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https://www.readbyqxmd.com/read/28716722/dynamics-of-proliferative-and-quiescent-stem-cells-in-liver-homeostasis-and-injury
#1
Wanlu Cao, Kan Chen, Michiel Bolkestein, Yuebang Yin, Monique M A Verstegen, Marcel J C Bijvelds, Wenshi Wang, Nesrin Tuysuz, Derk Ten Berge, Dave Sprengers, Herold J Metselaar, Luc J W van der Laan, Jaap Kwekkeboom, Ron Smits, Maikel P Peppelenbosch, Qiuwei Pan
BACKGROUND & AIMS: Adult liver stem cells are usually maintained in a quiescent/slow cycling state. However, a proliferative population, marked by leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), was recently identified as an important liver stem cell population. We aimed to investigate the dynamics and functions of proliferative and quiescent stem cells in healthy and injured livers. METHODS: We studied LGR5-positive stem cells using diphtheria toxin receptor (DTR) and green fluorescent protein (GFP) knock-in mice...
July 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28680748/mycn-is-an-immunosuppressive-oncogene-dampening-the-expression-of-ligands-for-nk-cell-activating-receptors-in-human-high-risk-neuroblastoma
#2
Elisa Brandetti, Irene Veneziani, Ombretta Melaiu, Annalisa Pezzolo, Aurora Castellano, Renata Boldrini, Elisa Ferretti, Doriana Fruci, Lorenzo Moretta, Vito Pistoia, Franco Locatelli, Loredana Cifaldi
Neuroblastoma (NB) is the most common extracranial solid tumor occurring in childhood. Amplification of the MYCN oncogene is associated with poor prognosis. Downregulation on NB cells of ligands recognized by Natural Killer (NK) cell-activating receptors, involved in tumor cell recognition and lysis, may contribute to tumor progression and relapse. Here, we demonstrate that in human NB cell lines MYCN expression inversely correlates with that of ligands recognized by NKG2D and DNAM1 activating receptors in human NB cell lines...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28678681/profiling-of-oxbs-450k-5-hydroxymethylcytosine-in-human-placenta-and-brain-reveals-enrichment-at-imprinted-loci
#3
Jose Ramon Hernandez Mora, Marta Sanchez-Delgado, Paolo Petazzi, Sebastian Moran, Manel Esteller, Isabel Iglesias-Platas, David Monk
DNA methylation (5-methylcytosine, 5mC) is involved in many cellular processes and is an epigenetic mechanism primarily associated with transcriptional repression. The recent discovery that 5mC can be oxidized to 5-hydromethylcytosine (5hmC) by TET proteins has revealed the "sixth base" of DNA and provides additional complexity to what was originally thought to be a stable repressive mark. However, our knowledge of the genome-wide distribution of 5hmC in different tissues is currently limited. Here, we sought to define loci enriched for 5hmC in the placenta genome by combining oxidative bisulphite (oxBS) treatment with high-density Illumina Infinium HumanMethylation450 methylation arrays and to compare our results with those obtained in brain...
July 5, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28668389/inducible-liver-specific-overexpression-of-gankyrin-in-zebrafish-results-in-spontaneous-intrahepatic-cholangiocarcinoma-and-hepatocellular-carcinoma-formation
#4
Shin-Jie Huang, Chih-Lun Cheng, Jim-Ray Chen, Hong-Yi Gong, Wangta Liu, Jen-Leih Wu
Liver cancer is the second leading cause of death worldwide. As such, establishing animal models of the disease is important for both basic and translational studies that move toward developing new therapies. Gankyrin is a critical oncoprotein in the genetic control of liver pathology. In order to evaluate the oncogenic role of gankyrin without cancer cell inoculation and drug treatment, we overexpressed gankyrin under the control of the fabp10a promoter. A Tet-Off system was used to drive expression in hepatocytes...
June 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28660881/ten-eleven-translocation-2-interacts-with-forkhead-box-o3-and-regulates-adult-neurogenesis
#5
Xuekun Li, Bing Yao, Li Chen, Yunhee Kang, Yujing Li, Ying Cheng, Liping Li, Li Lin, Zhiqin Wang, Mengli Wang, Feng Pan, Qing Dai, Wei Zhang, Hao Wu, Qiang Shu, Zhaohui Qin, Chuan He, Mingjiang Xu, Peng Jin
Emerging evidence suggests that active DNA demethylation machinery plays important epigenetic roles in mammalian adult neurogenesis; however, the precise molecular mechanisms and critical functional players of DNA demethylation in this process remain largely unexplored. Ten-eleven translocation (Tet) proteins convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and its downstream derivatives. Here we show that 5hmC is elevated during the differentiation of adult neural stem cells (aNSCs), and Tet2 is primarily responsible for modulating 5hmC dynamics...
June 29, 2017: Nature Communications
https://www.readbyqxmd.com/read/28652359/triplet-triplet-energy-transfer-in-artificial-and-natural-photosynthetic-antennas
#6
Junming Ho, Elizabeth Kish, Dalvin D Méndez-Hernández, Katherine WongCarter, Smitha Pillai, Gerdenis Kodis, Jens Niklas, Oleg G Poluektov, Devens Gust, Thomas A Moore, Ana L Moore, Victor S Batista, Bruno Robert
In photosynthetic organisms, protection against photooxidative stress due to singlet oxygen is provided by carotenoid molecules, which quench chlorophyll triplet species before they can sensitize singlet oxygen formation. In anoxygenic photosynthetic organisms, in which exposure to oxygen is low, chlorophyll-to-carotenoid triplet-triplet energy transfer (T-TET) is slow, in the tens of nanoseconds range, whereas it is ultrafast in the oxygen-rich chloroplasts of oxygen-evolving photosynthetic organisms. To better understand the structural features and resulting electronic coupling that leads to T-TET dynamics adapted to ambient oxygen activity, we have carried out experimental and theoretical studies of two isomeric carotenoporphyrin molecular dyads having different conformations and therefore different interchromophore electronic interactions...
June 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28651214/dna-methylation-and-the-preservation-of-cell-identity
#7
REVIEW
Ozren Bogdanović, Ryan Lister
DNA methylation is a major epigenetic modification of vertebrate genomes that is mostly associated with transcriptional repression. During embryogenesis, DNA methylation together with other epigenetic factors plays an essential role in selecting and maintaining cell identity. Recent technological advances are now allowing for the exploration of this mark at unprecedented resolution. This has resulted in a wealth of studies describing the developmental roles of DNA methylation in various vertebrate model systems...
June 23, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28642707/tetrandrine-an-activator-of-autophagy-induces-autophagic-cell-death-via-pkc-%C3%AE-inhibition-and-mtor-dependent-mechanisms
#8
Vincent Kam Wai Wong, Wu Zeng, Juan Chen, Xiao Jun Yao, Elaine Lai Han Leung, Qian Qian Wang, Pauline Chiu, Ben C B Ko, Betty Yuen Kwan Law
Emerging evidence suggests the therapeutic role of autophagic modulators in cancer therapy. This study aims to identify novel traditional Chinese medicinal herbs as potential anti-tumor agents through autophagic induction, which finally lead to autophagy mediated-cell death in apoptosis-resistant cancer cells. Using bioactivity-guided purification, we identified tetrandrine (Tet) from herbal plant, Radix stephaniae tetrandrae, as an inducer of autophagy. Across a number of cancer cell lines, we found that breast cancer cells treated with tetrandrine show an increase autophagic flux and formation of autophagosomes...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28642344/a-role-for-tet2-in-parathyroid-carcinoma
#9
Elham Barazeghi, Anthony J Gill, Stan Sidhu, Olov Norlén, Roberto Dina, F Fausto Palazzo, Per Hellman, Peter Stålberg, Gunnar Westin
Primary hyperparathyroidism (pHPT) is rarely caused by parathyroid carcinoma (PC, <1-5% of pHPT cases). The TET proteins oxidize the epigenetic mark 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) and inactivation by mutation or epigenetic deregulation of TET1 and TET2 play important roles in various cancers. Recently, we found that 5hmC was severely reduced in all of the analyzed PCs and with deranged expression of TET1 for the majority of PCs. Here, we have examined the expression of the TET2 protein in 15 5hmC-negative PCs from patients who had local invasion or metastases...
July 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28629934/recent-advances-in-leishmania-reverse-genetics-manipulating-a-manipulative-parasite
#10
REVIEW
Samuel M Duncan, Nathaniel G Jones, Jeremy C Mottram
In this review we describe the expanding repertoire of molecular tools with which to study gene function in Leishmania. Specifically we review the tools available for studying functions of essential genes, such as plasmid shuffle and DiCre, as well as the rapidly expanding portfolio of available CRISPR/Cas9 approaches for large scale gene knockout and endogenous tagging. We include detail on approaches that allow the direct manipulation of RNA using RNAi and protein levels via Tet or DiCre induced overexpression and destabilization domain mediated degradation...
June 16, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28623268/ascorbate-induces-apoptosis-in-melanoma-cells-by-suppressing-clusterin-expression
#11
Sushmita Mustafi, David W Sant, Zhao-Jun Liu, Gaofeng Wang
Pharmacological levels of ascorbate have long been suggested as a potential treatment of cancer. However, we observed that EC50 of ascorbate was at a similar level for cultured healthy melanocytes and melanoma cells, suggesting a limit of pharmacological ascorbate in treating cancer. Loss of 5-hydroxymethylcytosine (5 hmC) is an epigenetic hallmark of cancer and ascorbate promotes 5 hmC generation by serving as a cofactor for TET methylcytosine dioxygenases. Our previous work demonstrated that ascorbate treatment at physiological level (100 μM) increased 5 hmC content in melanoma cells toward the level of healthy melanocytes...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28613399/immunosuppressive-efficacy-of-tetrandrine-combined-with-methylprednisolone-against-mitogen-activated-peripheral-blood-mononuclear-cells-of-hemodialysis-patients
#12
Wencheng Xu, Kehan Meng, Junichi Kusano, Hiroto Matsuda, Yoshikazu Hara, Yoshiaki Fujii, Shinya Suzuki, Eiki Ando, Xiaoqin Wang, Yuanchao Tu, Sachiko Tanaka, Kentaro Sugiyama, Haruki Yamada, Toshihiko Hirano
Immunosuppressive therapy for prevention of acute rejection episode occasionally causes serious adverse effects, and thus it is important to develop new therapeutic approach for renal transplant recipients. This study evaluated the immunosuppressive pharmacodynamics of tetrandrine (TET) and/or methylprednisolone (MP) in hemodialysis patients in vitro by using the peripheral blood mononuclear cells (PBMCs) isolated from whole blood of hemodialysis patients. The median (range) of MP IC50 values against the proliferation of patients PBMCs was 7...
June 14, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28609472/no-evidence-for-genome-editing-in-mouse-zygotes-and-hek293t-human-cell-line-using-the-dna-guided-natronobacterium-gregoryi-argonaute-ngago
#13
Nay Chi Khin, Jenna L Lowe, Lora M Jensen, Gaetan Burgio
A recently published research article reported that the extreme halophile archaebacterium Natronobacterium gregoryi Argonaute enzyme (NgAgo) could cleave the cellular DNA under physiological temperature conditions in cell line and be implemented as an alternative to CRISPR/Cas9 genome editing technology. We assessed this claim in mouse zygotes for four loci (Sptb, Tet-1, Tet-2 and Tet-3) and in the human HEK293T cell line for the EMX1 locus. Over 100 zygotes were microinjected with nls-NgAgo-GK plasmid provided from Addgene and various concentrations of 5'-phosphorylated guide DNA (gDNA) from 2...
2017: PloS One
https://www.readbyqxmd.com/read/28607447/fam83h-is-involved-in-the-progression-of-hepatocellular-carcinoma-and-is-regulated-by-myc
#14
Kyoung Min Kim, See-Hyoung Park, Jun Sang Bae, Sang Jae Noh, Guo-Zhong Tao, Jung Ryul Kim, Keun Sang Kwon, Ho Sung Park, Byung-Hyun Park, Ho Lee, Myoung Ja Chung, Woo Sung Moon, Karl G Sylvester, Kyu Yun Jang
Recently, the roles of FAM83H in tumorigenesis have been interested and increased expression of FAM83H and MYC in hepatocellular carcinoma (HCC) have been reported. Therefore, we investigated the expression and role of FAM83H in 163 human HCCs and further investigated the relationship between FAM83H and oncogene MYC. The expression of FAM83H is elevated in liver cancer cells, and nuclear expression of FAM83H predicted shorter survival of HCC patients. In HLE and HepG2 HCC cells, knock-down of FAM83H inhibited proliferation and invasive activity of HCC cells...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28601635/silencing-hif-1%C3%AE-induces-tet2-expression-and-augments-ascorbic-acid-induced-5-hydroxymethylation-of-dna-in-human-metastatic-melanoma-cells
#15
Adam P Fischer, Sarah L Miles
Expression and function of Ten-eleven translocation (TET) enzymes, which initiate DNA demethylation by catalyzing the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine (5 hmC) on methylated DNA, are frequently lost in malignant tissue. This ultimately results in lost expression of methylated tumor suppressor genes. Many malignancies, including melanoma, also aberrantly overexpress the oncogenic hypoxia inducible factor-1α (HIF-1α) transcription factor, however the association between HIF-1α and TET enzyme expression is largely uninvestigated...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28600952/time-course-of-tau-toxicity-and-pharmacologic-prevention-in-a-cell%C3%A2-model-of-tauopathy
#16
Marcus Pickhardt, Jacek Biernat, Sabrina Hübschmann, Frank J A Dennissen, Thomas Timm, Annukka Aho, Eva-Maria Mandelkow, Eckhard Mandelkow
The aggregation of Tau protein is a hallmark of neurodegenerative diseases including Alzheimer's disease. Previously, we generated a cell model of tauopathy based on the 4-repeat domain with the FTDP-17 mutation ΔK280 (Tau(4RDΔK)) which is expressed in a regulatable fashion (tet-on). The deletion variant ΔK280 is highly amyloidogenic and forms fibrous aggregates in neuroblastoma N2a cells staining with the reporter dye Thioflavin S. The aggregation of Tau(4RDΔK) is toxic, contrary to wildtype or anti-aggregant variants of the protein...
May 3, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28597304/improved-tet-on-and-tet-off-systems-for-tetracycline-regulated-expression-of-genes-in-candida
#17
Swati Bijlani, Anubhav S Nahar, K Ganesan
Tetracycline-regulated expression of genes is often used for functional analysis of Candida albicans genes. However, the widely used Tet-On system has certain limitations such as prolonged lag time (up to 8 h) for induction and non-uniform expression among the cells. We speculated that poor expression of tetracycline-controlled transactivator (Tet-transactivator) from CaADH1 promoter could be responsible for this, and thus compared the effect of expressing this protein under the control of CaADH1, CaTDH3 and CaRP10 promoters on the expression of GFP from the TET promoter...
June 8, 2017: Current Genetics
https://www.readbyqxmd.com/read/28596758/a-functional-metagenomic-analysis-of-tetracycline-resistance-in-cheese-bacteria
#18
Ana B Flórez, Lucía Vázquez, Baltasar Mayo
Metagenomic techniques have been successfully used to monitor antibiotic resistance genes in environmental, animal and human ecosystems. However, despite the claim that the food chain plays a key role in the spread of antibiotic resistance, metagenomic analysis has scarcely been used to investigate food systems. The present work reports a functional metagenomic analysis of the prevalence and evolution of tetracycline resistance determinants in a raw-milk, blue-veined cheese during manufacturing and ripening...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28574626/assessment-of-phenotypic-and-genotypic-antibiotic-susceptibility-of-vaginal-lactobacillus-sp
#19
Jelena Štšepetova, Heleri Taelma, Imbi Smidt, Pirje Hütt, Eleri Lapp, Evi Aotäht, Reet Mändar
AIM: To assess antibiotic susceptibility of vaginal lactobacilli strains and provide the data required for assessing the potential of antibiotic resistance risk of new strains selected as probiotic. METHODS AND RESULTS: Potential probiotic vaginal lactobacilli used in the study included 31 vaginal strains of Lactobacillus crispatus, (n=27), L. gasseri (n=3) and L. jensenii (n=1) obtained from the collection of Competence Centre on Health Technologies. Two commercial probiotic strains were used as controls (L...
June 2, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28529589/tetrandrine-triggers-an-alternative-autophagy-in-du145-cells
#20
Wei Qiu, Ai-Li Zhang, Ye Tian
Tetrandrine (Tet), a potent lysosomal inhibitor, blocks autophagic flux and induces cancer cell death. Previously, the present authors identified the prostate cancer cell line DU145 to exhibit high sensitivity towards Tet in 11 cancer cell lines. In the present study, autophagy in Tet-treated DU145 cells was investigated. Similar to other cell lines, such as PC-3 and 786-O cells, Tet neutralized the acidity of lysosome and blocked autophagy in DU145 cells. However, Tet failed to induce microtubule-associated protein 1 light chain 3 (LC3) conversion in DU145 cells...
May 2017: Oncology Letters
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