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https://www.readbyqxmd.com/read/29352505/p53-independent-noxa-induction-by-cisplatin-is-regulated-by-atf3-atf4-in-head-and-neck-squamous-cell-carcinoma-cells
#1
Kanika Sharma, Thien-Trang Vu, Wade Cook, Mitra Naseri, Kevin Zhan, Wataru Nakajima, Hisashi Harada
The platinum-based DNA damaging agent cisplatin is used as a standard therapy for locally advanced head and neck squamous cell carcinoma (HNSCC). However, the mechanisms underpinning the cytotoxic effects of this compound are not entirely elucidated. Cisplatin produces anticancer effects primarily via activation of the DNA damage response, followed by inducing BCL-2 family-dependent mitochondrial apoptosis. We have previously demonstrated that cisplatin induces the expression of pro-apoptotic BCL-2 family protein, Noxa, that can bind to the pro-survival BCL-2 family protein, MCL-1, to inactivate its function and induce cell death...
January 19, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29352482/influence-of-pharmacogenetic-polymorphisms-and-demographic-variables-on-metformin-pharmacokinetics-in-an-admixed-brazilian-cohort
#2
Ana Beatriz Santoro, Mariana Rodrigues Botton, Claudio José Struchiner, Guilherme Suarez-Kurtz
AIM: To identify pharmacogenetic and demographic variables that influence the systemic exposure to metformin in an admixed Brazilian cohort. METHODS: The extreme discordant phenotype was used to select 106 data sets from nine metformin bioequivalence trials, comprising 256 healthy adults. Eleven single-nucleotide polymorphisms in SLC22A1, SLC22A2, SLC47A1 SLC47A2 and in transcription factor SP1 were genotyped and a validated panel of ancestry informative markers was used to estimate the individual proportions of biogeographical ancestry...
January 20, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29352445/effect-of-sevoflurane-anesthesia-on-brain-is-mediated-by-lncrna-hotair
#3
Jian-Yue Wang, Yong Feng, Yan-Hong Fu, Guang-Li Liu
Postoperative cognitive dysfunction in elderly patients has been related to neurodegenerative disorders and mortality. Sevoflurane anesthesia has been implicated in both postoperative cognitive dysfunction and neurotoxicity. Given the advantages of using inhaled anesthetics like sevoflurane, it is important to understand how their usage results in neurotoxicity and subsequently devise ways to circumvent or attenuate the anesthetic-mediated induction in neurotoxicity. Long noncoding RNAs (LncRNAs) are a group of > 200 bp long RNAs and show specific spatiotemporal expression profiles...
January 19, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29352428/hnf4%C3%AE-is-involved-in-the-regulation-of-vertebrate-lc-pufa-biosynthesis-insights-into-the-regulatory-role-of-hnf4%C3%AE-on-expression-of-liver-fatty-acyl-desaturases-in-the-marine-teleost-siganus-canaliculatus
#4
Shuqi Wang, Junliang Chen, Danli Jiang, Qinghao Zhang, Cuihong You, Douglas R Tocher, Óscar Monroig, Yewei Dong, Yuanyou Li
Long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis is an important metabolic pathway in vertebrates, especially fish, considering they are the major source of n-3 LC-PUFA in the human diet. However, most fish have only limited capability for biosynthesis of LC-PUFA. The rabbitfish (Siganus canaliculatus) is able to synthesize LC-PUFA as it has all the key enzyme activities required including Δ6Δ5 Fads2, Δ4 Fads2, Elovl5, and Elovl4. We previously reported a direct interaction between the transcription factor Hnf4α and the promoter regions of Δ4 and Δ6Δ5 Fads2, which suggested that Hnf4α was involved in the transcriptional regulation of fads2 in rabbitfish...
January 19, 2018: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/29352377/difference-of-acute-dissociation-and-1-day-culture-on-the-electrophysiological-properties-of-rat-dorsal-root-ganglion-neurons
#5
Yuanlong Song, Miaomiao Zhang, Xiaoqing Tao, Zifen Xu, Yunjie Zheng, Minjie Zhu, Liangpin Zhang, Jinhan Qiao, Linlin Gao
The dissociated dorsal root ganglion (DRG) neurons with or without culture were widely used for investigation of their electrophysiological properties. The culture procedures, however, may alter the properties of these neurons and the effects are not clear. In the present study, we recorded the action potentials (AP) and the voltage-gated Na+, K+, and Ca2+ currents with patch clamp technique and measured the mRNA of Nav1.6-1.9 and Cav2.1-2.2 with real-time PCR technique from acutely dissociated and 1-day (1-d) cultured DRG neurons...
January 19, 2018: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29352310/leishmania-proteophosphoglycans-regurgitated-from-infected-sand-flies-accelerate-dermal-wound-repair-and-exacerbate-leishmaniasis-via-insulin-like-growth-factor-1-dependent-signalling
#6
Emilie Giraud, Tereza Lěstinová, Tamsyn Derrick, Oihane Martin, Rod J Dillon, Petr Volf, Ingrid Műller, Paul A Bates, Matthew E Rogers
Leishmania parasites are transmitted to vertebrate hosts by female phlebotomine sand flies as they bloodfeed by lacerating the upper capillaries of the dermis with their barbed mouthparts. In the sand fly midgut secreted proteophosphoglycans from Leishmania form a biological plug known as the promastigote secretory gel (PSG), which blocks the gut and facilitates the regurgitation of infective parasites. The interaction between the wound created by the sand fly bite and PSG is not known. Here we nanoinjected a sand fly egested dose of PSG into BALB/c mouse skin that lead to the differential expression of 7,907 transcripts...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352283/using-a-model-comparison-approach-to-describe-the-assembly-pathway-for-histone-h1
#7
Carlos Contreras, Minaya Villasana, Michael J Hendzel, Gustavo Carrero
Histones H1 or linker histones are highly dynamic proteins that diffuse throughout the cell nucleus and associate with chromatin (DNA and associated proteins). This binding interaction of histone H1 with the chromatin is thought to regulate chromatin organization and DNA accessibility to transcription factors and has been proven to involve a kinetic process characterized by a population that associates weakly with chromatin and rapidly dissociates and another population that resides at a binding site for up to several minutes before dissociating...
2018: PloS One
https://www.readbyqxmd.com/read/29352272/nuclear-p53-mediated-repression-of-autophagy-involves-pink1-transcriptional-down-regulation
#8
Thomas Goiran, Eric Duplan, Lila Rouland, Wejdane El Manaa, Inger Lauritzen, Julie Dunys, Han You, Frédéric Checler, Cristine Alves da Costa
p53 is a transcription factor that is implicated in the control of both apoptotic and autophagic cell death. This tumor suppressor elicits both pro-autophagic and anti-autophagic phenotypes depending of its intracellular localization. The ability of p53 to repress autophagy has been exclusively associated to its cytoplasmic localization. Here, we show that transcriptional activity of p53 also contributes to autophagy down-regulation. Thus, nuclear p53 controls PINK1, a key protein involved in the control of mitophagy, by repressing its promoter activity, protein and mRNA levels, ex-vivo and in vivo...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352246/u-box-ubiquitin-ligase-ppil2-suppresses-breast-cancer-invasion-and-metastasis-by-altering-cell-morphology-and-promoting-snai1-ubiquitination-and-degradation
#9
Zhaojun Jia, Miao Wang, Shujing Li, Xiahui Li, Xiao-Yan Bai, Zhaowei Xu, Yangyang Yang, Bowen Li, Yanan Li, Huijian Wu
Metastasis is the leading cause of breast cancer fatalities. To develop new therapeutic strategies, the mechanisms underlying breast cancer invasion and metastasis need to be further investigated. Peptidylprolyl isomerase (cyclophilin)-like 2 (PPIL2) is a U-box-type E3 ubiquitin ligase belonging to the cyclophilin family. Proteins within this family are the major cytosolic binding proteins of the immunosuppressant drug cyclosporine A (CsA). Although PPIL2 has been reported to potentially be involved in cell migration, its role in breast cancer is still unclear...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352242/ptre-seq-reveals-mechanism-and-interactions-of-rna-binding-proteins-and-mirnas
#10
Kyle A Cottrell, Hemangi G Chaudhari, Barak A Cohen, Sergej Djuranovic
RNA binding proteins (RBP) and microRNAs (miRNAs) often bind sequences in 3' untranslated regions (UTRs) of mRNAs, and regulate stability and translation efficiency. With the identification of numerous RBPs and miRNAs, there is an urgent need for new technologies to dissect the function of the cis-acting elements of RBPs and miRNAs. We describe post-transcriptional regulatory element sequencing (PTRE-seq), a massively parallel method for assaying the target sequences of miRNAs and RBPs. We use PTRE-seq to dissect sequence preferences and interactions between miRNAs and RBPs...
January 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/29352229/expression-dynamics-of-mirnas-and-their-targets-in-seed-germination-conditions-reveals-mirna-ta-sirna-crosstalk-as-regulator-of-seed-germination
#11
Shabari Sarkar Das, Sandeep Yadav, Archita Singh, Vibhav Gautam, Ananda K Sarkar, Asis K Nandi, Prakash Karmakar, Manoj Majee, Neeti Sanan-Mishra
Seed germination paves the way for the dormant embryo to establish itself as a new plant marking the first critical step in postembryonic plant growth and development. Germination starts with the uptake of water (imbibition), followed by induction of transcription, translation, energy metabolism, and cell division processes. Although small RNAs have been implicated in many developmental processes, their role during seed germination stages and conditions remained elusive. Here we show that seed germination conditions, like imbibition and temperature, dynamically regulate the expression of many developmentally important miRNAs and their targets...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352223/zeb1-confers-chemotherapeutic-resistance-to-breast-cancer-by-activating-atm
#12
Xiang Zhang, Zhen Zhang, Qing Zhang, Quansheng Zhang, Peiqing Sun, Rong Xiang, Guosheng Ren, Shuang Yang
Although zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key factor in the regulation of breast cancer differentiation and metastasis, its potential role in modulating tumor chemoresistance has not been fully understood. Here, through the study of specimens from a large cohort of human breast cancer subjects, we showed that patients with tumors that expressed high levels of ZEB1 responded poorly to chemotherapy. Moreover, ZEB1 expression was positively correlated with expression of B-cell lymphoma-extra large (Bcl-xL) and cyclin D1, which are key components of tumor chemoresistant mechanisms...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352220/soce-induced-calcium-overload-regulates-autophagy-in-acute-pancreatitis-via-calcineurin-activation
#13
Zhen-Dong Zhu, Tao Yu, Hua-Jing Liu, Jing Jin, Jun He
Acute pancreatitis (AP) is an acute inflammatory process of the pancreas that is characterized by inflammation, edema, vacuolization and necrosis, which has significant morbidity and lethality. The pathogenesis of AP has not been established completely. An early and critical feature of AP is the aberrant signaling of Calcium (Ca2+) within the pancreatic acinar cell, termed Ca2+ overload. Store-operated Ca2+ (SOC) channels are the principal Ca2+ influx channels that contribute to Ca2+ overload in pancreatic acinar cells...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352201/cross-species-transcriptional-analysis-reveals-conserved-and-host-specific-neoplastic-processes-in-mammalian-glioma
#14
Nina P Connolly, Amol C Shetty, Jesse A Stokum, Ina Hoeschele, Marni B Siegel, C Ryan Miller, Anthony J Kim, Cheng-Ying Ho, Eduardo Davila, J Marc Simard, Scott E Devine, John H Rossmeisl, Eric C Holland, Jeffrey A Winkles, Graeme F Woodworth
Glioma is a unique neoplastic disease that develops exclusively in the central nervous system (CNS) and rarely metastasizes to other tissues. This feature strongly implicates the tumor-host CNS microenvironment in gliomagenesis and tumor progression. We investigated the differences and similarities in glioma biology as conveyed by transcriptomic patterns across four mammalian hosts: rats, mice, dogs, and humans. Given the inherent intra-tumoral molecular heterogeneity of human glioma, we focused this study on tumors with upregulation of the platelet-derived growth factor signaling axis, a common and early alteration in human gliomagenesis...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352183/environmental-enrichment-increases-transcriptional-and-epigenetic-differentiation-between-mouse-dorsal-and-ventral-dentate-gyrus
#15
Tie-Yuan Zhang, Christopher L Keown, Xianglan Wen, Junhao Li, Dulcie A Vousden, Christoph Anacker, Urvashi Bhattacharyya, Richard Ryan, Josie Diorio, Nicholas O'Toole, Jason P Lerch, Eran A Mukamel, Michael J Meaney
Early life experience influences stress reactivity and mental health through effects on cognitive-emotional functions that are, in part, linked to gene expression in the dorsal and ventral hippocampus. The hippocampal dentate gyrus (DG) is a major site for experience-dependent plasticity associated with sustained transcriptional alterations, potentially mediated by epigenetic modifications. Here, we report comprehensive DNA methylome, hydroxymethylome and transcriptome data sets from mouse dorsal and ventral DG...
January 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/29352152/selection-and-validation-of-reference-genes-for-qrt-pcr-analysis-of-gene-expression-in-microsporum-canis-growing-under-different-adhesion-inducing-conditions
#16
Anita Ciesielska, Paweł Stączek
Dermatophytes are the group of filamentous fungi infecting keratinized structures such as skin, hair, and nails. Knowledge about genes and molecular mechanisms responsible for pathogenicity, as well as other biological properties of Microsporum canis is still relatively poor. The qRT-PCR is a reliable technique for quantifying gene expression across various biological processes, and choosing a set of suitable reference genes to normalize the expression data is a crucial step of this technique. We investigated the suitability of nine candidate reference genes: β-act, β-tub, adp-rf, ef1-α, sdha, rpl2, mbp1, psm1, and rGTPa for gene expression analysis in the dermatophyte M...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352081/expression-of-the-pseudomonas-aeruginosa-biofilm-antibiotic-resistance-gene-ndvb-requires-the-rpos-stationary-phase-sigma-factor
#17
Clayton W Hall, Aaron J Hinz, Luke B-P Gagnon, Li Zhang, Jean-Paul Nadeau, Sarah Copeland, Bratati Saha, Thien-Fah Mah
Chronic, biofilm-based bacterial infections are exceptionally difficult to eradicate due to the high degree of antibiotic recalcitrance exhibited by cells in biofilm communities. In the opportunistic pathogen Pseudomonas aeruginosa, biofilm recalcitrance is multifactorial and arises in part from the preferential expression of resistance genes in biofilms compared to exponential phase planktonic cells. One such mechanism involves ndvB, which we have previously shown to be expressed specifically in biofilms. In this study, we investigated the regulatory basis of this lifestyle-specific expression by developing an unstable GFP transcriptional reporter to observe the expression pattern of ndvB We found that, in addition to its expression in biofilms, ndvB was also upregulated in planktonic cells as they enter stationary phase...
January 19, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29352065/a-role-for-miniyo-and-quatre-quart-2-in-the-assembly-of-rna-polymerases-ii-iv-and-v-in-arabidopsis
#18
Yaoxi Li, Yuxiang Yuan, Xiaofeng Fang, Xiuli Lu, Bi Lian, Gaozhan Zhao, Yijun Qi
RNA polymerases IV and V (Pol IV and Pol V) are required for the generation of noncoding RNAs in RNA-directed DNA methylation (RdDM). Their subunit compositions resemble that of Pol II. The mechanism and accessory factors involved in their assembly remain largely unknown. In this study, we identified mutant alleles of MINIYO (IYO), QUATRE-QUART 2 (QQT2) and NUCLEAR RNA POLYMERASE B11/D11/E11 (NRPB/D/E11) that cause defects in RdDM in Arabidopsis. We found that Pol IV-dependent small interfering RNAs (siRNAs) and Pol V-dependent transcripts were greatly reduced in the mutants...
January 18, 2018: Plant Cell
https://www.readbyqxmd.com/read/29352064/gif-transcriptional-co-regulators-control-root-meristem-homeostasis
#19
María Florencia Ercoli, Antonella Ferela, Juan M Debernardi, Ana Paula Perrone, Ramiro E Rodriguez, Javier Fernando Palatnik
In the root meristem, the quiescent center (QC) is surrounded by stem cells, which in turn generate the different cell types of the root. QC cells rarely divide under normal conditions but can replenish damaged stem cells. In the proximal meristem, the daughters of stem cells, which are referred to as transit amplifying cells, undergo additional rounds of cell division prior to differentiation. Here, we describe the functions of GRF-INTERACTING FACTORs (GIFs), including ANGUSTIFOLIA3 (AN3), in Arabidopsis thaliana roots...
January 18, 2018: Plant Cell
https://www.readbyqxmd.com/read/29352015/sox2-is-required-for-olfactory-pit-formation-and-olfactory-neurogenesis-through-bmp-restriction-and-hes5-upregulation
#20
Tamilarasan K Panaliappan, Walter Wittmann, Vijay K Jidigam, Sara Mercurio, Jessica A Bertolini, Soufien Sghari, Raj Bose, Cedric Patthey, Silvia K Nicolis, Lena Gunhaga
The transcription factor Sox2 is necessary to maintain pluripotency of embryonic stem cells, and to regulate neural development. Neurogenesis in the vertebrate olfactory epithelium persists from embryonic stages through adulthood. The role Sox2 plays for the development of the olfactory epithelium and neurogenesis within has, however, not been determined. Here, by analysing Sox2 conditional knockout mouse embryos and chick embryos deprived of Sox2 in the olfactory epithelium using CRISPR-Cas9, we show that Sox2 activity is crucial for the induction of the neural progenitor gene Hes5 and for subsequent differentiation of the neuronal lineage...
January 19, 2018: Development
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