bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depleting long noncoding RNA HOTAIR attenuates chronic myelocytic leukemia progression by binding to DNA methyltransferase 1 and inhibiting PTEN gene promoter methylation
Authors: Song Haiping , Chen Lijuan , Liu Wei , Xu Xiaoli , Zhou Yongming , Zhu Jianhua , Chen Xuexing , Li Ziping , Zhou Hao 
Published: May 2021

AbstractLong noncoding RNAs (lncRNAs) are known to play a key role in chronic myelocytic leukemia (CML) development, and we aimed to identify the involvement of the lncRNA HOX antisense intergenic RNA (HOTAIR) in CML via binding to DNA methyltransferase 1 (DNMT1) to accelerate methylation of the phosphatase and tensin homolog (PTEN) gene promoter. Bone marrow samples from CML patients and normal bone marrow samples from healthy controls were collected. HOTAIR, DNMT1, DNMT3A, DNMT3B, and PTEN expression was detected. The biological characteristics of CML cells were detected. The relationship among HOTAIR, DNMT1, and PTEN was verified. Tumor volume and weight in mice injected with CML cells were tested. We found that HOTAIR and DNMT1 expression was increased and PTEN expression was decreased in CML. We also investigated whether downregulated HOTAIR or DNMT1 reduced proliferation, colony formation, invasion, and migration and increased the apoptosis rate of CML cells. Moreover, we tested whether low expression of HOTAIR or DNMT1 reduced the volume and weight of tumors in mice with CML. Collectively, the results of this studied showed that depleted HOTAIR demonstrated reduced binding to DNMT1 to suppress CML progression, which may be related to methylation of the PTEN promoter.
Hypoxia-induced miR-210 modulates the inflammatory response and fibrosis upon acute ischemia
Authors: Zaccagnini Germana , Greco Simona , Longo Marialucia , Maimone Biagina , Voellenkle Christine , Fuschi Paola , Carrara Matteo , Creo Pasquale , Maselli Davide , Tirone Mario , Mazzone Massimiliano , Gaetano Carlo , Spinetti Gaia , Martelli Fabio 
Published: May 2021

AbstractHypoxia-induced miR-210 is a crucial component of the tissue response to ischemia, stimulating angiogenesis and improving tissue regeneration. Previous analysis of miR-210 impact on the transcriptome in a mouse model of hindlimb ischemia showed that miR-210 regulated not only vascular regeneration functions, but also inflammation. To investigate this event, doxycycline-inducible miR-210 transgenic mice (Tg-210) and anti-miR-210 LNA-oligonucleotides were used. It was found that global miR-210 expression decreased inflammatory cells density and macrophages accumulation in the ischemic tissue. To dissect the underpinning cell mechanisms, Tg-210 mice were used in bone marrow (BM) transplantation experiments and chimeric mice underwent hindlimb ischemia. MiR-210 overexpression in the ischemic tissue was sufficient to increase capillary density and tissue repair, and to reduce inflammation in the presence of Wt-BM infiltrating cells. Conversely, when Tg-210-BM cells migrated in a Wt ischemic tissue, dysfunctional angiogenesis, inflammation, and impaired tissue repair, accompanied by fibrosis were observed. The fibrotic regions were positive for α-SMA, Vimentin, and Collagen V fibrotic markers and for phospho-Smad3, highlighting the activation of TGF-β1 pathway. Identification of Tg-210 cells by in situ hybridization showed that BM-derived cells contributed directly to fibrotic areas, where macrophages co-expressing fibrotic markers were observed. Cell cultures of Tg-210 BM-derived macrophages exhibited a pro-fibrotic phenotype and were enriched with myofibroblast-like cells, which expressed canonical fibrosis markers. Interestingly, inhibitors of TGF-β type-1-receptor completely abrogated this pro-fibrotic phenotype. In conclusion, a context-dependent regulation by miR-210 of the inflammatory response was identified. miR-210 expression in infiltrating macrophages is associated to improved angiogenesis and tissue repair when the ischemic recipient tissue also expresses high levels of miR-210. Conversely, when infiltrating an ischemic tissue with mismatched miR-210 levels, macrophages expressing high miR-210 levels display a pro-fibrotic phenotype, leading to impaired tissue repair, fibrosis, and dysfunctional angiogenesis.
Histone modifications centric-regulation in osteogenic differentiation
Authors: Li Kun , Han Jinxiang , Wang Ziqiang 
Published: May 2021

AbstractHistone modification critically contributes to the epigenetic control of gene expression by changing the configuration of chromatin and modifying the access of transcription factors to gene promoters. Recently, we observed that histone acetylation and crotonylation mediated the expression of endocytosis-related genes and tumor-related immune checkpoint genes by regulating the enrichment of signal transducer and activator of transcription 3 on these gene promoters in Alzheimer’s disease and tumorigenesis, suggesting that histone modification plays an important role in disease development. Furthermore, studies performed in the past decade revealed that histone modifications affect osteogenic differentiation by regulating the expression of osteogenic marker genes. In this review, we summarize and discuss the histone modification-centric regulation of osteogenic gene expression. This review improves the understanding of the role of histone modifications in osteogenic differentiation and describes its potential as a therapeutic target for osteogenic differentiation-related diseases.
Estimation of coalescence probabilities and population divergence times from SNP data
Authors: Mualim Kristy , Theunert Christoph , Slatkin Montgomery 
Published: May 2021

AbstractWe present a method called the G(A|B) method for estimating coalescence probabilities within population lineages from genome sequences when one individual is sampled from each population. Population divergence times can be estimated from these coalescence probabilities if additional assumptions about the history of population sizes are made. Our method is based on a method presented by Rasmussen et al. (2014) to test whether an archaic genome is from a population directly ancestral to a present-day population. The G(A|B) method does not require distinguishing ancestral from derived alleles or assumptions about demographic history before population divergence. We discuss the relationship of our method to two similar methods, one introduced by Green et al. (2010) and called the F(A|B) method and the other introduced by Schlebusch et al. (2017) and called the TT method. When our method is applied to individuals from three or more populations, it provides a test of whether the population history is treelike because coalescence probabilities are additive on a tree. We illustrate the use of our method by applying it to three high-coverage archaic genomes, two Neanderthals (Vindija and Altai) and a Denisovan.
Brassinosteroids suppress ethylene-induced fruitlet abscission through LcBZR1/2-mediated transcriptional repression of LcACS1/4 and LcACO2/3 in litchi
Authors: Ma Xingshuai , Yuan Ye , Li Caiqin , Wu Qian , He Zidi , Li Jianguo , Zhao Minglei 
Published: May 2021

Abstract
Abscission in plants is tightly controlled by multiple phytohormones and the expression of various genes. However, whether the plant hormone brassinosteroids (BRs) are involved in this process is largely unknown. Here, we found that exogenous application of BRs reduced the ethylene-induced fruitlet abscission of litchi due to lower ethylene (ET) production and suppressed the expression of the ethylene biosynthetic genes LcACS1/4 and LcACO2/3 in the fruitlet abscission zone (FAZ). Two genes that encode the BR core signaling components brassinazole resistant (BZR) proteins, namely, LcBZR1 and LcBZR2, were characterized. LcBZR1/2 were localized to the nucleus and acted as transcription repressors. Interestingly, the LcBZR1/2 transcript levels were not changed during ET-induced fruitlet abscission, while their expression levels were significantly increased after BR application. Moreover, gel shift and transient expression assays indicated that LcBZR1/2 could suppress the transcription of LcACS1/4 and LcACO2/3 by specifically binding to their promoters. Importantly, ectopic expression of LcBZR1/2 in Arabidopsis significantly delayed floral organ abscission and suppressed ethylene biosynthesis. Collectively, our results suggest that BRs suppress ET-induced fruitlet abscission through LcBZR1/2-controlled expression of genes related to ethylene biosynthesis in litchi. In addition, similar results were observed in the Arabidopsis gain-of-function mutant bzr1-1D, which showed delayed floral organ abscission in parallel with lower expression of ACS/ACO genes and reduced ethylene production, suggesting that the mechanism of BZR-controlled organ abscission via regulation of ethylene biosynthesis might be conserved in Arabidopsis.
FKBP52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model
Authors: Criado-Marrero Marangelie , Gebru Niat T. , Gould Lauren A. , Blazier Danielle M. , Vidal-Aguiar Yamile , Smith Taylor M. , Abdelmaboud Salma S. , Shelton Lindsey B. , Wang Xinming , Dahrendorff Jan , Beaulieu-Abdelahad David , Dickey Chad A. , Blair Laura J. 
Published: May 2021

AbstractAbnormal accumulation of hyperphosphorylated tau induces pathogenesis in neurodegenerative diseases, like Alzheimer’s disease. Molecular chaperones with peptidyl-prolyl cis/trans isomerase (PPIase) activity are known to regulate these processes. Previously, in vitro studies have shown that the 52 kDa FK506-binding protein (FKBP52) interacts with tau inducing its oligomerization and fibril formation to promote toxicity. Thus, we hypothesized that increased expression of FKBP52 in the brains of tau transgenic mice would alter tau phosphorylation and neurofibrillary tangle formation ultimately leading to memory impairments. To test this, tau transgenic (rTg4510) and wild-type mice received bilateral hippocampal injections of virus overexpressing FKBP52 or GFP control. We examined hippocampal-dependent memory, synaptic plasticity, tau phosphorylation status, and neuronal health. This work revealed that rTg4510 mice overexpressing FKBP52 had impaired spatial learning, accompanied by long-term potentiation deficits and hippocampal neuronal loss, which was associated with a modest increase in total caspase 12. Together with previous studies, our findings suggest that FKBP52 may sensitize neurons to tau-mediated dysfunction via activation of a caspase-dependent pathway, contributing to memory and learning impairments.
Alternative splicing during mammalian organ development
Authors: Mazin Pavel V. , Khaitovich Philipp , Cardoso-Moreira Margarida , Kaessmann Henrik 
Published: May 2021

AbstractAlternative splicing (AS) is pervasive in mammalian genomes, yet cross-species comparisons have been largely restricted to adult tissues and the functionality of most AS events remains unclear. We assessed AS patterns across pre- and postnatal development of seven organs in six mammals and a bird. Our analyses revealed that developmentally dynamic AS events, which are especially prevalent in the brain, are substantially more conserved than nondynamic ones. Cassette exons with increasing inclusion frequencies during development show the strongest signals of conserved and regulated AS. Newly emerged cassette exons are typically incorporated late in testis development, but those retained during evolution are predominantly brain specific. Our work suggests that an intricate interplay of programs controlling gene expression levels and AS is fundamental to organ development, especially for the brain and heart. In these regulatory networks, AS affords substantial functional diversification of genes through the generation of tissue- and time-specific isoforms from broadly expressed genes.
Preoperative prediction of perineural invasion with multi-modality radiomics in rectal cancer
Authors: Guo Yu , Wang Quan , Guo Yan , Zhang Yiying , Fu Yu , Zhang Huimao 
Published: May 2021

AbstractPerineural invasion (PNI) as a grossly underreported independent risk predictor in rectal cancer is hard to identify preoperatively. We aim to predict PNI status in rectal cancer using multi-modality radiomics. In total, 396 radiomics features were extracted from T2-weighted images (T2WIs), diffusion-weighted images (DWIs), and portal venous phase of contrast-enhanced CT (CE-CT) respectively of 94 consecutive patients with histologically confirmed rectal cancer. T2WI score, DWI score, and CT score were calculated via the radiomics features selection and optimization. Discrimination, calibration, and clinical benefit ability were used to evaluate the performance of the radiomics scores in both training and testing datasets. CT score and T2WI score were independent risk predictors [CT score, OR (95% CI) = 4.218 (1.070–16.620); T2WI score, OR (95% CI) = 105.721 (3.091–3615.790)]. The concise score which combined CT score and T2WI score, showed the best performance [training dataset, AUC (95% CI) = 0.906 (0.833–0.979); testing dataset, AUC (95% CI) = 0.884 (0.761–1.000)] and good calibration (P > 0.05 in the Hosmer–Lemeshow test for the training and testing datasets). Decision curve analysis showed that the multi-modality radiomics nomogram had a higher clinical net benefit. The multi-modality radiomics score could be used to preoperatively assess PNI status in rectal cancer.
Cell-free synthetic biochemistry upgrading of ethanol to 1,3 butanediol
Authors: Liu Hongjiang , Bowie James U. 
Published: May 2021

AbstractIt is now possible to efficiently fix flue gas CO/CO2 into ethanol using acetogens, thereby making carbon negative ethanol. While the ethanol could be burned as a fuel, returning the CO2 to the atmosphere, it might also be possible to use the fixed carbon in more diverse chemicals, thereby keeping it fixed. Here we describe a simple synthetic biochemistry approach for converting carbon negative ethanol into the synthetic building block chemical 1,3 butanediol (1,3-BDO). The pathway completely conserves carbon from ethanol and can ultimately be powered electrochemically via formate oxidation. Our proof-of-principle system reached a maximum productivity of 0.16 g/L/h and, with replenishment of feedstock and enzymes, achieved a titer of 7.7 g/L. We identify a number of elements that can be addressed in future work to improve both cell-free and cell-based production of 1,3-BDO.
A novel, complex systems approach to modelling risk of psychological distress in young adolescents
Authors: Beaudequin Denise , Schwenn Paul , McLoughlin Larisa T. , Parker Marcella , Boyes Amanda , Simcock Gabrielle , Lagopoulos Jim , Hermens Daniel F. 
Published: May 2021

AbstractAdolescence is a period of significant anatomical and functional brain changes, and complex interactions occur between mental health risk factors. The Longitudinal Adolescent Brain Study commenced in 2018, to monitor environmental and psychosocial factors influencing mental health in 500 adolescents, for 5 years. Participants are recruited at age 12 from the community in Australia’s Sunshine Coast region. In this baseline, cross-sectional study of N = 64 participants, we draw on the network perspective, conceptualising mental disorders as causal systems of interacting entities, to propose a Bayesian network (BN) model of lifestyle and psychosocial variables influencing chances of individuals being psychologically well or experiencing psychological distress. Sensitivity analysis of network priors revealed that psychological distress (Kessler-10) was most affected by eating behaviour. Unhealthy eating increased the chance of moderate psychological distress by 600%. Low social connectedness increased the chance of severe psychological disorder by 200%. Certainty for psychological wellness required 33% decrease in unhealthy eating behaviours, 11% decrease in low social connectedness, and 9% reduction in less physical activity. BN can augment clinician judgement in mental disorders as probabilistic decision support systems. The full potential of BN methodology in a complex systems approach to psychopathology has yet to be realised.
Computer extracted gland features from H&E predicts prostate cancer recurrence comparably to a genomic companion diagnostic test: a large multi-site study
Authors: Leo Patrick , Janowczyk Andrew , Elliott Robin , Janaki Nafiseh , Bera Kaustav , Shiradkar Rakesh , Farré Xavier , Fu Pingfu , El-Fahmawi Ayah , Shahait Mohammed , Kim Jessica , Lee David , Yamoah Kosj , Rebbeck Timothy R. , Khani Francesca , Robinson Brian D. , Eklund Lauri , Jambor Ivan , Merisaari Harri , Ettala Otto , Taimen Pekka , Aronen Hannu J. , Boström Peter J. , Tewari Ashutosh , Magi-Galluzzi Cristina , Klein Eric , Purysko Andrei , NC Shih Natalie , Feldman Michael , Gupta Sanjay , Lal Priti , Madabhushi Anant 
Published: May 2021

AbstractExisting tools for post-radical prostatectomy (RP) prostate cancer biochemical recurrence (BCR) prognosis rely on human pathologist-derived parameters such as tumor grade, with the resulting inter-reviewer variability. Genomic companion diagnostic tests such as Decipher tend to be tissue destructive, expensive, and not routinely available in most centers. We present a tissue non-destructive method for automated BCR prognosis, termed "Histotyping", that employs computational image analysis of morphologic patterns of prostate tissue from a single, routinely acquired hematoxylin and eosin slide. Patients from two institutions (n = 214) were used to train Histotyping for identifying high-risk patients based on six features of glandular morphology extracted from RP specimens. Histotyping was validated for post-RP BCR prognosis on a separate set of n = 675 patients from five institutions and compared against Decipher on n = 167 patients. Histotyping was prognostic of BCR in the validation set (p < 0.001, univariable hazard ratio [HR] = 2.83, 95% confidence interval [CI]: 2.03–3.93, concordance index [c-index] = 0.68, median years-to-BCR: 1.7). Histotyping was also prognostic in clinically stratified subsets, such as patients with Gleason grade group 3 (HR = 4.09) and negative surgical margins (HR = 3.26). Histotyping was prognostic independent of grade group, margin status, pathological stage, and preoperative prostate-specific antigen (PSA) (multivariable p < 0.001, HR = 2.09, 95% CI: 1.40–3.10, n = 648). The combination of Histotyping, grade group, and preoperative PSA outperformed Decipher (c-index = 0.75 vs. 0.70, n = 167). These results suggest that a prognostic classifier for prostate cancer based on digital images could serve as an alternative or complement to molecular-based companion diagnostic tests.
Pleckstrin-2 is essential for erythropoiesis in β-thalassemic mice, reducing apoptosis and enhancing enucleation
Authors: Feola Maria , Zamperone Andrea , Moskop Daniel , Chen Huiyong , Casu Carla , Lama Dechen , Di Martino Julie , Djedaini Mansour , Papa Luena , Martinez Marc Ruiz , Choesang Tenzin , Bravo-Cordero Jose Javier , MacKay Matthew , Zumbo Paul , Brinkman Nathan , Abrams Charles S. , Rivella Stefano , Hattangadi Shilpa , Mason Christopher E. , Hoffman Ronald , Ji Peng , Follenzi Antonia , Ginzburg Yelena Z. 
Published: May 2021

AbstractErythropoiesis involves complex interrelated molecular signals influencing cell survival, differentiation, and enucleation. Diseases associated with ineffective erythropoiesis, such as β-thalassemias, exhibit erythroid expansion and defective enucleation. Clear mechanistic determinants of what make erythropoiesis effective are lacking. We previously demonstrated that exogenous transferrin ameliorates ineffective erythropoiesis in β-thalassemic mice. In the current work, we utilize transferrin treatment to elucidate a molecular signature of ineffective erythropoiesis in β-thalassemia. We hypothesize that compensatory mechanisms are required in β-thalassemic erythropoiesis to prevent apoptosis and enhance enucleation. We identify pleckstrin-2—a STAT5-dependent lipid binding protein downstream of erythropoietin—as an important regulatory node. We demonstrate that partial loss of pleckstrin-2 leads to worsening ineffective erythropoiesis and pleckstrin-2 knockout leads to embryonic lethality in β-thalassemic mice. In addition, the membrane-associated active form of pleckstrin-2 occurs at an earlier stage during β-thalassemic erythropoiesis. Furthermore, membrane-associated activated pleckstrin-2 decreases cofilin mitochondrial localization in β-thalassemic erythroblasts and pleckstrin-2 knockdown in vitro induces cofilin-mediated apoptosis in β-thalassemic erythroblasts. Lastly, pleckstrin-2 enhances enucleation by interacting with and activating RacGTPases in β-thalassemic erythroblasts. This data elucidates the important compensatory role of pleckstrin-2 in β-thalassemia and provides support for the development of targeted therapeutics in diseases of ineffective erythropoiesis.
Montessori Project
Authors: Mendoza Lucy , Escamilla Andres , Romero Ana Cristina García-Luna 
Published: May 2021

The architectural character of a building is based on different aspects. In order to understand the spirit of each building, we must study functional, associated and personal elements of it. Each architectural element differs in each aspect since each one is based on previous analysis and studies to be able to emerge and reach its purpose.
The Montessori architectural project is based on research on the method of this system that provides environments prepared for the proper development of children in education. The classrooms, materiality, socialization, environments and spaces are studied in order to be able to generate and gradually form design ideas to generate the project in a successful way.
It is decided based on the information obtained by previous studies, to use the neuroarchitecture design guideline to be able to meet the guidelines and objectives of this Montessori method, since this guiding concept goes beyond the study of space, but involves the emotions and feelings of the people who live the spaces. In this way, it is better understood that what guides us to the architectural design of the proposal based on the Montessori method are the studies of neuroarchitecture.