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https://www.readbyqxmd.com/read/29318513/targeted-elimination-of-mutant-mitochondrial-dna-in-melas-ipscs-by-mitotalens
#1
Yi Yang, Han Wu, Xiangjin Kang, Yanhui Liang, Ting Lan, Tianjie Li, Tao Tan, Jiangyun Peng, Quanjun Zhang, Geng An, Yali Liu, Qian Yu, Zhenglai Ma, Ying Lian, Boon Seng Soh, Qingfeng Chen, Ping Liu, Yaoyong Chen, Xiaofang Sun, Rong Li, Xiumei Zhen, Ping Liu, Yang Yu, Xiaoping Li, Yong Fan
Mitochondrial diseases are maternally inherited heterogeneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruction of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells (MiPSCs) that harbored a high proportion of m...
January 9, 2018: Protein & Cell
https://www.readbyqxmd.com/read/29306662/ciguatoxins-activate-the-calcineurin-signalling-pathway-in-yeasts-potential-for-development-of-an-alternative-detection-tool
#2
Hélène Martin-Yken, Camille Gironde, Sylvain Derick, Hélène Taiana Darius, Christophe Furger, Dominique Laurent, Mireille Chinain
Ciguatoxins (CTXs) are lipid-soluble polyether compounds produced by dinoflagellates from the genus Gambierdiscus spp. typically found in tropical and subtropical zones. This endemic area is however rapidly expanding due to environmental perturbations, and both toxic Gambierdiscus spp. and ciguatoxic fishes have been recently identified in the North Atlantic Ocean (Madeira and Canary islands) and Mediterranean Sea. Ciguatoxins bind to Voltage Gated Sodium Channels on the membranes of sensory neurons, causing Ciguatera Fish Poisoning (CFP) in humans, a disease characterized by a complex array of gastrointestinal, neurological, neuropsychological, and cardiovascular symptoms...
January 4, 2018: Environmental Research
https://www.readbyqxmd.com/read/29305530/role-of-purinergic-receptor-p2y1-in-spatiotemporal-ca2-dynamics-in-astrocytes
#3
Eiji Shigetomi, Yukiho J Hirayama, Kazuhiro Ikenaka, Kenji F Tanaka, Schuichi Koizumi
Fine processes of astrocytes enwrap synapses and are well-positioned to sense neuronal information via synaptic transmission. In rodents, astrocyte processes sense synaptic transmission via Gq-protein coupled receptors (GqPCR), including the P2Y1 receptor (P2Y1R), to generate Ca2+ signals. Astrocytes display numerous spontaneous microdomain Ca2+ signals; however, it is not clear if such signals are due to local synaptic transmission and/or in what timeframe astrocytes sense local synaptic transmission. To ask if GqPCRs mediate microdomain Ca2+ signals, we engineered mice (both sexes) to specifically overexpress P2Y1Rs in astrocytes and we visualized Ca2+ signals via a genetically encoded Ca2+ indicator, GCaMP6f, in astrocytes from adult mice...
January 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29285820/maldi-imaging-detects-endogenous-digoxin-in-glioblastoma-cells-infected-by-zika-virus-would-it-be-the-oncolytic-key
#4
Estela de O Lima, Tatiane M Guerreiro, Carlos Fernando O R Melo, Diogo N de Oliveira, Daisy Machado, Marcelo Lancelloti, Rodrigo R Catharino
Recently, microcephaly cases have increased in Americas and have been matter of concern due to Zika virus (ZIKV) recent outbreak. Previous studies have shown that ZIKV-infected progenitor neuronal cells present morphological abnormalities and increased rates of cell death, which may be indicators of microcephaly causes. As recent studies indicate Zika virus' tropism for brain cells, how would a glioblastoma (GBM) lineage behave under ZIKV infection, considering GBM the most common and malignant brain tumor in adults, presenting extreme chemoresistance and high morbidity and mortality rates? The current trend of using genetically engineered oncolytic pathogens as a safe way to eliminate tumors is under development, with trials already in course...
December 28, 2017: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/29250483/illuminating-brain-activities-with-fluorescent-protein-based-biosensors
#5
Zhijie Chen, Tan M Truong, Hui-Wang Ai
Fluorescent protein-based biosensors are indispensable molecular tools for life science research. The invention and development of high-fidelity biosensors for a particular molecule or molecular event often catalyze important scientific breakthroughs. Understanding the structural and functional organization of brain activities remain a subject for which optical sensors are in desperate need and of growing interest. Here, we review genetically encoded fluorescent sensors for imaging neuronal activities with a focus on the design principles and optimizations of various sensors...
2017: Chemosensors (Basel, Switzerland)
https://www.readbyqxmd.com/read/29242625/regulation-of-hyperoxia-induced-social-behaviour-in-pristionchus-pacificus-nematodes-requires-a-novel-cilia-mediated-environmental-input
#6
Eduardo Moreno, Bogdan Sieriebriennikov, Hanh Witte, Christian Rödelsperger, James W Lightfoot, Ralf J Sommer
Social behaviours are frequently utilised for defence and stress avoidance in nature. Both Caenorhabditis elegans and Pristionchus pacificus nematodes display social behaviours including clumping and bordering, to avoid hyperoxic stress conditions. Additionally, both species show natural variation in social behaviours with "social" and "solitary" strains. While the single solitary C. elegans N2 strain has evolved under laboratory domestication due to a gain-of-function mutation in the neuropeptide receptor gene npr-1, P...
December 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29231171/tracing-neuronal-circuits-in-transgenic-animals-by-transneuronal-control-of-transcription-tract
#7
Ting-Hao Huang, Peter Niesman, Deepshika Arasu, Daniel Lee, Aubrie De La Cruz, Antuca Callejas, Elizabeth J Hong, Carlos Lois
Understanding the computations that take place in brain circuits requires identifying how neurons in those circuits are connected to one another. We describe a technique called TRACT (TRAnsneuronal Control of Transcription) based on ligand-induced intramembrane proteolysis to reveal monosynaptic connections arising from genetically labeled neurons of interest. In this strategy, neurons expressing an artificial ligand ('donor' neurons) bind to and activate a genetically-engineered artificial receptor on their synaptic partners ('receiver' neurons)...
December 12, 2017: ELife
https://www.readbyqxmd.com/read/29144959/induction-of-innervation-by-encapsulated-adipocytes-with-engineered-vitamin-a-metabolism
#8
Qiwen Shen, Rumana Yasmeen, Jessica Marbourg, Lu Xu, Lianbo Yu, Paolo Fadda, Alan Flechtner, L James Lee, Phillip G Popovich, Ouliana Ziouzenkova
Innervation is a fundamental basis for function and survival of tissues. In the peripheral tissues, degenerative diseases create a neurotoxic metabolic milieu that either causes neurodegeneration or fails to sustain regenerative growth and reinnervation of injured/diseased tissues. Encapsulation of cells producing neurotrophic factors can augment axon growth and neuron survival; however, sustained innervation in vivo requires a combination of factors promoting axon growth and guidance pathway that are released in a tissue-specific context...
October 28, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29140243/a-versatile-genetic-tool-for-post-translational-control-of-gene-expression-in-drosophila-melanogaster
#9
Sachin Sethi, Jing W Wang
Several techniques have been developed to manipulate gene expression temporally in intact neural circuits. However, the applicability of current tools developed for in vivo studies in Drosophila is limited by their incompatibility with existing GAL4 lines and side effects on physiology and behavior. To circumvent these limitations, we adopted a strategy to reversibly regulate protein degradation with a small molecule by using a destabilizing domain (DD). We show that this system is effective across different tissues and developmental stages...
November 15, 2017: ELife
https://www.readbyqxmd.com/read/29120948/parvalbumin-containing-gaba-cells-and-schizophrenia-experimental-model-based-on-targeted-gene-delivery-through-adeno-associated-viruses
#10
Marta U Woloszynowska-Fraser, Peer Wulff, Gernot Riedel
Understanding the contribution of transmitter systems in behavioural pharmacology has a long tradition. Multiple techniques such as transmitter-specific lesions, and also localized administration of pharmacological toxins including agonists and antagonists of selected receptors have been applied. More recently, modern genetic tools have permitted cell-type selective interferences, for example by expression of light-sensitive channels followed by optogenetic stimulation in behaviourally meaningful settings or by engineered channels termed DREADDS that respond to peripherally administered drugs...
December 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/29097684/anion-conducting-channelrhodopsins-with-tuned-spectra-and-modified-kinetics-engineered-for-optogenetic-manipulation-of-behavior
#11
Jonas Wietek, Silvia Rodriguez-Rozada, Janine Tutas, Federico Tenedini, Christiane Grimm, Thomas G Oertner, Peter Soba, Peter Hegemann, J Simon Wiegert
Genetic engineering of natural light-gated ion channels has proven a powerful way to generate optogenetic tools for a wide variety of applications. In recent years, blue-light activated engineered anion-conducting channelrhodopsins (eACRs) have been developed, improved, and were successfully applied in vivo. We asked whether the approaches used to create eACRs can be transferred to other well-characterized cation-conducting channelrhodopsins (CCRs) to obtain eACRs with a broad spectrum of biophysical properties...
November 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29043563/malformation-of-the-posterior-cerebellar-vermis-is-a-common-neuroanatomical-phenotype-of-genetically-engineered-mice-on-the-c57bl-6-background
#12
Joshua A Cuoco, Anthony W Esposito, Shannon Moriarty, Ying Tang, Sonika Seth, Alyssa R Toia, Elias B Kampton, Yevgeniy Mayr, Mussarah Khan, Mohammad B Khan, Brian R Mullen, James B Ackman, Faez Siddiqi, John H Wolfe, Olga V Savinova, Raddy L Ramos
C57BL/6 mice exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the posterior vermis, indicative of neuronal migration defect during cerebellar development. Recognizing that many genetically engineered (GE) mouse lines are produced from C57BL/6 ES cells or backcrossed to this strain, we performed histological analyses and found that cerebellar heterotopia were a common feature present in the majority of GE lines on this background. Furthermore, we identify GE mouse lines that will be valuable in the study of cerebellar malformations including diverse driver, reporter, and optogenetic lines...
October 17, 2017: Cerebellum
https://www.readbyqxmd.com/read/28911965/physiological-roles-of-cns-muscarinic-receptors-gained-from-knockout-mice
#13
REVIEW
Morgane Thomsen, Gunnar Sørensen, Ditte Dencker
Because the five muscarinic acetylcholine receptor subtypes have overlapping distributions in many CNS tissues, and because ligands with a high degree of selectivity for a given subtype long remained elusive, it has been difficult to determine the physiological functions of each receptor. Genetically engineered knockout mice, in which one or more muscarinic acetylcholine receptor subtype has been inactivated, have been instrumental in identifying muscarinic receptor functions in the CNS, at the neuronal, circuit, and behavioral level...
September 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28903419/development-of-zebrafish-medulloblastoma-like-pnet-model-by-talen-mediated-somatic-gene-inactivation
#14
Jaegal Shim, Jung-Hwa Choi, Moon-Hak Park, Hyena Kim, Jong Hwan Kim, Seon-Young Kim, Dongwan Hong, Sunshin Kim, Ji Eun Lee, Cheol-Hee Kim, Jeong-Soo Lee, Young-Ki Bae
Genetically engineered animal tumor models have traditionally been generated by the gain of single or multiple oncogenes or the loss of tumor suppressor genes; however, the development of live animal models has been difficult given that cancer phenotypes are generally induced by somatic mutation rather than by germline genetic inactivation. In this study, we developed somatically mutated tumor models using TALEN-mediated somatic gene inactivation of cdkn2a/b or rb1 tumor suppressor genes in zebrafish. One-cell stage injection of cdkn2a/b-TALEN mRNA resulted in malignant peripheral nerve sheath tumors with high frequency (about 39%) and early onset (about 35 weeks of age) in F0 tp53(e7/e7) mutant zebrafish...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28802043/an-engineered-orco-mutation-produces-aberrant-social-behavior-and-defective-neural-development-in-ants
#15
Hua Yan, Comzit Opachaloemphan, Giacomo Mancini, Huan Yang, Matthew Gallitto, Jakub Mlejnek, Alexandra Leibholz, Kevin Haight, Majid Ghaninia, Lucy Huo, Michael Perry, Jesse Slone, Xiaofan Zhou, Maria Traficante, Clint A Penick, Kelly Dolezal, Kaustubh Gokhale, Kelsey Stevens, Ingrid Fetter-Pruneda, Roberto Bonasio, Laurence J Zwiebel, Shelley L Berger, Jürgen Liebig, Danny Reinberg, Claude Desplan
Ants exhibit cooperative behaviors and advanced forms of sociality that depend on pheromone-mediated communication. Odorant receptor neurons (ORNs) express specific odorant receptors (ORs) encoded by a dramatically expanded gene family in ants. In most eusocial insects, only the queen can transmit genetic information, restricting genetic studies. In contrast, workers in Harpegnathos saltator ants can be converted into gamergates (pseudoqueens) that can found entire colonies. This feature facilitated CRISPR-Cas9 generation of germline mutations in orco, the gene that encodes the obligate co-receptor of all ORs...
August 10, 2017: Cell
https://www.readbyqxmd.com/read/28800217/engineering-antibody-reactivity-for-efficient-derivatization-to-generate-nav1-7-inhibitory-gptx-1-peptide-antibody-conjugates
#16
Kaustav Biswas, Thomas E Nixey, Justin K Murray, James R Falsey, Li Yin, Hantao Liu, Jacinthe Gingras, Brian E Hall, Brad Herberich, Jerry Ryan Holder, Hongyan Li, Joseph Ligutti, Min-Hwa Jasmine Lin, Dong Liu, Brian D Soriano, Marcus Soto, Linh Tran, Christopher M Tegley, Anrou Zou, Kannan Gunasekaran, Bryan D Moyer, Liz Doherty, Les P Miranda
The voltage-gated sodium channel NaV1.7 is a genetically validated pain target under investigation for the development of analgesics. A therapeutic with a less frequent dosing regimen would be of value for treating chronic pain; however functional NaV1.7 targeting antibodies are not known. In this report, we describe NaV1.7 inhibitory peptide-antibody conjugates as an alternate construct for potential prolonged channel blockade through chemical derivatization of engineered antibodies. We previously identified NaV1...
September 15, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28794102/optogenetics-and-pharmacogenetics-principles-and-applications
#17
Jingwei Jiang, Huxing Cui, Kamal Rahmouni
Remote and selective spatiotemporal control of the activity of neurons to regulate behavior and physiological functions has been a long-sought goal in system neuroscience. Identification and subsequent bioengineering of light-sensitive ion channels (e.g., channelrhodopsins, halorhodopsin and archaerhodopsins) from the bacteria has made it possible to utilize light to artificially modulate neuronal activity, namely optogenetics. Recent advance in genetics has also allowed development of novel pharmacological tools to selectively and remotely control neuronal activity using engineered G-protein coupled receptors which can be activated by otherwise inert drug-like small molecules such as the Designer Receptors Exclusively Activated by Designer Drug (DREADD) - a form of chemogenetics...
August 9, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28753586/development-of-zebrafish-medulloblastoma-like-pnet-model-by-talen-mediated-somatic-gene-inactivation
#18
Jaegal Shim, Jung-Hwa Choi, Moon-Hak Park, Hyena Kim, Jong Hwan Kim, Seon-Young Kim, Dongwan Hong, Sunshin Kim, Ji Eun Lee, Cheol-Hee Kim, Jeong-Soo Lee, Young-Ki Bae
Genetically engineered animal tumor models have traditionally been generated by the gain of single or multiple oncogenes or the loss of tumor suppressor genes; however, the development of live animal models has been difficult given that cancer phenotypes are generally induced by somatic mutation rather than by germline genetic inactivation. In this study, we developed somatically mutated tumor models using TALEN-mediated somatic gene inactivation of cdkn2a/b or rb1 tumor suppressor genes in zebrafish. One-cell stage injection of cdkn2a/b-TALEN mRNA resulted in malignant peripheral nerve sheath tumors with high frequency (about 39%) and early onset (about 35 weeks of age) in F0 tp53e7/e7 mutant zebrafish...
July 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28734802/co-transplantation-of-mesenchymal-and-neural-stem-cells-and-overexpressing-stromal-derived-factor-1-for-treating-spinal-cord-injury
#19
Andrew N Stewart, Griffin Kendziorski, Zachary M Deak, Dara J Brown, Matthew N Fini, Katherine L Copely, Julien Rossignol, Gary L Dunbar
Genetic engineering of mesenchymal stem cells (MSCs) and neuronal stem cells (NSCs) has been used to treat spinal cord injuries (SCI). As a mechanism of therapy, MSCs secrete high amounts of anti-inflammatory cytokines and trophic factors, while NSCs can differentiate into neuronal lineages and aid in tissue replacement. Additionally, the forced overexpression of secreted proteins can enhance the secretome of transplanted cells, which can increase therapeutic efficacy. This study utilized a combinational treatment consisting of MSCs, NSCs, and the forced overexpression of the chemokine stromal-derived factor-1 (SDF-1) from MSCs (SDF-1-MSCs), to treat a rat model of SCI...
July 19, 2017: Brain Research
https://www.readbyqxmd.com/read/28699521/astrocyte-an-innovative-approach-for-alzheimer-s-disease-therapy
#20
Maria Rosanna Bronzuoli, Roberta Facchinetti, Luca Steardo, Caterina Scuderi
Alzheimer's disease is a devastating neurological illness with a heavy economic impact. Further comorbidity in combination with the social impact of this disorder increases the urgency of a clearer comprehension of its etiopathogenesis, allowing the execution of novel therapeutic strategies. Despite astrocytes have been widely described as active participant in the regulation of cerebral circuits, available data are still poor. Even less information is available about their precise role in the pathogenesis of illness...
July 10, 2017: Current Pharmaceutical Design
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