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Gene circuits

Lan Mi, Bin Yang, Xialu Hu, Yang Luo, Jianxin Liu, Zhongtang Yu, Jiakun Wang
The rumen and the hindgut represent two different fermentation organs in herbivorous mammals, with the former producing much more methane than the latter. The objective of this study was to elucidate the microbial underpinning of such differential methane outputs between these two digestive organs. Methane production was measured from 5 adult sheep and 15 adult rabbits, both of which were placed in open-circuit respiratory chambers and fed the same diet (alfalfa hay). The sheep produced more methane than the rabbits per unit of metabolic body weight, digestible neutral detergent fiber, and acid detergent fiber...
2018: Frontiers in Microbiology
Douglas W Brown, Arya J Bahrami, David A Canton, Anandaroop Mukhopadhyay, Jean S Campbell, Robert H Pierce, Richard J Connolly
Intratumoral electroporation of plasmid DNA encoding the proinflammatory cytokine interleukin 12 promotes innate and adaptive immune responses correlating with anti-tumor effects. Clinical electroporation conditions are fixed parameters optimized in preclinical tumors, which consist of cells implanted into skin. These conditions have little translatability to clinically relevant tumors, as implanted models cannot capture the heterogeneity encountered in genetically engineered mouse models or clinical tumors...
April 9, 2018: Bioelectrochemistry
Naoyuki Matsumoto, Nobuhiko Yamamoto
Axon branching and synapse formation are crucial processes for establishing precise neuronal circuits. During development, sensory thalamocortical (TC) axons form branches and synapses in specific layers of the cerebral cortex. Despite the obvious spatial correlation between axon branching and synapse formation, the causal relationship between them is poorly understood. To address this issue, we recently developed a method for simultaneous imaging of branching and synapse formation of individual TC axons in organotypic cocultures...
March 28, 2018: Journal of Visualized Experiments: JoVE
François Bertaux, Samuel Marguerat, Vahid Shahrezaei
The cell division rate, size and gene expression programmes change in response to external conditions. These global changes impact on average concentrations of biomolecule and their variability or noise. Gene expression is inherently stochastic, and noise levels of individual proteins depend on synthesis and degradation rates as well as on cell-cycle dynamics. We have modelled stochastic gene expression inside growing and dividing cells to study the effect of division rates on noise in mRNA and protein expression...
March 2018: Royal Society Open Science
Xiang Zhang, Xiao Zhang, Ting Wang, Lei Wang, Zhijun Tan, Wei Wei, Bo Yan, Jing Zhao, Kaichun Wu, Angang Yang, Rui Zhang, Lintao Jia
Overexpressed c-Myc and EZH2 usually mean high malignancy in cancers. Most of mortality from cancer is attributable to metastasis. MicroRNAs(miRNAs), like transcription factors, can regulate hundreds of genes. Here, we identify microRNA-26a (miR-26a) suppresses EZH2 and c-Myc by targeting EZH2 and CDK8 in Wnt pathway. MiR-26a is a well-known tumor-suppressive miRNA in multiple cancers, but how it is downregulated in hepatocellular carcinoma (HCC) is still unclear. Here, we disclose miR-26a is epigenetic silenced by a c-Myc-mediated PRC2-depandent way in HCC...
April 10, 2018: Cancer Letters
Richard W Pierce, Riad Abou Zahr, Sarah Kandil, E Vincent S Faustino, Jordan S Pober
OBJECTIVES: Children undergoing cardiopulmonary bypass develop clinically impactful capillary leak of unclear etiology. A widely held hypothesis that exposure of circulating cells to the cardiopulmonary bypass circuit induces the release of inflammatory mediators that act to disrupt intercellular junctions of capillary endothelial cells inducing paracellular capillary leak either directly or through new gene expression. DESIGN: Cohort study. SETTING: Tertiary pediatric hospital...
April 12, 2018: Pediatric Critical Care Medicine
Yidan Tang, Baiyang Lu, Zhentong Zhu, Bingling Li
The polymerase chain reaction and many isothermal amplifications are able to achieve super gene amplification. Unfortunately, most commonly-used transduction methods, such as dye staining and Taqman-like probing, still suffer from shortcomings including false signals or difficult probe design, or are incompatible with multi-analysis. Here a universal and rational gene detection strategy has been established by translating isothermal amplicons to enzyme-free strand displacement circuits via three-way junction-based remote transduction...
January 21, 2018: Chemical Science
Kelsey D Galimba, Jesús Martínez-Gómez, Verónica S Di Stilio
The floral organ identity gene APETALA3 ( AP3 ) is a MADS-box transcription factor involved in stamen and petal identity that belongs to the B-class of the ABC model of flower development. Thalictrum (Ranunculaceae), an emerging model in the non-core eudicots, has AP3 homologs derived from both ancient and recent gene duplications. Prior work has shown that petals have been lost repeatedly and independently in Ranunculaceae in correlation with the loss of a specific AP3 paralog, and Thalictrum represents one of these instances...
2018: Frontiers in Plant Science
Zhi-Wei Lu, Ming-Yu Du, Lu-Xi Qian, Nan Zhang, Jia-Jia Gu, Kai Ding, Jing Wu, Hong-Ming Zhu, Xia He, Li Yin
Background: In recent years, miR-152 has been dysregulated in a variety of tumors and used as a tumor suppressor. Nevertheless, its role in nasopharyngeal carcinoma (NPC) remains unidentified. Materials and methods: Real-time quantitative PCR (polymerase chain reaction) was performed to analyze the expression of miR-152 in NPC cell lines. MiR-152 expression profiles in NPC tissues were obtained from Gene Expression Omnibus (GEO GSE36682). The effect of miR-152 on the invasion and proliferation of NPC cells was determined through cell invasion, wound healing, and cell viability assays...
2018: OncoTargets and Therapy
Alexander Stewart, Pascal I Hablützel, Hayley V Watson, Martha Brown, Ida M Friberg, Joanne Cable, Joseph A Jackson
Seasonal patterns in immunity are frequently observed in vertebrates but are poorly understood. Here, we focused on a natural piscine model, the three-spined stickleback ( Gasterosteus aculeatus ), and asked how seasonal immune allocation is driven by physical variables (time, light, and heat). Using functionally-relevant gene expression metrics as a reporter of seasonal immune allocation, we synchronously sampled fish monthly from the wild (two habitats), and from semi-natural outdoors mesocosms (stocked from one of the wild habitats)...
2018: Frontiers in Immunology
Xiaoping Han, Haide Chen, Daosheng Huang, Huidong Chen, Lijiang Fei, Chen Cheng, He Huang, Guo-Cheng Yuan, Guoji Guo
BACKGROUND: Human pluripotent stem cells (hPSCs) provide powerful models for studying cellular differentiations and unlimited sources of cells for regenerative medicine. However, a comprehensive single-cell level differentiation roadmap for hPSCs has not been achieved. RESULTS: We use high throughput single-cell RNA-sequencing (scRNA-seq), based on optimized microfluidic circuits, to profile early differentiation lineages in the human embryoid body system. We present a cellular-state landscape for hPSC early differentiation that covers multiple cellular lineages, including neural, muscle, endothelial, stromal, liver, and epithelial cells...
April 5, 2018: Genome Biology
Kenji Saito, Huxing Cui
In addition to their well-known role in the female reproductive system, estrogens can act in the brain to regulate a wide range of behaviors and physiological functions in both sexes. Over the past few decades, genetically modified animal models have greatly increased our knowledge about the roles of estrogen receptor (ER) signaling in the brain in behavioral and physiological regulations. However, less attention has been paid to the estrogen-related receptors (ERRs), the members of orphan nuclear receptors whose sequences are homologous to ERs but lack estrogen-binding ability...
April 5, 2018: International Journal of Molecular Sciences
Xu Feng, Mengmeng Sun, Wenyuan Han, Yun Xiang Liang, Qunxin She
Previously it was shown that UV irradiation induces a strong upregulation of tfb3 coding for a paralog of the archaeal transcriptional factor B (TFB) in Sulfolobus solfataricus, a crenarchaea. To investigate the function of this gene in DNA damage response (DDR), tfb3 was inactivated by gene deletion in Sulfolobus islandicus and the resulting Δtfb3 was more sensitive to DNA damage agents than the original strain. Transcriptome analysis revealed that a large set of genes show TFB3-dependent activation, including genes of the ups operon and ced system...
March 30, 2018: Nucleic Acids Research
Venturina Stagni, Claudia Cirotti, Daniela Barilà
Ataxia-telangiectasia mutated kinase (ATM) plays a central role in the DNA damage response (DDR) and mutations in its gene lead to the development of a rare autosomic genetic disorder, ataxia telangiectasia (A-T) characterized by neurodegeneration, premature aging, defects in the immune response, and higher incidence of lymphoma development. The ability of ATM to control genome stability several pointed to ATM as tumor suppressor gene. Growing evidence clearly support a significant role of ATM, in addition to its master ability to control the DDR, as principle modulator of oxidative stress response and mitochondrial homeostasis, as well as in the regulation of autophagy, hypoxia, and cancer stem cell survival...
2018: Frontiers in Oncology
Raul M Luque, Rhonda D Kineman
Neuronostatin, a somatostatin gene-encoded peptide, exerts important physiological and metabolic actions in diverse tissues. However, the direct biological effects of neuronostatin on pituitary function of humans and primates are still unknown. This study used baboon (Papio anubis) primary pituitary cell cultures, a species that closely models human physiology, to demonstrate that neuronostatin inhibits basal, but not ghrelin-/GnRH-stimulated, GH and LH secretion in a dose- and time-dependent fashion, without affecting the secretion of other pituitary hormones (prolactin, ACTH, FSH, TSH) or changing mRNA levels...
April 3, 2018: Journal of Endocrinology
Peter V Lovell, Nicole A Huizinga, Samantha R Friedrich, Morgan Wirthlin, Claudio V Mello
BACKGROUND: The ability to imitate the vocalizations of other organisms, a trait known as vocal learning, is shared by only a few organisms, including humans, where it subserves the acquisition of speech and language, and 3 groups of birds. In songbirds, vocal learning requires the coordinated activity of a set of specialized brain nuclei referred to as the song control system. Recent efforts have revealed some of the genes that are expressed in these vocal nuclei, however a thorough characterization of the transcriptional specializations of this system is still missing...
April 3, 2018: BMC Genomics
Sabrina Sun, David V Schaffer
Optimization of traditional replication-competent viral tracers has granted access to immediate synaptic partners of target neuronal populations, enabling the dissection of complex brain circuits into functional neural pathways. The excessive virulence of most conventional tracers, however, impedes their utility in revealing and genetically perturbing cellular function on long time scales. As a promising alternative, the natural capacity of adeno-associated viral (AAV) vectors to safely mediate persistent and robust gene expression has stimulated strong interest in adapting them for sparse neuronal labeling and physiological studies...
March 31, 2018: Current Opinion in Neurobiology
Yoram Zarai, Tamir Tuller
Recent studies have demonstrated how the competition for the finite pool of available gene expression factors has important effect on fundamental gene expression aspects. In this study, based on a whole-cell model simulation of translation in S. cerevisiae, we evaluate for the first time the expected effect of mRNA levels fluctuations on translation due to the finite pool of ribosomes. We show that fluctuations of a single gene or a group of genes mRNA levels induce periodic behavior in all S. cerevisiae translation factors and aspects: the ribosomal densities and the translation rates of all S...
April 3, 2018: PLoS Computational Biology
C Beinke, M Port, R Ullmann, K Gilbertz, M Majewski, M Abend
Dicentric chromosome analysis (DCA) is the gold standard for individual radiation dose assessment. However, DCA is limited by the time-consuming phytohemagglutinin (PHA)-mediated lymphocyte activation. In this study using human peripheral blood lymphocytes, we investigated PHA-associated whole genome gene expression changes to elucidate this process and sought to identify suitable gene targets as a means of meeting our long-term objective of accelerating cell cycle kinetics to reduce DCA culture time. Human peripheral whole blood from three healthy donors was separately cultured in RPMI/FCS/antibiotics with BrdU and PHA-M...
April 3, 2018: Radiation Research
Ruoqi Gao, Nicolas H Piguel, Alexandria E Melendez-Zaidi, Maria Dolores Martin-de-Saavedra, Sehyoun Yoon, Marc P Forrest, Kristoffer Myczek, Gefei Zhang, Theron A Russell, John G Csernansky, D James Surmeier, Peter Penzes
Contactin associated protein-like 2 (CNTNAP2) has emerged as a prominent susceptibility gene implicated in multiple complex neurodevelopmental disorders, including autism spectrum disorders (ASD), intellectual disability (ID), and schizophrenia (SCZ). The presence of seizure comorbidity in many of these cases, as well as inhibitory neuron dysfunction in Cntnap2 knockout (KO) mice, suggests CNTNAP2 may be crucial for proper inhibitory network function. However, underlying cellular mechanisms are unclear. Here we show that cultured Cntnap2 KO mouse neurons exhibit an inhibitory neuron-specific simplification of the dendritic tree...
April 2, 2018: Molecular Psychiatry
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