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https://www.readbyqxmd.com/read/28821159/inhibition-of-dna-pk-enhances-chemosensitivity-of-b-cell-precursor-acute-lymphoblastic-leukemia-cells-to-doxorubicin
#1
Fatemeh Alikarami, Majid Safa, Mohammad Faranoush, Parisa Hayat, Ahmad Kazemi
DNA damage repair pathways greatly affect the response to genotoxic drugs in cancer cells, so inhibition of such pathways could be a potentially useful strategy to enhance chemosensitivity. DNA-dependent protein kinase (DNA-PK) plays a crucial role in the repair of DNA double-strand breaks (DSBs) that are probably one of the most detrimental types of DNA damage. It has been shown that DNA-PK is highly expressed in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. Less well appreciated was the effect of DNA-PK inhibition on sensitivity of BCP-ALL cells to DNA-damaging agents...
August 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28821014/efficient-and-accurate-causal-inference-with-hidden-confounders-from-genome-transcriptome-variation-data
#2
Lingfei Wang, Tom Michoel
Mapping gene expression as a quantitative trait using whole genome-sequencing and transcriptome analysis allows to discover the functional consequences of genetic variation. We developed a novel method and ultra-fast software Findr for higly accurate causal inference between gene expression traits using cis-regulatory DNA variations as causal anchors, which improves current methods by taking into consideration hidden confounders and weak regulations. Findr outperformed existing methods on the DREAM5 Systems Genetics challenge and on the prediction of microRNA and transcription factor targets in human lymphoblastoid cells, while being nearly a million times faster...
August 18, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28820907/positive-regulatory-interactions-between-yap-and-hedgehog-signalling-in-skin-homeostasis-and-bcc-development-in-mouse-skin-in-vivo
#3
Bassem Akladios, Veronica Mendoza Reinoso, Jason E Cain, Taopeng Wang, Duncan L Lambie, D Neil Watkins, Annemiek Beverdam
Skin is a highly plastic tissue that undergoes tissue turnover throughout life, but also in response to injury. YAP and Hedgehog signalling play a central role in the control of epidermal stem/progenitor cells in the skin during embryonic development, in postnatal tissue homeostasis and in skin carcinogenesis. However, the genetic contexts in which they act to control tissue homeostasis remain mostly unresolved. We provide compelling evidence that epidermal YAP and Hedgehog/GLI2 signalling undergo positive regulatory interactions in the control of normal epidermal homeostasis and in basal cell carcinoma (BCC) development, which in the large majority of cases is caused by aberrant Hedgehog signalling activity...
2017: PloS One
https://www.readbyqxmd.com/read/28820904/parametric-studies-of-metabolic-cooperativity-in-escherichia-coli-colonies-strain-and-geometric-confinement-effects
#4
Joseph R Peterson, John A Cole, Zaida Luthey-Schulten
Characterizing the complex spatial and temporal interactions among cells in a biological system (i.e. bacterial colony, microbiome, tissue, etc.) remains a challenge. Metabolic cooperativity in these systems can arise due to the subtle interplay between microenvironmental conditions and the cells' regulatory machinery, often involving cascades of intra- and extracellular signalling molecules. In the simplest of cases, as demonstrated in a recent study of the model organism Escherichia coli, metabolic cross-feeding can arise in monoclonal colonies of bacteria driven merely by spatial heterogeneity in the availability of growth substrates; namely, acetate, glucose and oxygen...
2017: PloS One
https://www.readbyqxmd.com/read/28820723/a-lncrna-fine-tunes-the-dynamics-of-a-cell-state-transition-involving-lin28-let-7-and-de-novo-dna-methylation
#5
Meng Amy Li, Paulo P Amaral, Priscilla Cheung, Jan H Bergmann, Masaki Kinoshita, Tüzer Kalkan, Meryem Ralser, Sam Robson, Ferdinand von Meyenn, Maike Paramor, Fengtang Yang, Caifu Chen, Jennifer Nichols, David L Spector, Tony Kouzarides, Lin He, Austin Smith
Execution of pluripotency requires progression from the naïve status represented by mouse embryonic stem cells (ESCs) to a state capacitated for lineage specification. This transition is coordinated at multiple levels. Non-coding RNAs may contribute to this regulatory orchestra. We identified a rodent-specific long non-coding RNA (lncRNA) linc1281, hereafter Ephemeron (Eprn), that modulates the dynamics of exit from naïve pluripotency. Eprn deletion delays the extinction of ESC identity, an effect associated with perduring Nanog expression...
August 18, 2017: ELife
https://www.readbyqxmd.com/read/28820713/quality-testing-of-artemisinin-based-antimalarial-drugs-in-myanmar
#6
Suqin Guo, Myat Phone Kyaw, Lishan He, Myo Min, Xiangxue Ning, Wei Zhang, Baomin Wang, Liwang Cui
Artemisinin-based combination therapies are the frontline treatment of Plasmodium falciparum malaria. The circulation of falsified and substandard artemisinin-based antimalarials in Southeast Asia has been a major predicament for the malaria elimination campaign. To provide an update of this situation, we purchased 153 artemisinin-containing antimalarials, as convenience samples, in private drug stores from different regions of Myanmar. The quality of these drugs in terms of their artemisinin derivative content was tested using specific dipsticks for these artemisinin derivatives, as point-of-care devices...
July 31, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28820405/antiphospholipid-syndrome-and-monocytes-new-aspects
#7
A Blbulyan, A Martirosyan, M Petrek, Z Navratilova, G Manukyan
After discovery of antiphospholipid syndrome (APS) our understanding of molecular mechanisms of living matter has become more sophisticated and on this way monocytes has become crucial player, particularly in pathogenesis of APS. Thrombotic and non-thrombotic complications of APS could be explained by monocytes' activation too. But mechanisms underlying their activation are poorly investigated. So we aimed to determine transcriptional activity of monocytes after exposing them to low concentrations of lipopolysaccharide (LPS) and LPS+ATP using comparative of RT-PCR...
July 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28820402/does-signaling-of-estrogen-related-receptors-affect-structure-and-function-of-bank-vole-leydig-cells
#8
P Pawlicki, A Milon, M Zarzycka, J Galas, W Tworzydlo, A Kaminska, L Pardyak, K Lesniak, A Pacwa, B Bilinska, E Gorowska-Wojtowicz, M Kotula-Balak
To get a deeper insight into the function of estrogen-related receptors (ERRs) and dissect underlying mechanism in Leydig cells, ERRs (type α, β and γ) were blocked or activated in testes of adult bank voles (Myodes glareolus) which show seasonal changes in the intratesticular sex hormones level. Both actively reproducing animals (long day conditions; LD) and those with regression of the reproductive system (short day conditions; SD) received intraperitoneal injections of selective ERRα antagonist 3-[4-(2,4-Bis-trifluoromethylbenzyloxy)-3-methoxyphenyl]-2-cyano-N-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)acrylamide (XCT 790) or selective ERRβ/ERRγ agonist N-(4-(Diethylaminobenzylidenyl)-N'-(4-hydroxybenzoyl)-hydrazine (DY131) (50 μ/kg bw; six doses every other day)...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28820337/paper-title-circular-rnas-isolation-characterisation-and-their-potential-role-in-diseases
#9
Lumei Liu, Jian Wang, Ramin Khanabdali, Bill Kalionis, Xiantao Tai, Shijin Xia
Circular RNA (circRNA) generated by alternative splicing represents a special class of non-coding RNA molecule. CircRNAs are abundant in the eukaryotic cell cytoplasm and have a characteristic organization, timing of action and disease specificity. In contrast to linear RNA, circRNAs are resistant to RNA exonuclease. Consequently, circRNA escapes normal RNA turnover and this improves circRNA stability. CircRNAs can be degraded by microRNA (miRNA) and this results in linearization of the circRNA, which can then act as competitor to endogenous RNA...
August 18, 2017: RNA Biology
https://www.readbyqxmd.com/read/28820325/small-alarmone-synthetases-as-novel-bacterial-rna-binding-proteins
#10
Vasili Hauryliuk, Gemma C Atkinson
The alarmone nucleotides guanosine pentaphosphate (pppGpp) and tetraphosphate (ppGpp), collectively referred to as (p)ppGpp, are key regulators of bacterial growth, stress adaptation, antibiotic tolerance and pathogenicity. We have recently shown that the Small Alarmone Synthetase (SAS) RelQ from the Gram-positive pathogen Enterococcus faecalis has an RNA-binding activity (Beljantseva et al. 2017). RelQ's activities as an enzyme and as a RNA-binding protein are mutually incompatible: binding of single-stranded RNA potently inhibits (p)ppGpp synthesis in a sequence-specific manner, and RelQ's enzymatic activity destabilizes the RNA:RelQ complex...
August 18, 2017: RNA Biology
https://www.readbyqxmd.com/read/28820318/7sk-small-nuclear-rna-a-multifunctional-transcriptional-regulatory-rna-with-gene-specific-features
#11
Sylvain Egloff, Cécilia Studniarek, Tamás Kiss
The 7SK small nuclear RNA is a multifunctional transcriptional regulatory RNA that controls the nuclear activity of the positive transcription elongation factor b (P-TEFb), specifically targets P-TEFb to the promoter regions of selected protein-coding genes and promotes transcription of RNA polymerase II-specific spliceosomal small nuclear RNA genes.
August 18, 2017: Transcription
https://www.readbyqxmd.com/read/28820316/cell-cycle-related-metabolism-and-mitochondrial-dynamics-in-a-replication-competent-pancreatic-beta-cell-line
#12
Chiara Montemurro, Suryakiran Vadrevu, Tatyana Gurlo, Alexandra E Butler, Kenny E Vongbunyong, Anton Petcherski, Orian S Shirihai, Leslie S Satin, Daniel Braas, Peter C Butler, Slavica Tudzarova
Cell replication is a fundamental attribute of growth and repair in multicellular organisms. Pancreatic beta-cells in adults rarely enter cell cycle, hindering the capacity for regeneration in diabetes. Efforts to drive beta-cells into cell cycle have so far largely focused on regulatory molecules such as cyclins and cyclin-dependent kinases (CDKs). Investigations in cancer biology have uncovered that adaptive changes in metabolism, the mitochondrial network, and cellular Ca(2+) are critical for permitting cells to progress through the cell cycle...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28820236/regulatory-mechanism-of-mycotoxin-tenuazonic-acid-production-in-pyricularia-oryzae
#13
Choong-Soo Yun, Takayuki Motoyama, Hiroyuki Osada
Tenuazonic acid (TeA) is a mycotoxin produced by the rice blast fungus Pyricularia oryzae and some plant pathogenic fungi. We previously demonstrated that TeA is biosynthesized in P. oryzae by TeA synthetase 1 (TAS1), and that its production is induced by osmo-sensory MAPK-encoding gene (OSM1) deletion or the addition of 1% DMSO to cultures; however, the regulatory mechanisms of TeA production were unknown. Here, we identified a Zn(II)2-Cys6-type transcription factor in the upstream region of TAS1, which is encoded by TAS2 and regulates TeA production...
August 18, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28820075/t-regulatory-cell-subsets-in-children-with-type-1-diabetes-mellitus-relation-to-control-of-the-disease
#14
Mabrouk Ghonaim, Rawhia El-Edel, Wafaa Abo El Fotoh, Samar Kamal Eldein, Samar Salman
BACKGROUND: Type 1 diabetes mellitus described as a chronic metabolic disorder characterized by aggressive immune β-cell destruction. There are numbers of varied immune mechanisms for sustaining self-tolerance in opposition to the autoimmune disorders. A recessive tolerance accomplished by thymic gland via a negative assortment of different clones while a dominant tolerance accomplished by the regulatory T cells (Treg) in the periphery. Treg (CD4+CD25+FOXP3+) are subsets of T cells which have an essential role in maintaining tolerance...
August 17, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28820073/immunomodulatory-role-of-arsenic-on-regulatory-t-cells
#15
Rizwanul Haque, Archana Chaudhary, Nadra Sadaf
Background and objective-Chronic Arsenic (As) exposure continued to be a cause of major problem associated with different kind of diseases including skin problem and different types of cancer. As exposure leads to numerous other pathological conditions that affect millions of people worldwide on a regular basis. It was recently established that As toxicity affects immune system and modulate the function and survival of cells involved in immune regulation. Arsenic trioxide (As2O3) was reported to be an effective apoptosis inducer in a variety of cell types...
August 17, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28820065/bcg-increased-membrane-expression-of-trim59-through-the-tlr2-tlr4-irf5-pathway-in-raw264-7-macrophages
#16
Jin Zheng, Tian Yuan, Yan Dongmei, Li Dong, Zhu Xun
OBJECTIVE: In our previous study, we showed that Bacillus Calmette-Guerin (BCG)-activated macrophages have the ability to directly kill tumor cells. One of the main properties of these macrophages is the high expression of tripartite motif family protein 59 (TRIM59). This study was conducted to investigate the mechanism of BCG-induced TRIM59 expression on macrophages and to identify the subcellular localization of TRIM59. METHODS: TRIM59 expression and TNF-α secretion were compared in RAW264...
August 18, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28820049/receptor-binding-assay-for-the-detection-of-paralytic-shellfish-poisoning-toxins-comparison-to-the-mouse-bioassay-and-applicability-under-regulatory-use
#17
Shiyamalie R Ruberu, Gregg W Langlois, Melisa Masuda, Clive Kittredge, S Kusum Perera, Raphael M Kudela
The receptor-binding assay (RBA) method for the detection of paralytic shellfish poisoning (PSP) toxins was evaluated for its overall performance in comparison with the mouse bioassay (MBA). An initial study to evaluate the effects of filtering shellfish extracts prior to running the RBA indicated no significant difference between filtered and unfiltered extracts on the determined saxitoxin concentrations. Next, we tested the RBA assay on 295 naturally contaminated mussel tissue samples, ranging in concentrations from 320 µg STX equiv...
August 18, 2017: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
https://www.readbyqxmd.com/read/28820004/drug-induced-liver-injury-in-children-clinical-observations-animal-models-and-regulatory-status
#18
Qiang Shi, Xi Yang, James J Greenhaw, Alec Thomas Salminen, Gary M Russotti, William F Salminen
Drug-induced liver injury in children (cDILI) accounts for about 1% of all reported adverse drug reactions throughout all age groups, less than 10% of all clinical DILI cases, and around 20% of all acute liver failure cases in children. The overall DILI susceptibility in children has been assumed to be lower than in adults. Nevertheless, controversial evidence is emerging about children's sensitivity to DILI, with children's relative susceptibility to DILI appearing to be highly drug-specific. The culprit drugs in cDILI are similar but not identical to DILI in adults (aDILI)...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28819992/insulin-delivery-and-nocturnal-glucose-control-in-children-and-adolescents-with-type-1-diabetes
#19
Martin Tauschmann, Roman Hovorka
Nocturnal glucose control remains challenging in children and adolescents with type 1 diabetes due to highly variable overnight insulin requirements. The issue may be addressed by glucose responsive insulin delivery based on real-time continuous glucose measurements. Areas covered: This review outlines recent developments of glucose responsive insulin delivery systems from a paediatric perspective. We cover threshold-based suspend application, predictive low glucose suspend, and more advanced single hormone and dual-hormone closed-loop systems...
August 18, 2017: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/28819808/mir398-and-mir395-are-involved-in-response-to-so2-stress-in-arabidopsis-thaliana
#20
Lihong Li, Huilan Yi, Meizhao Xue, Min Yi
Sulfur dioxide (SO2) is a common air pollutant that has adverse effects on plants. MicroRNAs (miRNAs) are small noncoding RNA that play critical roles in plant development and stress response. In this study, we found that two miRNAs, miR398 and miR395, were differentially expressed in Arabidopsis shoots under SO2 stress. The expression of miR398 was down-regulated, and the transcript levels of its target genes, Cu/Zn superoxide dismutases (CSD1 and CSD2), were increased during SO2 exposure. The activity of superoxide dismutase (SOD), one of the major antioxidant enzymes, was enhanced with the increase in the CSD transcript level, suggesting an important role of miR398 in response to SO2-induced oxidative stress...
August 17, 2017: Ecotoxicology
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