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https://www.readbyqxmd.com/read/28819289/escrt-iii-membrane-trafficking-misregulation-contributes-to-fragile-x-syndrome-synaptic-defects
#1
Dominic J Vita, Kendal Broadie
The leading cause of heritable intellectual disability (ID) and autism spectrum disorders (ASD), Fragile X syndrome (FXS), is caused by loss of the mRNA-binding translational suppressor Fragile X Mental Retardation Protein (FMRP). In the Drosophila FXS disease model, we found FMRP binds shrub mRNA (human Chmp4) to repress Shrub expression, causing overexpression during the disease state early-use critical period. The FXS hallmark is synaptic overelaboration causing circuit hyperconnectivity. Testing innervation of a central brain learning/memory center, we found FMRP loss and Shrub overexpression similarly increase connectivity...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818970/dna-replication-coupled-histone-modification-maintains-polycomb-gene-silencing-in-plants
#2
Danhua Jiang, Frédéric Berger
Propagation of patterns of gene expression through the cell cycle requires prompt restoration of epigenetic marks after the twofold dilution caused by DNA replication. Here, we show that the transcriptional repressive mark histone H3 lysine 27 trimethylation (H3K27me3) is restored in replicating plant cells through DNA replication-coupled modification of histone variant H3.1. Plants evolved a mechanism for efficient K27 trimethylation on H3.1, which is essential for inheritance of the silencing memory from mother to daughter cells...
August 17, 2017: Science
https://www.readbyqxmd.com/read/28818969/distinct-phases-of-polycomb-silencing-to-hold-epigenetic-memory-of-cold-in-arabidopsis
#3
Hongchun Yang, Scott Berry, Tjelvar S G Olsson, Matthew Hartley, Martin Howard, Caroline Dean
Gene silencing by Polycomb complexes is central to eukaryotic development. Cold-induced epigenetic repression of FLOWERING LOCUS C (FLC) in the plant Arabidopsis provides an opportunity to study initiation and maintenance of Polycomb silencing. Here, we show that a subset of Polycomb Repressive Complex 2 factors nucleate silencing in a small region within FLC, locally increasing H3K27me3 levels. This nucleation confers a silenced state that is metastably inherited, with memory held in the local chromatin. Metastable memory is then converted to stable epigenetic silencing through separate Polycomb factors, which spread across the locus after cold to enlarge the domain containing H3K27me3...
August 17, 2017: Science
https://www.readbyqxmd.com/read/28802842/the-role-of-g-protein-coupled-receptors-in-lymphoid-malignancies
#4
REVIEW
Adrienne Nugent, Richard L Proia
B cell lymphoma consists of multiple individual diseases arising throughout the lifespan of B cell development. From pro-B cells in the bone marrow, through circulating mature memory B cells, each stage of B cell development is prone to oncogenic mutation and transformation, which can lead to a corresponding lymphoma. Therapies designed against individual types of lymphoma often target features that differ between malignant cells and the corresponding normal cells from which they arise. These genetic changes between tumor and normal cells can include oncogene activation, tumor suppressor gene repression and modified cell surface receptor expression...
August 9, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28793261/the-conserved-disease-associated-rna-binding-protein-dnab2-interacts-with-the-fragile-x-protein-ortholog-in-drosophila-neurons
#5
Rick S Bienkowski, Ayan Banerjee, J Christopher Rounds, Jennifer Rha, Omotola F Omotade, Christina Gross, Kevin J Morris, Sara W Leung, ChangHui Pak, Stephanie K Jones, Michael R Santoro, Stephen T Warren, James Q Zheng, Gary J Bassell, Anita H Corbett, Kenneth H Moberg
The Drosophila dNab2 protein is an ortholog of human ZC3H14, a poly(A) RNA binding protein required for intellectual function. dNab2 supports memory and axon projection, but its molecular role in neurons is undefined. Here, we present a network of interactions that links dNab2 to cytoplasmic control of neuronal mRNAs in conjunction with the fragile X protein ortholog dFMRP. dNab2 and dfmr1 interact genetically in control of neurodevelopment and olfactory memory, and their encoded proteins co-localize in puncta within neuronal processes...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28771465/ebv-epigenetically-suppresses-the-b-cell-to-plasma-cell-differentiation-pathway-while-establishing-long-term-latency
#6
Christine T Styles, Quentin Bazot, Gillian A Parker, Robert E White, Kostas Paschos, Martin J Allday
Mature human B cells infected by Epstein-Barr virus (EBV) become activated, grow, and proliferate. If the cells are infected ex vivo, they are transformed into continuously proliferating lymphoblastoid cell lines (LCLs) that carry EBV DNA as extra-chromosomal episomes, express 9 latency-associated EBV proteins, and phenotypically resemble antigen-activated B-blasts. In vivo similar B-blasts can differentiate to become memory B cells (MBC), in which EBV persistence is established. Three related latency-associated viral proteins EBNA3A, EBNA3B, and EBNA3C are transcription factors that regulate a multitude of cellular genes...
August 2017: PLoS Biology
https://www.readbyqxmd.com/read/28751659/ferenczi-s-revolutionary-therapeutic-approach
#7
Clara Mucci
Many of the revolutionary principles introduced by Ferenczi in his clinical practice have now been widely accepted especially in the field of trauma and trauma therapy. Examples of these innovative views include his emphasis on empathy as opposed to technical neutrality and his stress on the real conditions of child caring and family environmental deficits and on the consequences of interpersonal violence and abuse that lead to "identification with the aggressor" by the victim thereby resulting in the internalization of both aggressiveness and guilt (the split guilt of the abuser)...
July 27, 2017: American Journal of Psychoanalysis
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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...
July 2017: EBioMedicine
https://www.readbyqxmd.com/read/28611595/mtorc1-is-a-local-postsynaptic-voltage-sensor-regulated-by-positive-and-negative-feedback-pathways
#18
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
#19
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
#20
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
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