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https://www.readbyqxmd.com/read/28934717/expression-of-c-ebp%C3%AE-in-myeloid-progenitors-during-sepsis-promotes-immunosuppression
#1
Jun Dai, Ajinkya Kumbhare, Dima Youssef, Zhi Q Yao, Charles E McCall, Mohamed El Gazzar
Sepsis-induced myeloid-derived suppressor cells (MDSCs) contribute to immunosuppression associated with sepsis. We reported that the CCAAT enhancer-binding protein C/EBPβ activates microRNA (miR)-21 and miR-181b expressions, which induce transcription factor NFI-A to support the generation and expansion of MDSCs in the bone marrow and spleens of septic mice. Here, using a conditional knockout mouse model lacking C/EBPβ in the myeloid lineage, we find that without C/EBPβ, myeloid progenitor cells could not express miR-21 or miR-181b, and ectopic expression of C/EBPβ in the C/EBPβ-deficient myeloid progenitors activated the expression of the two miRNAs...
September 18, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28934506/clip-seq-analysis-of-multi-mapped-reads-discovers-novel-functional-rna-regulatory-sites-in-the-human-transcriptome
#2
Zijun Zhang, Yi Xing
Crosslinking or RNA immunoprecipitation followed by sequencing (CLIP-seq or RIP-seq) allows transcriptome-wide discovery of RNA regulatory sites. As CLIP-seq/RIP-seq reads are short, existing computational tools focus on uniquely mapped reads, while reads mapped to multiple loci are discarded. We present CLAM (CLIP-seq Analysis of Multi-mapped reads). CLAM uses an expectation-maximization algorithm to assign multi-mapped reads and calls peaks combining uniquely and multi-mapped reads. To demonstrate the utility of CLAM, we applied it to a wide range of public CLIP-seq/RIP-seq datasets involving numerous splicing factors, microRNAs and m6A RNA methylation...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934500/a-synthetic-dna-binding-inhibitor-of-sox2-guides-human-induced-pluripotent-stem-cells-to-differentiate-into-mesoderm
#3
Junichi Taniguchi, Ganesh N Pandian, Takuya Hidaka, Kaori Hashiya, Toshikazu Bando, Kyeong Kyu Kim, Hiroshi Sugiyama
Targeted differentiation of human induced pluripotent stem cells (hiPSCs) using only chemicals would have value-added clinical potential in the regeneration of complex cell types including cardiomyocytes. Despite the availability of several chemical inhibitors targeting proteins involved in signaling pathways, no bioactive synthetic DNA-binding inhibitors, targeting key cell fate-controlling genes such as SOX2, are yet available. Here, we demonstrate a novel DNA-based chemical approach to guide the differentiation of hiPSCs using pyrrole-imidazole polyamides (PIPs), which are sequence-selective DNA-binding synthetic molecules...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934497/systematic-analysis-of-dna-crosslink-repair-pathways-during-development-and-aging-in-caenorhabditis-elegans
#4
David M Wilson, Matthias Rieckher, Ashley B Williams, Björn Schumacher
DNA interstrand crosslinks (ICLs) are generated by endogenous sources and chemotherapeutics, and pose a threat to genome stability and cell survival. Using Caenorhabditis elegans mutants, we identify DNA repair factors that protect against the genotoxicity of ICLs generated by trioxsalen/ultraviolet A (TMP/UVA) during development and aging. Mutations in nucleotide excision repair (NER) components (e.g. XPA-1 and XPF-1) imparted extreme sensitivity to TMP/UVA relative to wild-type animals, manifested as developmental arrest, defects in adult tissue morphology and functionality, and shortened lifespan...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934483/the-fused-snoal_2-domain-in-the-mycobacterium-tuberculosis-sigma-factor-%C3%AF-j-modulates-promoter-recognition
#5
Kapil Goutam, Arvind K Gupta, Balasubramanian Gopal
Extra-cytoplasmic function (ECF) σ-factors are widespread in bacteria, linking environmental stimuli with changes in gene expression. These transcription factors span several phylogenetically distinct groups and are remarkably diverse in their activation and regulatory mechanisms. Here, we describe the structural and biochemical features of a Mycobacterium tuberculosis ECF factor σJ that suggests that the SnoaL_2 domain at the C-terminus can modulate the activity of this initiation factor in the absence of a cognate regulatory anti-σ factor...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934477/a-structural-map-of-oncomir-1-at-single-nucleotide-resolution
#6
Saikat Chakraborty, Yamuna Krishnan
The miR-17-92a cluster, also known as 'oncomiR-1', is an RNA transcript that plays a pivotal regulatory role in cellular processes, including the cell cycle, proliferation and apoptosis. Its dysregulation underlies the development of several cancers. Oncomir-1 comprises six constituent miRNAs, each processed with different efficiencies as a function of both developmental time and tissue type. The structural mechanisms that regulate such differential processing are unknown, and this has impeded our understanding of the dysregulation of oncomiR-1 in pathophysiology...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934464/recruitment-and-delivery-of-the-fission-yeast-rst2-transcription-factor-via-a-local-genome-structure-counteracts-repression-by-tup1-family-corepressors
#7
Ryuta Asada, Miki Umeda, Akira Adachi, Satoshi Senmatsu, Takuya Abe, Hiroshi Iwasaki, Kunihiro Ohta, Charles S Hoffman, Kouji Hirota
Transcription factors (TFs) determine the transcription activity of target genes and play a central role in controlling the transcription in response to various environmental stresses. Three dimensional genome structures such as local loops play a fundamental role in the regulation of transcription, although the link between such structures and the regulation of TF binding to cis-regulatory elements remains to be elucidated. Here, we show that during transcriptional activation of the fission yeast fbp1 gene, binding of Rst2 (a critical C2H2 zinc-finger TF) is mediated by a local loop structure...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934298/transcriptome-analysis-of-callery-pear-pyrus-calleryana-reveals-a-comprehensive-signalling-network-in-response-to-alternaria-alternata
#8
Jialiang Kan, Tingli Liu, Na Ma, Hui Li, Xiaogang Li, Jinyan Wang, Baolong Zhang, Youhong Chang, Jing Lin
The pear is an important temperate fruit worldwide that is produced by a group of species in the genus Pyrus. Callery pear (Pyrus calleryana Decne) is characterized by high resistance to multiple diseases, good adaptability, and high ornamental value, and is therefore widely planted in pear orchards for edible fruit production or as stock. Plant pathogens are a major threat to pear yield. Black spot disease, caused by the filamentous fungus Alternaria alternata, is one of the most serious diseases in pear. Elucidation of resistant genes to black spot disease is extremely important for understanding the underlying mechanisms as well as for the development of resistant cultivars...
2017: PloS One
https://www.readbyqxmd.com/read/28934264/profiling-molecular-factors-associated-with-pyknosis-and-developmental-arrest-induced-by-an-opioid-receptor-antagonist-and-dihydroartemisinin-in-plasmodium-falciparum
#9
Hiroko Asahi, Shin-Ichi Inoue, Mamoru Niikura, Keisuke Kunigo, Yutaka Suzuki, Fumie Kobayashi, Fujiro Sendo
Malaria continues to be a devastating disease, largely caused by Plasmodium falciparum infection. We investigated the effects of opioid and cannabinoid receptor antagonists on the growth of intraerythrocytic P. falciparum. The delta opioid receptor antagonist 7-benzylidenenaltrexone (BNTX) and the cannabinoid receptor antagonists rimonaband and SR144528 caused growth arrest of the parasite. Notably BNTX and the established antimalarial drug dihydroartemisinin induced prominent pyknosis in parasite cells after a short period of incubation...
2017: PloS One
https://www.readbyqxmd.com/read/28934013/reconciling-conflicting-models-for-global-control-of-cell-cycle-transcription
#10
Chun-Yi Cho, Francis C Motta, Christina M Kelliher, Anastasia Deckard, Steven B Haase
Models for the control of global cell-cycle transcription have advanced from a CDK-APC/C oscillator, a transcription factor (TF) network, to coupled CDK-APC/C and TF networks. Nonetheless, current models were challenged by a recent study that concluded that the cell-cycle transcriptional program is primarily controlled by a CDK-APC/C oscillator in budding yeast. Here we report an analysis of the transcriptome dynamics in cyclin mutant cells that were not queried in the previous study. We find that B-cyclin oscillation is not essential for control of phase-specific transcription...
September 21, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28933981/tfpi2as1-a-novel-lncrna-that-inhibits-cell-proliferation-and-migration-in-lung-cancer
#11
Shenglan Gao, Ziying Lin, Chunyan Li, Yahong Wang, Lawei Yang, Baoan Zou, Jie Chen, Jianwen Li, Zeqing Song, Gang Liu
Accumulating evidence demonstrates that a series of differentially expressed lncRNAs is important in tumorigenesis. However, the function of many of the lncRNAs in lung cancer remains elusive. In the present study, we used microarray analysis to identify lncRNAs that are dysregulated in non-small-cell lung cancer (NSCLC) as compared with normal tissues. Among the dysregulated lncRNAs, we identified TFPI2AS1, an antisense transcript of the tumor suppressor TFPI2 (tissue factor pathway inhibitor 2). TFPI2AS1 was shown to be markedly upregulated in NSCLC patient tumors as compared to paired non-tumor samples...
September 21, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28933784/inhibition-of-the-deubiquitinase-usp5-leads-to-c-maf-protein-degradation-and-myeloma-cell-apoptosis
#12
Siyu Wang, Jiaxiang Juan, Zubin Zhang, Yanyun Du, Yujia Xu, Jiefei Tong, Biyin Cao, Michael F Moran, Yuanying Zeng, Xinliang Mao
The deubiquitinase USP5 stabilizes c-Maf, a key transcription factor in multiple myeloma (MM), but the mechanisms and significance are unclear. In the present study, USP5 was found to interact with c-Maf and prevented it from degradation by decreasing its polyubiquitination level. Specifically, the 308th and 347th lysine residues in c-Maf were critical for USP5-mediated deubiquitination and stability. There are five key domains in the USP5 protein and subsequent studies revealed that the cryptic ZnF domain and the C-box domain interacted with c-Maf but the UBA1/UBA2 domain partly increased its stability...
September 21, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28933766/involvement-of-the-integrin-%C3%AE-1%C3%AE-1-in-the-progression-of-colorectal-cancer
#13
Salah Boudjadi, Gérald Bernatchez, Blanche Sénicourt, Marco Beauséjour, Pierre H Vachon, Julie C Carrier, Jean-François Beaulieu
Integrins are a family of heterodimeric glycoproteins involved in bidirectional cell signaling that participate in the regulation of cell shape, adhesion, migration, survival and proliferation. The integrin α1β1 is known to be involved in RAS/ERK proliferative pathway activation and plays an important role in fibroblast proliferation. In the small intestine, the integrin α1 subunit is present in the crypt proliferative compartment and absent in the villus. We have recently shown that the integrin α1 protein and transcript (ITGA1) are present in a large proportion of colorectal cancers (CRC) and that their expression is controlled by the MYC oncogenic factor...
July 26, 2017: Cancers
https://www.readbyqxmd.com/read/28933735/clinical-outcomes-and-co-occurring-mutations-in-patients-with-runx1-mutated-acute-myeloid-leukemia
#14
Maliha Khan, Jorge Cortes, Tapan Kadia, Kiran Naqvi, Mark Brandt, Sherry Pierce, Keyur P Patel, Gautam Borthakur, Farhad Ravandi, Marina Konopleva, Steven Kornblau, Hagop Kantarjian, Kapil Bhalla, Courtney D DiNardo
(1) Runt-related transcription factor 1 (RUNX1) mutations in acute myeloid leukemia (AML) are often associated with worse prognosis. We assessed co-occurring mutations, response to therapy, and clinical outcomes in patients with and without mutant RUNX1 (mRUNX1); (2) We analyzed 328 AML patients, including 177 patients younger than 65 years who received intensive chemotherapy and 151 patients >65 years who received hypomethylating agents. RUNX1 and co-existing mutations were identified using next-generation sequencing; (3) RUNX1 mutations were identified in 5...
July 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28933695/cooperative-interactions-enable-singular-olfactory-receptor-expression-in-mouse-olfactory-neurons
#15
Kevin Monahan, Ira Schieren, Jonah Cheung, Alice Mumbey-Wafula, Edwin S Monuki, Stavros Lomvardas
The monogenic and monoallelic expression of only one out of >1000 mouse olfactory receptor (ORs) genes requires the formation of large heterochromatic chromatin domains that sequester the OR gene clusters. Within these domains, intergenic transcriptional enhancers evade heterochromatic silencing and converge into interchromosomal hubs that assemble over the transcriptionally active OR. The significance of this nuclear organization in OR choice remains elusive. Here, we show that transcription factors Lhx2 and Ebf specify OR enhancers by binding in a functionally cooperative fashion to stereotypically spaced motifs that defy heterochromatin...
September 21, 2017: ELife
https://www.readbyqxmd.com/read/28933518/mir-564-promotes-hypertrophic-scar-via-up-regulating-tgf-%C3%AE-1
#16
Long Xiao, Tianyi Tang, Yu Huang, Jianxing Guo
BACKGROUND: To evaluate the role of microRNA564 (miR-564) in the development of hypertrophic scar and investigate the possible mechanism of this process. METHODS: The hypertrophic scar (HS) tissues and adjacent normal skin (NS) tissues were selected from 10 patients. The fibrosis-related proteins were detected via hematoxylin eosin (HE) staining, Masson staining and immunohistochemical detection. The relative expression difference of miR-564 in NS tissues and HS tissues was detected via reverse transcription-polymerase chain reaction (RT-PCR)...
September 20, 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/28933413/the-role-of-the-nrf2-are-antioxidant-system-in-preventing-cardiovascular-diseases
#17
REVIEW
Robert E Smith, Kevin Tran, Cynthia C Smith, Miranda McDonald, Pushkar Shejwalkar, Kenji Hara
It is widely believed that consuming foods and beverages that have high concentrations of antioxidants can prevent cardiovascular diseases and many types of cancer. As a result, many articles have been published that give the total antioxidant capacities of foods in vitro. However, many antioxidants behave quite differently in vivo. Some of them, such as resveratrol (in red wine) and epigallocatechin gallate or EGCG (in green tea) can activate the nuclear erythroid-2 like factor-2 (Nrf2) transcription factor...
November 11, 2016: Diseases (Basel)
https://www.readbyqxmd.com/read/28933366/the-role-of-the-mapk-signaling-topoisomerase-and-dietary-bioactives-in-controlling-cancer-incidence
#18
REVIEW
Khaled A Selim, Hend Abdelrasoul, Mohamed Aboelmagd, Ahmed M Tawila
Reactive oxygen species (ROS) are common products of mitochondrial oxidative phosphorylation, xenobiotics metabolism and are generated in response to several environmental stress conditions. Some of them play important biochemical roles in cellular signal transduction and gene transcription. On the other hand, ROS are known to be involved in a wide range of human diseases, including cancer. The excessive production of such ROS together with disruption of homeostasis detoxifying mechanisms can mediate a series of cellular oxidative stresses...
April 26, 2017: Diseases (Basel)
https://www.readbyqxmd.com/read/28933287/modulation-of-abc-transporters-by-nuclear-receptors-physiological-pathological-and-pharmacological-aspects
#19
Juan Pablo Rigalli, Guillermo Nicolás Tocchetti, Johanna Weiss
ABC transporters are membrane proteins mediating the efflux of endo- and xenobiotics. Transporter expression is not static but instead is subject to a dynamic modulation aiming at responding to changes in the internal environment and thus at maintaining homeostatic conditions. Nuclear receptors are ligand modulated transcription factors that get activated upon changes in the intracellular concentrations of the respective agonists and bind to response elements within the promoter of ABC transporters, thus modulating their expression and, consequently, their activity...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28933215/withania-somnifera-extract-protects-model-neurons-from-in-vitro-traumatic-injury
#20
Jessica N Saykally, Haris Hatic, Kristen L Keeley, Subhash C Jain, Vijayalakshmi Ravindranath, Bruce A Citron
Withania somnifera has been used in traditional medicine for a variety of neural disorders. Recently, chronic neurodegenerative conditions have been shown to benefit from treatment with this extract. To evaluate the action of this extract on traumatically injured neurons, the efficacy of W. somnifera root extract as a neuroprotective agent was examined in cultured model neurons exposed to an in vitro injury system designed to mimic mild traumatic brain injury (TBI). Neuronal health was evaluated by staining with annexin V (an early, apoptotic feature) and monitoring released lactate dehydrogenase activity (a terminal cell loss parameter)...
July 2017: Cell Transplantation
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