bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tree Canopies Reflect Mycorrhizal Composition
Authors: Sousa Daniel , Fisher Joshua B. , Galvan Fernando Romero , Pavlick Ryan P. , Cordell Susan , Giambelluca Thomas W. , Giardina Christian P. , Gilbert Gregory S. , Imran‐Narahari Faith , Litton Creighton M. , Lutz James A. , North Malcolm P. , Orwig David A. , Ostertag Rebecca , Sack Lawren , Phillips Richard P. 
Published: May 2021

AbstractMycorrhizae alter global patterns of CO2 fertilization, carbon storage, and elemental cycling, yet knowledge of their global distributions is currently limited by the availability of forest inventory data. Here, we show that maps of tree‐mycorrhizal associations (hereafter “mycorrhizal maps”) can be improved by the novel technology of imaging spectroscopy because mycorrhizal signatures propagate up from plant roots to impact forest canopy chemistry. We analyzed measurements from 143 airborne imaging spectroscopy surveys over 112,975 individual trees collected across 13 years. Results show remarkable accuracy in capturing ground truth observations of mycorrhizal associations from canopy signals across disparate landscapes (R2 = 0.92, p < 0.01). Upcoming imaging spectroscopy satellite missions can reveal new insights into landscape‐scale variations in water, nitrogen, phosphorus, carotenoid/anthocyanin, and cellulose/lignin composition. Applied globally, this approach could improve the spatial precision of mycorrhizal distributions by a factor of roughly 104 and facilitate the incorporation of dynamic shifts in forest composition into Earth system models.
Investigation of Spontaneous Imbibition Behavior in a 3D Pore Space Under Reservoir Condition by Lattice Boltzmann Method
Authors: Zheng Jiangtao , Lei Wenhai , Ju Yang , Wang Moran 
Published: May 2021

AbstractSpontaneous imbibition (SI) of the injected fluid into the pore space of a tight oil reservoir and replacing the crude oil therein has been considered as one of the possible mechanisms in increasing oil recovery. Such deeply buried reservoir rocks is usually under high‐pressure and high‐temperature conditions. Besides, their interior porous structures are usually characterized as irregular pore bodies and slit‐shaped pore throats. As a result, an accurate description of the SI behavior driven by capillary force in the real pore space under reservoir conditions is crucial to understand the process and uncover the controlling mechanisms. An improved multi‐component pseudo‐potential lattice Boltzmann method was developed to simulate the SI behavior in a representative 3D pore space extracted from a tight sandstone reservoir rock. Comparison of the SI behavior under ambient condition and reservoir condition showed that the latter case exhibited two times faster of the imbibition. Moreover, a snap‐off of the oil droplet phenomenon was observed in the pore bodies surrounded by slit‐shaped pore throats. The snap‐off oil droplets stuck in pore bodies accounted for 9.47% of the pore volume. These results indicated the importance of investigating the SI in a real porous structure and under actual reservoir condition. The proposed pore‐scale simulation method provides a useful tool in understanding the complex SI pattern and the resulted enhanced oil recovery.
Efficacy and safety of a novel dosing strategy for ruxolitinib in the treatment of patients with myelofibrosis and anemia: the REALISE phase 2 study
Authors: Cervantes Francisco , Ross David M. , Radinoff Atanas , Palandri Francesca , Myasnikov Alexandr , Vannucchi Alessandro M. , Zachee Pierre , Gisslinger Heinz , Komatsu Norio , Foltz Lynda , Mannelli Francesco , Passamonti Francesco , Gilotti Geralyn , Sadek Islam , Tiwari Ranjan , Zor Evren , Al-Ali Haifa Kathrin 
Published: May 2021

AbstractAnemia is a frequent manifestation of myelofibrosis (MF) and there is an unmet need for effective treatments in anemic MF patients. The REALISE phase 2 study (NCT02966353) evaluated the efficacy and safety of a novel ruxolitinib dosing strategy with a reduced starting dose with delayed up-titration in anemic MF patients. Fifty-one patients with primary MF (66.7%), post-essential thrombocythemia MF (21.6%), or post-polycythemia vera MF (11.8%) with palpable splenomegaly and hemoglobin <10 g/dl were included. Median age was 67 (45–88) years, 41.2% were female, and 18% were transfusion-dependent. Patients received 10 mg ruxolitinib b.i.d. for the first 12 weeks, then up-titrations of up to 25 mg b.i.d. were permitted, based on efficacy and platelet counts. Overall, 70% of patients achieved a ≥50% reduction in palpable spleen length at any time during the study. The most frequent adverse events leading to dose interruption/adjustment were thrombocytopenia (17.6%) and anemia (11.8%). Patients who had a dose increase had greater spleen size and higher white blood cell counts at baseline. Median hemoglobin levels remained stable and transfusion requirements did not increase compared with baseline. These results reinforce the notion that it is unnecessary to delay or withhold ruxolitinib because of co-existent or treatment-emergent anemia.
Development of single-cell-level microfluidic technology for long-term growth visualization of living cultures of Mycobacterium smegmatis
Authors: Wang Han , Conover Gloria M. , Han Song-I , Sacchettini James C. , Han Arum 
Published: May 2021

AbstractAnalysis of growth and death kinetics at single-cell resolution is a key step in understanding the complexity of the nonreplicating growth phenotype of the bacterial pathogen Mycobacterium tuberculosis. Here, we developed a single-cell-resolution microfluidic mycobacterial culture device that allows time-lapse microscopy-based long-term phenotypic visualization of the live replication dynamics of mycobacteria. This technology was successfully applied to monitor the real-time growth dynamics of the fast-growing model strain Mycobacterium smegmatis (M. smegmatis) while subjected to drug treatment regimens during continuous culture for 48 h inside the microfluidic device. A clear morphological change leading to significant swelling at the poles of the bacterial membrane was observed during drug treatment. In addition, a small subpopulation of cells surviving treatment by frontline antibiotics was observed to recover and achieve robust replicative growth once regular culture media was provided, suggesting the possibility of identifying and isolating nonreplicative mycobacteria. This device is a simple, easy-to-use, and low-cost solution for studying the single-cell phenotype and growth dynamics of mycobacteria, especially during drug treatment.
High expression of PSMC2 promotes gallbladder cancer through regulation of GNG4 and predicts poor prognosis
Authors: Zhu Dawei , Gu Xing , Lin Zhengyu , Yu Dandan , Wang Jing 
Published: May 2021

AbstractGallbladder cancer (GBC) is a common malignant tumor of the biliary tract, which accounts for 80–95% of biliary tumors worldwide, and is the leading cause of biliary malignant tumor-related death. This study identified PSMC2 as a potential regulator in the development of GBC. We showed that PSMC2 expression in GBC tissues is significantly higher than that in normal tissues, while high PSMC2 expression was correlated with more advanced tumor grade and poorer prognosis. The knockdown of PSMC2 in GBC cells induced significant inhibition of cell proliferation, colony formation and cell motility, while the promotion of cell apoptosis. The construction and observation of the mice xenograft model also confirmed the inhibitory effects of PSMC2 knockdown on GBC development. Moreover, our mechanistic study recognized GNG4 as a potential downstream target of PSMC2, knockdown of which could aggravate the tumor suppression induced by PSMC2 knockdown in vitro and in vivo. In conclusion, for the first time, PSMC2 was revealed as a tumor promotor in the development of GBC, which could regulate cell phenotypes of GBC cells through the interaction with GNG4, and maybe a promising therapeutic target in GBC treatment.
Probiotics-induced changes in gut microbial composition and its effects on cognitive performance after stress: exploratory analyses
Authors: Bloemendaal Mirjam , Szopinska-Tokov Joanna , Belzer Clara , Boverhoff David , Papalini Silvia , Michels Franziska , van Hemert Saskia , Arias Vasquez Alejandro , Aarts Esther 
Published: May 2021

AbstractStress negatively affects cognitive performance. Probiotics remediate somatic and behavioral stress responses, hypothetically by acting on the gut microbiota. Here, in exploratory analyses, we assessed gut microbial alterations after 28-days supplementation of multi-strain probiotics (EcologicBarrier consisting of Lactobacilli, Lactococci, and Bifidobacteria in healthy, female subjects (probiotics group n = 27, placebo group n = 29). In an identical pre-session and post-session, subjects performed a working memory task before and after an acute stress intervention. Global gut microbial beta diversity changed over time, but we were not able to detect differences between intervention groups. At the taxonomic level, Time by Intervention interactions were not significant after multiple comparison correction; the relative abundance of eight genera in the probiotics group was higher (uncorrected) relative to the placebo group: Butyricimonas, Parabacteroides, Alistipes, Christensenellaceae_R-7_group, Family_XIII_AD3011_group, Ruminococcaceae_UCG-003, Ruminococcaceae_UCG-005, and Ruminococcaceae_UCG-010. In a second analysis step, association analyses were done only within this selection of microbial genera, revealing the probiotics-induced change in genus Ruminococcaceae_UCG-003 was significantly associated with probiotics’ effect on stress-induced working memory changes (rspearman(27) = 0.565; pFDR = 0.014) in the probiotics group only and independent of potential confounders (i.e., age, BMI, and baseline dietary fiber intake). That is subjects with a higher increase in Ruminococcaceae_UCG-003 abundance after probiotics were also more protected from negative effects of stress on working memory after probiotic supplementation. The bacterial taxa showing an increase in relative abundance in the probiotics group are plant fiber degrading bacteria and produce short-chain fatty acids that are known for their beneficial effect on gut and brain health, e.g., maintaining intestinal-barrier and blood–brain-barrier integrity. This study shows that gut microbial alterations, modulated through probiotics use, are related to improved cognitive performance in acute stress circumstances.
Transcriptomics identifies STAT3 as a key regulator of hippocampal gene expression and anhedonia during withdrawal from chronic alcohol exposure
Authors: Chen Wei-Yang , Chen Hu , Hamada Kana , Gatta Eleonora , Chen Ying , Zhang Huaibo , Drnevich Jenny , Krishnan Harish R. , Maienschein-Cline Mark , Grayson Dennis R. , Pandey Subhash C. , Lasek Amy W. 
Published: May 2021

AbstractAlcohol use disorder (AUD) is highly comorbid with depression. Withdrawal from chronic alcohol drinking results in depression and understanding brain molecular mechanisms that drive withdrawal-related depression is important for finding new drug targets to treat these comorbid conditions. Here, we performed RNA sequencing of the rat hippocampus during withdrawal from chronic alcohol drinking to discover key signaling pathways involved in alcohol withdrawal-related depressive-like behavior. Data were analyzed by weighted gene co-expression network analysis to identify several modules of co-expressed genes that could have a common underlying regulatory mechanism. One of the hub, or highly interconnected, genes in module 1 that increased during alcohol withdrawal was the transcription factor, signal transducer and activator of transcription 3 (Stat3), a known regulator of immune gene expression. Total and phosphorylated (p)STAT3 protein levels were also increased in the hippocampus during withdrawal after chronic alcohol exposure. Further, pSTAT3 binding was enriched at the module 1 genes Gfap, Tnfrsf1a, and Socs3 during alcohol withdrawal. Notably, pSTAT3 and its target genes were elevated in the postmortem hippocampus of human subjects with AUD when compared with control subjects. To determine the behavioral relevance of STAT3 activation during alcohol withdrawal, we treated rats with the STAT3 inhibitor stattic and tested for sucrose preference as a measure of anhedonia. STAT3 inhibition alleviated alcohol withdrawal-induced anhedonia. These results demonstrate activation of STAT3 signaling in the hippocampus during alcohol withdrawal in rats and in human AUD subjects, and suggest that STAT3 could be a therapeutic target for reducing comorbid AUD and depression.
Superior efficacy of co-targeting GFI1/KDM1A and BRD4 against AML and post-MPN secondary AML cells
Authors: Fiskus Warren , Mill Christopher P. , Nabet Behnam , Perera Dimuthu , Birdwell Christine , Manshouri Taghi , Lara Bernardo , Kadia Tapan M. , DiNardo Courtney , Takahashi Koichi , Daver Naval , Bose Prithviraj , Masarova Lucia , Pemmaraju Naveen , Kornblau Steven , Borthakur Gautam , Montalban-Bravo Guillermo , Manero Guillermo Garcia , Sharma Sunil , Stubbs Matthew , Su Xiaoping , Green Michael R. , Coarfa Cristian , Verstovsek Srdan , Khoury Joseph D. , Vakoc Christopher R. , Bhalla Kapil N. 
Published: May 2021

AbstractThere is an unmet need to overcome nongenetic therapy-resistance to improve outcomes in AML, especially post-myeloproliferative neoplasm (MPN) secondary (s) AML. Studies presented describe effects of genetic knockout, degradation or small molecule targeted-inhibition of GFI1/LSD1 on active enhancers, altering gene-expressions and inducing differentiation and lethality in AML and (MPN) sAML cells. A protein domain-focused CRISPR screen in LSD1 (KDM1A) inhibitor (i) treated AML cells, identified BRD4, MOZ, HDAC3 and DOT1L among the codependencies. Our findings demonstrate that co-targeting LSD1 and one of these co-dependencies exerted synergistic in vitro lethality in AML and post-MPN sAML cells. Co-treatment with LSD1i and the JAKi ruxolitinib was also synergistically lethal against post-MPN sAML cells. LSD1i pre-treatment induced GFI1, PU.1 and CEBPα but depleted c-Myc, overcoming nongenetic resistance to ruxolitinib, or to BETi in post-MPN sAML cells. Co-treatment with LSD1i and BETi or ruxolitinib exerted superior in vivo efficacy against post-MPN sAML cells. These findings highlight LSD1i-based combinations that merit testing for clinical efficacy, especially to overcome nongenetic therapy-resistance in AML and post-MPN sAML.
Endocrine role of bone in the regulation of energy metabolism
Authors: Zhou Ruoyu , Guo Qiaoyue , Xiao Ye , Guo Qi , Huang Yan , Li Changjun , Luo Xianghang 
Published: May 2021

AbstractsBone mainly functions as a supportive framework for the whole body and is the major regulator of calcium homeostasis and hematopoietic function. Recently, an increasing number of studies have characterized the significance of bone as an endocrine organ, suggesting that bone-derived factors regulate local bone metabolism and metabolic functions. In addition, these factors can regulate global energy homeostasis by altering insulin sensitivity, feeding behavior, and adipocyte commitment. These findings may provide a new pathological mechanism for related metabolic diseases or be used in the diagnosis, treatment, and prevention of metabolic diseases such as osteoporosis, obesity, and diabetes mellitus. In this review, we summarize the regulatory effect of bone and bone-derived factors on energy metabolism and discuss directions for future research.
TSP50 promotes the Warburg effect and hepatocyte proliferation via regulating PKM2 acetylation
Authors: Gao Feng , Zhang Xiaojun , Wang Shuyue , Zheng Lihua , Sun Ying , Wang Guannan , Song Zhenbo , Bao Yongli 
Published: May 2021

AbstractMetabolic reprogramming is a hallmark of malignancy. Testes-specific protease 50 (TSP50), a newly identified oncogene, has been shown to play an important role in tumorigenesis. However, its role in tumor cell metabolism remains unclear. To investigate this issue, LC–MS/MS was employed to identify TSP50-binding proteins and pyruvate kinase M2 isoform (PKM2), a known key enzyme of aerobic glycolysis, was identified as a novel binding partner of TSP50. Further studies suggested that TSP50 promoted aerobic glycolysis in HCC cells by maintaining low pyruvate kinase activity of the PKM2. Mechanistically, TSP50 promoted the Warburg effect by increasing PKM2 K433 acetylation level and PKM2 acetylation site (K433R) mutation remarkably abrogated the TSP50-induced aerobic glycolysis, cell proliferation in vitro and tumor formation in vivo. Our findings indicate that TSP50-mediated low PKM2 pyruvate kinase activity is an important determinant for Warburg effect in HCC cells and provide a mechanistic link between TSP50 and tumor metabolism.
Epidermal chloroplasts are defense-related motile organelles equipped with plant immune components
Authors: Irieda Hiroki , Takano Yoshitaka 
Published: May 2021

AbstractIn addition to conspicuous large mesophyll chloroplasts, where most photosynthesis occurs, small epidermal chloroplasts have also been observed in plant leaves. However, the functional significance of this small organelle remains unclear. Here, we present evidence that Arabidopsis epidermal chloroplasts control the entry of fungal pathogens. In entry trials, specialized fungal cells called appressoria triggered dynamic movement of epidermal chloroplasts. This movement is controlled by common regulators of mesophyll chloroplast photorelocation movement, designated as the epidermal chloroplast response (ECR). The ECR occurs when the PEN2 myrosinase-related higher-layer antifungal system becomes ineffective, and blockage of the distinct steps of the ECR commonly decreases preinvasive nonhost resistance against fungi. Furthermore, immune components were preferentially localized to epidermal chloroplasts, contributing to antifungal nonhost resistance in the pen2 background. Our findings reveal that atypical small chloroplasts act as defense-related motile organelles by specifically positioning immune components in the plant epidermis, which is the first site of contact between the plant and pathogens. Thus, this work deepens our understanding of the functions of epidermal chloroplasts.
Continent-wide genomic signatures of adaptation to urbanisation in a songbird across Europe
Authors: Salmón Pablo , Jacobs Arne , Ahrén Dag , Biard Clotilde , Dingemanse Niels J. , Dominoni Davide M. , Helm Barbara , Lundberg Max , Senar Juan Carlos , Sprau Philipp , Visser Marcel E. , Isaksson Caroline 
Published: May 2021

AbstractUrbanisation is increasing worldwide, and there is now ample evidence of phenotypic changes in wild organisms in response to this novel environment. Yet, the genetic changes and genomic architecture underlying these adaptations are poorly understood. Here, we genotype 192 great tits (Parus major) from nine European cities, each paired with an adjacent rural site, to address this major knowledge gap in our understanding of wildlife urban adaptation. We find that a combination of polygenic allele frequency shifts and recurrent selective sweeps are associated with the adaptation of great tits to urban environments. While haplotypes under selection are rarely shared across urban populations, selective sweeps occur within the same genes, mostly linked to neural function and development. Collectively, we show that urban adaptation in a widespread songbird occurs through unique and shared selective sweeps in a core-set of behaviour-linked genes.
Structural basis for allosteric regulation of Human Topoisomerase IIα
Authors: Vanden Broeck Arnaud , Lotz Christophe , Drillien Robert , Haas Léa , Bedez Claire , Lamour Valérie 
Published: May 2021

AbstractThe human type IIA topoisomerases (Top2) are essential enzymes that regulate DNA topology and chromosome organization. The Topo IIα isoform is a prime target for antineoplastic compounds used in cancer therapy that form ternary cleavage complexes with the DNA. Despite extensive studies, structural information on this large dimeric assembly is limited to the catalytic domains, hindering the exploration of allosteric mechanism governing the enzyme activities and the contribution of its non-conserved C-terminal domain (CTD). Herein we present cryo-EM structures of the entire human Topo IIα nucleoprotein complex in different conformations solved at subnanometer resolutions (3.6–7.4 Å). Our data unveils the molecular determinants that fine tune the allosteric connections between the ATPase domain and the DNA binding/cleavage domain. Strikingly, the reconstruction of the DNA-binding/cleavage domain uncovers a linker leading to the CTD, which plays a critical role in modulating the enzyme’s activities and opens perspective for the analysis of post-translational modifications.
40S ribosome profiling reveals distinct roles for Tma20/Tma22 (MCT-1/DENR) and Tma64 (eIF2D) in 40S subunit recycling
Authors: Young David J. , Meydan Sezen , Guydosh Nicholas R. 
Published: May 2021

AbstractThe recycling of ribosomes at stop codons for use in further rounds of translation is critical for efficient protein synthesis. Removal of the 60S subunit is catalyzed by the ATPase Rli1 (ABCE1) while removal of the 40S is thought to require Tma64 (eIF2D), Tma20 (MCT-1), and Tma22 (DENR). However, it remains unclear how these Tma proteins cause 40S removal and control reinitiation of downstream translation. Here we used a 40S ribosome footprinting strategy to directly observe intermediate steps of ribosome recycling in cells. Deletion of the genes encoding these Tma proteins resulted in broad accumulation of unrecycled 40S subunits at stop codons, directly establishing their role in 40S recycling. Furthermore, the Tma20/Tma22 heterodimer was responsible for a majority of 40S recycling events while Tma64 played a minor role. Introduction of an autism-associated mutation into TMA22 resulted in a loss of 40S recycling activity, linking ribosome recycling and neurological disease.
Multiscale influenza forecasting
Authors: Osthus Dave , Moran Kelly R. 
Published: May 2021

AbstractInfluenza forecasting in the United States (US) is complex and challenging due to spatial and temporal variability, nested geographic scales of interest, and heterogeneous surveillance participation. Here we present Dante, a multiscale influenza forecasting model that learns rather than prescribes spatial, temporal, and surveillance data structure and generates coherent forecasts across state, regional, and national scales. We retrospectively compare Dante’s short-term and seasonal forecasts for previous flu seasons to the Dynamic Bayesian Model (DBM), a leading competitor. Dante outperformed DBM for nearly all spatial units, flu seasons, geographic scales, and forecasting targets. Dante’s sharper and more accurate forecasts also suggest greater public health utility. Dante placed 1st in the Centers for Disease Control and Prevention’s prospective 2018/19 FluSight challenge in both the national and regional competition and the state competition. The methodology underpinning Dante can be used in other seasonal disease forecasting contexts having nested geographic scales of interest.