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https://www.readbyqxmd.com/read/28721361/role-of-endoplasmic-reticulum-stress-in-learning-and-memory-impairment-and-alzheimer-s-disease-like-neuropathology-in-the-ps19-and-app-swe-mouse-models-of-tauopathy-and-amyloidosis
#1
Denise Isabelle Briggs, Erwin Defensor, Pooneh Memar Ardestani, Bitna Yi, Michelle Halpain, Guy Seabrook, Mehrdad Shamloo
Emerging evidence suggests that endoplasmic reticulum (ER) stress may be involved in the pathogenesis of Alzheimer's disease (AD). Recently, pharmacological modulation of the eukaryotic translation initiation factor-2 (eIF2α) pathway was achieved using an integrated stress response inhibitor (ISRIB). While members of this signaling cascade have been suggested as potential therapeutic targets for neurodegeneration, the biological significance of this pathway has not been comprehensively assessed in animal models of AD...
July 2017: ENeuro
https://www.readbyqxmd.com/read/28706491/early-life-exposure-to-lead-induces-cognitive-impairment-in-elder-mice-targeting-sirt1-phosphorylation-and-oxidative-alterations
#2
Lijie Zhang, Runqi Tu, Yawei Wang, Yazhen Hu, Xing Li, Xuemin Cheng, Yanyan Yin, Wenjie Li, Hui Huang
Pb is a potential risk factor for cognition, mainly mediated by enhanced oxidative stress. Resveratrol, a natural polyphenol with crucial anti-oxidative property, is recently implicated in preventing cognitive deficits in normal aging and neurodegenerative disorders. Its beneficial effects have been linked to sirtuin 1(SIRT1) activation. The aim of this work is to investigate the possible linkage between alterations in Pb-induced oxidative damage and cognitive impairment by prolonged treatment of resveratrol...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28706074/germ-line-inherited-h3k27me3-restricts-enhancer-function-during-maternal-to-zygotic-transition
#3
Fides Zenk, Eva Loeser, Rosaria Schiavo, Fabian Kilpert, Ozren Bogdanović, Nicola Iovino
Gametes carry parental genetic material to the next generation. Stress-induced epigenetic changes in the germ line can be inherited and can have a profound impact on offspring development. However, the molecular mechanisms and consequences of transgenerational epigenetic inheritance are poorly understood. We found that Drosophila oocytes transmit the repressive histone mark H3K27me3 to their offspring. Maternal contribution of the histone methyltransferase Enhancer of zeste, the enzymatic component of Polycomb repressive complex 2, is required for active propagation of H3K27me3 during early embryogenesis...
July 14, 2017: Science
https://www.readbyqxmd.com/read/28687800/pkc%C3%AE-mediated-phosphorylation-of-lsd1-is-required-for-presynaptic-plasticity-and-hippocampal-learning-and-memory
#4
Chae-Seok Lim, Hye Jin Nam, Jaehyun Lee, Dongha Kim, Ja Eun Choi, SukJae Joshua Kang, Somi Kim, Hyopil Kim, Chuljung Kwak, Kyu-Won Shim, Siyong Kim, Hyoung-Gon Ko, Ro Un Lee, Eun-Hae Jang, Juyoun Yoo, Jaehoon Shim, Md Ariful Islam, Yong-Seok Lee, Jae-Hyung Lee, Sung Hee Baek, Bong-Kiun Kaang
Lysine-specific demethylase 1 (LSD1) is a histone demethylase that participates in transcriptional repression or activation. Recent studies reported that LSD1 is involved in learning and memory. Although LSD1 phosphorylation by PKCα was implicated in circadian rhythmicity, the importance of LSD1 phosphorylation in learning and memory is unknown. In this study, we examined the roles of LSD1 in synaptic plasticity and memory using Lsd1 (SA/SA) knock-in (KI) mice, in which a PKCα phosphorylation site is mutated...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28681984/brd4-promotes-gastric-cancer-progression-through-the-transcriptional-and-epigenetic-regulation-of-c-myc
#5
Mingchen Ba, Hui Long, Zhaofei Yan, Shuai Wang, Yinbing Wu, Yinuo Tu, Yuanfeng Gong, Shuzhong Cui
Although the significance of BRD4 in the epigenetic memory and cancer genesis has been intensively investigated, little is known about its function and potential roles during the generation and progression of gastric cancer. We report here that BRD4 increases the proliferation and represses the apoptosis of gastric cancer cells through activating c-MYC via transcriptional and epigenetic regulation mechanisms. Expression analyses in both small and large cohort of sample show that BRD4 is highly expressed in gastric cancer tissues/cells when compared with the adjacent non-tumor tissues/normal cells...
July 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28677680/ctcf-orchestrates-the-germinal-centre-transcriptional-program-and-prevents-premature-plasma-cell-differentiation
#6
Arantxa Pérez-García, Ester Marina-Zárate, Ángel F Álvarez-Prado, Jose M Ligos, Niels Galjart, Almudena R Ramiro
In germinal centres (GC) mature B cells undergo intense proliferation and immunoglobulin gene modification before they differentiate into memory B cells or long-lived plasma cells (PC). GC B-cell-to-PC transition involves a major transcriptional switch that promotes a halt in cell proliferation and the production of secreted immunoglobulins. Here we show that the CCCTC-binding factor (CTCF) is required for the GC reaction in vivo, whereas in vitro the requirement for CTCF is not universal and instead depends on the pathways used for B-cell activation...
July 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28674072/counterbalancing-regulation-in-response-memory-of-a-positively-autoregulated-two-component-system
#7
Rong Gao, Katherine A Godfrey, Mahir A Sufian, Ann M Stock
Fluctuations in nutrient availability often result in recurrent exposures to the same stimulus condition. The ability to memorize the past event and use the "memory" to make adjustments to current behaviors can lead to more efficient adaptation to the recurring stimulus. A short-term phenotypic memory can be conferred via carry-over of the response proteins to facilitate the recurrent response but the additional accumulation of response proteins can lead to deviation from response homeostasis. We used the Escherichia coli PhoB/PhoR two-component system (TCS) as a model system to study how cells cope with the recurrence of Pi starvation conditions...
July 3, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28634329/long-days-enhance-recognition-memory-and-increase-insulin-like-growth-factor-2-in-the-hippocampus
#8
Adriano Dellapolla, Ian Kloehn, Harshida Pancholi, Ben Callif, David Wertz, Kayla E Rohr, Matthew M Hurley, Kimberly M Baker, Samer Hattar, Marieke R Gilmartin, Jennifer A Evans
Light improves cognitive function in humans; however, the neurobiological mechanisms underlying positive effects of light remain unclear. One obstacle is that most rodent models have employed lighting conditions that cause cognitive deficits rather than improvements. Here we have developed a mouse model where light improves cognitive function, which provides insight into mechanisms underlying positive effects of light. To increase light exposure without eliminating daily rhythms, we exposed mice to either a standard photoperiod or a long day photoperiod...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28628228/epigenetic-mechanisms-underlying-nmda-receptor-hypofunction-in-the-prefrontal-cortex-of-juvenile-animals-in-the-mam-model-for-schizophrenia
#9
Yelena Gulchina, Song-Jun Xu, Melissa A Snyder, Felice Elefant, Wen-Jun Gao
Schizophrenia (SCZ) is characterized not only by psychosis, but also by working memory and executive functioning deficiencies, processes that rely on the prefrontal cortex (PFC). Because these cognitive impairments emerge prior to psychosis onset, we investigated synaptic function during development in the neurodevelopmental methylazoxymethanol acetate (MAM) model for SCZ. Specifically, we hypothesize that NMDAR hypofunction is attributable to reductions in the NR2B subunit through aberrant epigenetic regulation of gene expression, resulting in deficient synaptic physiology and PFC-dependent cognitive dysfunction, a hallmark of SCZ...
June 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28615147/hiv-specific-b-cell-frequency-correlates-with-neutralization-breadth-in-patients-naturally-controlling-hiv-infection
#10
Angeline Rouers, Jéromine Klingler, Bin Su, Assia Samri, Géraldine Laumond, Sophie Even, Véronique Avettand-Fenoel, Clemence Richetta, Nicodème Paul, Faroudy Boufassa, Laurent Hocqueloux, Hugo Mouquet, Christine Rouzioux, Olivier Lambotte, Brigitte Autran, Stéphanie Graff-Dubois, Christiane Moog, Arnaud Moris
HIV-specific broadly neutralizing antibodies (bnAbs) have been isolated from patients with high viremia but also from HIV controllers that repress HIV-1 replication. In these elite controllers (ECs), multiple parameters contribute to viral suppression, including genetic factors and immune responses. Defining the immune correlates associated with the generation of bnAbs may help in designing efficient immunotherapies. In this study, in ECs either positive or negative for the HLA-B*57 protective allele, in treated HIV-infected and HIV-negative individuals, we characterized memory B cell compartments and HIV-specific memory B cells responses using flow cytometry and ELISPOT...
May 31, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28611595/mtorc1-is-a-local-postsynaptic-voltage-sensor-regulated-by-positive-and-negative-feedback-pathways
#11
Farr Niere, Kimberly F Raab-Graham
The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) serves as a regulator of mRNA translation. Recent studies suggest that mTORC1 may also serve as a local, voltage sensor in the postsynaptic region of neurons. Considering biochemical, bioinformatics and imaging data, we hypothesize that the activity state of mTORC1 dynamically regulates local membrane potential by promoting and repressing protein synthesis of select mRNAs. Our hypothesis suggests that mTORC1 uses positive and negative feedback pathways, in a branch-specific manner, to maintain neuronal excitability within an optimal range...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28607146/epigenetic-transcriptional-memory-of-gal-genes-depends-on-growth-in-glucose-and-the-tup1-transcription-factor-in-saccharomyces-cerevisiae
#12
Varun Sood, Ivelisse Cajigas, Agustina D'Urso, William H Light, Jason H Brickner
Previously expressed inducible genes can remain poised for faster reactivation for multiple cell divisions, a conserved phenomenon called epigenetic transcriptional memory. The GAL genes in Saccharomyces cerevisiae show faster reactivation for up to seven generations after being repressed. During memory, previously produced Gal1 protein enhances the rate of reactivation of GAL1, GAL10, GAL2 and GAL7 These genes also interact with the nuclear pore complex (NPC) and localize to the nuclear periphery both when active and during memory...
June 12, 2017: Genetics
https://www.readbyqxmd.com/read/28587744/mathematical-comparison-of-memory-functions-between-mutual-activation-and-repression-networks-in-a-stochastic-environment
#13
A B M Shamim Ul Hasan, Hiroyuki Kurata
Biological memory is a ubiquitous function that can generate a sustained response to a transient inductive stimulus. To better understand this function, we must consider the mechanisms by which different structures of genetic networks achieve memory. Here, we investigated two competitive gene regulatory network models: the regulated mutual activation network (MAN) and the regulated mutual repression network (MRN). Stochasticity deteriorated the persistence of memory of both the MAN and the MRN. Mathematical comparison by simulation and theoretical analysis identified functional differences in the stochastic memory between the competitive models: specifically, the MAN provided much more robust, persistent memory than the MRN...
June 3, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28580133/the-elephant-shark-methylome-reveals-conservation-of-epigenetic-regulation-across-jawed-vertebrates
#14
Julian R Peat, Oscar Ortega-Recalde, Olga Kardailsky, Timothy A Hore
BACKGROUND: Methylation of CG dinucleotides constitutes a critical system of epigenetic memory in bony vertebrates, where it modulates gene expression and suppresses transposon activity. The genomes of studied vertebrates are pervasively hypermethylated, with the exception of regulatory elements such as transcription start sites (TSSs), where the presence of methylation is associated with gene silencing. This system is not found in the sparsely methylated genomes of invertebrates, and establishing how it arose during early vertebrate evolution is impeded by a paucity of epigenetic data from basal vertebrates...
2017: F1000Research
https://www.readbyqxmd.com/read/28537256/design-of-synthetic-epigenetic-circuits-featuring-memory-effects-and-reversible-switching-based-on-dna-methylation
#15
Johannes A H Maier, Raphael Möhrle, Albert Jeltsch
Epigenetic systems store information in DNA methylation patterns in a durable but reversible manner, but have not been regularly used in synthetic biology. Here, we designed synthetic epigenetic memory systems using DNA methylation sensitive engineered zinc finger proteins to repress a memory operon comprising the CcrM methyltransferase and a reporter. Triggering by heat, nutrients, ultraviolet irradiation or DNA damaging compounds induces CcrM expression and DNA methylation. In the induced on-state, methylation in the operator of the memory operon prevents zinc finger protein binding leading to positive feedback and permanent activation...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28527130/pulse-generation-in-the-quorum-machinery-of-pseudomonas-aeruginosa
#16
Cicik Alfiniyah, Martin A Bees, A Jamie Wood
Pseudomonas aeruginosa is a Gram-negative bacterium that is responsible for a wide range of infections in humans. Colonies employ quorum sensing (QS) to coordinate gene expression, including for virulence factors, swarming motility and complex social traits. The QS signalling system of P. aeruginosa is known to involve multiple control components, notably the las, rhl and pqs systems. In this paper, we examine the las system and, in particular, the repressive interaction of rsaL, an embedded small regulative protein, employing recent biochemical information to aid model construction...
June 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28511826/use-of-hypnosis-meditation-and-biofeedback-in-dermatology
#17
Philip D Shenefelt
Hypnosis utilizes trance to access otherwise inaccessible repressed or unconscious memories and features of the psyche and control of physiology not attainable in the ordinary conscious waking state. Medical uses of hypnosis in dermatology include reducing discomfort from itching or skin pain, altering ingrained dysfunctional habits such as scratching, promoting healing of skin disorders, searching for psychosomatic aspects of skin disorders and alleviating them, and reframing cognitive and emotional dysfunctional patterns related to skin disorders...
May 2017: Clinics in Dermatology
https://www.readbyqxmd.com/read/28498984/inheritance-of-vernalization-memory-at-flowering-locus-c-during-plant-regeneration
#18
Miyuki Nakamura, Lars Hennig
Specific gene states can be transmitted to subsequent cell generations through mitosis involving particular chromatin (epigenetic) states. During reproduction of plants and animals, however, most epigenetic states are reset to allow development to start anew. Flowering is one of the critical developmental steps by which plants acquire their reproductive capacity. This phase transition is controlled by environmental signals and autonomous regulation. The FLOWERING LOCUS C (FLC) gene is a flowering repressor that is epigenetically silenced after long-term exposure to cold, ensuring flowering in the spring season...
May 11, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28493559/mtor-referees-memory-and-disease-through-mrna-repression-and-competition
#19
REVIEW
Kimberly F Raab-Graham, Farr Niere
Mammalian target of rapamycin (mTOR) activity is required for memory and is dysregulated in disease. Activation of mTOR promotes protein synthesis; however, new studies are demonstrating that mTOR activity also represses the translation of mRNAs. Almost three decades ago, Kandel and colleagues hypothesised that memory was due to the induction of positive regulators and removal of negative constraints. Are these negative constraints repressed mRNAs that code for proteins that block memory formation? Herein, we will discuss the mRNAs coded by putative memory suppressors, how activation/inactivation of mTOR repress protein expression at the synapse, how mTOR activity regulates RNA binding proteins, mRNA stability, and translation, and what the possible implications of mRNA repression are to memory and neurodegenerative disorders...
May 11, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28461702/bach-transcription-factors-in-innate-and-adaptive-immunity
#20
REVIEW
Kazuhiko Igarashi, Tomohiro Kurosaki, Rahul Roychoudhuri
BTB and CNC homology (BACH) proteins are transcriptional repressors of the basic region leucine zipper (bZIP) transcription factor family. Recent studies indicate widespread roles of BACH proteins in controlling the development and function of the innate and adaptive immune systems, including the differentiation of effector and memory cells of the B and T cell lineages, CD4(+) regulatory T cells and macrophages. Here, we emphasize similarities at a molecular level in the cell-type-specific activities of BACH factors, proposing that competitive interactions of BACH proteins with transcriptional activators of the bZIP family form a common mechanistic theme underlying their diverse actions...
July 2017: Nature Reviews. Immunology
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