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https://www.readbyqxmd.com/read/29352615/gene-circuits-for-dynamically-regulating-metabolism
#1
Xiulai Chen, Liming Liu
Gene circuits are a functional innovation in synthetic biology for engineering cellular behavior. Recent advances have demonstrated that gene circuits can be exploited for dynamically controlling pathway redirection and pathway balance to produce valuable chemicals. The next frontier is to engineer robust, sensitive, and efficient circuits that adapt to changing conditions.
January 15, 2018: Trends in Biotechnology
https://www.readbyqxmd.com/read/29346770/integrative-analyses-of-de-novo-mutations-provide-deeper-biological-insights-into-autism-spectrum-disorder
#2
Atsushi Takata, Noriko Miyake, Yoshinori Tsurusaki, Ryoko Fukai, Satoko Miyatake, Eriko Koshimizu, Itaru Kushima, Takashi Okada, Mako Morikawa, Yota Uno, Kanako Ishizuka, Kazuhiko Nakamura, Masatsugu Tsujii, Takeo Yoshikawa, Tomoko Toyota, Nobuhiko Okamoto, Yoko Hiraki, Ryota Hashimoto, Yuka Yasuda, Shinji Saitoh, Kei Ohashi, Yasunari Sakai, Shouichi Ohga, Toshiro Hara, Mitsuhiro Kato, Kazuyuki Nakamura, Aiko Ito, Chizuru Seiwa, Emi Shirahata, Hitoshi Osaka, Ayumi Matsumoto, Saoko Takeshita, Jun Tohyama, Tomoko Saikusa, Toyojiro Matsuishi, Takumi Nakamura, Takashi Tsuboi, Tadafumi Kato, Toshifumi Suzuki, Hirotomo Saitsu, Mitsuko Nakashima, Takeshi Mizuguchi, Fumiaki Tanaka, Norio Mori, Norio Ozaki, Naomichi Matsumoto
Recent studies have established important roles of de novo mutations (DNMs) in autism spectrum disorders (ASDs). Here, we analyze DNMs in 262 ASD probands of Japanese origin and confirm the "de novo paradigm" of ASDs across ethnicities. Based on this consistency, we combine the lists of damaging DNMs in our and published ASD cohorts (total number of trios, 4,244) and perform integrative bioinformatics analyses. Besides replicating the findings of previous studies, our analyses highlight ATP-binding genes and fetal cerebellar/striatal circuits...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29345619/mir-9-regulates-basal-ganglia-dependent-developmental-vocal-learning-and-adult-vocal-performance-in-songbirds
#3
Zhimin Shi, Zoe Piccus, Xiaofang Zhang, Huidi Yang, Hannah Jarrell, Yan Ding, Zhaoqian Teng, Ofer Tchernichovski, XiaoChing Li
miR-9 is an evolutionarily conserved miRNA that is abundantly expressed in Area X, a basal ganglia nucleus required for vocal learning in songbirds. Here, we report that overexpression of miR-9 in Area X of juvenile zebra finches impairs developmental vocal learning, resulting in a song with syllable omission, reduced similarity to the tutor song, and altered acoustic features. miR-9 overexpression in juveniles also leads to more variable song performance in adulthood, and abolishes social context-dependent modulation of song variability...
January 18, 2018: ELife
https://www.readbyqxmd.com/read/29344862/cell-type-specific-laser-capture-microdissection-for-gene-expression-profiling-in-the-human-brain
#4
Sarah A Mauney, Tsung-Ung W Woo, Kai C Sonntag
Cell type-specific laser microdissection technologies in combination with molecular techniques to determine gene expression profiles have become powerful tools to gain insight into the neurobiological basis of neural circuit disturbances in various neurologic or psychiatric diseases. To identify specific cell populations in human postmortem brain tissue, one can use the inherent properties of the cells, such as pigmentation and morphology or their structural composition through immunohistochemistry (IHC). Here, we describe the isolation of homogeneous neurons and oligodendrocytes and the extraction of high-quality RNA from these cells in human postmortem brain using a combination of rapid IHC, Nissl staining, or simple morphology with Laser Capture Microdissection (LCM), or Laser Microdissection (LMD)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29343813/the-drosophila-gr28bd-product-is-a-non-specific-cation-channel-that-can-be-used-as-a-novel-thermogenetic-tool
#5
Aditi Mishra, Autoosa Salari, Benton R Berigan, Kayla C Miguel, Marzie Amirshenava, Abbey Robinson, Benjamin C Zars, Jenna L Lin, Lorin S Milescu, Mirela Milescu, Troy Zars
Extrinsic control of single neurons and neuronal populations is a powerful approach for understanding how neural circuits function. Adding new thermogenetic tools to existing optogenetic and other forms of intervention will increase the complexity of questions that can be addressed. A good candidate for developing new thermogenetic tools is the Drosophila gustatory receptor family, which has been implicated in high-temperature avoidance behavior. We examined the five members of the Gr28b gene cluster for temperature-dependent properties via three approaches: biophysical characterization in Xenopus oocytes, functional calcium imaging in Drosophila motor neurons, and behavioral assays in adult Drosophila...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343748/sac7-and-rho1-regulate-the-white-to-opaque-switching-in-candida-albicans
#6
Siwy Ling Yang, Guisheng Zeng, Fong Yee Chan, Yan-Ming Wang, Dongliang Yang, Yue Wang
Candida albicans cells homozygous at the mating-type locus stochastically undergo the white-to-opaque switching to become mating-competent. This switching is regulated by a core circuit of transcription factors organized through interlocking feedback loops around the master regulator Wor1. Although a range of distinct environmental cues is known to induce the switching, the pathways linking the external stimuli to the central control mechanism remains largely unknown. By screening a C. albicans haploid gene-deletion library, we found that SAC7 encoding a GTPase-activating protein of Rho1 is required for the white-to-opaque switching...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343640/single-cell-transcriptomics-of-the-developing-lateral-geniculate-nucleus-reveals-insights-into-circuit-assembly-and-refinement
#7
Brian T Kalish, Lucas Cheadle, Sinisa Hrvatin, M Aurel Nagy, Samuel Rivera, Megan Crow, Jesse Gillis, Rory Kirchner, Michael E Greenberg
Coordinated changes in gene expression underlie the early patterning and cell-type specification of the central nervous system. However, much less is known about how such changes contribute to later stages of circuit assembly and refinement. In this study, we employ single-cell RNA sequencing to develop a detailed, whole-transcriptome resource of gene expression across four time points in the developing dorsal lateral geniculate nucleus (LGN), a visual structure in the brain that undergoes a well-characterized program of postnatal circuit development...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339535/functional-changes-of-ampa-responses-in-human-induced-pluripotent-stem-cell-derived-neural-progenitors-in-fragile-x-syndrome
#8
Venkat Swaroop Achuta, Tommi Möykkynen, Ulla-Kaisa Peteri, Giorgio Turconi, Claudio Rivera, Kari Keinänen, Maija L Castrén
Altered neuronal network formation and function involving dysregulated excitatory and inhibitory circuits are associated with fragile X syndrome (FXS). We examined functional maturation of the excitatory transmission system in FXS by investigating the response of FXS patient-derived neural progenitor cells to the glutamate analog (AMPA). Neural progenitors derived from induced pluripotent stem cell (iPSC) lines generated from boys with FXS had augmented intracellular Ca2+ responses to AMPA and kainate that were mediated by Ca2+-permeable AMPA receptors (CP-AMPARs) lacking the GluA2 subunit...
January 16, 2018: Science Signaling
https://www.readbyqxmd.com/read/29333487/activation-of-the-medial-prefrontal-cortex-reverses-cognitive-and-respiratory-symptoms-in-a-mouse-model-of-rett-syndrome
#9
C James Howell, Michael P Sceniak, Min Lang, Wenceslas Krakowiecki, Fatimah E Abouelsoud, Saloni U Lad, Heping Yu, David M Katz
Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2; Amir et al., 1999), a transcriptional regulatory protein (Klose et al., 2005). Mouse models of RTT (Mecp2 mutants) exhibit excitatory hypoconnectivity in the medial prefrontal cortex (mPFC; Sceniak et al., 2015), a region critical for functions that are abnormal in RTT patients, ranging from learning and memory to regulation of visceral homeostasis (Riga et al...
November 2017: ENeuro
https://www.readbyqxmd.com/read/29329089/neural-circuit-dysfunction-in-mouse-models-of-neurodevelopmental-disorders
#10
REVIEW
Isabel Del Pino, Beatriz Rico, Oscar Marín
Neuropsychiatric disorders arise from the alteration of normal brain developmental trajectories disrupting the function of specific neuronal circuits. Recent advances in human genetics have greatly accelerated the identification of genes whose variation increases the susceptibility for neurodevelopmental disorders, most notably for autism spectrum disorder (ASD) and schizophrenia. In parallel, experimental studies in animal models-most typically in mice-are beginning to shed light on the role of these genes in the development and function of specific brain circuits...
January 9, 2018: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29326336/arid5b-as-a-critical-downstream-target-of-the-tal1-complex-that-activates-the-oncogenic-transcriptional-program-and-promotes-t-cell-leukemogenesis
#11
Wei Zhong Leong, Shi Hao Tan, Phuong Cao Thi Ngoc, Stella Amanda, Alice Wei Yee Yam, Wei-Siang Liau, Zhiyuan Gong, Lee N Lawton, Daniel G Tenen, Takaomi Sanda
The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-cell acute lymphoblastic leukemia (T-ALL) cells. However, the critical factors that are directly activated by TAL1 and contribute to T-ALL pathogenesis are largely unknown. Here, we identified AT-rich interactive domain 5B (ARID5B) as a collaborating oncogenic factor involved in the transcriptional program in T-ALL. ARID5B expression is down-regulated at the double-negative 2-4 stages in normal thymocytes, while it is induced by the TAL1 complex in human T-ALL cells...
January 11, 2018: Genes & Development
https://www.readbyqxmd.com/read/29325119/mir-96-is-required-for-normal-development-of-the-auditory-hindbrain
#12
Tina Schlüter, Christina Berger, Elena Rosengauer, Pascal Fieth, Constanze Krohs, Kathy Ushakov, Karen P Steel, Karen B Avraham, Alexander Hartmann, Felix Felmy, Hans Gerd Nothwang
The peripheral deafness gene Mir96 is expressed in both the cochlea and central auditory circuits. To investigate whether it plays a role in the auditory system beyond the cochlea, we characterized homozygous Dmdo/Dmdo mice with a point mutation in miR-96. Anatomical analysis demonstrated a significant decrease in volume of auditory nuclei in Dmdo/Dmdo mice. This decrease resulted from decreased cell size. Non-auditory structures in the brainstem of Dmdo/Dmdo mice or auditory nuclei of the congenital deaf Cldn14-/- mice revealed no such differences...
January 9, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29323298/a-metabolic-function-of-fgfr3-tacc3-gene-fusions-in-cancer
#13
Véronique Frattini, Stefano M Pagnotta, Tala, Jerry J Fan, Marco V Russo, Sang Bae Lee, Luciano Garofano, Jing Zhang, Peiguo Shi, Genevieve Lewis, Heloise Sanson, Vanessa Frederick, Angelica M Castano, Luigi Cerulo, Delphine C M Rolland, Raghvendra Mall, Karima Mokhtari, Kojo S J Elenitoba-Johnson, Marc Sanson, Xi Huang, Michele Ceccarelli, Anna Lasorella, Antonio Iavarone
Chromosomal translocations that generate in-frame oncogenic gene fusions are notable examples of the success of targeted cancer therapies. We have previously described gene fusions of FGFR3-TACC3 (F3-T3) in 3% of human glioblastoma cases. Subsequent studies have reported similar frequencies of F3-T3 in many other cancers, indicating that F3-T3 is a commonly occuring fusion across all tumour types. F3-T3 fusions are potent oncogenes that confer sensitivity to FGFR inhibitors, but the downstream oncogenic signalling pathways remain unknown...
January 11, 2018: Nature
https://www.readbyqxmd.com/read/29321169/the-actin-mrtf-srf-transcriptional-circuit-controls-tubulin-acetylation-via-%C3%AE-tat1-gene-expression
#14
Jaime Fernández-Barrera, Miguel Bernabé-Rubio, Javier Casares-Arias, Laura Rangel, Laura Fernández-Martín, Isabel Correas, Miguel A Alonso
The role of formins in microtubules is not well understood. In this study, we have investigated the mechanism by which INF2, a formin mutated in degenerative renal and neurological hereditary disorders, controls microtubule acetylation. We found that silencing of INF2 in epithelial RPE-1 cells produced a dramatic drop in tubulin acetylation, increased the G-actin/F-actin ratio, and impaired myocardin-related transcription factor (MRTF)/serum response factor (SRF)-dependent transcription, which is known to be repressed by increased levels of G-actin...
January 10, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29320737/genomic-circuitry-underlying-immunological-response-to-pediatric-acute-respiratory-infection
#15
Sarah E Henrickson, Sasikanth Manne, Douglas V Dolfi, Kathleen D Mansfield, Kaela Parkhouse, Rakesh D Mistry, Elizabeth R Alpern, Scott E Hensley, Kathleen E Sullivan, Susan E Coffin, E John Wherry
Acute respiratory tract viral infections (ARTIs) cause significant morbidity and mortality. CD8 T cells are fundamental to host responses, but transcriptional alterations underlying anti-viral mechanisms and links to clinical characteristics remain unclear. CD8 T cell transcriptional circuitry in acutely ill pediatric patients with influenza-like illness was distinct for different viral pathogens. Although changes included expected upregulation of interferon-stimulated genes (ISGs), transcriptional downregulation was prominent upon exposure to innate immune signals in early IFV infection...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29319503/synthesizing-artificial-devices-that-redirect-cellular-information-at-will
#16
Yuchen Liu, Jianfa Li, Zhicong Chen, Weiren Huang, Zhiming Cai
Natural signaling circuits could be rewired to reprogram cells with pre-determined procedures. However, it is difficult to link cellular signals at will. Here, we describe signal-connectors-a series of RNA devices-that connect one signal to another signal at the translational level. We use them to either repress or enhance the translation of target genes in response to signals. Application of these devices allows us to construct various logic gates and to incorporate feedback loops into gene networks. They have also been used to rewire a native signaling pathway and even to create novel pathways...
January 10, 2018: ELife
https://www.readbyqxmd.com/read/29318198/transcription-control-engineering-and-applications-in-synthetic-biology
#17
REVIEW
Michael D Engstrom, Brian F Pfleger
In synthetic biology, researchers assemble biological components in new ways to produce systems with practical applications. One of these practical applications is control of the flow of genetic information (from nucleic acid to protein), a.k.a. gene regulation. Regulation is critical for optimizing protein (and therefore activity) levels and the subsequent levels of metabolites and other cellular properties. The central dogma of molecular biology posits that information flow commences with transcription, and accordingly, regulatory tools targeting transcription have received the most attention in synthetic biology...
September 2017: Synthetic and Systems Biotechnology
https://www.readbyqxmd.com/read/29317598/enriched-expression-of-genes-associated-with-autism-spectrum-disorders-in-human-inhibitory-neurons
#18
Ping Wang, Dejian Zhao, Herbert M Lachman, Deyou Zheng
Autism spectrum disorder (ASD) is highly heritable but genetically heterogeneous. The affected neural circuits and cell types remain unclear and may vary at different developmental stages. By analyzing multiple sets of human single cell transcriptome profiles, we found that ASD candidates showed relatively enriched gene expression in neurons, especially in inhibitory neurons. ASD candidates were also more likely to be the hubs of the co-expression gene module that is highly expressed in inhibitory neurons, a feature not detected for excitatory neurons...
January 10, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29311651/identification-of-a-novel-gene-regulating-amygdala-mediated-fear-extinction
#19
Ozge Gunduz-Cinar, Emma Brockway, Lauren Lederle, Troy Wilcox, Lindsay R Halladay, Ying Ding, Hyunjung Oh, Erica F Busch, Katie Kaugars, Shaun Flynn, Aaron Limoges, Olena Bukalo, Kathryn P MacPherson, Sophie Masneuf, Courtney Pinard, Etienne Sibille, Elissa J Chesler, Andrew Holmes
Recent years have seen advances in our understanding of the neural circuits associated with trauma-related disorders, and the development of relevant assays for these behaviors in rodents. Although inherited factors are known to influence individual differences in risk for these disorders, it has been difficult to identify specific genes that moderate circuit functions to affect trauma-related behaviors. Here, we exploited robust inbred mouse strain differences in Pavlovian fear extinction to uncover quantitative trait loci (QTL) associated with this trait...
January 8, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29311262/multidimensional-quantitative-analysis-of-mrna-expression-within-intact-vertebrate-embryos
#20
Vikas Trivedi, Harry M T Choi, Scott E Fraser, Niles A Pierce
For decades, in situ hybridization methods have been essential tools for studies of vertebrate development and disease, as they enable qualitative analyses of mRNA expression in an anatomical context. Quantitative mRNA analyses typically sacrifice the anatomy, relying on embryo microdissection, dissociation, cell sorting and/or homogenization. Here, we eliminate the trade-off between quantitation and anatomical context, using quantitative in situ hybridization chain reaction (qHCR) to perform accurate and precise relative quantitation of mRNA expression with subcellular resolution within whole-mount vertebrate embryos...
January 8, 2018: Development
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