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https://www.readbyqxmd.com/read/29671217/cyproheptadine-regulates-pyramidal-neuron-excitability-in-mouse-medial-prefrontal-cortex
#1
Yan-Lin He, Kai Wang, Qian-Ru Zhao, Yan-Ai Mei
Cyproheptadine (CPH), a first-generation antihistamine, enhances the delayed rectifier outward K+ current (IK ) in mouse cortical neurons through a sigma-1 receptor-mediated protein kinase A pathway. In this study, we aimed to determine the effects of CPH on neuronal excitability in current-clamped pyramidal neurons in mouse medial prefrontal cortex slices. CPH (10 µmol/L) significantly reduced the current density required to generate action potentials (APs) and increased the instantaneous frequency evoked by a depolarizing current...
April 18, 2018: Neuroscience Bulletin
https://www.readbyqxmd.com/read/29664957/killer-cell-immunoglobulin-like-receptors-associate-with-hiv-1-infection-in-a-narrow-source-han-chinese-cohort
#2
Linghang Wang, Yonghong Zhang, Keyi Xu, Tao Dong, Sarah Rowland-Jones, Louis-Marie Yindom
BACKGROUND: The HIV pandemic remains the most serious challenge to public health worldwide. The hallmark characteristics of the disease is the eventual failure of the immune system to control opportunistic infections and death. However not everyone who has HIV develops the disease at the same rate and so we are studying how the immune system works to control the virus in those who have been infected for decades and remain relatively healthy without the need of anti-retroviral therapy (ART)...
2018: PloS One
https://www.readbyqxmd.com/read/29661190/a-manually-annotated-actinidia-chinensis-var-chinensis-kiwifruit-genome-highlights-the-challenges-associated-with-draft-genomes-and-gene-prediction-in-plants
#3
Sarah M Pilkington, Ross Crowhurst, Elena Hilario, Simona Nardozza, Lena Fraser, Yongyan Peng, Kularajathevan Gunaseelan, Robert Simpson, Jibran Tahir, Simon C Deroles, Kerry Templeton, Zhiwei Luo, Marcus Davy, Canhong Cheng, Mark McNeilage, Davide Scaglione, Yifei Liu, Qiong Zhang, Paul Datson, Nihal De Silva, Susan E Gardiner, Heather Bassett, David Chagné, John McCallum, Helge Dzierzon, Cecilia Deng, Yen-Yi Wang, Lorna Barron, Kelvina Manako, Judith Bowen, Toshi M Foster, Zoe A Erridge, Heather Tiffin, Chethi N Waite, Kevin M Davies, Ella P Grierson, William A Laing, Rebecca Kirk, Xiuyin Chen, Marion Wood, Mirco Montefiori, David A Brummell, Kathy E Schwinn, Andrew Catanach, Christina Fullerton, Dawei Li, Sathiyamoorthy Meiyalaghan, Niels Nieuwenhuizen, Nicola Read, Roneel Prakash, Don Hunter, Huaibi Zhang, Marian McKenzie, Mareike Knäbel, Alastair Harris, Andrew C Allan, Andrew Gleave, Angela Chen, Bart J Janssen, Blue Plunkett, Charles Ampomah-Dwamena, Charlotte Voogd, Davin Leif, Declan Lafferty, Edwige J F Souleyre, Erika Varkonyi-Gasic, Francesco Gambi, Jenny Hanley, Jia-Long Yao, Joey Cheung, Karine M David, Ben Warren, Ken Marsh, Kimberley C Snowden, Kui Lin-Wang, Lara Brian, Marcela Martinez-Sanchez, Mindy Wang, Nadeesha Ileperuma, Nikolai Macnee, Robert Campin, Peter McAtee, Revel S M Drummond, Richard V Espley, Hilary S Ireland, Rongmei Wu, Ross G Atkinson, Sakuntala Karunairetnam, Sean Bulley, Shayhan Chunkath, Zac Hanley, Roy Storey, Amali H Thrimawithana, Susan Thomson, Charles David, Raffaele Testolin, Hongwen Huang, Roger P Hellens, Robert J Schaffer
BACKGROUND: Most published genome sequences are drafts, and most are dominated by computational gene prediction. Draft genomes typically incorporate considerable sequence data that are not assigned to chromosomes, and predicted genes without quality confidence measures. The current Actinidia chinensis (kiwifruit) 'Hongyang' draft genome has 164 Mb of sequences unassigned to pseudo-chromosomes, and omissions have been identified in the gene models. RESULTS: A second genome of an A...
April 16, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29650538/kir-channel-blockages-by-proflavine-derivatives-via-multiple-modes-of-interaction
#4
Atsushi Inanobe, Hideaki Itamochi, Yoshihisa Kurachi
Many compounds inhibit tetrameric and pseudo-tetrameric cation channels by associating with the central cavity located in the middle of the membrane plane. They traverse the ion conduction pathway from intracellular side and access to the cavity. Previously we reported that the bacteriostatic agent, proflavine, preferentially blocked a subset of Kir channels. However, the development of the inhibition of Kir1.1 by the compound was obviously different from that operating in Kir3.2 as a pore blocker. To gain mechanistic insights into the compound-channel interaction, we analyzed its chemical specificity, subunit selectivity, and voltage dependency using 13 different combinations of Kir-channel family members and 11 proflavine derivatives...
April 12, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29615871/a-novel-kcnj2-mutation-identified-in-an-autistic-proband-affects-the-single-channel-properties-of-kir2-1
#5
Anna Binda, Ilaria Rivolta, Chiara Villa, Elisa Chisci, Massimiliano Beghi, Cesare M Cornaggia, Roberto Giovannoni, Romina Combi
Inwardly rectifying potassium channels (Kir) have been historically associated to several cardiovascular disorders. In particular, loss-of-function mutations in the Kir2.1 channel have been reported in cases affected by Andersen-Tawil syndrome while gain-of-function mutations in the same channel cause the short QT3 syndrome. Recently, a missense mutation in Kir2.1, as well as mutations in the Kir4.1, were reported to be involved in autism spectrum disorders (ASDs) suggesting a role of potassium channels in these diseases and introducing the idea of the existence of K+ channel ASDs...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29493017/plaque-dependent-morphological-and-electrophysiological-heterogeneity-of-microglia-in-an-alzheimer-s-disease-mouse-model
#6
Monika Plescher, Gerald Seifert, Jan Niklas Hansen, Peter Bedner, Christian Steinhäuser, Annett Halle
Microglia, the central nervous system resident innate immune cells, cluster around Aβ plaques in Alzheimer's disease (AD). The activation phenotype of these plaque-associated microglial cells, and their differences to microglia distant to Aβ plaques, are incompletely understood. We used novel three-dimensional cell analysis software to comprehensively analyze the morphological properties of microglia in the TgCRND8 mouse model of AD in spatial relation to Aβ plaques. We found strong morphological changes exclusively in plaque-associated microglia, whereas plaque-distant microglia showed only minor changes...
March 1, 2018: Glia
https://www.readbyqxmd.com/read/29447367/endometrial-natural-killer-nk-cells-reveal-a-tissue-specific-receptor-repertoire
#7
D Feyaerts, T Kuret, B van Cranenbroek, S van der Zeeuw-Hingrez, O W H van der Heijden, A van der Meer, I Joosten, R G van der Molen
STUDY QUESTION: Is the natural killer (NK) cell receptor repertoire of endometrial NK (eNK) cells tissue-specific? SUMMARY ANSWER: The NK cell receptor (NKR) expression profile in pre-pregnancy endometrium appears to have a unique tissue-specific phenotype, different from that found in NK cells in peripheral blood, suggesting that these cells are finely tuned towards the reception of an allogeneic fetus. WHAT IS KNOWN ALREADY: NK cells are important for successful pregnancy...
February 13, 2018: Human Reproduction
https://www.readbyqxmd.com/read/29422007/k-channels-of-m%C3%A3-ller-glial-cells-in-retinal-disorders
#8
Feng Gao, Linjie Xu, Yuan Zhao, Xinghuai Sun, Zhongfeng Wang
Müller cell is the major type glial cell in the vertebrate retina. Müller cells express various types of K+ channels, such as inwardly rectifying K+ (Kir) channels, big conductance Ca2+-activated K+ (BKCa) channels, delayed rectifier K+ channels (KDR), and transient A-type K+ channels. These K+ channels play important roles in maintaining physiological functions of Müller cells. Under some retinal pathological conditions, the changed expression and functions of K+ channels may contribute to retinal pathogenesis...
February 1, 2018: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/29409796/the-anti-diabetic-drug-dapagliflozin-induces-vasodilation-via-activation-of-pkg-and-kv-channels
#9
Hongliang Li, Sung Eun Shin, Mi Seon Seo, Jin Ryeol An, Il-Whan Choi, Won-Kyo Jung, Amy L Firth, Dae-Sung Lee, Mi-Jin Yim, Grace Choi, Jeong Min Lee, Sung Hun Na, Won Sun Park
AIM: Considering the clinical efficacy of dapagliflozin in patients with type 2 DM and the pathophysiological relevance of Kv channels for vascular reactivity. We investigate the vasodilatory effect of dapagliflozin and related mechanisms using phenylephrine (Phe)-induced contracted aortic rings. MATERIAL AND METHODS: Arterial tone measurement was performed in aortic smooth muscle. KEY FINDINGS: Application of dapagliflozin induced vasodilation in a concentration-dependent manner...
January 31, 2018: Life Sciences
https://www.readbyqxmd.com/read/29384924/association-between-kir-gene-polymorphisms-and-type-1-diabetes-mellitus-t1dm-susceptibility-a-prisma-compliant-meta-analysis
#10
Shu-Lan Liu, A-Juan Zheng, Li Ding
BACKGROUND: Type 1 diabetes mellitus (T1DM) is a T-cell mediated autoimmune disease with a complex genetic and immunological background. Evidence suggests that killer cell immunoglobulin-like receptor (KIR) genes are associated with T1DM, but the results are inconsistent. Here, we conducted a meta-analysis to comprehensively evaluate the effect of KIR genes on the risk of T1DM. METHODS: The PubMed, Web of Science, the Chinese Biomedical Database, and Chinese National Knowledge Infrastructure databases were systematically searched to select studies on the association between KIR polymorphisms and T1DM...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29383623/nk-cell-therapy-for-hematologic-malignancies
#11
REVIEW
Rohtesh S Mehta, Brion Randolph, May Daher, Katayoun Rezvani
Natural killer (NK) cells are part of the innate immune system and represent the first line of defense against infections and tumors. In contrast to T cells, NK cells do not require prior antigen sensitization to induce cytotoxicity and do not cause graft-versus-host disease. These, along with other advantages, make NK cells an attractive candidate for adoptive cellular therapy. Herein, we describe the mechanisms of NK cell cytotoxicity, which is governed by an intricate balance between various activating and inhibitory receptors, including the killer cell immunoglobulin-like receptors (KIRs)...
January 27, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29367714/selected-biological-issues-affecting-relapse-after-stem-cell-transplantation-role-of-t-cell-impairment-nk-cells-and-intrinsic-tumor-resistance
#12
Marcel van den Brink, Markus Uhrberg, Lorenz Jahn, John F DiPersio, Michael A Pulsipher
The graft vs. leukemia (GvL) effect as a method of preventing relapse is well described after allogeneic hematopoietic cell transplantation (HCT), but the mechanisms to this effect and how tumor sometimes develops resistance to GvL are just beginning to be understood. This article reviews and expands upon data presented at the Third International Workshop on Biology, Prevention and Treatment of Relapse after Stem Cell Transplantation held in Hamburg, Germany, in November 2016. We first discuss in detail the role that T-cell impairment early after HCT plays in relapse by looking at data from T cell-depleted approaches as well as the clear role that early T-cell recovery has shown in improving outcomes...
January 24, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29326855/all-types-of-age-related-macular-degeneration-in-one-patient
#13
Zafer Cebeci, Nur Kır
Herein, we describe a neovascular age-related macular degeneration patient with retinal angiomatous proliferation (RAP) and polypoidal choroidal vasculopathy (PCV) coexisting in the same eye at the time of diagnosis. A 55-year-old woman presented with a history of decreased vision in her left eye. Fundoscopy, fluorescein and indocyanine green angiography, and optical coherence tomography imaging revealed RAP and PCV lesions in her left eye at first diagnosis. The patient received intravitreal ranibizumab therapy but developed tachyphylaxis after the first dose despite having three monthly doses...
December 2017: Turkish Journal of Ophthalmology
https://www.readbyqxmd.com/read/29237245/molecular-mechanisms-and-physiological-relevance-of-rgk-proteins-in-the-heart
#14
REVIEW
U Meza, D Beqollari, R A Bannister
The primary route of Ca2+ entry into cardiac myocytes is via 1,4-dihydropyridine-sensitive, voltage-gated L-type Ca2+ channels. Ca2+ influx through these channels influences duration of action potential and engages excitation-contraction (EC) coupling in both the atria and the myocardium. Members of the RGK (Rad, Rem, Rem2 and Gem/Kir) family of small GTP-binding proteins are potent, endogenously expressed inhibitors of cardiac L-type channels. Although much work has focused on the molecular mechanisms by which RGK proteins inhibit the CaV 1...
December 13, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/29194614/immunomodulatory-effects-of-foreskin-mesenchymal-stromal-cells-on-natural-killer-cells
#15
Mehdi Najar, Mohammad Fayyad-Kazan, Nathalie Meuleman, Dominique Bron, Hussein Fayyad-Kazan, Laurence Lagneaux
Foreskin-mesenchymal stromal cells (FSK-MSCs) are immune-privileged thus making them valuable immunotherapeutic cell product. Characterization of the relationship between FSK-MSCs and natural killer (NK) cells is essential to improve cell-based therapy. In the present study, we studied for the first time FSK-MSCs-NK interaction and showed that the result of such cross talk was robustly dependent on the type of cytokines (IL-2, IL-12, IL-15, and IL-21) employed to activate NK cells. Distinctly activated-NK cells showed uneven cytotoxicity against FSK-MSCs, triggering their death in fine...
December 1, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29160618/deciphering-the-fine-nucleotide-diversity-of-full-hla-class-i-and-class-ii-genes-in-a-well-documented-population-from-sub-saharan-africa
#16
T Goeury, L E Creary, L Brunet, M Galan, M Pasquier, B Kervaire, A Langaney, J-M Tiercy, M A Fernández-Viña, J M Nunes, A Sanchez-Mazas
With the aim to understand how next-generation sequencing (NGS) improves both our assessment of genetic variation within populations and our knowledge on HLA molecular evolution, we sequenced and analysed 8 HLA loci in a well-documented population from sub-Saharan Africa (Mandenka). The results of full-gene NGS-MiSeq sequencing compared with those obtained by traditional typing techniques or limited sequencing strategies showed that segregating sites located outside exon 2 are crucial to describe not only class I but also class II population diversity...
January 2018: HLA
https://www.readbyqxmd.com/read/29149205/kir-content-genotypes-associate-with-carriage-of-hepatitis-b-surface-antigen-e-antigen-and-hbv-viral-load-in-gambians
#17
Louis-Marie Yindom, Maimuna Mendy, Christopher Bodimeade, Caroline Chambion, Peter Aka, Hilton C Whittle, Sarah L Rowland-Jones, Robert Walton
BACKGROUND: Hepatocellular carcinoma (HCC) causes over 800,000 deaths worldwide annually, mainly in low income countries, and incidence is rising rapidly in the developed world with the spread of hepatitis B (HBV) and C (HCV) viruses. Natural Killer (NK) cells protect against viral infections and tumours by killing abnormal cells recognised by Killer-cell Immunoglobulin-like Receptors (KIR). Thus genes and haplotypes encoding these receptors may be important in determining both outcome of initial hepatitis infection and subsequent chronic liver disease and tumour formation...
2017: PloS One
https://www.readbyqxmd.com/read/29136290/the-role-of-ca-2-dependent-k-channels-at-the-rat-corticostriatal-synapses-revealed-by-paired-pulse-stimulation
#18
Angel A Robles Gómez, Ana V Vega, Carolina Gónzalez-Sandoval, Jaime Barral
Potassium channels play an important role in modulating synaptic activity both at presynaptic and postsynaptic levels. We have shown before that presynaptically located KV and KIR channels modulate the strength of corticostriatal synapses in rat brain, but the role of other types of potassium channels at these synapses remains largely unknown. Here, we show that calcium-dependent potassium channels BK-type but not SK-type channels are located presynaptically in corticostriatal synapses. We stimulated cortical neurons in rat brain slices and recorded postsynaptic excitatory potentials (EPSP) in medium spiny neurons (MSN) in dorsal neostriatum...
February 2018: Synapse
https://www.readbyqxmd.com/read/29032017/next-generation-sequencing-technology-a-new-tool-for-killer-cell-immunoglobulin-like-receptor-allele-typing-in-hematopoietic-stem-cell-transplantation
#19
B Maniangou, C Retière, K Gagne
Killer cell Immunoglobulin-like Receptor (KIR) genes are a family of genes located together within the leukocyte receptor cluster on human chromosome 19q13.4. To date, 17 KIR genes have been identified including nine inhibitory genes (2DL1/L2/L3/L4/L5A/L5B, 3DL1/L2/L3), six activating genes (2DS1/S2/S3/S4/S5, 3DS1) and two pseudogenes (2DP1, 3DP1) classified into group A (KIR A) and group B (KIR B) haplotypes. The number and the nature of KIR genes vary between the individuals. In addition, these KIR genes are known to be polymorphic at allelic level (907 alleles described in July 2017)...
February 2018: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
https://www.readbyqxmd.com/read/29016852/potassium-channel-dysfunction-underlies-purkinje-neuron-spiking-abnormalities-in-spinocerebellar-ataxia-type-2
#20
James M Dell'Orco, Stefan M Pulst, Vikram G Shakkottai
Alterations in Purkinje neuron firing often accompany ataxia, but the molecular basis for these changes is poorly understood. In a mouse model of spinocerebellar ataxia type 2 (SCA2), a progressive reduction in Purkinje neuron firing frequency accompanies cell atrophy. We investigated the basis for altered Purkinje neuron firing in SCA2. A reduction in the expression of large-conductance calcium-activated potassium (BK) channels and Kv3.3 voltage-gated potassium channels accompanies the inability of Purkinje neurons early in disease to maintain repetitive spiking...
October 15, 2017: Human Molecular Genetics
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