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https://www.readbyqxmd.com/read/28545134/structures-of-the-inactive-and-active-states-of-rip2-kinase-inform-on-the-mechanism-of-activation
#1
Erika Pellegrini, Luca Signor, Saurabh Singh, Elisabetta Boeri Erba, Stephen Cusack
Innate immune receptors NOD1 and NOD2 are activated by bacterial peptidoglycans leading to recruitment of adaptor kinase RIP2, which, upon phosphorylation and ubiquitination, becomes a scaffold for downstream effectors. The kinase domain (RIP2K) is a pharmaceutical target for inflammatory diseases caused by aberrant NOD2-RIP2 signalling. Although structures of active RIP2K in complex with inhibitors have been reported, the mechanism of RIP2K activation remains to be elucidated. Here we analyse RIP2K activation by combining crystal structures of the active and inactive states with mass spectrometric characterization of their phosphorylation profiles...
2017: PloS One
https://www.readbyqxmd.com/read/28544941/time-based-expectations-entail-preparatory-motor-activity
#2
Gregor Volberg, Roland Thomaschke
Human behavior is guided by expectations that facilitate perception of upcoming events or reaction to them. In natural settings expectations are often implicitly based on time, e.g., when making a phone call one would expect to hear either a person answering (earlier) or a voicemail greeting (later). We investigated how time-based expectations can improve performance in the absence of explicit prior information on the pending stimulus or the associated response. Visual stimuli were presented after a characteristic short or long foreperiod, and a forced-choice categorization using either the left or the right hand was required...
May 4, 2017: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
https://www.readbyqxmd.com/read/28544607/spotted-gar-and-the-evolution-of-innate-immune-receptors
#3
Dustin J Wcisel, Tatsuya Ota, Gary W Litman, Jeffrey A Yoder
The resolution of the gar genome affords an opportunity to examine the diversification and functional specialization of immune effector molecules at a distant and potentially informative point in phylogenetic development. Although innate immunity is effected by a particularly large number of different families of molecules, the focus here is to provide detailed characterization of several families of innate receptors that are encoded in large multigene families, for which orthologous forms can be identified in other species of bony fish but not in other vertebrate groups as well as those for which orthologs are present in other vertebrate species...
May 24, 2017: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
https://www.readbyqxmd.com/read/28543786/immunohistochemical-colocalization-of-g-protein-alpha-subunits-and-5-ht-in-the-rectal-gland-of-the-cartilaginous-fish-scyliorhinus-canicula
#4
E R Lauriano, S Pergolizzi, J Gangemi, M Kuciel, G Capillo, M Aragona, C Faggio
Serotonin [5-hydroxytryptamine (5-HT)] is an important neuromodulator involved in a wide range of physiological functions. The effects of serotonin are mediated by an extended family of receptors coupled to multiple heterotrimeric G-proteins, associated with cellular membrane. G proteins connect receptors to effectors and thus trigger intracellular signaling pathways. These cellular processes several regulate systemic functions such as embryonic development, gonadal development, learning and memory, and organismal homeostasis...
May 22, 2017: Microscopy Research and Technique
https://www.readbyqxmd.com/read/28543695/mechanisms-and-strategies-to-overcome-resistance-to-molecularly-targeted-therapy-for-melanoma
#5
REVIEW
Su Yin Lim, Alexander M Menzies, Helen Rizos
The identification of driver mutations in melanoma has changed the field of cancer treatment. BRAF and NRAS mutations are predominant in melanoma and lead to overactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways. Selective inhibitors targeting key effectors of the MAPK pathway have revolutionized the treatment of patients with advanced metastatic BRAF-mutant melanoma. However, resistance to therapy is almost universal and remains a major challenge in clinical care, with the majority of patients progressing within 1 year...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28543637/evidence-of-the-immunomodulatory-role-of-dual-pi3k-mtor-inhibitors-in-graft-survival
#6
Valery Vilchez, Lilia Turcios, D Allan Butterfield, Mihail I Mitov, Cristin L Coquillard, Anthony J Brandon, Virgilius Cornea, Roberto Gedaly, Francesc Marti
The PI3K/mTOR signaling cascade is fundamental in T-cell activation and fate decisions. We showed the distinct regulation of PI3K/mTOR in regulatory and effector T-cells and proposed the potential therapeutic benefit of targeting this pathway to control the balance between effector and regulatory T-cell activities. Substantial adverse effects in long-term clinical usage of Rapamycin suggest the use of alternative treatments in restraining effector T-cell function in transplant patients. We hypothesize that dual PI3K/mTOR inhibitors may represent an immunosuppressant alternative...
May 24, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28542787/understanding-the-reconstitution-of-the-b-cell-compartment-in-bone-marrow-and-blood-after-treatment-for-b-cell-precursor-acute-lymphoblastic-leukaemia
#7
Prisca M J Theunissen, Anouk van den Branden, Alita Van Der Sluijs-Gelling, Valerie De Haas, Auke Beishuizen, Jacques J M van Dongen, Vincent H J Van Der Velden
A better understanding of the reconstitution of the B-cell compartment during and after treatment in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) will help to assess the immunological status and needs of post-treatment BCP-ALL patients. Using 8-colour flow cytometry and proliferation-assays, we studied the composition and proliferation of both the B-cell precursor (BCP) population in the bone marrow (BM) and mature B-cell population in peripheral blood (PB) during and after BCP-ALL therapy. We found a normal BCP differentiation pattern and a delayed formation of classical CD38(dim) -naive mature B-cells, natural effector B-cells and memory B-cells in patients after chemotherapy...
May 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28542641/platelet-proteome-reveals-novel-pathways-of-platelet-activation-and-platelet-mediated-immunoregulation-in-dengue
#8
Monique Ramos de Oliveira Trugilho, Eugenio Damaceno Hottz, Giselle Villa Flor Brunoro, André Teixeira-Ferreira, Paulo Costa Carvalho, Gustavo Adolfo Salazar, Guy A Zimmerman, Fernando A Bozza, Patrícia T Bozza, Jonas Perales
Dengue is the most prevalent human arbovirus disease worldwide. Dengue virus (DENV) infection causes syndromes varying from self-limiting febrile illness to severe dengue. Although dengue pathophysiology is not completely understood, it is widely accepted that increased inflammation plays important roles in dengue pathogenesis. Platelets are blood cells classically known as effectors of hemostasis which have been increasingly recognized to have major immune and inflammatory activities. Nevertheless, the phenotype and effector functions of platelets in dengue pathogenesis are not completely understood...
May 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542595/antifungal-tc17-cells-are-durable-and-stable-persisting-as-long-lasting-vaccine-memory-without-plasticity-towards-ifn%C3%AE-cells
#9
Som Gowda Nanjappa, Andrew J McDermott, J Scott Fites, Kevin Galles, Marcel Wüthrich, George S Deepe, Bruce S Klein
Our understanding of persistence and plasticity of IL-17A+ memory T cells is clouded by conflicting results in models analyzing T helper 17 cells. We studied memory IL-17A+ CD8+ T-cell (Tc17) homeostasis, persistence and plasticity during fungal vaccine immunity. We report that vaccine-induced memory Tc17 cells persist with high fidelity to the type 17 phenotype. Tc17 cells persisted durably for a year as functional IL-17A+ memory cells without converting to IFNγ+ (Tc1) cells, although they produced multiple type I cytokines in the absence of residual vaccine antigen...
May 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542501/a-rho-associated-coiled-coil-containing-kinases-rock-inhibitor-y-27632-enhances-adhesion-viability-and-differentiation-of-human-term-placenta-derived-trophoblasts-in-vitro
#10
Kenichiro Motomura, Naoko Okada, Hideaki Morita, Mariko Hara, Masato Tamari, Keisuke Orimo, Go Matsuda, Ken-Ichi Imadome, Akio Matsuda, Takeshi Nagamatsu, Mikiya Fujieda, Haruhiko Sago, Hirohisa Saito, Kenji Matsumoto
Although human term placenta-derived primary cytotrophoblasts (pCTBs) represent a good human syncytiotrophoblast (STB) model, in vitro culture of pCTBs is not always easily accomplished. Y-27632, a specific inhibitor of Rho-associated coiled-coil containing kinases (ROCK), reportedly prevented apoptosis and improved cell-to-substrate adhesion and culture stability of dissociated cultured human embryonic stem cells and human corneal endothelial cells. The Rho kinase pathway regulates various kinds of cell behavior, some of which are involved in pCTB adhesion and differentiation...
2017: PloS One
https://www.readbyqxmd.com/read/28542388/targeted-dna-methylation-in-pericentromeres-with-genome-editing-based-artificial-dna-methyltransferase
#11
Taiga Yamazaki, Yu Hatano, Tetsuya Handa, Sakiko Kato, Kensuke Hoida, Rui Yamamura, Takashi Fukuyama, Takayuki Uematsu, Noritada Kobayashi, Hiroshi Kimura, Kazuo Yamagata
To study the impact of epigenetic changes on biological functions, the ability to manipulate the epigenetic status of certain genomic regions artificially could be an indispensable technology. "Epigenome editing" techniques have gradually emerged that apply TALE or CRISPR/Cas9 technologies with various effector domains isolated from epigenetic code writers or erasers such as DNA methyltransferase, 5-methylcytosine oxidase, and histone modification enzymes. Here we demonstrate that a TALE recognizing a major satellite, consisting of a repeated sequence in pericentromeres, could be fused with the bacterial CpG methyltransferase, SssI...
2017: PloS One
https://www.readbyqxmd.com/read/28542376/the-cryptic-plasmid-is-more-important-for-chlamydia-muridarum-to-colonize-the-mouse-gastrointestinal-tract-than-to-infect-the-genital-tract
#12
Lili Shao, Jose Melero, Nu Zhang, Bernard Arulanandam, Joel Baseman, Quanzhong Liu, Guangming Zhong
Chlamydia has been detected in the gastrointestinal tracts of both animals and humans. However, the mechanism by which Chlamydia colonizes the gut remains unclear. Chlamydia muridarum is known to spread from the genital to the gastrointestinal tracts hematogenously. The C. muridarum plasmid is a key pathogenic determinant in the mouse upper genital tract although plasmid-deficient C. muridarum is still able to colonize the upper genital tract. We now report that plasmid-deficient C. muridarum exhibits significantly delayed/reduced spreading from the mouse genital to the gastrointestinal tracts...
2017: PloS One
https://www.readbyqxmd.com/read/28542350/t0001-a-variant-of-tnfr2-fc-fusion-protein-exhibits-improved-fc-effector-functions-through-increased-binding-to-membrane-bound-tnf%C3%AE
#13
Yijun Shen, Gang Li, Chunying Gu, Ben Chen, Aihua Chen, Hua Li, Bei Gao, Chencai Liang, Jingsong Wu, Tong Yang, Li Jin, Yong Su
T0001 is a recombinant human TNFR-Fc fusion protein mutant; it exhibits higher affinity to TNFα than etanercept and is now being tested in a Phase 1 study in China (ClinicalTrials.gov Identifier: NCT02481180). T0001 can inhibit the binding of soluble TNFα (sTNFα) or membrane-bound TNFα (mTNFα) to TNF receptors. When bound to mTNFα, the Fc-bearing TNFα antagonists have the potential to induce Fc-mediated effects, such as antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CDC) as well as outside-to-inside signals (apoptosis mainly)...
2017: PloS One
https://www.readbyqxmd.com/read/28541442/cbl-interacting-protein-kinase-6-negatively-regulates-immune-response-to-pseudomonas-syringae-in-arabidopsis
#14
Atish Sardar, Ashis Kumar Nandi, Debasis Chattopadhyay
Cytosolic calcium ion (Ca2+) is an essential mediator of the plant innate immune response. Here, we report that a calcium-regulated protein kinase Calcineurin B-like protein (CBL)-interacting protein kinase 6 (CIPK6) functions as a negative regulator of immunity against the bacterial pathogen Pseudomonas syringae in Arabidopsis thaliana. Arabidopsis lines with compromised expression of CIPK6 exhibited enhanced disease resistance to the bacterial pathogen and to P. syringae harboring certain but not all avirulent effectors, while restoration of CIPK6 expression resulted in abolition of resistance...
May 24, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28540936/antigen-presenting-cell-targeted-lentiviral-vectors-do-not-support-the-development-of-productive-t-cell-effector-responses-implications-for-in-vivo-targeted-vaccine-delivery
#15
C Goyvaerts, Y De Vlaeminck, D Escors, S Lienenklaus, M Keyaerts, G Raes, K Breckpot
Targeting transgene expression specifically to antigen-presenting cells (APCs) has been put forward as a promising strategy to direct the immune system towards immunity. We developed the nanobody-display technology to restrict the tropism of lentiviral vectors (LVs) to APCs. However, we observed that immunization with APC-targeted LVs (DC2.1-LVs) did not evoke strong antigen-specific T-cell immunity when compared to immunization with broad tropism LVs (VSV.G-LVs). In this study, we report that VSV.G-LVs are more immunogenic than DC2...
May 25, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28540539/involvements-of-%C3%AE-%C3%AE-t-lymphocytes-in-acute-and-chronic-skin-wound-repair
#16
Peng Xu, Xiujun Fu, Nin Xiao, Yuanyuan Guo, Qing Pei, Yinbo Peng, Yifan Zhang, Min Yao
Wound healing involves three stages including inflammation, proliferation, and tissue remodeling. The underlying mechanisms remain to be further elucidated. The inflammation is characterized by spatially and temporally changing patterns of various leukocyte subsets. It is regarded as the most crucial stage since the inflammatory response is instrumental to supplying various factors and cytokines that orchestrate healing events. As a subtype of T lymphocytes, γδ T cells play an important role in skin homeostasis, tumor immunosurveillance, and wound repair...
May 25, 2017: Inflammation
https://www.readbyqxmd.com/read/28540536/effects-of-robot-assisted-upper-limb-rehabilitation-in-stroke-patients-a-systematic-review-with-meta-analysis
#17
Rachele Bertani, Corrado Melegari, Maria C De Cola, Alessia Bramanti, Placido Bramanti, Rocco Salvatore Calabrò
Technology-supported training is emerging as a solution to support therapists in their efforts providing high-intensity, repetitive, and task-specific treatment, in order to enhance the recovery process. The aim of this review is to assess the effectiveness of different robotic devices (end-effector and exoskeleton robots) in comparison with any other type of intervention. Furthermore, we aim to assess whether or not better improvements are obtained in the sub-acute phase after stroke onset than in the chronic phase...
May 24, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28539707/effector-and-regulatory-t-cell-trafficking-in-corneal-allograft-rejection
#18
REVIEW
Afsaneh Amouzegar, Sunil K Chauhan
Corneal transplantation is among the most prevalent and successful forms of solid tissue transplantation in humans. Failure of corneal allograft is mainly due to immune-mediated destruction of the graft, a complex and highly coordinated process that involves elaborate interactions between cells of innate and adaptive immunity. The migration of immune cells to regional lymphoid tissues and to the site of graft plays a central role in the immunopathogenesis of graft rejection. Intricate interactions between adhesion molecules and their counter receptors on immune cells in conjunction with tissue-specific chemokines guide the trafficking of these cells to the draining lymph nodes and ultimately to the site of graft...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28539549/the-metabolic-regulation-in-immune-cells-and-pathogenesis-of-systemic-lupus-erythematosus-%C3%A2-toward-new-therapeutic-applications%C3%A2
#19
Yusuke Takeshima, Yukiko Iwasaki, Tomohisa Okamura, Keishi Fujio, Kazuhiko Yamamoto
  The importance of cellular metabolism has long been known as Warburg effect; cancer cells are characterized by mitochondrial defect that shifts towards aerobic glycolysis. Recently, many reports have revealed that immune metabolism is a key factor for controlling immune cell proliferation and differentiation. Resting lymphocytes generate energy through oxidative phosphorylation and fatty acid oxidation, whereas activated lymphocytes rapidly shift to glycolysis. Especially in T cells, more precise mechanism of regulating metabolism have been clarified on differentiation from naïve T cells to effector T cells...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28539429/bolstering-the-number-and-function-of-hsv-1-specific-cd8-effector-memory-t-cells-and-tissue-resident-memory-t-cells-in-latently-infected-trigeminal-ganglia-reduces-recurrent-ocular-herpes-infection-and-disease
#20
Arif A Khan, Ruchi Srivastava, Aziz A Chentoufi, Elizabeth Kritzer, Sravya Chilukuri, Sumit Garg, David C Yu, Hawa Vahed, Lei Huang, Sabrina A Syed, Julie N Furness, Tien T Tran, Nesburn B Anthony, Christine E McLaren, John Sidney, Alessandro Sette, Randolph J Noelle, Lbachir BenMohamed
HSV type 1 (HSV-1) is a prevalent human pathogen that infects >3.72 billion individuals worldwide and can cause potentially blinding recurrent corneal herpetic disease. HSV-1 establishes latency within sensory neurons of trigeminal ganglia (TG), and TG-resident CD8(+) T cells play a critical role in preventing its reactivation. The repertoire, phenotype, and function of protective CD8(+) T cells are unknown. Bolstering the apparent feeble numbers of CD8(+) T cells in TG remains a challenge for immunotherapeutic strategies...
May 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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