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https://www.readbyqxmd.com/read/29346381/control-of-recollection-by-slow-gamma-dominating-mid-frequency-gamma-in-hippocampus-ca1
#1
Dino Dvorak, Basma Radwan, Fraser T Sparks, Zoe Nicole Talbot, André A Fenton
Behavior is used to assess memory and cognitive deficits in animals like Fmr1-null mice that model Fragile X Syndrome, but behavior is a proxy for unknown neural events that define cognitive variables like recollection. We identified an electrophysiological signature of recollection in mouse dorsal Cornu Ammonis 1 (CA1) hippocampus. During a shocked-place avoidance task, slow gamma (SG) (30-50 Hz) dominates mid-frequency gamma (MG) (70-90 Hz) oscillations 2-3 s before successful avoidance, but not failures...
January 18, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29343554/biased-generation-and-in-situ-activation-of-lung-tissue-resident-memory-cd4-t-cells-in-the-pathogenesis-of-allergic-asthma
#2
Damian L Turner, Monica Goldklang, Filip Cvetkovski, Daniel Paik, Jordis Trischler, Josselyn Barahona, Minwei Cao, Ronak Dave, Nicole Tanna, Jeanine M D'Armiento, Donna L Farber
Asthma is a chronic inflammatory disease mediated by allergen-specific CD4 T cells that promote lung inflammation through recruitment of cellular effectors into the lung. A subset of lung T cells can persist as tissue-resident memory T cells (TRMs) following infection and allergen induction, although the generation and role of TRM in asthma persistence and pathogenesis remain unclear. In this study, we used a mouse model of chronic exposure to intranasal house dust mite (HDM) extract to dissect how lung TRMs are generated and function in the persistence and pathogenesis of allergic airway disease...
January 17, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29343437/memory-b-cells-that-cross-react-with-group-1-and-group-2-influenza-a-viruses-are-abundant-in-adult-human-repertoires
#3
Kevin R McCarthy, Akiko Watanabe, Masayuki Kuraoka, Khoi T Do, Charles E McGee, Gregory D Sempowski, Thomas B Kepler, Aaron G Schmidt, Garnett Kelsoe, Stephen C Harrison
Human B cell antigen-receptor (BCR) repertoires reflect repeated exposures to evolving influenza viruses; new exposures update the previously generated B cell memory (Bmem) population. Despite structural similarity of hemagglutinins (HAs) from the two groups of influenza A viruses, cross-reacting antibodies (Abs) are uncommon. We analyzed Bmem compartments in three unrelated, adult donors and found frequent cross-group BCRs, both HA-head directed and non-head directed. Members of a clonal lineage from one donor had a BCR structure similar to that of a previously described Ab, encoded by different gene segments...
January 16, 2018: Immunity
https://www.readbyqxmd.com/read/29341430/tuberculosis-vaccines-opportunities-and-challenges
#4
REVIEW
Bingdong Zhu, Hazel M Dockrell, Tom H M Ottenhoff, Thomas G Evans, Ying Zhang
Tuberculosis (TB) is a serious disease around the world. Bacillus Calmette-Guérin (BCG) is the only TB vaccine licensed for use in human beings, and is effective in protecting infants and children against severe miliary and meningeal TB. However, BCG's protective efficacy is variable in adults. Novel TB vaccine candidates being developed include whole-cell vaccines (recombinant BCG (rBCG), attenuated Mycobacterium tuberculosis, killed M. tuberculosis or Mycobacterium vaccae), adjuvanted protein subunit vaccines, viral vector-delivered subunit vaccines, plasmid DNA vaccines, RNA-based vaccines etc...
January 17, 2018: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/29339476/coding-of-episodic-memory-in-the-human-hippocampus
#5
John T Wixted, Stephen D Goldinger, Larry R Squire, Joel R Kuhn, Megan H Papesh, Kris A Smith, David M Treiman, Peter N Steinmetz
Neurocomputational models have long posited that episodic memories in the human hippocampus are represented by sparse, stimulus-specific neural codes. A concomitant proposal is that when sparse-distributed neural assemblies become active, they suppress the activity of competing neurons (neural sharpening). We investigated episodic memory coding in the hippocampus and amygdala by measuring single-neuron responses from 20 epilepsy patients (12 female) undergoing intracranial monitoring while they completed a continuous recognition memory task...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339462/direct-manipulation-of-t-lymphocytes-by-proteins-of-gastrointestinal-bacterial-pathogens
#6
Robin L Cassady-Cain, Jayne C Hope, Mark P Stevens
Gastrointestinal bacterial infection represents a significant threat to human health, as well as a burden on food animal production and welfare. Although there is advanced knowledge about the molecular mechanisms underlying pathogenesis, including the development of immune responses to these pathogens, gaps in knowledge persist. It is well established that gastrointestinal bacterial pathogens produce a myriad of proteins that affect the development and effectiveness of innate immune responses. However, relatively few proteins that directly affect lymphocytes responsible for humoral or cell-mediated immunity and memory have been identified...
January 16, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29339446/ontogeny-of-human-mucosal-associated-invariant-t-cells-and-related-t-cell-subsets
#7
Ghada Ben Youssef, Marie Tourret, Marion Salou, Liana Ghazarian, Véronique Houdouin, Stanislas Mondot, Yvonne Mburu, Marion Lambert, Saba Azarnoush, Jean-Sébastien Diana, Anne-Laure Virlouvet, Michel Peuchmaur, Thomas Schmitz, Jean-Hugues Dalle, Olivier Lantz, Valérie Biran, Sophie Caillat-Zucman
Mucosal-associated invariant T (MAIT) cells are semi-invariant Vα7.2+ CD161highCD4- T cells that recognize microbial riboflavin precursor derivatives such as 5-OP-RU presented by MR1. Human MAIT cells are abundant in adult blood, but there are very few in cord blood. We longitudinally studied Vα7.2+ CD161high T cell and related subset levels in infancy and after cord blood transplantation. We show that Vα7.2+ and Vα7.2- CD161high T cells are generated early during gestation and likely share a common prenatal developmental program...
January 16, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29339261/mumps-infection-but-not-childhood-vaccination-induces-persistent-polyfunctional-cd8-t-cell-memory
#8
Jelle de Wit, Maarten E Emmelot, Martien C M Poelen, Rob S van Binnendijk, Saskia van der Lee, Debbie van Baarle, Wanda G H Han, Cécile A C M van Els, Patricia Kaaijk
No abstract text is available yet for this article.
January 12, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29338160/higher-activities-of-hepatic-versus-splenic-cd8-t-cells-in-responses-to-adoptive-t-cell-therapy-and-vaccination-of-b6-mice-with-mhc-class-1-binding-antigen
#9
Mohamed Labib Salem, Randa E El Naggar, Sabry A El Naggar, Maysa A Mobasher, Mohamed H Mahmoud, Gamal Badr
The liver has unique microenvironment which is known to induce tolerance of cytolytic CD8+ T cells to hepatic and extra hepatic antigens, resulting in persistence of infection of the liver by the hepatitis B and C viruses. However, under some conditions, functional immune responses can be elicited in the liver in particular to show preferential retention of activated CD8+ T cells. It is not clear whether this retention depends on the type of the exogenous immunostimulatory or the endogenous innate immune cells...
December 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29338031/pre-existing-malignancy-results-in-increased-prevalence-of-distinct-populations-of-cd4-t-cells-during-sepsis
#10
Jianfeng Xie, Jennifer M Robertson, Ching-Wen Chen, Wenxiao Zhang, Craig M Coopersmith, Mandy L Ford
The presence of pre-existing malignancy in murine hosts results in increased immune dysregulation and risk of mortality following a septic insult. Based on the known systemic immunologic changes that occur in cancer hosts, we hypothesized that the presence of pre-existing malignancy would result in phenotypic and functional changes in CD4+ T cell responses following sepsis. In order to conduct a non-biased, unsupervised analysis of phenotypic differences between CD4+ T cell compartments, cohorts of mice were injected with LLC1 tumor cells and tumors were allowed to grow for 3 weeks...
2018: PloS One
https://www.readbyqxmd.com/read/29335016/autophagy-is-required-for-human-umbilical-cord-mesenchymal-stem-cells-to-improve-spatial-working-memory-in-app-ps1-transgenic-mouse-model
#11
Wen Li, Kai Li, Jing Gao, Zhuo Yang
BACKGROUND: Recent studies have shown that autophagy plays a central role in mesenchymal stem cells (MSCs), and many studies have shown that human umbilical cord MSCs (huMSCs) can treat Alzheimer's disease (AD) through a variety of mechanisms. However, no studies have looked at the effects of autophagy on neuroprotective function of huMSCs in the AD mouse model. Thus, in this study we investigated whether inhibition of autophagy could weaken or block the function of huMSCs through in vitro and in vivo experiments...
January 15, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29334373/prevention-of-tuberculosis-in-rhesus-macaques-by-a-cytomegalovirus-based-vaccine
#12
Scott G Hansen, Daniel E Zak, Guangwu Xu, Julia C Ford, Emily E Marshall, Daniel Malouli, Roxanne M Gilbride, Colette M Hughes, Abigail B Ventura, Emily Ainslie, Kurt T Randall, Andrea N Selseth, Parker Rundstrom, Lauren Herlache, Matthew S Lewis, Haesun Park, Shannon L Planer, John M Turner, Miranda Fischer, Christina Armstrong, Robert C Zweig, Joseph Valvo, Jackie M Braun, Smitha Shankar, Lenette Lu, Andrew W Sylwester, Alfred W Legasse, Martin Messerle, Michael A Jarvis, Lynn M Amon, Alan Aderem, Galit Alter, Dominick J Laddy, Michele Stone, Aurelio Bonavia, Thomas G Evans, Michael K Axthelm, Klaus Früh, Paul T Edlefsen, Louis J Picker
Despite widespread use of the bacille Calmette-Guérin (BCG) vaccine, tuberculosis (TB) remains a leading cause of global mortality from a single infectious agent (Mycobacterium tuberculosis or Mtb). Here, over two independent Mtb challenge studies, we demonstrate that subcutaneous vaccination of rhesus macaques (RMs) with rhesus cytomegalovirus vectors encoding Mtb antigen inserts (hereafter referred to as RhCMV/TB)-which elicit and maintain highly effector-differentiated, circulating and tissue-resident Mtb-specific CD4+ and CD8+ memory T cell responses-can reduce the overall (pulmonary and extrapulmonary) extent of Mtb infection and disease by 68%, as compared to that in unvaccinated controls, after intrabronchial challenge with the Erdman strain of Mtb at ∼1 year after the first vaccination...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29331730/exenatide-exerts-cognitive-effects-by-modulating-the-bdnf-trkb-neurotrophic-axis-in-adult-mice
#13
Manuela Bomba, Alberto Granzotto, Vanessa Castelli, Noemi Massetti, Elena Silvestri, Lorella M T Canzoniero, Annamaria Cimini, Stefano L Sensi
Modulation of insulin-dependent signaling is emerging as a valuable therapeutic tool to target neurodegeneration. In the brain, the activation of insulin receptors promotes cell growth, neuronal repair, and protection. Altered brain insulin signaling participates in the cognitive decline seen in Alzheimer's disease patients and the aging brain. Glucagon-like peptide-1 (GLP-1) regulates insulin secretion and, along with GLP-1 analogues, enhances neurotrophic signaling and counteracts cognitive deficits in preclinical models of neurodegeneration...
December 19, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29331266/human-papilloma-virus-specific-t-cells-can-be-generated-from-na%C3%A3-ve-t-cells-for-use-as-an-immunotherapeutic-strategy-for-immunocompromised-patients
#14
Sarah E McCormack, Conrad Russell Y Cruz, Kaylor E Wright, Allison B Powell, Haili Lang, Cornelia Trimble, Michael D Keller, Ephraim Fuchs, Catherine M Bollard
Human papilloma virus (HPV) is a known cause of cervical cancer, squamous cell carcinoma and laryngeal cancer. Although treatments exist for HPV-associated malignancies, patients unresponsive to these therapies have a poor prognosis. Recent findings from vaccine studies suggest that T-cell immunity is essential for disease control. Because Epstein-Barr Virus (EBV)-specific T cells have been highly successful in treating or preventing EBV-associated tumors, we hypothesized that the development of a manufacturing platform for HPV-specific T cells from healthy donors could be used in a third-party setting to treat patients with high-risk/relapsed HPV-associated cancers...
January 10, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29330372/non-estrogenic-xanthohumol-derivatives-mitigate-insulin-resistance-and-cognitive-impairment-in-high-fat-diet-induced-obese-mice
#15
Cristobal L Miranda, Lance A Johnson, Oriane de Montgolfier, Valerie D Elias, Lea S Ullrich, Joshua J Hay, Ines L Paraiso, Jaewoo Choi, Ralph L Reed, Johana S Revel, Chrissa Kioussi, Gerd Bobe, Urszula T Iwaniec, Russell T Turner, Benita S Katzenellenbogen, John A Katzenellenbogen, Paul R Blakemore, Adrian F Gombart, Claudia S Maier, Jacob Raber, Jan F Stevens
Xanthohumol (XN), a prenylated flavonoid from hops, improves dysfunctional glucose and lipid metabolism in animal models of metabolic syndrome (MetS). However, its metabolic transformation into the estrogenic metabolite, 8-prenylnaringenin (8-PN), poses a potential health concern for its use in humans. To address this concern, we evaluated two hydrogenated derivatives, α,β-dihydro-XN (DXN) and tetrahydro-XN (TXN), which showed negligible affinity for estrogen receptors α and β, and which cannot be metabolically converted into 8-PN...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330114/human-cd4-cd25-cd127hi-cells-and-the-th1-th2-phenotype
#16
Aditi Narsale, Rosita Moya, Joanna Davida Davies
CD4+ T cells that co-express CD25 and CD127 (CD25+CD127+) make up around 20% of all circulating CD4+ memory T cells in healthy people. The clinical significance of these cells is that in children with type 1 diabetes their relative frequency at diagnosis is significantly and directly correlated with rate of disease progression. The purpose of this study was to further characterize the CD25+CD127hi cells. We show that they are a mix of Th1 and Th2 cells however, they have a significantly higher relative frequency of pre-committed and committed Th2 cells, and secrete significantly higher levels of Th2-type cytokines than CD25- memory T cells...
January 9, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29329308/modeling-the-effect-of-boost-timing-in-murine-irradiated-sporozoite-prime-boost-vaccines
#17
Cristina Fernandez-Arias, Clemente F Arias, Min Zhang, Miguel A Herrero, Francisco J Acosta, Moriya Tsuji
Vaccination with radiation-attenuated sporozoites has been shown to induce CD8+ T cell-mediated protection against pre-erythrocytic stages of malaria. Empirical evidence suggests that successive inoculations often improve the efficacy of this type of vaccines. An initial dose (prime) triggers a specific cellular response, and subsequent inoculations (boost) amplify this response to create a robust CD8+ T cell memory. In this work we propose a model to analyze the effect of T cell dynamics on the performance of prime-boost vaccines...
2018: PloS One
https://www.readbyqxmd.com/read/29328908/metabolic-induction-of-trained-immunity-through-the-mevalonate-pathway
#18
Siroon Bekkering, Rob J W Arts, Boris Novakovic, Ioannis Kourtzelis, Charlotte D C C van der Heijden, Yang Li, Calin D Popa, Rob Ter Horst, Julia van Tuijl, Romana T Netea-Maier, Frank L van de Veerdonk, Triantafyllos Chavakis, Leo A B Joosten, Jos W M van der Meer, Henk Stunnenberg, Niels P Riksen, Mihai G Netea
Innate immune cells can develop long-term memory after stimulation by microbial products during infections or vaccinations. Here, we report that metabolic signals can induce trained immunity. Pharmacological and genetic experiments reveal that activation of the cholesterol synthesis pathway, but not the synthesis of cholesterol itself, is essential for training of myeloid cells. Rather, the metabolite mevalonate is the mediator of training via activation of IGF1-R and mTOR and subsequent histone modifications in inflammatory pathways...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29328786/connections-between-metabolism-and-epigenetics-in-programming-cellular-differentiation
#19
Danielle A Chisolm, Amy S Weinmann
Researchers are intensifying efforts to understand the mechanisms by which changes in metabolic states influence differentiation programs. An emerging objective is to define how fluctuations in metabolites influence the epigenetic states that contribute to differentiation programs. This is because metabolites such as S-adenosylmethionine, acetyl-CoA, α-ketoglutarate, 2-hydroxyglutarate, and butyrate are donors, substrates, cofactors, and antagonists for the activities of epigenetic-modifying complexes and for epigenetic modifications...
January 12, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29328782/the-role-of-nivolumab-in-melanoma
#20
Fabio Gomes, Patricio Serra-Bellver, Paul Lorigan
The incidence of melanoma continues to rise worldwide. Prior to 2010, there had been no progress in the treatment of advanced melanoma in living memory. Since then, immunotherapy has become a standard of care in the treatment of advanced melanoma. Nivolumab is a fully human monoclonal antibody against PD-1, which is a negative regulatory checkpoint in the T cells. The clinical benefit of nivolumab as a single agent is well established, with response rates of ≥40%, durable responses and a favorable tolerability profile...
January 12, 2018: Future Oncology
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