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https://www.readbyqxmd.com/read/28926616/co-ordinated-activation-of-classical-and-novel-pkc-isoforms-is-required-for-pma-induced-mtorc1-activation
#1
Mengling Liu, Christopher J Clarke, Mohamed F Salama, Yeon Ja Choi, Lina M Obeid, Yusuf A Hannun
Protein kinase C (PKC) has been shown to activate the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, a central hub in the regulation of cell metabolism, growth and proliferation. However, the mechanisms by which PKCs activate mTORC1 are still ambiguous. Our previous study revealed that activation of classical PKCs (cPKC) results in the perinuclear accumulation of cPKC and phospholipase D2 (PLD2) in recycling endosomes in a PLD2-dependent manner. Here, we report that mTORC1 activation by phorbol 12,13-myristate acetate (PMA) requires both classic, cPKC, and novel PKC (nPKC) isoforms, specifically PKCη, acting through distinct pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28919503/a-multilocus-phylogeny-of-the-genus-sarcohyla-anura-hylidae-and-an-investigation-of-species-boundaries-using-statistical-species-delimitation
#2
Itzue W Caviedes Solis, Adrián Nieto-Montes de Oca
The genus Sarcohyla is composed by 24 species endemic to México. Despite the large number of phylogenetic studies focusing on the family Hylidae, the relationships among the species of Sarcohyla are still poorly known, and the scarce numbers of specimens and tissue samples available for some of the species has hampered an appropriate phylogenetic analysis. We present the most comprehensive molecular phylogenetic study of Sarcohyla to date. We included 17 species of the genus Sarcohyla using data from two mitochondrial (ND1 and 12S) and three nuclear genes (Rag-1, Rhod, and POMc)...
September 14, 2017: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/28904861/a-modified-graft-versus-host-induced-model-for-systemic-sclerosis-with-pulmonary-fibrosis-in-rag2-deficient-mice
#3
Xue Yang, Chi Liu, Masayuki Fujino, Ji Yang, Xiao-Kang Li, Hejian Zou
Systemic sclerosis (SSc) is a connective tissue disease that results in fibrosis in multiple organs. Various animal models for this disease have been developed, both genetic and induced. One of the induced models, sclerodermatous graft-versus-host disease (scl-GvHD), exhibits the main characteristics of SSc, but involves lethal γ-irradiation of recipients. We sought to develop a modified scl-GvHD model. Spleen cells from B10.D2 donor mice were transplanted into immunodeficient Rag-2 recipients on the BALB/c genetic background...
September 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28904203/three-conserved-regions-in-baculovirus-sulfhydryl-oxidase-p33-are-critical-for-enzymatic-activity-and-function
#4
Wenhua Kuang, Huanyu Zhang, Manli Wang, Ning-Yi Zhou, Fei Deng, Hualin Wang, Peng Gong, Zhihong Hu
Baculoviruses encode a conserved sulfhydryl oxidase P33, which is necessary for budded virus (BV) production and multi-nucleocapsid occlusion-derived virus (ODV) formation. Here, the structural and functional relationship of P33 was revealed by X-ray crystallography, site-directed mutagenesis, and functional analysis. Based on crystallographic characterization and structural analysis, a series of P33 mutants within three conserved regions, i.e. the active site, dimer interface, and the R127-E183 salt bridge, were constructed...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28890383/interaction-between-rhein-acyl-glucuronide-and-methotrexate-based-on-human-organic-anion-transporters
#5
Yuan Yuan, Hua Yang, Linghua Kong, Yuan Li, Ping Li, Hongjian Zhang, Jianqing Ruan
Rhein, a major bioactive compound of many medicinal herbs and the prodrug of diacerein, is often used with low dose of methotrexate as drug combination to treat rheumatoid arthritis. In this study, potential drug-drug interaction between methotrexate and rhein was investigated based on organic anion transporters (OAT). Our study demonstrated that rhein acyl glucuronide (RAG), the major metabolite of rhein in the human blood circulation, significantly inhibited the uptake of p-aminohippurate in hOAT1 transfected cells with IC50 value of 691 nM and estrone sulfate uptake in hOAT3 transfected cells with IC50 value of 78...
September 7, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28882611/generation-and-crispr-cas9-editing-of-transformed-progenitor-b-cells-as-a-pseudo-physiological-system-to-study-dna-repair-gene-function-in-v-d-j-recombination
#6
Hélène Lenden Hasse, Chloé Lescale, Joy J Bianchi, Wei Yu, Marie Bedora-Faure, Ludovic Deriano
Antigen receptor gene assembly is accomplished in developing lymphocytes by the V(D)J recombination reaction, which can be separated into two steps: DNA cleavage by the recombination-activating gene (RAG) nuclease and joining of DNA double strand breaks (DSBs) by components of the nonhomologous end joining (NHEJ) pathway. Deficiencies for NHEJ factors can result in immunodeficiency and a propensity to accumulate genomic instability, thus highlighting the importance of identifying all players in this process and deciphering their functions...
September 4, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28875499/the-intestinal-microbiota-determines-the-colitis-inducing-potential-of-t-bet-deficient-th-cells-in-mice
#7
Jakob Zimmermann, Pawel Durek, Anja A Kühl, Florian Schattenberg, Patrick Maschmeyer, Francesco Siracusa, Katrin Lehmann, Kerstin Westendorf, Melanie Weber, René Riedel, Susann Müller, Andreas Radbruch, Hyun-Dong Chang
Conflicting evidence has been provided as to whether induction of intestinal inflammation by adoptive transfer of naïve T cells into Rag(-/-) mice requires expression of the transcription factor T-bet by the T cells. Here, we formally show that the intestinal microbiota composition of the Rag(-/-) recipient determines whether or not T-bet-deficient Th cells can induce colitis and we have resolved the differences of the two microbiomes, permissive or non-permissive to T-bet-independent colitis. Our data highlight the dominance of the microbiota over particular T cell differentiation programs in the pathogenesis of chronic intestinal inflammation...
September 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28867329/patchy-parasitized-skin-governs-leishmania-donovani-transmission-to-sand-flies
#8
Shaden Kamhawi, Tiago D Serafim
Doehl et al. have combined empirical data with computer simulation to demonstrate that RAG-2 mice intravenously infected with Leishmania donovani form heterogeneous skin parasite patches that govern infectiousness to sand flies. This model provides a much-needed tool to explore the relevance of asymptomatic and symptomatic visceral leishmaniasis patients as infection reservoirs.
August 31, 2017: Trends in Parasitology
https://www.readbyqxmd.com/read/28864286/abnormalities-of-t-cell-receptor-repertoire-in-cd4-regulatory-and-conventional-t-cells-in-patients-with-rag-mutations-implications-for-autoimmunity
#9
Jared H Rowe, Brian D Stadinski, Lauren A Henderson, Lisa Ott de Bruin, Ottavia Delmonte, Yu Nee Lee, M Teresa de la Morena, Rakesh K Goyal, Anthony Hayward, Huang Chiung-Hui, Maria Kanariou, Alejandra King, Taco W Kuijpers, Jian Yi Soh, Benedicte Neven, Jolan E Walter, Eric S Huseby, Luigi D Notarangelo
No abstract text is available yet for this article.
August 29, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28854233/protective-capacity-of-neutralizing-and-non-neutralizing-antibodies-against-glycoprotein-b-of-cytomegalovirus
#10
Anna Bootz, Astrid Karbach, Johannes Spindler, Barbara Kropff, Nina Reuter, Heinrich Sticht, Thomas H Winkler, William J Britt, Michael Mach
Human cytomegalovirus (HCMV) is an important, ubiquitous pathogen that causes severe clinical disease in immunocompromised individuals, such as organ transplant recipients and infants infected in utero. Antiviral chemotherapy remains problematic due to toxicity of the available compounds and the emergence of viruses resistant to available antiviral therapies. Antiviral antibodies could represent a valuable alternative strategy to limit the clinical consequences of viral disease in patients. The envelope glycoprotein B (gB) of HCMV is a major antigen for the induction of virus neutralizing antibodies...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28843605/the-right-ventricle-a-rags-to-riches-story
#11
EDITORIAL
Timothy M Maus
No abstract text is available yet for this article.
June 23, 2017: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/28837660/a-recombinant-multi-antigen-vaccine-with-broad-protection-potential-against-avian-pathogenic-escherichia-coli
#12
Angelica Van Goor, Zachary R Stromberg, Melha Mellata
Chickens are a major source of protein worldwide, yet infectious diseases continue to threaten the poultry industry. Avian pathogenic Escherichia coli (APEC), a subgroup of extraintestinal pathogenic E. coli (ExPEC), causes colibacillosis in chickens resulting in economic loss because of treatment, condemnation of products, and death. In this study, we evaluated a recombinant antigens (rAg) vaccine combining common ExPEC surface proteins EtsC, OmpA, OmpT, and TraT for broad protective potential against APEC infections in chickens...
2017: PloS One
https://www.readbyqxmd.com/read/28830581/severe-dermatitis-associated-with-spontaneous-staphylococcus-xylosus-infection-in-rag-tpl2-mice
#13
Nicole V Acuff, Monica LaGatta, Tamas Nagy, Wendy T Watford
Staphylococcus xylosus is a commensal bacterium found on the skin and mucosal surfaces of SPF mice. S. xylosus is rarely pathogenic, most often causing skin lesions and dermatitis in immunocompromised mice, particularly those with impaired NADPH oxidase function. Here we report spontaneous infection with S. xylosus in Rag1-/-Tpl2-/- mice. Infection was characterized by the presence of alopecia, crusts, and scaly skin. S. xylosus was detected in the feces, skin, lymph nodes, and lungs of Rag1-/-Tpl2-/- mice and led to mortality or euthanasia due to humane endpoints...
August 1, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28820278/does-additional-biceps-augmentation-improve-rotator-cuff-healing-and-clinical-outcomes-in-anterior-l-shaped-rotator-cuff-tears-clinical-comparisons-with-arthroscopic-partial-repair
#14
Yoon Sang Jeon, Juyeob Lee, Rag Gyu Kim, Young-Won Ko, Sang-Jin Shin
BACKGROUND: The repair of anterior L-shaped tears is usually difficult because of the lack of anterior rotator cuff tendon to cover the footprint. The biceps tendon is usually exposed from the retracted anterolateral corner of the torn tendon and can be easily used to augment rotator cuff repair. Hypothesis/Purpose: This study compared the clinical outcomes of the biceps augmentation technique with those of partial tendon repair for the arthroscopic treatment of large anterior L-shaped rotator cuff tears to evaluate the role of additional biceps augmentation in tendon healing...
August 1, 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/28816366/modification-of-the-paris-system-for-urinary-tract-washing-specimens-using-diagnostic-cytological-features
#15
J Suh, H Go, C Sung, S Baek, H Hwang, S Jeong, Y Cho
OBJECTIVE: The Paris System (TPS), which was recently introduced, emphasised the key features of malignant urine cytology: a high nuclear to cytoplasmic ratio, nuclear hyperchromasia, irregular nuclear membranes and coarse chromatin. Although other diagnostic features have been described, the diagnostic significance of such features and their application to TPS have not been fully defined for urinary tract washing specimens. METHODS: A total of 142 cases of urinary tract washing specimens with corresponding surgical pathology samples were examined for the key features of TPS and 13 previously described features...
August 17, 2017: Cytopathology: Official Journal of the British Society for Clinical Cytology
https://www.readbyqxmd.com/read/28808055/dynamin-dependent-amino-acid-endocytosis-activates-mechanistic-target-of-rapamycin-complex-1-mtorc1
#16
Shusaku Shibutani, Hana Okazaki, Hiroyuki Iwata
The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of protein synthesis and potential target for modifying cellular metabolism in various conditions, including cancer and aging. mTORC1 activity is tightly regulated by the availability of extracellular amino acids, and previous studies have revealed that amino acids in the extracellular fluid are transported to the lysosomal lumen. There, amino acids induce recruitment of cytoplasmic mTORC1 to the lysosome by the Rag GTPases, followed by mTORC1 activation by the small GTPase Ras homolog enriched in brain (Rheb)...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28790360/comprehensive-validation-of-t-and-b-cell-deficiency-in-rag1-null-zebrafish-implication-for-the-robust-innate-defense-mechanisms-of-teleosts
#17
Yumie Tokunaga, Masamichi Shirouzu, Ryota Sugahara, Yasutoshi Yoshiura, Ikunari Kiryu, Mitsuru Ototake, Takahiro Nagasawa, Tomonori Somamoto, Miki Nakao
rag1 (-/-) zebrafish have been employed in immunological research as a useful immunodeficient vertebrate model, but with only fragmentary evidence for the lack of functional adaptive immunity. rag1-null zebrafish exhibit differences from their human and murine counterparts in that they can be maintained without any specific pathogen-free conditions. To define the immunodeficient status of rag1 (-/-) zebrafish, we obtained further functional evidence on T- and B-cell deficiency in the fish at the protein, cellular, and organism levels...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28789694/co-infection-of-two-reoviruses-increases-both-viruses-accumulation-in-rice-by-up-regulating-of-viroplasm-components-and-movement-proteins-bilaterally-and-rna-silencing-suppressor-unilaterally
#18
Shu Li, Tong Zhang, Yingzhi Zhu, Guohui Zhou
BACKGROUND: Synergism between southern rice black-streaked dwarf virus (SRBSDV) and rice ragged stunt virus (RRSV) not only aggravates disease symptoms but also enhances their vector acquisition efficiencies by increasing both viruses' titers in co-infected rice plants, which may exacerbate the epidemic of both viruses and cause significant damage to rice production. The molecular mechanism of viral synergism of these two viruses remains unexplored. METHODS: Single and double infection of SRBSDV and RRSV were obtained with the viruliferous white-backed planthopper and brown planthopper inoculation on four-leaf stage rice seedlings, respectively, under experimental condition...
August 8, 2017: Virology Journal
https://www.readbyqxmd.com/read/28783691/characterization-of-t-and-b-cell-repertoire-diversity-in-patients-with-rag-deficiency
#19
Yu Nee Lee, Francesco Frugoni, Kerry Dobbs, Irit Tirosh, Likun Du, Francesca A Ververs, Heng Ru, Lisa Ott de Bruin, Mehdi Adeli, Jacob H Bleesing, David Buchbinder, Manish J Butte, Caterina Cancrini, Karin Chen, Sharon Choo, Reem A Elfeky, Andrea Finocchi, Ramsay L Fuleihan, Andrew R Gennery, Dalia H El-Ghoneimy, Lauren A Henderson, Waleed Al-Herz, Elham Hossny, Robert P Nelson, Sung-Yun Pai, Niraj C Patel, Shereen M Reda, Pere Soler-Palacin, Raz Somech, Paolo Palma, Hao Wu, Silvia Giliani, Jolan E Walter, Luigi D Notarangelo
Recombination-activating genes 1 and 2 (RAG1 and RAG2) play a critical role in T and B cell development by initiating the recombination process that controls the expression of T cell receptor (TCR) and immunoglobulin genes. Mutations in the RAG1 and RAG2 genes in humans cause a broad spectrum of phenotypes, including severe combined immunodeficiency (SCID) with lack of T and B cells, Omenn syndrome, leaky SCID, and combined immunodeficiency with granulomas or autoimmunity (CID-G/AI). Using next-generation sequencing, we analyzed the TCR and B cell receptor (BCR) repertoire in 12 patients with RAG mutations presenting with Omenn syndrome (n = 5), leaky SCID (n = 3), or CID-G/AI (n = 4)...
December 16, 2016: Science Immunology
https://www.readbyqxmd.com/read/28769923/natural-killer-cells-from-patients-with-recombinase-activating-gene-and-non-homologous-end-joining-gene-defects-comprise-a-higher-frequency-of-cd56-bright-nkg2a-cells-and-yet-display-increased-degranulation-and-higher-perforin-content
#20
Kerry Dobbs, Giovanna Tabellini, Enrica Calzoni, Ornella Patrizi, Paula Martinez, Silvia Clara Giliani, Daniele Moratto, Waleed Al-Herz, Caterina Cancrini, Morton Cowan, Jacob Bleesing, Claire Booth, David Buchbinder, Siobhan O Burns, Talal A Chatila, Janet Chou, Vanessa Daza-Cajigal, Lisa M Ott de Bruin, MaiteTeresa de la Morena, Gigliola Di Matteo, Andrea Finocchi, Raif Geha, Rakesh K Goyal, Anthony Hayward, Steven Holland, Chiung-Hui Huang, Maria G Kanariou, Alejandra King, Blanka Kaplan, Anastasiya Kleva, Taco W Kuijpers, Bee Wah Lee, Vassilios Lougaris, Michel Massaad, Isabelle Meyts, Megan Morsheimer, Benedicte Neven, Sung-Yun Pai, Alessandro Plebani, Susan Prockop, Ismail Reisli, Jian Yi Soh, Raz Somech, Troy R Torgerson, Yae-Jaen Kim, Jolan E Walter, Andrew R Gennery, Sevgi Keles, John P Manis, Emanuela Marcenaro, Alessandro Moretta, Silvia Parolini, Luigi D Notarangelo
Mutations of the recombinase-activating genes 1 and 2 (RAG1 and RAG2) in humans are associated with a broad range of phenotypes. For patients with severe clinical presentation, hematopoietic stem cell transplantation (HSCT) represents the only curative treatment; however, high rates of graft failure and incomplete immune reconstitution have been observed, especially after unconditioned haploidentical transplantation. Studies in mice have shown that Rag(-/-) natural killer (NK) cells have a mature phenotype, reduced fitness, and increased cytotoxicity...
2017: Frontiers in Immunology
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