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https://www.readbyqxmd.com/read/28531964/non-electron-transfer-chain-mitochondrial-defects-differently-regulate-hif-1%C3%AE-degradation-and-transcription
#1
Antonina N Shvetsova, Daniela Mennerich, Juha M Kerätär, J Kalervo Hiltunen, Thomas Kietzmann
Mitochondria are the main consumers of molecular O2 in a cell as well as an abundant source of reactive oxygen species (ROS). Both, molecular oxygen and ROS are powerful regulators of the hypoxia-inducible factor-1α-subunit (HIF-α). While a number of mechanisms in the oxygen-dependent HIF-α regulation are quite well known, the view with respect to mitochondria is less clear. Several approaches using pharmacological or genetic tools targeting the mitochondrial electron transport chain (ETC) indicated that ROS, mainly formed at the Rieske cluster of complex III of the ETC, are drivers of HIF-1α activation...
May 8, 2017: Redox Biology
https://www.readbyqxmd.com/read/28531759/interferon-regulatory-factors-a-key-to-tumour-immunity
#2
REVIEW
Yan-Jie Chen, Jing Li, Nan Lu, Xi-Zhong Shen
Interferon regulatory factors (IRFs), which have 10 members, belong to the transcription factor family and were named because of the regulation of interferon expression. They play important roles in the immune regulation, cell differentiation, cell apoptosis, and cell cycle regulation. This article will review the functional characteristics and immune activity of the family members, especially in the role of cell differentiation and autoimmune diseases. Intensive studies will help uncover the pathogenesis of the disease in a more comprehensive view, and provide novel targets for disease treatment...
May 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28531375/mouse-minipuberty-coincides-with-gonocyte-transformation-into-spermatogonial-stem-cells-a-model-for-human-minipuberty
#3
Ruili Li, Amanda Vannitamby, Sarah S K Yue, David Handelsman, John Hutson
As the transient postnatal hormone surge in humans, known as 'minipuberty', occurs simultaneously with key steps in germ-cell development, we investigated whether similar changes occur in the hypothalamic-pituitary-testicular axis of neonatal mice at a time that would coincide with gonocyte transformation into spermatogonial stem cells (SSC). Serum and testes were collected from C57Bl/6 mice at embryonic Day 17 (E17), birth (postnatal Day 0; P0) and daily until P10. Serum FSH and testosterone levels in both serum and testes were analysed and gene expression of FSH receptor (Fshr), luteinising hormone receptor (Lhr), anti-Müllerian hormone (Amh), octamer-binding transcription factor 4 (Oct-4), membrane type 1 metalloprotease (Mt1-mmp), proto-oncogene C-kit and promyelocytic leukaemia zinc finger (Plzf ) was quantified by real-time polymerase chain reaction...
May 23, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28531348/plant-derived-transcription-factors-for-orthologous-regulation-of-gene-expression-in-the-yeast-saccharomyces-cerevisiae
#4
Gita Naseri, Salma Balazadeh, Fabian Machens, Iman Kamranfar, Katrin Messerschmidt, Bernd Mueller-Roeber
Control of gene expression by transcription factors (TFs) is central in many synthetic biology projects where tailored expression of one or multiple genes is often needed. As TFs from evolutionary distant organisms are unlikely to affect gene expression in a host of choice, they represent excellent candidates for establishing orthogonal control systems. To establish orthogonal regulators for use in yeast (Saccharomyces cerevisiae), we chose TFs from the plant Arabidopsis thaliana. We established a library of 106 different combinations of chromosomally integrated TFs, activation domains (yeast GAL4 AD, herpes simplex virus VP64, and plant EDLL) and synthetic promoters harbouring cognate cis-regulatory motifs driving a yEGFP reporter...
May 22, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28531296/a-new-computational-method-to-predict-transcriptional-activity-of-a-dna-sequence-from-diverse-datasets-of-massively-parallel-reporter-assays
#5
Ying Liu, Takuma Irie, Tetsushi Yada, Yutaka Suzuki
In recent years, the dramatic increase in the number of applications for massively parallel reporter assay (MPRA) technology has produced a large body of data for various purposes. However, a computational model that can be applied to decipher regulatory codes for diverse MPRAs does not exist yet. Here, we propose a new computational method to predict the transcriptional activity of MPRAs, as well as luciferase reporter assays, based on the TRANScription FACtor database. We employed regression trees and multivariate adaptive regression splines to obtain these predictions and considered a feature redundancy-dependent formula for conventional regression trees to enable adaptation to diverse data...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28531287/bacterial-rna-polymerase-caps-rna-with-various-cofactors-and-cell-wall-precursors
#6
Christina Julius, Yulia Yuzenkova
Bacterial RNA polymerase is able to initiate transcription with adenosine-containing cofactor NAD+, which was proposed to result in a portion of cellular RNAs being 'capped' at the 5΄ end with NAD+, reminiscent of eukaryotic cap. Here we show that, apart from NAD+, another adenosine-containing cofactor FAD and highly abundant uridine-containing cell wall precursors, UDP-Glucose and UDP-N-acetylglucosamine are efficiently used to initiate transcription in vitro. We show that the affinity to NAD+ and UDP-containing factors during initiation is much lower than their cellular concentrations, and that initiation with them stimulates promoter escape...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28531220/highly-conserved-type-1-pili-promote-enterotoxigenic-e-coli-pathogen-host-interactions
#7
Alaullah Sheikh, Rasheduzzaman Rashu, Yasmin Ara Begum, F Matthew Kuhlman, Matthew A Ciorba, Scott J Hultgren, Firdausi Qadri, James M Fleckenstein
Enterotoxigenic Escherichia coli (ETEC), defined by their elaboration of heat-labile (LT) and/or heat-stable (ST) enterotoxins, are a common cause of diarrheal illness in developing countries. Efficient delivery of these toxins requires ETEC to engage target host enterocytes. This engagement is accomplished using a variety of pathovar-specific and conserved E. coli adhesin molecules as well as plasmid encoded colonization factors. Some of these adhesins undergo significant transcriptional modulation as ETEC encounter intestinal epithelia, perhaps suggesting that they cooperatively facilitate interaction with the host...
May 22, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28531166/-epiafzelechin-protects-against-ovariectomy-induced-bone-loss-in-adult-mice-and-modulate-osteoblastic-and-osteoclastic-functions-in-vitro
#8
Ka-Chun Wong, Sisi Cao, Xiaoli Dong, Man-Chun Law, Tak-Hang Chan, Man-Sau Wong
The present study was designed to characterize the bone protective effects of (-)-epiafzelechin (EAF), a flavan-3-ol, in mature ovariectomized mice model and its ability to stimulate osteoblastic activity and inhibit osteoclastic activity. Mature C57BL/6 mice (three to four months old) were either ovariectomised (OVX) or sham-operated and subjected to treatment (vehicle, 17β-oestradiol (E2, 200 μg/kg/day) or EAF (500 μg/kg/day) orally for six weeks. EAF and E2 significantly reduced urinary calcium (Ca) excretion, serum osteocalcin (OCN), and urinary deoxy-pyridinoline (DPD); increased bone mineral density (BMD); and improved micro-architectural properties in OVX mice...
May 22, 2017: Nutrients
https://www.readbyqxmd.com/read/28531131/the-role-of-interleukin-18-oxidative-stress-and-metabolic-syndrome-in-alzheimer-s-disease
#9
REVIEW
Johanna O Ojala, Elina M Sutinen
The role of interleukins (ILs) and oxidative stress (OS) in precipitating neurodegenerative diseases including sporadic Alzheimer's disease (AD), requires further clarification. In addition to neuropathological hallmarks-extracellular neuritic amyloid-β (Aβ) plaques, neurofibrillary tangles (NFT) containing hyperphosphorylated tau and neuronal loss-chronic inflammation, as well as oxidative and excitotoxic damage, are present in the AD brain. The pathological sequelae and the interaction of these events during the course of AD need further investigation...
May 21, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28531107/analysis-of-gene-expression-signatures-in-cancer-associated-stroma-from-canine-mammary-tumours-reveals-molecular-homology-to-human-breast-carcinomas
#10
Julia Ettlin, Elena Clementi, Parisa Amini, Alexandra Malbon, Enni Markkanen
Cancer-associated stroma (CAS) plays a key role in cancer initiation and progression. Spontaneously occurring canine mammary carcinomas are viewed as excellent models of human breast carcinomas. Considering the importance of CAS for human cancer, it likely plays a central role in canine tumours as well. So far, however, canine CAS lacks characterisation, and it remains unclear whether the biology between CAS from canine and human tumours is comparable. In this proof-of-principle study, using laser-capture microdissection, we isolated CAS and normal stroma from 13 formalin-fixed paraffin embedded canine simple mammary carcinomas and analysed the expression of seven known human CAS markers by RT-qPCR (Reverse Transcription quantitative PCR) and validated some targets by immunohistochemistry...
May 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28530800/label-free-multiplexed-single-molecule-analysis-of-protein-dna-complexes-with-nanopores
#11
Garbiñe Celaya, Judit Perales-Calvo, Arturo Muga, Fernando Moro, David Rodriguez-Larrea
Protein interactions with specific DNA sequences are crucial in the control of gene expression and the regulation of replication. Single-molecule methods offer excellent capabilities to unravel the mechanism and kinetics of these interactions. Here we develop a nanopore approach where a target DNA sequence is contained in a hairpin followed by a ssDNA. This system allows DNA-protein complexes to be distinguished from bare DNA molecules as they are pulled through a single nanopore detector, providing both equilibrium and kinetic information...
May 22, 2017: ACS Nano
https://www.readbyqxmd.com/read/28530713/bach2-immunodeficiency-illustrates-an-association-between-super-enhancers-and-haploinsufficiency
#12
Behdad Afzali, Juha Grönholm, Jana Vandrovcova, Charlotte O'Brien, Hong-Wei Sun, Ine Vanderleyden, Fred P Davis, Ahmad Khoder, Yu Zhang, Ahmed N Hegazy, Alejandro V Villarino, Ira W Palmer, Joshua Kaufman, Norman R Watts, Majid Kazemian, Olena Kamenyeva, Julia Keith, Anwar Sayed, Dalia Kasperaviciute, Michael Mueller, Jason D Hughes, Ivan J Fuss, Mohammed F Sadiyah, Kim Montgomery-Recht, Joshua McElwee, Nicholas P Restifo, Warren Strober, Michelle A Linterman, Paul T Wingfield, Holm H Uhlig, Rahul Roychoudhuri, Timothy J Aitman, Peter Kelleher, Michael J Lenardo, John J O'Shea, Nichola Cooper, Arian D J Laurence
The transcriptional programs that guide lymphocyte differentiation depend on the precise expression and timing of transcription factors (TFs). The TF BACH2 is essential for T and B lymphocytes and is associated with an archetypal super-enhancer (SE). Single-nucleotide variants in the BACH2 locus are associated with several autoimmune diseases, but BACH2 mutations that cause Mendelian monogenic primary immunodeficiency have not previously been identified. Here we describe a syndrome of BACH2-related immunodeficiency and autoimmunity (BRIDA) that results from BACH2 haploinsufficiency...
May 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28530712/the-microrna-mir-31-inhibits-cd8-t-cell-function-in-chronic-viral-infection
#13
Howell F Moffett, Adam N R Cartwright, Hye-Jung Kim, Jernej Godec, Jason Pyrdol, Tarmo Äijö, Gustavo J Martinez, Anjana Rao, Jun Lu, Todd R Golub, Harvey Cantor, Arlene H Sharpe, Carl D Novina, Kai W Wucherpfennig
During infection, antigen-specific T cells undergo tightly regulated developmental transitions controlled by transcriptional and post-transcriptional regulation of gene expression. We found that the microRNA miR-31 was strongly induced by activation of the T cell antigen receptor (TCR) in a pathway involving calcium and activation of the transcription factor NFAT. During chronic infection with lymphocytic choriomeningitis virus (LCMV) clone 13, miR-31-deficent mice recovered from clinical disease, while wild-type mice continued to show signs of disease...
May 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28530648/mechanism-of-human-somatic-reprogramming-to-ips-cell
#14
Rika Teshigawara, Junkwon Cho, Masahiro Kameda, Takashi Tada
Somatic reprogramming to induced pluripotent stem cells (iPSC) was realized in the year 2006 in mice, and in 2007 in humans, by transiently forced expression of a combination of exogenous transcription factors. Human and mouse iPSCs are distinctly reprogrammed into a 'primed' and a 'naïve' state, respectively. In the last decade, puzzle pieces of somatic reprogramming have been collected with difficulty. Collectively, dissecting reprogramming events and identification of the hallmark of sequentially activated/silenced genes have revealed mouse somatic reprogramming in fragments, but there is a long way to go toward understanding the molecular mechanisms of human somatic reprogramming, even with developing technologies...
May 22, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28530645/myc-dependent-oxidative-metabolism-regulates-osteoclastogenesis-via-nuclear-receptor-err%C3%AE
#15
Seyeon Bae, Min Joon Lee, Se Hwan Mun, Eugenia G Giannopoulou, Vladimir Yong-Gonzalez, Justin R Cross, Koichi Murata, Vincent Giguère, Marjolein van der Meulen, Kyung-Hyun Park-Min
Osteoporosis is a metabolic bone disorder associated with compromised bone strength and an increased risk of fracture. Inhibition of the differentiation of bone-resorbing osteoclasts is an effective strategy for the treatment of osteoporosis. Prior work by our laboratory and others has shown that MYC promotes osteoclastogenesis in vitro, but the underlying mechanisms are not well understood. In addition, the in vivo importance of osteoclast-expressed MYC in physiological and pathological bone loss is not known...
May 22, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28530641/the-many-ways-of-osteoclast-activation
#16
Joseph Lorenzo
Osteoclasts are the cells responsible for bone resorption, a process that is essential for the maintenance of healthy bones. Bone diseases, such as osteoporosis, which are characterized by high rates of bone resorption and loss of bone mass, may benefit from treatments that inhibit osteoclast formation and/or function. The RANKL/RANK pathway is critical for both osteoclast formation and function, and these effects are thought to be mediated by the transcription factor nuclear factor of activated T cells, cytoplasmic 1 (NFATc1)...
May 22, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28530640/genetic-regulation-of-the-runx-transcription-factor-family-has-antitumor-effects
#17
Ken Morita, Kensho Suzuki, Shintaro Maeda, Akihiko Matsuo, Yoshihide Mitsuda, Chieko Tokushige, Gengo Kashiwazaki, Junichi Taniguchi, Rina Maeda, Mina Noura, Masahiro Hirata, Tatsuki Kataoka, Ayaka Yano, Yoshimi Yamada, Hiroki Kiyose, Mayu Tokumasu, Hidemasa Matsuo, Sunao Tanaka, Yasushi Okuno, Manabu Muto, Kazuhito Naka, Kosei Ito, Toshio Kitamura, Yasufumi Kaneda, Paul P Liu, Toshikazu Bando, Souichi Adachi, Hiroshi Sugiyama, Yasuhiko Kamikubo
Runt-related transcription factor 1 (RUNX1) is generally considered to function as a tumor suppressor in the development of leukemia, but a growing body of evidence suggests that it has pro-oncogenic properties in acute myeloid leukemia (AML). Here we have demonstrated that the antileukemic effect mediated by RUNX1 depletion is highly dependent on a functional p53-mediated cell death pathway. Increased expression of other RUNX family members, including RUNX2 and RUNX3, compensated for the antitumor effect elicited by RUNX1 silencing, and simultaneous attenuation of all RUNX family members as a cluster led to a much stronger antitumor effect relative to suppression of individual RUNX members...
May 22, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28530531/the-complexity-of-dek-signaling-in-cancer-progression
#18
Yong Teng, Liwei Lang, Catherine E Jauregui
The DNA binding protein and chromatin structural regulator DEK regulates many cellular processes. These include proliferation, differentiation, apoptosis, senescence, DNA repairing and the maintenance of stem cell phenotype. DEK is increasingly recognized as a crucial player in many steps of cancer initiation and progression, and is precisely regulated by abundant promoting and inhibiting factors directly or indirectly. DEK may serve as an architectural modulating protein to regulate the expression and function of multiple human genes in cancer cells...
May 21, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28529954/%C3%AE-7-nicotinic-acetylcholine-receptor-stimulation-attenuates-neuroinflammation-through-jak2-stat3-activation-in-murine-models-of-intracerebral-hemorrhage
#19
Paul R Krafft, Devin McBride, William B Rolland, Tim Lekic, Jerry J Flores, John H Zhang
Accounting for high mortality and morbidity rates, intracerebral hemorrhage (ICH) remains one of the most detrimental stroke subtypes lacking a specific therapy. Neuroinflammation contributes to ICH-induced brain injury and is associated with unfavorable outcomes. This study aimed to evaluate whether α7 nicotinic acetylcholine receptor (α7nAChR) stimulation ameliorates neuroinflammation after ICH. Male CD-1 mice and Sprague-Dawley were subjected to intracerebral injection of autologous blood or bacterial collagenase...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28529924/regulation-of-cancer-cell-responsiveness-to-ionizing-radiation-treatment-by-cyclic-amp-response-element-binding-nuclear-transcription-factor
#20
REVIEW
Francesca D'Auria, Lucia Centurione, Maria Antonietta Centurione, Antonio Angelini, Roberta Di Pietro
Cyclic AMP response element binding (CREB) protein is a member of the CREB/activating transcription factor (ATF) family of transcription factors that play an important role in the cell response to different environmental stimuli leading to proliferation, differentiation, apoptosis, and survival. A number of studies highlight the involvement of CREB in the resistance to ionizing radiation (IR) therapy, demonstrating a relationship between IR-induced CREB family members' activation and cell survival. Consistent with these observations, we have recently demonstrated that CREB and ATF-1 are expressed in leukemia cell lines and that low-dose radiation treatment can trigger CREB activation, leading to survival of erythro-leukemia cells (K562)...
2017: Frontiers in Oncology
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