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https://www.readbyqxmd.com/read/28723950/high-affinity-anti-tim-3-and-anti-kir-monoclonal-antibodies-cloned-from-healthy-human-individuals
#1
Stefan Ryser, Angeles Estellés, Edgar Tenorio, Lawrence M Kauvar, Mikhail L Gishizky
We report here the cloning of native high affinity anti-TIM-3 and anti-KIR IgG monoclonal antibodies (mAbs) from peripheral blood mononuclear cells (PBMC) of healthy human donors. The cells that express these mAbs are rare, present at a frequency of less than one per 105 memory B-cells. Using our proprietary multiplexed screening and cloning technology CellSpot™ we assessed the presence of memory B-cells reactive to foreign and endogenous disease-associated antigens within the same individual. When comparing the frequencies of antigen-specific memory B-cells analyzed in over 20 screening campaigns, we found a strong correlation of the presence of anti-TIM-3 memory B-cells with memory B-cells expressing mAbs against three disease-associated antigens: (i) bacterial DNABII proteins that are a marker for Gram negative and Gram positive bacterial infections, (ii) hemagglutinin (HA) of influenza virus and (iii) the extracellular domain of anaplastic lymphoma kinase (ALK)...
2017: PloS One
https://www.readbyqxmd.com/read/28723570/dynamic-control-of-dendritic-mrna-expression-by-cnot7-regulates-synaptic-efficacy-and-higher-cognitive-function
#2
Rhonda L McFleder, Fernanda Mansur, Joel D Richter
Translation of mRNAs in dendrites mediates synaptic plasticity, the probable cellular basis of learning and memory. Coordination of translational inhibitory and stimulatory mechanisms, as well as dendritic transport of mRNA, is necessary to ensure proper control of this local translation. Here, we find that the deadenylase CNOT7 dynamically regulates dendritic mRNA translation and transport, as well as synaptic plasticity and higher cognitive function. In cultured hippocampal neurons, synaptic stimulation induces a rapid decrease in CNOT7, which, in the short-term, results in poly(A) tail lengthening of target mRNAs...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28723545/spineless-behavior-of-cx3cr1-monocytes-in-response-to-infection
#3
Paul A Muller, Daniel Mucida
Sickness in mammals can lead to cognition deficits, although the underlying mechanisms remain elusive. In a recent Nature Medicine article, Garré et al. (2017) report that sickness-induced cortical dendritic spine loss and impaired memory formation is mediated by CX3CR1(+) monocyte-derived TNF-α.
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28722058/activation-of-nrf2-are-signaling-pathway-attenuates-lanthanum-chloride-induced-injuries-in-primary-rat-astrocytes
#4
Lijin Zhang, Jinghua Yang, Shengwen Wu, Cuihong Jin, Xiaobo Lu, Xiaoyu Hu, Yaling Sun, Xiang Gao, Yuan Cai
Lanthanum (La) exposure can lead to learning and memory disorder in animals; however, the underlying mechanism of La induced neurotoxicity is still unknown. It has been demonstrated that Nrf2 activation by tert-butylhydroquinone (tBHQ) results in neuroprotection against brain injuries. However, little study has been done with respect to its effect on La induced neurotoxicity. Herein, experiments are undertaken to determine if there is a correlation between La damaged astrocytes and the Nrf2/ARE signalling pathway...
July 19, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28721398/calcium-stimulated-adenylyl-cyclase-subtype-1-ac1-contributes-to-ltp-in-the-insular-cortex-of-adult-mice
#5
Manabu Yamanaka, Takanori Matsuura, Haili Pan, Min Zhuo
Long-term potentiation (LTP) of synaptic transmission in the central nervous system is a key form of cortical plasticity. The insular cortex (IC) is known to play important roles in pain perception, aversive memory and mood disorders. LTP has been recently reported in the IC, however, the signaling pathway for IC LTP remains unknown. Here, we investigated the synaptic mechanism of IC LTP. We found that IC LTP induced by the pairing protocol was N-methyl-D-aspartate receptors (NMDARs) dependent, and expressed postsynaptically, since paired-pulse ratio (PPR) was not affected...
July 2017: Heliyon
https://www.readbyqxmd.com/read/28720858/gsk-3%C3%AE-deletion-in-dentate-gyrus-excitatory-neuron-impairs-synaptic-plasticity-and-memory
#6
Enjie Liu, Ao-Ji Xie, Qiuzhi Zhou, Mengzhu Li, Shujuan Zhang, Shihong Li, Weijin Wang, Xiaochuan Wang, Qun Wang, Jian-Zhi Wang
Increasing evidence suggests that glycogen synthase kinase-3β (GSK-3β) plays a crucial role in neurodegenerative/psychiatric disorders, while pan-neural knockout of GSK-3β also shows detrimental effects. Currently, the function of GSK-3β in specific type of neurons is elusive. Here, we infused AAV-CaMKII-Cre-2A-eGFP into GSK-3β(lox/lox) mice to selectively delete the kinase in excitatory neurons of hippocampal dentate gyrus (DG), and studied the effects on cognitive/psychiatric behaviors and the molecular mechanisms...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720379/inhibition-of-12-15-lox-ameliorates-cognitive-and-cholinergic-dysfunction-in-mouse-model-of-hypobaric-hypoxia-via-attenuation-of-oxidative-nitrosative-stress
#7
Richa Choudhary, Udayabanu Malairaman, Anju Katyal
12/15 Lipoxygenase has recently been described as potent propagator of oxidative stress and is closely associated with cognitive decline in neurodegenerative diseases. The mechanism/s behind 12/15 LOX involvement in cognitive deficits remain obscure. The current study has been designed to investigate the underlying role of 12/15LOX and effect of 12/15 LOX inhibition on hypobaric hypoxia induced memory impairment and cholinergic deficits. Male Balb/c mice subjected to simulated hypobaric hypoxia/reoxygenation condition for 3 days showed marked working memory impairment concomitant with hippocampal neuronal damage and malondialdehyde production which were significantly attenuated by baicalein, a specific inhibitor of 12/15LOX...
July 15, 2017: Neuroscience
https://www.readbyqxmd.com/read/28718763/a-theory-of-working-memory-without-consciousness-or-sustained-activity
#8
Darinka Trübutschek, Sébastien Marti, Andrés Ojeda, Jean-Rémi King, Yuanyuan Mi, Misha Tsodyks, Stanislas Dehaene
Working memory and conscious perception are thought to share similar brain mechanisms, yet recent reports of non-conscious working memory challenge this view. Combining visual masking with magnetoencephalography, we investigate the reality of non-conscious working memory and dissect its neural mechanisms. In a spatial delayed-response task, participants reported the location of a subjectively unseen target above chance-level after several seconds. Conscious perception and conscious working memory were characterized by similar signatures: a sustained desynchronization in the alpha/beta band over frontal cortex, and a decodable representation of target location in posterior sensors...
July 18, 2017: ELife
https://www.readbyqxmd.com/read/28718756/stereotypes-influence-destination-memory-in-normal-aging
#9
Mohamad El Haj
Background/Study Context: A substantial body of literature suggests that stereotypes can play a determining role in making judgments about the source of information. This study investigated this issue for destination memory or remembering to whom information has been previously told. METHODS: Younger adults and older adults told six medical and six mechanical facts to a picture depicting a physician, and also told six different medical and six different mechanical facts to a picture depicting a mechanic...
July 2017: Experimental Aging Research
https://www.readbyqxmd.com/read/28718002/infectious-pathogens-may-trigger-specific-allo-hla-reactivity-via-multiple-mechanisms
#10
REVIEW
Lloyd D'Orsogna, Heleen van den Heuvel, Cees van Kooten, Sebastiaan Heidt, Frans H J Claas
Transplant recipients can be sensitized against allo-HLA antigens by previous transplantation, blood transfusion, or pregnancy. While there is growing awareness that multiple components of the immune system can act as effectors of the alloresponse, the role of infectious pathogen exposure in triggering sensitization and allograft rejection has remained a matter of much debate. Here, we describe that exposure to pathogens may enhance the immune response to allogeneic HLA antigens via different pathways. The potential role of allo-HLA cross-reactivity of virus-specific memory T cells, activation of innate immunity leading to a more efficient induction of the adaptive alloimmune response by antigen-presenting cells, and bystander activation of existing memory B cell activation will be discussed in this review...
July 17, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28717968/deletion-of-type-2-cannabinoid-receptor-induces-alzheimer-s-disease-like-tau-pathology-and-memory-impairment-through-ampk-gsk3%C3%AE-pathway
#11
Lin Wang, Bing-Jin Liu, Yun Cao, Wei-Qi Xu, Dong-Sheng Sun, Meng-Zhu Li, Fang-Xiao Shi, Man Li, Qing Tian, Jian-Zhi Wang, Xin-Wen Zhou
Although several studies have shown that type-2 cannabinoid receptor (CB2R) is involved in Alzheimer's disease (AD) pathology, the effects of CB2R on AD-like tau abnormal phosphorylation and its underlying mechanism remain unclear. Herein, we employed the CB2R(-/-) mice as the animal model to explore roles of CB2R in regulating tau phosphorylation and brain function. We found that CB2R(-/-) mice display AD-like tau hyperphosphorylation, hippocampus-dependent memory impairment, increase of GSK3β activity, decrease of AMPK and Sirt1 activity and mitochondria dysfunction...
July 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28717525/differential-effects-of-awake-glioma-surgery-in-critical-language-areas-on-cognition-4-case-studies
#12
Djaina Satoer, Elke De Witte, Marion Smits, Roelien Bastiaanse, Arnaud Vincent, Peter Mariën, Evy Visch-Brink
Awake surgery with electrocorticosubcortical stimulation is the golden standard treatment for gliomas in eloquent areas. Preoperatively, mostly mild cognitive disturbances are observed with postoperative deterioration. We describe pre- and postoperative profiles of 4 patients (P1-P4) with gliomas in "critical" language areas ("Broca," "Wernicke," and the arcuate fasciculus) undergoing awake surgery to get insight into the underlying mechanism of neuroplasticity. Neuropsychological examination was carried out preoperatively (at T1) and postoperatively (at T2, T3)...
2017: Case Reports in Neurological Medicine
https://www.readbyqxmd.com/read/28717522/effect-of-hypoxic-injury-in-mood-disorder
#13
REVIEW
Fenglian Zhao, Junling Yang, Ranji Cui
Hypoxemia is a common complication of the diseases associated with the central nervous system, and neurons are highly sensitive to the availability of oxygen. Neuroplasticity is an important property of the neural system controlling breathing, memory, and cognitive ability. However, the underlying mechanism has not yet been clearly elucidated. In recent years, several pieces of evidence have highlighted the effect of hypoxic injury on neuronal plasticity in the pathogenesis and treatment of mood disorder. Therefore, the present study reviewed the relevant articles regarding hypoxic injury and neuronal plasticity and discussed the pathological changes and physiological functions of neurons in hypoxemia in order to provide a translational perspective to the relevance of hypoxic injury and mood disorder...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28717165/fabricating-fast-triggered-electro-active-shape-memory-graphite-silver-nanowires-epoxy-resin-composite-from-polymer-template
#14
Jie Zhou, Hua Li, Ran Tian, Roberto Dugnani, Huiyuan Lu, Yujie Chen, Yiping Guo, Huanan Duan, Hezhou Liu
In recent years shape-memory polymers have been under intense investigation due to their unique mechanical, thermal, and electrical properties that could potentially make them extremely valuable in numerous engineering applications. In this manuscript, we report a polymer-template-assisted assembly manufacturing strategy used to fabricate graphite/silver nanowires/epoxy resin (PGSE) composite. In the proposed method, the porous polymer foams work as the skeleton by forming three-dimensional graphite structure, whereas the silver nanowires act as the continuous conductive network...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716963/chemokine-ccl2-ccr2-signaling-induces-neuronal-cell-death-via-stat3-activation-and-il-1%C3%AE-production-after-status-epilepticus
#15
Dai-Shi Tian, Jiyun Peng, Madhuvika Murugan, Lijie Feng, Jun-Li Liu, Ukpong B Eyo, Li-Jun Zhou, Rochelle Mogilevsky, Wei Wang, Long-Jun Wu
Elevated levels of chemokine C-C motif ligand 2 (CCL2) and its receptor CCR2 have been reported in patients with temporal lobe epilepsy and in experimental seizures. However, the functional significance and molecular mechanism underlying CCL2-CCR2 signaling in epileptic brain remains largely unknown. In this study, we found that the upregulated CCL2 was mainly expressed in hippocampal neurons and activated microglia from mice 1d after kainic acid (KA)-induced seizures. Taking advantage of CX3CR1(GFP/+):CCR2(RFP/+) double transgenic mice, we demonstrated that CCL2-CCR2 signaling participated in resident microglial activation and blood-derived monocyte infiltration...
July 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28716957/ampa-receptors-control-fear-extinction-through-an-arc-dependent-mechanism
#16
Simon Trent, Philip Barnes, Jeremy Hall, Kerrie L Thomas
Activity-regulated cytoskeleton-associated protein (Arc) supports fear memory through synaptic plasticity events requiring actin cytoskeleton rearrangements. We have previously shown that reducing hippocampal Arc levels through antisense knockdown leads to the premature extinction of contextual fear. Here we show that the AMPA receptor antagonist CNQX elevates hippocampal Arc levels during extinction and blocks extinction that can be rescued by reducing Arc. Increasing Arc levels with CNQX also overcomes the actin-destabilizing properties of cytochalasin D and promotes extinction...
August 2017: Learning & Memory
https://www.readbyqxmd.com/read/28715973/the-molecular-basis-for-human-immunodeficiency-virus-latency
#17
Uri Mbonye, Jonathan Karn
Although potent combination antiretroviral therapy can effectively block viral replication in the host, human immunodeficiency virus (HIV) persists due to the existence of latent but replication-competent proviruses residing primarily in a very small population of resting memory CD4(+) T cells. Viral latency is established when the expression of the autoregulatory viral trans-activating factor Tat is reduced to subthreshold levels. The absence of Tat reduces HIV transcription and protein production to levels that make the host cell invisible to the immune system and refractory to antiretroviral treatment...
July 17, 2017: Annual Review of Virology
https://www.readbyqxmd.com/read/28715454/reduction-of-cav1-3-channels-in-dorsal-hippocampus-impairs-the-development-of-dentate-gyrus-newborn-neurons-and-hippocampal-dependent-memory-tasks
#18
Su-Hyun Kim, Ye-Ryoung Park, Boyoung Lee, Byungil Choi, Hyun Kim, Chong-Hyun Kim
Cav1.3 has been suggested to mediate hippocampal neurogenesis of adult mice and contribute to hippocampal-dependent learning and memory processes. However, the mechanism of Cav1.3 contribution in these processes is unclear. Here, roles of Cav1.3 of mouse dorsal hippocampus during newborn cell development were examined. We find that knock-out (KO) of Cav1.3 resulted in the reduction of survival of newborn neurons at 28 days old after mitosis. The retroviral eGFP expression showed that both dendritic complexity and the number and length of mossy fiber bouton (MFB) filopodia of newborn neurons at ≥ 14 days old were significantly reduced in KO mice...
2017: PloS One
https://www.readbyqxmd.com/read/28714866/ibrutinib-treatment-improves-t-cell-number-and-function-in-cll-patients
#19
Meixiao Long, Kyle Beckwith, Priscilla Do, Bethany L Mundy, Amber Gordon, Amy M Lehman, Kami J Maddocks, Carolyn Cheney, Jeffrey A Jones, Joseph M Flynn, Leslie A Andritsos, Farrukh Awan, Joseph A Fraietta, Carl H June, Marcela V Maus, Jennifer A Woyach, Michael A Caligiuri, Amy J Johnson, Natarajan Muthusamy, John C Byrd
BACKGROUND: Ibrutinib has been shown to have immunomodulatory effects by inhibiting Bruton's tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK). The relative importance of inhibiting these 2 kinases has not been examined despite its relevance to immune-based therapies. METHODS: Peripheral blood mononuclear cells from chronic lymphocytic leukemia (CLL) patients on clinical trials of ibrutinib (BTK/ITK inhibitor; n = 19) or acalabrutinib (selective BTK inhibitor; n = 13) were collected serially...
July 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28714396/differential-effects-of-nicotine-exposure-on-the-hippocampus-across-lifespan
#20
Dana Zeid, Munir Gunes Kutlu, Thomas J Gould
Nicotine exposure affects the hippocampus through activation of hippocampal nicotinic acetylcholine receptors (nAChRs), which are present throughout excitatory and inhibitory hippocampal circuitry. The role of cholinergic functioning in the hippocampus varies across developmental stages so that nicotine exposure differentially affects this region depending upon timing of exposure, producing developmentally distinct changes in structure, function, and behavior. The hippocampus continues to mature well into adolescence, and this development is modulated by cholinergic activity...
July 13, 2017: Current Neuropharmacology
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