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Emilia Pachulec, Vanessa Neitzke-Montinelli, João P B Viola
Nuclear factor of activated T cells (NFAT) 2 null mutant mice die in utero of cardiac failure, precluding analysis of the role of NFAT2 in lymphocyte responses. Only the NFAT2(-/-)/Rag-1(-/-) chimeric mice model gave insight into the role of NFAT2 transcription factor in T lymphocyte development, activation, and differentiation. As reports are mainly focused on the role of NFAT2 in CD4(+) T lymphocytes activation and differentiation, we decided to investigate NFAT2's impact on CD8(+) T lymphocyte responses...
2016: Frontiers in Immunology
Nina Lefeber, Eva Swinnen, Eric Kerckhofs
PURPOSE: The integration of sufficient cardiovascular stress into robot-assisted gait (RAG) training could combine the benefits of both RAG and aerobic training. The aim was to summarize literature data on the immediate effects of RAG compared to walking without robot-assistance on metabolic-, cardiorespiratory- and fatigue-related parameters. METHODS: PubMed and Web of Science were searched for eligible articles till February 2016. Means, SDs and significance values were extracted...
October 20, 2016: Disability and Rehabilitation. Assistive Technology
Jing Ni, Oliver Hölsken, Matthias Miller, Quirin Hammer, Merlin Luetke-Eversloh, Chiara Romagnani, Adelheid Cerwenka
Natural killer (NK) cell infusions can induce remissions in subsets of patients with different types of cancer. The optimal strategies for NK cell activation prior to infusion are still under debate. There is recent evidence that NK cells can acquire long-term functional competence by preactivation with the cytokines IL-12/15/18. The mechanisms supporting the maintenance of long-term NK cell antitumor activity are incompletely under-stood. Here, we show that NK cells preactivated in vitro with IL-12/15/18, but not with IL-15 alone, maintained high antitumor activity even 1 mo after transfer into lymphopenic RAG-2(-/-)γc(-/-) mice...
2016: Oncoimmunology
David Harrison
Hypertension remains an enormous health care burden that affects one third of the population. Despite its prevalence the cause of most cases of hypertension remains unknown. Our laboratory has defined a novel mechanism for hypertension involving adaptive immunity. We found that mice lacking lymphocytes (RAG-1 mice) develop blunted hypertensive responses to a variety of stimuli including chronic angiotensin II infusion, DOCA-salt challenge and norepinephrine infusion. Adoptive transfer of T cells, but not B cells, restores the hypertensive responses to these stimuli...
September 2016: Journal of Hypertension
Daniel Poveda-Martínez, Chrystian C Sosa, Katherine Chacón-Vargas, Víctor Hugo García-Merchán
Characidium is a Neotropical fish genus. Its distribution ranges from eastern Panama to northern Argentina, and it is an important component of the Neotropical ichthyofauna present in the major rivers of South America. We here provide an approximation to the dispersal and historical distributions of Characidium. The biogeographic history of five species of the genus was analyzed through nuclear RAG-2 and mitochondrial 16S genes and a time-calibrated phylogenetic analysis using three outgroup species. A biogeographical reconstruction was performed to estimate ancestral geographic ranges and infer the historical events that impacted the geographic distributions of Characidium species...
2016: PloS One
Maria Manifava, Matthew Smith, Sergio Rotondo, Simon Walker, Izabella Niewczas, Roberto Zoncu, Jonathan Clark, Nicholas T Ktistakis
Amino acids are essential activators of mTORC1 via a complex containing RAG GTPases, RAGULATOR and the vacuolar ATPase. Sensing of amino acids causes translocation of mTORC1 to lysosomes, an obligate step for activation. To examine the spatial and temporal dynamics of this translocation, we used live imaging of the mTORC1 component RAPTOR and a cell permeant fluorescent analogue of di-leucine methyl ester. Translocation to lysosomes is a transient event, occurring within 2 min of aa addition and peaking within 5 min...
October 11, 2016: ELife
Y-X Kang, Y-J Wang, Q Zhang, X-H Pang, W Gu
Kearns-Sayre syndrome (KSS) is a disorder caused by mutations in mitochondrial DNA. Here, we report an unusual case of Kearns-Sayre syndrome accompanied by hypopituitarism (deficiencies in reproductive and growth hormones). A 20-year-old male presented with growth retardation for the last 8 years, as well as the following findings: short stature, delayed puberty, myasthenia, an extraocular movement deficit, drooping eyelids, pectus carinatum and scoliosis. Cerebral enhanced magnetic resonance imaging revealed dysplasias of the pituitary, white matter and cerebellum...
October 6, 2016: Andrologia
Hui-Fang Wang, Juan Wang, Yan-Ling Wang, Jian-Jian Fan, Gui-Lin Mo, Feng-Yin Gong, Zhi-Ming Chai, Jin Zhang, Hua-Xing Meng, Chang-Xin Li, Jun-Hong Guo, Chuan-Qiang Pu
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder associated with mitochondrial alterations. MNGIE is characterized by severe gastrointestinal dysmotility, cachexia, ophthalmoplegia, ptosis, peripheral neuropathy, and leukoencephalopathy. The condition is caused by mutation of the TYMP gene. We studied the clinical and biochemical characteristics of a family with MNGIE. The proband was a 48-year-old male presenting with diarrhea and progressive weight loss. He also had ptosis and exhibited eyeball fixation...
October 5, 2016: Acta Neurologica Belgica
Jennifer Zagelbaum, Noriko Shimazaki, Zitadel Anne Esguerra, Go Watanabe, Michael R Lieber, Eli Rothenberg
Single-molecule FRET (smFRET) and single-molecule colocalization (smCL) assays have allowed us to observe the recombination-activating gene (RAG) complex reaction mechanism in real time. Our smFRET data have revealed distinct bending modes at recombination signal sequence (RSS)-conserved regions before nicking and synapsis. We show that high mobility group box 1 (HMGB1) acts as a cofactor in stabilizing conformational changes at the 12RSS heptamer and increasing RAG1/2 binding affinity for 23RSS. Using smCL analysis, we have quantitatively measured RAG1/2 dwell time on 12RSS, 23RSS, and non-RSS DNA, confirming a strict RSS molecular specificity that was enhanced in the presence of a partner RSS in solution...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
Sandhya R Pulivarthy, Mattia Lion, Guray Kuzu, Adam G W Matthews, Mark L Borowsky, John Morris, Robert E Kingston, Jonathan H Dennis, Michael Y Tolstorukov, Marjorie A Oettinger
We show that the physical distribution of nucleosomes at antigen receptor loci is subject to regulated cell type-specific and lineage-specific positioning and correlates with the accessibility of these gene segments to recombination. At the Ig heavy chain locus (IgH), a nucleosome in pro-B cells is generally positioned over each IgH variable (VH) coding segment, directly adjacent to the recombination signal sequence (RSS), placing the RSS in a position accessible to the recombination activating gene (RAG) recombinase...
October 3, 2016: Proceedings of the National Academy of Sciences of the United States of America
Liufeng Zheng, Wei Zhang, Yuanfei Zhou, Fengna Li, Hongkui Wei, Jian Peng
The mammalian target of rapamycin (mTOR) is the central regulator of mammalian cell growth, and is essential for the formation of two structurally and functionally distinct complexes: mTORC1 and mTORC2. mTORC1 can sense multiple cues such as nutrients, energy status, growth factors and hormones to control cell growth and proliferation, angiogenesis, autophagy, and metabolism. As one of the key environmental stimuli, amino acids (AAs), especially leucine, glutamine and arginine, play a crucial role in mTORC1 activation, but where and how AAs are sensed and signal to mTORC1 are not fully understood...
2016: International Journal of Molecular Sciences
Valerio Rossini, Katarina Radulovic, Christian U Riedel, Jan Hendrik Niess
Inflammatory bowel disease (IBD) is a chronic inflammation which affects the gastrointestinal tract (GIT). One of the best ways to study the immunological mechanisms involved during the disease is the T cell transfer model of colitis. In this model, immunodeficient mice (RAG(-/-) recipients) are reconstituted with naive CD4(+) T cells from healthy wild type hosts. This model allows examination of the earliest immunological events leading to disease and chronic inflammation, when the gut inflammation perpetuates but does not depend on a defined antigen...
2016: Journal of Visualized Experiments: JoVE
Junpei Koge, Shintaro Hayashi, Hiroo Yamaguchi, Takahisa Tateishi, Hiroyuki Murai, Jun-Ichi Kira
A 37-old-male with a history of early childhood mental retardation was admitted to our hospital. He experienced recurrent syncopes at 23 years old, and at age 35 gait disturbance and hearing impairment developed gradually and worsened over time. His grandparents were in a consanguineous marriage. He was of short stature and absent of tendon xanthomas. Neurological examinations revealed scanning speech, dysphagia, right sensorineural hearing loss, spasticity in both upper and lower extremities, and spastic gait...
September 28, 2016: Rinshō Shinkeigaku, Clinical Neurology
Andreas C Solomos, Kevin J O'Regan, Glenn F Rall
Immunity within the brain, specifically to virus-infected neurons, must be controlled to prevent neuron loss and impairment, though the process by which this occurs remains unclear. Here, we use a mouse model of neuron-restricted measles virus infection, in which immunocompetent adults survive challenge, whereas T and B cell-deficient mice succumb. This model allowed us to more precisely define the contributions of CD4(+) T cells, CD8(+) T cells, and B cells in neuroprotection. Both B cell knockout mice and mice depleted of CD8(+) T cells survive challenge and show no signs of illness, though are less able to control viral replication than immunocompetent mice...
September 24, 2016: Virology
Ankita Kothari, Marimikel Charrier, Yu-Wei Wu, Stephanie Malfatti, Carol E Zhou, Steven W Singer, Larry Dugan, Aindrila Mukhopadhyay
The hydrocarbonoclastic bacterium Acinetobacter venetianus RAG-1 has attracted substantial attention due to its powerful oil degrading capabilities and its potential to play an important ecological role in the cleanup of alkanes. In this study we compare the transcriptome of the strain RAG-1 grown in dodecane, the corresponding alkanol (dodecanol), and sodium acetate for the characterization of genes involved in dodecane uptake and utilization. Comparison of the transcriptional responses of RAG-1 grown on dodecane led to the identification of 1074 genes that were differentially expressed relative to sodium acetate...
September 22, 2016: FEMS Microbiology Letters
Victoria Leong, Usha Goswami
Over 30 years ago, it was suggested that difficulties in the 'auditory organization' of word forms in the mental lexicon might cause reading difficulties. It was proposed that children used parameters such as rhyme and alliteration to organize word forms in the mental lexicon by acoustic similarity, and that such organization was impaired in developmental dyslexia. This literature was based on an 'oddity' measure of children's sensitivity to rhyme (e.g. wood, book, good) and alliteration (e.g. sun, sock, rag)...
September 22, 2016: Developmental Science
Hiroaki Kijima, Shin Yamada, Natsuo Konishi, Hitoshi Kubota, Hiroshi Tazawa, Takayuki Tani, Norio Suzuki, Keiji Kamo, Yoshihiko Okudera, Ken Sasaki, Tetsuya Kawano, Naohisa Miyakoshi, Yoichi Shimada
PURPOSE: In femoral trochanteric fractures, fractures whose fracture lines extend to the basal neck or to the subtrochanteric part have high instability. Area classification can identify such instable fractures. The best choices of internal fixators for femoral trochanteric fractures were investigated according to area classification. METHODS: Femoral trochanteric fractures were investigated with respect to area classification. In area classification, the proximal femur is divided into 4 areas with 3 boundary lines: Line-1 is the center of the neck; Line-2 is the border between the neck and the trochanteric zone; and Line-3 links the inferior borders of the greater and lesser trochanters...
2016: SpringerPlus
Jing Xia, Rong Wang, Tianlong Zhang, Jianping Ding
The mechanistic Target Of Rapamycin Complex 1 (mTORC1) is central to the cellular response to changes in nutrient signals such as amino acids. CASTOR1 is shown to be an arginine sensor, which plays an important role in the activation of the mTORC1 pathway. In the deficiency of arginine, CASTOR1 interacts with GATOR2, which together with GATOR1 and Rag GTPases controls the relocalization of mTORC1 to lysosomes. The binding of arginine to CASTOR1 disrupts its association with GATOR2 and hence activates the mTORC1 signaling...
2016: Cell Discovery
Sofia Ahola, Mari Auranen, Pirjo Isohanni, Satu Niemisalo, Niina Urho, Jana Buzkova, Vidya Velagapudi, Nina Lundbom, Antti Hakkarainen, Tiina Muurinen, Päivi Piirilä, Kirsi H Pietiläinen, Anu Suomalainen
Mitochondrial myopathy (MM) with progressive external ophthalmoplegia (PEO) is a common manifestation of mitochondrial disease in adulthood, for which there is no curative therapy. In mice with MM, ketogenic diet significantly delayed progression of the disease. We asked in this pilot study what effects high-fat, low-carbohydrate "modified Atkins" diet (mAD) had for PEO/MM patients and control subjects and followed up the effects by clinical, morphological, transcriptomic, and metabolomic analyses. All of our five patients, irrespective of genotype, showed a subacute response after 1...
September 19, 2016: EMBO Molecular Medicine
M Tahara, H Tsuboi, S Segawa, H Asashima, M Iizuka-Koga, T Hirota, H Takahashi, Y Kondo, M Matsui, I Matsumoto, T Sumida
We showed recently that M3 muscarinic acetylcholine receptor (M3R)-reactive CD3(+) T cells play a pathogenic role in the development of murine autoimmune sialadenitis (MIS), which mimics Sjögren's syndrome (SS). The aim of this study was to determine the effectiveness and mechanism of action of retinoic acid-related orphan receptor-gamma t (RORγt) antagonist (A213) in MIS. Splenocytes from M3R knockout (M3R(-/-) ) mice immunized with murine M3R peptide mixture were inoculated into recombination-activating gene 1 knockout (Rag-1(-/-) ) mice (M3R(-/-) →Rag-1(-/-) ) with MIS...
September 19, 2016: Clinical and Experimental Immunology
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