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https://www.readbyqxmd.com/read/28330463/global-transcriptome-analysis-of-huperzia-serrata-and-identification-of-critical-genes-involved-in-the-biosynthesis-of-huperzine-a
#1
Mengquan Yang, Wenjing You, Shiwen Wu, Zhen Fan, Baofu Xu, Mulan Zhu, Xuan Li, Youli Xiao
BACKGROUND: Huperzia serrata (H. serrata) is an economically important traditional Chinese herb with the notably medicinal value. As a representative member of the Lycopodiaceae family, the H. serrata produces various types of effectively bioactive lycopodium alkaloids, especially the huperzine A (HupA) which is a promising drug for Alzheimer's disease. Despite their medicinal importance, the public genomic and transcriptomic resources are very limited and the biosynthesis of HupA is largely unknown...
March 22, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28326635/structure-enabled-discovery-of-a-stapled-peptide-inhibitor-to-target-the-oncogenic-transcriptional-repressor-tle1
#2
Sally McGrath, Marcello Tortorici, Ludovic Drouin, Savade Solanki, Lewis Vidler, Isaac Westwood, Peter Gimeson, Rob vanMontfort, Swen Hoelder
TLE1 is an oncogenic transcriptional co-repressor that exerts its repressive effects through binding of transcription factors. Inhibition of this protein-protein interaction represents a putative cancer target but no small molecule inhibitors have been published for this challenging interface. In this manuscript, we report the structure enabled design and synthesis of a constrained peptide inhibitor of TLE1. Our design featured introduction of a four carbon atom linker into the peptide epitope found in many TLE1 binding partners...
March 22, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28325259/vitamin-d-analogues-potential-use-in-cancer-treatment
#3
REVIEW
Michael J Duffy, Alyson Murray, Naoise C Synnott, Norma O'Donovan, John Crown
The vitamin D receptor (VDR) is a member of the thyroid-steroid family of nuclear transcription factors. Following binding of the active form of vitamin D, i.e., 1,25(OH)2D3 (also known as calcitriol) and interaction with co-activators and co-repressors, VDR regulates the expression of several different genes. Although relatively little work has been carried out on VDR in human cancers, several epidemiological studies suggest that low circulating levels of vitamin D are associated with both an increased risk of developing specific cancer types and poor outcome in patients with specific diagnosed cancers...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28322442/systems-analysis-of-dynamic-transcription-factor-activity-identifies-targets-for-treatment-in-olaparib-resistant-cancer-cells
#4
Joseph T Decker, Eric C Hobson, Yining Zhang, Seungjin Shin, Alexandra L Thomas, Jacqueline S Jeruss, Kelly B Arnold, Lonnie D Shea
The development of resistance to targeted therapeutics is a challenging issue for the treatment of cancer. Cancers that have mutations in BRCA, a DNA repair protein, have been treated with poly (ADP-ribose) polymerase (PARP) inhibitors, which target a second DNA repair mechanism with the aim of inducing synthetic lethality. While these inhibitors have shown promise clinically, the development of resistance can limit their effectiveness as a therapy. This study investigated mechanisms of resistance in BRCA-mutated cancer cells (HCC1937) to Olaparib (AZD2281) using TRACER, a technique for measuring dynamics of transcription factor (TF) activity in living cells...
March 21, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28319298/diversity-in-gold-finger-structure-elucidated-by-traveling-wave-ion-mobility-mass-spectrometry
#5
Zhifeng Du, Raphael E F de Paiva, Kristina Nelson, Nicholas P Farrell
Traveling wave ion mobility (TWIM) mass spectrometry (MS) is a powerful method for the structural and conformational analysis of proteins and peptides, enabling the differentiation of isomeric peptides (or proteins) that have the same sequence but are modified at different residues. In this study, the TWIM-MS technique was used to separate isomeric Au(I) metallopeptide ions that were formed by Zn(II) displacement from the parent zinc fingers (ZFs). The synthetic gold finger peptides were derived from the C-terminus of the HIV nucleocapsid p7 protein (NCp7-F2) and finger 3 of the Sp1 transcription factor (Sp1-F3)...
March 20, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28302010/discovery-of-hedgehog-antagonists-for-cancer-therapy
#6
Harleen Khatra, Chandra Bose, Surajit Sinha
BACKGROUND: The evolutionarily conserved Hedgehog (Hh) signaling cascade is one of the key mediators of embryonic development of many metazoans. This pathway has been extensively targeted by small molecule inhibitors as its misregulation leads to various malignancies and developmental disorders. Thus, blocking this pathway can be a novel therapeutic avenue for the treatment of Hedgehog-dependent cancers. This review covers the mechanism of hedgehog signaling in vertebrate cells, provides an overview of reported small molecule Hh pathway inhibitors, with the synthetic routes and SAR studies of some of them discussed briefly...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28301169/conformational-dynamics-of-cyanocobalamin-and-its-conjugates-with-peptide-nucleic-acids
#7
Tomasz Pieńko, Aleksandra J Wierzba, Monika Wojciechowska, Dorota Gryko, Joanna Trylska
Vitamin B12 also called cobalamin (Cbl) is an important enzymatic co-factor taken up by mammalian and also by many bacterial cells. Peptide nucleic acid (PNA) is a synthetic DNA analogue that has the ability to bind in a complementary manner to natural nucleic acids. Provided that PNA is efficiently delivered to cells, it could act as a steric blocker of functional DNA or RNA and regulate gene expression at the level of transcription or translation. Recently, Cbl has been examined as a transporter of various molecules to cells...
March 16, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28299675/a-regulatory-role-for-runx1-runx3-in-the-maintenance-of-genomic-integrity
#8
Vaidehi Krishnan, Yoshiaki Ito
All human cells are constantly attacked by endogenous and exogenous agents that damage the integrity of their genomes. Yet, the ensuing damage is mostly fixed and very rarely gives rise to genomic defects that promote cancer formation. This is due to the co-ordinated functioning of DNA repair proteins and checkpoint mechanisms that accurately detect and repair DNA damage to ensure genomic fitness. According to accumulating evidence, the RUNX family of transcription factors participate in the maintenance of genomic stability through transcriptional and non-transcriptional mechanisms...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28294630/peak-integrating-curated-and-noisy-prior-knowledge-in-gene-regulatory-network-inference
#9
Doaa Altarawy, Fatma-Elzahraa Eid, Lenwood S Heath
With abundance of biological data, computational prediction of gene regulatory networks (GRNs) from gene expression data has become more feasible. Although incorporating other prior knowledge (PK), along with gene expression data, greatly improves prediction accuracy, the overall accuracy is still low. PK in GRN inference can be categorized into noisy and curated. In noisy PK, relations between genes do not necessarily correspond to regulatory relations and are thus considered inaccurate by inference algorithms such as transcription factor binding and protein-protein interactions...
March 15, 2017: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
https://www.readbyqxmd.com/read/28285016/gper-modulators-opportunity-nox-on-the-heels-of-a-class-akt
#10
Eric R Prossnitz
The (patho)physiology of estrogen and its receptors is complex. It is therefore not surprising that therapeutic approaches targeting this hormone include stimulation of its activity through supplementation with either the hormone itself or natural or synthetic agonists, inhibition of its activity through the use of antagonists or inhibitors of its synthesis, and tissue-selective modulation of its activity with biased ligands. The physiology of this hormone is further complicated by the existence of at least three receptors, the classical nuclear estrogen receptors α and β (ERα and ERβ), and the 7-transmembrane G protein-coupled estrogen receptor (GPER/GPR30), with overlapping but distinct pharmacologic profiles, particularly of anti-estrogenic ligands...
March 8, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28281199/unraveling-new-functions-of-superoxide-dismutase-using-yeast-model-system-beyond-its-conventional-role-in-superoxide-radical-scavenging
#11
REVIEW
Woo-Hyun Chung
To deal with chemically reactive oxygen molecules constantly threatening aerobic life, cells are readily equipped with elaborate biological antioxidant systems. Superoxide dismutase is a metalloenzyme catalytically eliminating superoxide radical as a first-line defense mechanism against oxidative stress. Multiple different SOD isoforms have been developed throughout evolution to play distinct roles in separate subcellular compartments. SOD is not essential for viability of most aerobic organisms and intriguingly found even in strictly anaerobic bacteria...
March 9, 2017: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/28275002/high-constitutive-activity-of-a-broad-panel-of-housekeeping-and-tissue-specific-cis-regulatory-elements-depends-on-a-subset-of-ets-proteins
#12
Alessia Curina, Alberto Termanini, Iros Barozzi, Elena Prosperini, Marta Simonatto, Sara Polletti, Alessio Silvola, Monica Soldi, Liv Austenaa, Tiziana Bonaldi, Serena Ghisletti, Gioacchino Natoli
Enhancers and promoters that control the transcriptional output of terminally differentiated cells include cell type-specific and broadly active housekeeping elements. Whether the high constitutive activity of these two groups of cis-regulatory elements relies on entirely distinct or instead also on shared regulators is unknown. By dissecting the cis-regulatory repertoire of macrophages, we found that the ELF subfamily of ETS proteins selectively bound within 60 base pairs (bp) from the transcription start sites of highly active housekeeping genes...
March 8, 2017: Genes & Development
https://www.readbyqxmd.com/read/28266569/ogg1-dna-interactions-facilitate-nf-%C3%AE%C2%BAb-binding-to-dna-targets
#13
Lang Pan, Wenjing Hao, Xu Zheng, Xianlu Zeng, Adeel Ahmed Abbasi, Istvan Boldogh, Xueqing Ba
DNA repair protein counteracting oxidative promoter lesions may modulate gene expression. Oxidative DNA bases modified by reactive oxygen species (ROS), primarily as 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-oxoG), which is repaired by 8-oxoguanine DNA glycosylase1 (OGG1) during base excision repair (BER) pathway. Because cellular response to oxidative challenge is accompanied by DNA damage repair, we tested whether the repair by OGG1 is compatible with transcription factor binding and gene expression. We performed electrophoretic mobility shift assay (EMSA) using wild-type sequence deriving from Cxcl2 gene promoter and the same sequence bearing a single synthetic 8-oxoG at defined 5' or 3' guanine in runs of guanines to mimic oxidative effects...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28258224/transglutaminase-catalyzed-incorporation-of-polyamines-masks-the-dna-binding-region-of-the-transcription-factor-relish
#14
Kouki Maki, Toshio Shibata, Shun-Ichiro Kawabata
In Drosophila, the immune deficiency (IMD) pathway-dependent signal is finally transmitted through proteolytic conversion of the nuclear factor-κB-like transcription factor Relish to the active N-terminal fragment Relish-N to induce its translocation from the cytosol into the nucleus for the expression of IMD-controlled genes. We previously demonstrated that transglutaminase (TG) suppresses the IMD pathway by polymerizing Relish-N to inhibit its nuclear translocation. On the other hand, we also demonstrated that a synthetic amine, such as monodansylcadaverine (DCA) or biotin-labeled pentylamine, ingested by flies is TG-dependently incorporated into Relish-N, causing the nuclear translocation of modified Relish-N in gut epithelial cells...
March 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28257481/toll-like-receptor-2-activation-and-serum-amyloid-a-regulate-smooth-muscle-cell-extracellular-matrix
#15
Stephanie E Seidl, Lawrence G Pessolano, Christopher A Bishop, Michael Best, Celeste B Rich, Phillip J Stone, Barbara M Schreiber
Smooth muscle cells contribute to extracellular matrix remodeling during atherogenesis. De-differentiated, synthetic smooth muscle cells are involved in processes of migration, proliferation and changes in expression of extracellular matrix components, all of which contribute to loss of homeostasis accompanying atherogenesis. Elevated levels of acute phase proteins, including serum amyloid A (SAA), are associated with an increased risk for atherosclerosis. Although infection with periodontal and respiratory pathogens via activation of inflammatory cell Toll-like receptor (TLR)2 has been linked to vascular disease, little is known about smooth muscle cell TLR2 in atherosclerosis...
2017: PloS One
https://www.readbyqxmd.com/read/28256660/consensus-architecture-of-promoters-and-transcription-units-in-escherichia-coli-design-principles-for-synthetic-biology
#16
REVIEW
Cynthia Rangel-Chavez, Edgardo Galan-Vasquez, Agustino Martinez-Antonio
Genetic information in genomes is ordered, arranged in such a way that it constitutes a code, the so-called cis regulatory code. The regulatory machinery of the cell, termed trans-factors, decodes and expresses this information. In this way, genomes maintain a potential repertoire of genetic programs, parts of which are executed depending on the presence of active regulators in each condition. These genetic programs, executed by the regulatory machinery, have functional units in the genome delimited by punctuation-like marks...
March 3, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28254369/applying-attractor-dynamics-to-infer-gene-regulatory-interactions-involved-in-cellular-differentiation
#17
Ahmadreza Ghaffarizadeh, Gregory J Podgorski, Nicholas S Flann
The dynamics of gene regulatory networks (GRNs) guide cellular differentiation. Determining the ways regulatory genes control expression of their targets is essential to understand and control cellular differentiation. The way a regulatory gene controls its target can be expressed as a gene regulatory function. Manual derivation of these regulatory functions is slow, error-prone and difficult to update as new information arises. Automating this process is a significant challenge and the subject of intensive effort...
February 27, 2017: Bio Systems
https://www.readbyqxmd.com/read/28245285/the-platelet-derived-growth-factor-receptor-stat3-signaling-pathway-regulates-the-phenotypic-transition-of-corpus-cavernosum-smooth-muscle-in-rats
#18
Jun-Feng Yan, Wen-Jie Huang, Jian-Feng Zhao, Hui-Ying Fu, Gao-Yue Zhang, Xiao-Jun Huang, Bo-Dong Lv
Erectile dysfunction (ED) is a common clinical disease that is difficult to treat. We previously found that hypoxia modulates the phenotype of primary corpus cavernosum smooth muscle cells (CCSMCs) in rats, but the underlying molecular mechanism is still unknown. Platelet-derived growth factor receptor (PDGFR)-related signaling pathways are correlated with cell phenotypic transition, but research has been focused more on vascular smooth muscle and tracheal smooth muscle and less on CCSMCs. Here, we investigated the role of PDGFR-related signaling pathways in penile CCSMCs, which were successfully isolated from rats and cultured in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28238141/nanoscript-a-versatile-nanoparticle-based-synthetic-transcription-factor-for-innovative-gene-manipulation
#19
Kholud Dardir, Christopher Rathnam, KiBum Lee
Cellular reprogramming and stem cell-based therapies have shown tremendous potential in the field of regenerative medicine. To that end, developing tools to control stem cell fate is an attractive area of research for replacing damaged and diseased cells and reestablishing functional connections for tissue repair. Transcription factor (TFs) proteins are well known to regulate gene expression and direct stem cell fate. Inspired by natural TFs, NanoScript, a nanoparticle (NP)-based platform, mimics TFs to afford control over gene expression and stem cell fate for regenerative medicine...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28223915/oral-delivery-of-a-synthetic-sterol-reduces-axonopathy-and-inflammation-in-a-rodent-model-of-glaucoma
#20
Wendi S Lambert, Brian J Carlson, Cathryn R Formichella, Rebecca M Sappington, Clarence Ahlem, David J Calkins
Glaucoma is a group of optic neuropathies associated with aging and sensitivity to intraocular pressure (IOP). The disease is the leading cause of irreversible blindness worldwide. Early progression in glaucoma involves dysfunction of retinal ganglion cell (RGC) axons, which comprise the optic nerve. Deficits in anterograde transport along RGC axons to central visual structures precede outright degeneration, and preventing these deficits is efficacious at abating subsequent progression. HE3286 is a synthetic sterol derivative that has shown therapeutic promise in models of inflammatory disease and neurodegenerative disease...
2017: Frontiers in Neuroscience
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