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https://www.readbyqxmd.com/read/29149601/intersubunit-crosstalk-in-the-rag-gtpase-heterodimer-enables-mtorc1-to-respond-rapidly-to-amino-acid-availability
#1
Kuang Shen, Abigail Choe, David M Sabatini
No abstract text is available yet for this article.
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29144771/bursal-sided-rotator-cuff-tears-simple-versus-everted-type
#2
Hwan Jin Kim, Jung Youn Kim, Young Moon Kee, Yong Girl Rhee
BACKGROUND: No studies have focused on the everted type of bursal-sided partial-thickness rotator cuff tears (PTRCTs). PURPOSE: To evaluate the radiological characteristics, arthroscopic findings, and clinical and structural outcomes after arthroscopic repair of the everted type of bursal-sided PTRCTs. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Two groups of patients with bursal-sided PTRCTs (simple type, 25 shoulders; everted type, 25 shoulders) were enrolled...
November 1, 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/29136688/-characteristics-of-erg-fli-1-cd34-cd31-and-f%C3%A2-rag-expression-in-hepatic-malignant-vascular-tumors
#3
Z B Wang, X J An, J F Deng, J H Liu, H Y Shi
Objective: To investigate the expression of ERG, Fli-1, CD34, CD31 and factor Ⅷ-related antigen(FⅧRAg) in hepatic malignant vascular tumors. Methods: A retrospective analysis was conducted on 63 cases of primary hepatic malignant vascular tumors and 31 cases of hepatic other malignant spindle cell tumors collected during January 1986 to January 2014. EnVision method was used to detect the expression of ERG, Fli-1, CD34, CD31, FⅧRAg. Results: Sixty-three cases of malignant vascular tumors, including 24 cases of angiosarcoma, 38 cases of epithelioid hemangioendothelioma and 1 case of hepatic Kaposi's sarcoma...
November 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29123114/structural-basis-for-ragulator-functioning-as-a-scaffold-in-membrane-anchoring-of-rag-gtpases-and-mtorc1
#4
Tianlong Zhang, Rong Wang, Zhijing Wang, Xiangxiang Wang, Fang Wang, Jianping Ding
Amino acid-dependent activation of the mechanistic target of rapamycin complex 1 (mTORC1) is mediated by Rag GTPases, which are recruited to the lysosome by the Ragulator complex consisting of p18, MP1, p14, HBXIP and C7orf59; however, the molecular mechanism is elusive. Here, we report the crystal structure of Ragulator, in which p18 wraps around the MP1-p14 and C7orf59-HBXIP heterodimers and the interactions of p18 with MP1, C7orf59, and HBXIP are essential for the assembly of Ragulator. There are two binding sites for the Roadblock domains of Rag GTPases: helix α1 of p18 and the two helices side of MP1-p14...
November 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/29123071/samtor-is-an-s-adenosylmethionine-sensor-for-the-mtorc1-pathway
#5
Xin Gu, Jose M Orozco, Robert A Saxton, Kendall J Condon, Grace Y Liu, Patrycja A Krawczyk, Sonia M Scaria, J Wade Harper, Steven P Gygi, David M Sabatini
mTOR complex 1 (mTORC1) regulates cell growth and metabolism in response to multiple environmental cues. Nutrients signal via the Rag guanosine triphosphatases (GTPases) to promote the localization of mTORC1 to the lysosomal surface, its site of activation. We identified SAMTOR, a previously uncharacterized protein, which inhibits mTORC1 signaling by interacting with GATOR1, the GTPase activating protein (GAP) for RagA/B. We found that the methyl donor S-adenosylmethionine (SAM) disrupts the SAMTOR-GATOR1 complex by binding directly to SAMTOR with a dissociation constant of approximately 7 μM...
November 10, 2017: Science
https://www.readbyqxmd.com/read/29120231/impact-of-clear-corneal-incision-morphology-on-incision-site-descemet-membrane-detachment-in-conventional-and-femtosecond-laser-assisted-phacoemulsification
#6
Jeewan S Titiyal, Manpreet Kaur, Priyanka Ramesh, Pooja Shah, Ruchita Falera, Lalit M S Bageshwar, Ashutosh Kinkar, Namrata Sharma
PURPOSE: To assess intraoperative morphology of clear corneal incisions (CCI) and its impact on incision-site descemet membrane detachment (DMD) in conventional phacoemulsification and femtosecond laser-assisted cataract surgery (FLACS). METHODS: Prospective comparative study of 129 eyes that underwent either conventional phacoemulsification (Group I, n = 77) or FLACS (Group II, n = 52) was undertaken at an apex tertiary care ophthalmic setup. In group I, a 2...
November 9, 2017: Current Eye Research
https://www.readbyqxmd.com/read/29119604/anatomy-and-histology-of-the-prostate-and-glands-of-cowper-in-three-species-of-neotropical-bats
#7
María Daniela Miotti, Marcos I Mollerach, Ruben M Barquez
The reproductive accessory glands (RAG) are essential components in reproduction because their secretion products ensure survival, viability, and sperm motility. The objective of this study was to characterize and compare the morphological and histological structure of the RAG in three species of bats of the genus Sturnira (S. erythromos, S. lilium, and S. oporaphilum). The RAG complex comprise a compact gland (prostate), which surrounds the urethra, and a pair of Glands of Cowper at the base of penis. Anatomical and histologically, the prostate are differentiated in two regions, ventral and dorsal...
November 9, 2017: Journal of Morphology
https://www.readbyqxmd.com/read/29119228/macropinocytosis-mtorc1-and-cellular-growth-control
#8
REVIEW
Sei Yoshida, Regina Pacitto, Ken Inoki, Joel Swanson
The growth and proliferation of metazoan cells are driven by cellular nutrient status and by extracellular growth factors. Growth factor receptors on cell surfaces initiate biochemical signals that increase anabolic metabolism and macropinocytosis, an actin-dependent endocytic process in which relatively large volumes of extracellular solutes and nutrients are internalized and delivered efficiently into lysosomes. Macropinocytosis is prominent in many kinds of cancer cells, and supports the growth of cells transformed by oncogenic K-Ras...
November 8, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29113905/trim21-negatively-regulates-intestinal-mucosal-inflammation-through-inhibiting-th1-th17-cell-differentiation-in-inflammatory-bowel-diseases
#9
Guangxi Zhou, Wei Wu, Lin Yu, Tianming Yu, Wenjing Yang, Ping Wang, Xiaoping Zhang, Yingzi Cong, Zhanju Liu
BACKGROUND: Tripartite motif-containing (TRIM)21 has been implicated in pathogenesis of several types of autoimmune diseases. OBJECTIVE: We sought to elucidate expression of TRIM21 in patients with inflammatory bowel disease (IBD) and its role in regulating intestinal mucosal inflammation. METHODS: TRIM21 expression was analyzed in inflamed mucosa of IBD patients by qRT-PCR and immunohistochemistry. Peripheral blood CD4(+) T cells were transfected with lentivirus-expressing-TRIM21 (LV-TRIM21) or LV-sh-TRIM21, and cytokine expression was determined by qRT-PCR and ELISA...
November 4, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29107538/hybrid-structure-of-the-raga-c-ragulator-mtorc1-activation-complex
#10
Ming-Yuan Su, Kyle L Morris, Do Jin Kim, Yangxue Fu, Rosalie Lawrence, Goran Stjepanovic, Roberto Zoncu, James H Hurley
The lysosomal membrane is the locus for sensing cellular nutrient levels, which are transduced to mTORC1 via the Rag GTPases and the Ragulator complex. The crystal structure of the five-subunit human Ragulator at 1.4 Å resolution was determined. Lamtor1 wraps around the other four subunits to stabilize the assembly. The Lamtor2:Lamtor3 dimer stacks upon Lamtor4:Lamtor5 to create a platform for Rag binding. Hydrogen-deuterium exchange was used to map the Rag binding site to the outer face of the Lamtor2:Lamtor3 dimer and to the N-terminal intrinsically disordered region of Lamtor1...
October 25, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29104218/evolutionary-conservation-of-the-components-in-the-tor-signaling-pathways
#11
REVIEW
Hisashi Tatebe, Kazuhiro Shiozaki
Target of rapamycin (TOR) is an evolutionarily conserved protein kinase that controls multiple cellular processes upon various intracellular and extracellular stimuli. Since its first discovery, extensive studies have been conducted both in yeast and animal species including humans. Those studies have revealed that TOR forms two structurally and physiologically distinct protein complexes; TOR complex 1 (TORC1) is ubiquitous among eukaryotes including animals, yeast, protozoa, and plants, while TOR complex 2 (TORC2) is conserved in diverse eukaryotic species other than plants...
November 1, 2017: Biomolecules
https://www.readbyqxmd.com/read/29104089/rag-deficiency-with-alps-features-successfully-treated-with-tcr%C3%AE-%C3%AE-cd19-cell-depleted-haploidentical-stem-cell-transplant
#12
Emma Westermann-Clark, Alice Grossi, Francesca Fioredda, Stefano Giardino, Enrico Cappelli, Paola Terranova, Elena Palmisani, Jocelyn R Farmer, Zsofia Foldvari, Yasuhiro Yamazaki, Maura Faraci, Edoardo Lanino, Luigi D Notarangelo, Carlo Dufour, Isabella Ceccherini, Jolan E Walter, Maurizio Miano
No abstract text is available yet for this article.
November 2, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29084345/a-gis-based-quantitative-approach-for-the-search-of-clandestine-graves-italy
#13
Roberta Somma, Maria Cascio, Massimiliano Silvestro, Eliana Torre
Previous research on the RAG color-coded prioritization systems for the discovery of clandestine graves has not considered all the factors influencing the burial site choice within a GIS project. The goal of this technical note was to discuss a GIS-based quantitative approach for the search of clandestine graves. The method is based on cross-referenced RAG maps with cumulative suitability factors to host a burial, leading to the editing of different search scenarios for ground searches showing high-(Red), medium-(Amber), and low-(Green) priority areas...
October 30, 2017: Journal of Forensic Sciences
https://www.readbyqxmd.com/read/29078414/twenty-five-years-of-mtor-uncovering-the-link-from-nutrients-to-growth
#14
David M Sabatini
In my PNAS Inaugural Article, I describe the development of the mTOR field, starting with efforts to understand the mechanism of action of the drug rapamycin, which ∼25 y ago led to the discovery of the mTOR protein kinase. I focus on insights that we have contributed and on work that has been particularly influential to me, as well as provide some personal reflections and stories. We now appreciate that, as part of two distinct complexes, mTORC1 and mTORC2, mTOR is the major regulator of growth (mass accumulation) in animals and is the key link between the availability of nutrients in the environment and the control of most anabolic and catabolic processes...
October 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29075267/pd-1-controls-tonic-signaling-and-lymphopenia-induced-proliferation-of-t-lymphocytes
#15
Kristofor K Ellestad, Jiaxin Lin, Louis Boon, Colin C Anderson
Recovery of the T lymphocyte compartment within a lymphopenic host by lymphopenia-induced proliferation (LIP) is regulated by inter- and intraclonal competition for limited resources, including homeostatic cytokines and peptide:MHC (pMHC) complexes with which the TCR can interact at least weakly to yield a tonic signal. Importantly, the process of LIP can synergize with other factors that promote T cell activation to drive inflammatory disease. While reconstitution of the lymphoid compartment of immune deficient Rag(-/-) mice by transfer of wild-type hematopoietic stem cells (HSC) does not generally result in an overt disease phenotype, transfer of HSC deficient in expression of the co-inhibitory molecule PD-1 results in severe systemic autoimmunity driven by newly generated T cells that emerge from the thymus into the periphery and undergo LIP...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29069605/the-conserved-atm-kinase-rag2-s365-phosphorylation-site-limits-cleavage-events-in-individual-cells-independent-of-any-repair-defect
#16
Susannah L Hewitt, Jason B Wong, Ji-Hoon Lee, Mayilaadumveettil Nishana, Hongxi Chen, Marc Coussens, Suzzette M Arnal, Lili M Blumenberg, David B Roth, Tanya T Paull, Jane A Skok
Many DNA lesions associated with lymphoid malignancies are linked to off-target cleavage by the RAG1/2 recombinase. However, off-target cleavage has mostly been analyzed in the context of DNA repair defects, confounding any mechanistic understanding of cleavage deregulation. We identified a conserved SQ phosphorylation site on RAG2 365 to 366 that is involved in feedback control of RAG cleavage. Mutation of serine 365 to a non-phosphorylatable alanine permits bi-allelic and bi-locus RAG-mediated breaks in the same cell, leading to reciprocal translocations...
October 24, 2017: Cell Reports
https://www.readbyqxmd.com/read/29056322/intersubunit-crosstalk-in-the-rag-gtpase-heterodimer-enables-mtorc1-to-respond-rapidly-to-amino-acid-availability
#17
Kuang Shen, Abigail Choe, David M Sabatini
mTOR complex I (mTORC1) is a central growth regulator that senses amino acids through a pathway that converges on the Rag GTPases, an obligate heterodimer of two related GTPases. Despite their central role in amino acid sensing, it is unknown why the Rag GTPases are heterodimeric and whether their subunits communicate with each other. Here, we find that the binding of guanosine triphosphate (GTP) to one subunit inhibits the binding and induces the hydrolysis of GTP by the other. This intersubunit communication pushes the Rag GTPases into either of two stable configurations, which represent active "on" or "off" states that interconvert via transient intermediates...
November 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29055140/morphological-analysis-of-the-male-reproductive-accessory-glands-of-the-bat-artibeus-lituratus-phyllostomidae-chiroptera
#18
Renata T S Santos, Laís R M Pires, Edna S S Albernaz, Cleber S Andrade, Cornélio S Santiago, Eliana Morielle-Versute, Sebastião R Taboga, Mateus R Beguelini
Bats are distributed worldwide from tropical to temperate regions. Despite their wide geographical radiation and advances in studies using evolutionary approaches, aspects related to the reproduction of these animals remain poorly explored, especially those related to the male reproductive accessory glands (RAGs). Thus, the aim of this study was to analyze the morphophysiology of the male RAGs in the bat Artibeus lituratus. The RAGs in A. lituratus are composed of a compact intra-abdominal glandular complex, consisting of the prostate with two prostatic regions (ventral and dorsal), plus Littre glands and a pair of extra-abdominal bulbourethral glands...
October 21, 2017: Journal of Morphology
https://www.readbyqxmd.com/read/29050212/recombination-activating-gene-2-null-severe-combined-immunodeficient-pigs-and-mice-engraft-human-induced-pluripotent-stem-cells-differently
#19
Yun-Jung Choi, EunSu Kim, Abu Musa Md Talimur Reza, Kwonho Hong, Hyuk Song, Chankyu Park, Seong-Keun Cho, Kiho Lee, Randall S Prather, Jin-Hoi Kim
This study comparatively investigated the transcriptional, physiological, and phenotypic differences of the immune disorder between severe combined immunodeficient (SCID) mouse and pig models. We discovered that the recombination activating gene-2 (Rag-2) SCID mice, but not RAG-2 SCID pigs, showed intense, infrequent, and mild cluster of CD3(+)-, CD4(+)-, and CD8(+) signals respectively, suggesting that distinct species-specific effects exist. Furthermore, the expression of six relevant genes (NFATC1, CD79B, CD2, BLNK, FOXO1, and CD40) was more downregulated than that in the Rag-2 SCID mice, which provides a partial rationale for the death of T/B cells in the lymphoid organs of RAG-2 SCID pigs but not in Rag-2 SCID mice...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29038163/bcl11a-is-a-critical-component-of-a-transcriptional-network-that-activates-rag-expression-and-vdj-recombination
#20
Baeck-Seung Lee, Bum-Kyu Lee, Vishwanath R Iyer, Barry P Sleckman, Arthur L Shaffer, Gregory C Ippolito, Haley O Tucker, Joseph D Dekker
Recombination activating gene 1 (RAG1) and RAG2 are critical enzymes for initiating variable-diversity-joining (VDJ) segment recombination, an essential process for antigen receptor expression and lymphocyte development. The BCL11A transcription factor is required for B cell and Plasmacytoid dendritic cell (pDC) development, but its molecular function(s) in early B cell fate specification and commitment are unknown. We show here that the major B cell isoform, BCL11A-XL, binds directly to the RAG1 promoter as well as directly to regulatory regions of transcription factors previously implicated in both B cell and pDC development to activate RAG1 and RAG2 transcription in pro- and pre-B cells...
October 16, 2017: Molecular and Cellular Biology
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