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https://www.readbyqxmd.com/read/28635959/optogenetic-activation-of-plexin-b1-reveals-contact-repulsion-between-osteoclasts-and-osteoblasts
#1
Abhijit Deb Roy, Taofei Yin, Shilpa Choudhary, Vladimir Rodionov, Carol C Pilbeam, Yi I Wu
During bone remodelling, osteoclasts induce chemotaxis of osteoblasts and yet maintain spatial segregation. We show that osteoclasts express the repulsive guidance factor Semaphorin 4D and induce contact inhibition of locomotion (CIL) in osteoblasts through its receptor Plexin-B1. To examine causality and elucidate how localized Plexin-B1 stimulation may spatiotemporally coordinate its downstream targets in guiding cell migration, we develop an optogenetic tool for Plexin-B1 designated optoPlexin. Precise optoPlexin activation at the leading edge of migrating osteoblasts readily induces local retraction and, unexpectedly, distal protrusions to steer cells away...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28634005/semaphorin-3e-alleviates-hallmarks-of-house-dust-mite-induced-allergic-airway-disease
#2
Hesam Movassagh, Lianyu Shan, Jonathan S Duke-Cohan, Andrew J Halayko, Jude E Uzonna, Abdelilah S Gounni
Semaphorins are an essential family of guidance cues ubiquitously expressed in various organs, which play diverse developmental, homeostatic, and pathological roles. Semaphorin 3E (Sema3E), initially identified as a neuronal chemorepellent, is involved in the regulation of cell migration, proliferation, and angiogenesis. However, expression and function of Sema3E in allergic asthma has not been extensively investigated. We determined the expression of Sema3E in the airways and its effect on airway inflammation, hyperresponsiveness, and remodeling as pathological features of allergic asthma provoked by house dust mite in vivo...
July 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28632130/the-laminar-organization-of-the-drosophila-ellipsoid-body-is-semaphorin-dependent-and-prevents-the-formation-of-ectopic-synaptic-connections
#3
Xiaojun Xie, Masashi Tabuchi, Matthew P Brown, Sarah P Mitchell, Mark N Wu, Alex L Kolodkin
The ellipsoid body (EB) in the Drosophila brain is a central complex (CX) substructure that harbors circumferentially laminated ring (R) neuron axons and mediates multifaceted sensory integration and motor coordination functions. However, what regulates R axon lamination and how lamination affects R neuron function remain unknown. We show here that the EB is sequentially innervated by small-field and large-field neurons, and that early-developing EB neurons play an important regulatory role in EB laminae formation...
June 20, 2017: ELife
https://www.readbyqxmd.com/read/28626864/detecting-genetic-association-through-shortest-paths-in-a-bidirected-graph
#4
Masao Ueki, Yoshinori Kawasaki, Gen Tamiya
Genome-wide association studies (GWASs) commonly use marginal association tests for each single-nucleotide polymorphism (SNP). Because these tests treat SNPs as independent, their power will be suboptimal for detecting SNPs hidden by linkage disequilibrium (LD). One way to improve power is to use a multiple regression model. However, the large number of SNPs preclude simultaneous fitting with multiple regression, and subset regression is infeasible because of an exorbitant number of candidate subsets. We therefore propose a new method for detecting hidden SNPs having significant yet weak marginal association in a multiple regression model...
June 19, 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/28624895/semaphorin4d-plexinb1-signaling-attenuates-photoreceptor-outer-segment-phagocytosis-by-reducing-rac1-activity-of-rpe-cells
#5
Ayelen Bulloj, Arvydas Maminishkis, Masayuki Mizui, Silvia C Finnemann
Semaphorins form a family of secreted and membrane-bound molecules that were identified originally as axonal guidance factors during neuronal development. Given their wide distribution in many including mature tissues, semaphorin 4D (sema4D) and its main functional receptor plexin B1 (plxnB1) are expected to fulfill additional functions that remain to be uncovered. A main characteristic of the plexin receptor family is its ability to reorganize the cytoskeleton. PlxnB1 specifically may directly interact with Rho family GTPases to regulate F-actin driven pathways in cells in culture...
June 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28610953/a-thirty-year-quest-for-a-role-of-r-ras-in-cancer-from-an-oncogene-to-a-multitasking-gtpase
#6
Wai Nam Liu, Mingfei Yan, Andrew M Chan
Since the identification of R-Ras, which is the first Ras-related GTPase isolated based on sequence similarity to the classical RAS oncogene, more than 160 members of the Ras superfamily of GTPases have been identified and classified into the Ras, Rho, Rap, Rab, Ran, Arf, Rheb, RGK, Rad, Rit, and Miro subfamilies. R-Ras belongs to the Ras subfamily of small G-proteins, which are frequently implicated in cell growth and differentiation. Although the roles of R-Ras in cellular transformation and integrin-mediated cell adhesion have been extensively studied, the physiological function of this enigmatic G-protein was only revealed when a mouse strain deficient in R-Ras was generated...
June 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28602571/cytoplasmic-neuropilin-2-is-associated-with-metastasis-and-a-poor-prognosis-in-early-tongue-cancer-patients
#7
H S Ong, S Gokavarapu, Q Xu, Z Tian, J Li, T Ji, C P Zhang
Neuropilin 2 (Nrp2) plays an important role in regulating lymphangiogenesis. Nrp2 expression in early tongue cancer was investigated to predict lymph node metastasis and the long-term prognosis. The relationships between clinicopathological variables of cT1-T2N0 tongue squamous cell carcinoma (SCC) and overexpression of Nrp2, vascular endothelial growth factor C (VEGFC), vascular endothelial growth factor receptor 3 (VEGFR3), and semaphorin 3F (Sema3F) were analyzed. Expression levels were compared using oral SCC cell lines...
June 8, 2017: International Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/28581515/gata3-targets-semaphorin-3b-in-mammary-epithelial-cells-to-suppress-breast-cancer-progression-and-metastasis
#8
P Shahi, C-Y Wang, J Chou, C Hagerling, H Gonzalez Veloso, A Ruderisch, Y Yu, M-D Lai, Z Werb
Semaphorin 3B (SEMA3B) is a secreted axonal guidance molecule that is expressed during development and throughout adulthood. Recently, SEMA3B has emerged as a tumor suppressor in non-neuronal cells. Here, we show that SEMA3B is a direct target of GATA3 transcriptional activity. GATA3 is a key transcription factor that regulates genes involved in mammary luminal cell differentiation and tumor suppression. We show that GATA3 relies on SEMA3B for suppression of tumor growth. Loss of SEMA3B renders GATA3 inactive and promotes aggressive breast cancer development...
June 5, 2017: Oncogene
https://www.readbyqxmd.com/read/28558017/a-dual-strategy-expression-screen-for-candidate-connectivity-labels-in-the-developing-thalamus
#9
Olivia Bibollet-Bahena, Tatsuya Okafuji, Karsten Hokamp, Guy Tear, Kevin J Mitchell
The thalamus or "inner chamber" of the brain is divided into ~30 discrete nuclei, with highly specific patterns of afferent and efferent connectivity. To identify genes that may direct these patterns of connectivity, we used two strategies. First, we used a bioinformatics pipeline to survey the predicted proteomes of nematode, fruitfly, mouse and human for extracellular proteins containing any of a list of motifs found in known guidance or connectivity molecules. Second, we performed clustering analyses on the Allen Developing Mouse Brain Atlas data to identify genes encoding surface proteins expressed with temporal profiles similar to known guidance or connectivity molecules...
2017: PloS One
https://www.readbyqxmd.com/read/28555754/expression-patterns-of-sema3a-in-developing-amniote-limbs-with-reference-to-the-diversification-of-peripheral-nerve-innervation
#10
Kanami Noguchi, Ryota Ishikawa, Masahumi Kawaguchi, Kanako Miyoshi, Takahiko Kawasaki, Tatsumi Hirata, Makiko Fukui, Shigeru Kuratani, Mikiko Tanaka, Yasunori Murakami
Paired limbs were acquired in the ancestor of tetrapods and their morphology has been highly diversified in amniotes in relation to the adaptive radiation to the terrestrial environment. These morphological changes may have been induced by modification of the developmental program of the skeletal or muscular system. To complete limb modification, it is also important to change the neuronal framework, because the functions of the limbs rely on neural circuits that involve coordinated movement. Previous studies have shown that class 3 semaphorins (Sema3 semaphorins), which act as repulsive axonal guidance cues, play a crucial role in the formation of the peripheral nerves in mice...
May 29, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/28552057/exploitation-of-novel-molecular-targets-to-treat-idiopathic-pulmonary-fibrosis-a-drug-discovery-perspective
#11
Bhuvaneshwar Vaidya, Ruaab Patel, Aaron Muth, Vivek Gupta
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common fibrosing lung disease and is caused by excessive lung scarring. IPF-associated severe mortality can be attributed to late diagnosis due to its generic symptoms, and more importantly, due to the lack of effective therapies available. Despite extensive research in past decades, lung transplant still remains the most effective treatment for IPF. Though two drugs recently approved by FDA, Pirfenidone and Nintedanib, have shown an ability to reduce the progression of disease...
May 26, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28550439/baseline-anthropometric-and-metabolic-parameters-correlate-with-weight-loss-in-women-1-year-after-laparoscopic-roux-en-y-gastric-bypass
#12
Sans Arnaud, Bailly Laurent, Anty Rodolphe, Sielezenef Igor, Gugenheim Jean, Tran Albert, Gual Philippe, Iannelli Antonio
BACKGROUND: In this study, we explored in a prospective cohort of morbidly obese women undergoing laparoscopic Roux-en-Y gastric bypass (LRYGP) correlations between baseline anthropometrics, metabolic parameters, resting energy expenditure (REE), body composition, and 1-year % excess body mass index loss (%EBMIL). We also investigated risk factors for insufficient %EBMIL. METHODS: One hundred three consecutive women were prospectively evaluated at baseline (age 40...
May 26, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28508207/new-aspects-of-the-seam4d-dependent-control-of-lymphocyte-activation
#13
E M Kuklina, I V Nekrasova
Novel targets for action of the class IV semaphorin Seam4D have been identified in the immune system. The low-affinity CD72 receptor for Seam4D was detected not only on B lymphocytes, but also in a proportion of T cells, whereas the high-affinity semaphorin receptor, plexin B1, originally considered to belong to non-immune cells, proved to be in a great proportion of intact T and B cells. Seam4D is constitutively expressed in B cells, which, along with T cells, can serve as a source of both membrane and soluble semaphorin...
March 2017: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/28506853/expression-of-semaphorin-3e-is-suppressed-in-severe-asthma
#14
Hesam Movassagh, Lianyu Shan, Jamila Chakir, John F McConville, Andrew J Halayko, Latifa Koussih, Abdelilah S Gounni
The level of a previously unknown mediator, Semaphorin 3E, is diminished in the airways of severe allergic asthmatic patients. This study suggests a potential role of Semaphorin3E in the pathogenesis of asthma severity.
May 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28502680/semaphorin-3a-is-a-key-player-in-the-pathogenesis-of-asthma
#15
Ronen Cozacov, Katlin Halasz, Tharwat Haj, Zahava Vadasz
Immune semaphorins are key players in regulating immune mediated inflammation. Semaphorin3A (sema3A) a secreted and membrane bound member of this family, is well reported for its properties in maintaining self-tolerance. Semaphorin3A was recognized to be a marker for T-regulatory cells (Tregs), and as such is a useful tool for assessing the status of these cells in preventing immune mediated diseases. This study was designed aiming to evaluate how sema3A is possibly involved in bronchial asthma. Here, we found sema3A serum levels and the expression of sema3A on Tregs significantly lower in patients with moderate to severe asthma when compared to healthy individuals...
May 11, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28502679/the-association-between-semaphorin-3a-levels-and-gluten-free-diet-in-patients-with-celiac-disease
#16
Aharon Kessel, Chen Lin, Zahava Vadasz, Regina Peri, Nasren Eiza, Drora Berkowitz
Celiac disease (CD) is an inflammatory disease affecting the small intestine. We aim to assess serum level and expression of semaphorin 3A (Sema3A) on T regulatory (Treg) cells in CD patients. Twenty-six newly diagnosed celiac patients, 13 celiac patients on a gluten-free diet and 16 healthy controls included in the study. Sema3A protein level in the serum of celiac patients was significantly higher compared to healthy group (7.17±1.8ng/ml vs. 5.67±1.5ng/ml, p=0.012). Sema3A expression on Treg cells was statistically lower in celiac patients compared to healthy subjects (p=0...
May 11, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28498470/novel-role-of-semaphorin%C3%A2-3a-in-the-growth-and-progression-of-hepatocellular-carcinoma
#17
Xuedong Li, Qing Chen, Dan Yin, Shiming Shi, Lei Yu, Shaolai Zhou, Erbao Chen, Zhengjun Zhou, Yinghong Shi, Jia Fan, Jian Zhou, Zhi Dai
Semaphorin 3A (SEMA3A), a secretory protein, is a founding member of the semaphorin family and functions in both the biological behavior of tumor cells and the modulation of tumor-associated macrophages. However, the role of SEMA3A in hepatocellular carcinoma (HCC) is still not well established. In the present study, we investigated the expression levels of SEMA3A in 80 HCC tissues and cell lines, using RT-qPCR, western blotting and immunohistochemistry. Expression profile analysis revealed that SEMA3A was significantly overexpressed in human HCC patients and positively correlated with the metastatic potential of HCC cells...
May 2, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28480592/slow-myofiber-commitment-by-semaphorin-3a-secreted-from-myogenic-stem-cells
#18
Ryuichi Tatsumi, Takahiro Suzuki, Mai-Khoi Q Do, Yuki Ohya, Judy E Anderson, Ayumi Shibata, Mai Kawaguchi, Shunpei Ohya, Hideaki Ohtsubo, Wataru Mizunoya, Shoko Sawano, Yusuke Komiya, Riho Ichitsubo, Koichi Ojima, Shin-Ichiro Nishimatsu, Tsutomu Nohno, Yutaka Ohsawa, Yoshihide Sunada, Mako Nakamura, Mitsuhiro Furuse, Yoshihide Ikeuchi, Takanori Nishimura, Takeshi Yagi, Ronald E Allen
Recently, we found that resident myogenic stem satellite cells up-regulate a multi-functional secreted protein, semaphorin 3A (Sema3A), exclusively at the early- differentiation phase in response to muscle injury; however, its physiological significance is still unknown. Here we show that Sema3A impacts slow-twitch fiber generation through a signaling pathway, cell-membrane receptor (neuropilin2-plexinA3) → myogenin-myocyte enhancer factor 2D (MEF2D) → slow myosin heavy chain. This novel axis was found by small interfering RNA (siRNA)-transfection experiments in myoblast cultures, which also revealed an additional element that Sema3A-neuropilin1/plexinA1, A2 may enhance slow-fiber formation by activating signals that inhibit fast-myosin expression...
May 7, 2017: Stem Cells
https://www.readbyqxmd.com/read/28469004/sprouting-strategies-and-dead-ends-in-anti-angiogenic-targeting-of-nets
#19
Patricia Carrasco, Iratxe Zuazo-Gaztelu, Oriol Casanovas
Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms that arise from cells of the neuroendocrine system. NETs are characterized by being highly vascularized tumors that produce large amounts of proangiogenic factors. Due to their complexity and heterogeneity, progress in the development of successful therapeutic approaches has been limited. For instance, standard chemotherapy-based therapies have proven to be poorly selective for tumor cells and toxic for normal tissues. Considering the urge to develop an efficient therapy to treat NET patients, vascular targeting has been proposed as a new approach to block tumor growth...
May 3, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28467912/plexin-b2-and-semaphorin-4c-guide-t-cell-recruitment-and-function-in-the-germinal-center
#20
Hu Yan, Longyan Wu, Changming Shih, Shiyue Hou, Jingwen Shi, Tianyang Mao, Wenbin Chen, Bhavani Melvin, Robert J Rigby, Yingjia Chen, Haochen Jiang, Roland H Friedel, Carola G Vinuesa, Hai Qi
Follicular T helper (TFH) cells orchestrate the germinal center (GC) response locally. TFH localization in GCs is controlled by chemo-guidance cues and antigen-specific adhesion. Here. we define an antigen-independent, contact-dependent, adhesive guidance system for TFH cells. Unusual for amoeboid cell migration, the system is composed of transmembrane plexin B2 (PlxnB2) molecule, which is highly expressed by GC B cells, and its transmembrane binding partner semaphorin 4C (Sema4C), which is upregulated on TFH cells...
May 2, 2017: Cell Reports
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