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https://www.readbyqxmd.com/read/28092686/epigenomic-reprogramming-during-pancreatic-cancer-progression-links-anabolic-glucose-metabolism-to-distant-metastasis
#1
Oliver G McDonald, Xin Li, Tyler Saunders, Rakel Tryggvadottir, Samantha J Mentch, Marc O Warmoes, Anna E Word, Alessandro Carrer, Tal H Salz, Sonoko Natsume, Kimberly M Stauffer, Alvin Makohon-Moore, Yi Zhong, Hao Wu, Kathryn E Wellen, Jason W Locasale, Christine A Iacobuzio-Donahue, Andrew P Feinberg
During the progression of pancreatic ductal adenocarcinoma (PDAC), heterogeneous subclonal populations emerge that drive primary tumor growth, regional spread, distant metastasis, and patient death. However, the genetics of metastases largely reflects that of the primary tumor in untreated patients, and PDAC driver mutations are shared by all subclones. This raises the possibility that an epigenetic process might operate during metastasis. Here we report large-scale reprogramming of chromatin modifications during the natural evolution of distant metastasis...
January 16, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28092373/chronic-signaling-via-the-metabolic-checkpoint-kinase-mtorc1-induces-macrophage-granuloma-formation-and-marks-sarcoidosis-progression
#2
Monika Linke, Ha Thi Thanh Pham, Karl Katholnig, Thomas Schnöller, Anne Miller, Florian Demel, Birgit Schütz, Margit Rosner, Boris Kovacic, Nyamdelger Sukhbaatar, Birgit Niederreiter, Stephan Blüml, Peter Kuess, Veronika Sexl, Mathias Müller, Mario Mikula, Wolfram Weckwerth, Arvand Haschemi, Martin Susani, Markus Hengstschläger, Michael J Gambello, Thomas Weichhart
The aggregation of hypertrophic macrophages constitutes the basis of all granulomatous diseases, such as tuberculosis or sarcoidosis, and is decisive for disease pathogenesis. However, macrophage-intrinsic pathways driving granuloma initiation and maintenance remain elusive. We found that activation of the metabolic checkpoint kinase mTORC1 in macrophages by deletion of the gene encoding tuberous sclerosis 2 (Tsc2) was sufficient to induce hypertrophy and proliferation, resulting in excessive granuloma formation in vivo...
January 16, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28090081/metabolic-reprogramming-and-tolerance-during-sepsis-induced-aki
#3
REVIEW
Hernando Gómez, John A Kellum, Claudio Ronco
The host defence against infection is an adaptive response in which several mechanisms are deployed to decrease the pathogen load, limit tissue injury and restore homeostasis. In the past few years new evidence has suggested that the ability of the immune system to limit the microbial burden - termed resistance - might not be the only defence mechanism. In fact, the capacity of the host to decrease its own susceptibility to inflammation- induced tissue damage - termed tolerance - might be as important as resistance in determining the outcome of the infection...
January 16, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28089995/systematic-evaluation-of-markers-used-for-the-identification-of-human-induced-pluripotent-stem-cells
#4
Sumitha Prameela Bharathan, Kannan Vrindavan Manian, Syed Mohammed Musheer Aalam, Dhavapriya Palani, Prashant Ajit Deshpande, Mankuzhy Damodaran Pratheesh, Alok Srivastava, Shaji Ramachandran Velayudhan
Low efficiency of somatic cell reprogramming and heterogeneity among human induced pluripotent stem cells (hiPSCs) demand extensive characterization of isolated clones before their use in downstream applications. By monitoring human fibroblasts undergoing reprogramming for their morphological changes and expression of fibroblast (CD13), pluripotency markers (SSEA-4 and TRA-1-60) and a retrovirally expressed red fluorescent protein (RV-RFP), we compared the efficiency of these features to identify bona fide hiPSC colonies...
January 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28089908/human-aml-ipscs-reacquire-leukemic-properties-after-differentiation-and-model-clonal-variation-of-disease
#5
Mark P Chao, Andrew J Gentles, Susmita Chatterjee, Feng Lan, Andreas Reinisch, M Ryan Corces, Seethu Xavy, Jinfeng Shen, Daniel Haag, Soham Chanda, Rahul Sinha, Rachel M Morganti, Toshinobu Nishimura, Mohamed Ameen, Haodi Wu, Marius Wernig, Joseph C Wu, Ravindra Majeti
Understanding the relative contributions of genetic and epigenetic abnormalities to acute myeloid leukemia (AML) should assist integrated design of targeted therapies. In this study, we generated induced pluripotent stem cells (iPSCs) from AML patient samples harboring MLL rearrangements and found that they retained leukemic mutations but reset leukemic DNA methylation/gene expression patterns. AML-iPSCs lacked leukemic potential, but when differentiated into hematopoietic cells, they reacquired the ability to give rise to leukemia in vivo and reestablished leukemic DNA methylation/gene expression patterns, including an aberrant MLL signature...
December 26, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/28089831/monomethyltransferase-setd8-regulates-breast-cancer-metabolism-via-stabilizing-hypoxia-inducible-factor-1%C3%AE
#6
Run Huang, Yang Yu, Xiangyun Zong, Xiaolin Li, Lisi Ma, Qi Zheng
SETD8 is a methyltransferase that specifically catalyzes the monomethylation of lysine 20 on histone H4. Previous studies have demonstrated that SETD8 is associated with proper cell cycle progression, DNA damage response, and transcriptional regulation. A recent study revealed that SETD8 played an important role in epithelial-mesenchymal transition (EMT) in association with TWIST and enhanced metastatic potential of breast cancer cells. However, the contribution of SETD8 to metabolism reprogramming, one hallmark of cancer, has never been reported...
January 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28088583/environmental-carcinogenesis-and-ph-homeostasis-not-only-a-matter-of-dysregulated-metabolism
#7
REVIEW
Kévin Hardonniere, Laurence Huc, Odile Sergent, Jørn A Holme, Dominique Lagadic-Gossmann
According to the World Health Organization, around 20% of all cancers would be due to environmental factors. Among these factors, several chemicals are indeed well recognized carcinogens. The widespread contaminant benzo[a]pyrene (B[a]P), an often used model carcinogen of the polycyclic aromatic hydrocarbons' family, has been suggested to target most, if not all, cancer hallmarks described by Hanahan and Weinberg. It is classified as a group I carcinogen by the International Agency for Research on Cancer; however, the precise intracellular mechanisms underlying its carcinogenic properties remain yet to be thoroughly defined...
January 11, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28088067/tuning-neural-circuits-by-turning-the-interneuron-knob
#8
REVIEW
Nathalie Dehorter, Nicolás Marichal, Oscar Marín, Benedikt Berninger
Interneurons play a critical role in sculpting neuronal circuit activity and their dysfunction can result in neurological and neuropsychiatric disorders. To temporally structure and balance neuronal activity in the adult brain interneurons display a remarkable degree of subclass-specific plasticity, of which the underlying molecular mechanisms have recently begun to be elucidated. Grafting new interneurons to pre-existing neuronal networks allows for amelioration of circuit dysfunction in rodent models of neurological disease and can reopen critical windows for circuit plasticity...
January 11, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28088028/role-of-small-rnas-in-epigenetic-reprogramming-during-plant-sexual-reproduction
#9
REVIEW
German Martinez, Claudia Köhler
Sexual reproduction, the formation of a new individual from specialized reproductive cells after fertilization, involves the precise orchestration of different developmental and genomic processes. These processes are to a large extent governed by small RNAs (sRNAs) that either belong to the class of micro RNAs (miRNAs) or small-interfering RNAs (siRNAs). The latter are derived from transposable elements (TEs) and involved in genome defense and transgenerational inheritance of heterochromatin identity, ensuring genome stability...
January 11, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28087256/manganese-superoxide-dismutase-and-glutathione-peroxidase-1-contribute-to-the-rise-and-fall-of-mitochondrial-reactive-oxygen-species-which-drive-oncogenesis
#10
REVIEW
Dede N Ekoue, Chenxia He, Alan M Diamond, Marcelo G Bonini
Reactive oxygen species (ROS) largely originating in the mitochondria play essential roles in the metabolic and (epi)genetic reprogramming of cancer cell evolution towards more aggressive phenotypes. Recent studies have indicated that the activity of superoxide dismutase (SOD2) may promote tumor progression by serving as a source of hydrogen peroxide (H2O2). H2O2 is a form of ROS that is particularly active as a redox agent affecting cell signaling due to its ability to freely diffuse out of the mitochondria and alter redox active amino acid residues on regulatory proteins...
January 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28087003/in%C3%A2-vitro-generation-of-renal-tubular-epithelial-cells-from-fibroblasts-implications-for-precision-and-regenerative-medicine-in-nephrology
#11
Christina M Wyatt, Nicole Dubois
Prior efforts to generate renal epithelial cells in vitro have relied on pluripotent or bone marrow-derived mesenchymal stem cells. A recent publication in Nature Cell Biology describes the generation of induced tubular epithelial cells from fibroblasts, potentially offering a novel platform for personalized drug toxicity screening and in vitro disease modeling. This report serves as a promising proof of principle study and opens future research directions, including the optimization of the reprogramming process, efficient translation to adult human fibroblasts, and the generation of highly specific functional renal cell types...
February 2017: Kidney International
https://www.readbyqxmd.com/read/28086780/the-zygosaccharomyces-bailii-transcription-factor-haa1-is-required-for-acetic-acid-and-copper-stress-responses-suggesting-subfunctionalization-of-the-ancestral-bifunctional-protein-haa1-cup2
#12
Margarida Palma, Paulo Jorge Dias, Filipa de Canaveira Roque, Laura Luzia, Joana Fernandes Guerreiro, Isabel Sá-Correia
BACKGROUND: The food spoilage yeast species Zygosaccharomyces bailii exhibits an extraordinary capacity to tolerate weak acids, in particular acetic acid. In Saccharomyces cerevisiae, the transcription factor Haa1 (ScHaa1) is considered the main player in genomic expression reprogramming in response to acetic acid stress, but the role of its homologue in Z. bailii (ZbHaa1) is unknown. RESULTS: In this study it is demonstrated that ZbHaa1 is a ScHaa1 functional homologue by rescuing the acetic acid susceptibility phenotype of S...
January 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28079253/epithelial-mesenchymal-transition-emt-a-biological-process-in-the-development-stem-cell-differentiation-and-tumorigenesis
#13
REVIEW
Tong Chen, Yanan You, Hua Jiang, Zack Z Wang
The lineage transition between epithelium and mesenchyme is a process known as epithelial-mesenchymal transition (EMT), by which polarized epithelial cells lose their adhesion property and obtain mesenchymal cell phenotypes. EMT is a biological process that is often involved in embryogenesis and diseases, such as cancer invasion and metastasis. The EMT and the reverse process, mesenchymal-epithelial transition (MET), also play important roles in stem cell differentiation and de-differentiation (or reprogramming)...
January 12, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28079126/detecting-n-6-methyladenosine-sites-from-rna-transcriptomes-using-ensemble-support-vector-machines
#14
Wei Chen, Pengwei Xing, Quan Zou
As one of the most abundant RNA post-transcriptional modifications, N(6)-methyladenosine (m(6)A) involves in a broad spectrum of biological and physiological processes ranging from mRNA splicing and stability to cell differentiation and reprogramming. However, experimental identification of m(6)A sites is expensive and laborious. Therefore, it is urgent to develop computational methods for reliable prediction of m(6)A sites from primary RNA sequences. In the current study, a new method called RAM-ESVM was developed for detecting m(6)A sites from Saccharomyces cerevisiae transcriptome, which employed ensemble support vector machine classifiers and novel sequence features...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28077646/adenovirus-modulates-toll-like-receptor-4-signaling-by-reprogramming-orp1l-vap-protein-contacts-for-cholesterol-transport-from-endosomes-to-the-endoplasmic-reticulum
#15
Nicholas L Cianciola, Stacey Chung, Danny Manor, Cathleen R Carlin
: Human adenoviruses generally cause mild self-limiting infections but can lead to serious disease and even be fatal in high-risk individuals, underscoring the importance of understanding how the virus counteracts host defense mechanisms. This study had two goals. First, determine the molecular basis of cholesterol homeostatic responses induced by the early region 3 membrane protein RIDα via its direct interaction with the sterol-binding protein ORP1L. Second, determine how this interaction regulates innate immunity to adenovirus...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077297/exosomes-key-mediators-of-metastasis-and-pre-metastatic-niche-formation
#16
REVIEW
Richard J Lobb, Luize G Lima, Andreas Möller
While tumour cells are classically known to communicate via direct cell-to-cell contact and the secretion of soluble protein-based factors such as cytokines and growth factors, alternative novel mechanisms that promote tumour progression have recently emerged. Now, new critical components of the secretome thought to be involved in tumour progression are exosomes, small vesicles of endocytic origin that carry a variety of bioactive molecules, including proteins, lipids, RNA, as well as DNA molecules. Cancer cell-derived exosomes have been shown to participate in crucial steps of metastatic spread of a primary tumour, ranging from oncogenic reprogramming of malignant cells to formation of pre-metastatic niches...
January 8, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28077171/prostate-specific-il-6-transgene-autonomously-induce-prostate-neoplasm-through-amplifying-inflammation-in-the-prostate-and-peri-prostatic-adipose-tissue
#17
Gang Liu, Jinyu Zhang, Lewis Frey, Xiao Gang, Kongming Wu, Qian Liu, Michael Lilly, Jennifer Wu
BACKGROUND: The causative role of the pro-inflammatory cytokine IL-6 in prostate cancer progression has been well established at molecular level. However, whether and how IL-6 may play a role in prostate cancer risk and development is not well defined. One limitation factor to acquiring this knowledge is the lack of appropriate animal models. METHODS: We generated a novel line of prostate-specific IL-6 transgenic mouse model. We compared the prostate pathology, tumorigenic signaling components, and prostate tumor microenvironment of the IL-6 transgenic mice with wild type littermates...
January 11, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28076886/the-ectomycorrhizal-basidiomycete-hebeloma-cylindrosporum-undergoes-early-waves-of-transcriptional-reprogramming-prior-to-symbiotic-structures-differentiation
#18
Jeanne Doré, Annegret Kohler, Audrey Dubost, Hope Hundley, Vasanth Singan, Yi Peng, Alan Kuo, Igor V Grigoriev, Francis Martin, Roland Marmeisse, And Gilles Gay
To clarify the early molecular interaction between ectomycorrhizal partners, we performed a RNA-Seq study of transcriptome reprogramming of the basidiomycete Hebeloma cylindrosporum before symbiotic structure differentiation with Pinus pinaster. Mycorrhiza transcriptome was studied for comparison. By reference to asymbiotic mycelium, 47 and 46 genes were specifically up-regulated over five-fold (p≤0.05) upon rhizosphere colonization and root adhesion respectively. Other 45 were up-regulated throughout the symbiotic interaction, from rhizosphere colonization to differentiated mycorrhizas, whereas 274 were specifically up-regulated in mycorrhizas...
January 11, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28075486/highly-expandable-human-ips-cell-derived-neural-progenitor-cells-npc-and-neurons-for-central-nervous-system-disease-modeling-and-high-throughput-screening
#19
Chialin Cheng, Daniel M Fass, Kat Folz-Donahue, Marcy E MacDonald, Stephen J Haggarty
Reprogramming of human somatic cells into induced pluripotent stem (iPS) cells has greatly expanded the set of research tools available to investigate the molecular and cellular mechanisms underlying central nervous system (CNS) disorders. Realizing the promise of iPS cell technology for the identification of novel therapeutic targets and for high-throughput drug screening requires implementation of methods for the large-scale production of defined CNS cell types. Here we describe a protocol for generating stable, highly expandable, iPS cell-derived CNS neural progenitor cells (NPC) using multi-dimensional fluorescence activated cell sorting (FACS) to purify NPC defined by cell surface markers...
January 11, 2017: Current Protocols in Human Genetics
https://www.readbyqxmd.com/read/28075482/human-induced-pluripotent-stem-hips-cells-from-urine-samples-a-non-integrative-and-feeder-free-reprogramming-strategy
#20
Clara Steichen, Karim Si-Tayeb, Fanny Wulkan, Thayane Crestani, Graça Rosas, Rafael Dariolli, Alexandre C Pereira, Jose E Krieger
Human induced pluripotent stem (hiPS) cell technology has already revolutionized some aspects of fundamental and applied research such as study of disease mechanisms and pharmacology screening. The first clinical trial using hiPS cell-derived cells began in Japan, only 10 years after the publication of the proof-of concept article. In this exciting context, strategies to generate hiPS cells have evolved quickly, tending towards non-invasive protocols to sample somatic cells combined with "safer" reprogramming strategies...
January 11, 2017: Current Protocols in Human Genetics
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