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https://www.readbyqxmd.com/read/29777905/coupling-of-the-polyamine-and-iron-metabolism-pathways-in-the-regulation-of-proliferation-mechanistic-links-to-alterations-in-key-polyamine-biosynthetic-and-catabolic-enzymes
#1
Darius J R Lane, Dong-Hun Bae, Aritee R Siafakas, Yohan Suryo Rahmanto, Lina Al-Akra, Patric J Jansson, Robert A Casero, Des R Richardson
Many biological processes result from the coupling of metabolic pathways. Considering this, proliferation depends on adequate iron and polyamines, and although iron-depletion impairs proliferation, the metabolic link between iron and polyamine metabolism has never been thoroughly investigated. This is important to decipher, as many disease states demonstrate co-dysregulation of iron and polyamine metabolism. Herein, for the first time, we demonstrate that cellular iron levels robustly regulate 13 polyamine pathway proteins...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777213/semaphorin-6d-reverse-signaling-controls-macrophage-lipid-metabolism-and-anti-inflammatory-polarization
#2
Sujin Kang, Yoshimitsu Nakanishi, Yoshiyuki Kioi, Daisuke Okuzaki, Tetsuya Kimura, Hyota Takamatsu, Shohei Koyama, Satoshi Nojima, Masayuki Nishide, Yoshitomo Hayama, Yuhei Kinehara, Yasuhiro Kato, Takeshi Nakatani, Tomomi Shimogori, Junichi Takagi, Toshihiko Toyofuku, Atsushi Kumanogoh
Polarization of macrophages into pro-inflammatory or anti-inflammatory states has distinct metabolic requirements, with mechanistic target of rapamycin (mTOR) kinase signaling playing a critical role. However, it remains unclear how mTOR regulates metabolic status to promote polarization of these cells. Here we show that an mTOR-Semaphorin 6D (Sema6D)-Peroxisome proliferator receptor γ (PPARγ) axis plays critical roles in macrophage polarization. Inhibition of mTOR or loss of Sema6D blocked anti-inflammatory macrophage polarization, concomitant with severe impairments in PPARγ expression, uptake of fatty acids, and lipid metabolic reprogramming...
May 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29777051/cd36-initiates-the-secretory-phenotype-during-the-establishment-of-cellular-senescence
#3
Mengyang Chong, Tao Yin, Rui Chen, Handan Xiang, Lifeng Yuan, Yi Ding, Christopher C Pan, Zhen Tang, Peter B Alexander, Yinjun Jia, Qi-Jing Li, Xiao-Fan Wang
Cellular senescence is a unique cell fate characterized by stable proliferative arrest and the extensive production and secretion of various inflammatory proteins, a phenomenon known as the senescence-associated secretory phenotype (SASP). The molecular mechanisms responsible for generating a SASP in response to senescent stimuli remain largely obscure. Here, using unbiased gene expression profiling, we discover that the scavenger receptor CD36 is rapidly upregulated in multiple cell types in response to replicative, oncogenic, and chemical senescent stimuli...
May 18, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29775654/targeting-cancer-s-metabolic-co-dependencies-a-landscape-shaped-by-genotype-and-tissue-context
#4
REVIEW
Junfeng Bi, Sihan Wu, Wenjing Zhang, Paul S Mischel
Tumors cells reprogram their metabolism to fuel rapid growth. The ability to trace nutrient fluxes in the context of specific alterations has provided new mechanistic insight into the process of oncogenic transformation. A broad array of complementary genetic, epigenetic, transcriptional and translational mechanisms has been identified, revealing a metabolic landscape of cancer. However, cancer metabolism is not a static or uniform process, including within a single tumor. Tumor cells adapt to changing environmental conditions, profoundly shaping the enzymatic dependencies of individual cells...
May 15, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29774393/developmental-origin-of-the-cardiac-conduction-system-insight-from-lineage-tracing
#5
Rajiv A Mohan, Bastiaan J Boukens, Vincent M Christoffels
The components of the cardiac conduction system (CCS) generate and propagate the electrical impulse that initiates cardiac contraction. These interconnected components share properties, such as automaticity, that set them apart from the working myocardium of the atria and ventricles. A variety of tools and approaches have been used to define the CCS lineages. These include genetic labeling of cells expressing lineage markers and fate mapping of dye labeled cells, which we will discuss in this review. We conclude that there is not a single CCS lineage, but instead early cell fate decisions segregate the lineages of the CCS components while they remain interconnected...
May 17, 2018: Pediatric Cardiology
https://www.readbyqxmd.com/read/29773872/computational-identification-of-specific-genes-for-glioblastoma-stem-like-cells-identity
#6
Giulia Fiscon, Federica Conte, Valerio Licursi, Sergio Nasi, Paola Paci
Glioblastoma, the most malignant brain cancer, contains self-renewing, stem-like cells that sustain tumor growth and therapeutic resistance. Identifying genes promoting stem-like cell differentiation might unveil targets for novel treatments. To detect them, here we apply SWIM - a software able to unveil genes (named switch genes) involved in drastic changes of cell phenotype - to public datasets of gene expression profiles from human glioblastoma cells. By analyzing matched pairs of stem-like and differentiated glioblastoma cells, SWIM identified 336 switch genes, potentially involved in the transition from stem-like to differentiated state...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29772845/doxycycline-impairs-mitochondrial-function-and-protects-human-glioma-cells-from-hypoxia-induced-cell-death-implications-of-using-tet-inducible-systems
#7
Anna-Luisa Luger, Benedikt Sauer, Nadja I Lorenz, Anna L Engel, Yannick Braun, Martin Voss, Patrick N Harter, Joachim P Steinbach, Michael W Ronellenfitsch
Inducible gene expression is an important tool in molecular biology research to study protein function. Most frequently, the antibiotic doxycycline is used for regulation of so-called tetracycline (Tet)-inducible systems. In contrast to stable gene overexpression, these systems allow investigation of acute and reversible effects of cellular protein induction. Recent reports have already called for caution when using Tet-inducible systems as the employed antibiotics can disturb mitochondrial function and alter cellular metabolism by interfering with mitochondrial translation...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772764/the-making-of-leukemia
#8
REVIEW
Inés González-Herrero, Guillermo Rodríguez-Hernández, Andrea Luengas-Martínez, Marta Isidro-Hernández, Rafael Jiménez, Maria Begoña García-Cenador, Francisco Javier García-Criado, Isidro Sánchez-García, Carolina Vicente-Dueñas
Due to the clonal nature of human leukemia evolution, all leukemic cells carry the same leukemia-initiating genetic lesions, independently of the intrinsic tumoral cellular heterogeneity. However, the latest findings have shown that the mode of action of oncogenes is not homogeneous throughout the developmental history of leukemia. Studies on different types of hematopoietic tumors have shown that the contribution of oncogenes to leukemia is mainly mediated through the epigenetic reprogramming of the leukemia-initiating target cell...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29771935/cell-iron-status-influences-macrophage-polarization
#9
Rafiou Agoro, Meriem Taleb, Valerie F J Quesniaux, Catherine Mura
Macrophages play crucial roles in innate immune response and in the priming of adaptive immunity, and are characterized by their phenotypic heterogeneity and plasticity. Reprogramming intracellular metabolism in response to microenvironmental signals is required for M1/M2 macrophage polarization and function. Here we assessed the influence of iron on the polarization of the immune response in vivo and in vitro. Iron-enriched diet increased M2 marker Arg1 and Ym1 expression in liver and peritoneal macrophages, while iron deficiency decreased Arg1 expression...
2018: PloS One
https://www.readbyqxmd.com/read/29771334/%C3%AE-catenin-activation-in-hair-follicle-dermal-stem-cells-induces-ectopic-hair-outgrowth-and-skin-fibrosis
#10
Yixin Tao, Qingchun Yang, Lei Wang, Jie Zhang, Xuming Zhu, Qianqian Sun, Yunbin Han, Qian Luo, Yushu Wang, Xizhi Guo, Ji Wu, Baojie Li, Xiao Yang, Lin He, Gang Ma
Hair follicle dermal sheath (DS) harbors hair follicle dermal stem cells (hfDSCs), which can be recruited to replenish DS and dermal papilla (DP). Cultured DS cells can differentiate into various cell lineages in vitro. However, it is unclear how its plasticity is modulated in vivo. Wnt/β-catenin signaling plays an important role in maintaining stem cells of various lineages and is required for HF development and regeneration. Here we report that activation of β-catenin in DS generates ectopic HF outgrowth (EF) by reprogramming HF epidermal cells and DS cells themselves, and endows DS cells with hair inducing ability...
May 16, 2018: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29770269/ten-years-of-progress-and-promise-of-induced-pluripotent-stem-cells-historical-origins-characteristics-mechanisms-limitations-and-potential-applications
#11
Adekunle Ebenezer Omole, Adegbenro Omotuyi John Fakoya
The discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka in 2006 was heralded as a major breakthrough of the decade in stem cell research. The ability to reprogram human somatic cells to a pluripotent embryonic stem cell-like state through the ectopic expression of a combination of embryonic transcription factors was greeted with great excitement by scientists and bioethicists. The reprogramming technology offers the opportunity to generate patient-specific stem cells for modeling human diseases, drug development and screening, and individualized regenerative cell therapy...
2018: PeerJ
https://www.readbyqxmd.com/read/29769672/pancreas-regeneration
#12
REVIEW
Qiao Zhou, Douglas A Melton
The pancreas is made from two distinct components: the exocrine pancreas, a reservoir of digestive enzymes, and the endocrine islets, the source of the vital metabolic hormone insulin. Human islets possess limited regenerative ability; loss of islet β-cells in diseases such as type 1 diabetes requires therapeutic intervention. The leading strategy for restoration of β-cell mass is through the generation and transplantation of new β-cells derived from human pluripotent stem cells. Other approaches include stimulating endogenous β-cell proliferation, reprogramming non-β-cells to β-like cells, and harvesting islets from genetically engineered animals...
May 2018: Nature
https://www.readbyqxmd.com/read/29769670/new-approaches-for-brain-repair-from-rescue-to-reprogramming
#13
REVIEW
Roger A Barker, Magdalena Götz, Malin Parmar
The ability to repair or promote regeneration within the adult human brain has been envisioned for decades. Until recently, such efforts mainly involved delivery of growth factors and cell transplants designed to rescue or replace a specific population of neurons, and the results have largely been disappointing. New approaches using stem-cell-derived cell products and direct cell reprogramming have opened up the possibility of reconstructing neural circuits and achieving better repair. In this Review we briefly summarize the history of neural repair and then discuss these new therapeutic approaches, especially with respect to chronic neurodegenerative disorders...
May 2018: Nature
https://www.readbyqxmd.com/read/29768195/reprogramming-of-chromatin-accessibility-in-somatic-cell-nuclear-transfer-is-dna-replication-independent
#14
Mohamed Nadhir Djekidel, Azusa Inoue, Shogo Matoba, Tsukasa Suzuki, Chunxia Zhang, Falong Lu, Lan Jiang, Yi Zhang
Mammalian oocytes have the ability to reset the transcriptional program of differentiated somatic cells into that of totipotent embryos through somatic cell nuclear transfer (SCNT). However, the mechanisms underlying SCNT-mediated reprogramming are largely unknown. To understand the mechanisms governing chromatin reprogramming during SCNT, we profiled DNase I hypersensitive sites (DHSs) in donor cumulus cells and one-cell stage SCNT embryos. To our surprise, the chromatin accessibility landscape of the donor cells is drastically changed to recapitulate that of the in vitro fertilization (IVF)-derived zygotes within 12 hr...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29767721/bhd-associated-kidney-cancer-exhibits-unique-molecular-characteristics-and-a-wide-variety-of-variants-in-chromatin-remodeling-genes
#15
Hisashi Hasumi, Mitsuko Furuya, Kenji Tatsuno, Shogo Yamamoto, Masaya Baba, Yukiko Hasumi, Yasuhiro Isono, Kae Suzuki, Ryosuke Jikuya, Shinji Otake, Kentaro Muraoka, Kimito Osaka, Narihiko Hayashi, Kazuhide Makiyama, Yasuhide Miyoshi, Keiichi Kondo, Noboru Nakaigawa, Takashi Kawahara, Koji Izumi, Junichi Teranishi, Yasushi Yumura, Hiroji Uemura, Yoji Nagashima, Adam R Metwalli, Laura S Schmidt, Hiroyuki Aburatani, W Marston Linehan, Masahiro Yao
Birt-Hogg-Dubé (BHD) syndrome is a hereditary kidney cancer syndrome, which predisposes patients to develop kidney cancer, cutaneous fibrofolliculomas and pulmonary cysts. The responsible gene FLCN is a tumor suppressor for kidney cancer which plays an important role in energy homeostasis through the regulation of mitochondrial oxidative metabolism. However, the process by which FLCN-deficiency leads to renal tumorigenesis is unclear. In order to clarify molecular pathogenesis of BHD-associated kidney cancer, we conducted whole-exome sequencing analysis using next-generation sequencing technology as well as metabolite analysis using LC/MS and GC/MS...
May 14, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29766333/treatment-of-donor-cells-with-recombinant-kdm4d-protein-improves-preimplantation-development-of-cloned-ovine-embryos
#16
Yumei Zhang, Qianqian Wang, Kailing Liu, Enen Gao, Hong Guan, Jian Hou
Incomplete epigenetic reprogramming is one of the major factors affecting the development of embryos cloned by somatic cell nuclear transfer (SCNT). Histone 3 lysine 9 (H3K9) trimethylation has been identified as a key barrier to efficient reprogramming by SCNT. The aim of this study was to explore a method of downregulating H3K9me3 levels in donor cells by using histone lysine demethylase (KDM) protein. When sheep fetal fibroblast cells were treated with recombinant human KDM4D protein (rhKDM4D), the levels of H3K9 trimethylation and dimethylation were both significantly decreased...
May 15, 2018: Cytotechnology
https://www.readbyqxmd.com/read/29765429/the-potentials-and-caveats-of-mesenchymal-stromal-cell-based-therapies-in-the-preterm-infant
#17
REVIEW
Judith Gronbach, Tayyab Shahzad, Sarah Radajewski, Cho-Ming Chao, Saverio Bellusci, Rory E Morty, Tobias Reicherzer, Harald Ehrhardt
Preponderance of proinflammatory signals is a characteristic feature of all acute and resulting long-term morbidities of the preterm infant. The proinflammatory actions are best characterized for bronchopulmonary dysplasia (BPD) which is the chronic lung disease of the preterm infant with lifelong restrictions of pulmonary function and severe consequences for psychomotor development and quality of life. Besides BPD, the immature brain, eye, and gut are also exposed to inflammatory injuries provoked by infection, mechanical ventilation, and oxygen toxicity...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29765321/brain-lipopolysaccharide-preconditioning-induced-gene-reprogramming-mediates-a-tolerance-state-in-electroconvulsive-shock-model-of-epilepsy
#18
Elham Amini, Mojtaba Golpich, Abdoreza S Farjam, Behnam Kamalidehghan, Zahurin Mohamed, Norlinah M Ibrahim, Abolhassan Ahmadiani, Azman A Raymond
There is increasing evidence pointing toward the role of inflammatory processes in epileptic seizures, and reciprocally, prolonged seizures induce more inflammation in the brain. In this regard, effective strategies to control epilepsy resulting from neuroinflammation could be targeted. Based on the available data, preconditioning (PC) with low dose lipopolysaccharide (LPS) through the regulation of the TLR4 signaling pathway provides neuroprotection against subsequent challenge with injury in the brain. To test this, we examined the effects of a single and chronic brain LPS PC, which is expected to lead to reduction of inflammation against epileptic seizures induced by electroconvulsive shock (ECS)...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29765034/solvent-assisted-programming-of-flat-polymer-sheets-into-reconfigurable-and-self-healing-3d-structures
#19
Yang Yang, Eugene M Terentjev, Yen Wei, Yan Ji
It is extremely challenging, yet critically desirable to convert 2D plastic films into 3D structures without any assisting equipment. Taking the advantage of solvent-induced bond-exchange reaction and elastic-plastic transition, shape programming of flat vitrimer polymer sheets offers a new way to obtain 3D structures or topologies, which are hard for traditional molding to achieve. Here we show that such programming can be achieved with a pipette, a hair dryer, and a bottle of solvent. The polymer used here is very similar to the commercial epoxy, except that a small percentage of a specific catalyst is involved to facilitate the bond-exchange reaction...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29764987/rapid-and-dynamic-alternative-splicing-impacts-the-arabidopsis-cold-response-transcriptome
#20
Cristiane P G Calixto, Wenbin Guo, Allan B James, Nikoleta A Tzioutziou, Juan C Entizne, Paige E Panter, Heather Knight, Hugh Nimmo, Runxuan Zhang, John W S Brown
Plants have adapted to tolerate and survive constantly changing environmental conditions by re-programming gene expression. The dynamics of the contribution of alternative splicing (AS) to stress responses are unknown. RNA-sequencing of a time-series of Arabidopsis thaliana plants exposed to cold determines the timing of significant AS changes. This shows a massive and rapid AS response with coincident waves of transcriptional and AS activity occurring in the first few hours of temperature reduction, and further AS throughout the cold...
May 15, 2018: Plant Cell
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