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https://www.readbyqxmd.com/read/28441759/synaptic-homeostasis-and-its-immunological-disturbance-in-neuromuscular-junction-disorders
#1
REVIEW
Masaharu Takamori
In the neuromuscular junction, postsynaptic nicotinic acetylcholine receptor (nAChR) clustering, trans-synaptic communication and synaptic stabilization are modulated by the molecular mechanisms underlying synaptic plasticity. The synaptic functions are based presynaptically on the active zone architecture, synaptic vesicle proteins, Ca(2+) channels and synaptic vesicle recycling. Postsynaptically, they are based on rapsyn-anchored nAChR clusters, localized sensitivity to ACh, and synaptic stabilization via linkage to the extracellular matrix so as to be precisely opposed to the nerve terminal...
April 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28441480/metabolite-profiling-of-a-zn-accumulating-rice-mutant
#2
Yin Wang, Sha Mei, Zhixue Wang, Zhoulei Jiang, Zhangshicang Zhu, Jingwen Ding, Dianxing Wu, Xiao-Li Shu
Breeding crops with high Zn-density is an effective way to alleviate human dietary Zn deficiencies. We characterized a mutant Lilizhi (LLZ) accumulating at least 35% higher Zn concentration in grain than wild-type in hydroponics experiments. The mutant stored less Zn contents in the roots and transported more Zn to the grain. Metabolite profiling demonstrated that with high Zn treatment, the content of proline, asparagine, citric acid and malic acid were enhanced in both LLZ and the WT, which were thought to be involved in Zn transport in rice...
April 25, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28441383/the-oral-vegf-receptor-tyrosine-kinase-inhibitor-pazopanib-in-combination-with-the-mek-inhibitor-trametinib-in-advanced-cholangiocarcinoma
#3
Rachna T Shroff, Mark Yarchoan, Ashley O'Connor, Denise Gallagher, Marianna L Zahurak, Gary Rosner, Chimela Ohaji, Susan Sartorius-Mergenthaler, Vivek Subbiah, Ralph Zinner, Nilofer S Azad
BACKGROUND: Cholangiocarcinoma is an aggressive malignancy with limited therapeutic options. MEK inhibition and antiangiogenic therapies have individually shown modest activity in advanced cholangiocarcinoma, whereas dual inhibition of these pathways has not been previously evaluated. We evaluated the safety and efficacy of combination therapy with the oral VEGF receptor tyrosine kinase inhibitor pazopanib plus the MEK inhibitor trametinib in patients with advanced cholangiocarcinoma...
April 25, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28440510/migration-of-oral-squamous-cell-carcinoma-cells-are-induced-by-hgf-c-met-signalling-via-lamellipodia-and-filopodia-formation
#4
Hiroki Yasui, Yuichi Ohnishi, Masahiro Nakajima, Masami Nozaki
The activation of receptor tyrosine kinases (RTKs) results in cellular effects including cell proliferation, survival, migration and invasion; RTKs also play an important role in tumourigenesis. It has been reported that EGFR signalling controls the migration of oral squamous cell carcinoma (OSCC) SAS and HSC3 cells but not of HSC4 cells, although the proliferation of HSC4 cells is regulated by EGF/EGFR. In the present study, we investigated the roles of EGFR and the c-Met signalling pathway in cell migration via filopodia and lamellipodia formation, which may be prerequisites for migration...
April 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440492/axl-and-gas6-co-expression-in-lung-adenocarcinoma-as-a-prognostic-classifier
#5
Masahiro Seike, Cheol-Hong Kim, Fenfei Zou, Rintaro Noro, Mika Chiba, Arimi Ishikawa, Shinobu Κunugi, Kaoru Kubota, Akihiko Gemma
AXL, a receptor tyrosine kinase implicated in cell survival, proliferation, and migration, is also associated with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor therapy. However, its prognostic significance in lung adenocarcinoma (AD) remains unclear. We therefore evaluated the prognostic significance of the expression of AXL and/or its ligand, growth arrest-specific 6 (GAS6), in completely resected lung AD. We evaluated the relationship between AXL, GAS6, and vimentin expression, as determined by immunohistochemistry (IHC) analysis, with overall survival and disease-free survival in 113 patients with stages I-III lung AD...
April 21, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440469/clinical-significance-of-akt2-in-advanced-pancreatic-cancer-treated-with-erlotinib
#6
Eri Banno, Yosuke Togashi, Marco A de Velasco, Takuro Mizukami, Yu Nakamura, Masato Terashima, Kazuko Sakai, Yoshihiko Fujita, Ken Kamata, Masayuki Kitano, Masatoshi Kudo, Kazuto Nishio
Akt2 is an isoform of Akt, and an association between Akt2 and resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been suggested in pancreatic cancer (PC) in vitro. In this study, we investigated the association between Akt2 expression as evaluated using immunohistochemistry and the outcome of patients with advanced PC who had received treatment with erlotinib (an EGFR-TKI). Although the difference was not significant, patients with high levels of Akt2 expression tended to have a poorer response and a shorter progression-free survival period after treatment with erlotinib plus gemcitabine than those with low expression levels (P=0...
April 18, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28440408/identification-of-potential-gene-targets-in-systemic-vasculitis-using-dna-microarray-analysis
#7
Yiwen Feng, Miao Zheng, Shujie Gan, Lei Zhang, Zhong Wan, Yanping Zhang, Qin Qian, Jingdong Tang
The present study aimed to identify the involvement of critical genes in systemic vasculitis, to gain an improved understanding of the molecular circuity and to investigate novel potential gene targets for systemic vasculitis treatment. The dual‑color cDNA microarray data of GSE16945, consisting of peripheral mononuclear blood cell specimens from 13 patients with systemic vasculitis and 16 healthy controls, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened in systemic vasculitis compared with controls using BRB ArrayTools, followed by the construction of a protein‑protein interaction (PPI) network using the clusterProfiler package, and significant functional interaction (FI) module selection...
April 11, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28439935/neonatal-immune-challenge-followed-by-adult-immune-challenge-induces-epigenetic-susceptibility-to-aggravated-visceral-hypersensitivity
#8
J E Aguirre, J H Winston, S K Sarna
BACKGROUND: Abdominal pain is one of the major symptoms of inflammatory Bowel Disease (IBD). The inflammatory mediators released by colon inflammation are known to sensitize the afferent neurons, which is one of the contributors to abdominal pain. However, not all IBD patients have abdominal pain, and some patients report abdominal pain during remission, suggesting contributions of other pathological factors to abdominal pain in IBD. Epidemiological studies found early-life gastrointestinal infections a risk factor for IBD symptoms and adult-life gastrointestinal infections may trigger the onset of IBD...
April 25, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28439883/an-update-for-richter-syndrome-new-directions-and-developments
#9
REVIEW
Toby A Eyre, Anna Schuh
High-grade transformation of chronic lymphocytic leukaemia [Richter syndrome (RS)] is rare and represents a unique and uncommon clinical challenge. Clonally related diffuse large B cell type RS is a chemotherapy-resistant and devastating disease. Patients are typically elderly, immunosuppressed and present with a rapidly deteriorating performance status. Historical outcomes suggest a median overall survival of approximately 8 months. RS remains is an area of high unmet clinical need. The molecular profile and treatment needs of patients are likely to change over time with the advent of novel B cell receptor inhibitors, monoclonal antibodies and BH3 mimetics...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28439494/how-best-to-manage-gastrointestinal-stromal-tumor
#10
REVIEW
Gandhi Lanke, Jeffrey H Lee
Gastrointestinal stromal tumors (GISTs) are rare but most common nonepithelial tumor of gastrointestinal tract. They are often found incidentally on computed tomography and endoscopic investigations. Increasing knowledge of the pathogenesis of GISTs and the advent of tyrosine kinase inhibitors revolutionized the management of GISTs. The newer advanced endoscopic techniques have challenged the conventional surgery although the true efficacy and safety of endoscopic approach is not clear at this time. This review article focuses on pathogenesis, diagnosis and management of GISTs...
April 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28439271/cross-talk-between-inhibitory-immunoreceptor-tyrosine-based-activation-motif-signaling-and-toll-like-receptor-pathways-in-macrophages-and-dendritic-cells
#11
REVIEW
Ivan Hirsch, Vaclav Janovec, Ruzena Stranska, Nathalie Bendriss-Vermare
The innate immune cells sense microbial infection and self-ligands by pathogen recognition receptors (PRRs), such as toll-like receptors (TLRs) and regulatory receptors (RRs), associated with immunoreceptor tyrosine-based activation motif (ITAM). Rapid activation and concerted action of PRRs signaling and feedback inhibitory mechanisms must be engaged to ensure the host defense functions and to prevent cytotoxicity associated with excessive activation. ITAM-associated RRs can generate stimulatory or, paradoxically, inhibitory signals...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28439006/murine-model-indicates-22q11-2-signaling-adaptor-crkl-is-a-dosage-sensitive-regulator-of-genitourinary-development
#12
Meade Haller, Qianxing Mo, Akira Imamoto, Dolores J Lamb
The spectrum of congenital anomalies affecting either the upper tract (kidneys and ureters) or lower tract (reproductive organs) of the genitourinary (GU) system are fundamentally linked by the developmental origin of multiple GU tissues, including the kidneys, gonads, and reproductive ductal systems: the intermediate mesoderm. Although ∼31% of DiGeorge/del22q11.2 syndrome patients exhibit GU defects, little focus has been placed on the molecular etiology of GU defects in this syndrome. Among del22q11.2 patients exhibiting GU anomalies, we have mapped the smallest relevant region to only five genes, including CRKLCRKL encodes a src-homology adaptor protein implicated in mediating tyrosine kinase signaling, and is expressed in the developing GU-tract in mice and humans...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438896/mechanisms-that-shape-human-antibody-repertoire-development-in-mice-transgenic-for-human-ig-h-and-l-chain-loci
#13
Nancy S Longo, Tobias Rogosch, Michael Zemlin, Moncef Zouali, Peter E Lipsky
To determine the impact of the milieu on the development of the human B cell repertoire, we carried out a comprehensive analysis of productive and nonproductive Ig gene rearrangements from transgenic mice engineered to express single copies of the unrearranged human H chain and L chain Ig gene loci. By examining the nonproductive repertoire as an indication of the immediate product of the rearrangement machinery without an impact of selection, we discovered that the distribution of human rearrangements arising in the mouse was generally comparable to that seen in humans...
April 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28438613/stress-altered-synaptic-plasticity-and-damp-signaling-in-the-hippocampus-pfc-axis-elucidating-the-significance-of-igf-1-igf-1r-camkii%C3%AE-expression-in-neural-changes-associated-with-a-prolonged-exposure-therapy
#14
Olalekan M Ogundele, Philip J Ebenezer, Charles C Lee, Joseph Francis
Traumatic stress patients showed significant improvement in behavior after a prolonged exposure to an unrelated stimulus. This treatment method attempts to promote extinction of the fear memory associated with the initial traumatic experience. However, the subsequent prolonged exposure to such stimulus creates an additional layer of neural stress. Although the mechanism remains unclear, prolonged exposure therapy (PET) likely involve changes in synaptic plasticity, neurotransmitter function and inflammation; especially in parts of the brain concerned with the formation and retrieval of fear memory (Hippocampus and Prefrontal Cortex: PFC)...
April 21, 2017: Neuroscience
https://www.readbyqxmd.com/read/28438610/hyperglycemia-increases-interstitial-cells-of-cajal-via-mapk1-and-mapk3-signaling-to-etv1-and-kit-leading-to-rapid-gastric-emptying
#15
Yujiro Hayashi, Yoshitaka Toyomasu, Siva Arumugam Saravanaperumal, Michael R Bardsley, John A Smestad, Andrea Lorincz, Seth T Eisenman, Gianluca Cipriani, Molly H Nelson Holte, Fatimah J Al Khazal, Sabriya A Syed, Gabriella B Gajdos, Kyoung Moo Choi, Gary J Stoltz, Katie E Miller, Michael L Kendrick, Brian P Rubin, Simon J Gibbons, Adil E Bharucha, David R Linden, Louis James Maher, Gianrico Farrugia, Tamas Ordog
BACKGROUND & AIMS: Depletion of interstitial cells of Cajal (ICCs) is common in diabetic gastroparesis. However, in approximately 20% of patients with diabetes, gastric emptying (GE) is accelerated. GE is also faster in obese individuals, and is associated with increased blood levels of glucose in patients with type 2 diabetes. To understand the fate of ICCs in hyperinsulinemic, hyperglycemic states characterized by rapid GE, we studied mice with mutation of the leptin receptor (Lepr(db/db)), which in our colony had accelerated GE...
April 21, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28438474/tyrosine-kinase-inhibitors-and-heart-failure-risk
#16
Manjulika Das
No abstract text is available yet for this article.
April 21, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28438385/small-molecules-inhibit-stat3-activation-autophagy-and-cancer-cell-anchorage-independent-growth
#17
Donghui Zhou, Maya Z Springer, David Xu, Degang Liu, Andy Hudmon, Kay F Macleod, Samy O Meroueh
Triple-negative breast cancers (TNBCs) lack the signature targets of other breast tumors, such as HER2, estrogen receptor, and progesterone receptor. These aggressive basal-like tumors are driven by a complex array of signaling pathways that are activated by multiple driver mutations. Here we report the discovery of 6 (KIN-281), a small molecule that inhibits multiple kinases including maternal leucine zipper kinase (MELK) and the non-receptor tyrosine kinase bone marrow X-linked (BMX) with single-digit micromolar IC50s...
March 23, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28437785/the-retina-of-asian-and-african-elephants-comparison-of-newborn-and-adult
#18
Heidrun Kuhrt, Andreas Bringmann, Wolfgang Härtig, Gudrun Wibbelt, Leo Peichl, Andreas Reichenbach
Elephants are precocial mammals that are relatively mature as newborns and mobile shortly after birth. To determine whether the retina of newborn elephants is capable of supporting the mobility of elephant calves, we compared the retinal structures of 2 newborn elephants (1 African and 1 Asian) and 2 adult animals of both species by immunohistochemical and morphometric methods. For the first time, we present here a comprehensive qualitative and quantitative characterization of the cellular composition of the newborn and the adult retinas of 2 elephant species...
April 25, 2017: Brain, Behavior and Evolution
https://www.readbyqxmd.com/read/28437590/plant-dual-specificity-tyrosine-phosphorylation-regulated-kinase-optimizes-light-regulated-growth-and-development-in-arabidopsis
#19
Wen-Yu Huang, Yi-Chen Wu, Hsin-Yi Pu, Ying Wang, Geng-Jen Jang, Shu-Hsing Wu
Light controls vegetative and reproductive development of plants. For a plant, sensing the light input properly ensures coordination with the ever-changing environment. Previously, we found that LIGHT-REGULATED WD1 (LWD1) and LWD2 regulate the circadian clock and photoperiodic flowering. Here we identified Arabidopsis YET ANOTHER KINASE1 (AtYAK1), an evolutionarily conserved protein and a member of dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs), as an interacting protein of LWDs. Our study revealed that AtYAK1 is an important regulator for various light responses, including the circadian clock, photomorphogenesis and reproductive development...
April 24, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28437437/use-of-short-interfering-rna-delivered-by-cationic-liposomes-to-enable-efficient-down-regulation-of-ptpn22-gene-in-human-t-lymphocytes
#20
Valentina Perri, Marsha Pellegrino, Francesca Ceccacci, Anita Scipioni, Stefania Petrini, Elena Gianchecchi, Anna Lo Russo, Serena De Santis, Giovanna Mancini, Alessandra Fierabracci
Type 1 diabetes and thyroid disease are T cell-dependent autoimmune endocrinopathies. The standard substitutive administration of the deficient hormones does not halt the autoimmune process; therefore, development of immunotherapies aiming to preserve the residual hormonal cells, is of crucial importance. PTPN22 C1858T mutation encoding for the R620W lymphoid tyrosine phosphatase variant, plays a potential pathophysiological role in autoimmunity. The PTPN22 encoded protein Lyp is a negative regulator of T cell antigen receptor signaling; R620W variant, leading to a gain of function with paradoxical reduced T cell activation, may represent a valid therapeutic target...
2017: PloS One
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