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https://www.readbyqxmd.com/read/27926878/the-csk-associated-adaptor-pag-inhibits-effector-t-cell-activation-in-cooperation-with-phosphatase-ptpn22-and-dok-adaptors
#1
Dominique Davidson, Ming-Chao Zhong, Pier Paolo Pandolfi, Silvia Bolland, Ramnik J Xavier, Brian Seed, Xin Li, Hua Gu, André Veillette
The transmembrane adaptor PAG (Cbp) has been proposed to mediate membrane recruitment of Csk, a cytoplasmic protein tyrosine kinase playing a critical inhibitory role during T cell activation, by inactivating membrane-associated Src kinases. However, this model has not been validated by genetic evidence. Here, we demonstrate that PAG-deficient mice display enhanced T cell activation responses in effector, but not in naive, T cells. PAG-deficient mice also have augmented T cell-dependent autoimmunity and greater resistance to T cell anergy...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27920523/pegylated-and-nanoparticle-conjugated-sulfonium-salt-photo-triggers-necrotic-cell-death
#2
Alaa A Fadhel, Xiling Yue, Ebrahim H Ghazvini Zadeh, Mykhailo V Bondar, Kevin D Belfield
Photodynamic therapy (PDT) processes involving the production of singlet oxygen face the issue of oxygen concentration dependency. Despite high oxygen delivery, a variety of properties related to metabolism and vascular morphology in cancer cells result in hypoxic environments, resulting in limited effectiveness of such therapies. An alternative oxygen-independent agent whose cell cytotoxicity can be remotely controlled by light may allow access to treatment of hypoxic tumors. Toward that end, we developed and tested both polyethylene glycol (PEG)-functionalized and hydrophilic silica nanoparticle (SiNP)-enriched photoacid generator (PAG) as a nontraditional PDT agent to effectively induce necrotic cell death in HCT-116 cells...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27916440/characterisation-of-peroxisome-proliferator-activated-receptor-signalling-in-the-midbrain-periaqueductal-grey-of-rats-genetically-prone-to-heightened-stress-negative-affect-and-hyperalgesia
#3
Bright N Okine, Jessica C Gaspar, Manish K Madasu, Weredeselam M Olango, Brendan Harhen, Michelle Roche, David P Finn
The stress-hyperresponsive Wistar-Kyoto (WKY) rat strain exhibits a hyperalgesic phenotype and is a useful genetic model for studying stress-pain interactions. Peroxisome proliferator-activated receptor (PPAR) signalling in the midbrain periaqueductal grey (PAG) modulates pain. This study characterised PPAR signalling in the PAG of WKY rats exposed to the formalin test of inflammatory pain, versus Sprague-Dawley (SD) controls. Formalin injection reduced levels of the endogenous PPAR ligands N-palmitoylethanolamide (PEA) and N-oleoylethanolamide (OEA) in the lateral(l) PAG of SD rats, but not WKY rats which exhibited higher levels of these analytes compared with formalin-injected SD counterparts...
December 1, 2016: Brain Research
https://www.readbyqxmd.com/read/27911793/heterogeneous-yet-stable-v%C3%AE-2-t-cell-profiles-define-distinct-cytotoxic-effector-potentials-in-healthy-human-individuals
#4
Paul L Ryan, Nital Sumaria, Christopher J Holland, Claire M Bradford, Natalia Izotova, Capucine L Grandjean, Ali S Jawad, Lesley A Bergmeier, Daniel J Pennington
Human γδ T cells display potent responses to pathogens and malignancies. Of particular interest are those expressing a γδ T-cell receptor (TCR) incorporating TCRδ-chain variable-region-2 [Vδ2((+))], which are activated by pathogen-derived phosphoantigens (pAgs), or host-derived pAgs that accumulate in transformed cells or in cells exposed to aminobisphosphonates. Once activated, Vδ2((+)) T cells exhibit multiple effector functions that have made them attractive candidates for immunotherapy. Despite this, clinical trials have reported mixed patient responses, highlighting a need for better understanding of Vδ2((+)) T-cell biology...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27895565/challenges-to-the-pair-bond-neural-and-hormonal-effects-of-separation-and-reunion-in-a-monogamous-primate
#5
Katie Hinde, Chelsea Muth, Nicole Maninger, Benjamin J Ragen, Rebecca H Larke, Michael R Jarcho, Sally P Mendoza, William A Mason, Emilio Ferrer, Simon R Cherry, Marina L Fisher-Phelps, Karen L Bales
Social monogamy at its most basic is a group structure in which two adults form a unit and share a territory. However, many socially monogamous pairs display attachment relationships known as pair bonds, in which there is a mutual preference for the partner and distress upon separation. The neural and hormonal basis of this response to separation from the adult pair mate is under-studied. In this project, we examined this response in male titi monkeys (Callicebus cupreus), a socially monogamous New World primate...
2016: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/27873132/mechanisms-of-excessive-extracellular-glutamate-accumulation-in-temporal-lobe-epilepsy
#6
Jan Albrecht, Magdalena Zielińska
There is compelling evidence that initiation and maintenance of epileptic seizures in temporal lobe epilepsy (TLE) is facilitated by excessive accumulation in the extracellular (perisynaptic) space of the excitatory neurotransmitter glutamate (Glu). This review discusses the mechanisms underlying this phenomenon. Glu released from neurons is taken up by astrocytes and activated there by glutamine synthetase (GS) to form glutamine (Gln) which upon entry to neurons is degraded back to Glu by phosphate-activated glutaminase (PAG): this chain of reactions has been defined as the glutamine/glutamate/cycle (GGC)...
November 21, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27872027/how-the-emotional-motor-system-controls-the-pelvic-organs
#7
REVIEW
Gert Holstege
INTRODUCTION: The brain has two goals: survival of the individual and survival of the species. It ensures that the body resides in safe circumstances and can obtain sufficient drink and food. It also has to produce and protect offspring. Its most important tool is its motor system, which consists of the voluntary and emotional motor systems. AIM: To explain how the brain uses its emotional motor system to control the pelvic organs. METHODS: Anatomic and physiologic data in cats and humans are used to find out how this motor system works and what parts of the brain and brainstem are involved...
October 2016: Sexual Medicine Reviews
https://www.readbyqxmd.com/read/27864905/polyacrylamide-gel-as-a-culture-substrate-improves-in-vitro-oocyte-growth-from-porcine-early-antral-follicles
#8
Yasuhisa Munakata, Ryouka Kawahara-Miki, Koumei Shirasuna, Takehito Kuwayama, Hisataka Iwata
A major difference between in vivo and in vitro follicle culture is the stiffness of the substrate in which the follicles grow. In this study, we examined the effect of polyacrylamide gel (PAG), as a culture substrate, on the development of porcine oocytes derived from early antral follicles. Oocyte-granulosa cell complexes (OGCs) were collected from the early antral follicles of gilts, and incubated individually for 14 days in a 96-well culture plate with or without PAG. We then evaluated the number of granulosa cells present in OGCs as well as the abundance of ATP, lipid, and acetylated lysine in oocytes...
November 19, 2016: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/27864656/nitric-oxide-and-hydrogen-sulfide-interact-when-modulating-gastric-physiological-functions-in-rodents
#9
Larisse Tavares Lucetti, Renan Oliveira Silva, Ana Paula Macedo Santana, Bruno de Melo Tavares, Mariana Lima Vale, Pedro Marcos Gomes Soares, Francisco José Batista de Lima Júnior, Pedro Jorge Caldas Magalhães, Fernando de Queiroz Cunha, Ronaldo de Albuquerque Ribeiro, Jand-Venes Rolim Medeiros, Marcellus Henrique Loiola Ponte Souza
AIM: The objective was to evaluate the effects of nitric oxide (NO) and hydrogen sulfide (H2S) donors and possible interactions between these two systems in modulating gastric function. METHODS: Mice received saline, sodium nitroprusside (SNP), or sodium hydrosulfite (NaHS), and after 1 h, the animals were killed for immunofluorescence analysis of CSE or eNOS expressions, respectively. Other groups received saline, SNP, NaHS, Lawesson's reagent (H2S donor), PAG + SNP, L-NAME, L-NAME + NaHS, or L-NAME + Lawesson's reagent...
November 18, 2016: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/27825819/interaction-between-endogenous-carbon-monoxide-and-hydrogen-sulfide-in-the-mechanism-of-gastroprotection-against-acute-aspirin-induced-gastric-damage
#10
Marcin Magierowski, Katarzyna Magierowska, Magdalena Hubalewska-Mazgaj, Juliusz Adamski, Dominik Bakalarz, Zbigniew Sliwowski, Robert Pajdo, Slawomir Kwiecien, Tomasz Brzozowski
Acetylsalicylic acid (ASA) is mainly recognized as painkiller or anti-inflammatory drug. However, ASA causes serious side effects towards gastrointestinal (GI) tract which limits its usefulness. Carbon monoxide (CO) and hydrogen sulfide (H2S) have been described to act as important endogenous messengers and mediators of gastroprotection but whether they can interact in gastroprotection against acute ASA-induced gastric damage remains unknown. In this study male Wistar rats were pretreated with 1) vehicle (saline, i...
November 5, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27796733/nonspecific-periaqueductal-gray-lesions-on-t2wi-in-episodic-migraine
#11
Zhiye Chen, Xiaoyan Chen, Mengqi Liu, Shuangfeng Liu, Lin Ma, Shengyuan Yu
BACKGROUND: The specific periaqueductal gray (PAG) lesions with migraine-like headache were easily identified on conventional MR images in clinical practice, and the aim of this study is to investigate the nonspecific periaqueductal gray (PAG) lesions in episodic migraine (EM) patients based on T2 weighted imaging (T2WI). METHODS: T2WI images were obtained from 18 EM patients and 18 normal controls (NC) on 3.0 T MR system. The images were observed by two experienced radiologists, and the lesions were identified on T2WI by consensus by 2 experienced neuroradiologists blinded to the patient identity...
December 2016: Journal of Headache and Pain
https://www.readbyqxmd.com/read/27787475/enzyme-activities-involved-in-the-glutamate-glutamine-cycle-are-altered-to-reduce-glutamate-after-spinal-cord-injury-in-rats
#12
Araceli Diaz-Ruiz, Sergio Montes, Hermelinda Salgado-Ceballos, Valente Maldonado, Liliana Rivera-Espinosa, Camilo Ríos
Glutamate (Glu) neurotransmitter is involved in the excitotoxic damage after spinal cord injury (SCI). Glu is transformed into glutamine (Gln) by glutamine synthetase (GS) enzyme in glial cells. Once into the neurons, Gln is transformed back into Glu by phosphate-activated glutaminase (PAG). Glu is also a precursor for the synthesis of γ-aminobutyric acid through the action of the glutamic acid decarboxylase (GAD) enzyme. The contribution of all these Glu biotransformations after SCI has not been determined...
October 26, 2016: Neuroreport
https://www.readbyqxmd.com/read/27780778/resting-state-connectivity-of-the-human-habenula-at-ultra-high-field
#13
Salvatore Torrisi, Camilla L Nord, Nicholas L Balderston, Jonathan P Roiser, Christian Grillon, Monique Ernst
The habenula, a portion of the epithalamus, is implicated in the pathophysiology of depression, anxiety and addiction disorders. Its small size and connection to other small regions prevent standard human imaging from delineating its structure and connectivity with confidence. Resting state functional connectivity is an established method for mapping connections across the brain from a seed region of interest. The present study takes advantage of 7 T fMRI to map, for the first time, the habenula resting state network with very high spatial resolution in 32 healthy human participants...
October 22, 2016: NeuroImage
https://www.readbyqxmd.com/read/27751963/inward-rectifying-k-kir2-leak-conductance-dampens-the-excitability-of-lamina-i-projection-neurons-in-the-neonatal-rat
#14
Neil C Ford, Mark L Baccei
Spinal lamina I projection neurons serve as a major conduit by which noxious stimuli detected in the periphery are transmitted to nociceptive circuits in the brain, including the parabrachial nucleus (PB) and the periaqueductal gray (PAG). While neonatal spino-PB neurons are more than twice as likely to exhibit spontaneous activity compared to spino-PAG neurons, the underlying mechanisms remain unclear since nothing is known about the voltage-independent (i.e. 'leak') ion channels expressed by these distinct populations during early life...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27744121/s-propargyl-cysteine-attenuates-inflammatory-response-in-rheumatoid-arthritis-by-modulating-the-nrf2-are-signaling-pathway
#15
Wei-Jun Wu, Wan-Wan Jia, Xin-Hua Liu, Li-Long Pan, Qiu-Yan Zhang, Di Yang, Xiao-Yan Shen, Liang Liu, Yi Zhun Zhu
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder. Hydrogen sulfide (H2S), the third physiological gasotransmitter, is well recognized as an anti-inflammatory mediator in various inflammatory conditions. Herein, we explored the protective effects of S-propargyl-cysteine (SPRC, also known as ZYZ-802), an endogenous H2S modulator, on RA and determined the underlying mechanisms. In the present study, SPRC concentration-dependently attenuated inflammatory mediator expression, reactive oxidase species generation, and the expression and activity of matrix metalloproteinases (MMP)-9 in interleukin (IL)-1β-induced human rheumatoid fibroblast-like synoviocytes MH7A...
October 6, 2016: Redox Biology
https://www.readbyqxmd.com/read/27742580/mechanical-allodynia-corresponds-to-oprm1-downregulation-within-the-descending-pain-network-of-male-and-female-rats-exposed-to-neonatal-immune-challenge
#16
Siyang Yan, Amanda C Kentner
Exposure to painful procedures and/or stressors during the early neonatal period can reprogram the underlying neurocircuitry involved in nociception and neuropathic pain perception. The reprogramming of these systems can result in an enduring elevation in sensitivity towards mechanical and thermal stimuli. Recent evidence suggests that exposure to mild inflammatory mediators during the neonatal period can induce similar pain responses in both adolescent and adult rats. Therefore, we sought to profile changes in the expression of several genes across brain areas involved in the active modulation of nociception and neuropathic pain using a well-recognized model of neonatal inflammation...
October 11, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27742014/kdm4c-a-h3k9me3-histone-demethylase-is-involved-in-the-maintenance-of-human-escc-initiating-cells-by-epigenetically-enhancing-sox2-expression
#17
Xiang Yuan, Jinyu Kong, Zhikun Ma, Na Li, Ruinuo Jia, Yiwen Liu, Fuyou Zhou, Qimin Zhan, Gang Liu, Shegan Gao
Our studies investigating the existence of tumor-initiating cell (TIC) populations in human esophageal squamous cell carcinoma (ESCC) had identified a subpopulation of cells isolated from ESCC patient-derived tumor specimens marked by an ALDH(bri+) phenotype bear stem cell-like features. Importantly, KDM4C, a histone demethylase was enhanced in ALDH(bri+) subpopulation, suggesting that strategies interfering with KDM4C may be able to target these putative TICs. In the present study, by genetic and chemical means, we demonstrated that, KDM4C blockade selectively decreased the ESCC ALDH(bri+) TICs population in vitro and specifically targeted the TICs in ALDH(bri+)-derived xenograft, retarding engraftment...
October 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27739113/photochemistry-of-n-arylsulfonimides-an-easily-available-class-of-nonionic-photoacid-generators-pags
#18
Edoardo Torti, Stefano Protti, Daniele Merli, Daniele Dondi, Maurizio Fagnoni
The photochemical behavior of differently substituted N-arylsulfonimides was investigated. Homolysis of the S-N bond took place as the exclusive path from the singlet state to afford both N-arylsulfonamides and photo-Fries adducts, the amount of which depended on reaction conditions and aromatic substituents. Sulfinic and sulfonic acids were released upon irradiation under deaerated and oxygenated conditions, respectively. The nature of the excited states and intermediates involved were proved by laser flash photolysis and EPR experiments...
November 14, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27710864/the-effects-of-hydrogen-sulfide-on-electrical-field-stimulation-induced-neurogenic-contractile-responses-in-isolated-rabbit-lower-esophageal-sphincter-contribution-of-nitrergic-and-non-adrenergic-non-cholinergic-transmission
#19
Halil Kara, Fatma Isli, Gokce Sevim Ozturk Fincan, Seniz Yildirim, Sevim Ercan, Yusuf Sarioglu
BACKGROUND: Hydrogen sulfide (H2S) is a gaseous signaling molecule that, similar to nitric oxide (NO), plays an important role as an inhibitor neurotransmitter in the digestive tract. This study aimed to investigate the effect of H2S and to identify neurogenic contraction responses dependent on the electrical field stimulation (EFS) in the isolated lower esophageal sphincters of rabbits. METHODS: An isolated lower esophageal sphincter was placed in an organ bath system and mechanical responses were recorded using a force transducer...
September 6, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27706653/diallel-analysis-to-choose-parents-for-black-bean-phaseolus-vulgaris-l-breeding
#20
L M Moura, P C S Carneiro, N M Vale, L D Barili, L C Silva, J E S Carneiro, C D Cruz
In this study, conducted in two different seasons, we aimed to choose parents to obtain promising segregating populations for the extraction of black bean (Phaseolus vulgaris L.) lines that are superior in terms of disease resistance, plant architecture, and grain yield. Twelve parents were arranged in two groups to compose a partial diallel in a 5 x 7 scheme. Group 1 was composed of parents with black grains and erect plant architecture, while group 2 was composed of parents that had carioca grains and were resistant to the main fungal diseases that occur in the common bean...
August 29, 2016: Genetics and Molecular Research: GMR
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