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https://www.readbyqxmd.com/read/28931049/the-c5a-c5ar1-axis-controls-the-development-of-experimental-allergic-asthma-independent-of-lysm-expressing-pulmonary-immune-cells
#1
Anna V Wiese, Fanny Ender, Katharina M Quell, Konstantina Antoniou, Tillman Vollbrandt, Peter König, Jörg Köhl, Yves Laumonnier
C5a regulates the development of maladaptive immune responses in allergic asthma mainly through the activation of C5a receptor 1 (C5aR1). Yet, the cell types and the mechanisms underlying this regulation are ill-defined. Recently, we described increased C5aR1 expression in lung tissue eosinophils but decreased expression in airway and pulmonary macrophages as well as in pulmonary CD11b+ conventional dendritic cells (cDCs) and monocyte-derived DCs (moDCs) during the allergic effector phase using a floxed green fluorescent protein (GFP)-C5aR1 knock-in mouse...
2017: PloS One
https://www.readbyqxmd.com/read/28930687/the-rab2b-garil5-complex-promotes-cytosolic-dna-induced-innate-immune-responses
#2
Michihiro Takahama, Mitsunori Fukuda, Norihiko Ohbayashi, Tatsuya Kozaki, Takuma Misawa, Toru Okamoto, Yoshiharu Matsuura, Shizuo Akira, Tatsuya Saitoh
Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces the IFN antiviral response. However, the regulatory mechanisms that mediate cGAS-triggered signaling have not been fully explored. Here, we show the involvement of a small GTPase, RAB2B, and its effector protein, Golgi-associated RAB2B interactor-like 5 (GARIL5), in the cGAS-mediated IFN response. RAB2B-deficiency affects the IFN response induced by cytosolic DNA. Consistent with this, RAB2B deficiency enhances replication of vaccinia virus, a DNA virus...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28928446/tumour-derived-pgd2-and-nkp30-b7h6-engagement-drives-an-immunosuppressive-ilc2-mdsc-axis
#3
Sara Trabanelli, Mathieu F Chevalier, Amaia Martinez-Usatorre, Alejandra Gomez-Cadena, Bérengère Salomé, Mariangela Lecciso, Valentina Salvestrini, Grégory Verdeil, Julien Racle, Cristina Papayannidis, Hideaki Morita, Irene Pizzitola, Camille Grandclément, Perrine Bohner, Elena Bruni, Mukul Girotra, Rani Pallavi, Paolo Falvo, Elisabeth Oppliger Leibundgut, Gabriela M Baerlocher, Carmelo Carlo-Stella, Daniela Taurino, Armando Santoro, Orietta Spinelli, Alessandro Rambaldi, Emanuela Giarin, Giuseppe Basso, Cristina Tresoldi, Fabio Ciceri, David Gfeller, Cezmi A Akdis, Luca Mazzarella, Saverio Minucci, Pier Giuseppe Pelicci, Emanuela Marcenaro, Andrew N J McKenzie, Dominique Vanhecke, George Coukos, Domenico Mavilio, Antonio Curti, Laurent Derré, Camilla Jandus
Group 2 innate lymphoid cells (ILC2s) are involved in human diseases, such as allergy, atopic dermatitis and nasal polyposis, but their function in human cancer remains unclear. Here we show that, in acute promyelocytic leukaemia (APL), ILC2s are increased and hyper-activated through the interaction of CRTH2 and NKp30 with elevated tumour-derived PGD2 and B7H6, respectively. ILC2s, in turn, activate monocytic myeloid-derived suppressor cells (M-MDSCs) via IL-13 secretion. Upon treating APL with all-trans retinoic acid and achieving complete remission, the levels of PGD2, NKp30, ILC2s, IL-13 and M-MDSCs are restored...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28928394/rna-localization-is-a-key-determinant-of-neurite-enriched-proteome
#4
Alessandra Zappulo, David van den Bruck, Camilla Ciolli Mattioli, Vedran Franke, Koshi Imami, Erik McShane, Mireia Moreno-Estelles, Lorenzo Calviello, Andrei Filipchyk, Esteban Peguero-Sanchez, Thomas Müller, Andrew Woehler, Carmen Birchmeier, Enrique Merino, Nikolaus Rajewsky, Uwe Ohler, Esteban O Mazzoni, Matthias Selbach, Altuna Akalin, Marina Chekulaeva
Protein subcellular localization is fundamental to the establishment of the body axis, cell migration, synaptic plasticity, and a vast range of other biological processes. Protein localization occurs through three mechanisms: protein transport, mRNA localization, and local translation. However, the relative contribution of each process to neuronal polarity remains unknown. Using neurons differentiated from mouse embryonic stem cells, we analyze protein and RNA expression and translation rates in isolated cell bodies and neurites genome-wide...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28928283/vegetally-localised-vrtn-functions-as-a-novel-repressor-to-modulate-bmp2b-transcription-during-dorsoventral-patterning-in-zebrafish
#5
Ming Shao, Min Wang, Yuan-Yuan Liu, Yi-Wen Ge, Yan-Jun Zhang, De-Li Shi
The vegetal pole cytoplasm represents a crucial source of maternal dorsal determinants for patterning the dorsoventral axis of the early embryo. Removal of the vegetal yolk in the zebrafish fertilised egg before the completion of the first cleavage results in embryonic ventralisation, but removal of this part at the two-cell stage leads to embryonic dorsalisation. How this is achieved remains unknown. Here, we report a novel mode of maternal regulation of BMP signalling during dorsoventral patterning in zebrafish...
September 15, 2017: Development
https://www.readbyqxmd.com/read/28928161/the-immune-microenvironment-confers-chemoresistance-of-colorectal-cancer-through-macrophage-derived-il-6
#6
Zhaohui Huang, Yuan Yin, Surui Yao, Yaling Hu, Yuyang Feng, Min Li, Zehua Bian, Jiwei Zhang, Yan Qin, Xiaowei Qi, Le-Yuan Zhou, Bojian Fei, Jian Zou, Dong Hua
PURPOSE: Tumor-associated macrophages (TAMs) are frequently associated with poor prognosis in human cancers. However, the effects of TAM in colorectal cancer (CRC) are contradictory. We therefore investigated the functions, mechanisms and clinical significance of TAMs in CRC. EXPERIMENTAL DESIGN: We measured the macrophage infiltration (CD68), P-gp and Bcl2 expression in CRC tissues using Immunohistochemistry staining. Co-culture of TAMs and CRC cells both in vitro and in vivo models was used to evaluate the effects of TAMs on CRC chemoresistance...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28928093/effect-of-sodium-glucose-cotransporter-2-sglt2-inhibition-on-weight-loss-is-partly-mediated-by-liver-brain-adipose-neurocircuitry
#7
Yoshikazu Sawada, Yoshihiko Izumida, Yoshinori Takeuchi, Yuichi Aita, Nobuhiro Wada, EnXu Li, Yuki Murayama, Xiaoying Piao, Akito Shikama, Yukari Masuda, Makiko Nishi-Tatsumi, Midori Kubota, Motohiro Sekiya, Takashi Matsuzaka, Yoshimi Nakagawa, Yoko Sugano, Hitoshi Iwasaki, Kazuto Kobayashi, Shigeru Yatoh, Hiroaki Suzuki, Hiroaki Yagyu, Yasushi Kawakami, Takashi Kadowaki, Hitoshi Shimano, Naoya Yahagi
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have both anti-diabetic and anti-obesity effects. However, the precise mechanism of the anti-obesity effect remains unclear. We previously demonstrated that the glycogen depletion signal triggers lipolysis in adipose tissue via liver-brain-adipose neurocircuitry. In this study, therefore, we investigated whether the anti-obesity mechanism of SGLT2 inhibitor is mediated by this mechanism. Diet-induced obese mice were subjected to hepatic vagotomy (HVx) or sham operation and loaded with high fat diet containing 0...
September 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28927573/sex-differences-in-early-life-programming-of-the-hypothalamic-pituitary-adrenal-axis-in-humans
#8
REVIEW
Robert M Gifford, Rebecca M Reynolds
Increasing evidence supports fetal glucocorticoid exposure with associated altered offspring hypothalamic-pituitary-adrenal (HPA) axis activity as a key mechanism linking early life events with later life disease. Alterations in HPA axis activity are linked to a range of cardiometabolic and psychiatric diseases. As many of these diseases manifest sex differences in presentation we review the evidence for programmed sex-differences in the HPA axis. Available literature suggests vulnerability of the female HPA axis to prenatal stressors with female offspring demonstrating increased HPA axis reactivity...
September 15, 2017: Early Human Development
https://www.readbyqxmd.com/read/28927426/the-acid-sensing-ion-channel-asic2-promotes-invasion-and-metastasis-of-colorectal-cancer-under-acidosis-by-activating-the-calcineurin-nfat1-axis
#9
Zhi-Hang Zhou, Jin-Wen Song, Wen Li, Xue Liu, Liu Cao, Lu-Ming Wan, Ying-Xia Tan, Shou-Ping Ji, Yu-Mei Liang, Feng Gong
BACKGROUND: The tumor acidic microenvironment, a common biochemical event in solid tumors, offers evolutional advantage for tumors cells and even enhances their aggressive phenotype. However, little is known about the molecular mechanism underlying the acidic microenvironment-induced invasion and metastasis. METHODS: We examined the expression of the acid-sending ion channel (ASIC) family members after acidic exposure using RT-PCR and immunofluoresence. Gene manipulation was applied to reveal the potential of ASIC2 on invasion, proliferation, colony formation of colorectal cancer (CRC)...
September 19, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28927250/gut-microbiota-and-the-liver
#10
Alessandro Federico, Marcello Dallio, Giuseppe G Caprio, Vittorio M Ormando, Carmela Loguercio
Nowadays liver diseases represent one of major healthy problems in the world in terms of morbidity and mortality. The high prevalence of liver pathologies represents the key point to understand the necessity to identify the pathogenetic mechanisms that support these disorders in order to nurse them. Alterations of intestinal microbiota seem to play an important role in induction and promotion of liver damage progression, in addition to direct injury resulting from different causal agents. Gut microbiota is considered both as a promoting factor and as a potential therapeutic target of a large number of liver pathologies due to the connection between intestine and liver: the gut-liver axis...
December 2017: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/28926938/integrin-activation-contributes-to-lower-cisplatin-sensitivity-in-mv3-melanoma-cells-by-inducing-the-wnt-signalling-pathway
#11
Maria B R Piva, Bastian Jakubzig, Gerd Bendas
BACKGROUND: integrins have been associated with the development of chemotherapy resistant tumour cells, mostly those of hematopoietic origin, by mediating the binding to the extracellular matrix. The relevance for solid tumour cells and the underlying mechanisms remain elusive. METHODS: using MTT assays, we detected the loss in cisplatin sensitivity of human MV3 melanoma cells upon integrin activation. Underlying cellular pathways were evaluated by flow cytometry...
September 16, 2017: Cancers
https://www.readbyqxmd.com/read/28926843/the-genetic-basis-of-delayed-puberty
#12
S R Howard, Leo Dunkel
<br>The genetic control of puberty remains an important but mostly unanswered question. Late pubertal timing affects over 2% of adolescents and is associated with adverse health outcomes including short stature, reduced bone mineral density and compromised psychosocial health. Self-limited delayed puberty (DP) is a highly heritable trait, which often segregates in an autosomal dominant pattern; however, its neuroendocrine pathophysiology and genetic regulation remain unclear. Some insights into the genetic mutations that lead to familial DP have come from sequencing genes known to cause GnRH deficiency, most recently via next generation sequencing, and others from large-scale genome wide association studies in the general population...
September 18, 2017: Neuroendocrinology
https://www.readbyqxmd.com/read/28926761/the-cortisol-awakening-response-and-anterior-cingulate-cortex-function-in-maltreated-depressed-versus-non-maltreated-depressed-youth
#13
Karina Quevedo, Jennifer Doty, Leslie Roos, Justin J Anker
Symptomatology of depression among children who have (vs. have not) experienced maltreatment is greater in severity, more resistant to conventional treatment, and associated with elevated risk for suicide. Recent evidence implicates perturbations in stress regulatory systems and heightened negative self-appraisals as factors that increase the severity of psychopathology experienced by depressed maltreated (vs. non-maltreated) youth. Likely explanatory mechanisms for these differences are disturbances in the function of the hypothalamic-pituitary axis (HPA) and persistent negative self-referential biases supported by prefrontal cortex function including the dorsal anterior cingulate cortex (dACC)...
September 5, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28926118/chop-induced-loss-of-intestinal-epithelial-stemness-contributes-to-bile-duct-ligation-induced-cholestatic-liver-injury
#14
Runping Liu, Xiaojiaoyang Li, Zhiming Huang, Derrick Zhao, Bhagyalaxmi Sukka Ganesh, Guanhua Lai, William M Pandak, Phillip B Hylemon, Jasmohan S Bajaj, Arun J Sanyal, Huiping Zhou
Impaired intestinal barrier function promotes the progression of various liver diseases including cholestatic liver disease. The close association of primary sclerosing cholangitis (PSC) with inflammatory bowel disease highlights the importance of the gut-liver axis. It has been reported that bile duct ligation (BDL)-induced liver fibrosis is significantly reduced in C/EBP homologous protein knock out (CHOP(-/-) ) mice. However, the underlying mechanisms remain unclear. In the current study, we demonstrate that BDL induces striking and acute hepatic ER stress responses after 1 day, which return to normal after 3 days...
September 19, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28926115/long-non-coding-rna-malat1-promotes-oral-squamous-cell-carcinoma-development-via-microrna-125b-stat3-axis
#15
Shi-Min Chang, Wei-Wei Hu
Oral squamous cell carcinoma (OSCC), as the most common type of oral cancer, is responsible for almost 3% of all malignant tumors worldwide. Non-coding RNAs such as lncRNAs and microRNAs have been involved in many cancers including OSCC. Recently, lncRNA metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) has been reported to play an oncogenic role in OSCC metastasis. However, the underlying mechanism of MALAT1 in regulating OSCC progression remains unclear. The aim of this study was to investigate the specific role of MALAT1 in OSCC development...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28925949/a-generic-compliance-modeling-method-for-two-axis-elliptical-arc-filleted-flexure-hinges
#16
Lijian Li, Dan Zhang, Sheng Guo, Haibo Qu
As a kind of important flexible joint, two-axis flexure hinges can realize in-plane and out-of-plane motions and can be used for constructing flexure-based spatial compliant mechanisms. The paper introduces a common two-axis elliptical-arc-filleted flexure hinge that is generated by two different elliptical-arc-filleted cutout profiles and that provides some new hinge types. The analytical compliance equations of both half-segments of the two-axis elliptical-arc flexure hinges are firstly formulated, and then, based on a generic compliance modeling method of a flexure serial chain, the closed-form compliance and precision matrices of two-axis elliptical-arc-filleted flexure hinges are established and validated by the finite element method...
September 19, 2017: Sensors
https://www.readbyqxmd.com/read/28925886/the-microbiota-gut-brain-axis-in-neuropsychiatric-disorders-pathophysiological-mechanisms-and-novel-treatments
#17
Yong-Ku Kim, Cheolmin Shin
BACKGROUND: The human gut microbiome comprise a huge number of microorganisms with co-evolutionary associations with humans. It has been repeatedly revealed that bidirectional communication exists between the brain and the gut and involves neural, hormonal, and immunological pathways. Evidences from neuroscience researches over the past few years suggest that microbiota is essential for the development and maturation of brain systems that are associated to stress responses. METHOD: This review provides that the summarization of the communication among microbiota, gut and brain and the results of preclinical and clinical studies on gut microbiota used in treatments for neuropsychiatric disorders...
September 15, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28925881/coping-with-stress-during-aging-the-importance-of-a-resilient-brain
#18
P Sampedro-Piquero, P Álvarez-Suárez, A Begega
BACKGROUND: Resilience is the ability to achieve a positive outcome when we are in the face of adversity. It supposes an active resistance to adversity by coping mechanisms in which genetic, molecular, neural and environmental factors are involved. Resilience has been usually studied in early ages and few is known about it during aging. METHODS: In this review, we will address the age-related changes in the brain mechanisms involved in regulating the stress response...
September 15, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28925400/the-hif-and-other-quandaries-in-vhl-disease
#19
REVIEW
D Tarade, M Ohh
Mutations in VHL underlie von Hippel-Lindau (VHL) disease, a hereditary cancer syndrome with several subtypes depending on the risk of developing certain combination of classic features, such as clear cell renal cell carcinoma (ccRCC), hemangioblastoma and pheochromocytoma. Although numerous potential substrates and functions of pVHL have been described over the past decade, the best-defined role of pVHL has remained as the negative regulator of the heterodimeric hypoxia-inducible factor (HIF) transcription factor via the oxygen-dependent ubiquitin-mediated degradation of HIF-α subunit...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28925394/tissue-inhibitor-of-metalloproteinase-1-promotes-cell-proliferation-through-yap-taz-activation-in-cancer
#20
T Ando, D Charindra, M Shrestha, H Umehara, I Ogawa, M Miyauchi, T Takata
Tissue inhibitor of metalloproteinase-1 (TIMP-1), a member of the TIMP family (TIMP-1 to 4), is highly expressed in various types of cancer and forms a complex with its receptor CD63 and Integrin β1. However, the precise oncogenic mechanism of TIMP-1 remains unclear. Yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ) are transcription co-activators enhancing the transcription of specific genes related to cell proliferation. But the mechanism of aberrant YAP/TAZ activation in cancer is not fully understood...
September 18, 2017: Oncogene
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