neural tissues. Finally, future challenges and prospects of multifunctional neural probes will be discussed.
Determinants of survival and retrospective comparisons of 183 clinical trial patients with myelofibrosis treated with momelotinib, ruxolitinib, fedratinib or BMS- 911543 JAK2 inhibitor
Authors: Gangat Naseema , Begna Kebede H. , Al-Kali Aref , Hogan William , Litzow Mark , Pardanani Animesh , Tefferi Ayalew 
Published: January 2023

AbstractBetween October 2007 and July 2013, 183 Mayo Clinic patients (median age 65 years; 58% males) with high/intermediate risk myelofibrosis (MF) were enrolled in consecutive phase 1/2 JAK2 inhibitor (JAKi) clinical trials with momelotinib (n = 79), ruxolitinib (n = 50), fedratinib (n = 23) and BMS-911543 (n = 31). Using conventional criteria, the respective response rates for spleen and “transfusion-dependent anemia” were 47%, 32%, 83%, 62% and 51%, 30%, 10%, 44%, respectively, favoring momelotinib for anemia response (p = 0.02) and fedratinib for spleen response (p < 0.01). All study patients were followed to death or 2022, during which time 177 (97%) drug discontinuations, 27 (15%) leukemic transformations, and 22 (12%) allogeneic stem cell transplants (ASCT) were recorded. 5/10-year survival rate for all 183 patients was 41%/16% and not significantly different across the four drug cohorts (p = 0.33). Multivariable analysis of pre-treatment variables identified age >65 years (HR 3.5), absence of type 1/like CALR mutation (HR 2.8), baseline transfusion need (HR 2.1), and presence of ASXL1/SRSF2 mutation (HR 1.6) as risk factors for overall survival; subsequent HR-based modeling segregated three risk categories with 5/10-year survival rates of 84%/60%, 44%/14%, and 21%/5% (p < 0.01). In addition, spleen (p < 0.01) and anemia (p = 0.01) responses were independently associated with improved short-term survival while long-term survival was secured only by ASCT (5/10-year survival rate 91%/45% vs 47%/19% in non-transplanted patients; p < 0.01). The current retrospective study suggests the value of specific pre-treatment variables in identifying long-lived MF patients receiving JAKi and also confirms recent observations on the favorable impact of treatment response on short-term and of ASCT on long-term survival.
Intermediate water circulation drives distribution of Pliocene Oxygen Minimum Zones
Authors: Davis Catherine V. , Sibert Elizabeth C. , Jacobs Peter H. , Burls Natalie , Hull Pincelli M. 
Published: January 2023

AbstractOxygen minimum zones (OMZs) play a critical role in global biogeochemical cycling and act as barriers to dispersal for marine organisms. OMZs are currently expanding and intensifying with climate change, however past distributions of OMZs are relatively unknown. Here we present evidence for widespread pelagic OMZs during the Pliocene (5.3-2.6 Ma), the most recent epoch with atmospheric CO2 analogous to modern (~400-450 ppm). The global distribution of OMZ-affiliated planktic foraminifer, Globorotaloides hexagonus, and Earth System and Species Distribution Models show that the Indian Ocean, Eastern Equatorial Pacific, eastern South Pacific, and eastern North Atlantic all supported OMZs in the Pliocene, as today. By contrast, low-oxygen waters were reduced in the North Pacific and expanded in the North Atlantic in the Pliocene. This spatially explicit perspective reveals that a warmer world can support both regionally expanded and contracted OMZs, with intermediate water circulation as a key driver.
A Bayesian model for unsupervised detection of RNA splicing based subtypes in cancers
Authors: Wang David , Quesnel-Vallieres Mathieu , Jewell San , Elzubeir Moein , Lynch Kristen , Thomas-Tikhonenko Andrei , Barash Yoseph 
Published: January 2023

AbstractIdentification of cancer sub-types is a pivotal step for developing personalized treatment. Specifically, sub-typing based on changes in RNA splicing has been motivated by several recent studies. We thus develop CHESSBOARD, an unsupervised algorithm tailored for RNA splicing data that captures “tiles” in the data, defined by a subset of unique splicing changes in a subset of patients. CHESSBOARD allows for a flexible number of tiles, accounts for uncertainty of splicing quantification, and is able to model missing values as additional signals. We first apply CHESSBOARD to synthetic data to assess its domain specific modeling advantages, followed by analysis of several leukemia datasets. We show detected tiles are reproducible in independent studies, investigate their possible regulatory drivers and probe their relation to known AML mutations. Finally, we demonstrate the potential clinical utility of CHESSBOARD by supplementing mutation based diagnostic assays with discovered splicing profiles to improve drug response correlation.
Insights into the GSDMB-mediated cellular lysis and its targeting by IpaH7.8
Authors: Yin Hang , Zheng Jian , He Qiuqiu , Zhang Xuan , Li Xuzichao , Ma Yongjian , Liang Xiao , Gao Jiaqi , Kocsis Benjamin L. , Li Zhuang , Liu Xiang , Alto Neal M. , Li Long , Zhang Heng 
Published: January 2023

AbstractThe multifunctional GSDMB protein is an important molecule in human immunity. The pyroptotic and bactericidal activity of GSDMB is a host response to infection by the bacterial pathogen Shigella flexneri, which employs the virulence effector IpaH7.8 to ubiquitinate and target GSDMB for proteasome-dependent degradation. Furthermore, IpaH7.8 selectively targets human but not mouse GSDMD, suggesting a non-canonical mechanism of substrate selection. Here, we report the crystal structure of GSDMB in complex with IpaH7.8. Together with biochemical and functional studies, we identify the potential membrane engagement sites of GSDMB, revealing general and unique features of gasdermin proteins in membrane recognition. We further illuminate how IpaH7.8 interacts with GSDMB, and delineate the mechanism by which IpaH7.8 ubiquitinates and suppresses GSDMB. Notably, guided by our structural model, we demonstrate that two residues in the α1-α2 loop make the mouse GSDMD invulnerable to IpaH7.8-mediated degradation. These findings provide insights into the versatile functions of GSDMB, which could open new avenues for therapeutic interventions for diseases, including cancers and bacterial infections.
High-strength and machinable load-bearing integrated electrochemical capacitors based on polymeric solid electrolyte
Authors: Zhang Jinmeng , Yan Jianlong , Zhao Yanan , Zhou Qiang , Ma Yinxing , Zi Yaxian , Zhou Anan , Lin Shumin , Liao Longhui , Hu Xiaolan , Bai Hua 
Published: January 2023

AbstractLoad bearing/energy storage integrated devices (LEIDs) allow using structural parts to store energy, and thus become a promising solution to boost the overall energy density of mobile energy storage systems, such as electric cars and drones. Herein, with a new high-strength solid electrolyte, we prepare a practical high-performance load-bearing/energy storage integrated electrochemical capacitors with excellent mechanical strength (flexural modulus: 18.1 GPa, flexural strength: 160.0 MPa) and high energy storage ability (specific capacitance: 32.4 mF cm−2, energy density: 0.13 Wh m−2, maximum power density: 1.3 W m−2). We design and compare two basic types of multilayered structures for LEID, which significantly enhance the practical bearing ability and working flexibility of the device. Besides, we also demonstrate the excellent processability of the LEID, by forming them into curved shapes, and secondarily machining and assembling them into complex structures without affecting their energy storage ability.
Antagonizing cholecystokinin A receptor in the lung attenuates obesity-induced airway hyperresponsiveness
Authors: Panganiban Ronald Allan M. , Yang Zhiping , Sun Maoyun , Park Chan Young , Kasahara David I. , Schaible Niccole , Krishnan Ramaswamy , Kho Alvin T. , Israel Elliot , Hershenson Marc B. , Weiss Scott T. , Himes Blanca E. , Fredberg Jeffrey J. , Tantisira Kelan G. , Shore Stephanie A. , Lu Quan 
Published: January 2023

AbstractObesity increases asthma prevalence and severity. However, the underlying mechanisms are poorly understood, and consequently, therapeutic options for asthma patients with obesity remain limited. Here we report that cholecystokinin—a metabolic hormone best known for its role in signaling satiation and fat metabolism—is increased in the lungs of obese mice and that pharmacological blockade of cholecystokinin A receptor signaling reduces obesity-associated airway hyperresponsiveness. Activation of cholecystokinin A receptor by the hormone induces contraction of airway smooth muscle cells. In vivo, cholecystokinin level is elevated in the lungs of both genetically and diet-induced obese mice. Importantly, intranasal administration of cholecystokinin A receptor antagonists (proglumide and devazepide) suppresses the airway hyperresponsiveness in the obese mice. Together, our results reveal an unexpected role for cholecystokinin in the lung and support the repurposing of cholecystokinin A receptor antagonists as a potential therapy for asthma patients with obesity.
B cell analyses after SARS-CoV-2 mRNA third vaccination reveals a hybrid immunity like antibody response
Authors: Andreano Emanuele , Paciello Ida , Pierleoni Giulio , Piccini Giulia , Abbiento Valentina , Antonelli Giada , Pileri Piero , Manganaro Noemi , Pantano Elisa , Maccari Giuseppe , Marchese Silvia , Donnici Lorena , Benincasa Linda , Giglioli Ginevra , Leonardi Margherita , De Santi Concetta , Fabbiani Massimiliano , Rancan Ilaria , Tumbarello Mario , Montagnani Francesca , Sala Claudia , Medini Duccio , De Francesco Raffaele , Montomoli Emanuele , Rappuoli Rino 
Published: January 2023

AbstractThe continuous evolution of SARS-CoV-2 generated highly mutated variants able to escape natural and vaccine-induced primary immunity. The administration of a third mRNA vaccine dose induces a secondary response with increased protection. Here we investigate the longitudinal evolution of the neutralizing antibody response in four donors after three mRNA doses at single-cell level. We sorted 4100 spike protein specific memory B cells identifying 350 neutralizing antibodies. The third dose increases the antibody neutralization potency and breadth against all SARS-CoV-2 variants as observed with hybrid immunity. However, the B cell repertoire generating this response is different. The increases of neutralizing antibody responses is largely due to the expansion of B cell germlines poorly represented after two doses, and the reduction of germlines predominant after primary immunization. Our data show that different immunization regimens induce specific molecular signatures which should be considered while designing new vaccines and immunization strategies.
A super-efficient polyquaternium gel that can remove over-10-times masses of lignins from wastewater for resourcefulness
Authors: Hu Menghan , Xie Na , Gao Shan , Huang Yujia , Yu Yikai 
Published: January 2023

AbstractTo address the efficient resourcefulness of papermaking wastewater, this study designed a super-efficient gel material (SGPQG/SGPQ) that could remove over-10-times masses of lignins from wastewater, and subsequently realized the highly-efficient reuse of wastes. The mass of lignin removed by per unit mass of SGPQG/SGPQ was 10,157.71 mg•g-1, i.e., the mass of lignin removed was 10.16 times that of the mass of SGPQG/SGPQ itself, which was 1.23-50.55 times better than the existing similar materials, showing a super-efficient lignin removal ability. Meanwhile, the average lignin removal rate of SGPQG/SGPQ was 1.85-3.34 times higher than those of the pre-products. Moreover, the extended application of SGPQG/SGPQ in the purification of a complex wastewater and a real papermaking wastewater had been also successfully carried out. The mechanism investigations confirmed an integrated skeleton-space effect mechanism, which is the key factor for SGPQG/SGPQ to achieve the super-efficient lignin removal in the purification of papermaking wastewater. In addition, the SGPQG/SGPQ wastes after treating lignins, could be directly used for adsorption treatment of dyeing wastewater, and had 443.9 times adsorption capacity compared to the widely-used activated carbon, demonstrating an efficient resourcefulness reuse.
Cas12a2 elicits abortive infection through RNA-triggered destruction of dsDNA
Authors: Dmytrenko Oleg , Neumann Gina C. , Hallmark Thomson , Keiser Dylan J. , Crowley Valerie M. , Vialetto Elena , Mougiakos Ioannis , Wandera Katharina G. , Domgaard Hannah , Weber Johannes , Gaudin Thomas , Metcalf Josie , Gray Benjamin N. , Begemann Matthew B. , Jackson Ryan N. , Beisel Chase L. 
Published: January 2023

AbstractBacterial abortive-infection systems limit the spread of foreign invaders by shutting down or killing infected cells before the invaders can replicate1,2. Several RNA-targeting CRISPR–Cas systems (that is, types III and VI) cause abortive-infection phenotypes by activating indiscriminate nucleases3–5. However, a CRISPR-mediated abortive mechanism that leverages indiscriminate DNase activity of an RNA-guided single-effector nuclease has yet to be observed. Here we report that RNA targeting by the type V single-effector nuclease Cas12a2 drives abortive infection through non-specific cleavage of double-stranded DNA (dsDNA). After recognizing an RNA target with an activating protospacer-flanking sequence, Cas12a2 efficiently degrades single-stranded RNA (ssRNA), single-stranded DNA (ssDNA) and dsDNA. Within cells, the activation of Cas12a2 induces an SOS DNA-damage response and impairs growth, preventing the dissemination of the invader. Finally, we harnessed the collateral activity of Cas12a2 for direct RNA detection, demonstrating that Cas12a2 can be repurposed as an RNA-guided RNA-targeting tool. These findings expand the known defensive abilities of CRISPR–Cas systems and create additional opportunities for CRISPR technologies.
Impact of plasmapheresis on severe COVID-19
Authors: Fonseca-González G. , Alamilla-Sánchez M. , García-Macas V. , Herrera-Acevedo J. , Villalobos-Brito M. , Tapia-Rangel E. , Maldonado-Tapia D. , López-Mendoza M. , Cano-Cervantes J. H. , Orozco-Vázquez J. , Timarán-Montenegro D. , Cortés-Martínez S. , Escarela-Serrano M. , Muñoz-López S. , Montiel-López L. , Mondragón-Terán P. , Suárez-Cuenca J. A. 
Published: January 2023

AbstractThe clinical course of COVID-19 may show severe presentation, potentially involving dynamic cytokine storms and T cell lymphopenia, which are leading causes of death in patients with SARS-CoV-2 infection. Plasma exchange therapy (PLEX) effectively removes pro-inflammatory factors, modulating and restoring innate and adaptive immune responses. This clinical trial aimed to evaluate the impact of PLEX on the survival of patients with severe SARS-CoV-2 and the effect on the cytokine release syndrome. Hospitalized patients diagnosed with SARS-CoV-2 infection and cytokine storm syndrome were selected to receive 2 sessions of PLEX or standard therapy. Primary outcome was all-cause 60-days mortality; secondary outcome was requirement of mechanical ventilation, SOFA, NEWs-2 scores modification, reduction of pro-inflammatory biomarkers and hospitalization time. Twenty patients received PLEX were compared against 40 patients receiving standard therapy. PLEX reduced 60-days mortality (50% vs 20%; OR 0.25, 95%CI 0.071–0.880; p = 0.029), and this effect was independent from demographic variables and drug therapies used. PLEX significantly decreased SOFA, NEWs-2, pro-inflammatory mediators and increased lymphocyte count, accompanied with a trend to reduce affected lung volume, without effect on SatO2/FiO2 indicator or mechanical ventilation requirement. PLEX therapy provided significant benefits of pro-inflammatory clearance and reduction of 60-days mortality in selected patients with COVID-19, without significant adverse events.
The prevalence, presentation and outcome of colistin susceptible-only Acinetobacter Baumannii-associated pneumonia in intensive care unit: a multicenter observational study
Authors: Wang Sheng-Huei , Yang Kuang-Yao , Sheu Chau-Chyun , Lin Yu-Chao , Chan Ming-Cheng , Feng Jia-Yih , Chen Chia-Min , Chen Chih-Yu , Zheng Zhe-Rong , Chou Yu-Ching , Peng Chung-Kan 
Published: January 2023

AbstractHospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are both associated with significant morbidity and mortality in daily clinical practice, as well as in a critical care setting. It is unclear whether colistin susceptible-only Acinetobacter baumannii (CSO AB) is a unique phenotype separate from or a subset of CRAB-associated pneumonia. The aim of this study is to investigate the prevalence of CSO AB pneumonia and compare the presentation and outcome between CSO AB and CRAB-associated pneumonia in critically ill patients. This multicenter retrospective cohort study initially recruited 955 patients with CR-GNB pneumonia. After exclusion, 575 patients left who were ICU-admitted and had CRAB nosocomial pneumonia remained. Among them, 79 patients had CSO AB pneumonia, classified as the CSO AB group. The other 496 patients were classified as the CRAB group. We compared demographic characteristics, disease severity, and treatment outcomes between the two groups. The prevalence of CSO AB among all cases of CRAB pneumonia was 13.74% (79/575). The CSO AB and CRAB groups had similar demographic characteristics and disease severities at initial presentation. The in-hospital mortality rate was 45.6% and 46.4% for CSO AB and CRAB groups, respectively (p = 0.991). The CSO AB group had significantly better clinical outcomes at day 7 (65.8% vs 52.4%, p = 0.036) but longer length of ICU stay (27 days vs 19 days, p = 0.043) compared to the CRAB group. However, other treatment outcomes, including clinical outcomes at day 14 and 28, mortality, microbiological eradication, ventilator weaning, and newly onset dialysis, were similar. In conclusion, CSO AB accounted for 13.74% of all cases of CRAB pneumonia, and the clinical presentation and treatment outcomes of CSO AB and CRAB pneumonia were similar.