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https://www.readbyqxmd.com/read/29235474/engineering-cell-signaling-using-tunable-crispr-cpf1-based-transcription-factors
#1
Yuchen Liu, Jinghong Han, Zhicong Chen, Hanwei Wu, Hongsong Dong, Guohui Nie
The catalytically dead Cpf1 endonuclease from Acidaminococcus sp. BV3L6 (dAsCpf1) has been used to construct effective transcriptional repressors in bacteria and plants. However, it is still unclear if dAsCpf1 can function in human cells as a transcriptional regulator or a signal conductor. Here, we repurpose the dAsCpf1 system in human cells for a variety of functions, including the activation or repression of gene transcription. Moreover, we construct programmable ligand-controlled dAsCpf1 systems either by coupling crRNAs with engineered riboswitches or by fusing dAsCpf1 proteins with G protein-coupled receptors...
December 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29233099/pronounced-strain-specific-chemosensory-receptor-gene-expression-in-the-mouse-vomeronasal-organ
#2
Kyle Duyck, Vasha DuTell, Limei Ma, Ariel Paulson, C Ron Yu
BACKGROUND: The chemosensory system plays an important role in orchestrating sexual behaviors in mammals. Pheromones trigger sexually dimorphic behaviors and different mouse strains exhibit differential responses to pheromone stimuli. It has been speculated that differential gene expression in the sensory organs that detect pheromones may underlie sexually-dimorphic and strain-specific responses to pheromone cues. RESULTS: We have performed transcriptome analyses of the mouse vomeronasal organ, a sensory organ recognizing pheromones and interspecies cues...
December 12, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29232504/a-genetic-toolbox-for-modulating-the-expression-of-heterologous-genes-in-the-cyanobacterium-synechocystis-sp-pcc-6803
#3
Bo Wang, Carrie Eckert, Pin-Ching Maness, Jianping Yu
Cyanobacteria, genetic models for photosynthesis research for decades, have recently become attractive hosts for producing renewable fuels and chemicals, owing to their genetic tractability, relatively fast growth, and their ability to utilize sunlight, fix carbon dioxide and, in some cases, fix nitrogen. Despite significant advances, there is still an urgent demand for synthetic biology tools in order to effectively manipulate genetic circuits in cyanobacteria. In this study, we have compared a total of 17 natural and chimeric promoters, focusing on expression of the ethylene-forming enzyme (EFE) in the cyanobacterium Synechocystis sp...
December 12, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29229875/re-engineering-the-two-component-systems-as-light-regulated-in-escherichia-coli
#4
Siya Ma, Siwei Luo, L I Wu, Zhi Liang, Jia-Rui Wu
Bacteria live in environments with dynamic changes. To sense and respond to different external stimuli, bacteria make use of various sensor-response circuits, called two-component systems (TCSs). A TCS comprises a histidine protein kinase (HK) sensing environmental stimuli and a response regulator protein (RR) regulating downstream genes. The two components are coupled via a phosphorylation control mechanism. In a recent study, we adopted an optogenetics approach to re-engineer the sensor HKs in Escherichia coli as a light-sensing fusion protein...
December 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/29227103/a-robust-molecular-network-motif-for-period-doubling-devices
#5
Christian Cuba Samaniego, Elisa Franco
Life is sustained by a variety of cyclic processes such as cell division, muscle contraction, and neuron firing. The periodic signals powering these processes often direct a variety of other downstream systems, which operate at different time scales and must have the capacity to divide or multiply the period of the master clock. Period modulation is also an important challenge in synthetic molecular systems, where slow and fast components may have to be coordinated simultaneously by a single oscillator whose frequency is often difficult to tune...
December 11, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29226467/axon-guidance-pathways-and-the-control-of-gene-expression
#6
REVIEW
Samantha A Russell, Greg J Bashaw
Axons need to be properly guided to their targets to form synaptic connections, and this requires interactions between highly conserved extracellular and transmembrane ligands and their cell surface receptors. The majority of studies on axon guidance signaling pathways have focused on the role of these pathways in rearranging the local cytoskeleton and plasma membrane in growth cones and axons. However, a smaller body of work has demonstrated that axon guidance signaling pathways also control gene expression via local translation and transcription...
December 11, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/29226124/epigenetic-and-neural-circuitry-landscape-of-psychotherapeutic-interventions
#7
REVIEW
Christopher W T Miller
The science behind psychotherapy has garnered considerable interest, as objective measures are being developed to map the patient's subjective change over the course of treatment. Prenatal and early life influences have a lasting impact on how genes are expressed and the manner in which neural circuits are consolidated. Transgenerationally transmitted epigenetic markers as well as templates of enhanced thought flexibility versus evasion can be passed down from parent to child. This influences gene expression/repression (impacting neuroplasticity) and kindling of neurocircuitry which can perpetuate maladaptive cognitive processing seen in a number of psychiatric conditions...
2017: Psychiatry Journal
https://www.readbyqxmd.com/read/29225348/a-multi-dimensional-characterization-of-anxiety-in-monozygotic-twin-pairs-reveals-susceptibility-loci-in-humans
#8
Reid S Alisch, Carol Van Hulle, Pankaj Chopra, Anita Bhattacharyya, Su-Chun Zhang, Richard J Davidson, Ned H Kalin, H Hill Goldsmith
The etiology of individual differences in human anxiousness is complex and includes contributions from genetic, epigenetic (i.e., DNA methylation) and environmental factors. Past genomic approaches have been limited in their ability to detect human anxiety-related differences in these factors. To overcome these limitations, we employed both a multi-dimensional characterization method, to select monozygotic twin pairs discordant for anxiety, and whole genome DNA methylation sequencing. This approach revealed 230 anxiety-related differentially methylated loci that were annotated to 183 genes, including several known stress-related genes such as NAV1, IGF2, GNAS, and CRTC1...
December 11, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29225236/microfluidic-platform-for-analyzing-the-thermotaxis-of-c-elegans-in-a-linear-temperature-gradient
#9
Sunhee Yoon, Hailing Piao, Tae-Joon Jeon, Sun Min Kim
Caenorhabditis elegans (C. elegans), which shares a considerable amount of characteristics with human genes is one of the important model organisms for the study of behavioral responses. Thermotaxis is a representative behavior response of C. elegans; C. elegans stores the cultivation temperature in thermosensory neurons and moves to the cultivation temperature region in a temperature variation. In this study, we developed a microfluidic system for effective thermotaxis analysis of C. elegans. The microfluidic channel was fabricated using polydimethylsiloxane (PDMS) by soft lithography process...
2017: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
https://www.readbyqxmd.com/read/29222989/disrupted-circuits-in-mouse-models-of-autism-spectrum-disorder-and-intellectual-disability
#10
REVIEW
Carla Em Golden, Joseph D Buxbaum, Silvia De Rubeis
Autism spectrum disorder (ASD) and intellectual disability (ID) are caused by a wide range of genetic mutations, a significant fraction of which reside in genes important for synaptic function. Studies have found that sensory, prefrontal, hippocampal, cerebellar, and striatal regions, as well as the circuits that connect them, are perturbed in mouse models of ASD and ID. Dissecting the disruptions in morphology and activity in these neural circuits might help us to understand the shared risk between the two disorders as well as their clinical heterogeneity...
December 5, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29222758/differential-proteomics-based-on-2d-difference-in-gel-electrophoresis-and-tandem-mass-spectrometry-for-the-elucidation-of-biological-processes-in-antibiotic-producer-bacterial-strains
#11
Giuseppe Gallo, Andrea Scaloni
Proteomics based on 2D-Difference In Gel Electrophoresis (2D-DIGE) coupled with mass spectrometry (MS) procedures can be considered a "gold standard" to determine quantitatively and comparatively protein abundances in cell extracts from different biological sources/conditions according to a gel-based approach. In particular, 2D-DIGE is used for protein specie separation, detection, and relative quantification, whenever tandem MS is used to obtain peptide sequence information that is managed according to bioinformatic procedures to identify the differentially represented protein species...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29221158/epigenetic-silencing-of-mir-296-and-mir-512-ensures-htert-dependent-apoptosis-protection-and-telomere-maintenance-in-basal-type-breast-cancer-cells
#12
Roberto Dinami, Valentina Buemi, Rosanna Sestito, Antonina Zappone, Yari Ciani, Miguel Mano, Eleonora Petti, Andrea Sacconi, Giovanni Blandino, Mauro Giacca, Silvano Piazza, Roberta Benetti, Stefan Schoeftner
The catalytic subunit of the telomerase complex, hTERT, ensures unlimited proliferative potential of cancer cells by maintaining telomere function and protecting from apoptosis. Using a miRNA screening approach we identified miR-296-5p and miR-512-5p as miRNAs that target hTERT in breast cancer cells. Ectopic miR-296-5p and miR-512-5p reduce telomerase activity, drive telomere shortening and cause proliferation defects by enhancing senescence and apoptosis in breast cancer cells. In line with the relevance of hTERT expression for human cancer we found that miR-296-5p and miR-512-5p expression is reduced in human breast cancer...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29217690/re-positioning-of-somatic-golgi-apparatus-is-essential-for-the-dendritic-establishment-of-adult-born-hippocampal-neurons
#13
Sneha Rao, Gregory W Kirschen, Joanna Szczurkowska, Adrian Di Antonio, Jia Wang, Shaoyu Ge, Maya Shelly
New dentate granule cells are continuously generated, and integrate into the pre-existing hippocampal network in the adult brain. How an adult-born neuron with initially simple spindle-like morphology develops into a complex dentate granule cell (DGC), consisting of a single apical dendrite with further branches, remains largely unknown. Here, using retroviruses to birth-date and manipulate newborn neurons, we examined initial dendritic formation, and possible underlying mechanisms. We found that GFP-expressing newborn cells began to establish a DGC-like morphology at around 7 days after birth, with a primary dendrite pointing to the molecular layer, but at this stage, with several neurites in the neurogenic zone...
December 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29214211/targeted-kinase-inhibition-relieves-slowness-and-tremor-in-a-drosophila-model-of-lrrk2-parkinson-s-disease
#14
Amy C Cording, Nicolas Shiaelis, Stavroula Petridi, C Adam Middleton, Laurence G Wilson, Christopher J H Elliott
In a number of Drosophila models of genetic Parkinson's disease (PD) flies climb more slowly than wild-type controls. However, this assay does not distinguish effects of PD-related genes on gravity sensation, "arousal", central pattern generation of leg movements, or muscle. To address this problem, we have developed an assay for the fly proboscis extension response (PER). This is attractive because the PER has a simple, well-identified reflex neural circuit, in which sucrose sensing neurons activate a pair of "command interneurons", and thence motoneurons whose activity contracts the proboscis muscle...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29209770/androgen-and-estrogen-sensitivity-of-bird-song-a-comparative-view-on-gene-regulatory-levels
#15
REVIEW
Carolina Frankl-Vilches, Manfred Gahr
Singing of songbirds is sensitive to testosterone and its androgenic and estrogenic metabolites in a species-specific way. The hormonal effects on song pattern are likely mediated by androgen receptors (AR) and estrogen receptor alpha (ERα), ligand activated transcription factors that are expressed in neurons of various areas of the songbirds' vocal control circuit. The distribution of AR in this circuit is rather similar between species while that of ERα is species variant and concerns a key vocal control area, the HVC (proper name)...
December 6, 2017: Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural, and Behavioral Physiology
https://www.readbyqxmd.com/read/29207951/downstream-mediators-of-ten-m3-signalling-in-the-developing-visual-pathway
#16
Kelly A Glendining, Sam C Liu, Marvin Nguyen, Nuwan Dharmaratne, Rajini Nagarajah, Miguel A Iglesias, Atomu Sawatari, Catherine A Leamey
BACKGROUND: The formation of visuotopically-aligned projections in the brain is required for the generation of functional binocular circuits. The mechanisms which underlie this process are unknown. Ten-m3 is expressed in a broad high-ventral to low-dorsal gradient across the retina and in topographically-corresponding gradients in primary visual centres. Deletion of Ten-m3 causes profound disruption of binocular visual alignment and function. Surprisingly, one of the most apparent neuroanatomical changes-dramatic mismapping of ipsilateral, but not contralateral, retinal axons along the representation of the nasotemporal retinal axis-does not correlate well with Ten-m3's expression pattern, raising questions regarding mechanism...
December 6, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/29207313/regulation-of-host-pathogen-interactions-via-the-post-transcriptional-csr-rsm-system
#17
REVIEW
Maria Kusmierek, Petra Dersch
A successful colonization of specific hosts requires a rapid and efficient adaptation of the virulence-relevant gene expression program by bacterial pathogens. An important element in this endeavor is the Csr/Rsm system. This multi-component, post-transcriptional control system forms a central hub within complex regulatory networks and coordinately adjusts virulence properties with metabolic and physiological attributes of the pathogen. A key function is elicited by the RNA-binding protein CsrA/RsmA. CsrA/RsmA interacts with numerous target mRNAs, many of which encode crucial virulence factors, and alters their translation, stability or elongation of transcription...
December 2, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29204711/voltage-sensitive-potassium-channels-of-the-bk-type-and-their-coding-genes-are-alcohol-targets-in-neurons
#18
Alex M Dopico, Anna N Bukiya, Jill C Bettinger
Among all members of the voltage-gated, TM6 ion channel superfamily, the proteins that constitute calcium- and voltage-gated potassium channels of large conductance (BK) and their coding genes are unique for their involvement in ethanol-induced disruption of normal physiology and behavior. Moreover, in vitro studies document that BK activity is modified by ethanol with an EC50~23 mM, which is near blood alcohol levels considered legal intoxication in most states of the USA (0.08 g/dL = 17.4 mM). Following a succinct introduction to our current understanding of BK structure and function in central neurons, with a focus on neural circuits that contribute to the neurobiology of alcohol use disorders (AUD), we review the modifications in organ physiology by alcohol exposure via BK and the different molecular elements that determine the ethanol response of BK in alcohol-naïve systems, including the role of an ethanol-recognizing site in the BK-forming slo1 protein, modulation of accessory BK subunits, and their coding genes...
December 5, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29203587/nampt-is-a-potent-oncogene-in-colon-cancer-progression-that-modulates-cancer-stem-cell-properties-and-resistance-to-therapy-through-sirt1-and-parp
#19
Amancio Carnero, Antonio Lucena-Cacace, Daniel Otero-Albiol, Manuel P Jimenez-Garcia, Sandra Muñoz-Galvan
PURPOSE: Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men worldwide. However, despite current progress, many patients with advanced and metastatic tumors still die from the malignancy. Refractory disease often relies on nicotinamide adenine dinucleotide(NAD)-dependent mechanisms. NAD metabolism and a stable NAD regeneration circuit are required to maintain tissue homeostasis and metabolism. However, high levels of NAD confer therapy resistance to tumors...
December 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29203527/a-novel-chemical-inducer-of-streptococcus-quorum-sensing-acts-by-inhibiting-the-pheromone-degrading-endopeptidase-pepo
#20
Tiara G Pérez Morales, Kiira Ratia, Duo-Sheng Wang, Artemis Gogos, Tom G Driver, Michael J Federle
Bacteria produce chemical signals (pheromones) to coordinate behaviors across a population in a process termed quorum sensing (QS). QS systems comprising peptide pheromones and their corresponding Rgg receptors are widespread among Firmicutes and may be useful targets for manipulating microbial behaviors, like suppressing virulence. The Rgg2/3 QS circuit of the human pathogen Streptococcus pyogenes controls genes affecting resistance to host lysozyme in response to short hydrophobic pheromones (SHPs). Considering that artificial activation of a QS pathway may be as useful in the objective of manipulating bacteria as inhibiting it, we sought to identify small-molecule inducers of the Rgg2/3 QS system...
December 4, 2017: Journal of Biological Chemistry
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