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https://www.readbyqxmd.com/read/28214226/cd49a-expression-defines-tissue-resident-cd8-t-cells-poised-for-cytotoxic-function-in-human-skin
#1
Stanley Cheuk, Heinrich Schlums, Irène Gallais Sérézal, Elisa Martini, Samuel C Chiang, Nicole Marquardt, Anna Gibbs, Ebba Detlofsson, Andrea Introini, Marianne Forkel, Charlotte Höög, Annelie Tjernlund, Jakob Michaëlsson, Lasse Folkersen, Jenny Mjösberg, Lennart Blomqvist, Marcus Ehrström, Mona Ståhle, Yenan T Bryceson, Liv Eidsmo
Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8(+) Trm cells on a compartmental and functional basis. In human skin epithelia, CD8(+)CD49a(+) Trm cells produced interferon-γ, whereas CD8(+)CD49a(-) Trm cells produced interleukin-17 (IL-17). In addition, CD8(+)CD49a(+) Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response...
February 13, 2017: Immunity
https://www.readbyqxmd.com/read/28214100/nlrp6-a-multifaceted-innate-immune-sensor
#2
REVIEW
Maayan Levy, Hagit Shapiro, Christoph A Thaiss, Eran Elinav
NLRP6, a member of the nucleotide-binding domain, leucine-rich repeat-containing (NLR) innate immune receptor family, regulates inflammation and host defense against microorganisms. Similar to other NLRs, NLRP6 not only participates in inflammasome formation, but is also involved in nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling regulation and facilitation of gastrointestinal antiviral effector functions. Additionally, NLRP6 contributes to the regulation of mucus secretion and antimicrobial peptide production, thereby impacting intestinal microbial colonization and associated microbiome-related infectious, autoinflammatory, metabolic, and neoplastic diseases...
February 14, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28213517/the-p53-binding-protein-1-tudor-interacting-repair-regulator-complex-participates-in-the-dna-damage-response
#3
Aili Zhang, Bo Peng, Ping Huang, Junjie Chen, Zihua Gong
The 53BP1-dependent end-joining pathway plays a critical role in DSB repair and is uniquely responsible for cellular sensitivity to PARPi in BRCA1-deficient cancers. We and others have investigated the downstream effectors of 53BP1, including replication timing regulatory factor 1 (RIF1) and Pax transactivation domain-interacting protein (PTIP), in the past few years to elucidate how loss of the 53BP1-dependent repair pathway results in PARPi resistance in BRCA1 patients. However, questions regarding the upstream regulation of the 53BP1 pathway remain unanswered...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213500/inducible-t-cell-kinase-regulates-the-acquisition-of-cytolytic-capacity-and-degranulation-in-cd8-ctls
#4
Senta M Kapnick, Jane C Stinchcombe, Gillian M Griffiths, Pamela L Schwartzberg
Patients with mutations in inducible T cell kinase (ITK) are susceptible to viral infections, particularly EBV, suggesting that these patients have defective function of CD8(+) CTLs. In this study, we evaluated the effects of ITK deficiency on cytolysis in murine CTLs deficient in ITK, and both human and murine cells treated with an ITK inhibitor. We find that ITK deficiency leads to a global defect in the cytolysis of multiple targets. The absence of ITK both affected CTL expansion and delayed the expression of cytolytic effectors during activation...
February 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28213471/attenuation-of-endoplasmic-reticulum-stress-by-caffeine-ameliorates-hyperoxia-induced-lung-injury
#5
Ru-Jeng Teng, Xigang Jing, Teresa Michalkiewicz, Adeleye J Afolayan, Tzong-Jin Wu, Girija G Konduri
Rodent pups exposed to hyperoxia develop lung changes similar to bronchopulmonary dysplasia (BPD) in extremely premature infants. Oxidative stress from hyperoxia can injure developing lungs through endoplasmic reticulum (ER) stress. Early caffeine treatment decreases the rate of BPD, but the mechanisms remain unclear. We hypothesized that caffeine attenuates hyperoxia-induced lung injury through its chemical chaperone property. Sprague-Dawley rat pups were raised either in 90% (hyperoxia) or 21% (normoxia) oxygen from postnatal day 1 (P1) to postnatal day 10 (P10) and then recovered in 21% oxygen until P21...
February 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28213440/muscle-yap-is-a-regulator-of-neuromuscular-junction-formation-and-regeneration
#6
Kai Zhao, Chengyong Shen, Yisheng Lu, Zhihui Huang, Lei Li, Christopher D Rand, Jinxiu Pan, Xiang-Dong Sun, Zhibing Tan, Hongsheng Wang, Guanglin Xing, Yu Cao, Guoqing Hu, Jiliang Zhou, Wen-Cheng Xiong, Lin Mei
Yes-associated protein (Yap) is a major effector of the Hippo pathway that regulates cell proliferation and differentiation during development and restricts tissue growth in adult animals. However, its role in synapse formation remains poorly understood. In this study, we characterized Yap's role in the formation of neuromuscular junction (NMJ). In HSA-Yap(-/-) mice where Yap was mutated specifically in muscle cells, AChR clusters were smaller and were distributed in a broader region in the middle of muscle fibers, suggesting that muscle Yap is necessary for the size and location of AChR clusters...
February 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28213137/foxo1-is-a-downstream-effector-of-isl1-in-direct-pathway-striatal-projection-neuron-development-within-the-embryonic-mouse-telencephalon
#7
R R Waclaw, L A Ehrman, P Merchan-Sala, V Kohli, D Nardini, K Campbell
Recent studies have shown that the LIM-homeodomain transcription factor Isl1 is required for the survival and differentiation of direct pathway striatonigral neurons during embryonic development. The downstream effectors of Isl1 in these processes are presently unknown. We show here that Foxo1, a transcription factor that has been implicated in cell survival, is expressed in striatal projection neurons (SPNs) that derive from the Isl1 lineage (i.e. direct pathway SPNs). Moreover, Isl1 conditional knockouts (cKOs) show a severe loss of Foxo1 expression at E15...
February 14, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28212865/casein-kinase-2-interacting-protein-1-regulates-m1-and-m2-inflammatory-macrophage-polarization
#8
Yuhan Chen, Wen Liu, Yiwu Wang, Luo Zhang, Jun Wei, Xueli Zhang, Fuchu He, Lingqiang Zhang
The importance of macrophage plasticity, albeit being discovered recently, has been highlighted in a broad spectrum of biological processes operative in physiological and pathological environments. Macrophage polarized activation and inactivation has profound effects on immune and inflammatory responses with several major pathways being elucidated in the past few years. However, transcriptional regulation mechanisms governing macrophage polarization is still preliminary. In this study, we identify the Casein Kinase 2 Interacting Protein 1 (CKIP-1) as a molecular toggle manipulating macrophage speciation...
February 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28212799/rho-mancing-to-sensitize-calcium-signaling-for-contraction-in-the-vasculature-role-of-rho-kinase
#9
T Szasz, R C Webb
Vascular smooth muscle contraction is an important physiological process contributing to cardiovascular homeostasis. The principal determinant of smooth muscle contraction is the intracellular free Ca(2+) concentration, and phosphorylation of myosin light chain (MLC) by activated myosin light chain kinase (MLCK) in response to increased Ca(2+) is the main pathway by which vasoconstrictor stimuli induce crossbridge cycling of myosin and actin filaments. A secondary pathway for vascular smooth muscle contraction that is not directly dependent on Ca(2+) concentration, but rather mediating Ca(2+) sensitization, is the RhoA/Rho kinase pathway...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28212427/rbm46-regulates-mouse-embryonic-stem-cell-differentiation-by-targeting-%C3%AE-catenin-mrna-for-degradation
#10
Lei Zhai, Chenchen Wang, Yuanfan Chen, Shixin Zhou, Lingsong Li
Embryonic stem cells (ESCs) are pluripotent cells and have the capability for differentiation into any of the three embryonic germ layers. The Wnt/β-Catenin pathway has been shown to play an essential role in ESC differentiation regulation. Activation of β-Catenin by post-translational modification has been extensively studied. However, mechanism(s) of post-transcriptional regulation of β-Catenin are not well defined. In this study, we report an RNA recognition motif-containing protein (RNA binding motif protein 46, RBM46) which regulates the degradation of β-Catenin mRNA...
2017: PloS One
https://www.readbyqxmd.com/read/28212151/antibody-mediated-rejection-in-the-cardiac-allograft-diagnosis-treatment-and-future-considerations
#11
M Elizabeth H Hammond, Abdallah G Kfoury
PURPOSE OF REVIEW: This review summarizes the latest publications dealing with antibody-mediated rejection (AMR) and defines areas of controversy and future steps that may improve the outcome for patients with this virulent form of rejection. RECENT FINDINGS: Recent progress includes publication of standardized pathologic criteria for acute AMR by the International Society for Heart and Lung Transplantation (ISHLT) and guidelines for treatment of acute AMR by the American Heart Association, endorsed by ISHLT as well...
February 15, 2017: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/28211822/robot-assisted-end-effector-based-gait-training-in-chronic-stroke-patients-a%C3%A2-multicentric-uncontrolled-observational-retrospective-clinical-study
#12
Stefano Mazzoleni, Antonella Focacci, Marco Franceschini, Andreas Waldner, Chiara Spagnuolo, Elena Battini, Donatella Bonaiuti
BACKGROUND: Until now studies report inconclusive results as regards the effectiveness of exclusive use of robot-assisted training and clinical indications in stroke patients. OBJECTIVE: To evaluate if the only robot-assisted end-effector-based gait training can be feasible in chronic stroke subjects in terms of gait recovery. METHODS: Five rehabilitation centers participated and one hundred chronic post-stroke patients were recruited. Patients underwent a robot-assisted end-effector-based gait training as only rehabilitation treatment...
February 15, 2017: NeuroRehabilitation
https://www.readbyqxmd.com/read/28211040/anti-cd3-treatment-upregulates-pd-1-expression-on-activated-effector-t-cells-and-severely-impairs-their-inflammatory-capacity
#13
Maja Wallberg, Asha Recino, Jenny Phillips, Duncan Howie, Margaux Vienne, Christopher Paluch, Miyuki Azuma, F Susan Wong, Herman Waldmann, Anne Cooke
T cells play a key role in the pathogenesis of type 1 diabetes, and targeting the CD3 component of the TCR complex provides one therapeutic approach. Anti-CD3 treatment can reverse overt disease in spontaneously diabetic non-obese diabetic mice, an effect proposed to, at least in part, be caused by a selective depletion of pathogenic cells. We have used a transfer model to further investigate the effects of anti-CD3 treatment on green fluorescent protein (GFP)(+) islet-specific effector T cells in vivo. The GFP expression allowed us to isolate the known effectors at different time points during treatment to assess cell presence in various organs as well as gene expression and cytokine production...
February 17, 2017: Immunology
https://www.readbyqxmd.com/read/28210987/antiviral-activity-of-ctn-15-34-a-cathelicidin-derived-eicosapeptide-against-infectious-myonecrosis-virus-in-litopenaeus-vannamei-primary-hemocyte-cultures
#14
P R N Vieira-Girão, C B Falcão, I R C B Rocha, H M R Lucena, F H F Costa, G Rádis-Baptista
The shrimp farming has been converted into a mature aquaculture industry dealing with over millions of metric tonnes of processed commodities. Nevertheless, the global shrimp productions are constantly threatened by disease outbreaks, mainly triggered by rapidly disseminating viruses. Infectious myonecrosis virus (IMNV) is one of these epizootic agents affecting shrimp production in Brazil, of which no treatment exists. Herein, the antiviral activity against IMNV of an eicosapeptide, named Ctn[15-34], derived from a member of the cathelicidin family of antimicrobial peptides, was demonstrated...
February 16, 2017: Food and Environmental Virology
https://www.readbyqxmd.com/read/28210758/both-hands-at-work-the-effect-of-aging-on-upper-limb-kinematics-in-a-multi-step-activity-of-daily-living
#15
Philipp Gulde, Joachim Hermsdörfer
The kinematic performance of basic motor tasks shows a clear decrease with advancing age. This study examined if the rules known from such tasks can be generalized to activities of daily living. We examined the end-effector kinematics of 13 young and 13 elderly participants in the multi-step activity of daily living of tea-making. Furthermore, we analyzed bimanual behavior and hand dominance in the task using different conditions of execution. The elderly sample took substantially longer to complete the activity (almost 50%) with longer trajectories compared with the young sample...
February 16, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28210263/a-paradigm-shift-on-the-question-of-b-cells-in-transplantation-recent-insights-on-regulating-the-alloresponse
#16
REVIEW
Daniel J Firl, Gilles Benichou, James I Kim, Heidi Yeh
B lymphocytes contribute to acute and chronic allograft rejection through their production of donor-specific antibodies (DSAs). In addition, B cells present allopeptides bound to self-MHC class II molecules and provide costimulation signals to T cells, which are essential to their activation and differentiation into memory T cells. On the other hand, both in laboratory rodents and patients, the concept of effector T cell regulation by B cells is gaining traction in the field of transplantation. Specifically, clinical trials using anti-CD20 monoclonal antibodies to deplete B cells and reverse DSA had a deleterious effect on rates of acute cellular rejection; a peculiar finding that calls into question a central paradigm in transplantation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28210257/kinetics-of-cytotoxic-lymphocytes-reconstitution-after-induction-chemotherapy-in-elderly-aml-patients-reveals-progressive-recovery-of-normal-phenotypic-and-functional-features-in-nk-cells
#17
Jérôme Rey, Cyril Fauriat, Eloïse Kochbati, Florence Orlanducci, Aude Charbonnier, Evelyne D'Incan, Pascale Andre, François Romagne, Bernadette Barbarat, Norbert Vey, Daniel Olive
NK cells are defective in acute myeloid leukemia (AML) at diagnosis. Here, we studied the kinetic of expression of the major activating and inhibitory receptors of NK, CD8 T, and γδ T cells in patients undergoing chemotherapy (CT) for the treatment of AML (n = 29). We showed that NK cells are the main affected population at diagnosis and that expression of activating receptors is partially restored within a few weeks after CT. CD8 T cells and γδ T cells are only weakly affected at diagnosis. Killer cell immunoglobulin-like receptor expression by NK cells, but not NKG2A and CD85j, was downregulated...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28210073/macrophages-as-key-drivers-of-cancer-progression-and-metastasis
#18
REVIEW
Sebastian R Nielsen, Michael C Schmid
Macrophages are one of the most abundant immune cells in the tumour microenvironment of solid tumours and their presence correlates with reduced survival in most cancers. Macrophages are present at all stages of tumour progression and stimulate angiogenesis, tumour cell invasion, and intravasation at the primary site. At the metastatic site, macrophages and monocytes prepare for the arrival of disseminated tumour cells and promote their extravasation and survival by inhibiting immune-mediated clearance or by directly engaging with tumour cells to activate prosurvival signalling pathways...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28209925/the-stress-polarity-pathway-ampk-giv-es-protection-against-metabolic-insults
#19
Pradipta Ghosh
Loss of cell polarity impairs organ development and function; it can also serve as one of the first triggers for oncogenesis. In 2006-2007 two groups simultaneously reported the existence of a special pathway for maintaining epithelial polarity in the face of environmental stressors. In this pathway, AMPK, a key sensor of metabolic stress stabilizes tight junctions, preserves cell polarity, and thereby, maintains epithelial barrier functions. Accumulating evidence since has shown that pharmacologic activation of AMPK by Metformin protects the epithelial barrier against multiple environmental and pathological stressful states and suppresses tumorigenesis...
February 15, 2017: Aging
https://www.readbyqxmd.com/read/28209897/host-cell-attachment-elicits-posttranscriptional-regulation-in-infecting-enteropathogenic-bacteria
#20
Naama Katsowich, Netanel Elbaz, Ritesh Ranjan Pal, Erez Mills, Simi Kobi, Tamar Kahan, Ilan Rosenshine
The mechanisms by which pathogens sense the host and respond by remodeling gene expression are poorly understood. Enteropathogenic Escherichia coli (EPEC), the cause of severe intestinal infection, employs a type III secretion system (T3SS) to inject effector proteins into intestinal epithelial cells. These effectors subvert host cell processes to promote bacterial colonization. We show that the T3SS also functions to sense the host cell and to trigger in response posttranscriptional remodeling of gene expression in the bacteria...
February 17, 2017: Science
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