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https://www.readbyqxmd.com/read/28821013/rictor-positively-regulates-b-cell-receptor-signaling-by-modulating-actin-reorganization-via-ezrin
#1
Lu Huang, Yongjie Zhang, Chenguang Xu, Xiaomei Gu, Linlin Niu, Jinzhi Wang, Xiaoyu Sun, Xiaoming Bai, Xingtian Xuan, Qubei Li, Chunwei Shi, Bing Yu, Heather Miller, Gangyi Yang, Lisa S Westerberg, Wanli Liu, Wenxia Song, Xiaodong Zhao, Chaohong Liu
As the central hub of the metabolism machinery, the mammalian target of rapamycin complex 2 (mTORC2) has been well studied in lymphocytes. As an obligatory component of mTORC2, the role of Rictor in T cells is well established. However, the role of Rictor in B cells still remains elusive. Rictor is involved in B cell development, especially the peripheral development. However, the role of Rictor on B cell receptor (BCR) signaling as well as the underlying cellular and molecular mechanism is still unknown. This study used B cell-specfic Rictor knockout (KO) mice to investigate how Rictor regulates BCR signaling...
August 2017: PLoS Biology
https://www.readbyqxmd.com/read/28820402/does-signaling-of-estrogen-related-receptors-affect-structure-and-function-of-bank-vole-leydig-cells
#2
P Pawlicki, A Milon, M Zarzycka, J Galas, W Tworzydlo, A Kaminska, L Pardyak, K Lesniak, A Pacwa, B Bilinska, E Gorowska-Wojtowicz, M Kotula-Balak
To get a deeper insight into the function of estrogen-related receptors (ERRs) and dissect underlying mechanism in Leydig cells, ERRs (type α, β and γ) were blocked or activated in testes of adult bank voles (Myodes glareolus) which show seasonal changes in the intratesticular sex hormones level. Both actively reproducing animals (long day conditions; LD) and those with regression of the reproductive system (short day conditions; SD) received intraperitoneal injections of selective ERRα antagonist 3-[4-(2,4-Bis-trifluoromethylbenzyloxy)-3-methoxyphenyl]-2-cyano-N-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)acrylamide (XCT 790) or selective ERRβ/ERRγ agonist N-(4-(Diethylaminobenzylidenyl)-N'-(4-hydroxybenzoyl)-hydrazine (DY131) (50 μ/kg bw; six doses every other day)...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28819186/cd24-induces-changes-to-the-surface-receptors-of-b-cell-microvesicles-with-variable-effects-on-their-rna-and-protein-cargo
#3
D Craig Ayre, Ian C Chute, Andrew P Joy, David A Barnett, Andrew M Hogan, Marc P Grüll, Lourdes Peña-Castillo, Andrew S Lang, Stephen M Lewis, Sherri L Christian
The CD24 cell surface receptor promotes apoptosis in developing B cells, and we recently found that it induces B cells to release plasma membrane-derived, CD24-bearing microvesicles (MVs). Here we have performed a systematic characterization of B cell MVs released from WEHI-231 B lymphoma cells in response to CD24 stimulation. We found that B cells constitutively release MVs of approximately 120 nm, and that CD24 induces an increase in phosphatidylserine-positive MV release. RNA cargo is predominantly comprised of 5S rRNA, regardless of stimulation; however, CD24 causes a decrease in the incorporation of protein coding transcripts...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819150/the-g%C3%AE-i-giv-binding-interface-is-a-druggable-protein-protein-interaction
#4
Vincent DiGiacomo, Alain Ibáñez de Opakua, Maria P Papakonstantinou, Lien T Nguyen, Nekane Merino, Juan B Blanco-Canosa, Francisco J Blanco, Mikel Garcia-Marcos
Heterotrimeric G proteins are usually activated by the guanine-nucleotide exchange factor (GEF) activity of GPCRs. However, some non-receptor proteins are also GEFs. GIV (a.k.a Girdin) was the first non-receptor protein for which the GEF activity was ascribed to a well-defined protein sequence that directly binds Gαi. GIV expression promotes metastasis and disruption of its binding to Gαi blunts the pro-metastatic behavior of cancer cells. Although this suggests that inhibition of the Gαi-GIV interaction is a promising therapeutic strategy, protein-protein interactions (PPIs) are considered poorly "druggable" targets requiring case-by-case validation...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819122/anti-inflammatory-drugs-suppress-ultrasound-mediated-mesenchymal-stromal-cell-tropism-to-kidneys
#5
Scott R Burks, Ben A Nguyen, Michele N Bresler, Matthew E Nagle, Saejeong J Kim, Joseph A Frank
Mesenchymal stromal cells (MSC) are potential renal therapeutics. Clinically, results are mixed partly because MSC tropism to kidneys is minimal following infusion. Ultrasound augmentation of the renal microenvironment is becoming increasingly-important in renal MSC therapies. We demonstrated pulsed-focused-ultrasound (pFUS) increases enhanced homing permeability and retention of MSC in mouse kidneys. Here, we characterized the temporal proteomic response to pFUS in mouse kidneys and its association with MSC tropism...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818858/pai-1-plasminogen-activator-inhibitor-1-expression-renders-alternatively-activated-human-macrophages-proteolytically-quiescent
#6
Philipp J Hohensinner, Johanna Baumgartner, Julia B Kral-Pointner, Pavel Uhrin, Benjamin Ebenbauer, Barbara Thaler, Konstantin Doberer, Stefan Stojkovic, Svitlana Demyanets, Michael B Fischer, Kurt Huber, Gernot Schabbauer, Walter S Speidl, Johann Wojta
OBJECTIVE: Macrophages are versatile immune cells capable of polarizing into functional subsets depending on environmental stimulation. In atherosclerotic lesions, proinflammatory polarized macrophages are associated with symptomatic plaques, whereas Th2 cytokine-polarized macrophages are inversely related with disease progression. To establish a functional cause for these observations, we analyzed extracellular matrix degradation phenotypes in polarized macrophages. APPROACH AND RESULTS: We provide evidence that proinflammatory polarized macrophages rely on membrane-bound proteases including matrix metalloproteinase 14 and the serine protease uPA (urokinase plasminogen activator) together with its receptor uPAR for extracellular matrix degradation...
August 17, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28818855/paradigm-of-biased-par1-protease-activated-receptor-1-activation-and-inhibition-in-endothelial-cells-dissected-by-phosphoproteomics
#7
Bart L van den Eshof, Arie J Hoogendijk, Pelle J Simpson, Floris P J van Alphen, Sara Zanivan, Koen Mertens, Alexander B Meijer, Maartje van den Biggelaar
OBJECTIVE: Thrombin is the key serine protease of the coagulation cascade and mediates cellular responses by activation of PARs (protease-activated receptors). The predominant thrombin receptor is PAR1, and in endothelial cells (ECs), thrombin dynamically regulates a plethora of phosphorylation events. However, it has remained unclear whether thrombin signaling is exclusively mediated through PAR1. Furthermore, mechanistic insight into activation and inhibition of PAR1-mediated EC signaling is lacking...
August 17, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28818508/the-role-of-the-il-8-signaling-pathway-in-the-infiltration-of-granulocytes-into-the-livers-of-patients-with-alcoholic-hepatitis
#8
S W French, A S Mendoza, N Afifiyan, B Tillman, E Vitocruz, B A French
BACKGROUND AND AIM: IL-8 (C-X-L motif chemokine ligase 8) and CXCR2 (C-X-C-motif chemokine receptor 2) are up regulated in alcoholic hepatitis (AH) liver biopsies. One of the consequences is the attraction and chemotactic neutrophilic infiltrate seen at the AH stage of alcoholic liver disease. MATERIALS AND METHODS: Human formalin-fixed, paraffin-embedded (FFPE) liver biopsies from patients who have AH were studied by (2.1) RNA sequencing, (2.2) PCR and (2.3) semi quantitation of specific proteins in biopsy sections using immunohistochemical measurements of antibody fluorescent intensity with morphometric technology...
August 14, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28816549/implications-of-bcl-2-and-its-interplay-with-other-molecules-and-signaling-pathways-in-prostate-cancer-progression
#9
Ju-Ha Kim, Hyemin Lee, Eun Ah Shin, Dong Hee Kim, Jhin Baek Choi, Sung-Hoon Kim
Among several genetic alterations involved in the progression of prostate cancer, B cell lymphoma gene number 2 (BCL-2) is an important target molecule in the progression of androgen-independent prostate cancer (AIPC) after androgen ablation or castration. Nevertheless, the molecular mechanism of BCL-2 in prostate cancer progression remains elusive and controversial. In the current review, we discuss the critical role of BCL-2 in the carcinogenesis of prostate cancer with experimental evidences on the BCL-2 molecular networks in AIPC and androgen-dependent prostate cancer (ADPC) and subsequently suggest perspective research targeting BCL-2...
August 17, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28815730/loss-of-bmi-1-dampens-migration-and-emt-of-colorectal-cancer-in-inflammatory-microenvironment-through-tlr4-md-2-myd88-mediated-nf-%C3%AE%C2%BAb-signaling
#10
Kai Ye, Qi-Wei Chen, Ya-Feng Sun, Jian-An Lin, Jian-Hua Xu
Increasing evidence from various clinical and experimental studies has demonstrated that the inflammatory microenvironment created by immune cells facilitates tumor migration. Epithelial-mesenchymal transition (EMT) is involved in the progression of cancer invasion and metastasis in an inflammatory microenvironment. B-lymphoma Moloney murine leukemia virus insertion region 1 (BMI-1) acts as an oncogene in various tumors. Ectopic expression of Bmi-1 have an effect on EMT and invasiveness. The purpose of this study was to investigate the efficacy of BMI-1 on inflammation-induced tumor migration and EMT and the underlying mechanism...
August 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28815688/bmp2-controls-iron-homeostasis-in-mice-independent-of-bmp6
#11
Susanna Canali, Chia-Yu Wang, Kimberly B Zumbrennen-Bullough, Abraham Bayer, Jodie L Babitt
Hepcidin is a key iron regulatory hormone that controls expression of the iron exporter ferroportin to increase the iron supply when needed to support erythropoiesis and other essential functions, but to prevent the toxicity of iron excess. The bone morphogenetic protein (BMP)-SMAD signaling pathway, through the ligand BMP6 and the co-receptor hemojuvelin, is a central regulator of hepcidin transcription in the liver in response to iron. Here, we show that dietary iron loading has a residual ability to induce Smad signaling and hepcidin expression in Bmp6-/- mice, effects that are blocked by a neutralizing BMP2/4 antibody...
August 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28815225/chronic-in-vivo-interaction-of-dendritic-cells-expressing-the-ligand-rae-1%C3%AE%C2%B5-with-nk-cells-impacts-nkg2d-expression-and-function
#12
Maelig G Morvan, Marine Champsaur, Boris Reizis, Lewis L Lanier
To investigate how dendritic cells (DCs) interact with NK cells in vivo, we developed a novel mouse model in which Rae-1ε, a ligand of the NKG2D receptor, is expressed in cells with high levels of CD11c. In these CD11c-Rae1 mice, expression of Rae-1 was confirmed on all subsets of DCs and a small subset of B and T cells, but not on NK cells. DC numbers and activation status were unchanged, and NK cells in these CD11c-Rae1 mice presented the same Ly49 repertoire and maturation levels as their littermate wildtype controls...
May 1, 2017: Immunohorizons
https://www.readbyqxmd.com/read/28814669/neonatal-and-adult-recent-thymic-emigrants-produce-il-8-and-express-complement-receptors-cr1-and-cr2
#13
Marcin L Pekalski, Arcadio Rubio García, Ricardo C Ferreira, Daniel B Rainbow, Deborah J Smyth, Meghavi Mashar, Jane Brady, Natalia Savinykh, Xaquin Castro Dopico, Sumiyya Mahmood, Simon Duley, Helen E Stevens, Neil M Walker, Antony J Cutler, Frank Waldron-Lynch, David B Dunger, Claire Shannon-Lowe, Alasdair J Coles, Joanne L Jones, Chris Wallace, John A Todd, Linda S Wicker
The maintenance of peripheral naive T lymphocytes in humans is dependent on their homeostatic division, not continuing emigration from the thymus, which undergoes involution with age. However, postthymic maintenance of naive T cells is still poorly understood. Previously we reported that recent thymic emigrants (RTEs) are contained in CD31+CD25- naive T cells as defined by their levels of signal joint T cell receptor rearrangement excision circles (sjTRECs). Here, by differential gene expression analysis followed by protein expression and functional studies, we define that the naive T cells having divided the least since thymic emigration express complement receptors (CR1 and CR2) known to bind complement C3b- and C3d-decorated microbial products and, following activation, produce IL-8 (CXCL8), a major chemoattractant for neutrophils in bacterial defense...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28813462/a-comprehensive-profiling-of-t-and-b-lymphocyte-receptor-repertoires-from-a-chinese-origin-rhesus-macaque-by-high-throughput-sequencing
#14
Longfei Fu, Xinyang Li, Wei Zhang, Changxi Wang, Jinghua Wu, Huanming Yang, Jian Wang, Xiao Liu
Due to the close genetic background, high similarity of physiology, and susceptibility to infectious and metabolic diseases with humans, rhesus macaques have been widely used as an important animal model in biomedical research, especially in the study of vaccine development and human immune-related diseases. In recent years, high-throughput sequencing based immune repertoire sequencing (IR-SEQ) has become a powerful tool to study the dynamic adaptive immune responses. Several previous studies had analyzed the responses of B cells to HIV-1 trimer vaccine or T cell repertoire of rhesus macaques using this technique, however, there are little studies that had performed a comprehensive analysis of immune repertoire of rhesus macaques, including T and B lymphocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28812045/soluble-st2-predicts-outcome-and-hemorrhagic-transformation-after-acute-stroke
#15
Zoe Wolcott, Ayush Batra, Matthew B Bevers, Cristina Sastre, Jane Khoury, Matthew Sperling, Brett C Meyer, Kyle B Walsh, Opeolu Adeoye, Joseph P Broderick, W Taylor Kimberly
OBJECTIVE: ST2 is a member of the toll-like receptor superfamily that can alter inflammatory signaling of helper T-cells. We investigated whether soluble ST2 (sST2) could independently predict outcome and hemorrhagic transformation (HT) in the setting of stroke. METHODS: We measured sST2 in patients enrolled in the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) network biomarker study. 646 patients had plasma samples collected at the time of hospital admission and 210 patients had a second sample collected 48 h after stroke onset...
August 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28811973/nk-cell-dysfunction-in-chronic-lymphocytic-leukemia-is-associated-with-loss-of-the-mature-cells-expressing-inhibitory-killer-cell-ig-like-receptors
#16
Alexander W MacFarlane, Mowafaq Jillab, Mitchell R Smith, R Katherine Alpaugh, Marion E Cole, Samuel Litwin, Michael M Millenson, Tahseen Al-Saleem, Adam D Cohen, Kerry S Campbell
A prospective analysis of natural killer (NK) cell phenotype and function was performed on fresh peripheral blood samples from untreated patients with B-cell chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Compared to healthy controls, CD56(dim) NK cells in CLL patients displayed reduced expression of the NKG2D activating receptor and increased CD27 expression, which indicates declines in mature cells. In addition, NK cells from CLL patients showed reduced degranulation responses toward transformed B cells alone or with rituximab and were more sensitive to activation-induced cell death...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811710/single-amino-acid-mutation-of-sr-bi-decreases-infectivity-of-hepatitis-c-virus-derived-from-cell-culture-in-a-cell-culture-model
#17
Rong Gao, Wei Gao, Gang Xu, Jie Xu, Hao Ren
AIM: To investigate the effect of a single amino acid mutation in human class B scavenger receptor I (SR-BI) on the infectivity of cell culture-derived hepatitis C virus (HCVcc) in SR-BI knock-down Huh7-siSR-BI cells. METHODS: Site-directed mutagenesis was used to construct the SR-BI S112F mutation, and the mutation was confirmed by nucleotide sequencing. SR-BI knock-down Huh7-siSR-BI cells were transfected with SR-BI S112F, SR-BI wild type (WT) and control plasmids, and then infected with HCVpp (HCV pseudoparticles) and hepatitis C virus derived from cell culture (HCVcc)...
July 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28811651/inkt-cells-prevent-obesity-induced-hepatic-steatosis-in-mice-in-a-c-c-chemokine-receptor-7-dependent-manner
#18
H M Kim, R Lee, E S Lee, M H Kwon, J H Huh, B-E Kwon, E-K Park, S-Y Chang, M-N Kweon, P-H Kim, H-J Ko, C H Chung
Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are characterized by an increase in hepatic triglyceride content with infiltration of immune cells, which can cause steatohepatitis and hepatic insulin resistance. C-C chemokine receptor 7 (CCR7) is primarily expressed in immune cells, and CCR7 deficiency leads to the development of multi-organ autoimmunity, chronic renal disease, and autoimmune diabetes. Here, we investigated the effect of CCR7 on hepatic steatosis in a mouse model and its underlying mechanism...
August 16, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28811600/exploring-leishmania-secretory-proteins-to-design-b-and-t-cell-multi-epitope-subunit-vaccine-using-immunoinformatics-approach
#19
Nazia Khatoon, Rajan Kumar Pandey, Vijay Kumar Prajapati
Visceral leishmaniasis (VL) is a fatal form of leishmaniasis which affects 70 countries, worldwide. Increasing drug resistance, HIV co-infection, and poor health system require operative vaccination strategy to control the VL transmission dynamics. Therefore, a holistic approach is needed to generate T and B memory cells to mediate long-term immunity against VL infection. Consequently, immunoinformatics approach was applied to design Leishmania secretory protein based multi-epitope subunit vaccine construct consisting of B and T cell epitopes...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811575/biological-and-functional-characterization-of-bone-marrow-derived-mesenchymal-stromal-cells-from-patients-affected-by-primary-immunodeficiency
#20
Nadia Starc, Daniela Ingo, Antonella Conforti, Valeria Rossella, Luigi Tomao, Angela Pitisci, Fabiola De Mattia, Immacolata Brigida, Mattia Algeri, Mauro Montanari, Giuseppe Palumbo, Pietro Merli, Paolo Rossi, Alessandro Aiuti, Franco Locatelli, Maria Ester Bernardo
Mesenchymal stromal cells (MSCs) represent a key component of bone marrow (BM) microenvironment and display immune-regulatory properties. We performed a detailed analysis of biological/functional properties of BM-MSCs derived from 33 pediatric patients affected by primary immune-deficiencies (PID-MSCs): 7 Chronic Granulomatous Disease (CGD), 15 Wiskott-Aldrich Syndrome (WAS), 11 Severe Combined Immunodeficiency (SCID). Results were compared with MSCs from 15 age-matched pediatric healthy-donors (HD-MSCs). Clonogenic and proliferative capacity, differentiation ability, immunophenotype, immunomodulatory properties were analyzed...
August 15, 2017: Scientific Reports
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