bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of p53 in mesenchymal stem cells promotes alteration of bone remodeling through negative regulation of osteoprotegerin
Authors: Velletri Tania , Huang Yin , Wang Yu , Li Qing , Hu Mingyuan , Xie Ningxia , Yang Qian , Chen Xiaodong , Chen Qing , Shou Peishun , Gan Yurun , Candi Eleonora , Annicchiarico-Petruzzelli Margherita , Agostini Massimiliano , Yang Huilin , Melino Gerry , Shi Yufang , Wang Ying 
Published: July 2020

Abstractp53 plays a pivotal role in controlling the differentiation of mesenchymal stem cells (MSCs) by regulating genes involved in cell cycle and early steps of differentiation process. In the context of osteogenic differentiation of MSCs and bone homeostasis, the osteoprotegerin/receptor activator of NF-κB ligand/receptor activator of NF-κB (OPG/RANKL/RANK) axis is a critical signaling pathway. The absence or loss of function of p53 has been implicated in aberrant osteogenic differentiation of MSCs that results in higher bone formation versus erosion, leading to an unbalanced bone remodeling. Here, we show by microCT that mice with p53 deletion systemically or specifically in mesenchymal cells possess significantly higher bone density than their respective littermate controls. There is a negative correlation between p53 and OPG both in vivo by analysis of serum from p53+/+, p53+/−, and p53−/− mice and in vitro by p53 knockdown and ChIP assay in MSCs. Notably, high expression of Opg or its combination with low level of p53 are prominent features in clinical cancer lesion of osteosarcoma and prostate cancer respectively, which correlate with poor survival. Intra-bone marrow injection of prostate cancer cells, together with androgen can suppress p53 expression and enhance local Opg expression, leading to an enhancement of bone density. Our results support the notion that MSCs, as osteoblast progenitor cells and one major component of bone microenvironment, represent a cellular source of OPG, whose amount is regulated by the p53 status. It also highlights a key role for the p53-OPG axis in regulating the cancer associated bone remodeling.
Non-invasive early detection of cancer four years before conventional diagnosis using a blood test
Authors: Chen Xingdong , Gole Jeffrey , Gore Athurva , He Qiye , Lu Ming , Min Jun , Yuan Ziyu , Yang Xiaorong , Jiang Yanfeng , Zhang Tiejun , Suo Chen , Li Xiaojie , Cheng Lei , Zhang Zhenhua , Niu Hongyu , Li Zhe , Xie Zhen , Shi Han , Zhang Xiang , Fan Min , Wang Xiaofeng , Yang Yajun , Dang Justin , McConnell Catie , Zhang Juan , Wang Jiucun , Yu Shunzhang , Ye Weimin , Gao Yuan , Zhang Kun , Liu Rui , Jin Li 
Published: July 2020

AbstractEarly detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw. We also assay plasma samples from an additional 223 cancer patients, plus 200 primary tumor and normal tissues. We show that PanSeer detects five common types of cancer in 88% (95% CI: 80–93%) of post-diagnosis patients with a specificity of 96% (95% CI: 93–98%), We also demonstrate that PanSeer detects cancer in 95% (95% CI: 89–98%) of asymptomatic individuals who were later diagnosed, though future longitudinal studies are required to confirm this result. These results demonstrate that cancer can be non-invasively detected up to four years before current standard of care.
TRIB3-EGFR interaction promotes lung cancer progression and defines a therapeutic target
Authors: Yu Jiao-jiao , Zhou Dan-dan , Yang Xiao-xiao , Cui Bing , Tan Feng-wei , Wang Junjian , Li Ke , Shang Shuang , Zhang Cheng , Lv Xiao-xi , Zhang Xiao-wei , Liu Shan-shan , Yu Jin-mei , Wang Feng , Huang Bo , Hua Fang , Hu Zhuo-Wei 
Published: July 2020

AbstractHigh expression or aberrant activation of epidermal growth factor receptor (EGFR) is related to tumor progression and therapy resistance across cancer types, including non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (TKIs) are first-line therapy for NSCLC. However, patients eventually deteriorate after inevitable acquisition of EGFR TKI-resistant mutations, highlighting the need for therapeutics with alternative mechanisms of action. Here, we report that the elevated tribbles pseudokinase 3 (TRIB3) is positively associated with EGFR stability and NSCLC progression. TRIB3 interacts with EGFR and recruits PKCα to induce a Thr654 phosphorylation and WWP1-induced Lys689 ubiquitination in the EGFR juxtamembrane region, which enhances EGFR recycling, stability, downstream activity, and NSCLC stemness. Disturbing the TRIB3-EGFR interaction with a stapled peptide attenuates NSCLC progression by accelerating EGFR degradation and sensitizes NSCLC cells to chemotherapeutic agents. These findings indicate that targeting EGFR degradation is a previously unappreciated therapeutic option in EGFR-related NSCLC.
Mitochondrial respiration controls neoangiogenesis during wound healing and tumour growth
Authors: Schiffmann L. M. , Werthenbach J. P. , Heintges-Kleinhofer F. , Seeger J. M. , Fritsch M. , Günther S. D. , Willenborg S. , Brodesser S. , Lucas C. , Jüngst C. , Albert M. C. , Schorn F. , Witt A. , Moraes C. T. , Bruns C. J. , Pasparakis M. , Krönke M. , Eming S. A. , Coutelle O. , Kashkar H. 
Published: July 2020

AbstractThe vasculature represents a highly plastic compartment, capable of switching from a quiescent to an active proliferative state during angiogenesis. Metabolic reprogramming in endothelial cells (ECs) thereby is crucial to cover the increasing cellular energy demand under growth conditions. Here we assess the impact of mitochondrial bioenergetics on neovascularisation, by deleting cox10 gene encoding an assembly factor of cytochrome c oxidase (COX) specifically in mouse ECs, providing a model for vasculature-restricted respiratory deficiency. We show that EC-specific cox10 ablation results in deficient vascular development causing embryonic lethality. In adult mice induction of EC-specific cox10 gene deletion produces no overt phenotype. However, the angiogenic capacity of COX-deficient ECs is severely compromised under energetically demanding conditions, as revealed by significantly delayed wound-healing and impaired tumour growth. We provide genetic evidence for a requirement of mitochondrial respiration in vascular endothelial cells for neoangiogenesis during development, tissue repair and cancer.
Majority sensing in synthetic microbial consortia
Authors: Alnahhas Razan N. , Sadeghpour Mehdi , Chen Ye , Frey Alexis A. , Ott William , Josić Krešimir , Bennett Matthew R. 
Published: July 2020

AbstractAs synthetic biocircuits become more complex, distributing computations within multi-strain microbial consortia becomes increasingly beneficial. However, designing distributed circuits that respond predictably to variation in consortium composition remains a challenge. Here we develop a two-strain gene circuit that senses and responds to which strain is in the majority. This involves a co-repressive system in which each strain produces a signaling molecule that signals the other strain to down-regulate production of its own, orthogonal signaling molecule. This co-repressive consortium links gene expression to ratio of the strains rather than population size. Further, we control the cross-over point for majority via external induction. We elucidate the mechanisms driving these dynamics by developing a mathematical model that captures consortia response as strain fractions and external induction are varied. These results show that simple gene circuits can be used within multicellular synthetic systems to sense and respond to the state of the population.
Large positive magnetoresistance and Dzyaloshinskii–Moriya interaction in CrSi driven by Cr 3d localization
Authors: Banik Soma , Chattopadhyay M. K. , Tripathi Shilpa , Rawat R. , Jha S. N. 
Published: July 2020

AbstractSpin chiral systems with Dzyaloshinskii–Moriya (DM) interaction due to broken inversion symmetry are extensively studied for their technological applications in spintronics and thermoelectrics. Here, we report an experimental study on the magnetization, magnetoresistance (MR) and electronic structure of a non-centrosymmetric compound CrSi with B20 crystal structure. Both magnetization andMRshows competing ferromagnetic (FM) and antiferromagnetic (AFM) correlations with theFMcorrelations being comparatively weaker indicating the presence ofDMinteraction in CrSi. A large positiveMR$$\sim \,25\%$$∼25%obtained at 5 K and 5 T magnetic field arises due to the strongerAFMcorrelations. Resonant photoemission shows both localized and itinerant nature of Cr 3delectrons to be present in CrSi and this is supported by the temperature dependence of magnetic susceptibility. Drastic variation in the density of states along with valence band broadening at low temperature indicates the increase in hybridization between Cr 3dand Si 3s–3pstates which enhances the localization effects. Spin polarized itinerant Cr 3delectrons give rise toAFMspin density wave in CrSi. Magnetic interaction between the localized and itinerant Cr 3delectrons are found to be crucial for realizing DM interaction in this system. Spectral density of states derived from high resolution valence band measurements provides evidence of electronic topological transition in CrSi. Large density of polarized itinerant electrons which varies with temperature and the large positiveMRwithAFMcorrelations suggests CrSi as a potential candidate for both the thermoelectric and spintronics applications.
Rapid, precise, and reliable measurement of delay discounting using a Bayesian learning algorithm
Authors: Ahn Woo-Young , Gu Hairong , Shen Yitong , Haines Nathaniel , Hahn Hunter A. , Teater Julie E. , Myung Jay I. , Pitt Mark A. 
Published: July 2020

AbstractMachine learning has the potential to facilitate the development of computational methods that improve the measurement of cognitive and mental functioning. In three populations (college students, patients with a substance use disorder, and Amazon Mechanical Turk workers), we evaluated one such method, Bayesian adaptive design optimization (ADO), in the area of delay discounting by comparing its test–retest reliability, precision, and efficiency with that of a conventional staircase method. In all three populations tested, the results showed that ADO led to 0.95 or higher test–retest reliability of the discounting rate within 10–20 trials (under 1–2 min of testing), captured approximately 10% more variance in test–retest reliability, was 3–5 times more precise, and was 3–8 times more efficient than the staircase method. The ADO methodology provides efficient and precise protocols for measuring individual differences in delay discounting.
Blueberry red ringspot virus genomes from Florida inferred through analysis of blueberry root transcriptomes
Authors: Saad N. , Alcalá-Briseño R. I. , Polston J. E. , Olmstead J. W. , Varsani A. , Harmon P. F. 
Published: July 2020

AbstractA growing number of metagenomics-based approaches have been used for the discovery of viruses in insects, cultivated plants, and water in agricultural production systems. In this study, sixteen blueberry root transcriptomes from eight clonally propagated blueberry plants of cultivar ‘Emerald’ (interspecific hybrid of Vaccinium corymbosum and V. darrowi) generated as part of a separate study on varietal tolerance to soil salinity were analyzed for plant viral sequences. The objective was to determine if the asymptomatic plants harbored the latent blueberry red ringspot virus (BRRV) in their roots. The only currently known mechanism of transmission of BRRV is through vegetative propagation; however, the virus can remain latent for years with some plants of ‘Emerald’ never developing red ringspot symptoms. Bioinformatic analyses of ‘Emerald’ transcriptomes using de novo assembly and reference-based mapping approaches yielded eight complete viral genomes of BRRV (genus Soymovirus, family Caulimoviridae). Validation in vitro by PCR confirmed the presence of BRRV in 100% of the ‘Emerald’ root samples. Sequence and phylogenetic analyses showed 94% to 97% nucleotide identity between BRRV genomes from Florida and sequences from Czech Republic, Japan, Poland, Slovenia, and the United States. Taken together, this study documented the first detection of a complete BRRV genome from roots of asymptomatic blueberry plants and in Florida through in silico analysis of plant transcriptomes.
Relationship of preseismic, coseismic, and postseismic fault ruptures of two large interplate aftershocks of the 2011 Tohoku earthquake with slow-earthquake activity
Authors: Kubo Hisahiko , Nishikawa Tomoaki 
Published: July 2020

AbstractTo improve our understanding of the interactions between regular and slow earthquakes along the Japan Trench, we investigated the spatial relationship of slow-earthquake activity with the preseismic, coseismic, and postseismic fault ruptures of interplate earthquakes off the Iwate and Ibaraki coasts, Japan, including two large interplate aftershocks of the 2011 Tohoku earthquake: the 2011 off Iwate earthquake (MJMA 7.4) and the 2011 off Ibaraki earthquake (MJMA 7.6). We found that the coseismic ruptures of these earthquakes did not overlap with the active areas of slow earthquakes, while their foreshocks and aftershocks occurred in slow-earthquake-prone areas. Moreover, the 2011 off Iwate earthquake and the previous M7-class events shared common fault rupture characteristics: coseismic rupture occurred in a common asperity area, and afterslip with many aftershocks was triggered in the active area of slow earthquakes. Off the Ibaraki coast, tremor activity on a subducting seamount located updip of the coseismic rupture of the 2011 off Ibaraki earthquake implies that the seamount acted as a soft barrier to the coseismic rupture of the 2011 off Ibaraki earthquake. This study demonstrates that large earthquakes off the Iwate and Ibaraki coasts feature similar rupture behaviors, spatially complementary distributions of coseismic ruptures with slow-earthquake activity and foreshock and aftershock activities within and around slow-earthquake-prone areas. This information is useful in considering future large earthquakes along the Japan Trench.
The food contaminant deoxynivalenol provokes metabolic impairments resulting in non-alcoholic fatty liver (NAFL) in mice
Authors: Barbouche Rym , Gaigé Stéphanie , Airault Coraline , Poirot Kevin , Dallaporta Michel , Troadec Jean-Denis , Abysique Anne 
Published: July 2020

AbstractThe ribotoxin deoxynivalenol (DON) is a trichothecene found on cereals responsible for mycotoxicosis in both humans and farm animals. DON toxicity is characterized by reduced food intake, diminished nutritional efficiency and immunologic effects. The present study was designed to further characterize the alterations in energy metabolism induced by DON intoxication. We demonstrated that acute DON intoxication triggered liver steatosis associated with an altered expression of genes related to lipids oxidation, lipogenesis and lipolysis. This steatosis was concomitant to anorexia, hypoglycemia and a paradoxical transient insulin release. DON treatment resulted also in stimulation of central autonomic network regulating sympathetic outflow and adrenaline and glucocorticoids secretion. Furthermore, an increased expression of genes linked to inflammation and reticulum endoplasmic stress was observed in the liver of DON-treated mice. Finally, we propose that lipids mobilization from adipose tissues (AT) induced by DON intoxication drives hepatic steatosis since (1) genes encoding lipolytic enzymes were up-regulated in AT and (2) plasma concentration of triglycerides (TGs) and non-esterified fatty acids were increased during DON intoxication. Altogether, these data demonstrate that DON induced hormonal and metabolic dysregulations associated with a spectrum of hepatic abnormalities, evocative of a non-alcoholic fatty liver disease.
Rich essential properties of Si-doped graphene
Authors: Nguyen Duy Khanh , Tran Ngoc Thanh Thuy , Chiu Yu-Huang , Gumbs Godfrey , Lin Ming-Fa 
Published: July 2020

AbstractThe diverse structural and electronic properties of the Si-adsorbed and -substituted monolayer graphene systems are studied by a complete theoretical framework under the first-principles calculations, including the adatom-diversified geometric structures, the Si- and C-dominated energy bands, the spatial charge densities, variations in the spatial charge densities and the atom- and orbital-projected density of states (DOSs). These critical physical quantities are unified together to display a distinct physical and chemical picture in the studying systems. Under the Si-adsorption and Si-substitution effects, the planar geometric structures are still remained mainly owing to the very strong C–C and Si–C bonds on the honeycomb lattices, respectively. The Si-adsorption cases can create free carriers, while the finite- or zero-gap semiconducting behaviors are revealed in various Si-substitution configurations. The developed theoretical framework can be fully generalized to other emergent layered materials. The Si-doped graphene systems might be a highly promising anode material in the lithium-ion battery owing to its rich potential properties.
Effects of vegetation restoration and environmental factors on understory vascular plants in a typical karst ecosystem in southern China
Authors: Ou Zhiyang , Pang Shilong , He Qinfei , Peng Yuhua , Huang Xiaorong , Shen Wenhui 
Published: July 2020

AbstractUnderstory vegetation is an important component in most forest ecosystems. It is very important for soil and water conservation in karst region, study on understory will provide valuable information for understanding the interaction mechanism between understory flora and karst environment. Thirty-two plots were sampled in three vegetation types along with a restoration gradient (shrubland, forest–shrub transition, and mixed-species broadleaf forest) in typical karst mountains in Southwest Guangxi, China. Overstory trees, understory vascular plants, soil nutrients, and topographic factors were recorded in each 400-m2 plot. Multivariate statistics were used, including the multi-response permutation procedure (MRPP), indicator species analysis, and canonical correlation analysis (CCA). MRPP showed understory species composition significantly differed among the three vegetation types, with the greatest difference between the shrubland and the mixed forest. Twenty-one understory species were identified as significant indicator species, with 13 species being identified as indicators of the shrubland, two of forest–shrub transition, and six of the mixed forest. Light-demanding herbaceous seed plants were common in shrubland, while shade-tolerant calcicole assembled under the mixed forest. Forward selection of CCA ordination revealed that understory plant distribution was most strongly influenced by elevation, followed by soil pH, the concentration of total potassium and exchangeable calcium, slope aspect, slope degree, and the concentration of available potassium. The result reveals that vegetation types affect understory species composition by modifying understory environments. Elevation affects the spatial distribution of vegetation and soil factors, and then the understory plants. Meanwhile, soil Ca content also plays a key role in the understory species distribution. Understory diversity increased with increasing canopy structure complexity from shrubland to mixed-species forest. Thus, it is necessary to take measures to promote natural vegetation restoration and to protect the mixed forests in degraded karst areas.
Cortical network responses map onto data-driven features that capture visual semantics of movie fragments
Authors: Berezutskaya Julia , Freudenburg Zachary V. , Ambrogioni Luca , Güçlü Umut , van Gerven Marcel A. J. , Ramsey Nick F. 
Published: July 2020

AbstractResearch on how the human brain extracts meaning from sensory input relies in principle on methodological reductionism. In the present study, we adopt a more holistic approach by modeling the cortical responses to semantic information that was extracted from the visual stream of a feature film, employing artificial neural network models. Advances in both computer vision and natural language processing were utilized to extract the semantic representations from the film by combining perceptual and linguistic information. We tested whether these representations were useful in studying the human brain data. To this end, we collected electrocorticography responses to a short movie from 37 subjects and fitted their cortical patterns across multiple regions using the semantic components extracted from film frames. We found that individual semantic components reflected fundamental semantic distinctions in the visual input, such as presence or absence of people, human movement, landscape scenes, human faces, etc. Moreover, each semantic component mapped onto a distinct functional cortical network involving high-level cognitive regions in occipitotemporal, frontal and parietal cortices. The present work demonstrates the potential of the data-driven methods from information processing fields to explain patterns of cortical responses, and contributes to the overall discussion about the encoding of high-level perceptual information in the human brain.
Genetic architecture of complex traits and disease risk predictors
Authors: Yong Soke Yuen , Raben Timothy G. , Lello Louis , Hsu Stephen D. H. 
Published: July 2020

AbstractGenomic prediction of complex human traits (e.g., height, cognitive ability, bone density) and disease risks (e.g., breast cancer, diabetes, heart disease, atrial fibrillation) has advanced considerably in recent years. Using data from the UK Biobank, predictors have been constructed using penalized algorithms that favor sparsity: i.e., which use as few genetic variants as possible. We analyze the specific genetic variants (SNPs) utilized in these predictors, which can vary from dozens to as many as thirty thousand. We find that the fraction of SNPs in or near genic regions varies widely by phenotype. For the majority of disease conditions studied, a large amount of the variance is accounted for by SNPs outside of coding regions. The state of these SNPs cannot be determined from exome-sequencing data. This suggests that exome data alone will miss much of the heritability for these traits—i.e., existing PRS cannot be computed from exome data alone. We also study the fraction of SNPs and of variance that is in common between pairs of predictors. The DNA regions used in disease risk predictors so far constructed seem to be largely disjoint (with a few interesting exceptions), suggesting that individual genetic disease risks are largely uncorrelated. It seems possible in theory for an individual to be a low-risk outlier in all conditions simultaneously.