Faculty Opinions recommendation of Mutational activation of niche-specific genes provides insight into regulatory networks and bacterial function in a complex environment.

2007 ◽  
Author(s):  
Peter Williams
Keyword(s):  
Regulatory Networks ◽  
Complex Environment ◽  
Bacterial Function ◽  
Mutational Activation ◽  
Insight Into

scholarly journals Transcriptomic and chemical analyses to identify candidate genes involved in color variation of sainfoin flowers

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yu Qiao ◽  
Qiming Cheng ◽  
Yutong Zhang ◽  
Wei Yan ◽  
Fengyan Yi ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Flower Color ◽  
Color Variation ◽  
Anthocyanin Synthesis ◽  
Flower Formation ◽  
Factors Affecting ◽  
Phenylpropanoid Biosynthesis ◽  
Molecular Information ◽  
Illumina Hiseq4000 ◽  
Insight Into

Abstract Background Sainfoin (Onobrychis viciifolia Scop) is not only a high-quality legume forage, but also a nectar-producing plant. Therefore, the flower color of sainfoin is an important agronomic trait, but the factors affecting its flower phenotype are still unclear. To gain insights into the regulatory networks associated with metabolic pathways of coloration compounds (flavonoids or anthocyanins) and identify the key genes, we conducted a comprehensive analysis of the phenotype, metabolome and transcriptome of WF and AF of sainfoin. Results Delphinidin, petunidin and malvidin derivatives were the main anthocyanin compounds in the AF of sainfoin. These substances were not detected in the WF of sainfoin. The transcriptomes of WF and AF in sainfoin at the S1 and S3 stages were obtained using the Illumina HiSeq4000 platform. Overall, 10,166 (4273 upregulated and 5893 downregulated) and 15,334 (8174 upregulated and 7160 downregulated) DEGs were identified in flowers at S1 and S3 stages, respectively (WF-VS-AF). KEGG pathway annotations showed that 6396 unigenes were annotated to 120 pathways and contained 866 DEGs at S1 stages, and 6396 unigenes were annotated to 131 pathways and included 1546 DEGs at the S3 stage. Nine DEGs belonging to the “flavonoid biosynthesis”and “phenylpropanoid biosynthesis” pathways involved in flower color formation were identified and verified by RT-qPCR analyses. Among these DEGs, 4CL3, FLS, ANS, CHS, DFR and CHI2 exhibited downregulated expression, and F3H exhibited upregulated expression in the WF compared to the AF, resulting in a decrease in anthocyanin synthesis and the formation of WF in sainfoin. Conclusions This study is the first to use transcriptome technology to study the mechanism of white flower formation in sainfoin. Our transcriptome data will be a great enrichment of the genetic information for sainfoin. In addition, the data presented herein will provide valuable molecular information for genetic breeding and provide insight into the future study of flower color polymorphisms in sainfoin.

scholarly journals IMiDs prime myeloma cells for daratumumab-mediated cytotoxicity through loss of Ikaros and Aiolos

Blood ◽  
2018 ◽  
Vol 132 (20) ◽  
pp. 2166-2178 ◽  
Author(s):  
Pasquale L. Fedele ◽  
Simon N. Willis ◽  
Yang Liao ◽  
Michael S. Low ◽  
Jai Rautela ◽  
...  
Keyword(s):  
Cell Death ◽  
Regulatory Networks ◽  
Nk Cell ◽  
Surface Expression ◽  
Nucleosome Remodeling ◽  
Interferon Stimulated Genes ◽  
Cd38 Expression ◽  
Cycle Arrest ◽  
Transcriptional Changes ◽  
Insight Into

Abstract Recent studies have demonstrated that the immunomodulatory drugs (IMiDs) lead to the degradation of the transcription factors Ikaros and Aiolos. However, why their loss subsequently leads to multiple myeloma (MM) cell death remains unclear. Using CRISPR-Cas9 genome editing, we have deleted IKZF1/Ikaros and IKZF3/Aiolos in human MM cell lines to gain further insight into their downstream gene regulatory networks. Inactivation of either factor alone recapitulates the cell intrinsic action of the IMiDs, resulting in cell cycle arrest and induction of apoptosis. Furthermore, evaluation of the transcriptional changes resulting from their loss demonstrates striking overlap with lenalidomide treatment. This was not dependent on reduction of the IRF4-MYC “axis,” as neither protein was consistently downregulated, despite cell death occurring, and overexpression of either factor failed to rescue for Ikaros loss. Importantly, Ikaros and Aiolos repress the expression of interferon-stimulated genes (ISGs), including CD38, and their loss led to the activation of an interferon-like response, contributing to MM cell death. Ikaros/Aiolos repressed CD38 expression through interaction with the nucleosome remodeling and deacetylase complex in MM. IMiD-induced loss of Ikaros or treatment with interferon resulted in an upregulation of CD38 surface expression on MM cells, priming for daratumumab-induced NK cell-mediated antibody-dependent cellular cytotoxicity. These results give further insight into the mechanism of action of the IMiDs and provide mechanistic rationale for combination with anti-CD38 monoclonal antibodies.

scholarly journals The Expression Regulatory Network in the Lung Tissue of Tibetan Pigs Provides Insight Into Hypoxia-Sensitive Pathways in High-Altitude Hypoxia

2021 ◽  
Vol 12 ◽  
Author(s):  
Yanan Yang ◽  
Haonan Yuan ◽  
Tianliang Yang ◽  
Yongqing Li ◽  
Caixia Gao ◽  
...  
Keyword(s):  
High Altitude ◽  
Regulatory Networks ◽  
Alveolar Wall ◽  
Potential Candidate ◽  
Low Oxygen ◽  
Structure Damage ◽  
High Altitude Adaptation ◽  
Tibetan Pigs ◽  
Altitude Adaptation ◽  
Insight Into

To adapt to a low-oxygen environment, Tibetan pigs have developed a series of unique characteristics and can transport oxygen more effectively; however, the regulation of the associated processes in high-altitude animals remains elusive. We performed mRNA-seq and miRNA-seq, and we constructed coexpression regulatory networks of the lung tissues of Tibetan and Landrace pigs. HBB, AGT, COL1A2, and EPHX1 were identified as major regulators of hypoxia-induced genes that regulate blood pressure and circulation, and they were enriched in pathways related to signal transduction and angiogenesis, such as HIF-1, PI3K-Akt, mTOR, and AMPK. HBB may promote the combination of hemoglobin and oxygen as well as angiogenesis for high-altitude adaptation in Tibetan pigs. The expression of MMP2 showed a similar tendency of alveolar septum thickness among the four groups. These results indicated that MMP2 activity may lead to widening of the alveolar wall and septum, alveolar structure damage, and collapse of alveolar space with remarkable fibrosis. These findings provide a perspective on hypoxia-adaptive genes in the lungs in addition to insights into potential candidate genes in Tibetan pigs for further research in the field of high-altitude adaptation.

scholarly journals Degradation rate uniformity determines success of oscillations in repressive feedback regulatory networks

2018 ◽  
Vol 15 (142) ◽  
pp. 20180157 ◽  
Author(s):  
Karen M. Page ◽  
Ruben Perez-Carrasco
Keyword(s):  
Regulatory Networks ◽  
Oscillatory Behaviour ◽  
Sustained Oscillations ◽  
Degradation Rates ◽  
Number Of Genes ◽  
Computational Exploration ◽  
The Stability ◽  
Regulatory Functions ◽  
Insight Into

Ring oscillators are biochemical circuits consisting of a ring of interactions capable of sustained oscillations. The nonlinear interactions between genes hinder the analytical insight into their function, usually requiring computational exploration. Here, we show that, despite the apparent complexity, the stability of the unique steady state in an incoherent feedback ring depends only on the degradation rates and a single parameter summarizing the feedback of the circuit. Concretely, we show that the range of regulatory parameters that yield oscillatory behaviour is maximized when the degradation rates are equal. Strikingly, this result holds independently of the regulatory functions used or number of genes. We also derive properties of the oscillations as a function of the degradation rates and number of nodes forming the ring. Finally, we explore the role of mRNA dynamics by applying the generic results to the specific case with two naturally different degradation timescales.

Elements and Materials Improve the FDM Products: A Review

2016 ◽  
Vol 16 ◽  
pp. 33-51 ◽  
Author(s):  
Abduladim Salem Bala ◽  
Saidin bin Wahab ◽  
Mazatusziha binti Ahmad
Keyword(s):  
Matrix Material ◽  
Process Parameter ◽  
Correct Selection ◽  
Complex Environment ◽  
Technology Process ◽  
The Matrix ◽  
Additive Materials ◽  
Insight Into ◽  
Selection Of

This work aims to provide a review of available published literature that explores the opportunities to improve the quality of fused deposit modelling (FDM) products, particularly in medical applications. The paper presents details concerning the basis of the technology, process parameter settings and their responses, and reviews the properties of common FDM engineering/bio-materials and the available methods applied for improving their performance. Based on the researches which have been reviewed, FDM technology works within a complex environment from process parameters. Thus, it can achieve good results only with the proper settings for these parameters according to the properties of the material used. Improving the polymers is essentially based on the correct selection of additive materials, which can particularly enhance the key property/properties in the matrix material. This review provides a brief insight into FDM technology, provides an idea of the process parameter settings, the available materials and ways of modifying their properties to consequently improve the quality of FDM products.

scholarly journals The aging lung mucosa: A proteomics study

2021 ◽  
Author(s):  
Andreu Garcia-Vilanova ◽  
Angelica M. Olmo-Fontanez ◽  
Juan I. Moliva ◽  
Anna Allue Guardia ◽  
Harjinder Singh ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Elderly Population ◽  
Respiratory Infections ◽  
The Elderly ◽  
Pulmonary Diseases ◽  
Lung Cells ◽  
Molecular Fingerprints ◽  
Elderly Individuals ◽  
Increased Risk ◽  
Insight Into

The elderly population is at increased risk of acute and chronic respiratory infections and other pulmonary diseases, and it is estimated that this population will double in the next 30 years. Biochemical changes in the lung alveolar mucosa and lung cells alter local immune response as we age, creating opportunities for invading pathogens to establish successful infections. Indeed, the lungs of the elderly are a pro-inflammatory, pro-oxidative, dysregulated environment but this environment has remained understudied. We performed a comprehensive, quantitative proteomic profile of the lung mucosa in the elderly, developing insight into the molecular fingerprints, pathways, and regulatory networks that characterize the lung in old age. We identified neutrophils in the lungs of elderly individuals as possible contributors to dysregulated lung tissue environment. This study establishes a baseline for future investigations to develop strategies to mitigate susceptibility to respiratory infections in the elderly.

scholarly journals Super interactive promoters provide insight into cell type-specific regulatory networks in blood lineage cell types

2021 ◽  
Author(s):  
Taylor M. Lagler ◽  
Yuchen Yang ◽  
Yuriko Harigaya ◽  
Vijay G. Sankaran ◽  
Ming Hu ◽  
...  
Keyword(s):  
Blood Cell ◽  
Regulatory Networks ◽  
Transcriptional Control ◽  
Spatial Organization ◽  
Cell Types ◽  
Gene Promoters ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific ◽  
Insight Into

Existing studies of chromatin conformation have primarily focused on potential enhancers interacting with gene promoters. By contrast, the interactivity of promoters per se, while equally critical to understanding transcriptional control, has been largely unexplored, particularly in a cell type-specific manner for blood lineage cell types. In this study, we leverage promoter capture Hi-C data across a compendium of blood lineage cell types to identify and characterize cell type-specific super-interactive promoters (SIPs). Notably, promoter-interacting regions (PIRs) of SIPs are more likely to overlap with cell type-specific ATAC-seq peaks and GWAS variants for relevant blood cell traits than PIRs of non-SIPs. Further, SIP genes tend to express at a higher level in the corresponding cell type, and show enriched heritability of relevant blood cell trait(s). Importantly, this analysis shows the potential of using promoter-centric analyses of chromatin spatial organization data to identify biologically important genes and their regulatory regions.

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